June 2021 Volume 27, Number 6S

AACE Annual Meeting 2021 Abstracts Editorial board

Editor-in-Chief Pauline M. Camacho, MD, FACE Suleiman Mustafa-Kutana, BSC, MB, CHB, MSC Maywood, Illinois, United States Boston, Massachusetts, United States Vin Tangpricha, MD, PhD, FACE Atlanta, Georgia, United States Andrea Coviello, MD, MSE, MMCi Karel Pacak, MD, PhD, DSc Durham, North Carolina, United States Bethesda, Maryland, United States Associate Editors Natalie E. Cusano, MD, MS Amanda Powell, MD Maria Papaleontiou, MD New York, New York, United States Boston, Massachusetts, United States Ann Arbor, Michigan, United States Tobias Else, MD Gregory Randolph, MD Melissa Putman, MD Ann Arbor, Michigan, United States Boston, Massachusetts, United States Boston, Massachusetts, United States Vahab Fatourechi, MD Daniel J. Rubin, MD, MSc Harold Rosen, MD Rochester, Minnesota, United States Philadelphia, Pennsylvania, United States Boston, Massachusetts, United States Ruth Freeman, MD Joshua D. Safer, MD Nicholas Tritos, MD, DS, FACP, FACE New York, New York, United States New York, New York, United States Boston, Massachusetts, United States Rajesh K. Garg, MD Pankaj Shah, MD Boston, Massachusetts, United States Staff Rochester, Minnesota, United States Eliza B. Geer, MD Joseph L. Shaker, MD Paul A. Markowski New York, New York, United States Milwaukee, Wisconsin, United States CEO Roma Gianchandani, MD Lance Sloan, MD, MS Elizabeth Lepkowski Ann Arbor, Michigan, United States Lufkin, Texas, United States Chief Learning Officer Martin M. Grajower, MD, FACP, FACE Takara L. Stanley, MD Lori Clawges The Bronx, New York, United States Boston, Massachusetts, United States Senior Managing Editor Allen S. Ho, MD Devin Steenkamp, MD Corrie Williams Los Angeles, California, United States Boston, Massachusetts, United States Peer Review Manager Michael F. Holick, MD, PhD Dennis Styne, MD Editorial Board Boston, Massachusetts, United States Sacramento, California, United States Ejigayehu Abate, MD Michael S. Irwig, MD Auryan Szalat, MD Jacksonville, Florida, United States Washington, District of Columbia, United States Jerusalem, Israel fi Sonia Ananthakrishnan, MD Linda S. Jaffe, MD Mira So a Torres, MD, FACE, ECNU Boston, Massachusetts, United States Boston, Massachusetts, United States Worcester, Massachusetts, United States John L.D. Atkinson, MD Sina A. Jasim, MD, MPH Vera Vera Fajtova, MD Rochester, Minnesota, United States St. Louis, Missouri, United States Boston, Massachusetts, United States Irina Bancos, MD Irwin Klein, MD Joseph G. Verbalis, MD Rochester, Minnesota, United States Manhasset, New York, United States Washington, District of Columbia, United States Elena I. Barengolts, MD Matthew C. Leinung, MD, FACE Xiangbing Wang, MD, PhD Chicago, Illinois, United States Albany, New York, United States New Brunswick, New Jersey, United States

Shehzad Basaria, MD Virginia A. LiVolsi, MD Jingwei Wu, PhD Boston, Massachusetts, United States Philadelphia, Pennsylvania, United States Philadelphia, Pennsylvania, United States Rajib K. Bhattacharya, MD, FACE Ildiko Lingvay, MD, MPH, MSCS Kevin C.J. Yuen, MBChB, MD, FRCP(UK), FACE Kansas City, Kansas, United States Dallas, Texas, United States Phoenix, Arizona, United States Glenn D. Braunstein, MD Alan Malabanan, MD Farhad Zangeneh, MD Los Angeles, California, United States Boston, Massachusetts, United States Falls Church, Virginia, United States Lynn Burmeister, MD Lyle Mitzner, MD Donald Zimmerman, MD Minneapolis, Minnesota, United States Boston, Massachusetts, United States Chicago, Illinois, United States

Endocrine Practice Vol 27 No. 6S June 2021 A1 Endocrine Practice 27 (2021) S1eS23

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Endocrine Practice

journal homepage: www.endocrinepractice.org

ADRENAL DISORDERS

Abstract #977113 Abstract #984425 Use of Mifepristone in a Hypercortisolemic Patient Diffuse Large B-cell Lymphoma Presenting As with End Stage Renal Disease on Hemodialysis Shrinking Bilateral Adrenal Masses

Author Block: Albert Coo - Diabetes and Endocrine Associates, Author Block: Jennifer Fuh - University of New Mexico; Privia Medical Group; Rebecca Ray, APRN, FNP-C - Co-author, Kristen Gonzales, MD - co-author, University of New Mexico; Corcept Therapeutics; James J. Smith, PhD. - Co-author, Corcept Laura Shevy, MD - co-author, University of New Mexico; Therapeutics Patricia Kapsner, MD - co-author, University of New Mexico Introduction: There is currently no published data on the use of Introduction: Metastases from lung, breast, or colon cancer are mifepristone (Korlym®, Corcept Therapeutics) in patients with common causes for bilateral adrenal masses in areas without End Stage Renal Disease (ESRD) on hemodialysis diagnosed prevalent tuberculosis. Adrenal involvement in non-Hodgkin’s with hypercortisolism. We present a patient case with ESRD lymphoma with associated adrenal insufficiency is not uncommon. fi demonstrating the safe and ef cacious long-term use of We present a case where diagnosis was complicated and prolonged mifepristone. due to multiple negative needle biopsies and spontaneously Case Description: A 67-year-old woman presented with ESRD on shrinking adrenal masses. hemodialysis due to HIV-associated nephropathy and multiple Case Description: A 51 year old female with cervical cancer post comorbidities (T2DM, hypertension, hyperlipidemia, obesity, hysterectomy in remission, presented to the emergency room for hypothyroidism, HSV, anemia, depression, tertiary hyperpara- abdominal pain, 40 pound weight loss, sweating and nausea. CT thyroidism). She has a history of bilateral adrenal adenomas abdomen was remarkable for bilateral adrenal masses (right 6.1 cm, (2.0 cm left, 1.8 cm right) discovered incidentally in 2008 left 7.9 cm). MRI noted concern for lymphoma. PET/CT showed hy- during a hospital stay. ACTH-independent hypercortisolism was permetabolic adrenal lesions, a T12 spinal lesion, and diffuse bone fi con rmed with 1mg ODST, late-night salivary cortisol, and marrow activity. Biopsy of the T12 lesion with flow cytometry was ACTH. Anuria prevented the collection of the 24-hour UFC. Due negative for neoplasm. Plasma metanephrines, renin, aldosterone, ’ to the patient s poor surgical candidacy, she was conservatively androstenedione, 17-hydroxyprogesterone, random cortisol, testos- managed for 7 years. In 2015, she was started on mifepristone terone, and estradiol were normal. Dehydroepiandrosterone sulfate 300 mg QD. At 2 months, mifepristone was titrated to 600 mg was low and adrenocorticotropic hormone 2.5 times upper normal QD which is the maximum dose for patients with renal limit. Evaluation for infectious causes including histoplasmosis, impairment. No adjustments to the mifepristone dose were tuberculosis, and blastomycosis was negative. Two months after required to accommodate the 3 days a week hemodialysis initial presentation, the patient was hospitalized for worsening schedule. Mifepristone was dosed daily in the evenings of both abdominal pain. CT of the abdomen showed a decrease in size of the the hemodialysis and nonhemodialysis days. Over 55 months, adrenal masses [right 5.2 cm, 39 Hounsfield units (HU), -21% her HbA1c improved from 7.2 to 4.8 % with discontinuation of washout; left mass 5.7 cm, 39 HU, -27% washout], as well as new all insulin; blood pressure normalized with discontinuation of paraaortic and aortocaval lymph nodes. Morning cortisol was low, antihypertensive medications; weight decreased from 198 to and due to concern for adrenal insufficiency, hydrocortisone was 155 lbs with a BMI improvement of 36.2 to 28 kg/m2.Hypo- initiated. Left adrenal core biopsy was negative for malignancy. One kalemia was treated with KCl supplementation. HIV remained month later, patient had a syncopal episode with abdominal pain. CT undetectable. abdomen showed continued shrinkage of the adrenal masses (right Discussion: fi This is the rst published case of a complex patient 3.2cm and left 3.6cm). Two weeks later, patient had pleuritic pain, with ESRD on hemodialysis using mifepristone to control and CT angiogram demonstrated new enlarged mediastinal, left hypercortisolism. The long-term use of mifepristone in this axillary, and left supraclavicular lymph nodes. Left axillary lymph patient resulted in clinically meaningful improvements in hy- node core biopsy yielded inadequate tissue, so open biopsy was perglycemia, hypertension, and weight loss while offering an pursued, revealing double-hit high grade B cell lymphoma. Chemo- acceptable safety profile. therapy was initiated, and subsequent imaging demonstrated further https://doi.org/10.1016/j.eprac.2021.04.472 decrease in size of adrenal masses.

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Discussion: High index of suspicion for lymphoma in the setting of monitoring is needed for most patients in the form of routine bilateral adrenal masses should be maintained even with negative screening with serial BP monitoring, MRI brain and spine, needle biopsies and diminishing size of adrenal masses. Needle ophthalmological and audiological exams to prevent complications biopsy may be inadequate, thus consider open biopsy if needle with vision, hearing loss, neurological, and renal impairments from biopsy is negative with high clinical suspicion for lymphoma. tumor growth. https://doi.org/10.1016/j.eprac.2021.04.473 https://doi.org/10.1016/j.eprac.2021.04.474

Abstract #984820 Abstract #988358

Like Mother, Like Son e VHL Syndrome A Case of Gender Misassignment; Due To Rare Enzyme Disorder

Author Block: Nikhitha Chandrashekar - Gundersen Health System; Chinou Vang, MD - co-author(2nd author), Internal Author Block: Urooj lal Rehman - jinnah postgraduate medical Medicine, Gundersen Health System; Rachel McKenney, MD - centre; tasnim ahsan, MBBS, FRCP - co author, medicine and co-author, Gundersen Health System endocrinology, MEDICELL INSTITUTE OF DIABETES, ENDOCRINOLOGY AND METABOLISM; RUKHSHANDA JABEEN, Introduction: Von Hippel-Lindau (VHL) syndrome is a hereditary MBBS, FCPS - co author, medicine and endocrinology, jinnah autosomal dominant disease characterized by the growth of benign postgraduate medical centre; sehar aziz, MBBS, FCPS - co author, or malignant cysts and/or tumors affecting several organ systems. medicine and endocrinology, jinnah postgraduate medical centre Common manifestations include hemangioblastomas of the brain, spinal cord, and retina; pheochromocytoma and paraganglioma; Introduction: we describe a case of a gender misassignment due renal cell carcinoma; pancreatic cysts and neuroendocrine tumors. to rare enzyme defect that is 17 alpha hydroxylase deficiceincy or Renal cell carcinoma occurs in about 70% of individuals with VHL 17/20 lyase deficiency leading to complete sex reversal in genetic and is the leading cause of mortality. male. Case Description: 22 y.o. Caucasian male with a history of hyper- Case Description: a 16 year old female presented in endocrine tension on lisinopril presented to the clinic with complaints of clinic at Jinnah Post Graduate Medical Centre, Karachi, Pakistan insomnia, elevated blood pressure, palpitations, and chest pain. with complaints of head ache and primary amenorrhea. on exam- These symptoms had been worsening over the last 6 months. His ination she was tall, tan girl with height of 155cm, blood pressure of home blood pressure reads ranged from 130-150 systolic and via 180/100, absent secondary sexual characteristics. investigations his fitbit, he noticed episodes of elevated heart rates from 130 to done were hormonal analysis along with the stimulation test, 140 beats per minute. Interestingly, his mother at 27 experienced radiological evaluation and karyotyping was also done. similar symptoms and was diagnosed with pheochromocytoma. Discussion: on work up her serum FSH was 102.9(0.0-15mIU/ She urged him to be seen in the clinic. Plasma normetanephrines ML),LH 62.10(1.37-9 IU/L), estradiol 10.94 pg/ml (20-150), Serum were ordered and returned elevated at 8.1 nmol/L. Plasma meta- Prolactin 20.30 (3.8-23), Serum Potassium 2.6mmol, ultrasound nephrines, aldosterone, and renin were within normal limits. Renal and MRI showed absent uterus and ovaries with testis in the artery ultrasound showed a 3 cm nodule adjacent to the left renal inguinal canal bilaterally. karyotype was XY. further tests showed hilum, and subsequent CT abdomen and pelvis with contrast testosterone 0.06(0.52-2.43 nmol/l) , Dihydrotestosterone 21.18 showed bilateral enhancing adrenal lesions, consistent with (40-220 pg/ml), 17 alpha OHP 0.27ng/ml, serum cortisol 0.8 ug/dl pheochromocytoma. There was also a 2 cm enhancing left renal (4.33-2.4 AM), Plasma ACTH 504 (0-46 ug/dl). as we dont have mass suspicious for renal cell carcinoma, and a small simple cyst in genetci testing available in Pakistan on basis of clinical and the right kidney. The radiology report noted that pheochromocy- bichemical findings she was labelled as a case of 17 alpha hydrox- toma and renal cell carcinoma can be seen in VHL. In light of this, ylase deficiency or 17/20 lyase deficiency. After psychological endocrinology was consulted and started him on alpha blocking evaluation and discussion with patient and her family orchid- doxazosin. Genetic counselling confirmed a pathogenic vHL mu- ectomy was done. she was put on steroids and estrogen for sec- tation by DNA sequencing in him and his mother. He then under- ondary sexual characteristics. went a robotic left adrenalectomy and partial left nephrectomy, the https://doi.org/10.1016/j.eprac.2021.04.475 pathology of which confirmed both pheochromocytoma and grade 3 clear cell renal carcinoma. Ophthalmology reported an early retinal hemangioblastoma on fluorescein angiography which was Abstract #990069 not amenable to laser treatment . Post op, he is doing well and has since gone off all blood pressure medications. Normotensive Pheochromocytoma: An Unusual Discussion: This is a rare case of VHL which occurs in 1 in 36,000 Presentation live births. This case highlights the importance of obtaining a family history in young adults with hypertension. If left untreated, VHL can lead to fatal outcomes with life expectancy as low as 40-52 Author Block: Urooj lal Rehman - jinnah postgraduate medical years. Clinching a diagnosis is crucial in such cases as the admin- centre; RUKHSHANDA JABEEN, MBBS, FCPS - co author, medicine istration of a beta blocker in pheochromocytoma can precipitate a and endocrinology, jinnah postgraduate medical centre; hypertensive crisis from the unopposed alpha adrenergic effects of sidra mumtaz, MBBS - co author, medicine and endocrinology, catecholamines. After sufficient alpha blockade is established, a jinnah postgraduate medical centre beta blocker can be added on. Hemangioblastomas are the most common type of tumor which occurs in the CNS and retina and can Introduction: We present a case of catecholamine secreating ad- cause complications including ataxia and vision loss. Lifelong renal incidentiloma in a normotensive patient.

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Case Description: A 24 year old female presented with complaints examination e he was drowsy and low BP of 80/60 mmHg). Lab- of palpitations and occasional abdominal pain for last two years to oratory evaluation was significant for hyponatremia. Cortisol level the outpatient department of jinnah post graduate medical centre, was 1.65mcg/dl with an ACTH level of 285 pcg/ml which was Karachi, Pakistan. her cardivascular workup unremarkable however consistent with the diagnosis of primary adrenal insufficiency. A she was found to have hepatitus c. and radiologocal examination contrast-enhanced abdomen CT showed a bilateral adrenal mass, showed incidentiloma invoving the left supra renal gland. serial measuring 5.73.97.5 cm in the right adrenal gland and hormonal assays were performed.serial hormonal assays were 5.42.45.8cm in the left adrenal gland. The masses showed done, urinary metanephrines and normetanephrine were in hypodense homogeneous lesions. Thorax CT was suggestive of normal range ie 23.1ug/24hrs ( n< 350) and 103.7 ug/dl (n< 600) miliary TB. Treatment-A diagnosis of adrenal insufficiency sec- respectively.however concomitent plasma free metanephrine was ondary to tuberculosis was made, and treatment with hydrocorti- 321 pg/ml ( 0-90) and free normetanephrine 5495ug/ml (0-190). sone, fludrocortisone for adrenal insufficiency, and antitubercular ctscan abdomen confirmed the presence of left supra renal mass. therapy were continued. After 12 months of follow-up (January she was prepared for surgery using alpha and beta blockade and 2021) the masses were static in size. He is still using hydrocorti- adequate hydration. Interestingly no hypotension was observed sone, fludrocortisone. during this treatment. she had laproscopic adrenelectomy and Discussion: Conclusion- Disseminated tuberculosis evolving to there were two episodes of hypertension during the surgery primary adrenal insufficiency (PAI) during antituberculosis treat- controlled by labetalol. post op she developed perinephric collec- ment is rare but should be kept in the mind particularly when there tion which was treated adequatly and patient improved. the his- is both enlargement of adrenal glands. A watchful follow up is topathology confirmed the diagnosis of pheochromocytoma. necessary to diagnose PAI when a combination of disseminated TB Discussion: This case presents an unusual presentation of the with enlargement of adrenal glands pheochromocytoma leading to dilemma in treatment of these pa- https://doi.org/10.1016/j.eprac.2021.04.477 tients. despite being normotensive the need to be treated adequately like hypertensive pheochromocytoma as any manipu- lation during surgery can lead to hypertensive crises. Abstract #994509 https://doi.org/10.1016/j.eprac.2021.04.476 Adrenal Insufficiency: A Unique Presentation of Multicentric Castleman Disease with Human Herpes Abstract #992844 Virus 8 Positivity and Concomitant Kaposi Sarcoma

Development of Addison’s Disease during Treatment of Disseminated Tuberculosis with Bilateral Adrenal Author Block: Banafsheh Motazedi, M.D. - primary author, Mass: A Case Report Endocrinology, MedStar Georgetown University Hospital/MedStar Washington Hospital Center; Meeta Sharma, M.D. - co-author, Endocrinology, MedStar Washington Hospital Center Author Block: kishore behera - AIIMS, Bhubaneshwar; subhendu K. sahoo sr. - co-auther, endocrinology, AIIMS Introduction: Multicentric Castleman Disease (MCD) is a lympho- BHUBANESWAR; uttam K. soren sr. - co-auther, endocrinology, proliferative disorder involving multiple lymph nodes and can be AIIMS BHUBANESWAR; smruti r. behera sr. - co-auther, associated with human herpes 8 virus (HHV-8). Hyaline vascular endocrinology, AIIMS BHUBANESWAR; sibanada K. jena sr. - co- (HV) MCD is rare, occurring in < 10% of cases. MCD with concom- auther, endocrinology, AIIMS BHUBANESWAR itant HIV negative Kaposi Sarcoma (KS) is also uncommon and can peculiarly present with adrenal insufficiency. Introduction: Recently, the incidence of adrenal tuberculosis has Case Description: 53-year-old male with biopsy proven diagnosis been greatly decreased due to the introduction of antituberculosis of HHV-8 positive KS was transferred to our institution with (ATT) drugs. The estimated incidence of tuberculosis in India is 204/ persistent hypotension requiring pressor support. He described a 100,000 population in 2017. it is estimated that disseminated two-week history of night sweats, 20 Ib weight & appetite loss, tuberculosis accounting for < 2% of all cases of TB and up to 20% of fatigue, muscles aches, and subjective fevers. Vitals: BP: 99/50 all extrapulmonary TB cases. mmHg, HR: 90 bpm, RR: 19 and T: 103oF. Physical exam revealed Case Description: Case -A 51-year-old man presented with a 3- multiple violaceous, non-blanching plaques on his body, tender month history of generalized weakness, anorexia, weight loss, and inguinal & axillary lymphadenopathy, and bilateral lower extremity dizziness. He was admitted to the surgical ward for evaluation of edema. Initial labs: Na: 137 mmol/L, K: 3.6 mmol/L, WBC: 5.6 k/uL, spasmodic abdominal pain with vomiting; hence A USG abdomen Hg: 7.1 gm/dL, Hct: 21%, Plt: 91 k/uL, AM cortisol: 12.5 mcg/dL (5.3- was done which incidentally detected a bilateral adrenal mass. A 22.5), ACTH < 1 pg/mL, TSH: 7.5 uIU/mL, FTF: 0.63 ng/dL, PRL: 7 ng/ CECT abdomen and thorax was done, CECT suggestive of miliary mL, Total testosterone: 20 ng/dL, FSH: 4.2 mIU/mL, LH: 8.3 mIU/mL, tuberculosis. FNAC of the right adrenal gland was done; cytology IGF-1: 77 ng/mL (64-218), ESR >85 mm/hr (< 20), and CRP: 76 mg/ report was inconclusive Histopathology study of the transbronchial dL (< 3). HIV and COVID-19 tests were negative. He was started on biopsy showed caseating granuloma suggestive of Koch’s etiology oral Levothyroxine and IV Hydrocortisone with significant in September 2019 So, he was diagnosed as disseminated tuber- improvement in his BP leading to discontinuation of pressor culosis (TB). He was started on ATT. He was a diabetic and primary support. hypothyroid, on regular treatment. Follow up- Three months of ATT CT chest/abdomen/pelvis showed diffuse lymphadenopathy treatment, he developed sudden onset nausea, vomiting with low consistent with KS with normal adrenal glands. Left axillary lymph blood pressure. On further evaluation, he was hyponatremic (112 node biopsy revealed HV MCD. Additional labs; IL-6: 11.5 pg/mL mmol/l) with low serum cortisol (1.65 mg/dl) along with raised (< 2), IgG4: 45 mg/dL (1-123), normal CD4 count, renin and aldo- ACTH (285 pg/ml). He was confirmed as impending primary adre- sterone levels. 21 alpha hydroxylase antibody, T-spot, extensive nal insufficiency with a bilateral enlarged adrenal mass. Physical autoimmune and infectious work-up were negative. Pituitary MRI

S3 Adrenal Disorders Endocrine Practice 27 (2021) S1eS23 could not be obtained due to a metal object behind his right orbit. multifocal disease, and increased metastatic potential. Thoracic/ Head CT was negative for pituitary abnormality. He failed his ACTH mediastinal PGLs have been rarely reported in association with stimulation test with cortisol level: 13 mcg/dL at 90 minutes SDHA mutations, and they frequently secrete noradrenaline, which (baseline ACTH was not obtained). Thus, he was discharged on is often symptomatic. We report a case of an asymptomatic young physiological oral Hydrocortisone upon clinical improvement. He female with no family history of paragangliomas, but an incidentally began chemotherapy 1 week post discharge, however he discovered germline SDHA mutation who had an asymptomatic succumbed to his disseminated and aggressive disease 20 days noradrenaline secreting thoracic/mediastinal tumor. In hindsight, later. she may have had symptoms related to noradrenaline over secretion Discussion: MCD with concomitant KS is a rare and rapidly pro- that were attributed to other etiologies. This case demonstrates the gressive disease which can cause death within weeks. IL-6 over- importance of imaging surveillance of the chest in SDHA+ persons, production is thought to be associated with its symptom even if they are asymptomatic. Given the paucity of symptoms, even progression. Worse clinical outcomes are correlated with HIV or with a secreting tumor, lifelong biochemical and imaging surveil- HHV-8 positivity. It can uncommonly be associated with either lance is critical to assess for recurrence or the development of new primary or secondary adrenal insufficiency requiring prompt tumors. evaluation and treatment with systemic steroids to prevent https://doi.org/10.1016/j.eprac.2021.04.479 development of adrenal crisis. https://doi.org/10.1016/j.eprac.2021.04.478 Abstract #997249

Abstract #995146 A Case of a 68 Year Old Woman with Cushing's Syndrome due to 3.6cm Right Adrenal Tumor with Remarkable Asymptomatic Secreting Thoracic Paraganglioma In Improvement after Unilateral Adrenalectomy Succinate Dehydrogenase A (SDHA) Germline Mutation Author Block: Syeda Sumbul Zahra Zaidi, MBBS - Primary Author, Nishtar Medical college, Multan Pakistan; Jassimran Singh, MBBS - Author Block: Clifton Davis - University of Nebraska Medical co-author, Institute of medical sciences, BHU, India; Ritu yadav, Center; Karin Trujillo, MD - co-author, Surgery, Division of MBBS - co-author, Maulana Azad Medical College, New Delhi, Cardiothoracic Surgery, University of Nebraska Medical Center; India; Mohamed riad, MD - co-author, Mansoura University Faculty Whitney Goldner, MD - co-author, Internal Medicine, Division of of Medicine, Egypt; Maria Daniela Rendon, MD - co-author, Diabetes, Endocrinology, and Metabolism, University of Nebraska Universidad catolica de Santiago de Guayaquil, Ecuador; Medical Center Jose Duenas,~ MD - co-author, Universidad catolica de Santiago de Guayaquil, Ecuador; Lubna Mirza, MD - co-author, Norman Introduction: Paragangliomas (PGLs) are tumors derived from ex- endocrinology associates tra-adrenal cells of the sympathetic and parasympathetic ganglia that can arise anywhere from the base of the skull to the pelvis. A Introduction: Objective: To report a case of Cushing’s syndrome third of PGLs are hereditary and germline mutations in the SDHx due to an adrenal tumour, which improved remarkably after uni- account for up to 30% of hereditary tumors. SDHA mutations are lateral adrenalectomy. rare and only account for 3% of hereditary tumors. Hence, clinical Case Description: Method: We present the case of a 68-year-old phenotype has not been fully elucidated. Location of PGLs with woman with an adrenal mass which was discovered incidentally. SDHA mutations reported to date include thyroid, head and neck, She presented with hoarseness, sinus congestion, cold intolerance, thoracic, retroperitoneal, adrenal, extraadrenal, and pelvis. They are shortness of breath, depressed mood and anxiety in addition to often symptomatic, secrete noradrenaline, and have metastatic past medical history of Mitral annular calcification with mild Mitral potential. regurgitation, trace Atrial regurgitation, thyroid nodules, goitre, Case Description: An asymptomatic completely healthy 29-year- arthritis, type 2 diabetes, hypercholesterolemia, morbid obesity old female underwent germline SDHA testing when family and hypertension. members were incidentally discovered to have the SDHA CT confirmed unilateral benign adrenal mass producing cortisol, germline mutation for unrelated health reasons. She was SDHA consistent with the diagnosis of Cushing syndrome. +, so underwent biochemical and imaging screening for he- She underwent adrenalectomy and has been on steroid replace- reditary paraganglioma. Plasma normetanephrine was 1.85 ment therapy ever since. She was tapered off and now, she’s nmol/L (normal 0.89 nmol/L). MRI abdomen/ pelvis was completely off of her steroids. Her blood pressure has markedly normal. MRI neck and CT chest showed a 2.9-centimeter mass improved. within the left paraspinous musculature at the T5/T6 level. Discussion: Results: We are pleased to report that our patient Following outpatient alpha blockade, she underwent video responded quiet well to unilateral adrenalectomy and is now assisted thoracoscopic surgery (VATS) with posterior medias- thriving with the remaining functional adrenal gland without the tinal mass excision. Pathology showed a 3.8-centimeter need of steroids. completely excised paraganglioma. Post-operative imaging was Conclusion: It is important to consider the differential diagnosis negative and plasma normetanephrine level returned to normal of Cushing’s in patients presenting with uncontrolled hypertension, at 0.35 nmol/L. In hindsight, she reported preexisting anxiety obesity and other vague features of Cushing’s syndrome. We must had improved substantially post-operatively. try to diagnose Cushing’s early in its course and detect its under- Discussion: PGLs are rare, catecholamine secreting neuroendocrine lying pathology- ACTH Dependent or Independent and treat it tumors that arise from extra-adrenal sites spontaneously or as part accordingly before it progresses to an advanced form. of inherited syndromes. When compared to spontaneous tumors, hereditary paragangliomas can present at a younger age, with https://doi.org/10.1016/j.eprac.2021.04.480

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Introduction: Abstract #998357 Nelson syndrome has been reported in up to 25% of adults after bilateral adrenalectomy (BLA) for Cushing’s disease Rare Case of Pulmonary Spindle Cell Carcinoma with (CD). It usually manifests as an expanding pituitary mass, rising Bilateral Adrenal Gland Metastasis without Evidence adrenocorticotropic (ACTH) hormone levels and, in many patients, of Endocrinopathy the development of hyperpigmentation. We review the clinical course of a patient with rising ACTH levels after BLA for presumed Author Block: Serena Mistry - Stony Brook University; CD. Although the diagnosis of Nelson syndrome was considered, he Deviani Umadat, Doctor of Osteopathic Medicine - co-author, was found 9 years after BLA to have an ectopic ACTH secreting Endocrinology, Stony Brook; Carolyn Maxwell, MD, ECNU - co- bronchial carcinoid tumor as a cause for the elevated ACTH levels. author, Endocrinology, Stony Brook Case Description: A 35 year old male was evaluated at another Introduction: Pulmonary spindle cell carcinoma (PSCC), a type of institution in 2010 after he presented with weight gain, new onset non-small cell lung cancer (NSCLC), is a rare subset of pulmonary hypertension, muscle weakness with multiple falls, depression, ir- sarcomatoid carcinoma representing 0.2% to 0.3% of all lung can- ritability and emotional lability. He was diagnosed with CD and was cers. Resectable NSCLC with isolated adrenal masses is rare with an referred to a university center where he underwent trans-sphe- incidence rate of about 1 to 8%, and less than 3% of patients with noidal pituitary surgery in May 2011. An adenoma was seen on lung cancer have bilateral adrenal metastasis. We present a case not frozen section but not on the final pathology. He developed tran- previously reported in literature of PSCC with bilateral adrenal sient symptoms of adrenal insufficiency on the second post-oper- gland metastasis without endocrinopathies. ative day. Because of persistent hypercortisolism he underwent BLA Case Description: A 72 year old male who was a former smoker in November 2011. presented with hemoptysis, and was found to have a 5.4 cm right We started following him in 2012 and signs of hypercortisolism middle lobe lung mass. Biopsy showed a high-grade malignant gradually resolved. He appeared euadrenal on hydrocortisone 10 histiocytic and sarcomatoid neoplasm. He was treated with Car- mg am, 5 mg 12 noon and 5 mg 6 pm and fludrocortisone 0.05 mg boplatin and Etoposide, and lobectomy was performed. Pathology daily. ACTH levels increased from 54 pg/ml (6-50) in 2012 to 1024 revealed a 7.5 cm malignant spindle cell neoplasm. Four months pg/ml in 2019. He had no hyperpigmentation and MRI of the pi- later, a positron emission tomography (PET) scan showed bilateral tuitary from 2014-20 did not show a pituitary mass. During an adrenal masses which had not been present on initial imaging, with evaluation for COVID-19 infection in May 2020, a chest x ray no other sites of metastasis nor activity in the lungs. Right and left revealed a right lower lobe lung mass measuring 3.3 x 2.0 cm. He adrenal masses measured 6.1 x 5.5 cm (standard uptake value underwent right lower lobe lung lobectomy in July 2020 and pa- (SUV) fluorodeoxyglucose (FDG) avidity 91.5) and 4.3 x 1.8 cm (SUV thology revealed a carcinoid tumor-spindle cell pattern which FDG avidity 76.7), respectively. The patient lacked cushingoid stained strongly positive for ACTH and weakly positive for chro- appearance and clinical signs of adrenal insufficiency or pheo- mogranin. ACTH levels after the surgery decreased to 16.3 pg/ml. chromocytoma. Morning cortisol and plasma fractionated meta- Discussion: Some authors have suggested that Nelson syndrome be nephrine levels were within normal limits. Bilateral adrenalectomy considered in patients with BLA who have one of the following: an was performed, with pathology showing high grade neoplasm, expanding pituitary mass or ACTH levels >500 p/ml at 3 different similar to initial lung pathology. The patient was discharged on oral time points after surgery. This case highlights the need to consider hydrocortisone and fludrocortisone daily. ectopic ACTH syndrome as another cause for rising ACTH levels Discussion: Physicians should be aware of PSCC due to its rapid growth after BLA for CD especially in those patients who are not found to rate and metastasis, as bilateral adrenal metastatic lesions were found have a discreet adenoma after pituitary surgery. in our patient in less than 6 months from primary PSCC diagnosis. https://doi.org/10.1016/j.eprac.2021.04.482 Patients with adrenal metastases may have activation of the hy- pothalamic-pituitary-adrenal axis with elevated cortisol levels. We determined that biochemical evaluation was necessary to determine Abstract #999305 functionality of the adrenal masses prior to surgical intervention to exclude pheochromocytoma. We also evaluated to determine Reasons for Hospitalizations and Outcomes of Adults whether there was evidence of suppression of normal hormonal with Adrenal Insufficiency: A Nationwide Analysis secretion to rule out adrenal insufficiency. No evidence of associated endocrinopathies were found in our patient despite the large size of metastasis. This was interesting as adrenal insufficiency is typically Author Block: HAFEEZ SHAKA - John, H. Stroger Jr. Hospital of Cook seen in patients with bilateral metastases with destruction of over County; Emmanuel Akuna, MD - co-author, John H Stroger Jr 90% of the functional cortex. In our patient case, the treatment choice Hospital of Cook County; Iriagbonse Asemota, MD - co-author, was surgical resection given isolated adrenal metastatic disease, and John H Stroger Jr Hospital of Cook County; Ehizogie Edigin, MD - therefore postoperative steroid treatment was needed. co-author, John H. Stroger, Jr. Hospital of Cook County; Precious O. Eseaton, MBBS - co-author, University of Benin School https://doi.org/10.1016/j.eprac.2021.04.481 of Medicine; Pius E. Ojemolon, MD - co-author, Saint George's University Grenada Abstract #998862 Objective: Cardiovascular conditions and infections are the most Ectopic ACTH by Carcinoid Tumor Mimicking Nelson common reasons for hospitalizations in the US. However, chronic Syndrome in a Patient with Bilateral Adrenalectomy medical comorbidities are an important factor in determining the need for admission, risk stratification and management planning for these conditions. Adrenal insufficiency (AI) is the clinical Author Block: Mohammad Uzair Abdul Rauf - Lehigh Valley Health manifestation of deficient production or action of glucocorticoids, Network; Marc A. Vengrove, DO, FACP - co-author, Endocrinology, with or without deficiency also in mineralocorticoids and adrenal Lehigh Valley Health Network androgens. It is a life-threatening disorder that can result from

S5 Adrenal Disorders Endocrine Practice 27 (2021) S1eS23 primary adrenal failure or secondary adrenal disease due to mcg/dl. 24-hour urine free cortisol (UFC), however, was normal at impairment of the hypothalamic-pituitary axis. This study aimed to 35 mcg/24h. 24-hour urine metanephrine and aldosterone/renin identify the burden of AI in inpatient admissions. ratio were normal. DHEA-S was less than 30 mcg/dl. On subsequent Methods: Data was obtained from the Nationwide Inpatient Sample outpatient endocrinology visit, an MRI brain ruled out a pituitary (NIS) for 2018. The NIS contains hospital discharge information mass. The patient did exhibit several features of CS including estimating yearly US hospitalizations. All patients with any truncal obesity, uncontrolled DM and HTN, however had no other discharge diagnosis of AI were included. Hospitalizations in pa- physical signs including proximal muscle wasting, abdominal tients less than 18 years were excluded. The principal diagnosis striae, bruising, dorsocervical hump or supraclavicular fat pad. A among hospitalizations with AI, determined to be the reason for UFC was repeated twice and found to be normal at 7.30 mcg/24h admission was identified and represented as a proportion of the and 28 mcg/24h. He was subsequently noted to have worsening DM total AI hospitalizations. The inpatient mortality rate, mean length control with insulin requirements increasing from 20 units to 110 of hospital stay (LOS) and cost of hospitalization (COH) were units over a year with worsening HTN. A repeat 1 mg DST again calculated. showed unsuppressed cortisol at 17.3mcg/dl with baseline ACTH of Results: There were about 135,635 hospitalizations involving pa- 14 pg/ml. Patient was admitted a week later for heart failure tients with AI, with a prevalence of approximately 53 per 100,000 exacerbation and unfortunately suffered a cardiac arrest and passed adults in the US. Majority of hospitalizations were in females away. Autopsy revealed massive macronodular cortical hypertro- (56.4%) with a mean age of 61.4 (95% CI: 61.0 e 61.4) years. phy of bilateral adrenal glands with histology showing macro- Caucasians made of 72% of AI hospitalizations. The inpatient mor- nodular adrenal cortical hyperplasia. tality rate was 5.9% for all AI hospitalizations. The mean LOS was 8.3 Discussion: PBMAH is a rare diagnosis with a mean time to diag- (95% CI: 8.1 e 8.6) days, and the mean COH was $25,500 (95% CI: nosis of approximately eight years even when found to have overt 24,350 e 26,649). The top reasons for admission were sepsis from CS. Plasma ACTH is usually suppressed and the 1-mg DST fails to unspecified organism (14.1%), unspecified AI (3.0%), unspecified suppress cortisol production. However, in recent years, the occur- acute renal failure (2.4%), Addisonian crisis (2.0%), unspecified rence of subclinical CS defined as the absence of clinical signs of CS, pneumonia (1.6%), hypo-osmolality and hyponatremia (1.4%) hy- slightly elevated midnight plasma or salivary cortisol, subnormal pertensive heart disease with heart failure (1.2%), sepsis due to suppression following the 1-mg overnight DST, partially sup- Escherichia coli (1.2%). pressed ACTH, and a normal 24-hour UFC has been shown to occur Discussion/Conclusion: Sepsis is the major reason for hospitaliza- with PBMAH. This report illustrates that a high index of suspicion is tion in patients with AI. However, a proportion of patients with AI thus required when evaluating these patients. Making an early present with Addisonian crisis which is an endocrinological diagnosis is important as this can be treated either with pharma- emergency. Overall, there is high inpatient mortality in patients cological therapy if aberrant receptors are identified or bilateral/ with AI. Efforts to promote infection prevention and control such as unilateral adrenalectomy. vaccination against pneumonia should be encouraged to prevent https://doi.org/10.1016/j.eprac.2021.04.484 admissions in this population. AI hospitalization is also associated with significant healthcare utilization as shown by the cost and duration of hospital stay. Abstract #1000492 https://doi.org/10.1016/j.eprac.2021.04.483 Attempting to Define “Normal”: Variability in Catecholamine Levels from Adrenal Venous Sampling Abstract #999654 in Patients with Primary Aldosteronism

The Clinical Conundrum of Cushing's - A Case of Primary Bilateral Macronodular Adrenal Hyperplasia Author Block: Olivia DeLozier - Medical College of Wisconsin; Sophie Y. Dream, MD - Co-author, Surgery, Medical College of Wisconsin; James Findling, MD - Co-author, Endocrinology, Author Block: Aditi Thakkar - UCI Health; Constance Chen, MD - Medical College of Wisconsin; William Rilling, MD - Co-author, co-author, Endocrinology, UCI Radiology, Medical College of Wisconsin; Srividya Kidambi, MD - Co-author, Endocrinology, Medical College of Wisconsin; Introduction: Primary bilateral macronodular adrenal hyperplasia Steven B. Magill, MD - Co-author, Endocrinology, Medical College (PBMAH) is a rare cause of Cushing's syndrome (CS), representing of Wisconsin; Douglas B. Evans, MD - Co-author, Surgery, Medical less than 2% of all cases. It is characterized by enlarged adrenal College of Wisconsin; Tracy S. Wang, MD - Senior Author, Surgery, glands containing multiple non-pigmented nodules, usually more Medical College of Wisconsin than 10 mm. Most patients with PBMAH have no or mild clinical features of CS with indolent progression to overt CS. Here, we Objective: Adrenal venous sampling (AVS) is performed to differ- present a case of PBMAH, describing the difficulty in reaching the entiate between unilateral and bilateral disease in patients with diagnosis. primary aldosteronism (PA). It is unknown if AVS would be helpful Case Description: A 63-year-old male with a past medical history of in determining the laterality of a pheochromocytoma in patients morbid obesity, HTN, T2DM, atrial fibrillation, coronary artery with bilateral adrenal masses. The objective of this study was to disease, diastolic heart failure was admitted to the hospital with analyze adrenal vein (AV) epinephrine and norepinephrine levels in obstructive uropathy. CT abdomen showed bilateral adrenal non-pheochromocytoma patients to determine the range of normal enlargement with lobulated low density lesions, likely benign. An 8 values. am cortisol was found to be high at 24.5 mcg/dl. ACTH was within Methods: We reviewed all patients who underwent AVS for PA low to normal range at 7 pg/ml. 1 mg dexamethasone suppression between 2009-2019 at a single institution. Pheochromocytoma was test (DST) showed an unsuppressed am cortisol of 17.4 mcg/dl. 8 mg excluded. Aldosterone, cortisol, epinephrine, and norepinephrine DST also showed subnormal suppression with am cortisol of 12.9 levels were obtained from the inferior vena cava (IVC), left adrenal

S6 Adrenal Disorders Endocrine Practice 27 (2021) S1eS23 vein (LAV), and right adrenal vein (RAV); occasionally, >1AV respectively). Twenty-four hour urine cortisol was elevated to 120 sample was obtained. Successful cannulation of the AV was defined mcg/day (n < 45 mcg/day). Serum aldosterone was low (< 3.0 ng/ by an AV/IVC cortisol ratio of 3:1. All plasma measurements are dL, n 4-31 ng/dL). Dehydroepiandrosterone Sulfate (DHEA-S) level median values in pg/mL with interquartile ranges. Normal plasma was normal (39 mg, n 10-90mg). She denied typical symptoms of levels for epinephrine and norepinephrine are < 62 pg/mL and < pheochromocytoma prior to admission. She was discharged from 874 pg/mL, respectively. the hospital on alpha-blockade with doxazosin and a total daily Results: Successful AVS was completed in 174 patients. Data were dose of 85 units of basal-bolus insulin. On follow up two weeks obtained from 395 adrenal veins (178 LAV, 289 RAV). Median later, she reported that she was never able to fill her prescription for epinephrine levels were: IVC ¼ 19 (14, 33), LAV ¼ 3,721 (1,711, insulin due to an insurance issue. Despite not being on insulin, she 6,806), and RAV ¼ 2110 (408, 4,586). Median norepinephrine continued to check her blood glucose at home with values of 160- levels were: IVC ¼ 335 (188, 477), LAV ¼ 1,382 (844, 2,000), and 200 mg/dL. She was started on metformin at this time. Repeat 24- RAV ¼ 870 (432, 1,714). There was no difference between LAV and hour urine cortisol was normal at 6.5 mcg/day. Twenty-four hour RAV epinephrine levels (p¼0.402) or LAV and RAV norepineph- urine metanephrines and normetanephrines were elevated (1,376 rine (p¼0.533) levels. Peripherally obtained plasma epinephrine mcg/day, n 36-229 mcg/day and 678 mcg/day, n 95-650 mcg/day levels were available for 14 patients and were weakly correlated respectively). After appropriate alpha and beta blockade, she un- with IVC epinephrine levels: 31 (20, 48) vs 21 (15, 30), r¼0.213, derwent left adrenalectomy three months following diagnosis. p¼0.113. Peripherally obtained plasma norepinephrine levels Despite no escalation in her glycemic control regimen, her hemo- were available for 5 patients and were strongly correlated with globin A1c on admission for surgery was 7.5%. She had an un- IVC norepinephrine levels: 455 (246, 624) vs 369 (218, 659), complicated post-operative course with neither hypoglycemia nor r¼0.942, p¼0.096. hyperglycemia. Pathology revealed a 3.5cm pheochromocytoma Discussion/Conclusion: This extensive experience with AVS confined to the adrenal gland. Hemoglobin A1c measured five demonstrated that while IVC catecholamine levels were similar to months following surgery was 5.9%. peripheral levels, there was a wide range of adrenal vein cate- Discussion: Diabetes can be a presenting feature of pheochromo- cholamine levels in patients without pheochromocytoma. The cytoma. Catecholamines increase blood glucose levels via its action range is far too broad to employ AVS in determining laterality of of binding to alpha and beta adrenergic receptors in the pancreas, disease in patients with pheochromocytoma and bilateral adrenal liver and adipose tissue. Primarily epinephrine secreting tumors, as nodules. our patient has, may cause more hyperglycemia via its preferential binding to beta-2 receptors on the hepatic cells causing increased https://doi.org/10.1016/j.eprac.2021.04.485 gluconeogenesis and glycogenolysis. Glycemic control has been shown to improve with appropriate alpha and beta blockade in Abstract #1000846 some studies as it did in our patient, even prior to surgery. Pheo- chromocytomas rarely present with diabetic ketoacidosis but it can Pheochromocytoma Presenting as Diabetic Ketoacidosis be seen due to the actions of catecholamines on the adrenergic receptors.

https://doi.org/10.1016/j.eprac.2021.04.486 Author Block: Joy Wortham - University of Texas Health Sciences Center - San Antonio; Brenda Sandoval, MD - co-author, University of Texas Health Sciences Center - San Antonio; Maria Felix, MD - Abstract #1000926 co-author, University of Texas Health Sciences Center - San Antonio; Emad Ali, MD - co-author, University of Texas Health Progression of Adrenal Insufficiency with an Immune Sciences Center - San Antonio; Gustavo Armaiz Pena, MD - co- Checkpoint Inhibitor and Adrenal Metastases author, University of Texas Health Sciences Center - San Antonio; Maureen Koops, MD - co-author, University of Texas Health Sciences Center - San Antonio; Jan M. Bruder, MD - co-author, Author Block: Elizabeth Paul - New York Presbyterian Brooklyn University of Texas Health Sciences Center - San Antonio Methodist Hospital; Edmund Giegerich, MD, FACE - co-author, Department of Endocrinology, New York Presbyterian Brooklyn Introduction: Hypertension and tachycardia are the most Methodist Hospital frequently described clinical signs of pheochromocytoma. Hyper- glycemia is also highly prevalent in pheochromocytoma but less Introduction: Endocrinopathies are common immune-related often discussed. Here we present a case of pheochromocytoma adverse event (IRAE) of cancer therapy with immune checkpoint causing severe hyperglycemia resulting in diabetic ketoacidosis in a inhibitors. Pembrolizumab has been used in the treatment of patient without a previous diagnosis of diabetes. NSCLC. We report a case of adrenal insufficiency (AI) in a patient Case Description: A 77-year-old woman recently diagnosed with with a missed opportunity for diagnosis and unusual course of prediabetes presented to the emergency department with confu- illness. sion and abdominal pain and found to be in diabetic ketoacidosis. Case Description: 61 year old male with Stage 4 NSCLC (known On admission, she was notably hypertensive to 184/114 and adrenal metastases) on pembrolizumab presented for pain control tachycardic to 124 in sinus rhythm. Hemoglobin A1c on admission and initiation of chemotherapy. He was hyponatremic with normal was 12.0%. Abdominal CT scan done on admission for abdominal potassium levels; attributed to SIADH. He had a “normal” AM pain found an incidental left adrenal mass. Dedicated adrenal CT Cortisol level. He remained hyponatremic with fluid restriction. scan demonstrated a 3.6 x 2.8 x 3.6 cm left adrenal mass with Admission 2 was for NSTEMI with refractory hypotension on heterogenous enhancement with unenhanced density of 40 vasopressor therapy. He had a normal ejection fraction. With a low Hounsfield units and absolute washout of 50%. Serum meta- cortisol level, he was treated for AI crisis. The hypotension and nephrines and normetanephrine levels were significantly elevated hyponatremia resolved. The low cortisol and ACTH levels with an (10.98 nmol/L, n < 0.49 nmol/L and 4.78 nmol/L, n < 0.89 nmol/L MRI pituitary negative for tumor led to a diagnosis of central (2⁰)AI

S7 Adrenal Disorders Endocrine Practice 27 (2021) S1eS23 hypophysitis due to pembrolizumab. He was given replacement negative. DOTATE scan did not demonstrate any evidence of uptake. hydrocortisone therapy at discharge. His primary adrenal insufficiency was treated with hydrocortisone On later admissions, he presented for vomiting and abdominal and fludrocortisone. An adrenal biopsy was not performed due to pain with hyperkalemia and hyponatremia. He was started on invasiveness after discussing it with the multidisciplinary care stress dose steroids and fludrocortisone was added to his hydro- team. He was started on Methotrexate as steroid sparing agent for cortisone therapy. He had an esophageal stricture from his NSCLC. his sarcoidosis. The aldosterone level was undetectable with adrenal CT scan Discussion: After an extensive investigation for the causes of this showing bilateral doubling of adrenal metastases diameter (5.5 patient’s adrenal insufficiency, involvement by sarcoid appeared to cm). This confirmed a diagnosis of 1⁰ AI along with 2⁰ AI from drug be the most probable etiology. CT demonstrated enlargement of therapy. bilateral adrenal glands with diffuse sarcoid involvement with Discussion: In patients with cancer, AI may go unrecognized typical imaging characteristics and pattern. Histological confirma- because the symptoms and laboratory abnormalities are nonspe- tion of sarcoid was obtained via endoscopy and gastric sampling. cific and attributed to the underlying malignancy or its therapy. Autoimmune adrenalitis seemed unlikely considering his lack of Severe hyponatremia can occur as in our patient with central (2⁰)AI 21-hydroxylase antibodies which has a high sensitivity for auto- in the absence of hypovolemia and dehydration. The cortisol level immune adrenalitis. Adrenal gland involvement of a neuroendo- interpretation was incomplete at initial presentation. crine tumor seemed improbable due to lack of uptake DOTATE An IRAE of checkpoint inhibitors is autoimmune hypophysitis imaging. Bilateral adrenal gland involvement by sarcoidosis with with 2⁰ AI. Hypophysitis induced by anti-PD1 monotherapy (pem- resultant adrenal insufficiency has been described but is excep- brolizumab) is rare (1%). Our patient at initial diagnosis had evi- tionally rare. dence of 2⁰ AI which was successfully recognized and treated on his https://doi.org/10.1016/j.eprac.2021.04.488 2nd admission with adrenal crisis. Lung cancers metastasize (28-42%) to the adrenals and 1⁰AI is fi very uncommon as 90% of the glands must be destroyed. In the nal Abstract #1001397 stages of our patient’s treatment he developed increasing size of his adrenal metastases with new aldosterone deficiency resulting in Adrenal Insufficiency Related to Primary Adrenal both 1⁰ and 2⁰ AI from adrenal metastases and pembrolizumab drug Lymphoma therapy. https://doi.org/10.1016/j.eprac.2021.04.487 Author Block: Miya McKnight - Geisinger Medical Center; Aparna Baburaj, MD - Co-author, internal medicine, Geisinger; Abstract #1001107 Jodie Reider, M.D. - Co-author, Endocrinology, Geisinger Medical Center A Case of Adrenal Insufficiency due to Diffuse Sarcoid Introduction: Primary adrenal insufficiency (AI) is characterized by insufficient cortisol and aldosterone levels due to gland destruc- Author Block: Sujata Panthi, MBBS - Primary author, Kansas tion. Fatigue and weight loss are common symptoms of adrenal University Medical Center; Michael Holyoak, DO - Co-author, St. insufficiency that may be overlooked in patients with malignancy, Luke's Health System; Mariana Garcia-Touza, DO - Co-author, leading to a delay in diagnosis. We present a case of primary ad- kansas City VA medical center renal insufficiency caused by bilateral adrenal diffuse large B cell lymphoma in a 76-year-old male. Introduction: Sarcoidosis is a multisystem granulomatous disease Case Description: A 76-year-old male with a history of hyperten- that can manifest with various symptoms. We describe a case of sion presented to an outpatient clinic complaining of recent onset stage 4 sarcoidosis leading to primary adrenal insufficiency. unintentional 22-pound weight loss, early satiety, fatigue, and hy- Case Description: A 50-year-old man with a past medical history of potension. A CT scan revealed bilateral adrenal masses (right: 2.5 x sarcoidosis, anxiety, hypogonadism, hypertension, and asthma was 5.0 x 4.0 cm; left: 7.4 x 4.0 x 7.0 cm), with < 50% contrast washout at admitted to the hospital due to symptoms of nausea and vomiting 10 minutes, concerning for malignancy. Plasma fractionated met- present for several weeks. He had used steroids intermittently over anephrines were normal. Biopsy of the left adrenal mass showed the past five years as a treatment for sarcoidosis. but had not used diffuse large B cell lymphoma. Additional laboratory testing any steroids in the preceding 18 months. A review of systems was revealed low 8am cortisol level of 6.7 ug/dL, mild hyponatremia positive for decreased appetite and an unintentional weight loss of 128-133mmol/L (ref: 135-146 mmol/L), and high ACTH 151pg/ml 22.7 kg. Physical exam was notable for orthostatic hypotension and (ref: 0-46 pg/mL). Plasma renin activity was elevated at 6.66ng/ml/ hyperpigmentation of his skin. Laboratory tests revealed hypona- h (ref: 0.25-5.82 ng/mLh) with borderline low aldosterone 3ng/dl tremia and random cortisol of 0.8 (mg/dL). An ACTH stimulation test (ref: 3-16 ng/dL). He was diagnosed with primary AI related to was flat. ACTH was elevated at 664 mg/dL. ACE level 321 U/L (RR 9- gland destruction from bilateral primary adrenal lymphoma. He 67). Adrenal antibodies were undetectable. CT chest demonstrated was treated with hydrocortisone and fludrocortisone, resulting in innumerable pulmonary nodules with associated volume loss and significant clinical improvement in energy, appetite, weight, and bilateral hilar adenopathy compatible with diffuse, progressive blood pressure. He remains stable from an endocrinological sarcoid. CT abdomen showed significant bilateral adrenal gland perspective while undergoing chemotherapy. enlargement, splenomegaly, and adenopathy. MRI of pituitary Discussion: While solid tumors frequently metastasize to the ad- showed a 0.2 x 0.3 x 0.3 cm microadenoma. PET scan exhibited renal glands, primary adrenal lymphoma (PAL) is uncommon, with multiple areas of increased uptake including the right adrenal less than 200 cases reported in the current literature. PAL primarily gland. Upper endoscopy found both gastric sarcoidosis present on affects elderly males and presents with large bilateral adrenal the antrum and gastric body and a well-differentiated neuroen- masses. Though AI related to adrenal metastasis from other solid docrine tumor grade 1. Genetic screening for MEN syndromes was tumors occurs rarely, AI is common in PAL and associated with poor

S8 Adrenal Disorders Endocrine Practice 27 (2021) S1eS23 prognosis. This likely is related to tumor aggressiveness and size. evaluations. Currently, these recommendations are often not Most studies report that nearly 90% of the glands must be destroyed followed. before AI develops. The diagnosis of AI in patients with adrenal When combined with common manifestations associated with masses is frequently missed due to its rarity and the overlap of hypercortisolism (in this case, diabetes), the use of EMR can in- symptoms with those of malignancy. Patients with undiagnosed AI crease the detection rate of autonomous hypercortisolism in pa- are at high risk for developing adrenal crisis under stress, such as tients with adrenal adenomas. The use of EMR in this study resulted during treatment with chemotherapy. Clinicians should maintain a in the diagnosis of 13 of 30 patients (43.3%) with potentially high level of clinical suspicion for AI in patients presenting with treatable cortisol-secreting adrenal adenoma(s). large bilateral adrenal masses, particularly PAL, as early recognition https://doi.org/10.1016/j.eprac.2021.04.490 and treatment leads to improved quality of life and decreased risk of life-threatening adrenal crisis. https://doi.org/10.1016/j.eprac.2021.04.489 Abstract #1002270

A Rare Case of Pheochromocytoma Crisis Presenting Abstract #1001858 with NSTEMI

Prevalence of Hypercortisolism in Patients with Adrenal Adenoma(s) and Type 2 Diabetes Mellitus: Author Block: Khin Zin - Jersey Shore University Medical Center; Findings From EMR Search Katherine Hu, DO - co-author, Endocrinology, Jersey Shore University Medical Center; Monika Akula, MD - co-author, Endocrinology, Jersey Shore University Medical Center; Author Block: Issac Sachmechi - Icahn School of Medicine at Jennifer Cheng, DO - co-author, Endocrinology, Jersey Shore Mount Sinai j NYC Health + Hospitals/ Queens; Sanna Salam, MD - University Medical Center; Soemiwati Holland, MD - co-author, Co-author, Mount Sinai Services, NYC Health + Hospitals; Endocrinology, Jersey Shore University Medical Center; Muhammad Umair, MD - Co-author, Icahn School of Medicine at Raquel Ong, MD - co-author, Endocrinology, Jersey Shore Mount Sinai, NYC Health + Hospital; Kathleen Wade Tarnowski, University Medical Center M.s - Co-author, Corcept Therapeutics Introduction: Pheochromocytoma crisis is a rare life-threatening Objective: To examine the prevalence of hypercortisolism in pa- endocrine emergency that may present spontaneously or be tients with adrenal adenoma(s) and Type 2 Diabetes Mellitus unmasked by medications that cause catecholamine release. We (T2DM). present a case of pheochromocytoma crisis worsened by beta- Methods: A query of the electronic medical records (EMR) from blocker therapy for non-ST-elevation myocardial infarction 2014 to 2020 at NYC Health + Hospitals jQueens Diabetes was (NSTEMI). performed for patients >18 years old with radiologically confirmed Case Description: A 45-year-old woman with uncontrolled hyper- adrenal adenoma(s) and a diagnosis of T2DM. tension (HTN) presented to the ED of an outside hospital with Identified patients were required to have an evaluation for headaches, dizziness, nausea, vomiting, palpitations, and abdom- hypercortisolism. If such assessment was not available in the pa- inal pain for 3 days. She was treated with labetalol and heparin drip tient’s chart, the 1-mg DST and ACTH tests were ordered. for hypertensive emergency and NSTEMI in the ICU, but her blood Additionally, all patients were required to have two CT scans one pressure (BP) worsened. CT urogram revealed a 6.1 x 5.3 cm right year apart to evaluate the change in adenoma size. adrenal mass with 41 Hounsfield units (HU). She was transferred to Results: Thirty patients (mean age 64.9 yrs., 60% female) with an our hospital for clinical suspicion of pheochromocytoma. She was adrenal mass (range: 1.0 e 5.1 cm) and T2DM (mean HbA1c: 7.3%) lethargic upon arrival but had an otherwise unremarkable physical were consented and analyzed. exam. Her BP was challenging to control as her systolic BPs oscil- Eight patients had the required CT scans and evaluations for lated between 110-230 mmHg and her diastolic BPs were 60-140 hypercortisolism. Twenty-two patients required additional mmHg. Biochemical workup revealed significant elevations in biochemical testing and/or repeat imaging (CT scans > 12 months plasma metanephrines >50 nmol/L (< 0.49 nmol/L) and 24-hour prior to study visit). urine metanephrines and catecholamines were all greater than 3 Thirteen patients (13/30, 43%) had an abnormal 1-mg DST value times the upper limit of normal up to 10 times greater than the 1.8 mg/dL (range: 1.9mg/dL - 8mg/dL). upper limit of normal. CT scan of abdomen and pelvis with contrast Eight patients had validated ACTH results (range: 1.6-15.1 pg/mL) showed a 6.1 x 6.6 x 7.2 cm right adrenal mass with central necrosis that supported the adrenal etiology. In the other 5 patients, a without lymphadenopathy, unenhanced attenuation of 34 HU, and different assay was used to measure ACTH levels. All 5 patients had delayed 43% absolute contrast washout. She was given prazosin but ACTH values above the normal range. switched to doxazosin for a longer duration of action and proven The adrenal nodule size for the 13 patients ranged from 1 cm to efficacy in the perioperative management of pheochromocytoma 3.4 cm and remained stable over the observation period. since phenoxybenzamine was unavailable. Doxazosin was titrated Greater amounts of antihypertensive and diabetes medication up to a maximum of 32 mg daily with still uncontrolled BP. A high adjustments were in use in patients with a DST 1.8ug/dL (N¼13) sodium diet was started to prevent orthostatic hypotension. BP was compared to patients with a DST< 1.8ug/dL (N¼17). further stabilized by nicardipine drip then finally the addition of Discussion/Conclusion: Broad use and technical advances in labetalol prior to undergoing right adrenalectomy. Pathology abdominal imaging procedures have led to the discovery of un- showed pheochromocytoma with malignant potential due to Ad- suspected adrenal tumors at an increasing frequency. These adrenal renal Gland Scaled Score (PASS score) of 5 and tumor invasion into “incidentalomas” have been increasingly shown to be associated the adjacent adrenocortical tissue and its capsule. The patient had with clear clinical problems, leading to multiple guidelines normal postoperative BP and she was discharged home without recommending hormonal hypersecretion and/or malignancy anti-hypertensive medications.

S9 Adrenal Disorders Endocrine Practice 27 (2021) S1eS23

Discussion: Pheochromocytoma is extremely rare and challenging Patients were more likely to report a higher anxiety score (8) if to manage, representing only 0.1-1% of all secondary HTN. Clini- they had SAI or GIAI (OR 2.6, CI 95% 1.4-4.7), or found managing AI cians should have a high index of suspicion in a patient with un- challenging during the pandemic (OR 3.1, CI 95% 1.7-5.9). Younger controlled HTN and classic spells. This case highlights the age (OR 3.3, CI 95% 1.8-6.2) and higher difficulty managing AI (OR importance of avoiding beta-blockade without effective alpha 3.5, CI 95% 1.7-7.0) were associated with a higher stress score (15). blockade which could worsen the hypertensive crisis and precipi- Discussion/Conclusion: A third of patients with AI reported tate a fatal pheochromocytoma crisis. increasing challenges in AI management during the pandemic, especially younger patients, women, and those experiencing poor https://doi.org/10.1016/j.eprac.2021.04.491 access to healthcare, or with higher financial burden. Challenges with AI self-management in turn were associated with higher Abstract #1002271 anxiety and stress. Our study calls for a more robust education, easily accessible healthcare, and societal support, especially for Self-Management of Adrenal Insufficiency during the younger patients, women, and those with SAI or GIAI. COVID-19 Pandemic: A Survey Study from Two Tertiary https://doi.org/10.1016/j.eprac.2021.04.492 Centers in the United States

Abstract #1002357 Author Block: Dingfeng Li, MD, MSc - Primary author and presenter, Division of Endocrinology, Diabetes, Metabolism and A Rare Case of Acute Liver Failure following the use of Nutrition, Mayo Clinic, Rochester, MN, United States; Mitotane for Treatment of Adrenal Cortical Carcinoma Malavika Suresh, MB, BCh, BAO - co-author, Division of Endocrinology, Diabetes, Metabolism and Nutrition, Mayo Clinic, Rochester, MN, United States; Tiffany Abbondanza, BA - co-author, Author Block: Jayachidambaram Ambalavanan - Medstar Center for Adrenal Disorders, Division of Endocrinology, Diabetes, Washington Hospital Center; Ansha Goel, MD - Co-Author, and Hypertension, Brigham and Women’s Hospital, Boston, MA, Endocrinology, MedStar Georgetown University Hospital; United States; Anand Vaidya, MD, MMSc - co-author, Center for Jacqueline Jonklaas, MD, PhD, MPH - Co-Author, Endocrinology, Adrenal Disorders, Division of Endocrinology, Diabetes, and Georgetown University Medical Center Hypertension, Brigham and Women’s Hospital, Boston, MA, United States; Irina Bancos, MD - co-author, Division of Endocrinology, Introduction: Adrenal Cortical Carcinoma (ACC) is a rare tumor Diabetes, Metabolism and Nutrition, Mayo Clinic, Rochester, MN, (annual incidence 0.7e2.0 cases/million). Surgery is first line United States treatment, with mitotane being the choice for adjuvant therapy after surgical resection. Hepatotoxicity from mitotane is usually Objective: The COVID-19 pandemic is a global health emergency mild, transient, and associated with transaminitis. Though there that has impacted patients and the healthcare environment. Our have been cases of acute liver injury reported in animals, there are objective was to determine the impact of the pandemic on self- no documented cases of mitotane-induced acute liver failure in management, quality of life (QoL), and psychosocial measures in humans. We present the first reported case of ACC, associated with patients with adrenal insufficiency (AI). acute liver failure due to mitotane use, requiring a liver transplant. Methods: Patients with AI enrolled in the prospective longitudinal Case Description: A 27-year-old female with type 1 diabetes mel- survey study at two tertiary centers were sent a questionnaire in litus, stage II ACC (T2,N0,M0) post adrenalectomy was started on December 2020, on self-management and challenges including job adjuvant mitotane at 0.5 g twice daily by her oncologist in May security, finance, and access to medical care during the pandemic. 2017, along with steroid replacement. The dose was increased to 1.5 Mental health was assessed with the Depression Anxiety Stress g twice daily in July 2017. Her mitotane level remained sub-thera- Scales-21; QoL was reassessed with the Short Form-36. Survey re- peutic at < 1 mg/L. In August 2017, she had severe transaminitis sponses were compared with the responses obtained prior to the without jaundice or signs of acute liver failure. Labs were negative pandemic in January 2020. for hepatitis A, B, C, HSV, CMV, EBV, ANA, anti-smooth muscle Results: Of 342 patients, 157 (46%) had primary AI, 109 (32%) had antibody, ceruloplasmin. Mitotane was thought to be the culprit secondary AI (SAI), and 76 (22%) had glucocorticoid induced AI and was discontinued. During follow-up she continued to have (GIAI). Among 151 (44%) patients tested for COVID-19, 6 (4%) were elevated LFTs, and a MRCP was performed which showed no biliary positive, and all had mild symptoms, did not need hospitalization, or gallbladder disease. She further underwent a liver biopsy which or develop adrenal crisis. When compared to survey responses demonstrated acute and chronic portal inflammation, prominent prior to the pandemic (N¼242), daily glucocorticoid dose and lobular chronic inflammation and scattered apoptotic bodies. In number of adrenal crises did not change. However, patients re- October 2017, she presented with complaints of abdominal pain ported a higher financial impact from AI (34% vs 23%, p¼.006) and and encephalopathy. She was found to be in acute liver failure with difficulty accessing medical care (31% vs 7%, p< .0001) during the AST/ALT 830/940 units/L, total bilirubin-25 mg/dL, INR of 2.9 and pandemic. In contrast, QoL scores were similar in most dimensions albumin of 2.3 g/dL. A CT abdomen demonstrated moderate ascites. and physical component summary score was higher (39.6 vs 38.6, Acute liver failure was thought to be due to mitotane and she p¼.04) during the pandemic. received an orthotopic liver transplant. A third of all patients reported self-management of AI to be Discussion: Though the precise mechanism of action of mitotane is more challenging during the pandemic. After adjusting for AI unknown, it is thought to act by inhibiting esterification of subtype, younger patients (OR 2.6, CI 95% 1.5-4.5), women (OR cholesterol-the precursor of steroid hormones. This inhibits the 3.3, CI 95% 1.8-6.3), those with poor access to healthcare (OR production of the excess hormones in the adrenal gland, causing 4.6, CI 95% 2.6-8.2), and those experiencing a higher financial symptomatic relief. It also interferes with cytochrome oxidase in impact (OR 2.2, CI 95% 1.2-4.0) reported greater challenges the mitochondria, thereby inhibiting its respiratory activity, and managing their AI. plays a role in inhibiting steroidogenesis as well. The mechanism of

S10 Adrenal Disorders Endocrine Practice 27 (2021) S1eS23 liver injury is thought to be due to direct hepatotoxicity from Discussion: Mifepristone is a progestin-antagonist which has been accumulation of its metabolites in the liver via microsomal en- shown to control high blood sugar in patients with Cushing syn- zymes 2C9. Though acute liver failure has been reported in dogs, drome who have Type II Diabetes Mellitus, have failed adrenal there have been no reported cases in humans. The occurrence of surgery or are not candidates for surgery. Macroprolactinoma ( >10 mitotane-induced acute liver failure without even reaching thera- mm) or symptomatic microprolactinoma would require medical or peutic levels was unique and unexpected. surgical intervention depending on the size and symptoms. Our patient refused surgical intervention on religious grounds, and was https://doi.org/10.1016/j.eprac.2021.04.493 managed medically with significant improvement in symptoms. Further reporting of similar cases is encouraged.

Abstract #1002373 https://doi.org/10.1016/j.eprac.2021.04.494

A Case of Cushing Syndrome and Pituitary Microadenoma Managed with Mifepristone Abstract #1002474

An Aldosterone-Producing Adrenal Adenoma (APA) Author Block: Hira Akhlaq - Army Medical College, NUST RWP Progressed to Aldosterone and Cortisol Co-producing Pakistan; Syed Wajih Rizvi, MD - Co-author, Endocrinology, Adrenal Adenoma (A/CPA): A Case Report R-Endocrinology; Muntazir Ali Sayed, MBBS - Co-author, Internal Medicine, R-Endocrinology; Sulafa Mahmoud, MBBS - Co-author, Internal Medicine, University of Gezira, Sudan; Shameela Begum, Author Block: John Ryan Viar - University of Santo Tomas Hospital, MD - Co-author, Internal Medicine, Shandan Institute of Medical Manila, Philippines; Maria Honolina S. Gomez - Fellow, Philippine Sciences; Sadiq Ali Sayed, MBBS - Co-author, Internal Medicine, College of Physicians; Fellow, Philippine Society of Endocrinology, National Pirogov Memorial Medical University, Vinnytsya, Ukraine Diabetes and Metabolism e Co-author, Department of Internal Medicine, Section of Endocrinology, Diabetes & Metabolism, Introduction: Cushing syndrome (hypercortisolism) is the University of Santo Tomas Hospital; University of Santo Tomas constellation of symptoms and signs caused by an excess of cortisol Faculty of Medicine and Surgery; Maria Faye Anne S. Gomez - hormone. It is an extremely complex hormonal condition that in- Fellow, Philippine College of Physicians; Fellow, Philippine Society volves many areas of the body. Common symptoms are thinning of of Nephrology e Co-author, Department of Internal Medicine, the skin, weakness, weight gain, bruising, hypertension, osteopo- Section of Nephrology, University of Santo Tomas Hospital; rosis, facial puffiness, and, in women, cessation of menstrual pe- University of Santo Tomas Faculty of Medicine and Surgery riods. The causes of Cushing syndrome include exogenous steroids, growth of the pituitary gland (Cushing disease), a benign or ma- Introduction: Functional adrenal tumors possess cellular markers lignant growth within the adrenal gland or ectopic production. Our that show potential development of aldosterone to aldosterone & objective is to report a case of Cushing Syndrome and Pituitary cortisol co-producing cells in enlarging adrenal tumors. This report Microadenoma in a patient who refused surgical intervention, and aims to describe the first reported case of a patient with an aldo- was managed medically. sterone-producing adrenal adenoma (APA) that progressed to Case Description: A 49-years-old Asian female with a past medical aldosterone & cortisol co-producing adrenal adenoma (A/CPA) after history of Diabetes Mellitus Type II, Essential Hypertension, and several years. Non-toxic Thyroid Nodule was referred to our Endocrinology clinic Case Description: We present the clinical, imaging, surgical & with complaints of irregular menstrual cycles associated with pathologic findings of the patient. We also discuss the relevant heavy bleeding lasting 7-8 days, and acne, hair loss, hirsutism and literature available. lack of concentration. The referring physician had an MRI Pituitary Discussion: Case Report. A 43-year-old woman presented with without contrast done on the patient that showed a 0.58 x 0.73 cm weakness, hypertension & hypokalemia. Work-up revealed an focal area of low signal intensity on T1 with corresponding high increased aldosterone concentration (PAC, 144.75 ng/dL), a low signal on T2 within the right side of the pituitary gland, consistent renin activity (PRA, 0.1 ng/ml/hr), a suppressed cortisol (0.33 ug/dl) with a microadenoma or cyst (given its extremely high signal on after 1-mg ODST & a 2.0 x 2.9 x 3.0 cm right adrenal mass on CT T2), with a left stalk deviation. Simultaneously, MRI Abdomen scan, which confirmed an aldosterone-producing adrenal adenoma without contrast showed Bilateral Adrenal Hyperplasia. Lab-results (APA). She refused adrenalectomy. Spironolactone 50 mgs BID for our patient showed elevated levels of 24-hr Cortisol at 78 mcg/ resulted to the control of the abnormalities. The patient however dL/24hr (0-50 mcg/dL/24hr), AM cortisol at 20.7 mcg/dL (2.3-19.4 was lost to follow-up. Eight years later, she presented with un- mcg/dL), serum prolactin at 58.5 ng/dL (4.8- 23.3 ng/dL), and controlled hypertension, hypokalemia & discriminatory signs DHEA-Sulfate at 318.7 mcg/dL (41.2-243.7 mcg/dL), but normal consistent with overt Cushing’s syndrome. A low normal ACTH levels of serum ACTH at 39.7 pg/mL (7.2-63.3 pg/mL). Treatment (5.40 pg/mL), & unsuppressed cortisol after low dose & high dose wise, we started her on Cabergoline 0.5mg (PO x twice a week) DST (19.18 ug/dL & 23.68 ug/dL after 1-mg ODST & 8-mg DST which was later discontinued after stabilization of prolactin levels respectively), supports an ACTH-independent cause. The increased (11.93 ng/dL) back within normal range. For her hyper- PAC (80 ng/dL) & low PRA (0.2 ng/ml/hr) on repeat work-up sug- androgenemia, we started on Spironolactone 50mg (PO x OD); later gested persistent primary aldosteronism. These findings, together increased gradually to 100mg (PO x OD). We also started Mife- with hypercortisolism & a progressive enlargement of the mass (4.3 pristone 300mg (PO x OD) to manage her Cushing’s Syndrome. Her x 2.8 x 3.8 cm) pointed to a possible aldosterone & cortisol co- serum potassium levels are being monitored regularly, recent one producing adrenal mass. After right adrenalectomy, serum cortisol at 4.3 mmol/L (3.6-5.2 mmol/L). Patient is tolerating her medica- & aldosterone levels were normalized. Histology showed large tions well, and her symptoms have improved significantly attrib- watery clear cells with rich lipid related possibly with aldosterone uted to this regimen. secretion; & acidophilic cells with poor lipid related possibly with

S11 Adrenal Disorders Endocrine Practice 27 (2021) S1eS23 cortisol secretion. She was discharged with glucocorticoids, which for BAH which warrants early adrenal axis testing due to high were eventually tapered & removed a few months later. suspicion for primary adrenal insufficiency. Conclusion. An APA with suppressed ODST can progress & https://doi.org/10.1016/j.eprac.2021.04.496 autonomously over-secrete cortisol to cause Cushing’s syndrome (A/CPA) despite MRA therapy. This is attributed to the increase in tumor size & insufficient mineralocorticoid blockade. Unilateral Abstract #1003033 adrenalectomy resolves both mineralocorticoid & glucocorticoid excess & should be the optimal treatment for APA > 1.5 cm to Oncocytic Adrenocortical Neoplasm a Case Report mitigate cardio-vascular & metabolic risks. https://doi.org/10.1016/j.eprac.2021.04.495 Author Block: Roberto Mitsui Akagi - Marshall University; Rodhan Khthir, MD - co-author, Sanford Health; Omolola Olajide, Abstract #1002785 MD - co-author, Endocrinology, Marshall University

A Case of Bilateral Adrenal Hemorrhage Associated Introduction: Adrenocortical oncocytic neoplasms are a histologic with COVID-19 subtype of adrenal neoplasms characterized by the presence of abundant granular eosinophilic cytoplasm due to accumulation of mitochondria. Oncocytic adrenocortical neoplasms are extremely Author Block: Radhika Jaiswal - Long Island Jewish Medical Center rare, typically non-functional and benign. There is a potential for / North Shore University Hospital; Rifka Schulman-Rosenbaum, malignancy in these tumors, hence the Lin-Weiss-Bisceglia criteria MD - Co-author, 1. Department of Internal Medicine, Division of should be applied to establish the diagnosis of malignant adreno- Endocrinology, Long Island Jewish Medical Center cortical oncocytoma. Case Description: A 68-year-old male with past medical history of Introduction: COVID-19 infection has been reported to be associ- hypertension, hyperlipidemia, and peptic ulcer disease presented ated with coagulopathy and thromboembolic events. There are a to the emergency room with low back pain. few case reports of bilateral adrenal hemorrhage (BAH) associated Patient denied symptoms of episodic palpitation, muscle weak- with COVID-19 in the existing English literature. Here we report, to ness, weight loss or easy bruising. No prior history of cancer the best of our knowledge, the first such case of BAH associated diagnosis. with COVID-19 in the US. CT scan revealed a 6 x 5.7 x 7 cm circumscribed right adrenal Case Description: A 71-year-old woman with history of hyperten- mass without definite local invasion. The mass density post sion, hyperlipidemia and type 2 diabetes mellitus presented with contrast was 97 Hounsfield Units. PET scan showed a hypermeta- abdominal pain, nausea, vomiting and generalized weakness that bolic large adrenal mass with no other hypermetabolic lesion. started 3 days prior to the admission. Initial vital signs showed Hormonal evaluation showed normal plasma Aldosterone level (6.9 temperature 98.1 oF, blood pressure 152/68 mm hg, heart rate 73 ng/dl), normal DHEAS level (126 mcg/dl), normal plasma Norme- beats/minute, respiratory rate 18 breaths/minute and saturation tanephrine (66 pg/ml) and normal plasma Metanephrine (12 pg/ 98% on room air. Physical exam was remarkable for abdominal ml). Cortisol level after 1 mg Dexamethasone suppression test was tenderness and bibasilar crackles. Lab testing showed thrombocy- 1ug/dl. topenia to 53 K/uL, hyponatremia to 125 mmol/L and abnormal Open right adrenalectomy was performed and a large mass with coagulation markers such as D-dimer, fibrinogen assay and pro- close effacement of the right inferior cava was found. thrombin time. A polymerase chain reaction test for COVID-19 was Pathology showed a yellow to pink-red adrenal gland measuring positive. The patient was noted to have BAH on CT abdomen. She 9.1 x 8.3 x 5.7 cm and weighted 200 grams. Serial sectioning was started on hydrocortisone and fludrocortisone for presumed through the lesion did not reveal any necrosis. The lesion appeared primary adrenal insufficiency. Initial hormonal testing done while to be somewhat encapsulated; however, there were areas where on steroids resulted as low serum adrenocorticotrophic hormone the capsule could not be grossly identified. The tumor was onco- (ACTH) of 3 (range 7.2-63.3) pg/ml, low serum dehydroandroster- cytic and showed very little proliferative activity both mitotic one of 29 (range 31-701) ng/dl and low normal serum cortisol of 10 counts as well as the Ki-67 immunostain. The final pathology report (range 8-19) ug/dl. During the hospital course, hydrocortisone was was oncocytic adrenocortical adenoma. Tumor assessment per Lin- replaced few times by courses of high dose dexamethasone due to Weiss-Bisceglia criteria was oncocytic adrenocortical adenoma worsening thrombocytopenia. Fludrocortisone dose was up titrated with uncertain malignant potential and close follow-up was rec- due to ongoing hyponatremia and onset of hyperkalemia. MRI ommended. 5 year survival for this category is 88%. In our patient, abdomen prior to discharge showed slight decrease in size of BAH. there was no evidence of recurrency in the CT scan 22 months after Patient remained hemodynamically stable and was discharged on surgery. glucocorticoid and mineralocorticoid replacement therapy with Discussion: Adrenocortical oncocytic neoplasms are a histologic outpatient endocrine follow up. diagnosis of tumors that are often identified incidentally. The ma- Discussion: BAH is extremely rare with reported incidence of 0.14- jority of these tumors are asymptomatic and nonfunctional. 1.8% based on postmortem studies. The exact mechanism for Lin-Weiss-Bisceglia criteria can be used to determine malignant occurrence of BAH in COVID-19 is unknown but seems to be likely potential, prognosis and survival rate. A recent systematic review of related to thrombotic event occurring at the level of the adrenal these tumors showed that the majority of adrenocortical oncocytic vein resulting in hemorrhage. CT imaging is the diagnostic modality neoplasm were either malignant or have malignant potential. In of choice. Acute adrenal insufficiency and rarely adrenal crisis can this systematic review a potential publication bias was reported occur due to bilateral adrenal necrosis caused by hemorrhage and since most of the studies included were single case report and can be life threatening if treatment with steroids is not initiated authors may have been more apt to publish on malignant cases. promptly. Patients with COVID-19 infection who present with Other systematic reviews showed that only 20% on adrenocortical abdominal pain, hyponatremia or hyperkalemia should be screened oncocytic tumor are potentially malignant.

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In conclusion this is a case of a oncocytic adrenocortical adenoma diseases. An example of this is illustrated in a patient presenting that was classified as borderline or with uncertain malignant po- with severe electrolyte imbalance, followed by challenging clinical tential found incidentally during a work-up for back pain. course and work up, with ultimate resolution. Case Description: Age 51: Hypertension 1999; well controlled on https://doi.org/10.1016/j.eprac.2021.04.497 Indapamide 2.5 mg Age 59: Severe Hyponatremia 119 Hypokalemia 2.8; during Abstract #1003305 hospital ICU admission for febrile viral respiratory infection, excessive tiredness and muscle cramps of 3 days duration; dis- Double Challenges in Clinical Endocrinology: charged without definitive diagnosis on oral Na and K supplements, Panhypopituitarism and delayed diagnosis of Primary Amlodipine 2.5 mg and Torsemide 10 mg. Aldosteronism Age 59: Ref to Samatvam Endocrinology Center: Persistent tiredness and weakness Panhypopituitarism Partial - due to Empty Sella [MRI], subse- Author Block: Jayalakshmi Thimmaiah, MBBS, DNB, FEDM, CDE - quently diagnosed during work up for Hyponatremia etc]. Endo- Primary Author, Endocrinology Diabetes Medicine, Samatvam crine evaluation: Post-menopausal: FSH 0.97 mIU/L, LH 1.06 mIU/L, Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital Prolactin 2.3 ng/ml, S Cortisol 0 Min 8.7 ug/dl, S Cortisol post 1 ug and Medical Center; Mandyam D. Chitra, MBBS, FEDM, CDE - Co- ACTH IV 15.9 ug/dl, T4 7.1 ug/dl, TSH 3.0 uIU/ml, Free T4 0.64 ng/dl author, Endocrinology Diabetes Medicine, Samatvam [0.7-1.8], HGH 60 min post L-DOPA 0.07 ng/ml, S Creatinine 0.97 Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital mg/dl. Started on L Thyroxine and Prednisolone replacement [over and Medical Center; siddhartha dinesha, MBBS, FEDM CDE - Co years several episodes needing IV stress hydrocortisone: related to Author, Endocrinology Diabetes Medicine, Samatvam infection, surgery]; on follow up renal functions and serum elec- Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital trolytes normal and Medical Center; Apoorva Govind, MBBS, FEDM CDE - Co Age 62: T2DM Author, Endocrinology Diabetes Medicine, Samatvam Age 66: Accelerated Hypertension BP 210 e 229 / 97 e 101 [An- Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital tihypertensives: metoprolol, telmisartan, clonidine doses upgra- and Medical Center; Prateek Hongal, MBBS, FEDM CDE - Co Author, ded; hydrochlorothiazide 12.5 mg added]; Ambulatory BP Endocrinology Diabetes Medicine, Samatvam Endocrinology monitoring: day 232/111, night 199/95 [maximum] Diabetes Center, Jnana Sanjeevini Diabetes Hospital and Medical Age 66: Work up for Resistant Hypertension: Center; Reshma Harsha, MBBS, FEDM, FACE - Co Author, - Renal artery doppler: No renal artery stenosis Endocrinology Diabetes Medicine, Samatvam Endocrinology - Polysomnography: No OSA Diabetes Center, Jnana Sanjeevini Diabetes Hospital and Medical - 24 hours catecholamines and metanehprines: Normal Center; Chandrika K, MBBS, FEDM, FACE - Co Author, - Aldosterone: Renin Ratio: High 75.2 [< 20] [Plasma Renin Ac- Endocrinology Diabetes Medicine, Samatvam Endocrinology tivity suppressed 0.29 ng/ml/hour, S Aldosterone 21.8 ng/dl] Diabetes Center, Jnana Sanjeevini Diabetes Hospital and Medical - Aldosterone Suppression Test- Oral Salt loading: Urine Aldo- Center; Sumathi K, MBBS, FEDM, FACE - Co Author, Endocrinology sterone 35.2 ug/24 hours, Na 2310 mg/24 hours Diabetes Medicine, Samatvam Endocrinology Diabetes Center, - MRI adrenals: "Normal" Jnana Sanjeevini Diabetes Hospital and Medical Center; Age 66: Primary Aldosteronism [PA]: Spironolactone started 25 Sharda Ardhanareeswaran, MBBS, MD, FEDM, FACE, FRCP - Co to 50 mg/day; in one-month BP dramatically "normalised" 114-120 Author, Endocrinology Diabetes Medicine, Samatvam / 70-75. S Na 137, K 4.8 [BP meds doses decreased] Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital Discussion: In retrospect, the diagnosis of Primary Aldoste- and Medical Center; Kavitha Muniraj, MBBS, FEDM, FACE - Co ronism was delayed in our patient for seven years. In the Author, Endocrinology Diabetes Medicine, Samatvam beginning [Age 59], the severe hypokalaemia was obviously due Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital to both diuretic and underlying undiagnosed Primary Aldoste- and Medical Center; Tejeswini Patil, MBBS, FEDM, FACE - Co ronism, and severe hyponatremia was due to both diuretic and Author, Endocrinology Diabetes Medicine, Samatvam undiagnosed Panhypopituitarism [despite underlying PA] e ie: Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital Dual etiology for both the potentially life threatening electrolyte and Medical Center; Lakshmi Reddy, MBBS, FEDM, FACE - Co abnormalities.

Author, Endocrinology Diabetes Medicine, Samatvam https://doi.org/10.1016/j.eprac.2021.04.498 Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital and Medical Center; Chandraprabha siddalingappa, MBBS, FEDM, FACE - Co Author, Endocrinology Diabetes Medicine, Samatvam Abstract #1003513 Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital and Medical Center; Sathyanarayana Srikanta, MBBS, MD, FEDM, Cushing Syndrome Found to Late FACE, FRCP - Co-author, Endocrinology Diabetes Medicine, Samatvam Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital and Medical Center - Endocrinology Diabetes Author Block: Adele Amine - University of Kentucky Study Group, Endocrinology Diabetes e Co-author, Endocrinology Diabetes Medicine, Samatvam Endocrinology Diabetes Center, Introduction: Cushing syndrome, a disorder so frequently read Jnana Sanjeevini Diabetes Hospital and Medical Center about but rarely seen or is it? Perhaps we can blame it on the old adage, “when you hear hoof beats think horses not zebras.” As Introduction: Clinical diagnoses, especially in Endocrinology, are endocrinologists we can boast about how many Cushing’s cases we not always straight forward [“text book picture”]; unexpected find- come across but how often is it missed? How often do we see cases ings should never be brushed aside without valid scientific expla- to late in the game? And if discovered to late what is the best way to nation; often these are due to additional / confounding / coexistent treat?

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Case Description: Here I present a case of a 47-year-old male with a This is important as obesity has a significant impact on outcomes of past medical history significant for hypertension, HFpEF, hyperlip- numerous cardiopulmonary conditions. idemia and COPD who was referred to endocrinology in July 2020. Methods: Data was extracted from the Nationwide Inpatient At the time of his initial visit he reported increasing weight gain for Sample (NIS) for 2018. The NIS contains hospital discharge infor- over a year, worsening lower extremity swelling, bruising on his mation estimating yearly US hospitalizations. Patients with prin- arms, weakness and declining memory. From what could be gath- cipal diagnostic codes for AI were included. These patients had AI as ered, it was estimated that these symptoms had been at least the reason for hospitalization. Hospitalizations less than 18 years present since December 2019. Clinically the patient had appeared and elective hospitalizations were excluded. This cohort was to be ripped from the pages of Harrison’s. He exhibited the classic divided based on secondary diagnosis of obesity. Outcomes moon facies, facial plethora, wide striae, proximal muscle weak- included comparing inpatient mortality rates, length of hospital ness, thinning skin and multiple bruises on his arms. Baseline stay (LOS), hospitalization cost (HC), rates of septic shock, acute laboratory labs were obtained which were significant for a random myocardial infarction (AMI), acute respiratory failure (ARF), acute cortisol (drawn in the afternoon) to be elevated at 20 nmol/L with a renal failure (AKI), acute pulmonary edema (PE) in patients with suppressed ACTH and low DHEAS. Screening with 1 mg DST failed obesity relative to those without obesity. Adjustment was made for to suppress his cortisol. A 24-hour urine cortisol was obtained biodemographic, hospital factors and Carlson comorbidity index which was greater than 400-mcg/24 hour. A CT was completed using multivariate regression analysis. which demonstrated bilateral macronodular adrenal hyperplasia. Results: A total of 8,980 hospitalizations for AI were included Unfortunately the patient’s course became complicated. Following within the study period. Of these hospitalizations, 15.9% had co- his initial visit he sustained a non-traumatic fracture, which morbid obesity. Females had a larger proportion of AI hospitaliza- required surgical intervention and months of rehabilitation. He was tions with obesity (76.5 vs 58.4%, p< 0.001). Patients with obesity later admitted to the hospital for uncontrolled hypertension and an had lower mean age (56.5 vs 58.1 years, p< 0.001) and higher acute on chronic heart failure exacerbation. While inpatient, proportions of Blacks and Hispanics compared to patients without endocrinology was consulted along with endocrine surgery to obesity. There was no significant difference in adjusted odds ratio of decide the next best course of action. inpatient mortality (aOR: 0.95, 95% CI: 0.22 e 4.16, p¼0.949), mean Discussion: Cushing syndrome, when secondary to bilateral LOS (5.0 vs 4.5 days, p¼0.150) HC in USD (10,032 vs 10,649, macronodular adrenal hyperplasia, is typically treated with p¼0.640) in patients with obesity. Obesity was however associated adrenalectomy (bilateral vs. unilateral). In our case a decision with higher rates of AKI (aOR: 1.44, 95% CI: 1.09 e 1.89, p¼0.009), to use medical treatment as a bridge to surgery was the shared and ARF (aOR: 2.28, 95% CI: 1.48 e 3.53, p< 0.001) compared to decision with both patient and family. A decision that was patients without obesity. difficult to reach given the chonicity of his disease. The journey Discussion/Conclusion: Among patients with AI, obesity was not is still in progress with the hopes of achieving a better associated with higher inpatient mortality, length of hospitalization outcome. This patient has been suffering from endogenous or total hospital cost. Obesity was however associated with higher production likely for over a year perhaps many. The goal would odds of complications including AKI and ARF which may contribute be to ease his burden following surgery, to decrease his to the healthcare requirements of the patients following discharge. chances of steroid withdrawal syndrome, adrenal insufficiency This may likely exacerbate underlying comorbidities and impact and improvement in wound healing. the rate of future admissions. https://doi.org/10.1016/j.eprac.2021.04.499 https://doi.org/10.1016/j.eprac.2021.04.500

Abstract #1003618 Abstract #1003768

Association of Obesity with Outcomes of Patients with Non Classic Congenital Adrenal Hyperplasia Due to Adrenal Insufficiency: A Nationwide Retrospective Late Onset 3 Beta-Hydroxysteroid Dehydrogenase Analysis Deficiency Diagnosed as a Work Up of Infertility and Adrenal Adenoma

Author Block: OMOLABAKE ALABI - JACOBI MEDICAL CENTER, NEW YORK; Chukwudi Charles Muojieje, MD, MPH - Co-author, Author Block: Mohammad Qureshi - Endocrine and Diabetes Mountain View Regional Medical Center, New Mexico; Clinic; Hadiyah N. Qureshi, Undergraduate Student - primary Pius Ojemolon, MD - Co-author, Saint George’s University School of author, Rhodes College Medicine Grenada; Ramtej Atluri, MD - Co-author, John H. Stroger, Jr. Hospital of Cook County Chicago IL; Marcelo Ramirez, MD - Co- Introduction: 3 Beta-Hydroxysteroid Dehydrogenase (3B-HSD) author, John H. Stroger, Jr. Hospital of Cook County Chicago IL; deficiency is a rare form of Congenital Adrenal Hyperplasia (CAH). It Aguilera Maria, MD - Co-author, John H. Stroger, Jr. Hospital of is an autosomal recessive disease leading to varying degrees of Cook County, Chicago IL; Hafeez Shaka, MD - Co-author, John H. enzymatic defects. Presented is a case of late onset type 2 3B-HSD Stroger, Jr. Hospital of Cook County, Chicago IL deficiency, diagnosed as a work up of infertility, adrenal adenoma, and high dehydroepiandrosterone sulfate (DHEA-S) levels. Objective: Adrenal insufficiency (AI) is an uncommon but life- Case Description: A 39 year old female was referred to us by an threatening condition that occurs secondary to impaired secretion infertility clinic for high DHEA-S levels. She experienced menarche of adrenal glucocorticoid and mineralocorticoid hormones. This at 11 years of age and has had normal menstrual cycles. Pelvic condition can be caused by primary destruction or dysfunction of ultrasound showed cystic ovaries consistent with PCOS. On exam- the adrenal glands or impairment of the hypothalamic-pituitary- ination, she was normotensive without any signs of androgen adrenal axis. With the rising prevalence of obesity in the US, it is excess. Initial labs are as follows: 17-OH progesterone (17-OHP) necessary to study obesity in relation to various medical conditions. 99 ng/dL (35 to 290), testosterone 160 ng/dL (< 65), cortisol

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8.5 ug/dL (4 to 22), ACTH 65 pg/mL (7 to 63), DHEA-S 1000 ug/dL have bilateral upper lobe consolidations on CT chest, suggestive of (35 to 430). Due to her unusually high levels of DHEA-S, a CT invasive fungal infection. Patient was on fluconazole 400mg PO abdomen was done and revealed an indeterminate 4.5 cm left ad- daily for prophylaxis prior to hospital admission and was switched renal mass (26 Hounsfield [HU] pre contrast, 84 HU arterial phase, to voriconazole 200mg PO every 12 hours at outside hospital. He 40 HU delayed images), and a indeterminate 1.1 cm right adrenal was transferred to our facility due to persistent fever, despite mass (40 HU pre contrast,125 HU arterial phase, 69 HU delayed antifungal and broad-spectrum antibiotic treatment. Due to images). Further assessment of the adrenal adenomas revealed abnormal liver function tests, he was switched to Posaconazole normal plasma metanephrines, aldosterone, and 24 hour urine 300mg PO daily. After about 10 days of treatment on Posaconazole, cortisol levels. A brief work up for CAH was normal with a repeat the patient was noted to have dizziness spells and syncopal events. 17-OHP at 48 ng/dL (35 to 290), androstenedione at 115 ng/dL (51 to On exam he was found to be hypotensive with orthostasis. Patient 213), and 17-hydroxypregnenolone (17-OH preg) at 535 ng/dL (38 was on diuretics and despite stopping the diuretics he continued to to 378). As the left adrenal mass was larger than 4 cm in size with be hypotensive. Further evaluation showed a low random cortisol low fat content and high DHEA-S levels, she underwent left at 7.7 mcg/dL. This was followed by a Cosyntropin stimulation test, adrenalectomy due to a high suspicion of adrenocortical carcinoma. where his cortisol peaked only to 9.3 mcg/dL at 60 minutes from a Pathology revealed an adrenal cortical adenoma; additionally, her baseline of 7.3 mcg/dL. Adrenocorticotropic hormone level was DHEA-S failed to normalize at 868 ug/dL. She underwent ACTH elevated at 177 pg/mL (ref 0-46 pg/ml) indicating Primary Adrenal stimulation with results as follows (baseline level d > 60 minutes): Insufficiency. Electrolytes were difficult to interpret due to con- Cortisol 12.3 d > 16.3 ug/dL, 17-OHP 101 d > 236 ng/dL, 17-OH current diuretic use. His 21-hydroxylase antibodies were negative preg 1712 d > more than 4000 ng/dL. These results suggest 3B- and a CT of his abdomen showed normal appearing adrenal glands. HSD deficiency. Genetic testing confirmed heterozygous frameshift The patient’s symptoms and blood pressures improved with initi- (c.558:1 bp duplication of C; codon:187) and missense (c.518T >G; ation of hydrocortisone and fludrocortisone. Unfortunately, later p.Leu173Arg) mutations of the 3B-HSD gene. Interestingly, she is during his hospital stay patient developed complications from his also found to be a carrier of a 21-hydroxylase deficiency gene underlying illness and had elected for hospice care. (c.955C >T; p.Gln319X), the most common cause of CAH. Discussion: This case demonstrates that prolonged use of Pos- Discussion: 3B-HSD deficiency is a rare form of CAH. The type 2 3B- aconazole can precipitate Primary Adrenal Insufficiency. While this HSD enzyme is in adrenal glands and gonads and its deficiency patient was on other antifungal agents prior to the initiation of leads to altered steroidogenesis in both. Classic 3B-HSD presents at Posaconazole, his symptoms worsened significantly after its use. As birth with insufficiently virilized boys and clitoromegaly in girls, as its use becomes more frequent, it’s important for practitioners to well as salt wasting. Late onset 3B-HSD deficiency may present consider adrenal insufficiency as a potential diagnosis in patients with an initial, short-lived growth spurt but an eventual short who develop unexplained or worsening hypotension. stature due to advanced bone age. Patients often experience https://doi.org/10.1016/j.eprac.2021.04.502 infertility. Signs of hyperandrogenemia may be seen in females. This report highlights an unusual case of late onset 3B-HSD defi- ciency with an adrenal adenoma. Published cases exist which Abstract #1003799 showcase CAH presenting as different types of adrenal masses- adrenal adenomas, adrenal carcinomas, and adrenal myelolipoma. Persistent Hypertension After Adrenalectomy for To our knowledge, we have not come across another documented Pheochromocytoma/Paraganglioma (PPGL) in Young case of a late onset 3B-HSD deficiency with an adrenal adenoma. Adult: A Possible Case of Noradrenergic Extra Adrenal https://doi.org/10.1016/j.eprac.2021.04.501 PPGL?

Author Block: Abstract #1003792 Syahidatul Wafa - Division of Endocrine Metabolic Diabetes, Department of Internal Medicine, Faculty of Medicine, A Case of Posaconazole Induced Primary Adrenal University of Indonesia; Dante Saksono Harbuwono, Associate Insufficiency Professor - Co-author, Division of Endocrinology, Metabolism, and Diabetes, Department of Internal Medicine, Faculty of Medicine, University of Indonesia; dyah Purnamasari, Associate professor - Author Block: Ilia Bernstein, BMBS - Primary Author, University of Co-author, Division of Endocrinology, Metabolism, and Diabetes, Nebraska Medical Center; Emily Silverman, MD - co-author, Department of Internal Medicine, Faculty of Medicine, University University of Nebraska Medical Center; Padmaja Akkireddy, MBBS of Indonesia; Dicky Tahapary, Assistant Professor - co-author, - co-author, University of Nebraska Medical Center Division of Endocrinology, Metabolism, and Diabetes, Department of Internal Medicine, Faculty of Medicine, University of Indonesia Introduction: Posaconazole is a second-generation triazole agent with broad-spectrum antifungal activity. It is used in prevention Introduction: The prevalence of secondary hypertension in and treatment of invasive fungal infections. It inhibits lanosterol young adults is approximately 30%, most of which are endocrine 14a-demethylase and prevents synthesis of ergosterol, a compo- disorders such as primary aldosteronism, pheochromocytoma/ nent of the fungal cell wall. Other azole antifungals have been paraganglioma (PPGL), and Cushing syndrome. Pheochromocy- described as causing Adrenal Insufficiency (AI) due to their toma and paraganglioma (PPGL) are neuroendocrine tumors that inhibition of steroidogenesis, however, there have been only a few arise from adrenal or extra-adrenal chromaffin cells, and they can reported cases of Posaconazole as the causative agent (4 cases re- occur either sporadically or hereditary. It is a necessity to establish ported in literature). Here we present a case of Posaconazole an accurate diagnosis through careful workup to provide optimal induced Primary Adrenal Insufficiency. treatment. Case Description: A 61-year-old man with refractory acute myeloid Case Description: An 18 y/o female came with a history of hyper- leukemia was admitted with neutropenic fever. He was found to tensive urgency, accompanied by palpitations and progressive right

S15 Adrenal Disorders Endocrine Practice 27 (2021) S1eS23 abdominal pain for half a yeardno typical spell of paroxysmal Introduction: Cushing’s syndrome is a disorder that occurs when symptoms. She noticed hypertension three years ago that improved the body has excess level of cortisol hormone. This hormone is without drugs. On examination, the blood pressure (BP) was 150/90 made in the adrenal glands. Too much cortisol can be due to various mmHg, and heart rate was 100 bpm. We found no thyroid problems, one such problem is a rare tumor at the adrenal glands. enlargement or hypercortisolism features. No abnormality of renal We present a case of 33-year-old female patient with a history of and thyroid function, no arrhythmia, no elevation of morning typical cushing’s syndrome presentation. plasma aldosterone and cortisol levels. She had a 4x rise of plasma Case Description: She presented with a 3 month history of a 5 kg normetanephrine 10326 (< ¼148 pg/nl) with plasma metanephrine body weight gain and gradual rounding of the face. The patient also 111 (< ¼57 pg/nl). The abdominal CT showed high attenuation suffered from unexplained fatigue, easily bruised skin, muscle values of the large right adrenal mass (diameter 7 cm) with central weakness, thickened eyebrows, and hair growth on upper lip, chin, necrotic component and suppression of adjacent inferior vena cava. and arms. The patient had irregular menstrual period for 3 months. We established the diagnosis of noradrenergic PPGL and treated The patient eyes started to have yellowish color for 2 weeks. There her with prazosin, bisoprolol, and amlodipine as an add-on if was no history of headache and vision loss. No history of steroids needed, achieving controlled BP. She underwent right total adre- and traditional pain killers consumption. nalectomy that revealed a large tumor size of 7x6.5x6 cm with Physical examination showed hypertension, moon face, scleral multinodular appearance and positive staining of chromogranin A; icterus, thick eyebrows, facial hair at upper lip and chin region, histopathology suggested malignant pheochromocytoma. Howev- buffalo hump, visible thick hair at both arms, and stretch marks in er, at one-month post-surgery, the BP remained high despite still the abdomen. receiving triple antihypertensive drugs. Fluorodeoxyglucose (FDG) Laboratory findings revealed high level of morning cortisol, PET Scan and Iodine-123 meta-iodobenzylguanidine (MIBG) scin- elevated urinary free cortisol, and plasma acth level of 20 pg/mL. tigraphy were then planned to assess the possibility of extra-ad- The patient also had high blood glucose, 10.4% of HbA1C level, renal PPGL that commonly metastasize. hypokalemia, hypercholesterolemia, elevated liver enzyme and Discussion: Noradrenergic PPGL is a rare form of PPGL that pre- hyperbilirubinemia. No suppression was observed in the high-dose dominantly produces normetanephrine from chromaffin cells. As dexamethasone suppression test. norepinephrine works mainly on a1-adrenoceptors in the vascu- Abdominal computed tomography revealed 2.6 cm diameter of lature, the continuous vasoconstriction results in sustained rather right adrenal mass, suspected lipid-poor adenoma, with smaller than paroxysmal hypertension. Generally, surgery is the curative than normal size of left adrenal. Computed tomography also treatment of adrenal PPGL, providing surgical cure and prevention revealed fatty liver and bilateral cyst of the adnexa. of catecholamine excess complications. However, most noradren- Discussion: The patient came with typical presentation of cushing's ergic PPGL are also extra-adrenal, which may explain hypertension' syndrome. Laboratory workup confirmed the diagnosis and persistence despite complete surgical treatment. Besides, norad- computed tomography revealed adrenal mass that caused the renergic PPGL is mostly related to the mutation of succinate de- excessive cortisol production. The patient received treatment hydrogenase (SDH), von-Hippel Lindau (VHL), or HIF 2A genes. for hypertension, hyperglycemia, hypercholesterolemia, and hy- These mutations are linked to malignant PPGL that are associated pokalemia. The patient then prepared to undergo unilateral with tumorigenesis through pathogenesis of pseudohypoxia. Most adrenalectomy. malignant PPGL needs additional treatment of MIBG radio ablation https://doi.org/10.1016/j.eprac.2021.04.504 or chemotherapy that may provide a complete response in 50% of patients. https://doi.org/10.1016/j.eprac.2021.04.503 Abstract #1003814

Metachronous Bilateral Adrenocortical Adenomas - A Abstract #1003811 Rare Cause of Recurrent Cushing's Syndrome

Cushing’s Syndrome With Unilateral Adrenal Mass: A Case Report Author Block: Ivy Hoi Yee Ng, MBChB - primary author, United Christian Hospital; Grace Yee Wai Kam, MBChB - co-author, United Christian Hospital Author Block: Nur Hidayat, MD - primary author, Department of Internal Medicine, Division of Endocrinology and Metabolism, Introduction: Adrenocorticotropic hormone (ACTH)-independent Department of Internal Medicine, Faculty of Medicine, University Cushing’s syndrome from bilateral adrenocortical adenomas is an of Indonesia, Cipto Mangunkusumo Hospital, Jakarta, Indonesia; uncommon entity. Sequential development of such cortisol-pro- Dicky L. Tahapary, MD, PhD - co-author, Department of Internal ducing adrenal adenomas is even more rare. Medicine, Division of Endocrinology and Metabolism, Department Case Description: A 39 year old lady presented in 2002 with an of Internal Medicine, Faculty of Medicine, University of Indonesia, elevated serum cortisol of 400 nmol/L (N< 50) on 1 mg overnight Cipto Mangunkusumo Hospital, Jakarta, Indonesia; Tri Juli Edi dexamethasone suppression test (ONDST) during workup for sec- Tarigan, Doctor, Internist, Endocrinologist - co-author, Department ondary causes of hypertension. Clinically she was not overtly of Internal Medicine, Division of Endocrinology and Metabolism, Cushingoid apart from weight gain of 4 kg over 1 year. Serial 24 hr Department of Internal Medicine, Faculty of Medicine, University urine cortisol levels were raised by 1.4-3.8 fold, and ACTH was of Indonesia, Cipto Mangunkusumo Hospital, Jakarta, Indonesia; undetectable at < 2.2 pmol/L. CT showed a 3x2 cm right adrenal Subekti Imam, Professor, Internist, Endocrinologist - co-author, nodule [precontrast Hounsfield units (HU) 23, washout 86%] and a Department of Internal Medicine, Division of Endocrinology and normal left adrenal gland. Urine catecholamines, aldosterone renin Metabolism, Department of Internal Medicine, Faculty of Medicine, ratio, DHEAS, and testosterone levels were all normal. She University of Indonesia, Cipto Mangunkusumo Hospital, Jakarta, proceeded to laparoscopic right adrenalectomy in 2005, with pa- Indonesia thology confirming adrenal cortical adenoma. Six months postop

S16 Adrenal Disorders Endocrine Practice 27 (2021) S1eS23 she lost 8 kg of weight, and anti-hypertensives could be withdrawn. decrease exercise tolerance, and skin/tongue hyperpigmentation. Hydrocortisone replacement was stopped in 2009 when her short Throughout her life, she always had low-normal body mass index synacthen test showed recovery of adrenal function. and low normal blood pressure. She had a normal appetite and de- Five years after the adrenalectomy the lady was found to be hy- nied nausea, vomiting, lightheadedness, dizziness, syncope, or pertensive again and regained 4 kg of weight. Serum cortisol was serious illness in the past. Physical exam, was only pertinent for 317 nmol/L (N< 50) on 1 mg ONDST. Serial 24 hr urine cortisol melasma and darkening of the tongue; no other oral mucosa hy- levels were raised by 5-10 fold, with suppressed ACTH < 2.2 pmol/L perpigmentationwas present. Due to previous lab results and clinical and DHEAS 0.1 umol/L (N 1-7). Urine steroid profile showed no signs/symptoms, Addison’s Disease was suspected. Repeat ACTH elevation of atypical metabolites. CT in 2012 showed a 2.6x1.8 cm levels was 1,102 pg/mL, with normal renin (5.8 ng/mL/h) and aldo- left adrenal nodule [precontrast HU 20, washout 67%] with evi- sterone (6 ng/dL) levels. Serum sodium and potassium levels were dence of right adrenalectomy. The patient declined surgical inter- also normal. Cosyntropin stimulation test showed baseline cortisol of vention initially due to concern with the sequelae of bilateral total 7.9 mcg/dL with cortisol levels 9.5 mcg/dL and 7.5 mcg/dL at 30 min adrenalectomy. Followup imaging for 4 years showed no significant and 60 min after cosyntropin respectively; antibodies for 21-hy- interval change in the nodule. Metyrapone was started when the droxylase antibodies were positive confirming the diagnosis of morning serum cortisol progressed to 500-800 nmol/L (N 166-507), Addison’s Disease. She was started on hydrocortisone replacement but control of hypercortisolemia was suboptimal as she could only without florinef, her symptoms of fatigued resolved and the hyper- tolerate low dose of both metyrapone and fluconazole. As the dis- pigmentation disappeared in 2 months after treatment with steroids. ease evolves she also required metformin and diamicron for control Discussion: Addison’s disease is a rare endocrine disorder that af- of new onset diabetes (Hba1c 10.2%) and spironolactone for spon- fects 1 in 100,000 people, with several oral and systemic manifes- taneous hypokalaemia. Laparoscopic left adrenalectomy was tations1. Hyperpigmentation of the skin occurs in 41 e74% of patients eventually performed in 2019, with pathology once again con- and is considered a hallmark of Addison’s disease2. One of the most firming adrenal cortical adenoma. Her blood pressure and glycae- common manifestations are fatigue, generalized weakness, hypo- mic control improved postop, and she was educated for lifelong tension, and weight loss. These symptoms can progress slowly hydrocortisone and fludrocortisone replacement. throughout months to years, but an event or illness can exacerbate Discussion: ACTH-independent Cushing’s syndrome can recur the condition, leading to life-threatening crises. Early recognition years after adrenalectomy, and may involve the contralateral ad- and diagnosis are life-saving. This case emphasizes the point that not renal. A high clinical suspicion is required when there is return of all melasma is benign, but maybe the hallmark of this serious illness. hypertension, diabetes, or weight gain. https://doi.org/10.1016/j.eprac.2021.04.506 https://doi.org/10.1016/j.eprac.2021.04.505

Abstract #1003941 Abstract #1003843 Primary Aldosteronism Complicated and Confounded Mysterious Skin Changes, a Clue to a Unique by Hyponatremia of Independent Etiologies: Double e Presentation of Addison’s Disease Triple Endocrinology Challenge

Author Block: Maria M. Felix-Morales, MD - Primary Author, Author Block: Jayalakshmi Thimmaiah, MBBS, DNB, FEDM, CDE - Endocrinology, University of Texas Health Science Center - San Primary Author, Endocrinology Diabetes Medicine, Samatvam Antonio; Joy Wortham, MD - Co-Author, Endocrinology, University Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital of Texas Health Science Center - San Antonio; Brenda Sandoval, MD and Medical Center; Mandyam D. Chitra, MBBS, FEDM, CDE - Co- - Co-Author, Endocrinology, University of Texas Health Science author, Endocrinology Diabetes Medicine, Samatvam Center - San Antonio; Emad Ali, MD - Co-Author, Endocrinology, Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital University of Texas Health Science Center - San Antonio; and Medical Center; siddhartha dinesha, MBBS, FEDM CDE - Co Ramona Granda-Rodriguez, MD - Co-Author, Endocrinology, Author, Endocrinology Diabetes Medicine, Samatvam University of Texas Health Science Center - San Antonio; Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital Jan Bruder, MD - Co-Author, Endocrinology, UT Health San Antonio and Medical Center; Prateek Hongal, MBBS, FEDM CDE - Co Author, Endocrinology Diabetes Medicine, Samatvam Endocrinology Introduction: Melasma is a common skin pigmentation condition. Diabetes Center, Jnana Sanjeevini Diabetes Hospital and Medical Understanding the etiology and pathogenesis of melasma becomes Center; Apoorva Govind, MBBS, FEDM CDE - Co Author, critical to unmask the underlying condition. Rarely, melasma is Endocrinology Diabetes Medicine, Samatvam Endocrinology associated with Addison's disease. Diabetes Center, Jnana Sanjeevini Diabetes Hospital and Medical Case Description: A 33-year-old woman with asthma, presenting Center; Reshma Harsha, MBBS, FEDM, FACE - Co Author, with skin hyperpigmentation on her face, was recently evaluated bya Endocrinology Diabetes Medicine, Samatvam Endocrinology dermatologist, who diagnosed her with a typical melasma-like Diabetes Center, Jnana Sanjeevini Diabetes Hospital and Medical pigmentation. A few months after diagnosis, the patient developed Center; Muralidharakrishna C. S, MBBS, FEDM, FACE - Co Author, abdominal bloating, diarrhea, and indigestion. She was diagnosed by Endocrinology Diabetes Medicine, Samatvam Endocrinology GI with celiac disease by labs and biopsy and was placed on a gluten Diabetes Center, Jnana Sanjeevini Diabetes Hospital and Medical free diet. During this time, the patient's tongue became purple/black Center; Sumathi K, MBBS, FEDM, FACE - Co Author, Endocrinology in color. She was evaluated again by the dermatologist, who was Diabetes Medicine, Samatvam Endocrinology Diabetes Center, concerned by these new findings and ordered serum ACTH and Jnana Sanjeevini Diabetes Hospital and Medical Center; cortisol levels. Patient was referred to the endocrinology for evalu- Thummala Kamala, MBBS, FEDM, FACE - Co Author, Endocrinology ation of a morning ACTH levels of 809 pg/mL and Cortisol levels of 7.6 Diabetes Medicine, Samatvam Endocrinology Diabetes Center, mcg/dL. Her only symptoms were fatigued throughout the day, Jnana Sanjeevini Diabetes Hospital and Medical Center;

S17 Adrenal Disorders Endocrine Practice 27 (2021) S1eS23 vasanthi Nath, MBBS, FEDM, FACE - Co Author, Endocrinology Discussion: Our patient is not a straight forward case of “sim- Diabetes Medicine, Samatvam Endocrinology Diabetes Center, ple” PA, and a “second / third” diagnosis is necessary to explain Jnana Sanjeevini Diabetes Hospital and Medical Center; the confounding easy propensity to Recurrent Hyponatremia. Tejeswini Patil, MBBS, MD, FEDM, FACE - Co Author, Endocrinology Old medical records review indicated that the first two epi- Diabetes Medicine, Samatvam Endocrinology Diabetes Center, sodes of Severe Hyponatremia [and Hypokalemia] triggering Jnana Sanjeevini Diabetes Hospital and Medical Center; ICU hospitalisations were related to “inadvertent” addition / re- Sharda Ardhanareeswaran, MBBS, MD, FEDM, FACE, FRCP - Co addition of thiazide diuretics by different short term care Author, Endocrinology Diabetes Medicine, Samatvam teams. Hyponatremia recurred for the third time when we Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital were gradually titrating the dose of Spironolactone, indicating and Medical Center; Sathyanarayana Srikanta, MBBS, MD, FEDM, the existence of a yet another unidentified “third” diagnosis: FACE, FRCP - Co Author, Endocrinology Diabetes Medicine, (a) “Subclinical Hypopituitarism e Cortisol deficiency”,(b) Samatvam Endocrinology Diabetes Center, Jnana Sanjeevini Renal Tubular Dysfunction e Renal Salt Wasting, (c) SIADH, etc: Diabetes Hospital and Medical Center; Kavitha Muniraj, MBBS, Under investigation FEDM, FACE - Co-author, Endocrinology Diabetes Medicine, https://doi.org/10.1016/j.eprac.2021.04.507 Samatvam Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital and Medical Center - Endocrinology Diabetes Study Group, Endocrinology Diabetes e Co Author, Endocrinology Abstract #1004208 Diabetes Medicine, Samatvam Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital and Medical Center Glycemic Abnormalities Associated with Elevated Catecholamines in a Male with History of Introduction: Primary Aldosteronism [PA] in which aldosterone Hypertension and Diabetes Mellitus Type 2 secretion by the adrenal is excessive and autonomous is now known to be the most common specifically treatable and poten- tially curable form of hypertension, with most patients lacking the Author Block: Anum Khan - Windsor University School of clinical feature of hypokalemia. We present a case of delayed Medicine; Syed Wajih Rizvi, MD - Co-author, Endocrinology, diagnosis of PA, further confounded by hyponatremia [? apparently R-Endocrinology; Samir Beso, MD - Co-author, Emergency “Paradoxical”] of independent coincidental etiologies Medicine, Windsor University School of Medicine, St. Kitts & Nevis; Case Description: Birth 1936: Age (Years) 53: Hypertension; Age Muntazir Ali Sayed, MBBS - Co-author, Internal Medicine, 83: T2DM; Age 80: Bronchial Asthma; Renal Calculus; stable on R-Endocrinology; Cowthar Shurie, MD - Co-author, Family medications Medicine, Windsor University School of Medicine, St. Kitts & Nevis; 2019 Oct: Admitted to ICU in USA for Accelerated Hypertension, Shanaz Ahmad, MD - Co-author, Family Medicine, University of drowsiness, anorexia; found to have Severe Hyponatremia and Medicine and Health Sciences, St. Kitts & Nevis; Sadiq Ali Sayed, Hypokalemia; discharged after medical treatment, without a MBBS - Co-author, Internal Medicine, National Pirogov Memorial definitive diagnosis Medical University, Vinnytsya, Ukraine 2019 Nov: Returned to India, readmitted in ICU for tiredness and weakness; found to have Recurrent Severe Hyponatremia and Hypokalemia; Hypothyroidism Subclinical TSH; again, discharged Introduction: Pheochromocytoma (PCC) is defined as a catechol- after medical treatment, without a definitive diagnosis amine-secreting tumor of the adrenal medulla. Diagnosis is 2020 Feb: Attended Samatvam Endocrinology Diabetes Center frequently made by measuring catecholamines in the urine and for management of T2DM and HTN [Metformin, L-Thyroxine 25 plasma. Excess catecholamines directly stimulate the production of mcg/day, amlodipine, atorvastatin, clopidogrel]. PR 82, BP 149/81, glucose as well as impeded glucose disposal resulting in hyper- BMI 25.5; Random Blood Glucose 135 mg/dl; bilateral pedal edema glycemic state. Our objective is to report on a case of a patient with Endocrinology Work Up: HbA1c 6.6 %; TSH 10.7 mIU/ml; Thyroid PMHx of Diabetes Mellitus Type 2 (DMT2) with hyperglycemia and Peroxidase Antibodies 192 IU/ml [< 34]; eGFR 85 mL/min/1.73m2; hypertension with elevated catecholamines. Urine Albumin: Creatinine Ratio 59 mcg/mg, Creatinine 0.5 mg/dl; Case Description: A 60-year-old African American male with PMHx S Calcium 9.45 mg/dl, S Phosphorus 3.9 mg/dl, Hypercalciuria 843 of DMT2 with Hyperglycemia and HTN presented for a follow-up mg/24 hours; S Na 136 mmol/l; S K 3.9 mmol/l visit at our Endocrinology clinic. ROS was non-contributory. Patient Serum Aldosterone 40.8 ng/dl; Plasma Renin Activity 0.21 ng/ml/ reported that he stopped taking his medications as he ran out of hr; ARR 194 refills, while the following medications were self-discontinued: Bone Markers: S CTX 591 pg/ml, S P1NP 73.23 ng/ml; High Repaglinide 1mg (OD), Jardiance 25mg (OD), Glimepiride 2mg Turnover Osteopenia/Osteoporosis (BID), Acarbose 100mg (TID), Metoprolol 100mg (OD), Hydralazine MRI Adrenals: No significant abnormality 100mg (OD), Klor-Con ER 10mEq (OD), and Lisinopril 40mg (OD). Assessment: Primary Aldosteronism [with superimposed Patient has a history of hyperglycemia with frequent blood sugar diuretic induced hypokalemia and hyponatremia e cause of pre- level (BSL) measuring >200 mg/dL fasting and >300 mg/dL PP. His vious 2 ICU admissions]. LT4 increased to 50 mcg/day; Spi- BP on the recent encounter was 130/90 mmHg but previous BP ronolactone 25 mg OD added. readings ranged 156/90-136/70 mmHg. He was tachycardic on physical examination; other vitals were satisfactory. A thorough Month Year S Sodium S Potassium Spironolactone dose mg/day blood work was ordered which revealed elevated catecholamines as: NE 890 pg/mL (0-874 pg/mL) and E 71 pg/mL (0-62 pg/mL). Feb 2020 136 3.9 0 started 25 Mar 2020 133 3.9 25 e later increased to 50 Further workup included 24-hr urinalysis which revealed increase Sep 2020 127 4.7 50 e tired exhausted; decreased to in VMA 8.0 mg/24 hr (0.0-7.5 mg/24 hr), NE 150 ug/24 hr (0-135 ug/ 25 [+ Liberal salt intake] 24 hr), Dopamine 760 ug/24 hr (0-510ug/24hr) and NMN e Oct 2020 135 4.6 25 tiredness symptoms improved; 1975 ug/24 hr (156-729 ug/24 hr). Urine 24-hour MN (215 ug/25 hr; back to normal < Nov 2020 134 4.3 25 58-276 ug/24 hr) and E ( 5 ug/24 hr; 0-20 ug/24 hr) were within normal range. Furthermore, we have ordered an MRI Adrenal

S18 Adrenal Disorders Endocrine Practice 27 (2021) S1eS23

Glands and MIBG Scan which will be done in the upcoming weeks. Fluid restriction and salt tablets were discontinued. Hypotension He was ordered to chart his BP readings at home. He was also and hyponatremia resolved after initiation of Hydrocortisone IV 25 started on Amlodipine 10mg (Qam) and Lisinopril 40mg (Qam) to mg q8h. She was discharged on Hydrocortisone 30 mg daily and control his HTN. Additionally, we prescribed Januvia 100mg (OD) Fludrocortisone 0.05 mg daily. and Precose 100 mg (Qpm) for better glycemic control. Patient will Discussion: This patient presented with hyponatremia and require frequent monitoring of BP and BSL to assess treatment biochemical evidence of adrenal insufficiency confirmed by an modality. abnormal stress cortisol response to a high-dose ACTH stimulation Discussion: PCC is a catecholamine-secreting tumor derived from test. The markedly elevated ACTH level, inappropriately low aldo- chromaffin cells found in the adrenal glands. Secretion of cate- sterone level, and the presence of anti-21-hydroxylase antibodies cholamines results in paroxysmal HTN and associated symptoms support the diagnosis of Addison's disease. Primary adrenal insuf- like headaches, perspiration, and tachycardia.. Additionally, cate- ficiency (AI) after COVID-19 due to adrenal infarcts and hemorrhage cholamines have unfavorable effects on glucose and insulin ho- have been documented, but the normal CT suggested that the eti- meostasis resulting in glycemic abnormalities. Specifically, ology of AI, in this case, was not due to the aforementioned. This epinephrine is said to have high affinity to beta receptors which in case is the first to suggest the onset of Addison’s disease in the turn stimulate gluconeogenesis and alpha-1 receptors which COVID-19 sequelae. decrease insulin secretion. Excess catecholamine can further https://doi.org/10.1016/j.eprac.2021.04.509 induce insulin resistance in patients with DMT2. Diagnosis is made by measuring catecholamines in the urine and plasma, while im- aging tests help localize tumors. Approximately 50% of diagnosed Abstract #1004292 patients present with glucose intolerance. Treatment modality thus targets alpha-antagonist followed by beta-blockers prior to tumor Type 1 Diabetes, Adrenal Insufficiency and resection. It is critical that patients start on alpha-antagonist prior Preeclampsia: A Case Report to beta-antagonist as to avoid hypertensive crisis. https://doi.org/10.1016/j.eprac.2021.04.508 Author Block: Santh Silparshetty - St.Lukes University Health network; Bankim Bhatt, Program Director - Endocrinology e Abstract #1004257 Fellowship program, St.Lukes University Health network co- author, Endocrinology, St. Lukes University Health network Primary Adrenal Insufficiency after COVID-19 Infection Introduction: Preeclampsia is a common complication affecting 3- 5% of all human pregnancies and is associated with maternal and Author Block: Julienne Sanchez Perez - University of Illinois perinatal mortality risk. Type 1 diabetes (T1DM) in pregnancy, in- Hospital; Melissa Cohen, MD - Co-author, University of Illinois creases risk of preeclampsia 5-6 fold. Patients with T1DM also have Hospital; Joseph L. Zapater, MD - Co-author, University of Illinois a 10 fold increased risk of developing Adrenal Insufficiency (AI). Hospital; Yuval Eisenberg, MD - Co-author, Endocrinology, These conditions have conflicting clinical manifestations which Diabetes and Metabolism, University of Illinois Hospital pose diagnostic and management challenges. We present a rare case that highlights these. Introduction: The clinical presentation of SARS-CoV-2 ranges Case Description: A 20 year old african-american primiparous fe- greatly from asymptomatic disease to critical illness. The multi- male at 24 weeks gestation, was admitted with headache, blurred systemic effect of COVID-19 is becoming increasingly apparent, but vision, right upper quadrant pain and elevated blood pressure. She its impact on the endocrine system, in particular, the hypothalamic had a known history of T1DM since age 7 with recent poor control. adrenal axis has yet to be defined. She was on insulin therapy with glargine 14u bedtime and lispro Case Description: A 64-year-old woman with hypothyroidism and using ICR 1u:10g and correction factor 1u:50mg/dL above 120mg/ type 2 diabetes mellitus presented to the emergency room with a 1- dL. week history of abdominal pain, nausea, and vomiting. The patient She had elevated blood pressure in 154/100mmHg range, serum experienced an asymptomatic COVID-19 infection 5 months prior glucose 353mg/dL, anion gap 20mmol/L and platelets 356,000/mL. and reported an unintentional 30-lb weight loss since. She had She had proteinuria 1.2g/24hr. Liver function tests were normal. been admitted several times at an outside hospital for hypona- She was diagnosed with preeclampsia with severe features. tremia where she never received exogenous steroids. Physical exam Over next several days, she had persistent headaches, blurred was notable for hypotension, epigastric tenderness, and hyperpig- vision, nausea, labile plasma glucose with hypoglycemia/hyper- mentation of oral mucosa. Chemistry was significant for hypona- glycemia and labile blood pressures. Symptom management, in- tremia 117 mmol/L (135-145). Hyponatremia workup revealed a sulin dose titration and antihypertensive therapy was done. TSH of 0.33 mcIU/ml (0.35-4.00), free T4 1.4 ng/dl (0.6-1.7), serum On hospital day 11, she had transient unresponsiveness due to osmoles 253 mOsm/kg (279-300), urine osmoles 324 mOsm/kg iatrogenic hypoglycemia from her usual insulin regimen. Capillary (300-900) and urine sodium 104 mmol/l consistent with hypotonic glucose was 23mg/dL. Concomitant serum glucose was 38mg/dL hyponatremia. Fluid restriction and salt tablets were initiated. and blood pressure was 104/71mmHg. AI was suspected. Random Morning 8 AM cortisol returned low (2.6 mg/dl (ref: >18). A high- cortisol on the same serum sample that showed a glucose of 38mg/ dose 250 mcg ACTH stimulation test followed; cortisol levels dL was 10.7mg/mL. AI was diagnosed as this scenario represents an returned 2.3, 2.9, and 2.6 mg/dl (ref: >18) at baseline, 30, and 60 Insulin tolerance test. Patient improved with steroid replacement minutes, respectively. ACTH level was elevated to 1944 pg/ml (7.2- with better correlation of blood pressures to preeclampsia. 63.3), aldosterone was undetectable < 3.0 ng/dl (upright: 4.0-31.0), Discussion: Guidelines define preeclampsia based on 2 blood anti-21-hydroxylase antibody were positive (ref: neg). CT scan of pressure readings >140 systolic and 90 diastolic and proteinuria or the abdomen returned unremarkable for any adrenal pathologies. end organ dysfunction after 20 weeks gestation. AI associated

S19 Adrenal Disorders Endocrine Practice 27 (2021) S1eS23 relative hypotension may lead to under recognition of preeclampsia palliative care because of her advanced cancer with poor prognosis and increased fetal and maternal mortality risk. and sadly, she passed away a few days later. Although co-prevalence of T1DM and AI is well established, AI Discussion: While there have been reports of pembrolizumab diagnosis is often delayed due to relative hyperglycemia. Com- induced thyroid disorder and pituitary dysfunction, there is limited bined, they have been associated with increased risk of hypogly- literature documenting the effects of this chemotherapeutic drug cemia, hyperglycemia, DKA, adrenal crisis and mortality. on the adrenal glands. This case report illustrates the potential for Published literature on AI during pregnancy is limited due to the involvement of additional endocrine pathologies to encourage rarity. High index of suspicion is required for diagnosis of AI during practitioners to consider monitoring multiple endocrine systems, pregnancy and correlation of T1DM with both preeclampsia and including but not limited to the adrenal axis, for patients on adrenal insufficiency should be recognized. immunotherapy. https://doi.org/10.1016/j.eprac.2021.04.510 https://doi.org/10.1016/j.eprac.2021.04.511

Abstract #1004306 Abstract #1004319

Overcorrection of Hypothyroidism Presenting with Malignant Pheochromocytoma with Brain Metastasis: Adrenal Insufficiency Secondary to Pembrolizumab An Unusual Case-study

Author Block: Khin Zin - Jersey Shore University Medical Center; Author Block: Amar Patel - Texas Tech University Health Sciences Mostafa Meleis, MD - co-author, Endocrinology, Jersey Shore Center El Paso; Andrew Ortega, DO - Co-author, Internal Medicine, University Medical Center; Katherine Hu, DO - co-author, Texas Tech University Health Sciences Center El Paso; Luis Chavez, Endocrinology, Jersey Shore University Medical Center; MD - Co-author, Internal Medicine, Texas Tech University Health Monika Akula, MD - co-author, Endocrinology, Jersey Shore Sciences Center El Paso; Arianna Perez, MD - Co-author, University Medical Center; Soemiwati Holland, MD - co-author, Endocrinology, Texas Tech University Health Sciences Center El Endocrinology, Jersey Shore University Medical Center; Paso Jennifer Cheng, DO - co-author, Endocrinology, Jersey Shore University Medical Center; Raquel Ong, MD - co-author, Introduction: Most pheochromocytomas (PCCs) are benign tu- Endocrinology, Jersey Shore University Medical Center mors, but some of them exhibit malignant characteristics and may metastasize. Our case describes a patient with known past history Introduction: The toxicity of cancer immunotherapy targeting of PCC with new metastasis to the brain. immune checkpoints, especially anti-PD-1 therapy, on the endo- Case Description: A 61 year-old female with past history of PCC crine system has been widely reported. The two most commonly with liver metastasis, came to the emergency department with new affected organs are the pituitary and thyroid, however, other onset of headache. She had recently restarted chemotherapy after endocrine-related organs such as the adrenal glands may also be an eight month hiatus due to interval chronic cholecystitis. Physical impacted. In this unusual case, we present a patient with adrenal examination was remarkable for a blood pressure of 180/100 insufficiency after overcorrection of hypothyroidism related to mmHg. No focal neurological deficits noted. A previous head CT pembrolizumab. scan from 1 year prior showed a 1.1 cm subtle round hyper-dense Case Description: A 73-year-old Caucasian woman with a past lesion noted within the base of left middle cranial fossa suggestive medical history of stage 4 oropharyngeal melanoma on pem- of an extra-axial lesion such as a partially calcified meningioma. On brolizumab and axitinib, atrial fibrillation, inflammatory colitis, and this admission, a brain MRI showed an extra-axial T2 hyper-intense pembrolizumab induced hypothyroidism presented to the hospital enhancing lesion along the base of left temporal lobe within left with unstable gait, fall, fatigue, generalized weakness, nausea, and middle cranial fossa and measuring approximately 2.5 x 2.6 x 2.2 vomiting for one month. She was very cachectic and weak upon cm with mass effect on adjacent brain parenchyma. Patient’shy- admission. Physical examination was notable for dry skin and pertension was successfully managed with Prazosin. Neurosurgery mucous membranes as well as abdominal tenderness. On admis- performed a craniotomy with brain biopsy followed by intensive sion, her blood pressure was low at 99/61 mmHg and she had se- care unit postoperatively. Pathology revealed malignant PCC vere hypoglycemia with blood glucose found to be 27 mg/dL. It was metastasis to the brain. The patient underwent radiation therapy complicated by refractory hypotension despite fluid boluses and with overall poor prognosis. bouts of fever and hypothermia. Her lab results showed low TSH at Discussion: As with most tumors, PCC have the potential for ma- 0.073 uiU/L (0.300 - 4.500 uIU/mL) and elevated free T4 at 1.93 uiU/ lignant transformation (approximately 10%) with common meta- L (0.50 - 1.26 ng/dL). Her serum cortisol level at 8:30 am was 14.0 static sites including the lung, liver, and bone (1). Of note, through mg/dL with blood glucose at 33 mg/dL. She was taking levothyrox- medical literature review, it is found that direct CNS metastatic ine 200 mcg daily and her actual weight-based dose should be 75 involvement of PCC is extraordinarily rare (2). To the best of our mcg daily as she has lost an estimate of 80 lbs since diagnosis of literature review, there are only 4 previously documented case melanoma. Her serum cortisol level was expected to be higher in reports of cerebral metastatic PCC (2-5). Histologically, a malignant the setting of refractory hypotension, lactic acidosis, and severe PCC has the same features as a benign PCC so the diagnosis of hypoglycemia, however, it was inappropriately normal. Given this malignant metastatic PCC is done by identifying tumor deposits in patient’s recent history of fatigue, weakness, and nausea, as well as organs that should not contain chromaffin cells. Genetic mutations her inadequate adrenal response to hypotension and hypoglycemia, to the enzyme succinate dehydrogenase subunit B (SDH B gene) there was high clinical suspicion for adrenal insufficiency second- seems to be reported in as many as 83% of patients with malignant ary to pembrolizumab use. She was initiated on stress dose hy- PCC(6). As of today, our patient has not had genetic testing. As there drocortisone and her levothyroxine dose was decreased to her is no established treatment for malignant PCC, available therapies appropriate weight-based dose. Her family decided to set up are typically directed for palliative care such as controlling blood

S20 Adrenal Disorders Endocrine Practice 27 (2021) S1eS23 pressure and reducing tumor burden via chemotherapy or benign features, a low grade ACC cannot be distinguished from debulking surgery. benign adenoma and periodic clinical / imaging surveillance may Metastatic cerebral PCCs are extremely rare and can present in a be of benefit in such cases. symptomatic patient or remain subclinical. Once diagnosed, there There are pitfalls in the radiologic and histopathologic diagnosis is no established treatment. Treatment is aimed at controlling of adrenal tumors in borderline cases. In such cases clinical follow symptoms and reducing tumor burden via therapeutic agents and up and monitoring post-surgical resection may be reasonable. tumor debulking. https://doi.org/10.1016/j.eprac.2021.04.513 https://doi.org/10.1016/j.eprac.2021.04.512

Abstract #1004329 Abstract #1004320 Are Pain Injections as Harmless as They Seem? Right Adrenal Mass with New Central Necrosis on Computed Tomography after Showing Long-term Stability Author Block: Ekatherine Rivera - University of Cincinnati; Dima L. Diab, Associate Program Director - Co-author, Division of Endocrinology, Diabetes and Metabolism, University Of Cincinnati Author Block: Chandrika Reddy, Endocrine Fellow - Primary College of Medicine author, Endocrinology, Creighton School of Medicine; Christopher Gallagher, Professor - co-author, Endocrinology, Introduction: Intra-articular glucocorticoids (IAGC) are routinely Creighton SOM; alain Taylon, Endocrinologist - co-author, used for the localized treatment of joint pain. It is generally Endocrinology, Creighton SOM assumed that IAGC act only locally, but it has been shown that a single dose of intra-articular Triamcinolone can suppress the hy- Introduction: Distinguishing adrenal adenoma from adrenal pothalamic-pituitary-adrenal (HPA) axis for as long as seven weeks. cortical carcinoma ( ACC) in borderline cases can pose a challenge. The HPA axis can take at least 3 months or longer to recover, While radiologic features, clinical symptoms and biochemical depending on the dose and frequency of injections. IAGC admin- markers can overlap, surgical resection and histopathologic find- istered repeatedly can eventually lead to adrenal suppression. ings are considered more definitive. However histomorphologic Case Description: A 65-year-old man with history of cervical distinction between adenoma and low grade ACC can be difficult. A degenerative disc disease was referred to our clinic for severe fa- periodic clinical follow up may be warranted in such borderline tigue and an unintentional weight loss of 35 pounds over the past cases. year. He had been evaluated by his Internist and Rheumatologist Case Description: A 68 y/o Caucasian lady was referred for evalu- who were unable to find a cause for his symptoms. The patient was ation of a right adrenal mass of 3.8 cm in size on a CT abdomen in afebrile and normotensive. Physical examination revealed multiple 01/2020. Patient reported the incidental adrenal mass was first skin abrasions and ecchymoses on his forearms. Laboratory detected in 2006. Initial CT abdomen showed right adrenal mass of assessment showed normal Hb, renal, liver, and thyroid function 2.6 x 3.4 cm that was ovoid, well circumscribed, hypodense of -40 tests. His HbA 1 c was also unremarkable. His fasting morning Hounsfield units consistent with a lipid rich, benign adrenal ade- cortisol level was low at 0.7 mcg/dL (reference range 5 noma. Subsequently she had yearly CT abdomen from 2007 to 2010 22 mcg/dL) and his ACTH level was low at 1.8 pg/mL (reference that demonstrated the mass was stable, supporting its benign na- range 7.2 e 63.3 pg/mL). His medication list did not include any ture. No hormonal work up was performed from 2006 to 2010. glucocorticoids, but an extensive chart review revealed that he had Fourteen years later, CT scan abdomen in 01/2020 showed overall been receiving cervical Triamcinolone injections every three stable right adrenal mass of 3.8 cm. However a central soft tissue months for the past three years. He was started on Hydrocortisone component of 1.1 cm with arterial phase enhancement and indeter- and subsequently reported significant improvement in his minate wash out was noted. The change was new, not seen in prior symptoms. imaging studies. Possibility of a pheochromocytoma or collision tu- Discussion: This case highlights the importance of recognizing that mors was of concern. Patient denied symptoms of sympathetic excess IAGC have the potential to suppress the HPA axis and cause adrenal or virilization. Her weight was stable. A1c was 5.1%. She had well suppression. The degree of absorption of IAGC depends on the size controlled hypertension. DXA scan was normal. Hormonal work up of the joint injected, dosage, frequency and type of injectable for Conn’s and pheochromocytoma was negative. 1 mg dexametha- glucocorticoid preparation used. Our patient could have been sone suppression test showed non-suppressed 8 am serum cortisol at diagnosed and treated much earlier had an explicit verbal and/or 2.5 ug/dl with suspicion for subclinical hypercortisolism. written explanation about the presence and adverse effects of She underwent laparoscopic right adrenalectomy in 08/2020. glucocorticoids been provided by the pain specialist. Physicians Gross pathology showed a 33 gm adrenal gland, well circumscribed administering IAGC in their practice should be educated about this, with golden yellow color and a central gray brown discoloration of and measures to make this information more easily available to the 1.2 cm with focal capsular and periadrenal fat invasion. Presence of patient and more accessible to other physicians involved in the clear cell cytoplasm, without mitotic figures, or microscopic ne- patient’s care should be implemented. Such measures would pre- crosis indicated benign findings. Histochemical stain was negative vent unnecessary expensive investigations and would also reduce for Ki-67 of 2% or less and p53 negative with intact acinar patients’ morbidity by preventing delays in appropriate therapy. architecture. Unfortunately, there are no official guidelines regarding this issue, Discussion: Our patient had borderline adrenal mass with new and clinical suspicion based on a patient’s history and clinical signs central necrosis and indeterminate wash out . Gross pathology and symptoms remains the critical factor in such cases. showed central gray discoloration, focal capsular and periadrenal fat invasion concerning for malignancy. While histopathology had https://doi.org/10.1016/j.eprac.2021.04.514

S21 Adrenal Disorders Endocrine Practice 27 (2021) S1eS23

Abstract #1004341 Abstract #1004351

Protein-Energy Malnutrition Increases the Healthcare Subclinical Cushing's Syndrome, a Commonly Missed System Burden in Patients Hospitalized with Adrenal Phenomenon in Diabetic Patients Insufficiency: An Analysis of the National Inpatient Sample Registry Author Block: Padmini Giri - Wayne State University Internal Medicine; Verisha Khanam, MD - Co-Author, Internal Medicine, Wayne State University; Kulairi Zain, MD - Co-Author, Internal Author Block: Kevin Bustos, DO - Primary author, John H. Stroger Medicine, Wayne State University Jr. Hospital of Cook COunty; Ramtej Atluri, MD - co-author, John H. Stroger Jr. Hospital of Cook COunty; Marcelo Ramirez, MD - co- Introduction: Subclinical Cushing's syndrome (SCS) is a condition author, John H. Stroger Jr. Hospital of Cook COunty; Hafeez Shaka, of autonomous cortisol secretion in without the typical signs of MD - co-author, John H. Stroger Jr. Hospital of Cook COunty; hypercortisolism, like in Cushing’s Syndrome (CS). SC is the most Mukunthan Murthi, MD - co-author, John H. Stroger Jr. Hospital of common hormonal abnormality associated with adrenal inci- Cook COunty dentalomas (prevalence of 1-29%). SH with adrenal incidentalomas is often connected with obesity and insulin resistance. Type 2 Objective: Protein-Energy Malnutrition (PEM) is prevalent in pa- Diabetes mellitus (T2DM) is a condition characterized by insulin fi tients hospitalized with adrenal insuf ciency (AI). This can be resistance. These patients generally present with insulin resistance, attributed to factors such as reduced caloric intake due to fatigue, obesity, hyperlipidemia, and hypertension. It has been reported decreased appetite and increased nausea/vomiting. The impact of that many patients with T2DM may have an underlying SH given metabolic derangements such as PEM on outcomes in AI patients is the common clinical features. There are many implications to these fi not well de ned. We aimed to assess the impact of PEM on out- combined disorders. fi comes in patients admitted with adrenal insuf ciency. Case Description: 38-year-old Caucasian female who was diag- Methods: Data was extracted from the Nationwide Inpatient nosed with T2DM about 8-years prior to her initial admission in Sample (NIS) for 2018. The NIS contains hospital discharge infor- 2015, has presented multiple times to our facility with decom- mation estimating yearly US hospitalizations. Patients with prin- pensation of her glucose control, many times in diabetic ketoaci- fi cipal diagnostic codes for adrenal insuf ciency (AI) were included. dosis. From her initial presentation with her HbA1c of >12% she has These patients had AI as the reason for hospitalization. Hospitali- gained much better glucose control through insulin and the most zations less than 18 years were excluded. This cohort was divided current HbA1c is 6.5%. She did have many admissions despite based on secondary diagnosis of protein-energy malnutrition decreasing HbA1c levels. Initial CT abdomen/pelvis in 2015 showed (PEM). a left adrenal incidentaloma of 1.6x1.6x2.5cm, which steady Outcomes included inpatient mortality rates, length of hospital increased in size to 4.1x3.5x3.4cm in 2020. She did have mild stay (LOS), hospitalization cost (HC), rates of septic shock, acute cushingoid features such as obesity and insulin resistance, but was myocardial infarction (AMI), acute respiratory failure (ARF), acute not diagnosed with overt Cushing’s syndrome. Previously docu- renal failure (AKI), acute pulmonary edema (PE) between the sub mented AM cortisol levels were < 5 ug/dL which have increased to groups. Adjustment was made for biodemographic, hospital factors >64 in 2020. Urine 24H cortisol was significantly elevated and all and Carlson comorbidity index using a robust multivariate regres- other workup for adrenal hypersecretion was unremarkable. She sion analysis. did undergo a left adrenalectomy in 2020. Results: Out of the 7975 hospitalized patients with AI, 1005 in- Discussion: It was thought that this patient had brittle diabetes but dividuals had protein-energy malnutrition. Mean length of stay with further workup she was also found to have subclinical (LOS) and mean hospital charges (HC) were higher in the presence hypercortisolism. The effects of the adrenal incidentaloma may of protein-energy malnutrition compared to those without (6.80 have subtly contributed to her increasing and varying insulin re- & daysvs4.17days $16,632 vs $9,312 respectively). When adjusted quirements throughout the years as well as to her multiple in- to patient demographics, comorbidities, and hospital characteris- stances of diabetic decompensations. Many studies have reported < tics, AI patients with PEM had longer LOS by 3.4 days (p 0.000) on the findings of occult Cushing’s syndrome in T2DM patients. < and an additional HC of $6,978 (p 0.000). However, there was no There are no guidelines regarding testing for SH in T2DM although ¼ ¼ statistical difference in in-hospital mortality (aOR 2.30, p 0.16), it is a more common phenomenon. This is an important discussion ¼ ¼ ¼ ¼ septic shock (aOR 1.80, p 0.59), stroke (aOR 2.30, p 0.27), as hypercortisolism contributes to increased insulin requirements, ¼ ¼ myocardial infarction (aOR 2.14, p 0.095), acute renal failure obesity, and the overall picture of Metabolic X syndrome. There ¼ ¼ ¼ ¼ (aOR 0.94, p 0.75), acute respiratory failure (aOR 1.65, p 0.052) should be more research done on the topic to determine if it should ¼ ¼ or acute pulmonary edema (aOR 1.55, p 0.55) in AI patients with be standard practice to test those with Diabetes for SH. PEM. Discussion/Conclusion: AI patients with PEM had worse outcomes https://doi.org/10.1016/j.eprac.2021.04.516 in terms of length of stay and healthcare cost compared to those without PEM. This suggests that PCM is an adverse prognostic marker in this population. Current limitations include the under- Abstract #1038815 representation of metabolic derangements due to inadequate Bilateral Adrenal Ablation in patient with Persistent coding within this administrative database. Future models for Cushing's treating adrenal insufficiency should consider the potential advantage from nutritional supplementation and expertise of clinical dietitians to increase body weight in AI patients who are at Author Block: Lloyd Petty - University of Utah; Karma Elliott, MD - risk of malnutrition as a method of reducing length of stay and co-author, presenter, Endocrinology, university of utah; healthcare cost. Anu Sharma, MD - co-author, Endocrinology, university of utah; https://doi.org/10.1016/j.eprac.2021.04.515 Matthew Wahl, MD - co-author, university of utah

S22 Adrenal Disorders Endocrine Practice 27 (2021) S1eS23

Objective: Discussionon case report on patient with persistent Hospital Damas; Cesar Trabanco, MD - c–author, Endocrinology, Cushing's who underwent Bilateral Adrenal Ablation with good Hsopital Damas response. First report in literature of attempted of Bilateral Adrenal Abla- Objective: Autoimmune polyendocrinopathy-candidiasis-ecto- tion, which may be alternative to surgical bilateral adrenalectomy dermal dystrophy Type 1 (APECED) is a rare autosomal recessive in patient who are not candidates for surgery. disorder predisposing early in life to chronic mucosal candidiasis Methods: Case report poster submission. and the progressive development of various endocrinopathies such Results: The patient was a 72 year old male with atrial fibrillation, as Addison’s disease, primary hypoparathyroidism and Type I DVT, OSA on CPAP, Type II Diabetes Mellitus who was initially seen Diabetes. Few cases of renal involvement on this disorder have been in clinic in 2019 for T2DM and was noted to have signs/symptoms of described in literature,however there has been limited evidence on hypercortisolism (thin skin, bruising, poor wound healing) which Type I Renal Tubular Acidosis (RTA) and APECED. We describe the prompted subsequent extensive workup for Cushing's. case of a patient with APECED and hypokalemia as a result of 1mg DST, cortisol 29.6 concomitant Type I (Distal) RTA. 1mg DST, cortisol 23.7, dexamethasone 142, ACTH 79 Methods: Case of 47-year-old female patient with past medical 24h urine free cortisol 60.1mcg history of Autoimmune Polyglandular Syndrome Type I, Type 1 24h urine free cortisol 143.6mcg Diabetes Mellitus, Hypothyroidism and Nephrolithiasis who pre- AM cortisol 21.7, ACTH 86, DHEA-S 63 sents to the emergency department complaining of bilateral upper Midnight salivary cortisol 1.174ug/dL (nl < 0.112 ug/dL) and lower extremity weakness that started one week prior.On MRI Brain not notable for any lesion. No discrete pituitary lesion initial evaluation, patient reports that her symptoms worsened on identified. day of admission. Physical examination revealed decreased The patient then underwent IPSS suggestive of possible ACTH strength in all four extremities 2/5, deep tendon reflexes preserved dependent process. and no gross motor or sensory deficit present. Patient was taking Patient underwent TSRPT with pathology showing Pituitary Hy- oral steroids for Addison’s disease and calcitriol supplementation perplasia with production of ACTH. However patient continued for hypoparathyroidism since many years ago. Patient reported an with hypercortisolism. The patient then underwent repeat TSRPT episode of similar symptoms 17 years ago due to unexplained hy- and hypophysectomy, however even after second attempt the pa- pokalemia and since, she had been taking oral potassium chloride tient the patient continued with hypercortisolism. The patient supplementation. elected for bilateral adrenalectomy, but he was not a candidate for Results: Laboratory workup results: Sodium (Na): 140 mmol / L major surgery given multiple comorbidities. The decision was then (N:135-144mmol/L),Potassium(K):2.0mmol/L(N:3.4-4.5 made to attempt bilateral adrenal percutaneous microwave abla- mmol / L), Chloride (Cl): 110 mmol / L (93-107 mmol / L), Bicar- tion. The patient initially, after the procedure did not have evidence bonate: 18mmol / L (N: 23-31 mmol / L), Albumin: 3.4 g / dl (N: of adrenal insufficiency, but developed adrenal insufficiency 3.5-5.2 g / dl), Anion Gap: 12 (N: 10-12), Magnesium: 2.6 mg / dl requiring corticosteroids and mineralocorticoid replacement 6 (N: 1.7-2.5 mg / dl, blood glucose (BG): 313 mg / dl (N: 70-110 mg / months after his procedure. The patient has not demonstrated dl), Glycosylated Hemoglobin (HbA1c): 5.2% (N: 4.7-6.2%) and evidence of hypercortisolism since then. Anti-glutamic acid decarboxylase antibodies > 25,000 U / ml (N: < Discussion/Conclusion: Bilateral adrenal microwave ablation for 5U/ml).AdrenalInsufficiency was ruled out by laboratory curative purposes of cortisol hormone excess may be a therapeutic findings but significant for hyperchloremic, normal anion gap option in patient who are not candidates for surgical bilateral metabolic acidosis (NAGMA) and severe hypokalemia. Urinalysis adrenalectomy, which had not been explored before. Will discuss unremarkable for urinary tract infection but alkalotic pH:7.0 (N : the response this patient had and what providers may expect, 4.5-8.0). Also, urine spots were measured to differentiate the based on this patient and review of the literature of patient who etiology of NAGMA, yielding urine sodium: 92 mmol / L, urine had undergone single adrenal ablation. It's important to know that potassium: 10 mmol / L, urine chloride: 90 mmol / L and response to adrenal ablation can take several month to manifest. Urine Anion gap of 12 mEq / L, which suggests a low urinary NH4 +, consistent with Type I (Distal) RTA. Patient was started https://doi.org/10.1016/j.eprac.2021.04.517 on IV potassium replacement and symptoms improved. Labora- tory results after treatment showed improvement on potassium level: 3.8 mmol / L and acidotic state with bicarbonate of 29. Pa- Abstract #1042630 tient was discharged home with alkali therapy for Type I (Distal) RTA. Hypokalemia in Autoimmune Polyglandular Discussion/Conclusion: RTA is an underrecognized condition Syndrome: A Case of Newfound Type I (Distal) Renal that may be inherited or acquired. RTA should be considered Tubular Acidosis for any patient with otherwise unexplained hyperchloremic, metabolic acidosis and may be the presenting manifestation of autoimmune diseases. We present this case as evidence for the Author Block: Yineli Ortiz - hospital Damas; Astrid Aviles, MD - co- coexistence of several different immune-mediated diseases in author, Internal Medicine, Hospital Damas; Adriana Torres, MD - the clinical context of APECED with an unusual association of co-author, Internal Medicine, Hospital Damas; Type I (Distal) RTA. Alexandra Rodriguez, MD - co-author, Internal Medicine, Hospital Damas; Jesenia De Jesus, MD - co-author, Internal Medicine, https://doi.org/10.1016/j.eprac.2021.04.518

S23 Endocrine Practice 27 (2021) S24eS71

Contents lists available at ScienceDirect

Endocrine Practice

journal homepage: www.endocrinepractice.org

DIABETES/PREDIABETES/HYPOGLYCEMIA

Abstract #973458 Results: Over the final three months of the study period, an average of 1.2 aspart and 1.3 glargine pens/patient were deemed appro- Inpatient Insulin Pen Implementation, Waste, and priately dispensed. Conversely, 19% of aspart pens (0.3 aspart pens/ Potential Cost Savings: A Community Hospital patient) and 22% (0.4 glargine pens/patient) were deemed unnec- Experience essarily dispensed. The average monthly cost of this insulin pen waste was $11,820.68, which projects to a yearly cost of total waste of $141,848.16.After the main causes of insulin pen waste were Author Block: Urooj Najmi - American International school of identified, hospital-wide education was initiated, and the default medicine; mihail Zilbermint, MD - primary author, Endocrinology, insulin label printing function was disabled in Epic Willow, the Suburban Hospital Johns Hopkins; Lee Ann Alexander, RPh, BCGP4 monthly waste dropped to 48% in month 5 and 42% in month 6. - co-author, Pharmacy, Suburban Hospital Johns Hopkins; Discussion/Conclusion: In this study, we investigated the associ- Andrew Demidowich, MD - co-author, Endocrinology, Johns ated waste and cost of transitioning from insulin vials to pens in Hopkins Community Physicians at Howard County General an inpatient setting, as well as the effects of a quality improve- Hospital,Johns Hopkins University School of Medicine, Baltimore; ment effort to mitigate this waste. A methodological plan Christina Lee, CPhT - co-author, Pharmacy, Suburban Hospital involving nursing education, task force communication, pharmacy Johns Hopkins; Periwinkle Mackay, RN, MSN, CCRN - co-author, leadership, and proper handling of insulin pens were keys in this Department of Nursing Education, Suburban Hospital Johns cost-saving effort. Overall, the use of insulin pens has resulted in Hopkins; Mahsa Motevalli, DNP, CRNP7 - co-author, Johns Hopkins greater satisfaction among nurses, physicians, and patients. In Community Physicians at Suburban Hospital; Cindy Notobartolo, another study, the handling and dosing accuracy of insulin pens MS, BSN, CHEP, HEM9 - co-author, Safety, Security and Employee versus vials and syringes were evaluated and discovered that in- Health Services, Suburban Hospital Johns Hopkins; sulin pens were easier to administer for insulin-naïve healthcare Jennifer Raynor, RPh, MSM, MHA - co-author, Pharmacy, Suburban providers. The insulin pen devices were also associated with Hospital Johns Hopkins; Poroshat Sartippour, MSN, RN - co-author, delivering more accurate doses and fewer variations than vials Management Information System, Suburban Hospital Johns and syringes. This research may be of interest to other hospital Hopkins; Cynthia Tucker, BSN, RN, CDE - co-author, Department of administrators and clinicians interested in introducing insulin Nursing Education, Suburban Hospital Johns Hopkins; pens to their respective clinical settings. In a community hospital Eyerusalem Yemane, PharmD, MHA4 - co-author, Pharmacy, setting, identification of causes leading to unnecessary insulin Suburban Hospital Johns Hopkins; Urooj Najmi, MD - primary dispensation and implementation of a multi-pronged quality author, American International School of Medicine; umair ansari, improvement effort led to change in insulin pen dispensation Pharm D, BCCCP, BCPS, MBA - co-author, Pharmacy, Suburban practice and reduction in waste. These changes may be translated Hospital Johns Hopkins; waqas Z. Haque, MPH, MPhil - co-author, into considerable cost savings. University of Texas Southwestern Medical School, Dallas, TX, USA https://doi.org/10.1016/j.eprac.2021.04.521 Objective: Insulin pen injectors (“pens”) are intended to facilitate a patient’s self-administration of insulin and can be used in hospi- Abstract #973787 talized patients. Unnecessary or duplicate dispensation of insulin pens is associated with increased healthcare costs. Tailored Insulin Sensitivity Factor Based Scales for Methods: This quality improvement project was carried out at Hospitalized Patients with Diabetes Suburban Hospital, a 240-bed community hospital in the Johns Hopkins Hospital System located in suburban Maryland, between July 2018 and July 2019, to assess inpatient insulin pen dispensa- Author Block: Joi C. Hester, Resident Physician - Primary author tion. Our institution used two types of insulin pens: insulin aspart and presenter, Internal Medicine, Morehouse School of Medicine; (NovoLog® FlexPen®) and insulin glargine (Lantus® SoloSTAR®). Seth Coleman, Faculty - Co-author, Internal Medicine, Unity The cost of each pen was $16.19 and $25.08, respectively. A phar- Health; Stephen Wagner, Associate Program Director - Co-author, macist-led insulin pen task force consisting of nurses, Epic Willow- Internal Medicine, Unity Health; Teresa Nimmo, Faculty - certified systems analyst, certified diabetes care and educator Co-author, Med/Peds Endocrinology, Arkansas Diabetes and specialist (formerly certified diabetes educator), hospitalist and Endocrinology Center; Suporn Sukpraprut-Braaten, Faculty - endocrinologist implemented a hospital-wide awareness campaign Co-author, Biostatistics, Unity Health; Stephanie Igtiben, Resident and collaborated with the hospital leadership to define goals and Physician - Co-author, Internal Medicine, Unity Health; interventions. Francisco Pasquel, Faculty - Co-author, Endocrinology, Emory

1530-891X Diabetes/Prediabetes/Hypoglycemia Endocrine Practice 27 (2021) S24eS71

Objective: Patients with diabetes are very heterogeneous and impact on the health status of affected individual. DEB are frequent require individualized treatment approaches in the outpatient in type 1 diabetes and are associated with remarkable impairment setting. However, in the inpatient setting, patients are frequently of metabolic control. However there is less data regarding the started on standard insulin sliding scale order sets. These sets are prevalence of eating disorders in patients with type 2 diabetes often ordered regardless of the patient’s type of diabetes, insulin (T2DM) and that too with variable results. There is hardly any data dependence, sensitivity, or their current glycemic control. regarding the disordered eating behaviours in subjects with T2DM Methods: Following quality improvement processes, we imple- in the Indian state of Punjab which has the prevalence of diabetes mented six order sets for insulin correction scales based on around 10%. This study was done to evaluate the prevalence of DEB outpatient diabetes practices considering the most commonly used and their association with glycaemic control and metabolic pa- insulin sensitivity factors (ISF) e 50, 40, 30, 25, 20, and 15. We then rameters in adult subjects with T2DM in Punjab. delivered hospital-wide education on the proper selection of the Methods: This cross sectional study was conducted in 512 T2DM new ISF-based scales. We conducted a retrospective cohort study patients (271 males and 241 females) who were attending the out - involving hospitalized patients with diabetes to determine if the patient department of an endocrine centre in a city of Punjab. new tailored ISF-based scales can improve glycemic control versus Control group included 250 age matched, healthy, non-diabetic a single sliding scale. Using the R.3.5.2 program, we compared the subjects. Participants were subjected to detailed medical history, percentage of blood glucose (BG) values within the target range anthropometric measurements and the relevant investigations. (70-180 mg/dl) and the percentage of BG values that were out of the Eating Attitudes Test (EAT-26) questionnaire was used to determine target range e hypoglycemic (< 70 mg/dl) and hyperglycemic the probability of having DEB. A score of 20 on EAT-26 was (>180 mg/dl). We also constructed logistic regression models defined as abnormal, indicating high probability of having DEB. adjusting for age, body mass index (BMI), days of hospital stay, race, Statistical analysis was done with SPSS and p value of < 0.05 was gender, and smoking status to determine the odds of achieving BG significant. values in the target range using the new tailored ISF-based scales. Results: Mean age of subjects with T2DM was 47.2 ± 18.1 and 46.8 ± Results: A total of 310 patients with either type 1 or type 2 diabetes 19.8 years in the control group (p-0.19). Mean BMI of subjects with mellitus admitted to the hospital were included in the study. We T2DM was 28.9 ± 8.4 and 23.1 ± 9.1 in the control group (p-0.21). excluded patients with end stage renal disease and women who Out of all participants, 8.2% of subjects with T2DM and 7.1 % of those were pregnant. The average age was 59.2 (±15.3) years old, 59.6% in control group had an EAT-26 score of 20 indicating that they were males, and 40.4% were females. A total of 282 patients were were at high risk of developing DEB. There was no statistically placed on the single sliding scale, which yielded 3,097 BG values. A significant difference in the prevalence of abnormal EAT-26 score total of 28 patients were placed on the new tailored ISF-based between the two groups (p-0.12). scales, which yielded 585 BG values. In the single sliding scale Discussion/Conclusion: The topic of eating disorders in subjects group, 909 (29.4%) of the BG values were in the target glycemic with type 2 diabetes has been of great interest but the early range and 2,188 (70.6%) were out of the target range (2.5% in hy- detection, prevention strategies, and treatment approaches are less poglycemia range; 68.1% in hyperglycemia range). In the new well defined. Data regarding the prevalence of DEB in T2DM are tailored ISF-based scales group, 327 (55.9%) of the BG values were inconsistent and a review by Ricardio et al with studies mainly from in the target glycemic range and 258 (44.1%) were out of the target western countries has mentioned the prevalence of DEB in T2DM range (2.4% in hypoglycemia range; 41.7% in hyperglycemia range). up to 40 %. In the present study by using a simple screening clinical After adjusting for age, BMI, race, gender, and smoking status, pa- tool EAT-26 questionnaire, we have found that the prevalence rate tients in the new tailored ISF-based scales group had 2.57 higher of DEB in subjects with T2DM in Indian state of Punjab is around odds of being within target range compared to the patients in the 8.2% which is much less than what has been reported in the single sliding scale group (odds ratio¼2.57; 95% CI 2.13 to 3.10; western literature. Also it has been noted that the prevalence of p-value< 0.0001). This association remained significant after DEB in the present sample of subjects with T2DM is not higher than adjusting for days of hospital stay (odds ratio¼1.87; 95% CI 1.51 to the non-diabetic subjects. We conclude that the eating disorders 2.32; p-value< 0.0001). are less prevalent in Indian subjects with T2DM than in western Discussion/Conclusion: For patients with diabetes admitted to the counterparts. hospital, being placed on the new tailored ISF-based scales signif- https://doi.org/10.1016/j.eprac.2021.04.523 icantly improves the likelihood of achieving BG values in the target range compared to being placed on a single sliding scale. https://doi.org/10.1016/j.eprac.2021.04.522 Abstract #975885

Euglycemic Diabetic Ketoacidosis Secondary to SGLT2- Abstract #974467 inhibitor Use in Combination with a Ketogenic Diet: A Case Report Prevalence of Disturbed Eating Behaviours In Subjects with T2DM in the Indian State of Punjab Author Block: Joi C. Hester, Resident Physician - Primary author and presenter, Internal Medicine, Morehouse School of Medicine; Author Block: Vipan Talwar, MD, FACE - Presenter or primary Stacy Zimmerman, Program Director - Co-author, Internal author, Endocrinology, Golden hospital; Gourav Talwar, Medicine, Unity Health; Teresa Nimmo, Faculty - Co-author, Med/ Department of Endocrinology - co-author, Endocrinology, Golden Peds Endocrinology, Arkansas Diabetes and Endocrinology Center; hospital Wesley Cunningham, Faculty - Co-author, Internal Medicine, Unity Health; Joshua Liu, Resident Physician - Co-author, Internal Objective: Disturbed eating behaviours (DEB) encompass extreme Medicine, Unity Health; Suporn Sukpraprut-Braaten, Faculty - Co- dieting behavior, binge eating attacks, and compensatory behavior author, Biostatistics, Unity Health; Francisco Pasquel, Faculty - Co- for weight control and can have a potentially life-threatening author, Endocrinology, Emory

S25 Diabetes/Prediabetes/Hypoglycemia Endocrine Practice 27 (2021) S24eS71

Introduction: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors potential diabetogenic effect of SARS-COV-2 (Severe Acute respi- are cardiorenal protective agents increasingly used in patients with ratory syndrome coronavirus). diabetes. Cases of euglycemic diabetic ketoacidosis (euDKA) have Case Description: We present a case series of observations among 8 been reported particularly among patients with type 1 diabetes. patients of age group ranging from 34 to 74 years with a BMI range Our case is an example that highlights the role SGLT-2 inhibitors of 26.61 to 53.21 Kilogram/square meters that developed new- play in the development of euDKA in a patient with type 2 diabetes onset diabetes after COVID-19 infection. with confounding factors of strict adherence to a ketogenic diet and There was no past medical history of diabetes, pre-diabetes in ankle fracture. our patients as evidenced by lab work/Hba1c done prior to Case Description: A 72-year-old female with a history of type 2 hospitalization by their primary care doctors. At admission, they diabetes presented to the emergency department (ED) with right were diagnosed to have COVID-19 based on PCR testing. All ankle pain and obvious deformity after a mechanical fall. Radiog- patients had severe COVID-19 infection (defined by requiring raphy of the right lower extremity confirmed distal fracture of the nasal cannula oxygen therapy of more than 3litres/minute to tibia and fibula. After reduction of her fracture in the ED, she was maintain pulse saturation above 93%), which warranted their admitted in anticipation of an open reduction internal fixation. Her admission to the hospital. Initial random blood glucose levels in diabetes was controlled on empagliflozin monotherapy and the basic metabolic panel were elevated, which prompted us to adhering to a ketogenic diet. She monitored her blood ketones daily check the Hemoglobin A1C, which ranged between 6.7 to 11.8%. at home and reported values in the 3-4 mmol/L range. On admis- All patients received subcutaneous basal-bolus insulin therapy in sion, her basic metabolic panel (BMP) revealed a blood glucose of the hospital for glucose management. As part of the COVID-19 148 mg/dL, bicarbonate of 20 mEq/L, anion gap of 18 mEq/L, Cr of treatment protocol in our hospital, patients received steroids, 1.3 mg/dl, and eGFR of 40 mL/min. Her beta-hydroxybutyrate (BHB) empirical antibiotics, and were placed on deep vein thrombosis was 5.09 mmol/L. The initial assessment was presumed starvation prophylaxis. A dexamethasone loading dose of 8 milligrams and ketosis. followed by 6 milligrams daily for a total duration of 10 days On hospital day three, she complained of continued nausea, was given to the patients. All patients followed with outpatient polydipsia, and abdominal pain. Chart review revealed nocturia providers, where they continued to require blood glucose- with approximately 3-4 voids per night. Repeat BMP showed a lowering treatment despite stopping getting steroids. Out of blood glucose of 152 mg/dL, bicarbonate of 16 mEq/L, anion gap still them, five patients had fasting detectable C-peptide ranging at 18 mEq/L, Cr 1.4 mg/dl, and eGFR of 37 mL/min. Since admission, between 2-3ng/ml (0.80-3.85 ng/mL) with negative GAD(Gluta- all of her blood glucose levels ranged between 118-178 mg/dL. She mic acid decarboxylase)-65 antibody levels. denied dyspnea but exhibited Kussmaul respirations on physical Discussion: The 8 patients without a past medical history of dia- exam. Repeat labs revealed a BHB of 8.92 mmol/L, and arterial blood betes admitted with COVID-19 infection developed new-onset gas (ABG) showed pH 7.2, pCO2 23, pO2 100, bicarbonate 8.6 mEq/L, diabetes mellitus due to plausible interaction of SARS-COV-2 with consistent with high-anion gap metabolic acidosis, confirming the ACE 2 receptors. SARS-COV-2 binds to Angiotensin-converting diagnosis of euDKA. Her empagliflozin had been held since enzyme-2(ACE-2) receptors located in essential metabolic tissues admission, but she had not received any insulin up to this point due including the pancreas, adipose tissue, small intestine, and kidneys. to euglycemia. She was immediately started on a weight-based The resulting downregulation of ACE-2 and ACE-2 receptor dose of 12 units of insulin glargine with subsequent improvement expression caused islet-call damage resulting in diabetes. of her BHB and anion gap. The resulting observation has the potential to adversely impact a Discussion: This patient’s use of an SGLT2-inhibitor in combination significant number of the globally affected population. Screening with her being on a ketogenic diet, contributed to a nonregulated patients with COVID-19 for diabetes routinely can help in early state of ketone production leading to euDKA in the perioperative detection, significantly reducing morbidity and mortality associ- period. As SGLT2-inhibitors become more readily available, it is ated with diabetes. important to educate physicians and patients about the risk of Due to limitations of observational study with a small sample size euDKA during fasting, ketogenic diets, and the perioperative will require further investigation in the form of Clinical trial. period. https://doi.org/10.1016/j.eprac.2021.04.525 https://doi.org/10.1016/j.eprac.2021.04.524

Abstract #978492 Abstract #976395 To Access the Risk of Developing Diabetes Among the Case Series: COVID-19 Infection Causing New-Onset First Degree Adult Relatives of Patients with TYPE 2 Diabetes Mellitus? DM using Indian Diabetes Risk Score (IDRS)

Author Block: Narasa Madam, MD - Co author, Yuma Regional Author Block: Vipan Talwar, MD, FACE - Presenter or primary Medical Center; Rujuta Katkar, MD - Presenter, Yuma Regional author, Endocrinology, Golden hospital; Gourav Talwar, Medical Center Department of Endocrinology - co-author, Endocrinology, Golden hospital Introduction: There is a bidirectional relationship between COVID- 19 and diabetes. Not only diabetes is associated with an increased Objective: India has the second largest population of diabetics in risk of severe COVID-19 but also new-onset diabetes and severe the world. About 50% of the diabetic subjects in India remain un- metabolic complications of preexisting diabetes, including diabetic aware of their diabetes status. Evidence suggest that the detection ketoacidosis and hyperosmolarity for which exceptionally high of subjects having high risk of developing diabetes in future can doses of insulin are warranted, have been observed in patients with help to intercept or delay the onset of diabetes and associated Covid-19. This paper seeks to explore the hypothesis of the vascular complications. This study was planned to access the risk of

S26 Diabetes/Prediabetes/Hypoglycemia Endocrine Practice 27 (2021) S24eS71 developing diabetes among first degree asymptomatic adult rela- C-peptide. Further workup included measurement of IGF-2 and tives of patients with Type 2 diabetes mellitus (T2DM). IGF-1 levels which showed a ratio greater than ten, suggestive of Methods: Participants were 832 adult asymptomatic first degree IGF-2 paraneoplastic hypoglycemia syndrome. Hypoglycemia relatives of T2DM patients. Detailed history and Anthropometric improved with prednisolone, permitting discontinuation of measurements were carried out. All participants were adminis- dextrose infusion. tered the “Indian Diabetes Risk Score” (IDRS), which is a simple, Other results included suppressed TSH, elevated Free T4, and cost effective tool for screening the people at high risk of devel- elevated thyroid-stimulating immunoglobulin which confirmed a oping diabetes. IDRS analyses data accessed from four risk factors, Toxic Diffuse Goiter. Further treatment included methimazole, two modifiable (waist circumference and physical activity) and two beta-blocker, and iodine solution. A biopsy of the liver mass non-modifiable (age and family history of T2DM). Based upon the revealed hepatocellular carcinoma (HCC). She underwent trans- IDRS value, the subjects are categorised as having High (IDRS: > 60), arterial chemoembolization. Moderate (IDRS : 30-60) and Low risk (IDRS : < 30) of developing Discussion: There are multiple pathogenic mechanisms that may diabetes. Data was analysed using SPSS and P value < 0.05 was lead to tumor-induced hypoglycemia. Insulinomas are the most significant. common cause of tumor-induced hypoglycemia. NICT may cause Results: The participants included 437 Males (52.6.%) and 395 Fe- hypoglycemia from the secretion of a variety of factors such as IGF- males (47.4%) with the the mean age of 49.92+13.12 years. As per 2, IGF-1, somatostatin, GLP-1, and autoantibodies to the insulin their IDRS value, out of all the participants, 285 (34.3%) were at low receptors. Tumors may also cause hypoglycemia from excess risk, 304 (36.5%) were at moderate and 243 (29.2%) at high risk of glucose consumption. developing diabetes (p< 0.01). The mean IDRS was significantly After evidence of hypo-insulinemic hypoglycemia, confirmatory higher among female than male subjects (p-0.012). IDRS had sig- testing for NICT should include measurement of IGF-2, IGF-1, Pro- nificant correlation with age , BMI, waist circumference and level of IGF-2, IGFBP-3, and GH. Paraneoplastic overproduction of IGF-2 or exercise (all p< 0.01) Pro-IGF-2 leads to the activation of insulin receptors promoting Discussion/Conclusion: Indian diabetic risk score is a screening tool glucose uptake in peripheral tissues. Pro-IGF-2 suppresses the used to assess the risk of diabetes among general population. It has secretion of GH and insulin. Due to a decrease in GH, secretion of a sensitivity of 72.5% and specificity of 60.1% in predicting diabetes. IGF-1 and IGFBP-3 are decreased. A ratio of IGF-2/IGF-1 >10 is In Our study about 65.7% of first degree relatives of T2DM patients highly suggestive for the IGF-2 secreting tumor. Measurement of were at medium to high risk of developing diabetes in future. Age Pro-IGF-2 can be also useful in the diagnosis. Treatment involves and BMI showed a significant linear increase with IDRS scores and immediate correction of hypoglycemia and surgical resection of the the most of subjects in high risk group were practicing sedentary tumor, when possible. Glucocorticoids may reduce recurrent hy- life style. Early identification of high risk individuals using IDRS poglycemia when a surgical approach is not possible. would help to emphasise the appropriate non-pharmacological https://doi.org/10.1016/j.eprac.2021.04.527 interventions like healthy eating habits, intense physical activity and weight reduction. This may help in halting the progression to the onset of diabetes and thus reduce the clinical, social and eco- Abstract #984349 nomic burden of the disease. We conclude that the simple clinical tools like IDRS can be useful Transition from Insulin pump to Multiple Daily in clinical practice to detect the asymptomatic subjects having high Injections using Insulin Degludec in Adults with Type risk of T2DM in future and plan timely interventions. 1 Diabetes: A Randomized controlled trial https://doi.org/10.1016/j.eprac.2021.04.526

Author Block: Viral Shah - Barbara Davis Center for Diabetes, Abstract #984008 University of Colorado; Halis K. Akturk, MD - Co-author, Barbara Davis Center for Diabetes; Hal Joseph, PA-C - Co-author, Barbara Recurrent Hypoglycemia in Hepatocellular Carcinoma Davis Center for Diabetes; Nicole Schneider, MD - Co-author, Barbara Davis Center for Diabetes; janet K. Snell-Bergeon, PhD - co-author, Barbara Davis Center for Diabetes Author Block: Padigar S. Tantry, MD - Primary, Endocrinology, University of South Florida; Sean Amirzadeh, MD - co-author, Objective: Currently there is no guidance on transition from insulin Endocrinology, University of South Florida; Alejandro Ramirez, MD pump to multiple daily injections (MDI) using ultra-long acting - co-author, Endocrinology, University of South Florida; insulin degludec (IDeg). We evaluated two methods for successful Madeline Candelario, MD - co-author, Endocrinology, University of transition from insulin pump to MDI using IDeg in adults with type South Florida 1 diabetes (T1D). Methods: This is a 3-week, randomized control, open label, single Introduction: Non-islet cell tumor (NICT) induced hypoglycemia is center clinical trial. After 1 week of run-in-period, adults with T1D a rare entity associated with increased tumor production of IGF-2. > 1 year, using insulin pump for > 6 months, and A1c between 6.5% Case Description: A 42-year-old woman with a history of a 10-cm and 8.5% were randomly transitioned from insulin pump to MDI liver mass presents to the ER with worsening nausea, abdominal using either standard of care (stopped insulin pump and started pain, and weight loss. Vital signs were normal, except for a heart IDeg in 1:1 dose) or overlap (IDeg 1:1 at pump basal dose, but pump rate of 112/min. BMI was 25.5 kg/m2. Physical exam revealed a continued for the first 48hrs with a gradual basal reduction; 50% goiter and a palpable right liver mass. On initial evaluation, plasma from 0-24 hrs, 75% from 24-48hrs and then stopped). Participants glucose was 44 mg/dL. During hospitalization, glucose levels were wore blinded Dexcom G6 and IDeg dose was not changed during frequently < 50 mg/dL, mostly asymptomatic, requiring intrave- the trial. Exploratory analysis of continuous glucose monitor nous dextrose. During one fasting hypoglycemic episode, results (CGM)-based percent time in range (70-180 mg/dL), time below showed a glucose of 55 mg/dL, undetectable insulin level, and low range (< 70 mg/dL) and time above range ( >180 mg/dL) were

S27 Diabetes/Prediabetes/Hypoglycemia Endocrine Practice 27 (2021) S24eS71 compared between groups during first 72 hours of randomization the combination of basal insulin and ISS”. When asked about NPH is presented here. insulin, most of the participants correctly identified it as interme- Results: 17 adults (age 35.7±9.1 years, A1c 7.5±0.5%, diabetes diate-acting insulin (92.2%), its duration of action (54.9%), the cir- duration 21.6±11.8 years, 53% females) were randomized to stan- cumstances when NPH should be used (58.8%), and its different dard of care, and 13 adults (age 38.2±9.5, A1c 7.2±0.6%, diabetes brand names (33.3%). Only 23.5% of residents identified the duration 20.5±13.0, 46% females) were randomized to overlap. At composition of insulin 70/30. 66.7% failed to identify Humulin R as baseline, CGM-based time spent in normal range (median 57.3% short-acting insulin. Most of them knew Humulin R U-500 and the [IQR 39.7-60.5] vs 61.3% [46.7-70.8], p¼0.19), time above range indications for its use (54.9%). For diabetic ketoacidosis (DKA), most (40.7% [31.2-56.1] vs 31.7% [26.1-52.7], p¼ 0.41) and time below of them correctly identified regular insulin as an initial type of in- range (4.8% [1.5-11.5] vs 2.2% [1.4-9.5], p¼0.46) were not statisti- sulin for infusion (86.3%) and selected the correct transition from cally different between patients randomized to standard of care or insulin infusion to subcutaneous (SQ) insulin (80.4%). 68.6% overlap group. During first 72 hours of randomization, standard of selected both insulin glargine and NPH as acceptable transition care group spent clinically significant (though statistically non- options from intravenous to SQ insulin. significant) less time in normal range (median 49.1% [IQR 37.9-53.1] Discussion/Conclusion: Our survey was a useful tool to gauge the vs 60.4 [44.4-65.4], p¼ 0.069), and more time spent above range knowledge of IM residents regarding diabetes and insulin. Most of (48.8% [40.7-59.1] vs 36.5% [20.4-48.5], p¼ 0.063) without differ- them were unaware of the need of starting both basal insulin and ences in time below range (3.0% [1.9-7.8] vs 3.7% [1.5-7.6], p¼ 0.92). ISS for admitted patients. Two-third of residents were unaware of Patients randomized to standard of care also required median of 2.5 the common names of different types of insulin and the composi- more correction boluses per day compared to patients randomized tion of 70/30 insulin. Most of the residents correctly answered to overlap in the first 72 hours of transition [6.5 correction boluses/ questions about DKA management. Hence, the lack of knowledge day [IQR 4.5-8.7] vs 4.0 [3.0-6.5], p¼0.2]. Regarding safety, both about insulin names and uses is an important limitation and a methods of transition were safe and there were no treatment- barrier to good patient care. Education in this regard could prove to related adverse events in either group. be vital to learn these common facts. Discussion/Conclusion: Overlap of IDeg and insulin pump for first https://doi.org/10.1016/j.eprac.2021.04.529 48 hours results in better glycemic control without increasing hy- poglycemia during first 72 hours of transition to MDI using IDeg in adults with T1D. Abstract #987382 https://doi.org/10.1016/j.eprac.2021.04.528 Perception of Controlled Carbohydrate Diet for Hospitalized Patients with Diabetes Abstract #986678

Internal Medicine Residents' Knowledge about Insulin Author Block: Yoon Kook Kim - University of Maryland; Kashif Munir, MD - Co-author, Medicine, University of Maryland School of Medicine; Shisi He, MS - Co-author, University of Author Block: Iqra Iqbal - Abington Jefferson Health; Maryland School of Medicine Artem Minalyan, MD - co-author, Internal Medicine, Abington Jefferson health; Muhammad Atique A. Khan, MD - co-author, Background: Approximately one-third of hospitalized patients Internal Medicine, Abington Jefferson health; Shristi Khanal, MD - have diabetes. Medical nutrition therapy, in addition to pharma- co-author, Internal Medicine, Abington Jefferson Health; cologic therapy, plays an important role in glycemic control, yet Jonathan D. Slusser, MD, Endocrinologist - co-author, there is lack of data regarding the patient experience of controlled Endocrinology, Abington Jefferson Health carbohydrate diet. These diets consist of a fixed amount of carbo- hydrates per meal, yet often contain concentrated sweets which, Objective: Internal Medicine (IM) residents take care of the vast anecdotally, result in patient dissatisfaction. majority of diabetic patients. Managing their blood sugar levels Objectives: Understand patients’ perception of controlled carbo- (BSL) in the hospital is an integral part of their training. Sometimes hydrate diet and investigate for any correlation with the patients’ residents are not fully aware of the important details of diabetes demographic information or glycemic control. management and insulin nomenclature. We designed a survey Methods: We surveyed 101 patients with diabetes on a controlled asking simple questions about insulin and glucose management to carbohydrate diet admitted to the University of Maryland Medical have a determination of the residents’ knowledge in this area. Center in Baltimore, Maryland. The questionnaire examined pa- Methods: The survey was conducted among IM residents of a large tients’ degree of satisfaction with their controlled carbohydrate diet university-affiliated community hospital using an anonymous and their inpatient glycemic control in relation to the hospital diet. web-based questionnaire. Overall, 16 questions related to the The patients were also asked to rate how similar the inpatient management of diabetes in the inpatient setting (types of insulin, diabetes diet is to meals they eat at home, and to rate the degree of choosing appropriate regimens, transitioning from infusion to consistency in the amount of carbohydrate in each meal. These data subcutaneous administration of insulin, etc.) were included in the were analyzed in relation to the patients’ hemoglobin A1c, outpa- survey. The survey was followed by their education via an inter- tient use of insulin, duration of diabetes diagnosis, and self-iden- active session. tified race. Results: We collected the responses from 51 Internal Medicine Results: No significant association between the patients’ opinions residents. 62.7% of participants correctly identified BSL targets for of consistent carbohydrate diet and hemoglobin A1c, outpatient in-hospital patients (140-180mg/dL). For the initial regimen of in- diabetes regimen, duration of diabetes diagnosis, or race was found. sulin in hospitalized patients after stopping oral antidiabetic drugs, Overall, patients felt the types of carbohydrates (3.8/5) and bever- the majority of respondents chose to start with sliding scale insulin ages (4.1/5) they received in the consistent carbohydrate meal were (ISS) alone (54.9%). Only 19.6% of people selected the option “start appropriate for patients with diabetes.

S28 Diabetes/Prediabetes/Hypoglycemia Endocrine Practice 27 (2021) S24eS71

Conclusion: Medical nutrition therapy is a key component of As this was a retrospective chart review over a two-year period, inpatient diabetes management. Patients’ perception of diet may limitations were evident as it may be beneficial for further analysis lead to dissatisfaction with their medical care and impact glycemic to be conducted with longer follow up data. The sample size of control. Our study showed patients were, in general, satisfied with patients tested for Glycomark was small and may be a reason sta- their inpatient consistent carbohydrate diets and their perception tistical significance could not be reached. After testing for Glyco- was not associated with glycemic control, race, or outpatient use of mark, a steady decline was noted in hemoglobin A1c for both type 1 insulin. Previous studies have shown a possible link between and type 2 diabetics. The diabetics tested for Glycomark noted an inpatient diabetes diet adherence and strong family support. The earlier reduction of hemoglobin A1c than the control group. This is potential benefits of controlled carbohydrate diets for hospitalized useful for clinicians to intervene earlier and modify treatment op- patients with diabetes, and whether alternative or personalized tions. Glycomark testing should not replace hemoglobin A1c diets (i.e. low carbohydrate or no concentrated sweets) may be testing; it should be used in conjunction to help guide treatment more beneficial requires further investigation. strategies. Glycomark is of clinical importance for all physicians as a reliable indicator of postprandial control. https://doi.org/10.1016/j.eprac.2021.04.530 https://doi.org/10.1016/j.eprac.2021.04.531

Abstract #991324 Abstract #992206 The Utility of 1,5 Anhydroglucitol as a Reliable Indicator of Glycemic Control in Diabetes Mellitus A Rare of Adverse Reactions of Pioglitazone: Hypersensitivity to the Active Substance Lactose

Author Block: Merlyn Mathew - Coney Island Hospital; Silvia Bercovici, MD, FACE - Co-author, Internal Medicine / Author Block: Ewelina Bryll-Perzan, MD - Primary author, SUNY Endocrinology, Coney Island Hospital Downstate Medical Center; Alice Yau, MD - Co-author, Woodhull Medical Center; Dave Paulomi, MD - Co-author, Woodhull Medical Objective: Serum hemoglobin A1c is the gold standard to Center; Gul Bahtiyar, MD - Co-author, Woodhull Medical Center; assess glycemic control. This study aims to examine an alter- Giovanna Rodriguez, MD - Co-author, Woodhull Medical Center native test, serum 1,5 anhydroglucitol, (Glycomark). The addition of Glycomark test is postulated to help toward significant re- Introduction: The thiazolidinediones (TZDs) are the only anti- ductions in serum hemoglobin A1c levels and improve glycemic hyperglycemic agents to directly reduce insulin resistance. Piogli- control. tazone appears to act via activation of specific nuclear receptors Methods: This is a retrospective chart review examining patients (peroxisome proliferator activated receptor gamma) leading to tested for Glycomark and serum hemoglobin A1c levels obtained increased insulin sensitivity of liver, fat and skeletal muscle cells in at baseline, 6-months, and 1-year intervals for both the test animals. Treatment with pioglitazone has been shown to reduce group and the control group. Goal of hemoglobin A1c reduction hepatic glucose output and to increase peripheral glucose disposal of at least 0.5%, at either the 6-month or 1-year mark, was in the case of insulin resistance. Pioglitazone has relatively potent considered as significant. All diabetic patients over the age of 21 A1C-lowering properties, a low risk of hypoglycemia, and durable years, regardless of treatment modality, were included in the glycemic effects. Side effects that have limited TZD use include study. Excluded from the study were all patients with cirrhosis, weight gain, increased bone fracture risk in postmenopausal fe- on home total parenteral nutrition, CKD stage 4-5 or requiring males and elderly males, and elevated risk for chronic edema or hemodialysis, and on sodium-glucose cotransporter-2 inhibitors. heart failure (1). Pioglitazone is available as a tablet for oral Results: 45 of the 873 patients seen in clinic were tested for administration containing 15 mg, 30 mg, or 45 mg formulated with Glycomark at least once. At baseline, pretesting showed an the following excipients: lactose monohydrate NF, hydrox- average hemoglobin A1c of 8.9% in type 2 vs 9.8% in type 1. By 6 ypropylcellulose NF, carboxymethylcellulose calcium NF, and months, the average hemoglobin A1c for a type 2 diabetic was magnesium stearate NF. Allergic reactions have been reported with 8.2% vs 8.9% in type 1. At 1 year, the average hemoglobin A1c frequency not known in patients taking pioglitazone (2). We report dropped to 7.8% in type 2 DM. The average baseline hemoglobin a rare adverse reaction of a patient with lactose allergy who A1c for the Glycomark group was 10.3% and 9.9% for control developed hypersensitivity to pioglitazone. group. At 1 year, the average hemoglobin A1c was 7.85% for Case Description: 45-year-old man with type 2 diabetes since 2004 Glycomark group and 6.86% for control group. The group that with no complications, overweight (BMI 28), hypertension, dysli- was tested for Glycomark achieved an average reduction in he- pidemia and s/p left hemithyroidectomy due to thyroid nodule ~2 moglobin A1c of 2.27% by the 1-year mark, as compared to 2.5% cm was referred to endocrine clinic for follow-up for his thyroid in the control group. Based on statistical analysis with a Kaplan nodule. Cytopathology report was consistent with benign pathol- Meier survival curve, the time elapsed to reach a significant ogy and had normal TSH. His most recent HbA1c was 7.8%. He de- hemoglobin A1c reduction for the group who tested for Glyco- nied hyper- or hypoglycemia. He stated that he had itching all over mark was 6.4 months, earlier than the 7.5 months compared his body after taking one of the medications. He denied nausea, with the control group (p-value of 0.0006). vomiting, diarrhea, bloating, abdominal pain, and rash. His current Discussion/Conclusion: This study was conducted with the goal of medications included metformin 1000 mg twice a day, acarbose applying Glycomark testing, in addition to hemoglobin A1c, in the 100 mg three times a day, glipizide 10 mg twice a day, pioglitazone setting of primary clinics as a reliable indicator for glycemic control. 15 mg daily, and atorvastatin 10 mg once daily. He started taking There was a statistically significant difference in the time elapsed to pioglitazone two months prior to this visit. He researched all of his reach a hemoglobin A1c reduction; the group who was tested for medications on the internet and found that lactose is one of the Glycomark achieved a significant reduction earlier than the control excipients of pioglitazone. Patient had known lactose allergy and group. his symptoms resolved after discontinuation of pioglitazone.

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Discussion: To our knowledge this is the first case report describing Author Block: Anand Shankar - Shankar Diabetes Care and a patient with allergy to pioglitazone due to preexisting lactose Research; Shamshad Alam, Cardiologist - Co-author, Ruban allergy. Pioglitazone contains 92.87 mg of lactose monohydrate Hospital, Patna; Nishant Anubhaw, Diabetologist - co-author, according to pharmaceutical package. Our goal is to bring aware- Ruban Hospital, Patna; Amit Kumar Das, Diabetologist - co-author, ness to other doctors who prescribe pioglitazone to patients with Shree Hospital, Muzaffarpur; Manish Kumar Prasad, Diabetologist - diabetes. This patient’s clinical symptom was a side effect of the co-author, Darbhanga additive rather than the active medication itself. Good history taking and medication review are essential to prevent drug al- Objective: The aim of this multicentre observational study is to lergies. It is important to listen and learn from patients and understand the usage and effect of remogliflozin as first add on consider alternate therapy in those with lactose allergy. after metformin in Indian patients. Also to assess effect on HbA1c reduction, side effects, hypoglycaemia and changes in quality of life https://doi.org/10.1016/j.eprac.2021.04.532 scores. Methods: This was a multicenter, observational, prospective study Abstract #992852 which 250 patients from 5 centres and each patient was followed up for 3 months. Patients with T2DM who were not controlled on Persistent Lactic Acidosis in Young Patients with metformin alone and remogliflozin 100mg BD was added. Poorly Controlled Diabetes Mellitus Results: At 12 weeks, average HbA1c levels had declined from 7.8 ± 0.6% to 7.1 ± 0.5% (p < 0.05) which further reduced to 6.9 ± 0.4% (p < 0.05) at week 24. FPG decreased from 158.8 ± 12.7 to 114.8 ± 10.5 Author Block: M Nauman Jadoon - Queen Elizabeth University and PPG from 236.4 ± 25.6 to 171.0 ± 19.4 respectively (p < 0.05). Hospital Glasgow; Muhammad Imran Khan, MBBS, MRCP - Co- Body weight (81.3 ± 14.8 vs. 78.2 ± 13.7 kg), BMI (30.6 ± 3.8 vs. 29.1 author, Royal Alexandria Hospital, Paisley; Sajjad Noor, MBBS, ± 2.6 kg/m2), waist circumference (102.44 ± 14.23 vs. 97.11 ± 12.74 MRCP - co-author, University Hospital Wishaw cm) has changed after 24 week of treatment. SBP declined from 136.8 ± 7.2 to 127.5± 5.3 and DBP from 83.1 ± 3.8 to 81.0 ± 2.6. Introduction: Lactic acidosis is a common finding in critically ill Neither severe hypoglycemia nor other serious adverse events patients with Type A being the most common one. In patients with developed during the study period. poorly controlled diabetes for a prolonged period of time, there is Discussion/Conclusion: Adding remogliflozin 100mg BD to Met- another condition, Glycogenic hepatopathy (GH), which can cause formin showed promising role in improving glycemic parameters, lactic acidosis. It is a rare condition that develops due to excessive lipid components and blood pressure. Low hypoglycemia risk accumulation of glycogen in the hepatocytes, leading to hepato- makes the drug a suitable add-on option for those with high HbA1c megaly and elevated transaminases levels in patients with uncon- values. trolled type 1 DM. https://doi.org/10.1016/j.eprac.2021.04.534 Case Description: Two cases with poorly controlled diabetes and glycogenic hepatopathy are presented. First patient was a 28 year old female with 20 year history of diabetes, HbA1c of 77 mmol/mol, Abstract #994997 BMI 24.1 kg/m2, 4 admissions with DKA in last 12 months; was admitted with lactic acid of 3.0 mmol/L. On presentation, labs Open-Source Automated Insulin Delivery Systems for showed Glucose 37.1 mmol/L, H+ 114 nmol/L, HCO3 3 mmol/L. She the Management of T1D: A Case Study on Closing the was treated for DKA which resolved in 34 hours. Lactate peaked at Loop during Pregnancy 7.4 mmol/L. Ultrasound showed hepatomegaly with normal LFTs apart from ALP of 163 U/L. Second case was another 28 year old with a 17 year history of diabetes, HbA1c of 118 mmol/mol, BMI Author Block: Khulood Bukhari, MBBS - Presenter and primary 23.6 kg/m2, 3 admissions with DKA in last 12 months; was author, Department of Medicine, University of Maryland Medical admitted with lactic acid of 2.7 mmol/L. On presentation, labs Center Midtown Campus; Rana Malek, MD - Co-author, Division of showed H+ 88 nmol/L, HCO3 6 mmol/L, Glucose 41.6 mmol/L. She Endocrinology, Metabolism and Nutrition, University of Maryland was treated for DKA which resolved in 29 hours. Lactate peaked at School of Medicine 5.5 mmol/L. Ultrasound showed hepatomegaly (19.5cm) with normal LFTs apart from ALP of 153 U/L. Basal bolus insulin regimen Introduction: Open-source automated insulin delivery (AID) sys- was continued and biopsy was not permed in either of the cases. tems integrate community-developed software with commercially Discussion: In these 2 patients with history of poorly controlled available continuous glucose monitors (CGM) and insulin pumps to diabetes and hepatomegaly on ultrasound, lactate levels continued deliver insulin in an automated and glucose-responsive fashion. A to rise during and after resolution of the DKA, with GH likely cause growing number of persons with diabetes are turning to open- of the hepatomegaly. It is important to differentiate it from NAFLD source technology to help manage their type 1 diabetes (T1D), as it does not progress to cirrhosis and can improve with better however, little is known about their efficacy and safety during glycemic control. pregnancy. Case Description: A 40-year-old female, G2 P1, presented for dia- https://doi.org/10.1016/j.eprac.2021.04.533 betes care in her 6th week of pregnancy. Her medical history was significant for T1D diagnosed at the age of 11 and Grave's disease in fi Abstract #994025 remission. Her rst pregnancy 5 years prior was complicated with recurrent episodes of nocturnal hypoglycemia, acceleration of An Observational Study to Understand Usage and proliferative diabetic retinopathy requiring laser treatment, and Effect of Remogliflozin as First Add-on After neonatal hypoglycemia requiring neonatal intensive care unit Metformin in Indian Type 2 Diabetes Patients (NICU) admission.

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She started ‘looping’ 6 months prior to conception. The code for ( >9 mmol/L), confirming presence of ketoacidosis. Blood alcohol building the iPhone application called ‘Loop’ that carried the al- level was undetectable (< 10 mg/dL). The patient was immediately gorithm for the automated insulin delivery (AID) system was started on insulin and dextrose infusion in accordance with the available online. She used a device called ‘RileyLink’ to connect her institutional protocol for diabetic ketoacidosis. Her ketoacidosis iPhone to a compatible Medtronic insulin pump and a Dexcom G6 promptly resolved and she developed persistent hypokalemia ul- CGM to build the open-source AID system. She used an interface timately requiring complete cessation of insulin infusion. Her blood called ‘Tidepool’ to view her CGM, insulin pump, and blood glucose glucose remained normal after stopping insulin infusion and meter data in one place and share it with her endocrinologist. She ketoacidosis did not recur. Her hemoglobin A1c returned normal expressed a clear understanding of potential risks associated with (5.4%), confirming our suspicion that her ketoacidosis was related the use of a non-FDA-approved system, and agreed to have supplies to alcohol consumption and not diabetes as had been initially for her Tandem T:slim insulin pump in case Loop failed to accu- assumed. She was subsequently discharged without any antidia- rately adjust for pregnancy-related changes. betic medications. Her A1C prior to conception was 6.4%. Between 6 and 12 weeks Discussion: Ketosis is commonly encountered in chronic alcoholics gestation, she spent 66% time-in-range (TIR), 28% time-above- due to accumulation of metabolites of alcohol such as acetaldehyde range (TAR) and 6% time-below-range (TBR). Between 18 to 24 and acetate that contribute to synthesis of acetyl-CoA. Progression weeks gestation she spent 68% TIR, 27% TAR, and 5% TBR. During to ketoacidosis, conversely, is rare partly because of the suppressive her third trimester, she spent 72% TIR, 21% TAR, and 7% TBR. The effect of alcohol on lipolysis. Abrupt cessation of alcohol con- newborn weighed 8lbs 4oz, did not experience hypoglycemia and sumption with inadequate caloric intake can lead to florid and did not require NICU admission. symptomatic ketoacidosis as was seen in our patient. Of note, blood Discussion: The three main open-source AID systems include alcohol level from a visit to the emergency room a week ago was OpenAPS, AndroidAPS, and Loop. The algorithm of Loop takes into more than 300 mg/dL, in sharp distinction to the current admission, account insulin effect, carbohydrate intake, blood glucose mo- suggesting onset of ketoacidosis coincided with reduced con- mentum, and retrospective correction to predict blood glucose sumption of alcohol. levels and generate recommendations for bolus and temporary https://doi.org/10.1016/j.eprac.2021.04.536 basal rates. Data from observational studies on open-source AID systems report increased TIR, decreased HBA1C, and reduced epi- sodes of hypoglycemia. Abstract #995396 The Continuous Glucose Monitoring in Women with Type 1 Diabetes in Pregnancy Trial showed that at baseline, pregnant Inpatient Sulfonylurea-induced Hypoglycemia and the women with T1D using CGM in combination with an insulin pump Transition to Outpatient: Addressing Chronic or multiple injections spent 52% TIR, 39% TAR, and 8% TBR; at 34 Overtreatment in High-risk Patients weeks gestation they spent 68% TIR, 27% TAR, and 3% TBR. Our patient had lower TBR during her first trimester and achieved guideline-recommended TIR during her third trimester. Healthcare Author Block: L. Maria Belalcazar - University of Texas Medical providers should have an informed discussion with patients about Branch; Jamie Mathews, BA - Presenter and first author, School of potential risks associated with using such systems while respecting Medicine, University of Texas Medical Branch their right to choose treatments that best fit their needs. Introduction: https://doi.org/10.1016/j.eprac.2021.04.535 The risk of severe hypoglycemia in patients with diabetes treated aggressively with glucose-lowering therapies is well recognized and may result in serious cardiovascular and Abstract #995384 cognitive complications and even death. Sulfonylureas (SU) remain a common cause of severe hypoglycemia but are still used in high- A Bottle a Day Keeps the Acid Away: An Unexpected risk individuals due to affordability and the convenience of routine. Cause for Ketoacidosis in a Patient with Stress We present the case of an elderly patient with multiple comor- Hyperglycemia bidities and hypoglycemia unawareness in whom inpatient evalu- ation led to the recognition of inappropriate SU therapy use and, importantly, resulted in a change in his aggressive long-term dia- Author Block: Sowjanya Naha - University of Missouri-Columbia; betes management. Joseph T. Parimi, MD - co-author, University of Missouri-Columbia Case Description: A 78-year-old man with type 2 diabetes (T2DM) was admitted to the hospital with worsening bilateral necrotic toe Introduction: Ketoacidosis is perhaps the most frequently lesions. He underwent a right metatarsal bone amputation and a encountered and well described acute complication of diabetes left popliteal to anterior tibial artery bypass. Three days post- mellitus. Not surprisingly, it is often reflexively attributed to un- procedure he began to experience recurrent hypoglycemia (glucose derlying diabetes especially in the presence of hyperglycemia. 56 mg/dL). It was found that his pre-admission regimen of glipizide Case Description: A 60-year-old female presented with abdominal 10 mg twice daily had been restarted in the hospital despite poor pain, nausea and vomiting for three days. Past medical history was intake. The patient denied any symptoms of hypoglycemia associ- notable for chronic alcoholism. Importantly there was no past ated with the hypoglycemic events. He reported a 28-year history history of diabetes mellitus. On physical examination, the patient of T2DM treated since diagnosis with glipizide monotherapy and was in mild distress; abdominal examination showed generalized complicated by neuropathy, diabetic foot ulcers, coronary artery tenderness with guarding. Routine blood work at admission disease and stage 3 chronic kidney disease. Patient took his glipi- showed elevated random blood glucose (305 mg/dL), low bicar- zide at home twice daily even when not eating; he did not monitor bonate (8 mmol/L) and an increased anion gap (42 mmol/L), his glucose levels at home. The patient saw his primary provider consistent with high anion gap metabolic acidosis. Serum lactate regularly. Over the past year he had hemoglobin A1C (HgbA1c) was normal (2.3 mmol/L) and beta-hydroxybutyrate was increased levels below 6%, with a most recent level obtained a month prior to

S31 Diabetes/Prediabetes/Hypoglycemia Endocrine Practice 27 (2021) S24eS71 admission, of 5.3%; no changes in therapy had been implemented. subcutaneous tissue with surrounding inflammation, but no ab- In the hospital, glipizide was discontinued and he was managed scess. Initially, she was empirically started on IV antibiotics. On the with conservative pre-meal correctional bolus insulin with no following day, the patient mentioned that she had been suffering further hypoglycemia. At the time of discharge, the patient was from skin “abscesses” for several years (ever since she started using counseled on the adverse effects of hypoglycemia, particularly in insulin injections). She admitted pressing the insulin plunger the setting of hypoglycemia unawareness. He was instructed to not rapidly which always resulted in the appearance of a “water blister” restart glipizide and was given a prescription of low dose metfor- under the skin. She was then showed a proper technique (slow min instead. plunging) after which she did not notice any painful reactions or Discussion: This case alerts physicians about the uncritical use of rash. Her antibiotics were stopped and she was discharged home. SU in the inpatient setting and in the long-term management of Reportedly, during her 1-month outpatient follow-up, she was elderly patients at high risk of hypoglycemia. SU are not recom- noted to have a near-complete resolution of the abdominal rash. mended for use in the hospital setting and are not first line in the Discussion: The recognition of poor injection technique and asso- treatment algorithm of diabetes due to their increased risk of hy- ciated skin reactions is of paramount importance in diabetic pa- poglycemia. The occurrence of hypoglycemia in the hospital should tients using insulin. It is suggested that those reactions are not not only result in changes in inpatient therapy but should also uncommon and can lead to poor patient adherence to insulin prompt a thorough evaluation of the patient’s long-term diabetes therapy and subsequently cause increased morbidity and mortality. management to determine if medication-induced hypoglycemia is We believe that in all insulin-dependent diabetic patients, physi- also occurring at home. A below target HgbA1c in a high-risk cians should always inquire about proper injection techniques to asymptomatic patient may be a signal of hypoglycemia unaware- improve compliance and minimize allergic skin reactions. ness and should lead to major revisions in treatment. The inpatient https://doi.org/10.1016/j.eprac.2021.04.538 setting offers an opportunity to modify diabetes regimens associ- ated with high risk of severe hypoglycemia. Elderly patients with multiple comorbidities and aggressive glucose control on SU ther- Abstract #996027 apy are of particular concern. https://doi.org/10.1016/j.eprac.2021.04.537 Does SARS-COV 2 Causes Diabetes?

Author Block: Abstract #995863 Ihtisham Malik - Khyber Medical University

“How Do You Inject insulin?”: A Mysterious Case of Introduction: Little is known on the impact of acute COVID-19 Chronic Painful Skin Lumps infection on causation of diabetes. At the end of 2019, a novel coronavirus was identified as the cause of a cluster of pneumonia cases in Wuhan, China. It rapidly Author Block: Artem Minalyan, MD - primary author, Abington spread, resulting in an epidemic throughout China, followed by Jefferson Health; Iqra Iqbal, MD - co-author, Abington Jefferson global pandemic. In February 2020, the World Health Organization health; Muhammad Atique A. Khan, MD - co-author, Abington designated the disease COVID-19, which stands for coronavirus Jefferson health; Franklin Thelmo, MD - co-author, Abington disease 2019. The virus that causes COVID-19 is designated severe Jefferson Health; Jonathan D. Slusser, MD, Endocrinologist - co- acute respiratory syndrome coronavirus 2 (SARS-CoV-2). author, Endocrinology, Abington Jefferson Health Case Description: We report a case of 36 years old man from Nigeria who presented with diabetic ketoacidosis (DKA) with Introduction: Skin reactions at the site of insulin injections are not typical osmotic symptoms of polyuria and polydipsia, fatigue and uncommon and have been described in the literature. Lipoatrophy weight loss over 2 weeks. He tested positive for SARS-COV2 by PCR. The initial laboratory results: Random glucose 30.6mmol/L, capil- (retracted scar on the skin at the site of multiple insulin injections) is a well-recognized phenomenon. In contrast, lipohypertrophy lary blood ketones 7.4mmol/L, pH 7.22, bicarbonate 7.5mmol/L. Despite insulinopaenic state, at presentation, he was insulin (tissue swelling leading to the appearance of skin lumps) is a commonly overlooked entity. We present a case of chronic painful resistant requiring several upward adjustment of IV insulin therapy, requiring over 200 units IV Actrapid infusion in the first 24 hours skin “abscesses” in a young woman with type 2 diabetes, occurring at the sites of insulin injections. i.e. 8-9 units per hour. At 2 weeks, basal bolus subcutaneous insulin requirement was 1.2 U/Kg/day. Case Description: A 40-year-old Caucasian woman with a past medical history significant for obesity, insulin-dependent type 2 Currently, 6 weeks after diagnosis, insulin requirement was lower at 0.52 U/Kg with drop in HbA1c from 125 to 67 mmol/mol. diabetes, hyperlipidemia, and hypothyroidism, presented to the emergency department (ED) for evaluation of worsening abdom- Retrospectively, random C-Peptide 0.41 ug/L (1.1-4.4) and repeated 6 weeks 0.9ug/L , Islet cell Ab 14 U/ml (< 28), AntiGAD Ab 24 IU/ml inal wall “infections”. She reported that she always develops “ab- < scesses” at sites of insulin injections. She tried rotating sites of ( 17) repeated 6 weeks 11 IU/ml. Discussion: New presentation of DKA with acute COVID-19 in a injections as per her endocrinologist’s recommendations but continued to develop new “infections” at new sites. She took young Nigerian man. Initially insulin resistant despite insulinopaenia but resolution of amoxicillin for 1 week prior to the ED visit without any improve- ment. In the ED, her vitals were unremarkable. On physical exam, insulin resistance by 6 weeks, and persistence of ketonemia despite normal acid base. Initially elevated Anti GAD Ab but six weeks later several tender papules (~1-2 cm in diameter) with surrounding erythema were noted in the periumbilical area. No fluctuance or normalised. Is it latent autoimmune diabetes, or ketosis prone drainage was seen. In labs, she had hyperglycemia (255 mg/dL) diabetes, or a hybrid pleiotropic metabolic effects of COVID-19 fi with normal lactic acid and cell count. Her urine drug screen was infection from as yet unde ned mechanism? unremarkable. Computerized tomograph (CT) abdomen and pelvis Case has been set up for registration at CoviDIAB registry. with intravenous (IV) contrast did show nodular areas in the https://doi.org/10.1016/j.eprac.2021.04.539

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Abstract #998274 Abstract #998751

Evaluating the Thirty-Day Risk of Hospital Revisits in The Polycythemia Caused by Concomitant Use of Patients Previously Discharged from the Emergency Testosterone Replacement Therapy and Empagliflozin Department with Any Blood Glucose ≥ 300 mg/dL

Author Block: Ehab Abdelgyed - Albany Medical center Author Block: Martin Gozar - Northwell Health; Caitlyn Cummings, PharmD, BCPS, CDCES - Co-author, Long Island Introduction: Polycythemia is an increased hemoglobin (Hb) con- Jewish Medical Center; Lori Ohanesian, PharmD, BCPS - Co-author, centration >16.5 g/dL and/or hematocrit (Hct) >49% in men. Long Island Jewish Medical Center; Robert Silverman, MD - Co- Testosterone replacement therapy (TRT) increases erythrocytosis author, Long Island Jewish Medical Center; Rifka Schulman- and causes polycythemia in 3-14% of cases. Sodium-glucose Rosenbaum, MD, FACE, CNSC - Co-author, Long Island Jewish cotransporter 2 inhibitors (SGLT2i) e.g., Empagliflozin cause poly- Medical Center cythemia in 3-4% of cases by different mechanisms. Case Description: Objective: In the emergency department (ED), patients often Case 1 demonstrate hyperglycemia regardless of the reason for pre- A 72-year-old man with a history of (h/o) Hypogonadotropic sentation to the ED. The purpose of this study is to evaluate the hypogonadism (HH) since 2016 secondary to type 2 Diabetes Mellitus risk of all-cause hospital revisits (including ED) within 30 days (T2DM), obesity, chronic opioid therapy. Androgel was started with among patients with diabetes mellitus (DM) with severe hy- up-titration to 4 pumps daily. The patient was on metformin/glipizide perglycemia and discharged from the ED compared to patients for DM. Due to uncontrolled DM and intolerance of acarbose and with DM discharged from the ED with normal glucose or saxagliptin, Empagliflozin 10 mg was started in 12/2017and increased moderate hyperglycemia. to 25 mg in 08/2018. Hct was significantly increased from 50.1 to 56.1 Methods: This was a retrospective chart review of patients aged in 05/2019 which was attributed to TRT and Empagliflozin. Reduction 18 years and older who were discharged from an academic of Androgel dose to 3 pumps daily resulted in a reduction of his Hct to tertiary care ED between January 1, 2018, and March 31, 2018. 53.9 in 07/2019 and a further reduction was achieved later. Eligible patients were split into 3 groups based on their glucose Case 2 levels in the ED. Patients in the first group (severe hyperglyce- A 63-year-old man with a h/o T2DM since 2010. He developed HH mia) had any glucose of 300 mg/dL or greater. Patients in the secondary to DM in 2012 and was started on 1 pump of Androgel, second group (moderate hyperglycemia) had a history of DM, all increased to 2 pumps daily due to low testosterone level. In 06/ glucose values less than 300 mg/dL, and at least one glucose 180 2019, Empagliflozin was added to his diabetic regimen metformin/ mg/dL or greater. Patients in the third group (normal glucose) glimepiride/acarbose/alogliptin for better diabetic control. After 3 had a history of DM and all glucose values less than 180 mg/dL. months, His Hct was significantly increased up to 55.1. Androgel Current practice at our institution has higher risk patients was decreased to 1 pump daily, with a subsequent decrease in Hct. requiring more focused DM care admitted to the ED observation Case 3 unit, and thus these patients were excluded from our study. The A 71-year-old man with a h/o hypogonadism since 2006 on primary outcome was the frequency of hospital revisits at 30 injectable TRT due to intolerance of other TRT forms. After 3 years, days after the index visit. His Hct was found to be 54.4. He was evaluated by Hematology and Results: There were 302 patients who met inclusion criteria. Of was found to have HFE heterozygous mutation. Intermittent phle- these, 117 patients had severe hyperglycemia, 68 had moderate botomy was initiated to allow an increase in TRT dose. The patient hyperglycemia, and 117 had normal glucose. There were more pa- was diagnosed with T2DM in 2010. He was started on Metformin. He tients in the severe hyperglycemia group with 30-day all-cause couldn't tolerate sulfonylurea, acarbose, Thiazolidinedione and he hospital revisits compared to the moderate hyperglycemia and was unwilling to take insulin. Dulaglutide was added to his regimen normal glucose groups, but this was not found to be statistically but his DM was still uncontrolled. Empagliflozin was started in 4/ significant (19.5% vs. 10.4% vs. 15.4%, respectively, p¼0.25). In a 2018. After 2 months, His Hb increased from 17.6 to 19.2 and his Hct multivariable model, the glucose cohorts did not predict 30 day was 56.5, so TRT was held temporarily to reduce his polycythemia revisits although a past medical history of atherosclerotic cardio- Discussion: HH is found in 25% of men with T2DM. Diabetic men vascular disease (ASCVD) (p¼0.001), as well as one or more prior are more likely to have low serum testosterone concentrations than ED visits in the past year (p¼0.025), were predictors of outcome. nondiabetic. The use of SGLT2i is emerging for its renal/car- Similar findings were noted when 90 day ED revisits was evaluated dioprotective effect and becoming standard of care in heart failure. as the outcome. So, concomitant use of TRT and SGLT2i is common and this can Discussion/Conclusion: While it was common to have glucose cause worsening polycythemia which can present with headache, levels over 300 mg/dL among patients with diabetes dis- dizziness, visual disturbances, chest pain, etc., and can be compli- charged from the ED, the results suggest that there is no cated by vascular thrombosis, cerebrovascular accident, etc. Phy- significant association between hyperglycemia in the ED and sicians should be aware of the risk of worsening polycythemia 30-day hospital revisits. Among patients with diabetes, a his- when TRT and SGLT2i are concomitantly prescribed. Hct should be tory of ASCVD or any ED visit in the previous year increased monitored closely. TRT induced polycythemia is dose-dependent the risk of 30-day and 90-day hospital revisits. Clinicians and is lower with long-acting injectable/transdermal forms. If should be aware of these risk factors as the findings suggest polycythemia develops, TRT should be either decreased or stopped that patients with diabetes together with these characteristics if the Hct increases to 54 % as per The Endocrine Society guide- should be targeted for more aggressive follow-up post ED lines. Reducing TRT to the lowest possible dose is an effective way discharge. to avoid polycythemia and its complications. https://doi.org/10.1016/j.eprac.2021.04.540 https://doi.org/10.1016/j.eprac.2021.04.541

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Abstract #998903 Abstract #998910

Euglycemic Relapsing Diabetic Ketaocidosis Due to A Decade Trend in National 30-Day Readmissions in SGLT-2 Inhibitor Use: A Metabolic Challenge in Need of Patients with Diabetic Ketoacidosis: An Ominous Sign? Substrate

Author Block: HAFEEZ SHAKA - John, H. Stroger Jr. Hospital of Cook Author Block: L. Maria Belalcazar - University of Texas Medical County; Maria C. Aguilera, MD - co-author, John H. Stroger, Jr. Branch; Christina Davis, BA - First author, School of Medicine, Hospital of Cook County; Omolabake Alabi, MD - co-author, Jacobi University of Texas Medical Branch; Hammad Nazeer, MD - Co- Medical Center; Asim Kichloo, MD - co-author, Central Michigan author, Division of Endocrinology and Metabolism, University of University College of Medicine; Chukwudi C. Muojieje, MD, MPH - Texas Medical Branch co-author, Mountain View regional medical center; Marcelo Ramirez, MD - co-author, John H. Stroger, Jr. Hospital of Cook County Introduction: Sodium-glucose co-transporter 2 inhibitors (SGLT- 2i) are increasingly used in the management of type 2 diabetes due Objective: Diabetic ketoacidosis (DKA) is an endocrinologic to their cardiovascular, renal and metabolic benefits. Euglycemic emergency which is associated with in-hospital morbidity and diabetic ketoacidosis (DKA) is an unusual but well documented mortality. A significant proportion of patients hospitalized with complication of SGLT-2i use. We present a case that expands the DKA get readmitted within 30 days of discharge for various need of awareness of this metabolic complication among health reasons including recurrent DKA. The 30-day readmission providers to include the high risk of DKA relapse that occurs in the rate is often used as a quality metric for hospitals as well acute setting when patients have a recent history of SGLT2i use. The as the Center for Medicare and Medicaid Services (CMS). The importance of modifying DKA protocols to provide abundant CMS tracks hospital admissions for Acute and Chronic Ambu- glucose is highlighted. latory Care-Sensitive Condition as these hospitalizations are Case Description: A 46-year-old man with a 2-year history of preventable given appropriate primary and preventive care. uncontrolled Latent Autoimmune Diabetes in Adults on metfor- This study highlights the trend in DKA readmissions since min, canagliflozin and poor adherence to basal-bolus insulin was 2010. transferred from an outside hospital after presenting with altered Methods: Data was extracted from the US Nationwide Read- mental status, nausea, vomiting, worsening cough and abdominal missions Databases for 2010, 2012, 2014, 2016 and 2018. Index pain. He was diagnosed with DKA and managed with insulin and hospitalizations with principal discharge diagnosis codes for DKA fluids prior to transfer. Upon arrival, he was lethargic and quickly were included. Hospitalizations less than 18 years, December and found febrile and progressively tachypneic, requiring mechanical elective admissions were excluded. Non-elective, non-traumatic ventilation; cellulitis of the right hand was also identified. Empiric 30-day all-cause readmissions following DKA index hospitaliza- antibiotic coverage was provided and oral anti-hyperglycemic tions were identified. The readmission rate, readmission mortality agents were held. Admission laboratories were significant for rate and mean cost of hospitalizations for readmissions were glucose of 65 mg/dL, anion gap (AGAP) of 13, TCO2 of 15 mmol/L calculated. These were plotted on a graph with a trend line (ref 23-31 mmol/L), 3-hydroxy-butyrate of 3.2mmol/L (ref < 0.4 established. mmol/L)) and large ketones in the urine (80 mg/dL; ref: negative). Results: From 2010, the 30-day all cause readmission rates for Due to normoglycemia, insulin infusion was delayed 5 hours, the queried years were 14.6%, 15.8%, 15.8%, 17.1% and 16.7% in when TCO2 decreased to 9 mmol/ L, gap widened to 19 and then sequence with a trend towards increasing readmission rates 31, with a rise in glucose levels of up to 326 mg/dL on saline fluids with time. Since 2012, there has also been a trend towards with dextrose. After initial transition to subcutaneous (subQ) in- increasing inpatient mortality among readmitted patients sulin the next day, the patient’s AGAP metabolic acidosis recurred following an index hospitalization for DKA. The inpatient mor- and insulin infusion had to be restarted. The patient suffered two tality for readmission was 0.85% in 2012, 0.98% in 2014, 0.99% in additional instances of DKA relapse after transition to subQ insu- 2016 and 1.11% in 2018. During the study period, there has also lin. All instances of DKA relapse were due in part to the recurring been a steady increase in inflation adjusted mean cost of hos- challenge posed by below target glucose levels that resulted in pitalizations following readmission. subtherapeutic insulin administration. Transition to subQ insulin Discussion/Conclusion: The study period coincided with the was successful only after the patient was kept on enteral nutrition Hospital Readmissions Reduction Program (HRRP); an initiative and dextrose fluids and was then able to eat well after extubation. enforced by CMS to avoid preventable readmissions. DKA is not Ketonuria did not resolve until the tenth day of admission. one of the conditions actively reported by CMS. This trend to- Discussion: SLGT-2i promote the development of euDKA by wards increasing rates of readmission and readmission mortality creating a glucose-deprived pro-ketogenic environment that re- may signify an increasing burden of avoidable readmissions in duces insulin secretion and limits exogenous insulin administra- patients with DKA. Since hyperglycemic emergencies are a tion. Metabolic derangements are maximized by ongoing acute common reason for readmission, there may be a gap between stressors, decreased food intake and underlying beta-cell insuffi- hospital management of hyperglycemic emergencies and tran- ciency. To avoid the risk of relapse, DKA treatment protocols in sition to chronic hyperglycemia treatment. Increasing comor- patients on SGLT-2i need to be modified to provide increased bidity burden in the population may also account for the glucose substrate intravenously in the acute setting and maintained increasing trend. Hence, improved multidisciplinary care coor- after transition to subQ insulin to allow for adequate insulin dination and outpatient follow up is recommended to stem the replacement until nutrition resumes and precipitating factors are tide of readmissions, especially giving the rising inpatient mor- under control. tality associated with it. https://doi.org/10.1016/j.eprac.2021.04.542 https://doi.org/10.1016/j.eprac.2021.04.543

S34 Diabetes/Prediabetes/Hypoglycemia Endocrine Practice 27 (2021) S24eS71

Abstract #999342 Figueroa, MD - Co-Author, Internal Medicine, Internal Medicine department, University of Puerto Rico School of medicine; Non-Islet Cell Tumor Hypoglycemia Secondary to Yadiel Rivera-Nieves, MD - Co-Author, Endocrinology, Department Metastatic Bladder Urothelial Carcinoma: A Case Report of Endocrinology, University of Puerto Rico School of medicine; Juan J. Rivera-Torres, MD - Co-Author, Internal Medicine, Internal Medicine department, University of Puerto Rico School of Author Block: Dan Auger, OMS-III - Primary Author, University of medicine; Jose Colon-Marquez, MD - Co-Author, Internal Medicine, New England college of osteopathic medicine; Shazia Ahmad, MD - Internal Medicine department, University of Puerto Rico School of coauthor/presenter, Northern Light Health/University of New medicine England Introduction: Neurologic complications are major health problems Introduction: Non-islet cell tumor hypoglycemia (NICTH) is a rare in patients with diabetes mellitus (DM). Interventions to reduce the but life-threatening paraneoplastic syndrome which is marked by risk of developing these complications are limited. Bladder cyst- the autonomous secretion of incompletely processed precursors of opathy represents end-stage bladder failure with symptoms of insulin-like growth factor-II (IGF-II), known as “big” IGF-II . Many infrequent voiding, difficulty initiating miction, and postvoid full- types of tumors have been associated with NICTH in the literature; ness. Bladder instability or hypersensitivity as the most common Of the tumors from epithelial origin that cause NICTH, less than 1% findings while decreased bladder contractility, sensation, and are of bladder origin. Our literature search only revealed one case of acontractile bladder tend to be rare. Overflow incontinence (OI) NICTH caused by urothelial carcinoma of the bladder. carries a significant detrimental effect on the quality of life of pa- Case Description: This case report examines a 64-year-old female tients with DM as this condition could result in chronic renal fail- with metastatic urothelial carcinoma of the bladder with biopsy- ure, skin infections, and recurrent urinary tract infections (UTI) confirmed liver metastases and radiologic evidence of bilateral lung with the potential to develop diabetes ketoacidosis (DKA), a life- nodules and abdominal and retroperitoneal lymphadenopathy. Her threatening condition. history of cancer was complicated by refractory hypoglycemia Case Description: A 29 years-old Male with history of DM type 1, requiring multiple hospitalizations. She was initially able to keep neuropathy, erectile dysfunction, chronic kidney disease, and sickle her blood sugars within normal range by consuming hourly meals cell trait admitted to the internal medicine ward with diagnosis of at her residential facility, however with worsening severity of left gluteal pyomyositis, UTI, and DKA. After initiation of intrave- symptoms, she often needed medical intervention. Initial work up nous antibiotics and intravenous insulin, the anion gap was closed for hypoglycemia showed undetectable insulin, proinsulin, and C- successfully but renal failure continues to worsen. As no resolving peptide levels. Adrenal insufficiency was ruled out with random kidney injury, a bedside point-of-care ultrasonography showed a cortisol of 22.6 (5.0-20.0 ug/dL). Beta hydroxy butyrate was normal distended bladder with more than 400mL of estimated bladder at 0.8mg/dL (0.0-3.0mg/dL). Insulin antibodies were undetectable. volume for which a renal ultrasound order. Resultsshowed severe Insulin like growth factor 1 was 32ng/mL (36-244). Unfortunately, bilateral hydroureteronephrosis with associated bilateral cortical IGF-II levels were not available as patient died prior to labs could thinning demarking an advanced renal disease secondary to chro- have been drawn. Tissue staining of the pathology remains nicity of bladder distention. A multidisciplinary team approach was pending. During hospitalization, she required constant dextrose made where pharmacological therapy was tried and failed to 10% infusion with intermittent dextrose 50% injections while blood improve retention. Reluctance by patient to intermittent self- sugars were ranging between 20s-130s. The workup suggested a catheterization to resolve overflow contributes to worsening renal diagnosis of NICTH secondary to metastatic urothelial carcinoma failure. and patient was managed with high dose steroids. Discussion: Our patient had a history of more than 12 DKA Discussion: Here we present a case of refractory hypoglycemia as a secondary to recurrent UTI's in less than 2 years, highlighting paraneoplastic syndrome associated with metastatic urothelial the burden of this chronic condition. Pathophysiology by which carcinoma of the bladder. This case highlights a rare but life- diabetes might promote urologic complications is not clear but threatening syndrome which in our patient was not recognized alterations in detrusor muscle physiology, neuronal impairment, until her last hospitalization as a possible paraneoplastic syndrome. and urothelial dysfunctions are considered as participating fac- Refractory hypoglycemic episode can be difficult to manage but tors. OI initial treatment consists of removal of medications that frequency and severity can be reduced in a dose-dependent impair detrusor activity or agents that increase urethral manner with glucocorticoids. The only definitive treatment for this sphincter tone, strict voluntary urination schedule, and advanced disease is complete tumor resection. cases require intermittent catheterization. While other modal- ities such as pharmacologic and surgical intervention have been https://doi.org/10.1016/j.eprac.2021.04.544 described, none have been consistently effective. Additional studies are needed to further understand the burden of urologic complications as a health outcome in men and women with Abstract #999711 diabetes.

The Burden of A Complication without Too Many https://doi.org/10.1016/j.eprac.2021.04.545 Alternatives, Diabetic Cystopathy

Abstract #999916 Author Block: Juan Santiago Gonzalez - University of Puerto Rico school of medicine; Gabriela M. Negron-Ocasio, MD - Co-Author, Comparing the Clinical Outcome of Diabetic and Non- Internal Medicine, Internal Medicine department, University of Diabetic Covid-19 Patients Puerto Rico School of medicine; Ian J. Da Silva-Lugo, MD - Co- Author, Internal Medicine, Internal Medicine department, University of Puerto Rico School of medicine; Juan G. Feliciano- Author Block: Abhishek Bhargava - S.M.S. Hospital, jaipur

S35 Diabetes/Prediabetes/Hypoglycemia Endocrine Practice 27 (2021) S24eS71

Objective: Introductione Covid-19 which emerged from China has complications in patients having acute MI. We also studied the heralded the pandemic era of lockdown and restrictions. Since its association of HbA1c levels with prognosis in MI patients. emergence the virus has infected more than 95 million people Methods: 100 eligible consecutive patients of AMI were enrolled worldwide and caused loss of more than 2 million lives. While most and grouped according to their RBS whether < 180(group 1) or of the patients remain asymptomatic or have mild symptoms but >180(group 2) irrespective of prior history of diabetes. Simulta- few patients develop life threatening acute lung injury, especially neously, these 100 patients were also evaluated for HBA1c levels patients who have diabetes mellitus. This article compares the and divided whether< 6% (group 1) and >6% (group 2) and analysed morbidity and mortality in Covid-19 patients with and without using particle enhanced immunoturbidimetric test. Simulta- diabetes mellitus. neously, routine investigations viz. complete blood count, renal and Methods: Material & Methodse 1085 Covid-19 patients admitted in liver profile, 2D ECHO and serial ECG were performed. S.M.S. Hospital, Rajasthan, India between 1st April - 1st July 2020, Results: Bio-physiological processes involving RAAS activation, were included in the study. Demographics, signs and symptoms sympathetic modalities and inflammatory cascade due to AMI and mortality were compared in patients with and without induced stress potentiates reactionary hyperglycemia which high- diabetes. lighted more risk of complications thereby developing heart failure Main outcomes e Discharge, Death. in 36% cases(group 2) contrasting 6% (group 1). Further, arrhyth- Results: Resultse Greater number of Covid-19 diabetic patients had mias occurred in 30% (group 2) contrasting 6% (group 1) and shock symptoms such as fever (60.34%) and dyspnea (66.20%) as in 26% (group 2) with 6% (group 1). Hyperglycemia was associated compared to non-diabetic patients in whom the incidence of fever with higher mortality viz. 28% (group 2) in comparison to 6% (group and dyspnea was 30.37% and 33.80% respectively. Requirement of 1) with significant difference. The HBA1c levels underlined higher respiratory support in diabetic patients (24.45%) was also much complications viz. 23.1% (group 2) than 12.5% (group 1) with overall higher than in non-diabetics (15.39%). Mean duration of hospital mortality higher in diabetics (group 2) as compared to non- stay was greater in diabetic patients (9.83 days) as compared to diabetics. non-diabetics (6.53 days). Mortality was higher in ICU patients with Discussion/Conclusion: The study tends to highlight the stress diabetes (57.14%) as compared to non-diabetes (15.38%). Diabetic response initiated by myocardial injury that triggers pro-inflam- patients with HbA1c >9 had more mortality than in patients with matory cascades and sympathetic over-activity causing pseudo- HbA1c < 9 (68.22% vs 34.12%). emergency states that engender extensive myocardial damage and Discussion/Conclusion: Conclusion- Diabetic patients have a pre- further deteriorations in prognosis. dilection for more severe Covid-19 infection. Diabetic patients with https://doi.org/10.1016/j.eprac.2021.04.547 uncontrolled blood sugar have increased morbidity and mortality. Ensuring strict glycemic control is of paramount importance in better outcomes in diabetic patients. Abstract #1000825 https://doi.org/10.1016/j.eprac.2021.04.546 Pembrolizumab Induced Diabetes; An Atypical Presentation Abstract #1000082

The Association of Hyperglycemia with Complications Author Block: FNU Komal - Marshall University; Omolola Olajide, in Patients with Acute Myocardial Infarction: An MD - Co-author, Marshall University WV Observational Study Introduction: Immune check point inhibitors are now commonly used in cancer treatment regimens. Pembrolizumab acts by binding Author Block: sharikant sharma - SMS Medical college and and blocking of the Program cell Death 1 Ligand (PDL1) receptor on hospital jaipur INDIA; Mukul Singhal, senior registrar - co-author, T cells and augments T cell antitumor activity. Pembrolizumab has Internal medicine, SMS Medical college; Abhishek Bhargava, senior been associated with various immune related adverse effects like registrar - co-author, Internal medicine, SMS Medical college; thyroiditis, hypophysitis, adrenal insufficiency and less commonly anu D. rajpurohit, senior registrar - co-author, Internal medicine, Diabetes mellitus (DM). We present a case of a patient treated with SMS Medical college; Prakash Keswani, senior Profeesor - co- Pembrolizumab (PDL1 Antagonist) for renal cell carcinoma who author, Internal medicine, SMS Medical college was diagnosed with new onset DM. Case Description: A 77-year-old female with a PMH of hyperten- Objective: Acute myocardial infarction (AMI) is one of the most sion, metastatic renal cell carcinoma treated with Pembrolizumab common causes of morbidity and mortality globally. Myocardial and Axitinib for the last 18 months presented to the emergency ischemia, defined as diminished blood supply to the heart, exceeds department (ED) with weakness, dizziness and near syncope. She a particular threshold and saturates the myocardial repair mecha- was noted to have atrial Fibrillation with a rapid ventricular rate. nisms capacity to maintain normal function and homeostasis. She also had polyuria, polydipsia since the last dose of pem- Furthermore, adjunct hyperglycemia substantiates electrophysio- brolizumab three weeks prior. Random blood glucose at the time logical alteration, impairs LV function and causes perfusion defects was 142 mg/d/. Labs in the ED were remarkable for plasma glucose promoting multiple cardiac complications viz. arrhythmias, of 514 mg/dl, anion Gap of 12, bicarbonate 22 mEq/L, BUN 33 mg/dl, cardiogenic shock, heart failure and death. Raised admission serum creatinine 1.56 mg/dl, Hba1c 7.5%. She was initially treated random blood sugar (RBS) and high HbA1c values serve a prog- with IV fluids and an insulin infusion and then transitioned to nostic purpose in patients of MI to be watchful regarding basal/bolus insulin therapy. Her c e peptide level was 2.5 ng/ml, complications. Glutamic Acid Decarboxylase antibodies came back negative. Aim: The present study was conducted to study the association Notably her Hba1c was 5.1% before starting immunotherapy between admission blood glucose levels and the development of months ago. She was discharged home on insulin therapy.

S36 Diabetes/Prediabetes/Hypoglycemia Endocrine Practice 27 (2021) S24eS71

Discussion: Immunotherapy has revolutionized oncological treat- non-Covid hospital. Among the admitted cases many of them ment; however, their use has been associated with endo- hides Covid symptoms. X-ray or relevant test was strongly sus- crinopathies. Autoimmune diabetes mellitus is an uncommon picious. Diabetes management does not differ much from pre endocrine adverse reaction associated with Immunotherapy. The Covid-19 era in hospital, specially when steroid use was not mechanism of the production of autoantibodies due to PD-L1 recommended as such for management of moderate to severe therapy is not well known but possibly due to the destruction of the Covid-19 disease. beta islet cells of the pancreas by host T-cells that are no longer https://doi.org/10.1016/j.eprac.2021.04.549 inhibited due to the effects of the PD-L1 therapy. Many of the re- ported cases presented with diabetic ketoacidosis (DKA ) within few weeks of treatment with Pembrolizumab. Our patient pre- Abstract #1000873 sented many months after onset of treatment without DKA. The presence of autoantibodies has been shown in more than half of the Euglycemic Relapsing Diabetic Ketaocidosis Due to SGLT-2 documented cases with this condition. Her clinical picture is more Inhibitor Use: A Metabolic Challenge in Need of Substrate in keeping with autoimmune diabetes due to the rapid deteriora- tion in her glycemic control though her c-peptide was in the normal range. These patients with c-peptide persistence need to be Author Block: Christina Davis - University of Texas Medical monitored closely as the levels are more likely to decline and they Branch; Hammad Nazeer, MD - co-author, Internal Medicine- will become insulin dependent over time. Endocrinology, University of Texas Medical Branch at Galveston; New onset Diabetes is one of the recognized adverse effects of L. Maria Belalcazar, MD - co-author, Internal Medicine- Pembrolizumab. There needs to be an increased awareness of this Endocrinology, University of Texas Medical Branch at Galveston complication as this could occur even up to several months after their initiation. Introduction: Sodium-glucose co-transporter 2 inhibitors (SGLT- https://doi.org/10.1016/j.eprac.2021.04.548 2i) are increasingly used in the management of type 2 diabetes due to their cardiovascular, renal and metabolic benefits. Euglycemic diabetic ketoacidosis (DKA) is an unusual but well documented Abstract #1000868 complication of SGLT-2i use. We present a case that expands the need of awareness of this metabolic complication among health Experience of Diabetes Management in Early Covid-19 providers to include the high risk of DKA relapse that occurs in the Period acute setting when patients have a recent history of SGLT2i use. The importance of modifying DKA protocols to provide abundant glucose is highlighted. Author Block: Ashrafuzzaman SM - BIRDEM; Rahim MA, Associate Case Description: A 46-year-old man with a 2-year history of Professor - Co-author, Nephrology- Endocrinology, BIRDEM Dhaka uncontrolled Latent Autoimmune Diabetes in Adults on metfor- Bangladesh min, canagliflozin and poor adherence to basal-bolus insulin was transferred from an outside hospital after presenting with Objective: On 8th March 2020 first 3 cases are detected Covid 19 RT altered mental status, nausea, vomiting, worsening cough and POCR positive in Bangladesh. Since then, Covid 19 cases started in abdominal pain. He was diagnosed with DKA and managed with increase and spreaded all of the division and gradually to most of insulin and fluids prior to transfer. Upon arrival, he was lethargic the districts of the country. About 9 % of adult population of the and quickly found febrile and progressively tachypneic, requiring country is diabetic. Ina tertiary care hospital of Endocrinology many mechanical ventilation; cellulitis of the right hand was also suspected patients were admitted in that time. Many of them hides identified. Empiric antibiotic coverage was provided and oral or can’t understand their sign or symptoms of Covid-19 disease. anti-hyperglycemic agents were held. Admission laboratories They were mostly admitted for management of other illnesses with were significant for glucose of 65 mg/dL, anion gap (AGAP) of diabetes. 13, TCO2 of 15 mmol/L (ref 23-31 mmol/L), 3-hydroxy-butyrate Methods: Retrospective data was collected. Covid-19 test (RT PCR of 3.2mmol/L (ref < 0.4 mmol/L)) and large ketones in the urine for Covid-19 disease) were done in all cases. Diabetes management (80 mg/dL; ref: negative). Due to normoglycemia, insulin infu- pre- and post-admission in this period is observed. Associated drug sion was delayed 5 hours, when TCO2 decreased to 9 mmol/ L, treatment is recorded. Outcome is analyzed. gap widened to 19 and then 31, with a rise in glucose levels of Results: Total 45 patients with known diabetes and on treatment up to 326 mg/dL on saline fluids with dextrose. After initial with variable clinical presentation were admitted in hospital. transition to subcutaneous (subQ) insulin the next day, the pa- Among them 34(75.5%) was HbA1c > 7 %. HbA1c Mean ± SD tient’s AGAP metabolic acidosis recurred and insulin infusion (8.9±1.3). FPG 8.5 ±2.1 mmol/L. RT PCR for Covid 19 disease was had to be restarted. The patient suffered two additional in- present in 17(37.7%) cases. Chest x-ray, CRP, Ferritin D-dimer was stances of DKA relapse after transition to subQ insulin. All in- done is all cases. HRCT was done in 25 cases. Three (3/17) required stances of DKA relapse were due in part to the recurring low flow Oxygen 1-3 days. Thirteen patients (28.8%) were on in- challenge posed by below target glucose levels that resulted in sulin± OAD. Among these 45 patients 4 was DKA (treated in subtherapeutic insulin administration. Transition to subQ insulin designated Covid-19 disease ward) and 6 was admitted for hypo- was successful only after the patient was kept on enteral glycemia Level 3. Among total 10 subjects of DKA & Hypo, two nutrition and dextrose fluids and was then able to eat well after (50%) of DKA and 4 (66 %) of hypoglycemia were Covid-19 Positive. extubation. Ketonuria did not resolve until the tenth day of All patients were treated with insulin± OAD (specially Metformin, admission. DPP4i). All the patients discharged with advice. Discussion: SLGT-2i promote the development of euDKA by Discussion/Conclusion: Variable presentation is observed among creating a glucose-deprived pro-ketogenic environment that re- diabetic subjects in early Covid-19 era. Many of the admitted in duces insulin secretion and limits exogenous insulin

S37 Diabetes/Prediabetes/Hypoglycemia Endocrine Practice 27 (2021) S24eS71 administration. Metabolic derangements are maximized by preventive measures, DKA risk can be mitigated. It is also ongoing acute stressors, decreased food intake and underlying important to have a high index of suspicion for euglycemic DKA beta-cell insufficiency. To avoid the risk of relapse, DKA treatment in order to timely diagnose and treat these patients given that protocols in patients on SGLT-2i need to be modified to provide DKA has an overall mortality rate of 0.2-2%. increased glucose substrate intravenously in the acute setting and https://doi.org/10.1016/j.eprac.2021.04.551 maintained after transition to subQ insulin to allow for adequate insulin replacement until nutrition resumes and precipitating fac- tors are under control. Abstract #1000943 https://doi.org/10.1016/j.eprac.2021.04.550 Hidden In Plain Sight: The Complexity of Euglycemic DKA Induced by Severe Alcoholic Pancreatitis Abstract #1000886

SGLT-2 Inhibitor-Induced Euglycemic Diabetic Author Block: Madeline Fasen, DO - primary author, University of Ketoacidosis in a Type 2 Diabetes Mellitus patient with Florida College of Medicine; Naji Maaliki, MD - co-author, Acute Pancreatitis University of Florida College of Medicine; Vandana Seeram, MD - co-author, University of Florida College of Medicine

Author Block: Sanjana Thota-Kammili - Appalachian Regional Introduction: The diagnostic challenge of euglycemic diabetic Healthcare; Mary E. Kimbrough, DO - Co-author, Internal Medicine, ketoacidosis (EDKA) is attributed to its relatively uncommon Appalachian Regional Healthcare; Edilfavia Mae S. Uy, MD - Co- presentation and similarity to other forms of ketoacidosis. Often author, Endocrinology, Appalachian Regional Healthcare unrecognized at initial presentation, appropriate treatment for this life-threatening complication is delayed and potentially Introduction: SGLT-2 inhibitors have gained increasing popularity fatal. To emphasize EDKA as a differential diagnosis in severe and widespread use among patients with type 2 diabetes mellitus metabolic derangement and highlight the complexity of ketoa- (T2DM) and congestive heart failure due to mounting evidence of cidosis with alcoholic pancreatic injury, we describe a case of both cardiovascular and renal benefits. Euglycemic diabetic ketoa- EDKA with severe acute pancreatitis in a patient without known cidosis (DKA) is a rare but serious adverse effect of SGLT-2 in- diabetes. hibitors. We present a case of euglycemic DKA in a patient with Case Description: A 30 year-old female presented to the emer- pancreatitis on SGLT-2 inhibitors. gency department from jail due to altered mental status and Case Description: A 45-year-old male with a history of T2DM, severe epigastric pain. Medical history included heavy alcohol coronary artery disease, hypertension presented to the emer- abuse. The patient’s mental status progressively deteriorated gency department complaining of persistent epigastric pain, until she became unresponsive into cardiac arrest. She achieved nausea, vomiting, and decreased oral intake. Initial work up was return of spontaneous circulation after advanced cardiac life significant for hyponatremia, hypokalemia, elevated lipase of 789 support and intubation. Drug screen was positive for amphet- U/L, elevated amylase of 177 U/L, serum creatinine of 1.29 mg/dl, amines, CO2 6 mmol/L, glucose 98 mg/dL, B-hydroxybutyrate > glucose of 200 mg/dl, bicarbonate of 24.6 mmol/L and an 46.8 mmol/L, urine ketones 80 mg/dL, lipase 1,041 U/L, A1C 4.4%, elevated anion gap of 20.4 mmol/L. Patient’s hemoglobin A1C anion gap 35 mmol/L, undetectable alcohol level and arterial was 12.8%. CT of the abdomen/pelvis showed moderate blood gas pH 6.69. Chest x-ray showed bilateral infiltrates sug- pancreatitis. Patient’s home medications, including SGLT-2 in- gestive of ARDS and CT abdomen confirmed interstitial edema- hibitor, were all discontinued on admission. Patient was placed tous pancreatitis. Treatment in the ICU started with aggressive on an NPO diet with continuous IV fluids and electrolyte IV fluids, sodium bicarbonate and fomepizole for possible toxic replacement. He was clinically improving until day 3 of admis- alcohol ingestion. After a non-resolving course of her metabolic sion when his morning labs were significant for a CO2 of 8.2 acidosis, pancreatitis-induced EDKA emerged as an inciting fac- mmol/L, anion gap of 27.8 mmol/L, and a glucose of 90 mg/dl. tor. Management transitioned to continuous insulin and trickle Arterial blood gas showed metabolic acidosis with a pH of 7.060 feeds via nasogastric tube with subsequent resolution of her and pCO2 of 11 mmHg. Patient’s qualitative serum ketones were metabolic acidosis over two days. Treatment of her EKDA proved moderate. Patient was subsequently admitted to the ICU and crucial as she was subsequently started on IV steroids for severe started on an insulin drip and treated for euglycemic DKA. Pa- ARDS in addition to lung protective ventilation and prone tient’s clinical condition improved and he was discharged on positioning. She continued on a steroid taper after extubation Metfomin 1000 mg twice daily, Glimepride 4 mg twice daily and and completed aggressive physical therapy due to prolonged Insulin Humalog correction scale with out-patient follow up. hospitalization. At this time she is doing well at home, limiting Discussion: Euglycemic DKA caused by SGLT-2 inhibitors is her alcohol intake and pending further evaluation of insulin relatively rare and is usually triggered by a known precipitant, in resistance after severe acute pancreatitis. our case acute pancreatitis. Other predisposing factors are Discussion: The pathogenesis of EDKA involves insulin deficiency reduction or omission of insulin, severe acute illness, dehydra- as a consequence to beta cell destruction from severe pancrea- tion, extreme physical activity, surgery, low carbohydrate diets titis and reduced glycogen reserve from chronic alcoholism and or excessive alcohol intake. During periods of carbohydrate prolonged fasting. Despite typical EDKA findings of normogly- deficiency, volume depletion, and upregulation of counter-regu- cemia and persistent metabolic acidosis, the concern for latory stress hormones, SGLT-2 inhibitor therapy can promote toxic ingestion, starvation ketoacidosis and rapid development lipolysis and ketogenesis while maintaining euglycemia. Pro- of ARDS contributed to this patient’s treatment delay. Increased viders should consider these situations so that, with adequate awareness and high suspicion of EDKA is necessary to

S38 Diabetes/Prediabetes/Hypoglycemia Endocrine Practice 27 (2021) S24eS71 tailor treatment especially in this case where steroids were susceptible to metformin therapy than wild genotype carriers. required. Further studies are needed to confirm our findings and to explain potential mechanisms by which the KCNJ11 variant can modulate https://doi.org/10.1016/j.eprac.2021.04.552 therapeutic response to metformin.

https://doi.org/10.1016/j.eprac.2021.04.553 Abstract #1001320

Effects of KCNJ11 RS5219 Variant on Metformin Abstract #1001454 Pharmacodynamics in Patients With Newly Diagnosed Type 2 Diabetes Mellitus Dietary Intake of Type 1 Diabetic Patients in Southern Rajasthan of India

Author Block: Polina Shorokhova - North-Western State Medical University named after I.I. Mechnikov; Vitaly Baranov, DMSc, Author Block: Abhilasha Mangal, MSc (Dietetics) - Co author, Professor - co-author, Department of Endocrinology named after Ramchandani diabetes care and research centre; acad. V.G. Baranov, North-Western State Medical University named Rahul Ramchandani, MBBS - Co author, Ramchandani diabetes care after I.I. Mechnikov; Natalya Vorokhobina, DMSc, Professor, Head and research centre; Akhil Agrawal, MBBS, DNB, FAIPS - Co author, of Department of Endocrinology named after acad. V.G. Baranov - Manash hospital, Kota; Divyansh Mathur, MBBS - Co author, NKP co-author, Department of Endocrinology named after acad. V.G. Salve Institute of Medical Sciences Nagpur Maharashtra India; Baranov, North-Western State Medical University named after I.I. Dinesh Sharma, MD, FICP - Co author, Internal Medicine, Haribux Mechnikov Kanwatia Govt Hospital, Jaipur; Girish Mathur, MD, FACP, FCCPE, FRCPG, FRCPL - Co author, S. N. Pareek Memorial Hospital & Objective: High variability of the response to metformin is Research Center 3, Basant Vihar, Kota; K.K. Pareek, MD, FACP, commonly associated with genetic markers, predicting the indi- FCCPE, FRCPG, FRCPL - Co author, S. N. Pareek Memorial Hospital & vidual pharmacokinetics. Genetic studies investigating the influ- Research Center 3, Basant Vihar, Kota; G.D. Ramchandani, MD, ence of single nucleotide polymorphisms that determinate FACE, FACP, FCCPE, FRCPG - Presenter and Author, Ramchandani individual drug pharmacodynamics are more recent. The aim was diabetes care and research centre; Sarojini Ramchandani, BDS, to find out the possible influence of the KCNJ11 rs5219 (C >T) Dental Surgeon - Co author, Ramchandani diabetes care and variant on the diverse pharmacological response of metformin. research centre; Ranjana Rohira, MSc, Dietician - Co author, Methods: This prospective cohort study included 77 newly diag- Ramchandani diabetes care and research centre; j k Sharma, MD, nosed patients with type 2 diabetes mellitus (T2DM) (30 males), FACE, FCCPE, FRCPG, FRCPL - Co author, Central Delhi Diabetes incident users of metformin. The average age of the participants Centre, New Delhi was 54.7±7.6 years; starting metformin daily dose was 1500 mg. Fasting venous blood samples were taken from all subjects for the Objective: Adequate nutrition is one of the cornerstones in the determination of HbA1C, fasting plasma glucose (FPG) and fasting management of IDDM. The ISPAD guidelines recommend that total C-peptide; all these characteristics were measured prior to met- daily energy intake should be distributed approximately as carbo- formin therapy, and 6 months after the treatment. Baseline body hydrate >50%, fat 30e35% and protein 10e15%. To compare the mass index (BMI) and BMI after 6 month’s therapy with metformin dietary intake of patients with IDDM with the intake meets the was also recorded. Patients were genotyped for the KCNJ11 rs5219 C current ISPAD recommendations. >T variant using real-time PCR methods. A p-value less than 0.05 Methods: Methodology: The dietary intake of 50 IDDM children was considered significant. [age: 6e25 years] ; duration of IDDM: at least from one year] was Results: The frequencies of the CC, CT and TT genotypes were studied by the frequency questionnaire method. Data were 38.9%, 48.1% and 13% respectively. The genotype distribution was analyzed for the content of macronutrients. in accordance with the Hardy-Weinberg equilibrium (p >0.05). Results: Energy intake was lower in the patients (1600 ± 300 kcal/ All participants were divided into two groups: CC genotype day vs. 1958 ± 448 kcal/day). Carbohydrate intake (percentage of carriers (n¼30) and CT+TT genotypes carriers (n¼47). There was daily energy intake) was 48.9 ± 4.6%. IDDM did not reach the >50% a significant decrease in BMI, FPG, fasting C-peptide and HbA1C carbohydrate limit. The intake of mono- and disaccharides was 16.7 levels after 6 month’s treatment period in newly diagnosed ± 4.9%. Fiber intake was although higher in patients (21.7 ± 5.9% vs. T2DM patients both with or without the risk T allele. HbA1C of 17.5 ± 5.3%, p < 0.01). Fat intake was >35% in 20 (40%) IDDM pa- less than or equal to 7% was considered as good treatment tients. Protein intake was >15% in 19 (38%) IDDM patients. response and was observed in 71.4% CC genotype carriers Discussion/Conclusion: Although patients were diabetic so they compared with 83.3% T allele carriers. There was a trend of T were not consuming high carbohydrate food stuffs but mostly allele association with better glycemic control, although this did were taking cereals in more amount. Young patients don’t like not reach statistical significance (p¼0.29). However, after 6 green vegetables, so they were again consuming potatoes months of metformin therapy the dynamics (D%) of BMI mostly. Some patients were using vegetables in appropriate lowering was -2.6 [-4.1; -1,4] % vs. -5.0 [-6.8; -3.1] % (p¼0.0062) amount, some were taking in small amount. Fat is consumed and D% of FPG lowering was -3.2 [-7.4; -3.0] % vs. -10.3 [-13.5; although enough amount mostly. Protein diet was in a very low -6.9]% (p¼0.031) in patients with CC genotype compared to T amount in their diet. Mostly patients were vegetarian. Yet, they allele carriers respectively; the T allele was associated with didn’t take pulses, sprouts, milk and milk products in regular significantly lower fasting C-peptide level (3,20 [2,50; 4,20]ng/ml basis, may be the reason was poverty and their food habits for CC vs. 2,42 [2,10; 3,10]ng/ml for CT+TT; p¼0.0074). because they can’t afford high protein diet. So muscle wasting Discussion/Conclusion: Our results suggest that newly diagnosed was seen in mostly diabetic patients. Consumption of pulses, T2D patients with the KCNJ11 rs5219 polymorphism are more leafy vegetables, milk and milk products was grossly deficit in

S39 Diabetes/Prediabetes/Hypoglycemia Endocrine Practice 27 (2021) S24eS71 their diet. Only negligible amount of protective food were Abstract #1001507 consumed by these diabetic patients. Macronutrient malnutrition often occurs when diets lack to variety. Continuous nutritional A Case of Ketoacidosis with Complex Acid-Base education and advice remain indicated at least once a year. Disturbances in a Patient with Type 2 Diabetes https://doi.org/10.1016/j.eprac.2021.04.554 Mellitus, Pregnancy, and COVID-19

Author Block: Abstract #1001503 Samridhi Syal, MBBS - Primary author, Department of Medicine, Houston Methodist Hospital; Jessica Lucier, MD - Co- Safety And Efficacy of Empagliflozin in Pakistani author, Division of Endocrinology and Bone Metabolism, Muslim Patients with Type 2 Diabetes (SAFE-PAK) Department of Medicine, Houston Methodist Hospital; Anish Bhakta, DO - Co-author, Division of Nephrology, Department of Medicine, Houston Methodist Hospital; Horacio E. Adrogue, MD, Author Block: Azizul H. Aamir, MBBS (PAK), MRCP (UK), FRCP FASN - Co-author, Division of Nephrology, Department of (Edin), FACE(US) - presenter and primary author, Hayatabad Medicine, Houston Methodist Hospital; Archana R. Sadhu, MD, Medical Complex; Umar Y. Raja, FCPS - co-author, Shifa FACE - Co-author, Division of Endocrinology and Bone metabolism, International Hospital; Ali Asghar, FCPS - co-author, Fatimiyah Department of Medicine, Houston Methodist Hospital Hospital; Saeed A. Mahar, FCPS - co-author, National Institute of Introduction: Pregnancy, diabetes, and COVID-19 are each associ- Cardiovascular Disease; tahir Ghaffar, FCPS - co-author, Hayatabad ated with ketosis/ketoacidosis and changes in acid-base status. We Medical Complex; Ibrar Ahmed, FCPS - co-author, Lady Reading present our approach to a case of complex acid-base disturbances Hospital; Faisal M. Qureshi, FCPS - co-author, Al-Khaliq Hospital; in the presence of all three conditions. Jamal Zafar, FCPS - co-author, Hanif Medical Center; Imtiaz Hassan, Case Description: A 27-year-old female with type 2 diabetes and FCPS - co-author, Diabetes Institute of Pakistan; Amna Riaz, FCPS - 31 weeks gestation presented with shortness of breath and co-author, Jinnah Hospital; Irshad khoso, FCPS - co-author, COVID-19 pneumonia. She was tachypneic and required oxygen Balochistan Medical Center; Jahanzeb K. khan, MBBS - co-author, (3L/min) via nasal cannula on presentation. Laboratory evalua- Dow University of Health Sciences; Mahwish Raza, MsPH - co- tion on day 0 showed bicarbonate (CO ) 14 mEq/L and a cor- author, Shaheed Zulfikar Ali Bhutto Institute of Science And 2 rected anion gap (AG) 21 mEq/L consistent with high and Technology; Jaffer B. Baqar, MSc (Statistics) - co-author, University normal anion gap metabolic acidosis (arterial blood gas and of Karachi; Abbas Raza, DBIM - co-author, National Defence Center ketones were not available). A1C was 7.5% and glucose 226 mg/ dL. Home insulin regimen was resumed on admission. She Objective: Glycosuria increases the risk of genitourinary infections received convalescent plasma and remdesivir for COVID-19 along in diabetes. To establish the safety and efficacy of empagliflozin with beclomethasone for fetal lung maturity. However, on day 2 versus usual care in Pakistani Muslim diabetic patients having wet the patient decompensated with worsening tachypnea and personal hygiene practices. acidosis. She was now found to have acidemia (pH 7.32) with Methods: A multicenter randomised clinical trial conducted in metabolic acidosis (CO2 9 mEq/L, AG 23 mEq/L) and appropri- five cities across Pakistan from July-19 to August-20. Twelve ately compensated respiratory alkalosis (pCO2 22 mmHg). participating centers screened 745 patients and of these 244 Further workup showed a combination of normal and high AG (32.7%) were enrolled. Both gender aged 18-75 years, Body Mass metabolic acidosis in addition to hyperglycemia (239 mg/dL), Index 45kg/m2, HbA1c 7%-10% and treatment naïve to empa- ketonuria, and elevated beta hydroxybutyrate level (2.83 mmol/ gliflozin were included. Exclusion criteria included estimated L). A component of diabetic ketoacidosis (DKA) was suspected. glomerular filtration rate < 45mL/min/1.73m2, positive urine Treatment with DKA protocol resolved the acidemia (pH 7.42) culture, presence of serum ketones, and impaired liver functions. and normalized the AG (15 mEq/L) on day 3. However, metabolic Treatment allocation was done through randomization; G-1: acidosis (CO2 14 mEq/L) and respiratory alkalosis (pCO2 empagliflozin over and above standard care and G-2: standard 24mmHg) persisted. She was also treated with systemic corti- care group (without empagliflozin). Patients were followed-up for costeroids for COVID-19 and did not require intubation. Prenatal 24 weeks. non-stress testing was consistent with a low risk of fetal com- Results: Out of 244, total 129 (52.7%) were randomized to G-1. All plications and daily fetal monitoring was stable. The patient was baseline demographics and laboratory investigations were com- transitioned to a subcutaneous insulin regimen and discharged parable with p-value >0.05. Hypoglycemic events were signifi- home on day 7. At 37 weeks gestation, an elective cesarean cantly more in G-2 (G-1:12.9% vs G-2:17.8%; p¼0.041) whereas section was performed without complications. Neonatal hypo- positive urine culture (G-1:7.4% vs G-2: 9.9%; p¼0.521), fungal glycemia was noted in an otherwise healthy infant requiring 48- infection (G-1:0 vs G-2:2%; p¼0.522), dehydration (G-1:3.7% vs hour monitoring before discharge. 3.9%; p¼0.923) and hypotension (G-1:0.9% vs 2.9%; p¼0.281) Discussion: COVID-19 has been associated with ketosis and were insignificant. The 6 months mean HbA1c reduction was ketoacidosis in patients with and without diabetes. It is postu- significant in both groups; [G-1:0.91±0.2; p< 0.001 vs G- lated that SARS-CoV-2 virus can damage pancreatic islets 2:0.8±0.1; p< 0.001]. The mean reduction of weight [G-1:1.4±0.4; resulting in insulin deficiency. Pregnancy itself is associated with p¼0.002 vs G-2:0.01±0.5; p¼0.999] and systolic blood pressure respiratory alkalosis with incompletely compensated metabolic [G-1:9.5±3.3; p¼0.025 vs G-2:7.6±3.5; p¼0.120] were significant acidosis due to hormonal changes. Also, pregnancy is a state of in G-1. insulin resistance predisposing to ketoacidosis; however, the Discussion/Conclusion: Empagliflozin showed better safety profile occurrence of DKA in pregnancy is generally rare. Our patient as compared to standard care group and achieved better glycemic had complex acid-base changes consisting of metabolic acidosis control without weight gain and no additional risk of genitourinary (high & normal AG) and appropriately compensated respiratory infections in muslim diabetic patients. alkalosis. We concluded that high AG metabolic acidosis was https://doi.org/10.1016/j.eprac.2021.04.555 likely from ketoacidosis (diabetes, COVID-19, and/or pregnancy)

S40 Diabetes/Prediabetes/Hypoglycemia Endocrine Practice 27 (2021) S24eS71 and normal AG acidosis was compensatory from respiratory Abstract #1002088 alkalosis (COVID-19 and pregnancy). After treatment with DKA protocol, pregnancy-related respiratory alkalosis and metabolic Correlation between Obesity and Type 1 diabetes acidosis persisted. This complex case required a detailed analysis mellitus (DM1): A Single Centre Study of the many etiologies of acid-base disturbances for appropriate management. Author Block: https://doi.org/10.1016/j.eprac.2021.04.556 Dinesh Sharma, MD, FICP - Co author, Haribux Kanwatia Govt Hospital, Jaipur; Rahul Ramchandani, MBBS - Co author, Ramchandani diabetes care and research centre; Abstract #1002065 Divyansh Mathur, MBBS - Co author, NKP Salve Institute of Medical Sciences Nagpur Maharashtra India; Abhilasha Mangal, MSc, A Rare Case of Adult Nonketotic Hyperglycemic Dietician - Co author, Ramchandani diabetes care and research Hemichorea Misdiagnosed as Partial Seizure centre; Akhil Agrawal, MBBS, DNB, FAIPS - Co author, Manash hospital, Kota; K.K. Pareek, MD, FACP, FCCPE, FRCPG, FRCPL - Co author, S. N. Pareek Memorial Hospital & Research Center 3, Basant Author Block: Smit Mehta - Advocate Christ Medical Center; Vihar, Kota; Girish Mathur, MD, FACP, FCCPE, FRCPG, FRCPL - Co Safiya Elahi, D.O. - Co-Author, Internal Medicine, Advocate Christ author, S. N. Pareek Memorial Hospital & Research Center 3, Basant Medical Center Vihar, Kota; J.K. Sharma, MD, FACE, FRCPE, FRCPG, FRCPL - Co author, Central Delhi Diabetes Centre, New Delhi; Introduction: Nonketotic Hyperglycemic Hemichorea (NHH) is a Sarojini Ramchandani, BDS, Dental Surgeon - Co author, rare clinical syndrome characterized by severe hyperglycemia Ramchandani diabetes care and research centre; Ranjana Rohira, without ketoacidosis, hemichorea/hemiballismus, and basal MSc, Dietician - Co author, Ramchandani diabetes care and research ganglia enhancement on MRI. The pathogenesis is related to centre; G.D. Ramchandani, MD, FACP, FCCPE, FRCPG, FACE - Presenter cerebral hypoperfusion secondary to hyperglycemia, resulting in and Author, Ramchandani diabetes care and research centre depletion of GABA neurons in the basal ganglia. NHH has high potential for misdiagnosis, leading to treatment that may be Objective: Introduction: The increase in the global childhood detrimental to patient safety. We present an unusual case of obesity is one of the biggest problems all over the word . As we NHH. know that 1 in 300e500 infants and adolescents with less of 18 Case Description: A 72-year-old lady with a history of Type 2 years suffer from DM1. Obesity is directly associated with elevated DM treated with insulin presented after one day of upper ex- blood sugar and HbA1c. Objectiveof study is to know the preva- tremity weakness. She was severely hyperglycemic (609 mg/dL) lence of obesity in DM1 and this distribution by sex, age and its without evidence of DKA. She reported nonadherence with correlation with glycated hemoglobin (HbA1). home insulin and her HbA1c was 14%. She underwent extensive Methods: Methodology: Transversal revision of DM1 anthropo- cerebrovascular imaging with no evidence of stroke. Subsequent metric measurements from patients in follow-up at Ramchandani MRI brain demonstrated enhancement of bilateral basal ganglia. Diabetic Care & Research centre, Kota , Rajasthan , India was con- The patient reported resolution of her weakness after normali- ducted. Weight, sex, age and values of the HbA1c measured by fi zation of blood glucose. She clari ed that her initial symptoms HPLC were reviewed. “ ” involved wobbling of her arm, and suspicion was raised for an Results: Results: Out of 50 subjects 10% (5) subjects were very atypical seizure presentation. Though EEG was negative for severely underweight having BMI below 15kg/m2, 30% (15) were epileptiform activity, she was diagnosed with complex hyper- found to be severely underweight their BMI falls in between 15 to glycemia-related partial seizures and discharged. One week later, 16kg/m square.16% (8) subjects were under weight were coming in the patient presented with similar complaints and visible the range of 16-18.5 kg/m square. 42% (21) subjects were in the choreiform movements of the left face as well as severe hy- normal range between 18.5-25 kg/m2. Only one female subject was perglycemia. Given her recent diagnosis of seizures, the patient overweight with BMI 25.1 kg/m2. No one subject was found to was started on levetiracetam without effect. Repeat MRI brain obese. There are female BMI is slightly higher than male BMI, was negative for subthalamic stroke. Repeat EEG was negative. although both were mostly severely underweight. 98% subjects had Chorea improved noticeably after blood sugar control was ach- higher sugar level and high HbA1c level. HBA1c median was of ieved. She was started on haloperidol twice daily for movement 9.44% with standard deviation of 2.45%. Only one patient had control. Further chorea workup was negative for evidence of normal HbA1c value below 7%. Out of 50, 8% had between 7-8%, 22% ’ ’ Wilson s disease, SLE, APLS, or Huntington s. Diagnosis of NHH patients had 8-9% , 22% had 9-10, 16% had 10-11, 4% had 11-12%, 14% was made and the patient was discharged on haloperidol and had 12-13%, 10% had between 13-14% and 1 patient had A1c level insulin. between 14-15% which was very high. Discussion: NHH is a rare neurological complication of uncon- Discussion/Conclusion: Conclusion: The prevalence that we have trolled diabetes that is important to recognize, as reversal of found of obesity and overweight was not a very big deal in type 1 symptoms is achievable with strict glycemic control. Patients diabetic population. Mostly when there is elevated HbA1c level with NHH can be misdiagnosed with more common causes of then obesity and overweight is rare. chorea such as subthalamic stroke, Wilson’s disease, and Hun- tington’s disease. For our patient, failure to recognize NHH https://doi.org/10.1016/j.eprac.2021.04.558 resulted in expensive workup for other neurologic syndromes and inappropriate initiation of antiepileptics. Ultimately, prompt recognition of NHH and timely initiation of insulin therapy is Abstract #1002210 vital for patients with this clinical syndrome. Echocardiographic Assessment and Correlates Among https://doi.org/10.1016/j.eprac.2021.04.557 Long Standing Type 2 Diabetics

S41 Diabetes/Prediabetes/Hypoglycemia Endocrine Practice 27 (2021) S24eS71

Author Block: Kapil Dev, Physician - Primary author, Internal with Misoprostol and Mifepristone and developed Diabetic Ketoa- medicine, Dayanand medical college and hospital; Dinesh Gupta, cidosis (DKA). Physician - Co-author, Medicine, Dayanand medical college and Case Description: A 31-year-old female G2P1 with type 1 DM with hospital; Parminder Singh, Endocrinologist - Co-author, microvascular complications including neuropathy, retinopathy Endocrinology, Dayanand medical college and hospital; and nephropathy, presented to the hospital with nausea, vomiting, Gurpreet singh Wander, Cardiologist - Co-author, Cardiology, abdominal pain, and vaginal bleeding. Her home insulin regimen Dayanand medical college and hospital; Rahul Aggrawal - Co- included Glargine 12 units at bedtime and Lispro 5-10 units before author, Cardiology, Dayanand medical college and hospital meals. Prior to admission patient had taken Misoprostol and Mifepristone at home for medical abortion at her fifth week of Objective: To study the pattern of Echocardiographic findings and gestation. She had been compliant with the long-acting insulin but to correlates the findings in long standing diabetics, to measure the skipped short-acting insulin due to poor oral intake because of relation of left ventricular systolic and diastolic dysfunction with nausea and vomiting. In the emergency department, she was noted age, duration of diabetes, HBa1c, obesity indices. to have elevated blood glucose with evidence of DKA. Initial blood Methods: We did an observational prospective study at Dayanand glucose was 364 mg/dL, anion gap 15 mmol/L, serum bicarbonate medical college and hospital,ludhiana,punjab, india between 2018 17 mmol/L, beta-hydroxybutyrate >46 and positive ketones in the and 2020. Subjects were 300 type2 diabetes mellitus patients who urine. Hemoglobin A1C was found to be 10.5%. She was admitted to came for regular health check-up. The informed consent was ob- the Intensive Care Unit (ICU) for the management of DKA. She tained from the participants after explaining them about the study responded adequately to fluid resuscitation and insulin drip and in their first language, punjabi or hindi. was successfully transitioned to basal-bolus insulin regimen. OB/ Results: In our study majority of the patients belonged to age group GYN followed up and monitored the patient who had appropriately 51-60years(n¼126,42.0%). out of total 300 patients,206(68.7%)were declining HCG levels. The patient was discharged on her home in- males and 94(31.3%) were females.interventricular septal thickness sulin therapy and followed up as outpatient with her Endocrinol- was high in both systolic(68.7%)and diastolic(51.3%).left ventricular ogist and her OB/GYN. internal diameter was high in both the group systolic (19.3%)and Discussion: Elective medical abortion has been used more diastole(9%).left ventricular posterior wall thickness was high in frequently in obstetrical practice due to a higher likelihood of both systolic (74.7%) and diastolic(46%) group.global hypokinesia successful management of first-trimester pregnancy loss. Preex- was seen in 5.3% patients.23 % showed regional wall motion ab- isting medical conditions such as DM, require coordination of care normalities. Left ventricular hypertrophy was seen in 36.3% between patient and medical providers, especially during this patients.the study showed that 82(27.3%) patients had systolic transitional time. Our patient developed DKA shortly after using dysfunction,84(28.1%) patients had diastolic dysfunction, and Misoprostol and Mifepristone. We report this case as the use of 140(46.7%) patients had both systolic and diastolic dysfunction abortive medications is common and these therapeutics may lead .based on multivariate analysis ,the parameters such as age to metabolic dysregulations, including DKA, in patients with type 1 ,BMI,LVH,FBS were statistically significant (p-value< 0.05). DM. The underlying mechanism is not well understood. We Discussion/Conclusion: Patients with type2 diabetes should be recommend caution when abortive medications are being pre- screened for subclinical left ventricular diastolic dysfunction by scribed to patients with type 1 DM and further investigation of the Echocardiography regardless of cardiac symptoms and clinical underlying mechanism of dysglycemia in these cases. characteristics. Diastolic dysfunction in diabetics is independent of https://doi.org/10.1016/j.eprac.2021.04.560 duration of diabetes . Early diagnosis and institution of treatment with ACE inhibitors, angiotensin-II receptor blockers, aldosterone antagonists, and diuretics will reduce the morbidity and improve Abstract #1002308 the outcome of diastolic heart failure. https://doi.org/10.1016/j.eprac.2021.04.559 Causes of Diabetic Ketoacidosis among Adults Admitted to a Comprehensive Cancer Center

Abstract #1002287 Author Block: Rebecca Jeun - Baylor College of Medicine; A Case of Diabetic Ketoacidosis in Medical Sonali Thosani, MD - co-author, Endocrine Neoplasia and Management of Miscarriage Hormonal Disorders, MD Anderson Cancer Center

Objective: Diabetic ketoacidosis (DKA) is a life-threatening mani- Author Block: Andrea Santos - Saint Peters University Hospital; festation of diabetes associated with significant morbidity and Natalia Branis, MD - Co- Author, Endocrinology, Saint Peters health care utilization. While DKA is commonly seen in patients University Hospital with poorly controlled Type 1 or Type 2 diabetes, it can also occur due to the use of drugs such sodium-glucose co-transporter-2 Introduction: Elective medical abortion is a common obstetric (SGLT2) inhibitors and immune checkpoint inhibitors (ICI). While procedure performed among women. There are many abortive the etiology of DKA in the general population is most commonly methods used in clinical practice. This can be either completed with insulin nonadherence, there is limited data on cancer patients with medication or by a surgical procedure. Women may have an elec- DKA. In this study, we characterize the demographic and clinical tive first-trimester miscarriage through a non-surgical treatment characteristics of cancer patients admitted with DKA at a compre- approach either with Misoprostol alone, a prostaglandin analog, or hensive cancer center. in combination with Mifepristone, a glucocorticoid progesterone Methods: This was a retrospective single-center study of admis- receptor antagonist. We present a case of a 31-year-old female with sions for DKA between January and December 2019 with 29 pa- type 1 diabetes mellitus (DM) who underwent medical abortion tients in total identified, each with 1 admission for DKA during the

S42 Diabetes/Prediabetes/Hypoglycemia Endocrine Practice 27 (2021) S24eS71 study period. Demographic, clinical, and biochemical data were effects (ADE) occurrence among patients with newly diagnosed obtained from review of the electronic medical record. T2DM treated with vildagliptin. Results: Median age at presentation was 64 years old. Median Methods: Our prospective study with convenience sampling hospital length of stay was 7 days. The most prevalent type of included 48 patients with newly detected T2DM, comprised for diabetes represented in this cohort was 9/29 (31%) patients with 37,5% of males. The mean age of the study population was 58.5±5.6 immune checkpoint inhibitor related diabetes mellitus (ICI DM) years, the mean body mass index was 31.1±4.5 kg/m2, the baseline followed by T1DM and T2DM, with 7 patients each (24%). The mean HbA1c was 7.7±1.1%. All patients had clinical indications and remaining patients had a diagnosis of ketosis-prone diabetes, had no contraindications to start vildagliptin therapy in initial dose latent autoimmune diabetes in adults (LADA), or pancreatogenic of 50 mg once a day. All participants were genotyped for the TCF7L2 diabetes. The median baseline A1c was 8.1% prior to presenta- rs7903146 polymorphism by Real-Time PCR system using the tion. The most common precipitating factor for presentation was appropriate reagent kit (Syntol, Russia) according to the manufac- use of a medication directly leading to DKA (ICI, SGTL2 in- turer’s instructions. Adverse effects were based on self-report by hibitors, or steroids). Nonadherence to insulin was a contributing individuals during clinical follow-up. Any ADE observed with vil- factor in only 3/29 (10%) admissions. Inappropriate withholding dagliptin were recorded and were considered as the clinical end- of basal insulin or an insulin pump was seen in 17% of admis- points in this analysis. Fisher’s exact test was used; a p-value less sions. Almost ¾ of the admissions were characterized by mod- than 0.05 was considered significant. erate to severe DKA. The 30-day all-cause mortality rate was 17% Results: The minor T allele frequency was 0.25. The frequencies of and the 1-year all-cause mortality rate was 38%. the CC, CT and TT genotypes were 58.4%, 33.3% and 8.3% respec- Discussion/Conclusion: In this study of patients admitted to a tively. The genotype distribution was in accordance with the Hardy- cancer center, a heterogeneous mixture of underlying diabetes Weinberg equilibrium (p > 0.05). All participants were divided into classification and provoking factors of DKA were identified. two groups: wild genotype carriers (n¼28) and the minor T allele Precipitating factors for DKA that are seen in the general pop- carriers (n¼20). There was a significant decrease in HbA1C levels ulation such as medication nonadherence with underlying poor after 6 months of vildagliptin treatment in newly diagnosed T2DM glycemic control were not commonly seen in cancer patients. patients both with or without the risk T allele (p< 0,001). However, Instead, specific pharmacologic agents such as immune check- at 6 months of treatment 20% of patients with rs7903146 poly- point inhibitors, steroids, and SGLT2 inhibitors were more likely morphism prescribed vildagliptin experienced adverse effects, to provoke DKA in cancer patients. As the median age of pre- particularly nausea and loss of appetite. Specific symptoms were sentation in this cohort was much higher than the general not described for CC genotype carriers. The incidence of gastroin- population admitted with DKA, there is a higher risk of mor- testinal adverse events was significantly higher in the minor T allele tality than seen with the general population. Most admissions carriers compared with CC genotype carriers (p¼0.025). No other were characterized by moderate to severe DKA on presentation. adverse effects of therapy were observed in all participants treated These findings suggest that cancer patients with diabetes may with vildagliptin. need a different approach in management and more specific Discussion/Conclusion: In our study, we found an association of the counseling for prevention and timely treatment for DKA in these TCF7L2 rs7903146 variant with gastrointestinal adverse effects of circumstances. Further investigation into factors contributing to vildagliptin in patients with newly diagnosed T2DM. Personalizing hospitalizations for DKA should consider the unique de- diabetes treatment based on patients genetic can improve patient mographic and clinical characteristics of this patient population. care by decreasing the number of adverse drug events. https://doi.org/10.1016/j.eprac.2021.04.561 https://doi.org/10.1016/j.eprac.2021.04.562

Abstract #1002380 Abstract #1002435

The Common Variant in the TCF7L2 Gene Is Associated A Severe Case of Recurrent Hypertriglyceridemia- With Adverse Effects in Type 2 Diabetic Patients Induced Pancreatitis Associated With Splenic Vein Treated With Vildagliptin Thrombosis in a Patient With Poorly Controlled Diabetes Mellitus Type 2

Author Block: Vitaly Baranov - North-Western State Medical University named after I.I. Mechnikov; Polina Shorokhova, MD - Author Block: Shumail Syed - Creighton University; Sana Fatima, co-author, Department of Endocrinology named after acad. V.G. MD - co-author, Yale University; Sudha Nandala, MD - co-author, Baranov, North-Western State Medical University named after I.I. Creighton University; Alain Taylon, MD - co-author, Creighton Mechnikov; Natalya Vorokhobina, DMSc, Professor - Head of University Department of Endocrinology named after acad. V.G. Baranov e co-author, Department of Endocrinology named after acad. V.G. Introduction: Hypertriglyceridemia-induced pancreatitis (HTGP) is Baranov, North-Western State Medical University named after I.I. an important cause of pancreatitis causing about 1-14 % of all cases Mechnikov of acute pancreatitis. As compared to other causes of pancreatitis, it usually involves a patient population that is predominantly male, Objective: Currently vildagliptin can be used for treating type 2 younger, obese and diabetic. Incidence of splenic vein thrombosis diabetes mellitus (T2DM) as a first-line monotherapy. The main in patients with HTGP has been estimated to be about 3.6%. This adverse drug events which have been reported with the use of abstract describes a female patient who presented with recurrent vildagliptin include nausea, loss of appetite, diarrhea, peripheral HTGP and was also found to have splenic vein thrombosis in the edema, headache, dizziness and upper respiratory infection. This setting of poorly controlled diabetes mellitus type 2. study was conducted to determine possible association between Case Description: A 47-year-old female patient with a history of the TCF7L2 rs7903146 (C >T) polymorphism and adverse drug type 2 diabetes mellitus, hypothyroidism and hypertriglyceridemia

S43 Diabetes/Prediabetes/Hypoglycemia Endocrine Practice 27 (2021) S24eS71 presented to the emergency department with rapid onset of Health Questionnaire-9 (PHQ-9); a standardized questionnaire epigastric pain which started on day of arrival. She had history of developed in the United States of America. Demographic, clinical, noncompliance with fenofibrate. She denied using any alcohol or and diabetes-related information were collected using a semi- other recreational drugs. She had abdominal tenderness on structured questionnaire after written informed consent of the palpation. Her labs on admission were: Hb 9.6 g/dl, HCT 28.0 %, patients. WBC 10.1 K/ul, PLT 216 K/ul, Glucose 298 mg/dl, Sodium 124 mmol/ Results: Of the 318 patients, 72.01% were female. Mean age was l, BUN 28 mg/dl, Creatinine 1.28 mg/dl, AST 43 u/l, ALT 14 u/l, Lipase 49.04 ±1.11 years and mean duration of diabetes was 7.51 ±6.18 4247 u/l, triglycerides >4000 mg/dl, albumin 2.3 mg/dl, calcium 6.9 years. The prevalence of depression among T2DM patients was mg/dl and HbA1c 11.3%. Her imaging revealed acute interstitial 64.2% (male vs. female: 17.9% vs. 46.2%). According to PHQ-9 tool, edematous pancreatitis, splenic vein thrombosis and hepatic stea- 35.5% of patients showed no depression (male vs. female: 9.7% vs. tosis. She was treated with intravenous hydration, pain control and 25.8 %), 30.8% had mild depression (male vs. female: 11.0 % vs. 19.8 kept NPO. She became febrile, tachycardic and tachypneic and was %),18.9% had moderate depression (male vs. female: 5.0 % vs. 13.8%), transferred to ICU. Her antibiotics were broadened to vancomycin some (11.6%) had moderately severe depression (male vs. female: and piperacillin-tazobactam. She was started on insulin drip. Tri- 1.6% vs. 10.1 %), and only a few (3.1%) had severe depression (male glyceride levels were monitored every 12 hours. Her hospital vs. female: 0.6 % vs. 2.5 %); [p¼0.12]. Several socio-demographic course was complicated by multiorgan failure characterized by factors were found to be significantly associated with depression acute tubular necrosis (ATN), altered mental status and acute including increasing age, rural residence, low education, unem- hypoxic respiratory failure. She underwent 3 rounds of plasma- ployment or retired, and the status of being unmarried or widow; pheresis as well as became dialysis-dependent during this hospi- [p< 0.05]. The longer duration of diabetes ( >10 years), presence of talization due to progressive ATN. She was transitioned to diabetic complications and other chronic diseases (such as hyper- subcutaneous insulin when her triglycerides were less than 500 tension, dyslipidemia, etc.) also were found to be associated with mg/dl. Due to absence of portal vein or SMV involvement and no depression; [p< 0.001]. liver dysfunction or bowel ischemia, anticoagulation was not Discussion/Conclusion: Diabetes and depression can have a bidi- initiated for splenic vein thrombosis. She was placed on atorvas- rectional relationship. Patients with diabetes are liable to become tatin and could not be placed on fenofibrate due to her dialysis depressed due to the chronic nature of the disease and its dependence. She was later started on gemfibrozil. She was subse- numerous complications while diabetes can arise in depression due quently found to have multiple pancreatic pseudocysts with walled to an increase in counter regulatory hormones. off necrosis. The largest one of these was drained by interventional Depression was found to be particularly high among the study radiology. population. Since depression could significantly hinder patient’s Discussion: Triglyceride levels of 1000 mg/dl or greater have been adherence to treatment, there is an urgent need for early diagnosis known to trigger acute pancreatitis. In our case, poorly controlled and treatment. This calls for the integration of mental health care diabetes mellitus in the setting of noncompliance with fibrates into the management of diabetes. likely contributed to secondary hypertriglyceridemia. Our patient https://doi.org/10.1016/j.eprac.2021.04.564 had one prior episode of HTGP one year ago which had also required plasmapheresis. Therapeutic options for long term man- agement of hypertriglyceridemia are limited in patients who are Abstract #1002634 dialysis dependent. fi https://doi.org/10.1016/j.eprac.2021.04.563 Ef cacy of Hydroxychloroquine as a Fourth Add-On in T2DM Patients who were inadequately Controlled on Triple Drug Therapy Abstract #1002493

Prevalence of Depression and Assessment of Author Block: Sajjad Ahsan - Indira Gandhi Institute of Medical Associated Factors among Patients with Type 2 Sciences; Abhishek Kumar, Diabetologist - co-author, J.L.N. Medical Diabetes Mellitus in A Tertiary Care Hospital College and Hospital,; Manish Kumar, Diabetologist - co-author, Patna Medical College and Hospital; Naveen Kumar, Diabetologist - co-author, Global diabetes Care and Research Centre; Vivek Kumar, Author Block: Nazma Akter - MARKS Medical College & Hospital, Diabetologist - co-author, Madhubani Medical College & Hospital Dhaka, Bangladesh Objective: To evaluate the efficacy of hydroxychloroquine 400 mg Objective: Patients with diabetes mellitus (DM) have a poorer as a fourth therapeutic agent in type 2 diabetes mellitus (T2DM) quality of life when compared with patients without DM. Any patients with poorly controlled blood glucose despite receiving an chronic illness will have a negative impact on its sufferer. In fact, optimum dose of three oral antidiabetic drugs (OAD). one in every five diabetic patients suffers from co-morbid depres- Methods: A retrospective analysis of 558 T2DM patients with 3 sion, which can lead to poor management, poor compliance with regular follow-ups visiting a Diabetes Specialty Clinic, who received treatment, and low quality of life. hydroxychloroquine 400 mg as the fourth drug despite optimum This study aimed to estimate the prevalence of depression and to doses of three OADs, metformin, sulfonylureas, pioglitazone or identify its associated factors influencing depression among pa- alpha-glucosidase inhibitors to achieve glycemic control was un- tients with type 2 diabetes mellitus attending an out-patient clinic dertaken. Patients with inadequate glycaemic control despite at a tertiary care hospital. receiving optimum doses of at least any other three OADs were Methods: A cross-sectional study was conducted among 318 type 2 included in this analysis. diabetic (T2DM) patients attending a diabetic clinic at a tertiary Results: 330 (60%) patents were male. Mean age was 55.2 ± 11.62 care hospital in Dhaka, Bangladesh during July 2019 to February years and 80% of patients had BMI 23 kg/m2, while 85% had T2DM 2020. Depression was assessed among the subjects using Patient for 10 yrs. Patients achieving glycemic control with the addition

S44 Diabetes/Prediabetes/Hypoglycemia Endocrine Practice 27 (2021) S24eS71 of hydroxychloroquine were 88% (P< 0.05). The mean duration of - equal to 6.0 mmol/l, and HbA1c - equal to 38 mmol/mol. time required to introduce hydroxychloroquine 400 mg/day was Values above these and below diabetic levels (11.1 mmol/l, 6.9 119.59 months (~10 years) for the study population. The mean mmol/l, and 47.5 mmol/mol respectively) can be considered as duration required to achieve glycemic control after adding prediabetes. hydroxychloroquine was 8.2 weeks. At the end of the monitoring https://doi.org/10.1016/j.eprac.2021.04.566 period, there was significant reduction in mean FPG by-28.1 ± 16.1 mg/dL(P¼0.001), mean PPG by -55.3 ± 17.0 mg/dL(P¼0.001), and mean HbA1c by -1.2 ± 0.7 (P¼ 0.001). There was no significant Abstract #1002698 difference between the groups with respect to reduction in PPG and HbA1c. The response in age group < 55 years was 88%, whereas in A case of Necrobiosis Lipoidica Diabeticorum: A rare 55 years group, it was 81%. The males responded more (94%) complication of Diabetes Mellitus compared to females (82%). Those with BMI 23 kg/m2 had significantly higher response (98%) as compared to 78% in patients with BMI < 23 kg/m2. Author Block: Shameela Begum - Shadan Institute of Medical Discussion/Conclusion: Hydroxychloroquine 400 mg OD is effec- Sciences; Syed Wajih Rizvi, MD - Co-author, Endocrinology, tive in achieving desired glycaemic goals even when used as a R-Endocrinology; Muntazir Ali Sayed, MBBS - Co-author, Internal fourth drug in patients with inadequate glycaemic control despite Medicine, R-Endocrinology; Shahnaz Begum, MBBS - Co-author, receiving an optimum dose of at least 3 OADs. GMC/NHS; Ammar Mushtaq, MD - Co-author, Internal Medicine, https://doi.org/10.1016/j.eprac.2021.04.565 AMITA Health; Mohammed Samiulla Hussaini, MBBS - Co-author, DCMS; Sadiq Ali Sayed, MBBS - Co-author, Internal Medicine, National Pirogov Memorial Medical University, Vinnytsya, Ukraine; Abstract #1002645 Fatima Sameen, MBBS - Co-author, Gulf Medical University

Definition of Norma / Prediabetes Cut-off Point for Introduction: Necrobiosis Lipoidica Diabeticorum (NLD) is an un- Glycated Hemoglobin on the Basis of Glucose common, idiopathic, granulomatous disease of collagen degenera- Tolerance Test and Fasting Glucose Interrelationships. tion with the risk of ulceration, often associated with diabetes mellitus. The incidence rate among individuals with diabetes is 0.3% to 1.2%. It usually presents in the pretibial surface. The disease Author Block: Sevil Ismayilova, MD - Primary author, Azerbaijan course is more common in women but shows more severity in men State Postgraduate Institute for Physicians; Sadagat Sultanova, PhD as they have a higher probability of ulceration in their lesions. We - Co-author, Azerbaijan State Postgraduate Institute for Physicians; report a rare case of Diabetes Mellitus associated with exemplary Aygun Huseynova, MD - Co-author, Azerbaijan State Postgraduate NLD in a female patient. Institute for Physicians; Valeh Mirzazade, Professor - Co-author, Case Description: A 75-year-old Asian female with Diabetes Azerbaijan State Postgraduate Institute for Physicians Mellitus Type II for the past 28 years, being managed by a combination of oral hypoglycemics and insulin, presented to our Objective: The unification of approaches to the diagnosis of out-patient Endocrinology clinic for a routine follow-up. During prediabetes (PD) is doubtless. The borderline between PD and the evaluation, she reported a rash on her lower extremities. On diabetes is well known by all, as well as the upper and lower physical examination, there was a small, non-tender, irregular, bounds of PD according to the results of glycemia 120 minutes poorly demarcated, red-brown colored shiny rash on her both after 75 g glucose loading (GL120). There is still vagueness shins, more noticeable on the right side, also associated with regarding glycohemoglobin (HbA1c) and fasting glycemia (FG). decreased sensation and alopecia around the rash. Recent blood- The aim of this study was to determine the Norma/PD cut-off work results showed a fasting glucose of 201 mg/dL and HbA1c point for HbA1c of 7.1%. Other laboratory investigations were within normal Methods: 85 nondiabetic glucose tolerance test results (Samples of limits. Her lower extremity doppler ultrasound showed no evi- fasting blood, and 120 minutes after glucose loading, and HbA1c dence of DVT, and nerve conduction study revealed no signifi- results were analyzed by using correlation and regression analysis. cant changes. We reassured her about the benign nature of the Glycemic values were measured in mmol/l, HbA1c values were rash and how it could be managed with better glycemic control. measured in mmol/mol. To achieve this goal, we increased her Basaglar insulin dosage to Results: The fact of identifying the relationship between HbA1c and 34 units with lunch and 14 units with dinner (from 20 units BID GL120 (r¼+0.58 [95%CI +0.419, +0.705]; p< 0.001), as well as be- previously), increased her Novolog insulin dosage to 10 units at tween HbA1c and FG (r¼+0.59 [95%CI +0.432, +0.713]; p< 0.001) breakfast, 10 units at lunch, and 5 units at dinner (from 8-8-4 were the basis of study. Based on the result of regression analysis, previously), and continued other medications as Metformin multiple regression equations were received. 1000mg (PO x BID), Glimepiride 2mg (PO x BID), and Acarbose HbA1C¼ 12.3514+2.2549*GL0 +1.5751*GL120 100mg (PO x TID). On a follow-up visit after 14 weeks, her If GL120 is equal to 7.7 mmol / l (in accordance with all recom- HbA1c was 6.6% and CGMS report showed 71% of her blood mendations), and FG is equal to 5.5 mmol/l (as recommended by glucose levels were in target range. We noticed cessation of the American Diabetes Association) the maximal normal value for progress of the rash over a period of 12 weeks which had not HbA1c should be equal to 37 mmol/mol (5.5%). If GL120 is equal to resolved completely. We would be monitoring her in subsequent 7.7 mmol / l, and FG is equal to 6.0 mmol/l (in accordance with the encounters. recommendations of NICE, Canadian Diabetes Association, Austra- Discussion: NLD is an uncommon skin complication of Diabetes lian Diabetes Association, et al.), the maximal normal value of Mellitus. There are various medications available for NLD, all with HbA1c should be 38 mmol/mol. variable efficacy but no specific treatment. The key is to maintain a Discussion/Conclusion: The optimal upper limit of normal car- good glycemic control. Although NLD is usually asymptomatic, bohydrate metabolism is levels of GL120 equal to 7.7 mmol/l, FG patients with NLD should be periodically monitored for indications

S45 Diabetes/Prediabetes/Hypoglycemia Endocrine Practice 27 (2021) S24eS71 of ulceration or malignant transformation, in which case more Abstract #1003105 aggressive treatment might be warranted. https://doi.org/10.1016/j.eprac.2021.04.567 Reducing ED Visits and Hospital Readmissions and Improving Glucose Control of Patients with Uncontrolled Type 2 Diabetes by Use of Continuous Abstract #1002952 Glucose Monitoring Sensors Placed at Hospital Discharge

Rare Case of Falsely Elevated Hemoglobin A1c (HbA1c) in a Patient with a Heterozygous Hb-Hope Author Block: Carmen Cartwright - Einstein HealthCare Network; Hemoglobinopathy Mumtaheena Miah, MD - co-author, Endocrinology, Einstein HealthCare Network; Peter Ucciferro, DO - co-author, Endocrinology, Einstein HealthCare Network; Author Block: Sheetal Bulchandani - University of Missouri- Catherine Anastasopoulou, MD, PhD, FACE - co-author, Kansas City; Peminda Cabandugama, MD - Co Author, Universit of Endocrinology, Einstein HealthCare Network Missouri Kansas City; Varundeep Rakhra, D.O - Co-Author, Universit of Missouri Kansas City Objective: Diabetes mellitus is a widespread entity with crude es- timates that 13% of adults within the US population had the disease Introduction: Hemoglobin A1c (HbA1c) is the current standard of as of 2018; encompassing 34.1 million people. Diabetes is associ- care used to monitor long term glycemic control in people with ated with significant morbidity and mortality largely affected by diabetes mellitus (DM). However, the accuracy of HbA1c mea- glycemic control. 16 million emergency department (ED) visits and surements can be affected adversely by the presence of hemoglobin 7.8 million hospital discharges for diabetic patients were reported (Hb) variants. Hemoglobin Hope (HbHope) is one of those rare in 2016. Studies anticipate that the prevalence of diabetes is to variants. Here, we report a rare case of falsely elevated HbA1c due increase by 54% between 2015 and 2030; annual deaths attributed to heterozygous HbHope, which is commonly a benign condition as to diabetes will rise by 38% and total annual medical and societal per the literature. costs related to diabetes will increase 53% by 2030. Case Description: A 44-year-old male with a medical history Our study aimed to investigate if continuous glucose monitoring significant for type 1 DM presented to the Endocrinology clinic post hospitalization, would lead to improvements in glycemic for routine follow-up. His insulin regimen consisted of Glar- control and consequently reduction in emergency room visits and gine 40 units in the morning and Aspart 3 units with meals. hospital readmission rates. His lab values were significant for HbA1c of 10.1% with Fruc- Methods: Our prospective, non-blinded study randomized subjects tosamine of 279.91 umol/L which is an equivalent HbA1c of to continuous glucose monitoring for 2 weeks upon discharge from 6.8%. The patient also reported morning hypoglycemia with the hospital versus usual care with self-monitoring of blood glucose blood glucose (BG) levels of 50mg/dL. At this point, Hb elec- levels with fingersticks. Subjects were type 2 diabetics with he- trophoresis was performed on the patient due to discrepancies moglobin A1c of 9% within 3-4 months prior to enrollment. between the patient’s HbA1c and Fructosamine/BG reports Hemoglobin A1c levels at 3- and 6-months post hospital discharge, which demonstrated a pattern that was consistent with het- ED visits and hospital readmissions were assessed up to 6 months erozygous HbHope. During subsequent follow-up visits, it was post hospital discharge. noted that multiple paired Fructosamine and HbA1c mea- Results: A total of 58 patients were enrolled in the study between surements differed in value with a clinically significant dif- October 2018 and September 2020. 28 study subjects (48%) were ference of approximately 3% between the two. The patient’sBG randomly assigned to wear a freestyle libre pro continuous glucose was much more compatible with the lower Fructosamine monitor for 2 weeks post discharge. The mean starting hemoglobin levels and this was confirmed with multiple glucometer A1c for the intervention group was 11.35% compared to 11.12% in downloads which demonstrated that the patient was regularly the control group. The hemoglobin A1c levels improved in both checking his BG levels (approximately 8x/d) and was having control and intervention groups, at 3- and 6-months follow-up his BG in the range of 74-75% of the time. without statistically nor clinically significant difference between Discussion: HbA1c is the product of a non-enzymatic reaction groups. The mean hemoglobin A1c levels at 3 months follow up of glycation and an important biochemical marker that is were 8.4% for the control group and 8.3% for the continuous glucose widely used to estimate long-term glycemic control in diabetic monitor group respectively. At 6 months follow up levels were 9.1% patients. However, the accuracy of its measurement can be vs. 8.9% respectively. When assessing the impact of ED visits and affected by red blood cell dyscrasias and hemoglobinopathies. hospital readmissions in the 6-months post hospitalization follow- HbHope is a beta chain Hb variant where the aspartic acid is up there was a marked, although not statistically significant dif- substituted for glycine at position 136 of the beta chain. As per ference, in that 57.1% of those in the intervention group had at least literature review, HbHope in its heterozygous form is clinically 1 ED visit vs. 35.7% in the control group (p¼ 0.18, 95% CI¼ -0.04% to benign and in the homozygous form, HbHope can be co-eluted 46.9%). 42% of patients within the intervention group had a hospital with A1c and lead to the spurious elevation of HbA1c in ion- admission compared to 32.1% in the control group (p¼0.58, 95 CI ¼ exchange chromatographic and electrophoretic assays. How- -0.14 to + 35.9%). ever, our case brings up the point that there could be some Discussion/Conclusion: Subjects whether assigned to continuous mosaic forms of Heterozygous HbHope that may also interfere glucose monitoring or self-monitoring of blood glucose levels were with HbA1c measurements. Thus it is imperative for physicians able to achieve similar hemoglobin A1c reductions. to be aware of unusual Hb variants such as HbHope and We propose this is due to improved education and patient self- consider alternative testing when the HbA1c and patient’sBG awareness for disease monitoring during sentinel hospital visit. report provide discrepant results so as to safely optimize the Contrary to our expectation and hypothesis, continuous glucose patient’sdiabeticregimen. monitor use for two weeks immediately post hospitalization did https://doi.org/10.1016/j.eprac.2021.04.568 not lead to reductions in ED visits or hospital readmissions.

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Our study suggests that further exploration regarding the use of thus we advocate for a gradual decrease of 2% every 3 months till continuous glucose monitors for reduction of hospital read- target goals are reached. missions, specifically in type 2 diabetics, is needed. https://doi.org/10.1016/j.eprac.2021.04.570 https://doi.org/10.1016/j.eprac.2021.04.569

Abstract #1003158 Abstract #1003139 Study of Association of Hyperglycemia with Acute Stroke Treatment Induced Neuropathy of Diabetes : Too Fast is Not Too Good Author Block: Swati Srivastava, M.D, FRCP (Edin), FICP - Primary author and presenter, SMS Medical College, Jaipur; Author Block: Pranathi Vemparala - St Luke's University Health Mukesh K. Chopra, M.D, Resident - Co-author, SMS Medical Network; Yididia Bekele, MD - Co-author, Internal Medicine, St College, Jaipur; Aishwarya Malode, M.D, Resident - Co-author, SMS Luke's University Health Network; Mahesh Krishnamurthy, MD, Medical College; Vishal Kalwaan, M.D, Resident - Co-author, SMS FACP, SFHM - Co-author, St Luke's University Health Network Medical College; Rakesh K. Bhamu, M.D - Co-author, SMS Medical College; Vikas Kumar, M.D, Resident - Co-author, SMS Medical College Introduction: Treatment-induced neuropathy of diabetes (TIND) presenting as a new-onset peripheral neuropathy usually associ- Objective: Diabetes mellitus is a well-known risk factor of acute ated with autonomic dysfunction has been documented in litera- stroke. In patients with diabetes mellitus developing acute cere- ture. It can occur when there is a drop of more than 2% in HbA1C in brovascular stroke, glycemic control is a key variable influencing a three month period. Worsening of existing peripheral neuropathy the intensity of neurological involvement. Our present study was and retinopathy has also been observed suggesting a common designed to assess the effect of hyperglycemia on the severity and pathophysiological mechanism. However, the onset of a cranial outcome of acute cerebrovascular stroke in patients with type 2 neuropathy temporally linked to intensified glycemic control has diabetes mellitus. not been well reported. Methods: We conducted an observational cross-sectional descrip- Case Description: A 32-year-old male patient presented to the tive study in the Department of Medicine at the SMS Medical Col- emergency department with double vision, preceded by head- lege Jaipur. 55 individuals aged 20 to 65 were included in this study. ache, and increased burning in his feet. No other neurologic All patients with features of new-onset stroke with HbA1C levels symptoms were reported. Past medical history was significant more than 6.5 and established cases of diabetes mellitus were for poorly controlled, labile type 1 diabetes mellitus. His home included in the study. Semi structural data collection form was used medications included gabapentin for peripheral neuropathy, to record basic investigation reports, radiological findings. After the long-acting and short-acting meal time insulin regimen. Physical confirmation of stroke, HbA1c level was estimated. The severity of examination was unremarkable except for a neurological exam stroke was assessed using NIH Score Scale (NIHSS) on day 1, day 4, which showed pupil-sparing third cranial nerve palsy. CT angi- and day 28. The outcome was assessed on the 4th and 28th day of ography of the head and neck revealed no acute ischemia, he- hospital admission. Univariate analysis using a Chi-square test with modynamically significant stenosis, aneurysm or dissection. MRI a significance level of 5% was used to determine the association of the brain also showed no abnormality. Review of his prior between variables. Spearman's correlation was used to determine HbA1c values showed a decrease of 3.6 % ( 14% to 10.4%) over 3 any association. months. The patient was diagnosed with TIND presenting with Results: On day1, day 4, day 28 of admission, the association be- simultaneous worsening of peripheral neuropathy and new tween HbA1c level and NIHSS score was found to be statistically onset right oculomotor nerve palsy. He was discharged on significant (p¼0.001). All patients with HbA1C less than 7% had reduced doses of insulin, targeting a gradual decline in HbA1c mild/ moderate stroke, 7-9% had moderate/ severe stroke, whereas after initial stabilization.The patient was also asked to liberalize all patients with HbA1C more than 9% had severe stoke. On his diet and was given an eye patch. While his peripheral Spearman’s correlation, a strong positive correlation was found neuropathy improved, there was not much improvement in his between HbA1C levels and NIHSS score (correlation coefficient, r diplopia at a two week follow-up visit. value being 0.760). As the HbA1C value increased NIHSS score also Discussion: Our patient presented with worsening of peripheral increased significantly. Outcome evaluation revealed that mortality neuropathy and pupil sparing oculomotor palsy. Secondary causes occurred only in patients with HbA1C greater than 9 (4 patients). including CVA and aneurysm were excluded with brain imaging. Mortality in relation to HbA1C was found to be statistically signif- Diabetes related microvascular disease presenting with pupil icant (p¼0.001). sparing oculomotor palsy is commonly seen in patients older than Discussion/Conclusion: The present study revealed that in patients 50 years of age with uncontrolled diabetes and other vascular risk with diabetes mellitus the severity of stroke correlated with gly- factors like hypertension and dyslipidemia. Absence of hyperten- cemic control. Patients with higher HbA1c level had a more severe sion and hyperlipidemia, sudden onset of presentation and an neurological impairment and unfavourable functional outcome. intense control of DM as evidenced by rapid decline of A1C make Efficacious reduction of HbA1c to the target range in patients with TIND the likely cause for his presentation. The paradoxical wors- diabetes may lessen the occurrence of a severe stroke. ening of his peripheral neuropathy also supports the diagnosis of CONCLUSION: Estimation of HbA1c levels on admission might be TIND. Through this case, we highlight the importance of recog- a predictor of the severity of neurological impairment as well as nizing this entity as management differs significantly. Quality outcome in patients with type 2 Diabetes mellitus developing an improvement metrics for practitioners in various institutions often acute stroke. include HbA1c target ranges in diabetic patients. Our case high- lights the issues associated with rapid corrections of HbA1c and https://doi.org/10.1016/j.eprac.2021.04.571

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Abstract #1003193 patients with hyperglycemic chorea with normal imaging studies, as seen in our patient.

Hyperglycemic Hemichorea Hemiballismus With https://doi.org/10.1016/j.eprac.2021.04.572 Atypical Imaging

Abstract #1003259 Author Block: Aparna Baburaj - Geisinger Medical Center; Pranav Dineshkumar Patel, MD - Co author, Geisinger Medical Systematic Review and Meta-Analysis of MiniMed™ Center; Anuraj Mambazhathu Sudhakaran, MD - Co author, 670G System Therapy on Change in A1C and Time Internal Medicine, Geisinger Medical Center Spent in Target Glucose Range

Introduction: Chorea and Ballism refer to abnormal involuntary Author Block: Robert A. Vigersky, MD - Primary, Medical Affairs, movement characterized by violent involuntary limb move- Medtronic; Iram E. Mohammed, MBBS, MPH - Co-author, Clinical ments resulting from the damage to subthalamic nucleus. Such Research, Medtronic; David Bogumil, MPH - Co-author, involuntary movements are commonly caused by vascular Department of Epidemiology, University of Southern California; disease, autoimmune disorders, paraneoplastic or neurological Toni L. Cordero, PhD - Co-author, Medical Affairs, Medtronic; disorders. Hyperglycemia causing hemichorea, hemiballismus Victoria K. Cortessis, PhD - Co-author, Department of is not common. Such neurological presentation of hypergly- Epidemiology, University of Southern California cemia improves with blood glucose control and neuroleptics or benzodiazepine. We report the case of hemichorea hemi- Objective: Despite pharmacological and technological advances, a ballismus secondary to nonketotic hyperglycemia with normal majority of patients still fail to achieve national and international neuroimaging studies. consensus-recommended goals for glycated hemoglobin (A1C) and Case Description: A 61-year-old Male with hypertension pre- percentage of time spent in target glucose range (TIR). Technolog- sented to the ED with elevated blood sugars. He initially went to ical advances including hybrid closed-loop (HCL) systems, that his Primary care physician because of involuntary right arm automatically deliver basal insulin based on continuous glucose movement for two weeks. This was preceded by polyuria and monitoring (CGM) data, have demonstrated improved A1C and TIR, polydipsia. The movement of his right limb occurs every couple compared to baseline. A systematic review and meta-analysis of minutes and happens when he is awake and asleep. On exam, synthesized data from scholarly evaluations of the MiniMed™ patient was hemodynamically stable. Neurological exam revealed 670G system, the first HCL system approved for T1D in the U.S., to rhythmic involuntary high amplitude flexion at the elbow and determine its impact on A1C and TIR. slight shoulder flexion. He had decreased vibratory sensations in Methods: Embase™, PubMed™ and Web of Science™ databases bilateral lower extremities. Laboratory tests showed blood were searched (from April to September 2020) using the following glucose of 739, serum creatinine of 1.8, serum sodium of 115, terms without a time-range filter: “type 1 diabetes”, “hybrid closed negative urine ketones and hemoglobinA1c of 21.9. He under- loop” and “Medtronic”. Effect size estimates were captured from went CT head and MRI brain which were unremarkable. EEG retrospective and prospective trials investigating MiniMed™ 670G was without any epileptiform activity. He received insulin infu- Auto Mode therapy versus comparator and change in A1C and TIR, sion normalizing blood glucose. Diagnosis of hemichorea hemi- in non-pregnant individuals with T1D. Mean differences in A1C and ballismus caused by non ketotic hyperglycemia was made. Along TIR (70-180mg/dL) were summarized across studies using a with achieving optimal glycemic control, patient was started on random-effects meta-analysis, with a DerSimonian-Laird estimator low dose clonazepam. His symptoms started to improve. He was and corresponding 95% confidence intervals (95%CI), due to discharged with short term benzodiazepines with endocrinology differing distributions of demographic characteristics, which likely and neurology follow up. correspond with different effect sizes. Heterogeneity between Discussion: Hemichorea hemiballismus as a sign of hyperglyce- studies was quantified using the inconsistency index value (I2) and mia is unusual. It is found first in 1960 and most commonly tests of Q-Statistic p-values. reported among asian females. Various hypotheses have been Results: Of 136 articles identified, 12 warranted inclusion after proposed to explain the pathophysiology, including hypervis- removal of duplicate or irrelevant works. Twelve articles under- cosity, cerebral vascular insufficiency, and depletion of GABA in went meta-analysis for A1C and 11 for TIR. Ten investigated the neural pathways. Acute putaminal dysfunction secondary to MiniMed™ 670G Auto Mode therapy versus open-loop Manual hyperglycemia leading to Wallerian degeneration has been Mode therapy, one assessed the former versus multiple daily in- considered to play a role in chorea. Most patients present with jections with CGM, and another versus sensor-augmented pump acute or subacute involuntary limb movements accompanied by therapy. Auto Mode use (averaging 12-14 weeks) demonstrated a uncontrolled blood sugars and negative ketones in the urine. change in A1C of -0.5% (95%CI -0.59, -0.42) and an increase in TIR of MRI brain usually shows characteristic radiographic changes in 9.05% (95%CI 7.31, 10.79). Significant heterogeneity was observed in the contralateral striatum. CT head may show high-density both meta-analyses (A1C I2¼70%, p< 0.01; TIR I2¼92%, p< 0.01). changes but may fail to show any abnormality in the basal Discussion/Conclusion: Compared to other therapies, use of Min- ganglia. There are very few patients with negative imaging iMed™ 670G Auto Mode appeared to result in significant glycemic studies as seen in our patient. Non-Ketotic Hyperglycemic control improvement, as shown by lowered A1C and increased TIR. chorea has an overall excellent prognosis with rare exceptions. These comprehensive findings demonstrate a safe and clinically Treatment mainly involves controlling blood sugars and typical meaningful impact of a first-of-its-kind device for T1D neuroleptic drugs or benzodiazepines. To date, there are only management. very few cases with non ketotic hyperglycemic chorea with negative imaging studies. This may be an uncommon type in https://doi.org/10.1016/j.eprac.2021.04.573

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Author Block: Abstract #1003366 Helen M. Lawler, MD - primary author, Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, Maternal and Foetal Outcomes in IADPSG Vs DIPSI University of Colorado, Anschutz Medical Campus, Aurora, CO based diagnosed GDM 80014; Mary Elizabeth Patti, MD - co-author, Research Division, Joslin Diabetes Center, Boston, MA, USA. Harvard Medical School, Boston, MA, USA; Valentina Conoscenti, MD - co-author, Xeris Author Block: Shalini Jaggi, PG Diploma Diabetes(UK), Diploma Pharmaceuticals; M. Khaled Junaidi, MD - co-author, Xeris Endocrinology (UK), FRCP, FACE - Presenting author, Diabetes, Pharmaceuticals; Nicole C. Close, PhD - co-author, EmpiriStat, Inc; Lifecare Diabetes Centre Kirti Nagar New Delhi; Shubhaa Chawla, David J. Sequeira, PhD - co-author, Xeris Pharmaceuticals; MBBS - co-author, Diabetes, North Delhi Diabetes Centre, Rohini, Anh Nguyen, MD - co-author, Xeris Pharmaceuticals New Delhi; Aastha Chawla Trehan, MD - co-author, Diabetes, North Delhi Diabetes Centre, Rohini, New Delhi; Siddhant Trehan, DM Objective: A novel ready-to-use (RTU) liquid stable glucagon (XP- Resident - co-author, Cardiology, Sri Jayadeva Institute of 5387; Xeris Pharmaceuticals) was evaluated as treatment for Cardiovascular Sciences and Research, Bengaluru; Rajeev Chawla, symptomatic postprandial hypoglycemia after bariatric surgery. MD, FRCP(UK), FACE - co-author, Diabetes, North Delhi Diabetes Methods: A Phase 2 randomized, placebo-controlled, double-blind, Centre, Rohini, New Delhi two-treatment, two-period, crossover, pilot study enrolled 14 adults with post-bariatric hypoglycemia (PBH) to evaluate efficacy and Objective: GDM is any degree of dysglycemia with onset or first safety of XP-5387 to treat symptomatic postprandial hypoglycemia. recognition during pregnancy. Diabetes in Pregnancy Study Group Subjects were randomly assigned once to receive subcutaneous in- of India (DIPSI) identifies GDM as dysglycemia in any trimester jections of XP-5387 (300 mcg) or placebo during two separate warranting early recognition and management to improve provocation meal challenges in an in-clinic stage crossover design maternal & foetal outcomes. and a parallel design outpatient stage (XP-5387 or placebo; 12 Methods: This prospective, observational twin centre study fol- weeks). Subjects self-administered assigned study drug when they lowed maternal & foetal outcomes in two Groups 1. 50 patients experienced neurogenic or neuroglycopenic symptoms. Blood identified by IADPSG criteria by performing a 75 g glucose OGTT in glucose (BG) response was measured 15 minutes post-dosing. Where fasting state at 24-28 weeks and GDM diagnosed if fasting 92 mg/ hypoglycemia (BG 70 mg/dl) was present at dosing, subjects were dl or 1-hour 180 mg/dl or 2-hour 153mg/dl. 2. 50 patients advised to use oral glucose tablets in addition to study drug. identified by DIPSI criteria by performingsingle-step non-fasting 75 Results: All outcomes were summarized descriptively. Of 14 gm oral Glucose challenge at 24-28 weeks and GDM diagnosed enrolled subjects, 12 entered the outpatient stage and 10 completed with values 140 mg/dL at 2 hours. Pre GDM or dysglycemia in Ist the study. More than 200 postprandial hypoglycemic events were trimester was ruled out in both groups by Ist trimester screening. recorded across both treatment arms. Treatment group XP-5387 Results: Group 1 IADPSG based Vs Group 2 DIPSI Based GDM : subjects successfully self-administered treatment during these Mean age was 30.4yrs S.D+6.8, 31.5yrs S.D+7.2 , Mean ht 153.72cms events resulting in restoration of normal BG levels within 15 mi- S.D+3.4, 154.76cms S.D +3.6 & Weight was 70.8kgs S.D +5.4, 71.2 Kg nutes (maintenance up to 120 minutes). During episodes when BG SD+5.6 respectively. Family H/o diabetes was there in 36% ,39% BOH 70 mg/dL at drug dosing and without the use of glucose tablets, 28%, 31% respectively. FBS mean was 98.8mg% & 99.2 mg%, PPBS XP-5387 successfully restored BG levels to normal levels (BG >70 mean was 146.3mg% & 148 mg%, mean HbA1c was 6.4% & 6.5% mg/dL) within 15 minutes, at a higher frequency when compared to respectively. Insulin was used in 40% & 44% respectively while diet placebo (91% versus 73%), representing a 67% reduction in post- control was sufficient in 60% & 56% in Group1 & Group 2 dose hypoglycemia. In the placebo arm, glucose tablets were used respectively. during 17 of the 162 dosed episodes and often resulted in rebound Maternal & Foetal outcomes Birth weight in Group 1 & 2 hypoglycemia. Glucose tablet use was absent in the XP-5387 was 3.31 kgs SD+1.6,3.2 Kgs SD+1.5 respectively. 12% & 10% treatment arm. Treatment emergent adverse events were compa- had weight more than 4.5 kg respectively. Mean Head rable between treatment groups. No serious adverse events were circumference was 35.16 cms S.D + 2.4, 34.2 cms S.D + 2.3 reported and the most common related adverse events were hy- respectively. LGA 20% & 18%, prematurity 16% & 13% , hypo- perhidrosis (16.7%), nausea (16.7%) and vomiting (8.3%) which were glycaemia 44% & 41 % respectively. RDS, Hyperbilirubinemia, mild in severity and self-limited. NICU admission & IUD were similar in both groups. LSCS was Discussion/Conclusion: Without the use of glucose tablets and 11%, 10%, NVD 66%, 64%, Assisted delivery 23%, 26% respec- BG70 mg/dL, self-administered XP-5387 when compared to pla- tively. There was no statistical difference in Foetal and cebo exhibited a 67% reduction in post-dose hypoglycemia. With maternal outcomes in both the groups. XP-5387 use, glucose tablet utilization was absent. XP-5387 was Discussion/Conclusion: Single step DIPSI Criteria can be used for safe and well tolerated and may be a potential future therapy for screening and diagnosis of GDM for it’s simplicity, feasibility, treatment of PBH. economy and convenience. It has potential to be applied to the https://doi.org/10.1016/j.eprac.2021.04.575 entire obstetric population meeting the needs of the developing worldwhere 3 step IADPSG can be challenging. https://doi.org/10.1016/j.eprac.2021.04.574 Abstract #1003586

Smart Insulin Pens Uncover the Need For Long Acting Abstract #1003503 Insulin Dose Optimization in Multiple Daily Insulin Therapy A Phase 2, Interventional, Randomized, Double-Blind, Placebo-Controlled Pilot Study of Glucagon Ready-To- Use in Subjects Who Experience Hyperinsulinemic Author Block: Madison B. Smith, PhD, RN, CDCES - Presenter, Hypoglycemia After Bariatric Surgery primary author, Clinical Product Development, Medtronic

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Diabetes; Angela Gaetano, MS - Co-author, Data Science, Medtronic Florida HCA Healthcare GME, Greater Orlando, FL, USA; Diabetes; Robert Vigersky, MD - Co-author, Medical Affairs Jorge Esteban Mosquera, MD - Co author, Department of Internal Department, Medtronic Diabetes; Toni Cordero, PhD - Co-author, Medicine, University of Central Florida College of Medicine, Medical Affairs Department, Medtronic Diabetes; Janice MacLeod, Orlando, FL, USA, University of Central Florida HCA Healthcare MA, RD, CDCES, FADCES - Co-author, Professional Affairs and GME, Greater Orlando, FL, USA; Kanya Rajagopalan, MBBS - Co Clinical Education, Medtronic Diabetes author, Department of Internal Medicine, University of Central Florida College of Medicine, Orlando, FL, USA, University of Central Objective: Barriers to timely insulin titration include therapeutic Florida HCA Healthcare GME, Greater Orlando, FL, USA; inertia, lack of integrated care, the complexity of titration algo- Alejandro Ruiz Toledo, MD - Co author, Department of Internal rithms and insulin types, and concerns for appropriateness of in- Medicine, University of Central Florida College of Medicine, sulin management by a primary care physician.1 The American Orlando, FL, USA, University of Central Florida HCA Healthcare Association of Clinical Endocrinology and American Diabetes As- GME, Greater Orlando, FL, USA; Mustafa Kinaan, MD - Co author, sociation call for the titration of long-acting insulin every 3 days (or Department of Internal Medicine, University of Central Florida twice weekly). Here, we use a novel methodology to analyze bolus College of Medicine, Orlando, FL, USA, University of Central Florida insulin delivery and glucose data from InPen™ smart insulin pen HCA Healthcare GME, Greater Orlando, FL, USA users to assess the adequacy of long-acting insulin doses in both type 1 and type 2 diabetes patients on multiple daily injections Objective: (MDI) therapy. Since the emergence of the COVID-19 pandemic, the fi Methods: Fasting glucose and change in overnight glucose in scienti c community has been hard at work identifying patients individuals with 3 days of InPen™ smart insulin pen use, when who are most susceptible to poor outcomes. Diabetes has been paired with either continuous glucose monitoring (CGM) or established as a major risk factor. Our study aims to identify which blood glucose measurement (BGM) data, between November sub-population of diabetic patients are most vulnerable. Methods: 19th to December 23rd, 2020, were evaluated. Fasting glucose We performed a multicenter retrospective study of was defined as the glucose value closest to the end of a user’s 1,796 diabetic patients with 1,818 distinct hospital admissions. fi typical fasting window (their most frequent 6-hr window free The outcome of severe COVID-19 infection was de ned based on from bolus data) and prior to their first meal/insulin bolus. ICU admission, mortality, and clinical criteria indicating respi- Change in overnight glucose was calculated, for CGM users only, ratory decompensation. Logistic regression analysis was per- as the mean difference between the glucose at start of fasting formed for different variables to identify the odds of window minus end of the fasting window. Days with rapid- experiencing severe infection. We examined demographic char- acting boluses logged in the 4 hours prior to the start of the acteristics, body mass index, HbA1C, presence of diabetes com- fasting window were excluded from the change in overnight plications and metabolic comorbidities, and pre-hospitalization fi glucose analysis to mitigate measuring overnight change in medication pro le (diabetes medications, statins, antihyperten- glucose related to recent bolus. sives, and steroids). Additionally, we performed chi-square Results: The mean ±SD of 3-day fasting glucose was 176±53 mg/dL analysis examining inpatient glycemic control in patients with (range 51-401 mg/dL) in CGM users (N¼3858) and 199±72 mg/dL severe vs. non-severe infection. Results: fi (range 70-600mg/dL) in BGM users (N¼2683). Only 12.4% of CGM Our study showed statistically-signi cant increased odds ¼ users and 10.3% of BGM users achieved a 3-day mean fasting of experiencing severe infection with older age (OR 1.018), male ¼ > ¼ glucose between 70-120 mg/dL. During the 6-hr fasting glucose gender (OR 1.371), BMI 35 (OR 1.838), nephropathy ¼ ¼ window (median of 1:00AM-7:00AM), 30% of CGM users saw a rise (OR 1.659), and cardiovascular disease (OR 1.3). An increased in glucose of 30 mg/dL (an increase of 79.5±47.4 mg/dL) and 30% risk was observed in patients with pre-hospitalization exposure ¼ ¼ of CGM users saw a reduction in glucose of 30 mg/dL (a decrease to steroids (OR 1.498) and SGLT-2 inhibitors (OR 1.856); ¼ of 75.5±42.8 mg/dL). whereas the risk was decreased with ACEI (OR 0.75) and statins ¼ fi Discussion/Conclusion: Using a novel analytic methodology that (OR 0.661). Other variants were not associated with signi cant takes advantage of the automatic logging of the breakfast bolus changes in risk. Patients with severe infection, compared to fi insulin timing, we found that InPen™ users have high fasting those with non-severe infection, had signi cantly more hyper- > glucose levels and that 60% of them have substantial increases glycemia 180mg/dL (44.35% vs. 37.6%), and hypoglycemia or decreases in glucose overnight during the user’s identified (9.75% vs. 8.90%). Discussion/Conclusion: fi fasting window. These data reveal opportunities for long-acting Our study outlines a risk pro le for severe fi insulin dose optimization. Further research should explore how infection in diabetic patients. The ndings of this study can help data obtained through integrated technologies may help identify identify diabetics who are at highest risk. Older age, obesity, and ways to personalize treatment while reducing therapeutic the presence renal and cardiac disease are all risk factors that have inertia. been linked to impaired immune response to infections. Interest- ingly, pre-hospitalization use of steroids, which is now a common https://doi.org/10.1016/j.eprac.2021.04.576 treatment option for hospitalized COVID patients, could be detri- mental. SGLT-2 inhibitors prior to hospitalization could be harmful as well. Statins and ACEIs were associated with better outcomes, Abstract #1003696 which further stresses the importance of using these medications for prevention of diabetes complications. Additionally, patients Diabetes and COVID-19: Identifying Diabetes-Related with severe infection had significantly more hyperglycemia and Predictors of Severe Infection hypoglycemia during hospitalization. Future studies and clinical trials can reaffirm these findings and establish whether early intensive clinical care in these vulnerable patients can reduce poor Author Block: Samarth Virmani, MBBS - Primary author and outcomes. presenter, Department of Internal Medicine, University of Central Florida College of Medicine, Orlando, FL, USA, University of Central https://doi.org/10.1016/j.eprac.2021.04.577

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Author Block: Abstract #1003750 Hassan Heshmati - Endocrinology Metabolism Consulting, LLC Risk Factors of Peripheral Arterial Disease in Type 2 Diabetes Patients: A Systematic Review and Meta- Objective: Prediabetes and type 2 diabetes are global pandemics. In analysis the United States, the numbers of adult subjects with prediabetes and type 2 diabetes are around 90 million and 35 million, respec- tively. Prediabetes and type 2 diabetes are closely related to over- Author Block: Martha Rosana - Department of Internal Medicine weight and obesity. Adequate weight loss is a key objective in the Faculty of Medicine Universitas Indonesia; Ninik Saragih, management of these individuals. The purpose of this review is to Medical staff - Co-author, Metabolic Vascular and Aging Cluster, present the impact of glycemic status and antidiabetic treatments the Indonesian Medical Education and Research Institute, Faculty on body weight in prediabetes and type 2 diabetes. of Medicine Universitas Indonesia; Pradana Soewondo, Medical Methods: A systematic search of literature was conducted using the staff - Co-author, Division of Endocrinology, Metabolism, and search terms prediabetes, type 2 diabetes, overweight, obesity, Diabetes, Department of Internal Medicine, Dr. Cipto glycemic status, lifestyle, antidiabetic drugs, weight loss, and Mangunkusumo National Referral Hospital, Faculty of Medicine weight gain. Universitas Indonesia; Dicky L. Tahapary, Medical staff - Co-author, Results: In subjects with prediabetes, a higher fasting plasma Division of Endocrinology, Metabolism, and Diabetes, Department glucose is associated with a higher extent of weight loss following of Internal Medicine, Dr. Cipto Mangunkusumo National Referral the New Nordic diet (diet rich in fiber, whole grain, fruits, and Hospital, Faculty of Medicine Universitas Indonesia; Lusiani Rusdi, vegetables) compared to control diet (diet similar to an average Medical staff - Co-author, Division of Cardiology, Department of Western diet). Weight loss in subjects with type 2 diabetes has Internal Medicine, Dr. Cipto Mangunkusumo National Referral always been a challenge. If subjects are on hypocaloric diet alone, as Hospital, Faculty of Medicine Universitas Indonesia; Em Yunir, glycemic control improves, urinary glucose decreases or disappears Medical staff - Co-author, Division of Endocrinology, Metabolism, leading to a reduction of weight loss or a weight gain. The weight and Diabetes, Department of Internal Medicine, Dr. Cipto loss in these subjects usually reaches a plateau after 6 months. Mangunkusumo National Referral Hospital, Faculty of Medicine Antidiabetic drugs have varying effects on body weight. They can Universitas Indonesia either promote weight loss (e.g., biguanides, glucagon-like peptide- 1 agonists), be weight neutral (e.g., alpha-glucosidase inhibitors, dipeptidyl peptidase-4 inhibitors), or cause weight gain (insulin, Objective: Peripheral arterial disease (PAD) is one of the macro- sulfonylureas). When combined with lifestyle changes in a weight- vascular complications of type 2 diabetes mellitus (T2DM), which loss program, antidiabetic drugs can either potentiate or antago- cause serious rate of morbidities and mortality. To date, there have nize weight loss. The weight loss and weight gain caused by these not been any systematic and comprehensive review regarding the drugs usually occur within the first year of treatment. The extent of risk factors of incidence of PAD in T2DM populations. Our study weight change can be up to approximately 4 to 5 kg for either aims to analyze the pooled effect estimates of each risk factors of weight loss or weight gain. PAD incidence in T2DM populations. Discussion/Conclusion: Weight loss is an important objective in the Methods: This systematic review and meta-analysis was conducted treatment of most subjects with prediabetes and type 2 diabetes. using the PRISMA standard. A systematic and comprehensive Fasting plasma glucose and several antidiabetic drugs can impact literature searching was conducted in PubMed/MEDLINE, ProQuest, body weight and the efficacy of weight-loss programs. Treatment and EMBASE database, to obtain any cohort or case-control studies decision for the use of antidiabetic drugs should give priority to reporting the risk factors of PAD incidence in T2DM populations. weight-friendly strategies, especially in the presence of overweight We also conducted searching on gray literature and hand-search- or obesity. ing. We assessed risk of bias using Newcastle-Ottawa Scale https://doi.org/10.1016/j.eprac.2021.04.579 assessment tool. The pooled effect estimates of each risk factors was analyzed using RevMan version 5.4. Results: Ten studies were included in this review comprising 73834 Abstract #1003782 T2DM patients in total. All the studies had good quality based on Newcastle-Ottawa Scale. Significant association with the incidence Neuromodulation for Treatment of Painful Diabetic of PAD in T2DM was found in the group of age 70 years old (OR Neuropathy - Sustained Benefits of 10kHz Spinal Cord 3.44; 95% CI 2.11, 5.62), diabetes duration 5 years (OR 1.81; 95% CI Stimulation in a Randomized Controlled Trial 1.24, 2.64), coronary artery disease history (OR 1.55; 95% CI 1.30, 1.83), hypertension (OR 1.43; 95% CI 1.10, 1.86), and increased LDL (OR 2.51; 95% CI 1.38, 4.56). All the evidences have moderate cer- Author Block: Erika A. Petersen, MD - primary author, presenter, tainty (GRADE rating). University of Arkansas for Medical Sciences; Thomas G. Stauss, Discussion/Conclusion: Age 70 years old, diabetes duration 5 MD - co-author, Pain Physicians of Wisconsin; James A. Scowcroft, years, coronary artery disease history, hypertension dan increased MD - co-author, Pain Management Associates; Elizabeth S. Brooks, LDL are significant risk factors of PAD incidence in T2DM PhD - co-author, Nevro Corp; Judith L. White, MD - co-author, AES population. Compass Orlando; Shawn M. Sills, MD - co-author, Touchstone Interventional Pain Center; Kasra Amirdelfan, MD - co-author, IPM https://doi.org/10.1016/j.eprac.2021.04.578 Medical Group; Maged N. Guirguis, MD - co-author, Ochsner Clinic Foundation; Jijun Xu, MD, PhD - co-author, Cleveland Clinic; & Abstract #1003779 Cong Yu, MD - co-author, Swedish Pain Headache Center; Charles E. Argoff, MD - co-author, Albany Medical Center; Impact of Glycemic Status and Antidiabetic Treatments Christian E. Nasr, MD - co-author, Cleveland Clinic; Rod S. Taylor, on Body Weight in Prediabetes and Type 2 Diabetes MSc, PhD - co-author, University of Glasgow; David L. Caraway,

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MD, PhD - co-author, Nevro Corp; Nagy A. Mekhail, MD, PhD - co- underserved patients in the United States. One population of author, Cleveland Clinic complex patients commonly referred to the LAC+USC Complex Diabetes Clinic is the severe insulin resistance type 2 diabetes Objective: Globally, 422 million people are living with diabetes and group, defined by patients requiring greater than the total daily approximately 20% will develop painful diabetic neuropathy (PDN). insulin dose of 200 units. Most interventions for this group use Pharmacotherapy may not provide adequate pain relief or the side more potent insulin concentrations such as U-500 or cocktails of effects may be intolerable. Neuromodulation, specifically spinal more expensive drugs. Given that this population has a higher cord stimulation (SCS), has been investigated as a treatment. Pre- prevalence of food insecurity, interventions without addressing liminary observational data suggest high frequency (10 kHz) SCS nutrition are generally less effective. In this case series of two pa- may relieve pain and improve sensory deficits. tients, we present the results of managing two longstanding, poorly Methods: Prospective, multicenter, randomized controlled trial controlled severe insulin resistant patients with a history of poor (SENZA-PDN) with 216 subjects assigned 1:1 to either continued response to intensive interventions by primary care using care conventional medical management (CMM) or the addition of managers, PharmD, and/or Occupational Therapy. Patients were 10 kHz SCS (Nevro Corp.) to CMM. Patients with PDN symptoms referred to the LAC+USC Complex Diabetes Clinic where they were 12 months, refractory to medications, lower limb pain intensity enrolled in a Medically Tailored Meal Program for 26 weeks. At the 5 cm (0-10 cm visual analog scale [VAS]), hemoglobin A1c 10%, start of the recruitment, the emergence of COVID-19 required the and upper limb pain intensity < 3 cm were included. Outcomes program to be rapidly redesign into a telehealth model leveraging include pain, neurological function, and health-related quality of nutritionists from LA Care and Project Angel Food's Medically life. Subjects could opt to crossover to the other treatment arm at 6 Tailored Meals, funded by LA Care. months if they had insufficient pain relief (< 50%), were dissatisfied Case Description: This is a retrospective case series of two long- with treatment, and were appropriate to proceed as determined by standing Type 2 Diabetes patients managed through a 26 week their physician. telehealth program with medically tailored meals as the main Results: Randomization of 113 subjects to 10 kHz SCS+CMM and intervention during the COVID-19 pandemic: 103 to CMM resulted in well-matched groups. For subjects who continued with CMM alone, there was no change in the average Demographics Patient 1 Patient 2 pain VAS score over 6 months (Baseline: 7.0±1.6 cm, 6 months: 6.9±2.1 cm). A majority (51.6%) reported worsening of their pain AGE (yrs) 74 58 and just 5.4% were deemed responders, defined as 50% pain relief. BMI (Kg/m2) 36.1 47.48 Diabetes Duration (yrs) 18 10 In contrast, SCS+CMM subjects averaged 76.3% pain relief over 6 Complications Retinopathy, Retinopathy, months (Baseline: 7.6±1.6 cm, 6 months: 1.7±1.9 cm). Just 2.3% of nephropathy, nephropathy, subjects reported worsening pain and 85.1% were responders (p< neuropathy neuropathy 0.001 compared to CMM). Investigators observed neurological ex- Total Daily Dose Insulin Units 248 200 Baseline HBA1C 10.2% 13.10% amination improvements in 61.9% SCS+CMM subjects compared to Baseline Fructosamine 398 455 3.3% CMM subjects (p< 0.001). There were two infections requiring 26 Week HBA1C 8.10% 9.8% explant in the SCS+CMM group (2.2%). Sleep disturbance due to 26 Week Fructosamine 312 268 pain was unchanged in CMM subjects, but those in the SCS+CMM 26 Week Total Daily Dose Insulin Units 238 202 group reported an average 61.9% improvement. Average HbA1c 26 Week BMI 36.0 47.49 Change in HBA1C 2.1% 3.3% level and BMI did not change for either group. At 6-month follow- Total Daily Insulin Dose Change 4% Reduction 1 % Increase up, 81.7% (76/93) CMM subjects both met criteria and elected to Hospitalizations 0 0 crossover, whereas 0% (0/87) SCS+CMM subjects met criteria for crossover (p< 0.001). Discussion/Conclusion: SENZA-PDN is the largest RCT to date of Discussion: To our knowledge, we present the first case series of SCS management of PDN and results through 6 months demon- severe insulin resistant, type 2 diabetes being managed successfully strate substantial pain relief, improved findings on neurological through a telehealth intervention using medically tailored meals on examination, and enhanced health-related quality of life. This study a vulnerable, predominantly Medicaid population. There was a shows 10 kHz SCS is safe, effective, and should be recommended as dramatic improvement in glycemic control (-4% and -3.3%) yet an option for patients with inadequate response to conservative without any significant changes in weight nor total daily insulin care. dosage. The preliminary results in this series are encouraging and demonstrate that telehealth using medically tailored meals can https://doi.org/10.1016/j.eprac.2021.04.580 substantially improve metabolic control even in the setting of the COVID-19 pandemic, severe insulin resistance, and low socio-eco- nomic, vulnerable patients in Los Angeles County. Abstract #1003783 https://doi.org/10.1016/j.eprac.2021.04.581 COVID-19 Telehealth Model for Severe Insulin Resistant Type 2 Diabetes using Medically Tailored Meals Abstract #1003789

Author Block: Wei An (Andy) Lee, DO - Primary Author, Internal Insulin Autoimmune Syndrome Coexisting with Medicine, LAC+USC Medical Center; Anna Parra, Program Manager Multiple Myeloma but Persisting after Successful - co-author, The Wellness Center, LA Treatment of the Myeloma

Introduction: Los Angeles County + University Southern California (LAC+USC) Medical Center, the largest county medical center in Los Author Block: Mark Niven - Laniado Hospital, Netanya, Israel; Angeles, provides care to some of the most vulnerable and complex Esther Kafri, MA, RN - Co-author, Endocrine and Diabetes Unit,

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Laniado Hospital, Netanya; Shlomo Bulvik, MD - Co-author, Abstract #1003791 Department of Hematology, Laniado Hospital, Netanya Interrelation Between ACE Gene I/D Polymorphism Introduction: Insulin autoimmune syndrome (IAS) is a rare cause and Chronic Kidney Disease Severity in Uzbek Children of hypoglycemia in which an autoantibody binds large quantities of and Adolescents with Type 1 Diabetes Mellitus insulin in the circulation. The syndrome has been described in Japanese with the HLA-DR4 genotype, as a sequel of drugs such as antibiotics, and also in association with myeloma or monoclonal Author Block: Ozoda Azimova - Republican Specialized Scientific gammopathy. medical center of Endocrinology, named after acad.prof. Case Description: A51yearoldmanwasadmittedbecause Turakulov.Ya.X; Akidahon Sadikova, Non - Primary author, of extreme weakness together with obtunded consciousness. Diabetology, Republican Specialized Scientific Center of Blood glucose was 30mg/dl. During the admission he Endocrinology, named after academic prof. Turakulov,Ya.X; had further episodes of hypoglycemia documented down to Gulnara Rakhimova, Non - Co-author, Diabetology, Tashkent 24mg/dl. He also described previous admissions elsewhere Insitutut for postgraduate medical education because of loss of consciousness, but further details were not available. He also had a history of bipolar disorder Objective: To assess renal function and to study interrelation be- treated with Lithium, but no other medication. He had tween ACE gene I/D polymorphism and chronic kidney disease in never received insulin. Physical examination showed no Uzbek children and adolescents with type 1 diabetes mellitus as per abnormality. K/DOQI (2012) recommendations. Investigations showed massively elevated serum insulin levels Methods: We examined 120 children and adolescents with type 1 around 1500 mIU/ml (NR 3-25) with modestly elevated C-peptide diabetes mellitus, 53 (44.2%) boys and 67 (55.8%) girls among them 6.57 ng/ml (NR 1.1-5.0) and very high anti-insulin autoantibodies with mean age 13.8±2.7 лет (Ме 15.0; IQR 13.0-16.0). Schwartz around 85% (NR < 5.5%). equation was used to calculate the estimated GFR for all children. Imaging studies including EUS, abdominal CT and MRI, and PET- CKD severity was classified according to K/DOQI (2012) recom- CT and gallium-octreotide scans showed nothing suspicious for mendations. Isolation of genomic DNA and genotyping by ACE gene insulinoma/NET. Ambulatory CGMS showed consistent fails in I/D polymorphism was performed in the Human Functional Ge- glucose overnight and sporadically at other times particularly after nomics Laboratory, Institute of Genetics and Experimental Biology exercise. of Plants, Uzbekistan Academy of Sciences. DNA was isolated by A putative diagnosis was made of insulin autoimmune syndrome Higuchi R. and Erlich H. method (1989) with dry kit of Diatom with no obvious trigger. A trial of high dose corticosteroid did not DNAPrep 200. improve his hypoglycemia but exacerbated his psychiatric condi- Results: Analysis of НbА1с by chronic kidney disease severity tion. Rituximab resulted in a temporary remission with no response demonstrated presence of II CKD stage in 23.8% and III CKD stage in to retreatment. Plasmapheresis was likewise ineffective in pre- 8.3% of children with НbА1с 7.5%. By increase in the disease venting hypoglycemia. duration cases of progression in II and IV CKD stages were found to Immunoglobulin electrophoresis revealed a monoclonal band become more frequent. Among the examined patients with type 1 IgG kappa, with elevated serum free kappa light chains but diabetes mellitus no cases of V CKD stage (< 15 ml/min/1.73m2) normal kappa/lambda ratio. On bone marrow aspirate and bi- were registered. According to K/DOQI (2012) in most children and opsy myeloma cells constituted 50% of nucleated cells. Cell adolescents (75.0% OR 9.0; 95%CI 5.02-16.1; р< 00001) with type I characterization tests confirmed myeloma There were no other diabetes mellitus I and II CKD stages were registered. GFR can be manifestations of myeloma such as hypercalcemia or skeletal significantly declined even on the stage of normoalbuminuria, lesions. when no clinical signs of diabetic nephropathy were present. Thus, Treatment has been complicated by variable adherence to GFR value of 80.6±7.5 ml/min/1.73m2 corresponding to II CKD stage therapy depending on his psychiatric state. In addition cortico- was found in 61.9% of normoalbuminuric Uzbek children and ad- steroids severely exacerbate his bipolar condition.. After trials of olescents with type I diabetes mellitus. Analysis of ACE gene dis- several therapies he is currently treated with Carfilziomib with tribution demonstrated that 49 (40.8%) patients were the carriers of good results: plasma protein electrophoresis, immunoglobulins II genotype; I/D and DD genotypes occurred in 28 (23.4%) and 43 and serum free light chains are normal. Whole body PET-CT (35.8%) of the patients, respectively. Among the patients, homo- showed no lesions. Insulin autoantibodies have only fallen from zygous carriers of ACE gene II (40.8%) and DD (35.8%) genotypes around 85% to 51% (NR < 5.5%) and fasting insulin from around prevailed. 1500 mIU/ml to 170 (NR 3-25). C-peptide is normal at 4.71 ng/ml Discussion/Conclusion: New classification as per K/DOQI (2012) (4.71). However he continues to have hypoglycemic episodes allows earlier detecting renal function decline in children and ad- despite remission of the myeloma. olescents with type I diabetes mellitus. GFR value of 80.6±7.5 ml/ Discussion: We present a case of IAS presenting together with min/1.73m2 corresponding to II CKD stage was found in 61.9% of multiple myeloma, with persistent hypoglycemia despite normoalbuminuric Uzbek children and adolescents with type I apparent remission of the myeloma. Although it is most likely diabetes mellitus; in 16.7% GFR value was 45.1±9.5 ml/min/1.73m2, that the myeloma is responsible, two unrelated conditions corresponding to III CKD stage. In 28.6% and 75.0% of micro- cannot be ruled out. It remains to characterize the albuminuric children and adolescents II and III CKD stages, monoclonal immunoglobulin and define its insulin binding respectively, were registered.GFR decline could be seen even in the properties. The patient continues to have hypoglycemic disease duration less than 5 years (n¼38, 31.7%). In 31.6% (n¼12) episodes and relies on CGMS to alert him to consume GFR decline corresponded to the one typical of II, III and IV CKD carbohydrate. stages. Significant correlation of DD genotype with CKD severity https://doi.org/10.1016/j.eprac.2021.04.582 was found in analysis of interrelation between ACE gene genotype

S53 Diabetes/Prediabetes/Hypoglycemia Endocrine Practice 27 (2021) S24eS71 distributions in Uzbek children and adolescents with type I dia- participants attributed insulin resistance as an important reason for betes mellitus to confirm effect of genetic factors in CKD progres- autonomic dysfunction in patients with T2DM. The DAPA-CKD and sion. ACE gene I/D polymorphism is a molecular-genetic marker of DAPA-HF trials appears to have a potential scientific impact in the CKD onset and progression in this population. real-world utilisation of Dapagliflozin in patients with DKD and HFrEF. https://doi.org/10.1016/j.eprac.2021.04.583 Discussion/Conclusion: The results of this study suggest that irre- spective of presence of diabetes, dapagliflozin has a potential to optimise the management of patients. Dapagliflozin, beyond the Abstract #1003808 ability to increase glycosuria, with relatively higher level of evi- Treatment Recommendations for Dapagliflozin across dence, across the CRV-M continuum, appears to be a promising a Cardio-Renal and Viscero Metabolic (CRV-M) agent. Continuum: An Expert Consensus Delphi Study https://doi.org/10.1016/j.eprac.2021.04.584

Author Block: Ashok Das, DM - Presenter, Pondicherry Institute of Abstract #1003872 Medical Sciences, Puducherry, India; Abhay K. Sahoo, DM - Co Author, SUM Hospital, Bhubaneswar, India; Navneet Agrawal, MD - Maturity Onset Diabetes of the Young Misdiagnosed as Co Author, Diabetes Obesity and Thyroid Center, Gwalior, India; Type 2 Diabetes Mellitus Manisha Sahay, DM - Co Author, Osmania General Hospital, Hyderabad, India; Rajiv Awasthi, MD - Co Author, Prarthana Clinic & Diabetes Care Centre, Lucknow, India; Rakesh Sahay, DM - Co Author Block: Deekchha Uprety, MD - Primary author, Geisinger Author, Osmania General Hospital, Hyderabad, India; Medical Center; Jodie A. Reider, MD - Co-author, Endocrinology, Tiven Marwah, MD - Co Author, le Bonheur Diabetes Thyroid And Geisinger Medical Center Endocrine Centre, Ahmedabad, India; Mangesh Tiwaskar, MD - Co Author, Shilpa Medical Research Centre, Mumbai, India; Introduction: Maturity onset diabetes of the young (MODY) is an Banshi Saboo, MD - Co Author, Dia Care - Diabetes Hormone Clinic, uncommon cause of diabetes mellitus (DM) that is frequently Ahmedabad, India; Prakash Hazra, DM - Co Author, AMRI Hospital overlooked. Timely and accurate diagnosis is essential to ensure - Dhakuria, Kolkata, India; Kaushik Pandit, DM - Co Author, Fortis proper treatment, recognize syndromic features, and identify at- Medical Centre, Kolkata, India; Nitin Kapoor, DM - Co Author, CMC risk family members. We present a case of a 60 year old man Vellore; Prafulla Kerkar, DM - Co Author, King Edward Memorial diagnosed with MODY after being misdiagnosed with Type 2 (T2) Hospital, Mumbai, India; Prashant Bhandarkar, DM - Co Author, DM. Gastroenterology And Endoscopy Centre, Nagpur, India; Case Description: A 60 year old man with history of DM compli- Sanjay Kalra, DM - Co Author, Bharti Research Institute of Diabetes cated by retinopathy and coronary artery disease presented to and Endocrinology (BRIDE), Karnal, India; Shalini Jaggi - Lifecare establish care. He reported being diagnosed with T2DM at age 26 Diabetes Centre through health screening. His weight was normal, and he had no features suggestive of insulin resistance, such as acanthosis nig- Objective: Dapagliflozin is sub-optimally utilised in the real world. ricans, hypertension, low HDL, high triglycerides, or abdominal There is a lack of a comprehensive collaborative guidance for a obesity. Treatment included repaglinide and metformin, with most practical approach to manage patients with cardiometabolic, HbA1c < 7.0% and no history of DKA. His family history included renometabolic and viscerometabolic disorders. Patients across the non-insulin dependent DM diagnosed at a young age in his mother CRV-M continuum includes patients with varied clinical profiles. (age 14), daughter (age 25), and son (age 22). Fasting laboratory Methods: Two round Delphi study was conducted using a virtual testing revealed glucose 110mg/dl, normal C- peptide 1.1ng/ml, and online-digital connect approach with 35 clinicians with cumulative negative GAD65. Genetic testing was recommended and positive clinical experience of 1050 man years of experience across different for mutation in Hepatocyte Nuclear Factor 1-Alpha (HNF1A) gene, specialties. This was preceded by contemporary evidence-based consistent with diagnosis of HNF1A-MODY (formerly MODY 3). discussion on therapeutic approaches, through multidisciplinary Repaglinide and metformin were discontinued. He was treated modules for six hours covering cardiometabolic, renometabolic and with glipizide, resulting in good glycemic control. Family members viscerometabolic disorders, with focus on dapagliflozin. A were encouraged to consider genetic testing. consensus was reached on the clinical aspects that were endorsed Discussion: MODY is a heterogeneous monogenic, autosomal by 50% or more of the experts. dominant group of disorders that causes non-autoimmune DM and Results: Of the total 33 questions, seven were unanimously (100%) presents in adolescence or young adulthood. Prevalence is esti- rated with the same response and 12 received the same response mated to be relatively high, though diagnosis is frequently missed. by > 50% of the participants. The mean man years of experience of MODY should be considered in individuals with atypical features of the respondents with unanimous response was 175.7 years DM, such as young age at diagnosis, negative antibodies, and (±43.92, minimum 120, maximum 240, 95% CI 135.1 to 216.3) multiple family members with DM not suggestive of type 1 or significantly higher as compared to respondents > 50% similar T2DM. If history is suggestive and antibodies are negative, genetic response 122.5 years (±10.74, minimum 60, maximum 180, 95% CI testing for MODY should be performed. HNF1A-MODY is the most 98.86 to 146.1) (p¼0.0118). The index weighted impact score based common form, occurring in 30 to 65% of cases. HNF1A mutation on the man years of experience was higher for the unanimous re- reduces insulin secretion and lowers renal threshold for glucose sponses group (1.43). There was a unanimous consensus, with ab- resulting in glycosuria. Patients are at risk for microvascular and solute agreement for the cardiometabolic based chronic disease macrovascular complications. Many patients are treated success- (CMBCD) approach, SGLT2 inhibitors as emerging approach to fully with sulfonylurea monotherapy, though progressive beta cell address the residual risk, and reduction of single-nephron dysfunction may result in need for additional therapy. Meglitinides, glomerular filtration rate as a mechanism for renoprotection. 88% GLP-1 RA, DPP-4 inhibitors, and insulin are considered reasonable

S54 Diabetes/Prediabetes/Hypoglycemia Endocrine Practice 27 (2021) S24eS71 second line options, though SGLT2 inhibitors should be avoided. don't have a proper place or a designated room for these said Distinguishing MODY from other forms of diabetes is essential to procedures and we need to educate School authorities and spread ensure proper treatment, recognize risk of complications and co- awareness to make the lives of these children slightly more morbid conditions, and counsel family members. comfortable. https://doi.org/10.1016/j.eprac.2021.04.585 https://doi.org/10.1016/j.eprac.2021.04.586

Abstract #1003892 Abstract #1003912

InsulinTherapy at Their School in Rural Area of Southern Erythema Annulare Centrifugum- A Rare Cutaneous Rajasthan : How do Type-1 Diabetic Children Manage Complication of Insulin Therapy

Author Block: Rahul Ramchandani, MBBS - Co author, Author Block: Swayamsidha Mangaraj - IMS and SUM Medical Ramchandani diabetes care and research centre; Arnav Saroya, College and Hospital, Bhubaneswar; Liza Mohapatra, MD - Co MBBS - Co author, MMIMSR, Ambala Punjab India; Dinesh Sharma, author, Dermatology, IMS and SUM Medical College MD, FICP - Co author, Haribux Kanwatia Govt Hospital , Jaipur; Divyansh Mathur, MBBS - Co author, NKP Salve Institute of Medical Introduction: To report a rare dermatological complication(Er- Sciences Nagpur Maharashtra India; Abhilasha Mangal, MSc, ythema annulare centrifugum) associated with insulin use. Dietician - Co author, Ramchandani diabetes care and research Case Description: A 52 year old male known case of T2DM for eight centre; Akhil Agrawal, MBBS, DNB, FAIPS - Co author, Manash years, presented with peripherally spreading erythematous hospital, Kota; Girish Mathur, MD, FACP, FCCPE, FRCPG, FRCPL - Co annular eruptions over anterior aspect of bilateral thighs for two author, S. N. Pareek Memorial Hospital & Research Center 3, Basant days. The patient stated that the lesion started after initiation of Vihar, Kota; K.K. Pareek, MD, FACP, FCCPE, FRCPG, FRCPL - Co subcutaneous premix human insulin injection twice daily for author, S. N. Pareek Memorial Hospital & Research Center 3, Basant management of hyperglycemia. There was no history of insect or Vihar, Kota; J.K. Sharma, MD, FACP, FCCPE, FRCPG, FRCPL - Co tick bite. There was no new drug taken apart from his usual anti author, Central Delhi Diabetes Centre, New Delhi; diabetic medications(tablet glimiperide 4mg/day and metformin Sarojini Ramchandani, BDS, Dental Surgeon - Co author, 1000mg/day) in preceding month. He had a body mass index (BMI) Ramchandani diabetes care and research centre; Ranjana Rohira, of 23.4 kg/m2. His vitals were stable and systemic examination was MSc, Dietician - Co author, Ramchandani diabetes care and normal. On local examination, two well defined annular erythem- research centre; G.D. Ramchandani, MD, FACP, FCCPE, FRCPG, FACE atous plaques of size around 10cm x 5cm with a rim of trailing scale - Presenter and Author, Ramchandani diabetes care and research over the margin were seen over anterior aspect of bilateral thighs. centre Fundus examination was normal. Complete blood count was normal except for the presence of mild hypochromic microcytic Objective: Type 1 diabetic children need to manage multiple things anemia. Evaluation of glycemic status revealed fasting plasma such as insulin injection and self-monitoring of blood gluco- glucose level of 165mg/dl and post prandial plasma glucose level of se(SMBG) levels even at schools. Ideally they should be able to 242mg/dl. His glycosylated hemoglobin (HbA1c) level was perform these procedures in the classrooms without any distur- 8.8%(normal < 6.5%). Hepatic function tests, renal function tests and bance. However because of lack of awareness and support from serum electrolytes were within normal limits. Serum markers for school authorities most children are forced to do these in bath- human immunodeficiency virus, hepatitis B viral antigen and rooms. We have had multiple meetings with staff from various hepatitis virus were negative. Thyroid function tests and autoim- schools in rural area over the course of the last few years in an mune profile (antinuclear antibody and extractable nuclear antigen attempt to spread awareness and make the lives of these children antibodies) revealed no abnormality. Histopathological examina- easier. Objectiveis to see how the type 1 diabetic patients can tion of the lesion revealed uninvolved epidermis along with clas- perform their disease management (Insulin injection and self- sical coat sleeve appearance of perivascular lymphocytic infiltration monitoring of blood glucose (SMBG) ) at schools in rural areas of and dermal edema in upper dermis. A potassium hydroxide mount Southern Rajasthan of India. from affected skin showed no evidence of fungal infection. Based on Methods: A questionnaire survey was performed with 50 type 1 above findings a diagnosis of Erythema annulare centrifugum (EAC) diabetic patients (children belonging to primary and secondary due to insulin injection was made. The lesions resolved completely section) from the Ramchandani diabetes care and research centre, in two weeks after stoppage of insulin. As insulin was stopped, the Kota Rajasthan, India. patient was put on sitagliptin 100 mg and voglibose 0.3 mg twice Results: The data were obtained from 50 type 1 diabetic patients. daily in addition to his previous antidiabetic medication. All children treated with multiple daily Insulin injections (MDI). Discussion: Insulin administration is associated with many cuta- 60% of children do not prefer SMBG in school, 4% children did SMBG neous adverse reactions. Lipohypertrophy, lipoatrophy, edema and in their classroom. There were 10% children who performed in allergic reactions are commonly reported. Other relatively rare health care room or the staff room. 26% children had to perform dermatological complications include acanthosis nigricans, acan- SMBG in toilets. Similarly, 10% of children do not inject insulin due thosis nigricans co-localizing with amyloidosis and post inflam- to not having proper place, 5% children took insulin in classroom, matory hyperpigmentation. Erythema annulare centrifugum(EAC) 30% children had gone to their home to inject insulin, who had their is an uncommon inflammatory dermatologic condition whose house nearby school while 20% children took insulin in health room exact etiology is unknown. EAC is thought to represent a hyper- or staff room and 25% children had to inject insulin in toilets. sensitivity reaction to a wide variety of underlying conditions Discussion/Conclusion: Healthy life with diabetes requires some which include drugs, infections, malignancy, autoimmune diseases procedures that need to be done every day to manage and measure and endocrine diseases. To the best of our knowledge, no such as- blood sugar levels. These type 1 diabetic children going to school sociation of insulin injection and EAC has been earlier reported in

S55 Diabetes/Prediabetes/Hypoglycemia Endocrine Practice 27 (2021) S24eS71 literature. Knowledge about this rare entity among physicians will Abstract #1003947 be helpful for early identification and appropriate management. https://doi.org/10.1016/j.eprac.2021.04.587 Retinopathy Status in Young Type 1 Diabetes Patients in Hadoti Region of Rajasthan in India

Abstract #1003943 Author Block: Arnav Saroya, MBBS - Co author, MMIMSR, Ambala Dapagliflozin is Superior to Metformin as Punjab India; Sarojini D. Ramchandani, BDS, Dental Surgeon - Co Monotherapy in Improving HbA1c and BMI in Drug author, Ramchandani diabetes care and research centre; Naive Type 2 Diabetic Adults Abhilasha Mangal, MSc, Dietician - Co author, Ramchandani diabetes care and research centre; Divyansh Mathur, MBBS - Co author, NKP Salve Institute of Medical Sciences Nagpur Author Block: Hariballav Mahapatra - Sevayan Diabetes Centre; Maharashtra India; Akhil Agrawal, MBBS, DNB, FAIPS - Co author, Laxminarayan Mahapatra, MBBS, FCGP (I) - co-author, Sevayan Manash hospital, Kota; Rahul Ramchandani, MBBS - Co author, Diabetes Centre; Monalisa Khuntia, MSW, NDEP - co-author, Ramchandani diabetes care and research centre; Girish Mathur, Sevayan Diabetes Centre; Abhay Kumar Sahoo, MD, DM MD, FACP, FCCPE, FRCPG, FRCPL - Co author, S. N. Pareek Memorial (Endocrinology) - co-author, IMS & SUM Hospital, SOA University Hospital & Research Center 3, Basant Vihar, Kota; Dinesh Sharma, MD, FICP - Co author, Haribux Kanwatia Govt Hospital , Jaipur; Objective: Type 2 diabetes is a myocardial equivalent and cardio- K.K. Pareek, MD, FACP, FCCPE, FRCPG, FRCPL - Co author, S. N. vascular disease is the major cause of mortality among people with Pareek Memorial Hospital & Research Center 3, Basant Vihar, Kota; diabetes. Drugs that are capable of reducing the adverse cardiac Ranjana Rohira, MSc, Dietician - Co author, Ramchandani diabetes events in addition to improving glycemia can lower morbidity and care and research centre; J.K. Sharma, MD, FACP, FCCPE, FRCPG, mortality in diabetes. Metformin and SGLT2 inhibitors are two FRCPL - Co author, Central Delhi Diabetes Centre, New Delhi; diabetic medicines with proven cardic benefits. We studied the G.D. Ramchandani, MD, FACP, FCCPE, FRCPG, FACE - Co author, glucose lowering potential of dapagliflozin and compared that with Ramchandani diabetes care and research centre metformin in subjects who never received an antidiabetic medi- cation. We also looked into the adverse reactions of the individual Objective: In association with DOST (Diabetes Organization Sup- agents. porting Type1 diabetic children) society, A study was done at Methods: This was a prospective, single centre, open label, active Ramchandani Diabetic care and research centre Kota, Rajasthan, in comparator study. It involved drug naïve type 2 diabetic adults who which a 50 type 1 diabetic patients were taken, who had IDDM were on life style intervention and had an HbA1c more than 8%. The since above five years. Long time diabetes and elevated sugar level individuals were given either dapagliflozin 10mg once daily with can affect retina and may develop retinopathy. breakfast or sustained release metformin 1gm once daily with Methods: At Ramchandani diabetic care and research centre, Kota breakfast. They were followed up after 12 weeks’ of treatment with Rajasthan, India, the following parameters insulin regimen, height, comparison of HbA1c and BMI at baseline and at study completion. weight, blood pressure, pubertal stage, the prevalence of severe Adverse drug reactions were recorded meticulously keeping spe- hypoglycaemia and ketoacidosis, other diseases, other medicine cific focus on hypoglycemia, gastrointestinal adverse effects and and smoking etc are measured and registered at thir every visit the genital infections. patients are screened for retinopathy and elevated vibrations Results: Out of 370 participants who completed the study period, perception threshold. Fundus examination was done by non- 162 subjects were randomized into dapagliflozin arm and there mydriatic fundus photography (NMFP) of posterior segment were 208 participants in the comparator metformin arm. After 12 ophthalmic images, obtained by an indigenous equipment (3 weeks of treatment, reductions in HbA1c with dapagliflozin and nethra-FORUS innovation) and vibration perception threshold test metformin were 2.3±1.7% (from 9.3±2.2% to 8.24±1.6%, p< 0.01) done by biothesiometer (Diabetes care India). and 1.4±1.3% (from 9.6±1.3% to 9.0±1.2%, p< 0.04) respectively. Results: Among 50 type 1 patients, 86% (43) patients were normal Moreover, the intergroup change in HbA1c was significantly with no changes in fundus examination, while 8% (4) patients higher with dapagliflozin (p< 0.05). The mean weight loss in diagnosed with mild non- proliferative retinopathy (NPDR), 2% (1) dapagliflozin arm was also statistically higher (69.6± 2.1kg to patients are diagnosed with severe proliferative retinopathy, 2% (1) 64.5±10.1kg) when compared to metfromin group (68.4±15.0kg patients are diagnosed with cataract and 2% (1) patients are diag- to 66.5±5.4kg), though both of the arms had significant weight nosed with dryness in cornea. Among 50 diabetic patients only 4% loss compared to their baseline values. BMI was reduced signifi- (2) patients shows neuropathy, in which one patient showed cantly with both the agents, but improvement in BMI was more moderate neuropathy, while one girl patient showed severe neu- significant with dapagliflozin when compared to metformin (p< ropathy with foot ulcer in both heels. Because of foot ulcer she had 0.02). Gastrointestinal adverse effects were statistically more to amputate her right feet below knee. common with metformin (p< 0.05) and genital infections were Discussion/Conclusion: Presently there is a low prevalence of dia- numerically higher in the dapagliflozin arm (p >0.05). Hypogly- betic retinopathy in young patients with type 1 diabetes at our cemic reactions were similar in incidences with dapagliflozin and centre. But there is a great need for continuous screening for reti- metformin. nopathy every six months. Other eye problem and normal type 1 Discussion/Conclusion: Dapagliflozin as monotherapy, is more diabetes patients should always go for fundus examination once in efficacious than metformin in drug naïve type 2 diabetes in a year. Government should develop common national guidelines lowering HbA1c and is associated with an additional advantage of and help for retinopathy and neuropathy screening of children and weight loss. adolescents with type 1 diabetes. https://doi.org/10.1016/j.eprac.2021.04.588 https://doi.org/10.1016/j.eprac.2021.04.589

S56 Diabetes/Prediabetes/Hypoglycemia Endocrine Practice 27 (2021) S24eS71

Abstract #1003971 life, increased cost of care, poor treatment adherence, poor gly- caemia control and increased emergency room visits. The present Efficacy and Safety of Empagliflozin and Linagliptin study was planned to assess the psychiatric comorbidity in type 2 Combination in Non-hospitalized COVID-19 Positive diabetic patients at tertiary care medical teaching hospital in Bihar Patients with T2DM in Real World Setting: A Single a state of India. Center Retrospective Study Methods: A cross-sectional study was conducted after enrolling the eligible diabetic patients attending outpatient department services of medicine department, Nalanda Medical College and Hospital, Author Block: Supratik Bhattacharya, MBBS, MD, MRCP (UK), FACP Patna, Bihar. The Brief Illness Perception Questionnaire was used to (USA), FRCP Edin., MS (Endocrinology & Diabetes), London - assess the cognitive and emotional aspects of illness, Hamilton Primary author, Endocrinology, Consultant, Department of Depression Rating Scale for assessment of depression, Hamilton Endocrinology, AMRI Hospital Anxiety Rating Scale for assessing severity of anxiety and Mini- International Neuropsychiatric Interview 6.0 for screening all major Objective: The purpose of this study was to evaluate the clinical Axis I disorders. effectiveness and safety of empagliflozin and linagliptin combina- Results: Out of 320 patients of type 2 diabetes mellitus screened, tion (Empa/Lina) in non-hospitalized COVID-19 positive patients 202 eligible patients were enrolled. The age of the patients ranged with pre-existing type 2 diabetes in real world clinical setting. from 24 years to 60 years with mean age of 50.63 ± 09.37 years. Out Methods: A single center, retrospective study was conducted after of the 202 patients, 118 (58.4%) patients had psychiatric comor- reviewing the electronic medical records between April 14 and bidity. Depression was the most common psychiatric comorbid August 21, 2020. Subjects with type 2 diabetic patients who were illness present in (41.9%) patients. Depression was slightly higher in on Empa/Lina (25/5mg) with background glucose lowering agents female patients and persons aged >50 years. Greater prevalence of and diagnosed with COVID-19 but non-hospitalized due to mild or depressive episodes was there in people with longer duration of asymptomatic nature of disease were included. Primary endpoints diabetes. In the current study, psychiatric comorbidity especially were change in glycemic parameters like fasting plasma glucose depression was higher in patients having uncontrolled DM (HbA1c (FPG) and postprandial glucose level (PPG) over follow-up of 4 > 9) and also who were on insulin along with oral hypoglycemic weeks. Appropriate statistical test was applied. medications. The crude prevalence of the psychiatric comorbidity Results: A total 133 laboratory-confirmed COVID-19 asymptomatic in T2DM patients was found to be around 58.4%. Out of these, 9.4% T2DM patients (Median age , male (%), mean (SD) body weight, BMI patients were diagnosed as cases of dysthymia. Majority of the and diabetes duration were 48.90±12.34 years, 61%, 70.82 patients were suffering from mild depression. Second most com- ±10.97kg, 26.42±7.15 kg/m2, and 7.35 ±5.69 years respectively) mon psychiatric comorbid illness found was generalized anxiety who are on Empa/ Lina included in the study. At baseline, HbA1c disorder which was present in (6.8%). Most of the patients had mild level was 7.42±1.86 gm%, FPG 133.01±56.15 mg/dl and PPG level degree of anxiety according to the Hamilton Anxiety scale. Panic 189.41±93.05 mg/dl. About 27% of subjects were associated with disorder was present in almost 12 patients (6.0%). Social phobia was cardiovascular disease. All subjects were asymptomatic and well present in (2.6%) and agoraphobia was seen in two patients (0.9%). controlled with Empa/ Lina (25/5 mg) with background therapy Discussion/Conclusion: There were a significant percentage of such as Metformin (95%), Sulfonylureas (48%), Pioglitazone (21%), diabetic patients having psychiatric illnesses. Prevalence of the and Insulin therapy (17%). Mean CRP, D-dimer and IL-6 level at the psychiatric comorbidity in T2DM patients was found to be 58.4% diagnosis were 9.8 mg/L, 0.4 mg/L, 11.5 pg/ml respectively. At 4- and the most common comorbid psychiatric illness was depression week follow-up, glycemic control was well maintained with mean followed by generalized anxiety disorder. Depression was slightly FPG (SD) 128.42 ±45.32, PPG level 168.46±78.25 mg/dl and HbA1c higher in female patients and person aged >50 years. Greater 7.32±1.76 with minimal hypoglycemic events and no major change prevalence of depressive episodes was there in people with longer required in treatment approach. Other laboratory parameters were duration of diabetes and uncontrolled diabetes. Their attitude to- stable over four weeks like mean CRP, D-dimer and IL-6 level were wards these comorbidities may be changed by psychiatric coun- 1.3 mg/L, 0.33 mg/L, 1.6 pg/ml, respectively. There were no major selling at regular intervals. adverse event and treatment was well tolerated. https://doi.org/10.1016/j.eprac.2021.04.591 Discussion/Conclusion: Empa/Lina combination (25/5 mg) as add- on therapy can be continued as an effective approach in mild or asymptomatic COVID-19 patients with T2DM and was well Abstract #1004000 tolerated. Hyperosmolar Hyperglycemia Syndrome (HHS): A https://doi.org/10.1016/j.eprac.2021.04.590 complication of Diabetes Mellitus

Abstract #1003997 Author Block: Anum Khan - Windsor University School of Prevalence of Psychiatric Comorbidity among Patients Medicine; Syed Wajih Rizvi, MD - Co-author, Endocrinology, of Type 2 Diabetes Mellitus in Bihar a state of India R-Endocrinology; Muntazir Ali Sayed, MBBS - Co-author, Internal Medicine, R-Endocrinology; Samir Beso, MD - Co-author, Emergency Medicine, Windsor Unversity School of Medicine, St. Author Block: Ajay Sinha - Nalanda Medical College & Hospital, Kitts & Nevis; Shanaz Ahmad, MD - Co-author, Family Medicine, Patna University of Medicine and Health Sciences, St. Kitts & Nevis; Cowthar Shurie, MD - Co-author, Family Medicine, Windsor Objective: Psychiatric comorbidity with diabetes mellitus is com- Unversity School of Medicine, St. Kitts & Nevis; Sadiq Ali Sayed, mon. Comorbidity of diabetes and psychiatric disorders can present MBBS - Co-Author, Internal Medicine, National Pirogov Memorial in different patterns, which are associated with impaired quality of Medical University, Vinnytsya, Ukraine

S57 Diabetes/Prediabetes/Hypoglycemia Endocrine Practice 27 (2021) S24eS71

Introduction: The HHS is a syndrome characterized by severe hy- Sterlingkare The Diabetes Clinic, Mumbai, India; Shefali Karkhanis, perglycemia, hyperosmolality, and dehydration in the absence of MD - Co Author, Karkhanis Hospital, Mumbai, India; Amit Rajput, ketoacidosis. Symptoms include but not limited to confusion, hal- MD - Co Author, Diabetes Clinic - Sheetal Hospital, Jalgaon, India; lucinations, drowsiness or passing out, dry mouth, frequent uri- Bensley Gonsalves, MD - Co Author, Bliss Diabetes Center, Mumbai, nation, weakness, blurred vision, and fever over 100.4F. Our India objective is to report a case with uncontrolled hyperglycemic epi- sodes [blood sugar level (BSL) > 500 mg/dL] resulting in frequent Objective: Elderly age is documented as the highest risk factor for hospitalization and increased risk of HSS. the requirement of intensive care in COVID-19 patients. Diabetes Case Description: A 34-year-old African American female with and obesity are the risk enhancers in COVID-19. However, there is PMHx of Diabetes Mellitus Type II and Familial Hypercholester- limited evidence for the modifiable risk factors like body weight as olemia was referred to our Endocrinology outpatient clinic for a predictor for the need for Intensive Care Unit (ICU) care in T2DM multiple episodes of elevated blood sugar above 500 mg/dL. Patient patients. We evaluated the association of body weight as a pre- was recently hospitalized due to a fasting BSL of 598 mg/dL. During dictor of ICU admissions. hospitalization, she received IV fluids and insulin; an EKG was or- Methods: We evaluated 187 patients T2DM patients (111 males, 76 dered which was inconclusive. Upon discharge, her BSL was 280 females), recovered from COVID-19, on follow up for diabetes care, mg/dL. Post-hospitalization, her BSL remained elevated despite from eight diabetes clinics who had association of the metabolic compliance to medication and diet. During our encounter, the pa- risk factors with the need for intensive care. Descriptive statistics tient endorsed headache, dizziness, blurry vision, deep rapid and Fisher's exact test were performed. breathing, and dry mouth. She denied fruity breath and abdominal Results: There were 100 known hypertensives and 140 patients pain during hyperglycemic episodes. On referral, we proceeded recovered without intensive care. The mean age (years), BMI (kg/ with blood work which revealed an HbA1c of 14.7%. Her current m2), HbA1c (%), was 56 (±14, minimum 11, maximum 94, range 83, medication is Janumet 50 mg-1000mg tablet (sig. one tablet PO 95% CI 55 to 58), 27 (±4.7, minimum 17, maximum 44, range 83, 95% QD). In lieu of her multiple hyperglycemic episodes and symptoms CI 27 to 28), 8.1 (±1.6, minimum 4.8, maximum 15, range 10, 95% CI we increased her Janumet 50mg-1000mg to PO x BID (from PO x 7.9 to 8.4), respectively. 50 patients (26.7%) at follow up, for dia- OD). Additionally, we prescribed Repaglinide 2mg (PO x TID with betes consultation, post COVID-19 had good glycemic control, with meals) and Jardiance 25mg (PO x OD in the afternoon), and coun- HbA1c of less than 7%. 47/187 (25.1%) of the T2DM needed ICU care. seled on sugar charting. With Janumet and Jardiance not covered by 79 (42.2%) patients were age 60. Higher proportion with age 60, her insurance, patient was instead ordered to take Alogliptin- 30.3% (n¼24) required ICU as compared to 21.2% (n¼23) out of 108 Metformin 12.5-1000mg (PO x BID) and Steglatro 15mg (PO x OD) patients with age < 60, (relative risk ¼ 1.42, p¼0.17 NS). 125 (66.8%) which she was compliant on. Her blood sugar has shown patients were either overweight or obese (BMI 25 kg/m2). Higher improvement since starting medication but still needs better dia- proportion with BMI 25, 27.2% (n¼34) required ICU as compared betic control. Due to additional complaints of lethargy, heart pal- to 20.9% (n¼13) out of 62 patients with BMI < 25 kg/m2 (relative pitations, and decreased appetite, we further prescribed risk ¼ 1.29, p¼0.37 NS). Th most frequent associated morbidities in Pioglitazone 30mg (PO x OD in the afternoon) and Glimepiride 2mg T2DM were, overweight-obesity (n¼125), followed by hyperten- (PO X BID). Patient has been tolerating her medications well and sion (n¼100) and Chronic Kidney Disease (CKD) (n¼12). has shown significant improvement. We will continue to monitor Discussion/Conclusion: ICU admission risk was elevated for both her regularly on subsequent encounters to decrease risk of HSS. elderly age and overweight - obese patients in T2DM patients diag- Discussion: HSS is an acute hyperglycemic emergency in patients nosed with COVID-19. Our findings reinforce risk imposed by obesity- with DM. The diagnostic criteria for HHS include a plasma glucose related metabolic derangements leading to systemic metabolic level >600 mg/dL and increased effective plasma osmolality >320 inflammation (metaflammation). We postulate the need to manage mOsm/kg in the absence of ketoacidosis. HSS most often affects in- the burden of obesity to reduce the severity of COVID-19. Reduction of dividuals with DMT2 who are elderly but a number of cases have been body weight would help to mitigate the need of ICU care and free the identified in African American, Native Americans, and Hispanics. HSS limited healthcare resources that are already constrained due to is associated with a mortality rate between 10-20% and significantly COVID-19 and has the potential to improve the outcomes. higher than the mortality rate of patients with DKA. The incidence of https://doi.org/10.1016/j.eprac.2021.04.593 HHS is estimated to be < 1% of hospital admissions of patients with diabetes. Very little research is available on the most appropriate treatment modality of HSS as studies are pooled with incidents of Abstract #1004015 DKA. There are many unresolved questions that need to be addressed regarding the pathogenesis and treatment in individuals with HHS. Uninterrupted Medical Care and Counselling in the DISHA https://doi.org/10.1016/j.eprac.2021.04.592 DOSTI Free Diabetes Clinic for the Poor During the Covid Pandemic: Challenges, Philanthropy and Creativity

Abstract #1004004 Author Block: Mandyam D. Chitra, MBBS, FEDM, CDE - Primary Diabesity as the Predictor for The Need For Intensive Author, Endocrinology Diabetes Medicine, Samatvam Care For Management of COVID-19 Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital and Medical Center; Jayalakshmi Thimmaiah, MBBS, FEDM CDE - Co Author, Endocrinology Diabetes Medicine, Samatvam Author Block: Sonali Patange, MD - Presenter, Dr Sonali Patange’s Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital Speciality Diabetes Centre, Mumbai, India; Dakshata Padhye, MD - and Medical Center; siddhartha dinesha, MBBS, FEDM CDE - Co Co Author, Conquer Diabetes Centre, Mumbai, India; Alka Gandhi, Author, Endocrinology Diabetes Medicine, Samatvam MD - Co Author, Aayushi Diabetes Care Clinic, Mumbai, India; Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital Ami Sanghvi, MD - Co Author, Sanghvi Eye and Diabetes Care and Medical Center; Apoorva Govind, MBBS, FEDM CDE - Co Centre, Mumbai, India; Ambrish Patange, MD - Co Author, Author, Endocrinology Diabetes Medicine, Samatvam

S58 Diabetes/Prediabetes/Hypoglycemia Endocrine Practice 27 (2021) S24eS71

Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital Laboratory Evaluations e Quarterly and Annual: Nil and Medical Center; Prateek Hongal, MBBS, FEDM CDE - Co Author, Free Insulin, Medicines, Blood Glucose Strips etc distribution: Endocrinology Diabetes Medicine, Samatvam Endocrinology Collection at the “Open Air Garden Clinic / Clinic Gate” by patients, Diabetes Center, Jnana Sanjeevini Diabetes Hospital and Medical family members or proxy; during complete lockdown few had to Center; Reshma Harsha, MBBS, FEDM, FACE - Co Author, procure locally through personal funds. Endocrinology Diabetes Medicine, Samatvam Endocrinology DISHA and DOSTI service disruption was mitigated through (a) Diabetes Center, Jnana Sanjeevini Diabetes Hospital and Medical Telemedicine [TM] Care: “Virtual Diabetes Clinics”; (b) Clinic Visit Center; Chandrika K, MBBS, FEDM, FACE - Co Author, [CV] Care [not during full lockdowns]; (c) Hybrid [HY] Care: ie TM + Endocrinology Diabetes Medicine, Samatvam Endocrinology CV, as per need. Each and every totally “Computer / IT Illiterate” Diabetes Center, Jnana Sanjeevini Diabetes Hospital and Medical beneficiaries of DISHA and DOSTI were provided all the benefits of Center; Sumathi K, MBBS, FEDM, FACE - Co Author, Endocrinology TM - via most creative involvement of our staff and volunteers who Diabetes Medicine, Samatvam Endocrinology Diabetes Center, serve as “proxy family” to these patients. All their Medical Records Jnana Sanjeevini Diabetes Hospital and Medical Center; were digitised on the innovative cloud based “Wellzio” EMR e Thummala Kamala, MBBS, FEDM, FACE - Co Author, Endocrinology Telemedicine platform. Diabetes Medicine, Samatvam Endocrinology Diabetes Center, Discussion/Conclusion: Generous philanthropy [Life for a Child with Jnana Sanjeevini Diabetes Hospital and Medical Center; Diabetes, Changing Diabetes in Children, The Kurtzigs Family, Sri GC Kavitha Muniraj, MBBS, FEDM, FACE - Co Author, Endocrinology Surana Family and Micro Labs, and other individual and institutional Diabetes Medicine, Samatvam Endocrinology Diabetes Center, benefactors], the Wellzio Telemedicine platform and the continued Jnana Sanjeevini Diabetes Hospital and Medical Center; infinite love and gratitude of DISHA DOSTI beneficiaries, together vasanthi Nath, MBBS, FEDM, FACE - Co Author, Endocrinology with the unflinching “Service with Devotion” of Samatvam Staff Diabetes Medicine, Samatvam Endocrinology Diabetes Center, and Volunteers were crucial for the successful sustenance of these Jnana Sanjeevini Diabetes Hospital and Medical Center; charity projects. “Think of giving not as a duty but as a privilege.” Pushpa Ravikumar, MBBS, FEDM, FACE - Co Author, Endocrinology dJohn D. Rockefeller Jr. Diabetes Medicine, Samatvam Endocrinology Diabetes Center, https://doi.org/10.1016/j.eprac.2021.04.594 Jnana Sanjeevini Diabetes Hospital and Medical Center; Chandraprabha siddalingappa, MBBS, FEDM, FACE - Co Author, Endocrinology Diabetes Medicine, Samatvam Endocrinology Abstract #1004017 Diabetes Center, Jnana Sanjeevini Diabetes Hospital and Medical Center; Sathyanarayana Srikanta, MBBS, MD, FEDM, FACE, FRCP - Prevalence of Recurrent Urinary Tract Infection in Co Author, Endocrinology Diabetes Medicine, Samatvam Patients with Type 2 Diabetes Mellitus Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital and Medical Center - Endocrinology Diabetes Study Group, Endocrinology Diabetes e Co Author, Endocrinology Diabetes Author Block: Ajay Sinha - Nalanda Medical College & Hospital, Medicine, Samatvam Endocrinology Diabetes Center, Jnana Patna Sanjeevini Diabetes Hospital and Medical Center Objective: Patients with type 2 diabetes (T2D) are at increased Objective: Over the last 3 decades, Samatvam Trust,Bangalore,India, risk of infections, with the urinary tract being the most frequent has continued to innovate and implement several FREE health care site, and good diabetic control has been recommended as a programs to provide best possible care to all socioeconomic seg- means of decreasing this risk. Adult women with diabetes are at ments of the society. We present Samatvam’s struggles during the increased risk of urinary tract infection (UTI), especially re- COVID 19 pandemic to mitigate the physical and psychological currences. The identification of risk factors can help pinpoint distress for people with diabetes, and reduce the disruptions in modifiable factors amenable to a disease prevention strategy for clinical diabetes services to the economically challenged. recurrent UTI. The aim is to study the clinical, etiological profile, Methods: Project DISHA [“direction”]: D iabetes I nteraction S complications, and follow-up of UTI in T2D patients. Mean FBG upport H ealth and A chievement [1987 e current]: Type I diabetes and blood glucose PP reduced at follow-up from baseline in T2D [612 since 2011] patients with nonrecurrent UTI (102 patients) (P < 0.001), but Project DOSTI [“friendship”]: D iabetes O rganization S upport T HbA1c insignificantly (P ¼ 0.729) changed from 10.34% ± 1.85% raining and I nteraction [1994 e current]: Type II diabetes [6000 +] to 10.27% ± 1.03% at follow-up. eGFR increased insignificantly (P Results: Complete lockdown dates: (a) 14 March to 19 May; (b) 25 ¼ 0.114) at follow-up. Renal function improved at follow-up in June to 6 July [Clinics closed for 14 weeks] nonrecurrent UTI patients.

YEAR 2019 2020 2019 2020 2019 2020 2019 2020 2019 2020

Months Mar- May Mar- May Jun- Aug Jun- Aug Sep- Nov Sep- Nov Dec- Jan Dec- Jan Total Total Number Patient Clinic Visits* DISHA: T1DM Follow Up 239 97 258 100 264 102 146 108 907 407 DISHA: T1DM New 5 0 9 0 5 1 2 0 21 1 DISHA: Hospitalisations 3 DISHA: COVID Illness 2

DOSTI: T2DM Follow Up 2584 629 2629 529 2431 600 1655 460 9299 2281 DOSTI: T2DM New 147 25 151 51 182 36 183 50 663 162

Number Patient Clinic “Physical” Visits: Does not include Telemedicine Support / Virtual Clinic services DISHA: Hospitalisations: DKA [1], Hypoglycemia seizures and coma [1], Infection and hyperglycemia [1]

S59 Diabetes/Prediabetes/Hypoglycemia Endocrine Practice 27 (2021) S24eS71

Methods: This was a hospital-based prospective study done on (95.6%) and sulphonylureas (66.7%) were the most commonly consecutive 250 T2D symptomatic UTI patients admitted in the prescribed anti-diabetic medications. Significant reduction in medicine department having age >30 years. Various clinical, HbA1c from baseline to week 24 (8.9 ± 1.2% vs. 7.4 ± 1.2% respec- biochemical parameters and urine examination and culture were tively, mean difference: -1.5 ± 0.7%, P < 0.0001) was seen. Reduc- monitored. All the patients were followed for 6 months with tion in FPG (mean difference: -66.0 ± 42.4 mg/dL, P < 0.0001) and respect to the number of UTIs, glycemic control and renal PPG (mean difference: -98.6 ± 58.6 mg/dL, P < 0.0001) was also parameters. significant. Mean reduction in weight was -4.2 ± 1.8 kg (P < 0.0001) Results: Of the 250 UTI patients, only 212 had completed follow-up at 24 weeks. Reductions in WC, SBP and DBP were also significant at at 6 months. 84 (39.6%) developed recurrent UTI, 45 patients week 24 (P < 0.0001 for all). Changes in all these parameters were developed one episode, 25 patients, two episodes, 12 patients, also significant at week 12. Proportion of patients achieving the three episodes, 4 patients four episodes, and 1 patient five episodes. target HbA1c of < 7% was 32% and 58% at week 12 and week 24, UTI was more common in females (82%) as compared to males respectively. Genital mycotic infections were seen in 20% patients (18%). Lower UTI (cystitis) was present in 56.5% and pyelonephritis and was present in higher proportion of females than males (29% 43.5%, emphysematous pyelonephritis (EPN) in 9.5% and bacter- vs. 12%, P ¼ 0.082). No episodes of hypoglycaemia were found. emia in 58.1% of UTI patients. EPN was present only in females. Of Discussion/Conclusion: Remogliflozin provides effective reduction the 169 T2D UTI patients followed till 6 months, 67 (39.6%) in glycemia in overweight/obese patients with T2DM in India. The developed recurrent UTI. The presence of chronic kidney disease, benefits are extended to reduction in body weight and WC which is uncontrolled diabetes, and renal calculi increased the risk of beneficial in obese and overweight patients. Improvement in these recurrent UTI in T2D females. While in males poor glycemia and parameters suggest that remogliflozin can be effectively used in lower estimated glomerular filtration rate increases risk of recur- patients of T2DM with metabolic syndrome. rent UTI. The recurrent UTI patients had significantly higher HbA1c https://doi.org/10.1016/j.eprac.2021.04.596 at follow-up than at baseline, but renal parameters did no differ. Discussion/Conclusion: Recurrent UTI is consequences of and leads fi to uncontrolled glycemia. Signi cant number of patients develop Abstract #1004040 recurrent UTI on follow-up. Recurrent UTI patients have poor gly- cemic control on follow-up while renal parameters did not differ. Relationship of the Continuity of Care and Glycemic https://doi.org/10.1016/j.eprac.2021.04.595 Control in Outpatients with Type 2 Diabetes Mellitus- A Five Year Longitudinal Analysis

Abstract #1004035 Author Block: Rajeev Chawla, MD, FRCP(UK), FACE - Presenting Efficacy and Safety of Remogliflozin in Overweight and author, Diabetes, North Delhi Diabetes Centre, Rohini, New Delhi; Obese Type 2 Diabetes Mellitus Patients in a Real- Shubhaa Chawla, MBBS - co-author, Diabetes, North Delhi Diabetes world Setting Centre, Rohini, New Delhi; Shalini Jaggi, PG Diploma Diabetes(UK), Diploma Endocrinology (UK) , FRCP, FACE - co-author, Diabetes, Lifecare Diabetes Centre Kirti Nagar New Delhi; Siddhant Trehan, Author Block: Ajay Sinha - Nalanda Medical College & Hospital, DM, Resident - co-author, Cardiology, Sri Jayadeva Institute of Patna Cardiovascular Sciences and Research, Bengaluru; Aastha Chawla Trehan, MD - co-author, Dermatology, North Delhi Objective: Beside glycemic lowering, additional pleotropic effects Diabetes Centre, Rohini, New Delhi; Rohit Kumar, Statistical analyst of SGLT2 inhibitors (SGLT2i) are beneficial in reducing the CV out- - co-author, Statistics and Software, North Delhi Diabetes Centre, comes and proving it to be a class effect. In Indian patients with Rohini, New Delhi T2DM, the phenotype is different and is associated with increased levels of insulin resistance. Remogliflozin is the SGT2i which has Objective: Continuity of care has demonstrated positive outcomes recently approved to use in India and gain popularity among cli- from the advanced countries with insurance care model. There is nicians. The main objective of this study was to assess the efficacy limited evidence for the benefits from developing countries, in and safety of remogliflozin (100 mg BD) in overweight and obese limited resource setting where the patients directly pay from the patients with type 2 diabetes mellitus (T2DM). pocket for the diabetes care. Methods: In a single centre, retrospective, observational study, Methods: We retrospectively analysed the relationship between included overweight or obese patients (Body mass index (BMI) the continuity of care and the glycemic control in patients who >25.0 kg/m2) with T2DM who had HbA1c >7% and received atleast had a biannual visit to our comprehensive care centre from Remogliflozin 100 mg BD as addition to existing therapy for at least 2016 to 2020 (n¼1160). 24 weeks. Primary endpoint assessed was changes in HbA1c, fast- Results: The mean number of visits in the year 2016, 2017, 2018, ing and post-prandial plasma glucose (FPG and PPG), and second- 2019 and 2020 were 3.6 (±1.6, max 11, 95% CI 3.38 to 3.98), 5 (±2.5, ary endpoints included changes in weight, waist circumference max 16, 95% CI 4.5 to 5.5), 4.8 (±2.1, max 12, 95% CI 4.4 to 5.2), 4.7 (WC), systolic blood pressure (SBP) and diastolic BP (DBP) over 12 (±2.2, max 14, 95% CI 4.3 to 5.1), 3.4 (±1.6, max 12, 95% CI 3 to 3.7) and 24 weeks. (p< 0.0001), respectively. The mean number of visits cumulatively Results: In total, we included 90 patients in the final analysis. Mean for the continuous five years for each patient was 22 (±7.9, min 11, age was 53.5 ± 10.8 years and 42.2% were females. Hypertension max 56, 95% CI 20 to 23). The mean number of HbA1c readings done with coexisting dyslipidemia (31.1%) was the most common co- cumulatively for the continuous five years for each patient was 22 morbid condition in study patients. Among existing antidiabetic (±3.8, min 1, max 17, 95% CI 3.3 to 4.4). The mean interval (days) drugs, most patients were receiving two drugs (46.7%) followed by between the two consecutive visits was 85 (±26, min 33, max 155, a single drug (28.9%) or three or more drugs (24.4%). Metformin 95% CI 81 to 90). The mean number of HbA1c tests were 3.8 (±2.8,

S60 Diabetes/Prediabetes/Hypoglycemia Endocrine Practice 27 (2021) S24eS71 min 1, max 17, 95% CI 3.3 to 4.4). The mean number of visits were Patients with diabetes mellitus type 2 and age 18-65 years 4.3 (±1.6, min 2.2, max 11, 95% CI 4 to 4.6). There was a non-sig- were offered this program. Pregnant or Lactating mother were nificant positive correlation between the mean number of visits excluded. All patients were investigated for CBC, HbA1c, C- and the mean HbA1c readings (Pearson r 0.113, p¼ 0.22). The peptide, Lipid Profile, RFT, LFT, ECG and Fundus Examination at baseline value of HbA1c (%) was 8.0 (±1.5, min 5.3, max 13.3, 95% CI base line and at the end of a year. Patients with low c peptide 7.7 to 8.3), which reduced by 0.7 when compared for the minimum (< 1 ng/ml), eGFR < 60, Liver enzymes more than 3 times upper value of HbA1c achieved at any point of time as mean 7.2 (±7.2, min limit, abnormal ECG, Retinopathy or cognitive impairment were 4.8, max 10.9, 95% CI 7 to 7.5), (p< 0.0001). There were 360 patients excluded. who had atleast one visit in 3 months and achieved HbA1c < 7, as Patients were asked to send picture of their all meal on a dedi- compared to 250 patients with more than 3 months interval for cated dietitian through whatsapp and the meals were corrected by consecutive visits and with HbA1c 7(p¼0.0404, OR 1.2 95% CI dietitian. Patient must send at least three or more times their meal 1.01 to 1.62). COVID-19 induced lockdown led to the decrease in the pictures. Not more than two consecutive days were granted for not patient visits in the year 2020. There were 55 all cause sending their meal pictures. Patients were offed structured exercise hospitalizations. program including aerobic exercise for two days, muscle Discussion/Conclusion: The results of our study demonstrate that strengthening exercise using dumbbells or own weight for two comprehensive diabetes care have a potential positive implication, days and yoga and meditation for one day. No two consecutive days even in out-of-pocket ecosystem, which can drive the demand for a were kept off for exercise. continuous follow up visits. We attribute long continuity of care for Results: Total 106 patient were enrolled and 94 patients were able the smaller number of hospitalizations. to follow up for one year as per program. At the end of the year following was the result. https://doi.org/10.1016/j.eprac.2021.04.597 At the one year follow-up assessment, mean (± standard devia- tion) HbA1c had decreased from 8.9 ± 2.2% at baseline by 2.8 to 6.1 ± ± Abstract #1004045 1.1%, mean weight had decreased from 84.0 11.2 kg at baseline to 72.2 ± 10.7 kg. Total 73 patients (77.66%) were in diabetes Role of Personalized Diet and Structured Exercise reversal stage. Average Blue Index was 24±2 at baseline, which Program Reversal in Diabetes Mellitus Type 2 improved to 43±2 at the end of one year. There was 79% improvement in blue index over the one year. Discussion/Conclusion: The results provide evidence that daily Author Block: Dharmendra Panchal, Diabetologist - Primary precision nutrition guidance based on food intake data and Author, Diabetes Care And Hormone Clinic; Shivani Arya, Dietitian structured exercise program can benefit patients with type 2 - co-author, Diabetes care and Hormone Clinic; Banshi Saboo, diabetes into reversal of the disease. Using clinical staging can Diabetologist - co-author, Diabetes Care And Hormone Clinic; be a simple and useful approach for monitoring of patients Sanjeev phatak, Diabetologist - co-author, Vijayratna Diabetes clinical progress into diabetes type 2. It can also be useful as Clinic; Rutul Goklani, Diabetologist - co-author, AHC DIACARE motivational tool for educating the patients along with blue index. Objective: The objective of this study was to examine changes in https://doi.org/10.1016/j.eprac.2021.04.598 HbA1c and reversal stage into type 2 diabetes between baseline and after 1 year of participation in the personalized diet and structured exercise program. Abstract #1004058 Methods: This was a retrospective study of patients with type 2 diabetes who participated in the personalized diet and structured Glycometabolic Profile in Type 2 Diabetic Patients with exercise program and had at least 3 follow-up quarterly over the Erectile Dysfunction year. Diabetes treatment options were classified into six groups based on their mechanism of actions. 1. Insulin (I) Author Block: Sajjad Ahsan - Indira Gandhi Institute of Medical 2. Insulin Provider (IP): Sulfonylurea and Glinides Sciences 3. Incretin Enhancer (IE): DPP4 inhibitors and GLP1 receptor agonists Objective: To study the glycometabolic and hormonal profile of 4. Glucose Excretor (GE): SGLT2 Inhibitors type 2 diabetic patients suffering from erectile dysfunction (ED) 5. Insulin Sensitizers (IS): Metformin and Pioglitazone and to determine the risk factors of ED in these for early 6. Glucose Restrictors (GR): Alpha Glucosidase Inhibitors intervention. The clinical stages of reversal in diabetes mellitus type 2 were Methods: The study was a cross sectional (analytical) study defined based on HbA1c achieved and maintained for more than 3 and included 110 type 2 diabetic males. After applying exclu- months and medication used. sion criteria, patients were screened for presence of ED (IIEF criteria). Patients without ED were also studied for comparison and to serve as control group. Patients were subjected to detailed history, physical examination, anthropometric mea- Stage Description HbA1c (%) Medication surements and laboratory investigations. Microsoft Word and < Excelwereusedtogenerategraphsandtablesanddescriptive Stage 0 Stage of Control 7 Any fi Stage 1 Reversal Stage 1 < 6.5 GR±IS+IE+GE statistical analysis was carried out. Statistical signi cance (P Stage 2 Reversal Stage 2 < 6.5 GR±IS+IE value < 0.05) of variables was determined among two groups. Stage 3 Reversal Stage 3 < 6.5 GR±IS Results: The overall prevalence of ED was 65%. The mean age of the Stage 4 Reversal Stage 4 < 5.7 GR±IS patients was higher in ED group (50.12 years) compared to non ED Stage 5 Stage of Remission < 5.7 None group (39.84 years). Patients with ED have a higher mean duration

S61 Diabetes/Prediabetes/Hypoglycemia Endocrine Practice 27 (2021) S24eS71 of diabetes (9.68 years) compared to patients without ED (4.49 Abstract #1004129 years). The presenting symptoms, use of drugs and smoking habit was comparable in the two groups. Absent ankle reflex was Telemedicine Enriched Diabetes Care for Covid significantly more common in patients with ED. No association was Patients in Home and Hospital Settings: A Real-World found with any sign of autonomic dysfunction. ED was significantly Experience from India associated with obesity (higher BMI), central adiposity (higher waist/hip ratio), insulin resistance (HOMA-IR) and high hsCRP levels. ED was significantly associated with poor glycemic control Author Block: Sathvik Reddy, MBBS, CDE - Primary Author, (higher HbA1c%) and low HDL cholesterol levels. No significant Endocrinology Diabetes Medicine, Samatvam Endocrinology association was found with testosterone levels and SHBG levels. Diabetes Center, Jnana Sanjeevini Diabetes Hospital and Medical Discussion/Conclusion: The management of ED in diabetes should Center; Jayalakshmi Thimmaiah, MBBS, DNB, FEDM, CDE - Co- focus on weight reduction, strict glycemic control and maintaining author, Endocrinology Diabetes Medicine, Samatvam a healthy lifestyle rather than focusing on exogenous testosterone Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital therapy. and Medical Center; Mandyam Chitra, MBBS, FEDM, CDE - Co- https://doi.org/10.1016/j.eprac.2021.04.599 author, Endocrinology Diabetes Medicine, Samatvam Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital and Medical Center; siddhartha dinesha, MBBS, FEDM CDE - Co Abstract #1004069 Author, Endocrinology Diabetes Medicine, Samatvam Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital Effectiveness of Remogliflozin and Vildagliptin and Medical Center; Apoorva Govind, MBBS, FEDM CDE - Co Combination in Type 2 Diabetes Mellitus Patients Author, Endocrinology Diabetes Medicine, Samatvam Uncontrolled on Triple Oral Drug Therapy Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital and Medical Center; Prateek Hongal, MBBS, FEDM CDE - Co Author, Endocrinology Diabetes Medicine, Samatvam Endocrinology Author Block: Sajjad Ahsan - Indira Gandhi Institute of Medical Diabetes Center, Jnana Sanjeevini Diabetes Hospital and Medical Sciences Center; Sumathi K, MBBS, FEDM, FACE - Co Author, Endocrinology Diabetes Medicine, Samatvam Endocrinology Diabetes Center, Objective: Remogliflozin has recently approved in India and Vil- Jnana Sanjeevini Diabetes Hospital and Medical Center; dagliptin recently off patented and both the are economically Thummala Kamala, MBBS, FEDM, FACE - Co Author, Endocrinology priced in India. The aim of this study was to evaluate the effec- Diabetes Medicine, Samatvam Endocrinology Diabetes Center, tiveness of remogliflozin and Vildagliptin combination (Remo+v- Jnana Sanjeevini Diabetes Hospital and Medical Center; ilda) as an add-on therapy in patients with type 2 diabetes mellitus Sharda Ardhanareeswaran, MBBS, MD, FEDM, FACE, FRCP - Co (T2DM) with inadequate glycemic control with three oral antidia- Author, Endocrinology Diabetes Medicine, Samatvam betic drugs. Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital Methods: Retrospective data with T2DM patients receiving and Medical Center; Kavitha Muniraj, MBBS, FEDM, FACE - Co Remo+vilda as an add-on therapy to the triple-drug therapy Author, Endocrinology Diabetes Medicine, Samatvam (metformin, sulfonylurea, and thiazolidinedione or alpha-glucosi- Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital dase inhibitor) for at least 3 months were collected and analyzed. and Medical Center; Tejeswini Patil, MBBS, MD, FEDM, FACE - Co The effectiveness of Remo+vilda was assessed by analyzing the Author, Endocrinology Diabetes Medicine, Samatvam mean changes in fasting plasma glucose (FPG), postprandial plasma Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital glucose (PPG), and glycosylated hemoglobin (HbA1c) after 3 and Medical Center; Pushpa Ravikumar, MBBS, FEDM, FACE - Co months of duration. Author, Endocrinology Diabetes Medicine, Samatvam Results: Data of eligible 45 patients were included in the anal- Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital ysis. Remo (100 mg BD) +vilda (50 mg BD) was initiated in and Medical Center; Lakshmi Reddy, MBBS, FEDM, FACE - Co patients who were uncontrolled on triple-drug therapy. The Author, Endocrinology Diabetes Medicine, Samatvam mean age of the patients was 58.3 years, with a mean duration Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital of diabetes 8.2 years and mean body weight 72.3 kg. Almost 78% and Medical Center; Sathyanarayana Srikanta, MBBS, MD, FEDM, of patients had comorbid conditions, hypertension (56%), and FACE, FRCP - Co Author, Endocrinology Diabetes Medicine, dyslipidemia (32%) being the most common. Metformin, glime- Samatvam Endocrinology Diabetes Center, Jnana Sanjeevini piride, and pioglitazone (84%) combination was the most Diabetes Hospital and Medical Center - Endocrinology Diabetes preferred triple combination. Statistically significant reduction Study Group, Endocrinology Diabetes - Co Author, Endocrinology was seen in HbA1c, FPG, and PPG at the end of 3 months by 1.2 Diabetes Medicine, Samatvam Endocrinology Diabetes Center, ± 0.8%, 47.37 ± 24.3 mg/dl, and 68.24 ± 38.6 mg/dl from the Jnana Sanjeevini Diabetes Hospital and Medical Center baseline of 8.6 ± 1.2%, 174.32 ± 22.42 mg/dl, and 251.47 ± 48.11 mg/dl, respectively. At the end of 3 months, HbA1c target of < Objective: We share our experiences related to a Diabetes Care for 7% was achieved by 44% of patients receiving Remo + vilda Covid patients rendered over the last 11 months, by the Samatvam medication. No adverse safety-related event was reported during Endocrinology Diabetes Team, Bangalore, India. Unprecedented 3-month duration. public health crisis forced the “Endocrinology Team” to serve also Discussion/Conclusion: Remo + vilda was found to be effective in as General Physicians in providing and coordinating overall the management of T2DM uncontrolled on triple oral therapy and comprehensive “Covid 19 Infectious Disease Care” [out of sheer was well tolerated. social need and humanitarian duty], even to people and families https://doi.org/10.1016/j.eprac.2021.04.600 without Diabetes or other Endocrine disorders. The emphasis has

S62 Diabetes/Prediabetes/Hypoglycemia Endocrine Practice 27 (2021) S24eS71 been on prompt day to day acquisition and assimilation of global hormones estrogen, cortisol, and human placental lactogen com- scientific data, often confusing/conflicting, and practically and bined with increased lipolysis causes greater insulin resistance and effectively delivering the same to both “Providers” and “Patients” in an overall catabolic state which improves nutrient availability for need. vital fetal growth. However, this also allows for a magnified Methods: “Telemedicine [TM] Care and Creativity” included: (a) response to fasting that results in increased ketone production and Remote diagnostic and therapeutic specialist guidance: to both in- in rare cases “accelerated starvation.” In this case, we present a 25- hospital/ ICU physicians and nursing staff, as well as patients and year-old pregnant patient who presented with nausea, vomiting, family members in home care under isolation and quarantine; (b) and poor oral intake, who was found to be in starvation Individual “serious / complicated” patient centric “Whats app ketoacidosis. groups” and “email chains”: for 24x7 data gathering, patient Case Description: A 25-year-old G2P1001 cis female with a monitoring, therapy guidance and counselling, with both physician previous medical history of migraines presented at 33 weeks [clinic and hospitalist] and patient/ family participation and post- gestation with nausea, vomiting, and poor oral intake for four ings; (c) Tele-self-care technique trainings for “naïve/new/ un- days prior to admission in the setting of COVID-19 infection. trained” patients under home care/quarantine [Eg: Glucose Patient presented hemodynamically stable and in no acute Monitoring, Insulin/GLP-1 and Heparin Injections, via archived or distress. Fetal non stress test on admission was reactive. Initial real time video demonstrations. These services have been provided lab work revealed a glucose of 95, anion gap of 21, and a bi- to patients within Bangalore City and Karnataka State [urban and carbonate level of 7. A beta hydroxybutyrate (BHB) level was rural], and also from far off places within India and even few elevated at 5.26. Arterial blood gas showed a pH of 7.2 and a overseas [touching the lives of more than 1000 patients directly or PCO2 of 23, consistent with an anion gap metabolic acidosis. indirectly]. Samatvam has implemented Covid Antibodies Sero- Urinalysis revealed 3+ ketones. Overall labs were consistent with surveillance and is participating in the National Vaccination starvation ketoacidosis and the patient was immediately resus- Program. citated with dextrose containing intravenous fluids and an in- Results: In hospital Diabetes Care: Treatment Order Sheets for sulin drip to help shunt away from ketoacidosis. Her BHB rapidly Doctors and Nurses on Duty: These included: Useful 'Front Door' downtrended to 1.28 within 12 hours and within 24 hours it guidance for individual patients [Eg: Discontinuation of SGLT-2 normalized. Her metabolic acidosis continued to improve inhibitors and metformin in all patients on acute presentation; throughout her hospitalization. She was able to tolerate a reg- Urine ketone testings]; Diabetes Management Flow Charts: ular diet prior to being discharged home. A few weeks later, she Scheduled Insulin / Medication Doses and Supplements; Special had an uncomplicated full term delivery of a healthy baby. Protocols for: 1: People with no past history of Diabetes and no Discussion: Starvation ketoacidosis outside of pregnancy is rare Stress Hyperglycaemia; 2: People with no past history of Diabetes and takes at least two weeks to manifest as a mild ketoacidosis. and Stress Hyperglycaemia diagnosed in Hospital; 3: People with In pregnancy, patients are in an insulin resistant state which past history of Diabetes on Oral Diabetes Medicines OHA [+/- In- increases with gestational age, making them prone to ketoaci- sulin]; 4: Sick / ICU diabetes patients with severe hyperglycaemia, dosis particularly in the second and third trimesters. Ketoaci- DKA or HHNK: 5: Intravenous Insulin; 6: Steroid e Glucocorticoid dosis in pregnancy is not only harmful for the pregnant Therapy - Special precautions; 7. Potential Covid related benefits of individual, but for the developing fetus as well. Ketones can DPP-4 inhibitors- immunomodulatory. cross the placental barrier, leading to neurological impairment Discussion/Conclusion: Implementable and pragmatic guidance for and even fetal demise if the acidosis is not addressed quickly. health care providers [especially those unfamiliar with speciality Prompt treatment with IV fluids, dextrose, and insulin is diabetes care] caring for patients hospitalized for Covid-19 has imperative to prevent neurodevelopmental compromise. Patients been an imminent need. Diabetes care for Covid patients in home with appropriate and timely treatment can continue on to have settings can also be challenging. Diabetes care must be synchro- uncomplicated pregnancies and deliveries. nized with other complex Covid medical management as a way of https://doi.org/10.1016/j.eprac.2021.04.602 minimizing risk for complications and death. https://doi.org/10.1016/j.eprac.2021.04.601 Abstract #1004285

Abstract #1004265 Diabetes Mellitus as an Initial Manifestation of Pancreatic Cancer Starvation Ketoacidosis in the Third Trimester of Pregnancy Author Block: Goonja Patel - Crozer Chester Medical Center; Pooja Jotwani, MD - Co-author, Crozer Chester Medical Center; Author Block: Kirit Gill - Kent Hospital/Brown University; Praveena Gandikota, MD - Co-author, Crozer Chester Medical Shamila Panjwani, D.O. - Co-Author, Family Medicine, Kent Center Hospital/Brown University; Kenneth K. Chen, M.D. - Co-Author, Endocrinology/Obstetric Medicine, Women & Infants Hospital of Introduction: The global incidence of diabetes mellitus (DM) is Rhode Island over 400 million cases. Multiple factors contribute to the increased risk of developing DM including obesity, family his- Introduction: Starvation ketoacidosis represents one of the three tory, smoking status, ethnicity, lifestyle, and more. However, in metabolic acidoses caused by the accumulation of ketone bodies the absence of obvious risk factors or the presence of other within the bloodstream. Outside of late pregnancy, it is a relatively alarming symptoms, it is crucial to rule out other dangerous rare condition. In late pregnancy, the placental production of the underlying precipitating factors. Herein we describe the case of

S63 Diabetes/Prediabetes/Hypoglycemia Endocrine Practice 27 (2021) S24eS71 rapidly progressing new-onset diabetes induced by pancreatic HbA1c, LDL-C, Ankle Brachial Index (ABI), Toe Brachial Index (TBI) cancer. or Albumin Creatinine Ratio (ACR). The percentage of patients Case Description: The patient is a 58-year-old male with a his- achieving the target values were classified as ATV (Achievers for the tory of HTN who presented to the Endocrinology office after a Target Value). Descriptive statistics was used for the analysis diagnosis of new-onset DM. He had developed severe polyuria Results: A total of 202 patients (53 males, 47 females) were eval- and polydipsia over a 2 week period. Over the past 3 months, he uated for the glycemic and non e glycemic parameters (lipid pro- experienced a 15-pound unintentional weight loss. A physical file, ABI, TBI, UACR). The mean age was 53 (±13 years (minimum 19, exam was performed and disclosed no abnormalities. Blood maximum 85, 95% CI 51 to 55). The mean duration of the diabetes work revealed a blood glucose of over 500 without an anion gap was 7.7 (±6.5 minimum 1, maximum 36, 95% CI 6.8 to 8.6). The acidosis and an HbA1c of 9.2 percent. Of note, HbA1c from 3 mean HbA1c was 8.5 % (±2 minimum 5.3, maximum 15, 95% CI 8.2 months prior was 5.4 percent. There was no evidence of to 8.8). 4 patients reported macroalbuminuria (ACR > 300) and 49 obstructive bilirubinemia. Therapy was initiated with metformin patients had microalbuminuria (ACR 30-300). The HbA1c and non and an eventual addition of daily insulin to optimize glucose glycemic measures as a marker for comprehensive diabetes care are control. He was evaluated with an abdominal CT scan which depicted in the table. unveiled a mass in the pancreatic head concerning for pancre- atic ductal carcinoma. He was referred for surgical resection of Table- HbA1c and Non Glycemic Measures as a Marker for Comprehensive Diabetes Care his mass. Unfortunately, while the surgery was underway, met- astatic lesions to the liver were discovered. Instead of a full Mean ± SD 95% CI n (%) within resection, the patient received surgical palliation with chole- target cystectomy, retrocolic isoperistaltic gastrojejunostomy, and roux- HbA1c (< 7%) 8.7 2.1 8.3 to 9.1 54 (26.7) < en-y hepaticojejunostomy accompanied by a celiac nerve block. LDL-C (target 100mg/dl) 73 18 69 to 76 102 (50.4) ¼ Discussion: (n 102) Long standing DM is an established risk factor for ABI- Right (target 1-1.29) 1.2 0.07 1.2 to 1.2 146 (72.2) pancreatic cancer, but it is an uncommon initial manifestation of ABI- Left (target 1-1.29) 1.2 0.08 1.2 to 1.2 141 (69.8) the malignancy. The abysmal survival rates tied to pancreatic can- TBI- Right (target 0.5-0.75) 0.65 0.066 0.62 to 0.68 25 (12.3) cer are largely attributable to the fact that patients often remain TBI- Left (target 0.5-0.75) 0.63 0.077 0.60 to 0.67 22 (10.8) Albumin Creatinine Ratio 12 6.7 11 to 14 92 (45.5) asymptomatic until the disease has progressed to its advanced (ACR) stages. However, constructing a guideline for pancreatic cancer (Normal < 30) screening in patients with new-onset DM remains difficult considering the extensive list of other common etiological factors of DM and the low incidence of pancreatic cancer. Some clues to Discussion/Conclusion: The achievement of the TBI (left side) was indicate the possibility of an underlying malignancy include the the most compromised with just 10.8 % of the patients demon- absence of family history, rapidly progressing symptoms, sudden strating the desired values, followed by TBI (right side) within the onset, weight loss, advanced age, and absence of well-recognized normal values in 12.3 % of the patients and HbA1c of < 7 was not risk factors. In such cases, screening with an abdominal CT or achieved by 73.3% of the patients. The highest proportion of ATV endoscopic ultrasound may be appropriate. Screening all patients were for the ABI value-right (72.2%). The results from our study with new-onset DM would not be clinically sound or cost-effective. provide the indicators for formulation of patient outcome Nevertheless, in cases where the clinical presentation does not fit improvement plan. The evidence from our comprehensive care the usual mold of the disease course, clinicians must broaden their approach complements the clinical decision-making tool to allo- differential to consider other atypical etiologies. cate the resources to intervene early to minimize the complications of diabetes and improve outcome. https://doi.org/10.1016/j.eprac.2021.04.603 https://doi.org/10.1016/j.eprac.2021.04.604

Abstract #1004350 Abstract #1004361 Achieving Target Values for Measures for Peripheral Arterial Disease, Nephropathy and Dyslipidemia in Von Gierke Disease in A Patient with Insulin Dependent Type 2 Diabetes- Two Year Assessment Diabetes Mellitus: Polar Opposites in the Same Patient

Author Block: Ragini Rohatgi, MD - Presenter, Rohit Diabetes Author Block: Valentina Celis - Mount Sinai Medical Center of Centre, Mumbai, India; Sonali Ghodke, Dietician - Co Author, Rohit Florida; Ayoola Olayiwola, MD - Co-author, Mount Sinai Medical Diabetes Centre, Mumbai, India; Daisy Alfred, Dietician - Co Center of Florida Author, Rohit Diabetes Centre, Mumbai, India Introduction: Glycogen storage disease (GSD) type I, also known as Objective: Type 2 Diabetes (T2DM) is a major risk factor of pe- Von Gierke disease (VGD), is an autosomal recessive disorder ripheral artery disease (PAD), leading to increased morbidity and characterized by deficient glucose-6-phosphatase activity, an mortality as well as an accelerated disease course. Micro- enzyme needed in glycogenolysis and gluconeogenesis to convert albuminuria is an indicator for overt nephropathy and early car- glucose-6-phosphate to free glucose. This leads to hypoglycemia diovascular disease with associated lactic acidosis, hypertriglyceridemia and hyper- Methods: We analysed the data from the outpatients attending a uricemia. Paradoxically, despite hypoglycemia, patients with VGD comprehensive diabetes care centre (n¼202), from 2019 till 2020, usually don’t develop significant ketosis due to inhibition of fatty who had any of the values beyond the normal targets, for either of acid beta-oxidation by high levels of malonyl-CoA.

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Case Description: A 33 year old male Ashkenazi Jew with diag- Methods: We observed 48 patients who were divided into 2 nosis of type Ia GSD since 3 weeks old controlled on strict groups: group 1 - patients with type 2 diabetes associated with scheduled doses of corn starch, and insulin dependent diabetes tuberculosis, who made up the main group (n¼ 42), group 2 - a mellitus (IDDM) since 16 years old due to recurrent pancreatitis control group, represented by patients with tuberculosis (n ¼ 12). secondary to hypertriglyceridemia arrived to the ED with Research methods included general clinical, biochemical complaint of abdominal discomfort, nausea and vomiting. He (glucose, glycated hemoglobin, coagulogram, lipid spectrum, reported recent poor compliance with his insulin regime and etc.), hormonal (insulin, C-peptide) blood and urine tests. In inability to take his corn starch during the previous day due to patients of both groups, the content of vitamin B12 and vitamin incapacity to tolerate oral intake. On physical exam he was D was studied. Instrumental studies included ECG, Doppler ul- lethargic, tachypneic, tachycardic and hypotensive with blood trasonography of the great vessels, ultrasound of internal organs, pressure 98/48 mmHg. Laboratory work up revealed Na 131 and X-ray studies. (136-145 mmol/L), K 4.2 (3.5-5.1 mmol/L), glucose 60 (74-106 Results: The first group consisted of 17 men and 19 women, whose mg/dL), pH 6.9 (7.31-7.41), HCO3 5.8 (21.0-32.0 mmol/L), anion average age was 54.4 ± 2.2 / 55.5 ± 1.7 (m / f), respectively. The gap (AG) 39 (5.0-15.0 mmol/L), lactic acid 10.2 (0.4-2.0 mmol/L), duration of diabetes in men was within 6.8 ± 1.4 years, and in beta-hydroxybutyrate (BHB) 88.1 (0.2-5.6 mg/dL) and ketones women, 4.6 ± 0.7 years. The duration of tuberculosis in men was 1.8 present in urine. He was admitted to ICU for severe combined ± 0.3 years, and in women 1.9 ± 0.2 years. The average HbA1 C anion gap metabolic acidosis (AGMA) due to diabetic ketoaci- content was within 8.9 ± 0.50 / 9.9 ± 0.51, and glucose 10.6 ± 0.61 / dosis (DKA) and lactic acidosis. Treatment was initiated with IV 15.0 ± 0.82 nmol / L in patients of group 1. The average insulin level fluids as 10% dextrose with KCl, IV insulin and bicarbonate was 11.3 ± 2.09 / 11.7 ± 2.2 pg / ml, and vit B12 403 ± 33.7 / 407 ± infusion. DKA resolved within 24 hours with normalization of 45.7 ( normal 193-982 pg / ml, average 450 pg / ml ), the content of AG, HCO3 and BHB. However, lactic acidosis persisted > 7 mmol/ Vit D was in the range of 13.1 ± 2.1 / 11.1 ± 3.08 ng / ml, respectively L up to day 3 of hospitalization until he was able to tolerate oral (normal range from 30-100 ng / ml). intake and corn starch was slowly reintroduced. He was dis- The second group consisted of 9 men and 3 women, the average charged in stable condition on corn starch 30g every 4 hours, age was 49.5 ± 5.2 / 45.0 ± 8.0 years. The duration of tuberculosis in glargine 10 units nightly, lispro sliding scale with meals, allo- this group was 1.8 ± 0.4 / 1.0 ± 0.2 years. The average content of purinol 300 mg, rosuvastatin 10 mg and omega-3 acid. HbA1 C was within 4.1 ± 0.2 / 4.9 ± 0.7, and glucose was 5.1 ± 0.1 / Discussion: Our patient presented with the hallmark clinical and 5.8 ± 0.4 nmol / L in patients of group 1. The average insulin level biochemical features of VGD in an acute lactic acidotic episode. was 9.6 ± 1.9 / 16.3 ± 1.3 pg / ml, and vit B12 376.7 ± 91.1 / 402.0 ± However, the unusual co-existence of IDDM posed a diagnostic 13.3 ( normal 193-982 pg / ml, on average 450 pg / ml ), the content and therapeutic dilemma in the context of AGMA. DKA could of Vit D was in the range of 14.5 ± 1.4 / 11.6 ± 1.7 ng / ml, respec- easily have been disregarded in the presence of hypoglycemia, tively (normal from 30-100 ng / ml). but the large amount of ketone bodies was reflective of a dual Discussion/Conclusion: In both groups of patients, the average etiology to his acidosis. The peculiarity of this case also entails a content of vitamin D in the blood was significantly reduced , management challenge in the outpatient setting, with the while the average levels of vitamin B12 in both groups were meticulous goal of achieving glycemic control while prioritizing within the normal range, remaining below the average normal the avoidance of hypoglycemia to prevent secondary metabolic values. derangements. https://doi.org/10.1016/j.eprac.2021.04.606 https://doi.org/10.1016/j.eprac.2021.04.605

Abstract #1022296 Abstract #1004369 Association between Laboratory Parameters on Characteristic of Homeostasis of Vitamins b12 and d in Admission and Poor Clinical Outcome of COVID-19 in Patients with Type 2 Diabetes Mellitus Associated with Patients with Type 2 Diabetes Mellitus: A Cross- Tuberculosis Sectional Study

Author Block: Ozoda Azimova - Republican Specialized Scientific Author Block: Md Ikhsan Mokoagow - Fatmawati General medical center of Endocrinology, named after acad.prof. Hospital; Dante S. Harbuwono, MD, PhD - Co-author, Department Turakulov.Ya.X; Zamira Khalimova, none - co-author, of Internal Medicine, Dr. Cipto Mangunkusumo National Referral Neuroendocrinology, Republican Specialized scientific Practical Hospital, Faculty of Medicine Universitas Indonesia, Division of Medical Center of Endocrinology named after Academician Endocrinology and Metabolism; Ida Ayu Kshanti, MD - Co-author, Y.K.Turakulov, Tashkent; Gulhayo Kholmatova, none - primary Department of Internal Medicine, Fatmawati General Hospital, author, Neuroendocrinology, Republican Specialized scientific Jakarta, Indonesia, Division of Endocrinology, Metabolism, and Practical Medical Center of Endocrinology named after Diabetes; C Martin Rumende, MD, PhD - co-author, Department of Academician Y.K.Turakulov, Tashkent Internal Medicine, Dr. Cipto Mangunkusumo National Referral Hospital, Faculty of Medicine, Division of Respirology and Critical Objective: Diabetes and tuberculosis are among the world's Illness deadliest epidemics. People suffer from diabetes and are sus- ceptible to tuberculosis/Objectiveis to study the features of ho- Objective: This study aims to assess the association between lab- meostasis of vitamin B12 and vitamin D deficiency in patients oratory parameters on admission and poor clinical outcome i.e. with type 2 diabetes mellitus (DM 2 ) associated with intensive care admission, and mortality of COVID-19 in-patients tuberculosis presented with T2DM in a tertiary hospital.

S65 Diabetes/Prediabetes/Hypoglycemia Endocrine Practice 27 (2021) S24eS71

Methods: This is a cross-sectional study conducted in Fatmawati mechanical ventilation, or transfer to a critical care unit) related to General Hospital, Jakarta, Indonesia, recruiting COVID-19 adult COVID-19. patients hospitalized during the period March to November Results: We evaluated 169 patients mean age was 61 years old, 2020. Using the medical records data, we collected random and 64.5% were male. 71% had at least one comorbidity, of blood glucose (RBG), C-reactive protein (CRP), ferritin, D-dimer, which hypertension (34%), obesity (30%) and DM (26%) were the lactate dehydrogenase (LDH), neutrophil to lymphocyte (NLR), most frequent. About symptoms, dyspnea, cough and fever were and monocyte to lymphocyte ratio (MLR) levels upon admission. the most frequent. 70% presented tomographic severity. mean Poor clinical outcomes defined as intensive care unit admission admission blood glucose was 126.5 ± 48 mg / dL, 1 in 2 had and in-hospital mortality. T-test or Mann-Whitney u-test were glycemia greater than 140 mg / dL. Cohort mortality rate was 9.7 used to assess the association between variables where per 100 person-week. Mortality rate was 9.7 deaths per 100 applicable. person-weeks, with a frequency of 21.3%. There was no signifi- Results: Of the 506 patients admitted to our hospital, 144 (28.46%) cant difference between hyperglycemia and mortality, nor in patients had diabetes. Intensive care admission documented in 297 composite outcome. Hyperglycemic group had a longer hospital (58.70%) patients with a higher proportion in within diabetes stay than normoglycemic one (19 days vs 13 days, p < 0.01). In compared to non-diabetes group (86.11% vs. 47.79%) and mortality subanalysis with multivariate logistic regression for composite documented in 140 (27.67%) patients (45.14% in diabetes and outcome among diabetic patients, admission blood glucose > 20.72% in non-diabetes groups). Compared to their counterparts, 180mg / dL had 6.42 (1.07-38.6) greater risk for adverse com- subjects with diabetes had higher RBG, CRP, Ferritin, D-dimer, and posite outcome than patients with blood glucose 180mg / dL, LDH levels (p< 0.05). Of patients admitted to intensive care , sub- this adjusted to age and admission clinical severity. jects with diabetes had higher d-dimer, MLR, and RBGs levels than Discussion/Conclusion: Hyperglycemia on admission is a factor non-diabetes subjects (p< 0.05). However, we observed no differ- associated with adverse outcomes in diabetic patients and is ence between diabetes and non-diabetes subjects in mortality in correlated with hospital stay among survivors. regards to their laboratory parameters (p >0.05) excepts for RBG https://doi.org/10.1016/j.eprac.2021.04.608 level (p< 0.001). Discussion/Conclusion: Diabetes increased the risk of poor fl outcome in COVID-19 due to a higher in ammatory state docu- Abstract #1039882 mented by laboratory examinations on admission. https://doi.org/10.1016/j.eprac.2021.04.607 Recurrent Diabetic Ketoacidosis in A Community Teaching Hospital

Abstract #1030455 Author Block: Nicole Pant, MD - Primary/First author, Glycemia on Admission Associated with Hospital Stay Endocrinology, Diabetes and metabolism, UTHSC-Memphis; and Mortality in a Peruvian National Hospital Nidhi Agarwal, MD - Co-author, UTHSC-Memphis; (GLUCOVID Study) Vamsee K. Mupparaju, MD - co-author, Methodist Le Bonheur Healthcare; Helmut Steinberg, MD - Co-author, UTHSC-Memphis; Samuel Dagogo-Jack, MD, DSc - Co-author, UTHSC-Memphis Author Block: Jose Paz-Ibarra - HOSPITAL NACIONAL EDGARDO REBAGLIATI MARTINS - ESSALUD. UNIVERSIDAD NACIONAL Objective: To describe factors associated with recurrent diabetic MAYOR DE SAN MARCOS. LIMA - PERU; Victor Garcia, MD - co- ketoacidosis (DKA) in a community hospital in Memphis. author, Servicio de Endocrinologia, Hospital Nacional Edgardo Methods: We identified all patients admitted with the diagnosis of Rebagliati Martins, Lima e Peru; Carolina Salas, MD - co-author, DKA to a community hospital in Memphis, TN, from January 2013 Servicio de Endocrinologia, Hospital Nacional Edgardo Rebagliati (index admission) to September 2015. Patients with multiple DKA Martins, Lima e Peru; Sofia Saenz, MD - co-author, Servicio de admissions were identified and compared to patients who had Endocrinologia, Hospital Nacional Edgardo Rebagliati Martins, single admission. Lima e Peru; Julio Alvarez, MD - co-author, Servicio de Results: A total of 116 patients accounted for 349 admissions Endocrinologia, Hospital Nacional Edgardo Rebagliati Martins, during the 33-month period of study. Of the 116 patients with Lima e Peru; Fernando Quinto, MD - co-author, Servicio de DKA, 58 patients had only one episode and 58 had multiple Endocrinologia, Hospital Nacional Edgardo Rebagliati Martins, admissions. The mean age was 38.3 ±15.3 for subjects with Lima e Peru multiple DKA admissions and 42.5±14 years for those with a single admission (P >0.5). At index admission, HbA1c levels Objective: Diabetes mellitus and hyperglycemia have been described were similar (12.4±2.5% vs. 11.9±2.7%) but BMI was lower in as risk factors for adverse outcome in COVID-19. The aim of this study patients with recurrent DKA vs. single episode of DKA was to evaluate the association between admission blood glucose and (22.0±4.20 kg/m2 vs. 28.2±7.90 kg/m2, P < 0.0001). Counting adverse outcomes in non-critical hospitalized patients with COVID- from the index date, the cumulative number of recurrent DKA 19 in a multidisciplinary service of a Peruvian hospital. episodes/patient was 3.31 ± 2.92 (range 2-15) at 12 months, Methods: This is a retrospective cohort-type observational study, 4.48 ±4.20 (range 2-22) at 24 months and 5.0±5.2 (range 2-30) which included all patients hospitalized for COVID-19 during the at 33 months. Of the 58 patients with recurrent DKA, 44 pa- months of April to June 2020, followed until discharge or death, in a tients had < 3 DKA admissions and 14 patients had > 3 ad- COVID-19 medical specialities ward . We classified patients ac- missions during the 33-month study period. Those 14 patients cording to history of DM and blood glucose levels at admission. The (24%) accounted for 95 out of 251 total DKA admissions (37.8%) primary endpoint was composite outcome (death, septic shock, at 12 months, 268 out of 319 total DKA admissions (84%) at 24

S66 Diabetes/Prediabetes/Hypoglycemia Endocrine Practice 27 (2021) S24eS71 months and 300 out of 349 DKA admissions (85%) at 33 months Results: Of the eligible 1340 patients with comorbid T2DM and from the index date. The proportion of patients with single DKA heart failure, 129 patients were prescribed an SGLT-2 inhibitor episode vs. recurrent episodes were similar in men vs. women during this time perioddonly 9.6 percent. Of those patients and in Blacks vs. Whites. Compared with single DKA patients, started on an SGLT-2 inhibitor, 54 (42.9%) had discontinued this those with recurrent DKA episodes were more likely to be medication as determined by last prescription greater than one smokers (34.4% vs. 22%), had a longer duration of DM year prior to study start. When comparing patients who received (14.56±9.47 vs. 11.1±10.8 years), and were more likely to be an SGLT-2 inhibitor versus those who did not, those who were uninsured (31% vs. 25%). Cessation of insulin therapy was the prescribed were more likely to be younger 58.3 vs 64.4 years, major precipitating factor for single or recurrent DKA episodes (p< 0.001) and have private (commercial) insurance (42.6% vs (70.6% vs. 64.9%). 25.8%). Race also played a significant role in prescribing Discussion/Conclusion: Our analysis showed that 24% of pa- practicesda higher proportion of the SGLT-2 users were cauca- tients accounted for 85% of recurrent DKA admissions at a sian (26.4% vs 16.2%). However, none of these demographic community hospital. Focusing interventions on those high- differences showed significant discrepancy for discontinuation of frequency DKA patients could have individual, societal and the medication. The factor most predictive of discontinuation economic benefits. was the initial choice of SGLT-2 inhibitor, with those started on canagliflozin more likely to discontinue for any reason (42.6% of https://doi.org/10.1016/j.eprac.2021.04.609 users). There was no difference in adverse event rates before or after treatment with SGLT-2 inhibitors, and there was no sig- fi Abstract #1040609 ni cant change in outcomes markers (BMI, A1C, left ventricular ejection fraction, or kidney function) in any group. SGLT-2 Inhibitor Prescribing Patterns at Tertiary Care Discussion/Conclusion: SGLT-2 inhibitors overall are under-pre- Diabetes Center for Individuals with Diabetes and scribed and are more likely to be prescribed for younger patients Heart Failure with commercial insurance. The racial background of the patient may influence prescribing practices.

https://doi.org/10.1016/j.eprac.2021.04.610 Author Block: Megan Kristan - University of Maryland School of Medicine; Yoon K. Kim, MD - co-author, University of Maryland Medical Center; Angie Molina, MD - co-author, University of Abstract #1042199 Maryland Medical Center; Toby Nelson, MD - co-author, University of Maryland Medical Center; Ozlem Onal, MS4 - co-author, High Alert Settings in Continuous Glucose Monitoring University of Maryland Medical Center; Johanna Thompson- are Associated with Time-in-Range and Hypoglycemia Westra, MS4 - co-author, University of Maryland School of Duration Medicine; Terry Yip, PhD - co-author, University of China Hong Kong; Rana Malek, MD - co-author, University of Maryland School of Medicine; Kashif Munir, MD - co-author, Endocrinology, Author Block: Francis A. Osowik, BS - primary author, Ohio University of Maryland School of Medicine University Heritage College of Osteopathic Medicine; Kevin Pantalone, DO - co-author, Endocrinology, Cleveland Clinic; Objective: Diabetes mellitus type 2 (T2DM) affects more than 30 Elizabeth A. Beverly, PhD - co-author, Primary Care, Ohio million adults nationally, many have co-morbid cardiovascular University Heritage College of Osteopathic Medicine diseases. Sodium-glucose Cotransporter-2 (SGLT-2) inhibitors have been shown to improve heart failure (HF) outcomes, including Objective: Increased glycemic variability is associated with micro- reduced hospitalization, and improved left ventricular ejection vascular complications in people with type 1 diabetes (T1D). fraction, and reduced major adverse cardiac events. Despite the Continuous glucose monitoring (CGM) reduces glycemic variability evident benefits and prescribing recommendations by major by increasing time-in-range (TIR) and reducing severe episodes of endocrine and cardiovascular societies, a 2019 study (1) showed hypoglycemia. Higher thresholds for low CGM alert settings have that only 7.2% of individuals with diabetes were treated with SGLT- been shown to reduce hypoglycemia; however, the impact on TIR is 2 inhibitors. The goal of this study is to review prescribing practices inconsistent. Thus, the purpose of this study was to examine CGM within an academic endocrinology practice including frequency of alert settings and their association with TIR, number of hypogly- complications, contraindications, and demographic characteristics cemic events, duration of hypoglycemic events, and prolonged of selected patients. hypoglycemic events. (1) McCoy, RG. Et al. “Adoption of New Glucose-Lowering Medi- Methods: Adults diagnosed with T1D using Dexcom CGMs, 18 cations in the U.S.dThe Case of SGLT2 Inhibitors: Nationwide years who were able to read and speak English and living in the Cohort Study.” Diabetes Technology & Therapeutics. Volume 21 United States were invited to participate. Participants completed Number 12, 2019. a brief demographic questionnaire and uploaded a copy of their Methods: All patients with a visit to the practice with at least one 90-day CGM readings. Linear regression models were conducted encounter between January 1, 2015 through February 5, 2021 to examine high and low alert settings and their association who had co-existing diagnoses of T2DM and HF based on ICD-10 with TIR (70-180 mg/dl), number of hypoglycemic events, codes were extracted from the electronic medical record. Addi- duration of hypoglycemic events, and prolonged hypoglycemic tional data including prescribing information, left ventricular events. Multiple regression models controlled for age, gender, ejection fraction, estimated renal function, hemoglobin A1c, and diabetes duration, and treatment type (multiple daily injections presence of potential complications from SGLT-2 inhibitors was (MDI), insulin pumps). Analyses were performed using SPSS collected. version 26.0.

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Results: A total of 36 adults with T1D participated (mean (TPN): a novel whole-body digital twin enabled precision treat- age¼37.2±12.4, 73.7% women (n¼28), 86.8% White (n¼33), ment for reversing diabetes. The TPN program entailed detailed A1C¼6.8±1.2%, duration¼23.8±12.3, BMI¼28.8±5.6). The mean TIR patient food intake information with CGM readings as inputs to a for participants was 68.0±20.6%. On average, participants experi- machine learning. The machine learning algorithm integrated these enced 5.7±6.4 hypoglycemia events lasting a mean duration of multi-dimensional data to predict personalized postprandial 50.6±27.7 with a mean number of 0.6±1.1 prolonged hypoglycemic glucose response. This led to a predictive model, which enabled events. The median for high alert settings was 180 mg/dl and the daily precision nutrition guidance to the patient. Physicians utilized median for low alert settings was 70 mg/dl. Participants’ high alert the TWIN app recommendations as a decision-enabling tool to settings differed by treatment type, with participants on insulin customize the therapeutic approaches. Clinical Trial Registration pumps reporting higher thresholds (median¼200 mg/dl) Number - CTRI/2020/08/027072. compared to participants on MDI (median¼160.0 mg/dl, p¼.033); Results: The mean age (years) was 41 (±9.2, minimum 16, low alert settings did not differ by treatment type. Regression maximum 62, 95% CI 39 to 44). The duration of diabetes (years) models showed higher CGM alert thresholds were independently was 3.1 (±2.7, maximum 8, 95% CI 2.4 to 3.8). There was a sta- associated with less TIR (b¼ -.476, p¼.012), after controlling for age tistically significant improvement in HbA1c % (8.5 ± 1.6, 95% CI (b¼.553, p¼.017), gender (p¼.974), diabetes duration (p¼.429), and 8.17 to 8.99 reduced to 5.6 ± 0.52, 95% CI 5.52 to 5.79; p< 0.0001), treatment type (p¼.860). Low alert settings were not associated HOMA2-IR (1.81 ± 0.71, 95% CI 1.63 to 1.99 decreased to 1.11 ± with TIR (b¼ -.188, p¼.312). Additional models revealed higher 0.51, 95% CI 0.98 to 1.24; p< 0.0001), HOMA2 Beta (51.78 ± 28, thresholds were associated with greater duration of hypoglycemia 95% CI 44.6 to 58.97 increased to 94.42 ± 38.9, 95% CI 84.62 to (t¼ -2.229, p¼.033) and prolonged hypoglycemia (t¼ -2.240, 104.2; p< 0.0001), body weight (kg) (79.8 ± 14.67, 95% CI 76.14 to p¼.032), but not total number of hypoglycemic events (t¼ -.877, 83.53 decreased to 70.58 ± 12.31, 95% CI 67.48 to 73.68; p¼.387). Interestingly, low alert settings were not associated with p¼0.0002) and waist circumference (cms) (97.13 ± 10.82, 95% CI total number of hypoglycemic events (t¼ -1.889, p¼.068), duration 94.41 to 99.86 decreased to 89.58 ± 8.9, 95% CI 87.31 to 91.84.684; of hypoglycemia (t¼ -1.721, p¼.095), or prolong hypoglycemia (t¼ p¼0.0002). There was a decrease in the visceral fat (12.44 ± 7.7, -1.269, p¼.213). 95% CI 10.5 to 14.39 reduced to 10.31 ± 8.2, 95% CI 8.23 to 12.39, Discussion/Conclusion: The findings suggest that higher thresholds p¼0.136 ns). There was a negative correlation for the change in for high alert settings were associated with decreased TIR, and the HbA1c and body weight (Pearson r - 0.15, 95% CI -0.38 to 0.10, lower thresholds for high alert settings were associated with p¼ 0.022 ns), and visceral fat (Pearson r e 0.14, 95% CI -0.38 to increased duration and prolonged hypoglycemia. Providers need to 0.10, p¼ 0.24 ns). There was a positive correlation between address alert settings with their patients in order to optimize TIR HbA1c and waist circumference (Pearson r 0.034, 95% CI -0.21 to without increasing hypoglycemia duration. 0.27, p¼ 0.78 ns). Discussion/Conclusion: There was an independent significant https://doi.org/10.1016/j.eprac.2021.04.611 decrease in HbA1c (34%), HOMA2IR (39%), body weight (4.63%), waist circumference (7.7%) with a significant increase Abstract #1042655 of 82% in HOMA2Beta, from baseline. However, there was no significant correlation between the glycemic parameters and Digital Twin Enabled Precision Nutrition Induces the markers of obesity. Technology enabled precision nutrition, Remission of Diabetes Independent of Improvement a combination of macro, micro and biota nutrients, with in the Markers of Obesity physician-led adoption and technology-driven intervention had positive implications for diabetes remission which is in- dependent of the weight loss and the reduction in the waist Author Block: Shashank Joshi, DM, Endocrinology - Primary, Twin circumference.

Health and Joshi Clinic; Paramesh Shamanna, MD - Co Author, https://doi.org/10.1016/j.eprac.2021.04.612 Twin Health; Lisa Shah, MD - Co Author, Twin Health; Mala Dharmalingam, DM - Co Author, MS Ramaiah (MSR) Medical College (Bangalore), and Director of the Bangalore Endocrinology Abstract #1042688 & Diabetes Research Centre (BEDRC); Arun Vadavi, MD - Co Author, Sudha Prevention Center; Jahangir Mohammed, MD - Co Author, Glycemic Control Metrics using Flash Glucose Twin Health; Maluk Mohamed, md - Co Author, Twin Health; Monitoring in People with Type 2 Diabetes: Three Year Terrence Poon, md - Co Author, Twin Health; Trends in Real Life Clinical Setting Ashok Keshavamurthy, MD - Co Author, Twin Health; Suchitra Bhonsley, md - Co Author, Twin Health; Mohamed Thajudeen, MD - Co Author, Twin Health Author Block: Shalini Jaggi, MD - Primary, Lifecare Diabetes Centre, Delhi, India; Shubhaa Chawla, MD - Co Author, North Delhi Objective: Technology-enabled precision nutrition, a combina- Diabetes Centre; Aastha Chawla, MD - Co Author, North Delhi tion of macro, micro and biota nutrients, along with Continuous Diabetes Centre; Siddhant Trehan, MD - Co Author, 4. Sri Jayadeva Glucose Monitoring (CGM) have been demonstrated to be a key Institute of Cardiovascular Sciences and Research; Rajeev Chawla, for reversal of diabetes. We explored the association between MD - Co Author, North Delhi Diabetes Centre change in the glycated hemoglobin (HbA1c) and parameters of obesity that included body weight, waist circumference and Objective: Flash Continuous Glucose Monitoring (flash CGM) has visceral obesity. been rapidly accepted in real life clinical setting. Methods: We conducted an initial analysis (n¼63) of the ongoing Methods: We conducted a cross sectional study across two centres, randomized controlled trial of Twin Precision Nutrition Treatment delivering the similar standard of care, over three years (n¼362), in

S68 Diabetes/Prediabetes/Hypoglycemia Endocrine Practice 27 (2021) S24eS71 patients who utilised FreeStyle Libre Pro CGM to understand gly- The teleconsultations were distinctively structured to not just cemic metrics and variability. The key glycemic metrics; TIR, Time the reactively address the medical issues but also were struc- Below Range (TBR), Time Above Range (TAR), estimated HbA1c, tured to proactively deliver E health education over the online average glucose was analysed. Descriptive statistics, Pearson r and platform. ANOVA were utilised for analysis. Results: There was a significant reduction in HbA1c from the Results: Overall, in total 24.8% (90/362) were in TIR >70%, with mean baseline 9.5% (±1.7, 95% CI 9-10) to 8.6% (±2.5, 95% CI 14.7% (18/122) patients in 2018, 17.6% (30/170) in 2019 and 60% 7.9 to 9.3) (reduction of 0.9%, p ¼ 0.0393). The overall time (42/70) in 2020. In total 37% (134/362) were in TAR < 25%, 29.5% span in the HbA1c evaluation was 2.9 years (±1.3, 95% CI 2.5 (36/122) in 2018, 28.2% (48/170) in 2019 and 71.4% (50/70) in to 3.3). 27 patients were from Mumbai and rest were from 2020. In total 45.3% (164/362) were in TBR < 4%, 44.2% (54/122) MENA, with majority of patients from Saudi Arabia. Varied in 2018, 46.4% (79/170) in 2019 and 44.2% (31/70) in 2020. issues were addressed ranging from HbA1c follow up to Overall, 9.3% (34/362) achieved all three metrices (TIR >70%, TAR providing advise for management of diabetic foot ulcers.The < 25%, TBR < 4%), with 4.9% (6/122) in 2018, 7.6% (13/170) in patients expressed satisfaction over the virtual connect for the 2019, 24.2 (17/70) in 2020. There was a significant negative undivided attention that was provided, with reliable internet correlation between the eHbA1c and TIR (Pearson r e 0.74, 95% connectivity. CI -0.79 to -0.69, p < 0.0001). There was significant improve- Discussion/Conclusion: The new eyeball connect based, remote ment in TIR and TAR over three years. The eHbA1c (6.5%) and digital diabetes consultation model has potential to improve average glucose (139.7mg/dl) were lowest in the year 2020, glycemic care, which appears to have improvement in the which were comparable with values in previous years. Lesser overall quality of life and in long term would mitigate com- hypoglycaemic events were noticed in CGM. (figure). plications due to T2DM. We attribute the impact of tele-

Table: Glycemic Metric overall across three years and year-on-year comparison (mean ± SD, 95% CI)

Glycemic Metric Overall, 3 years (n¼362) 2018 (n¼122) 2019 (n¼170) 2020 (n¼70) p value

Time in Range 53 ±13, 95% 44.3 ± 21.74, 95% 45.63 ± 23.77, 95% 68.01 ± 21.11, 95% < 0.0001 (TIR % of time/ day >70%) CI 20 to 86 CI 40.44 to 48.23 CI 42.03 to 49.23 CI 62.98 to 73.05 Time Above Range (TAR % 38 ± 13, 95% 45.16 ± 26.71, 95% 44.77 ± 27.49, 95% 23.09 ± 23.69, 95% < 0.0001 of time/ day < 25%) CI 7.3 to 6.3 CI 40.38 to 49.95 CI 40.61 to 48.93 CI 17.44 to 28.73 Time Below Range (TBR % 9.7 ± 0.8, 95% 10.5 ± 11.87, 95% 9.6 ± 12.5 95% 8.9 ± 9.9, 95% 0.64 ns of time/ day < 4%) CI 7.7 to 12 CI 8.37 to 12.63 CI 7.7 to 11.49 CI 6.52 to 11.28 eHbA1c (%) 6.7 ± 1.4, 95% 6.61 ± 1.29, 95% 6.7 ± 1.5 95% 6.5 ± 1.4, 95% 0.37 ns CI 6.5 to 6.8 CI 6.38 to 6.84 CI 6.56 to 7.0 CI 6.2 to 6.89 Average Glucose (mg/dl) 145 ± 42, 95% 141.4 ± 38.4, 95% 148.4 ± 43.4, 95% 139.7 ± 44.17, 95% 0.22 ns CI 140 to 149 CI 134.5 to 148.3 CI 141.8 to 155 CI 139.2 to 150.2

Discussion/Conclusion: There was a significant change in the gly- consultations for the efficient delivery of diabetes care for the cemic metrics. We attribute the remarkable improvement, over past efforts during the earlier face to face consultations to three years, to the better awareness in the patients to manage drive the importance of self-management of diabetes. The role diabetes, greater adoption of guideline directed, contemporary of telehealth in T2DM has expanded dramatically during the therapeutics including SGLT2 inhibitors, advanced insulins. This coronavirus pandemic and would remain a major practical coincided with the COVID-19 induced fear of mortality and lock- health care delivery modality going forward. down led better metabolic health, that resulted in better self-care of https://doi.org/10.1016/j.eprac.2021.04.614 diabetes. https://doi.org/10.1016/j.eprac.2021.04.613 Abstract #1042711

Abstract #1042704 Analysis of the Glycemic Parameters using Flash Glucose Monitoring in Difficult to Manage Patients Effectiveness of Teleconsultations Across Middle East with Type 2 Diabetes And Africa (MENA) and India In T2DM To Deliver Continuity of Care During The COVID-19 Pandemic Author Block: Alok Modi, MD - Primary, Kevalya Hospital, Jupiter Hospital and Dr Alok Modi’s Diabetes Centre, Mumbai, India; Author Block: Suresh Purohit, MD - Co Author, SugarDoctor Alpa Modi, MD - Co Author, Kevalya Hospital, Jupiter Hospital and Medicare and Diabetes Care Centre; Lotika Purohit, MD - Co Dr Alok Modi’s Diabetes Centre, Mumbai, India Author, SugarDoctor Medicare and Diabetes Care Centre; Kiran Shah, MD - Co Author, Diabetes and Thyroid Care Center Objective: Flash Continuous Glucose Monitoring (CGM) has been widely accepted and complements self-monitoring of blood Objective: The COVID-19 pandemic has accelerated growth and glucose. acceptance of telemedicine services. Methods: We analysed a cluster of difficult to manage T2DM Methods: We evaluated 110 patients across the SugarDoctor patients (n¼152) over a period of one year, by utilising Free- database who were already registered before the pandemic and Style Libre Pro CGM to understand glycemic metrics and were provided the teleconsultations during COVID-19 pandemic. variability. The key glycemic metrics were TIR (Time in Range),

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Time Below Range (TBR), Time Above Range (TAR), average LIPID PROFILE :- TOTAL CHO e 162mg/dl, TG- 204 mg/dl, HDL e glucose, % Coefficient of Variation (%CV) and Standard Devia- 37mg/dl, LDL e 84.2 mg/dl tion (SD) was analysed. We followed a clinical decision sup- SERUM IRON STUDIES:- SR. IRON e 55.8ug/dl, TIBC 237ug/dl, port mechanism to identify difficult to treat (either with PERCENTAGE SATURATION 23.4% persistent hyperglycemia reported by SMBG, or diabetes MRI BRAIN (P & C) WITH MR ANGIOGRAPHY BRAIN AND NECK :- related complications). Descriptive statistics, Pearson r and NORMAL ANOVA were utilised for analysis. EEG SHOWS MILD GENERALISED SLOWING Results: There were 19.7% (30/152), 43.4 % (66/152), 40.1% (61/ CT SCAN Brain ( P & C) :- CEREBRAL ATROPHY, AGE RELATED 152), patients who achieved TIR, TAR and TBR, respectively. ISCHAEMIC CHANGES The mean TIR, TAR, TBR, %CV, SD was 50, 38, 12, 33 and 45, Patient treated with regular insulin infusion and sugar controlled. respectively (table). The glucose levels were consistently above Treatment started with split doses of subcutaneous insulin with the average glucose (140 mg/dl) from 10 am till 2am, with OHA, Antihypertensive started, Statin introduced. specific post prandial spikes at post-breakfast and post lunch. DAY 2 ; PATIENT WAS STABLE , NO EPISODES OF SEIZURE . Persistent hyperglycaemia was identified as a distinctive SUGAR LEVEL BBF- 168mg/dl, BL e 167mg/dl, BD e 183 mg/dl feature of these patients. There was a highly statistically sig- DAY 6 :- PATIENT WAS STABLE, AND PATIENT DISCHARGED. nificant difference in the 2 hourly glucose levels (p< 0.0001), DISCHARGED TREATMENT across 24 hours. There was a significant negative correlation Insulin, OHA, Anti Hypertensive, Statin, Tab. Ecosprin (75mg) 0- between the group of patients who achieved TIR >70% (n¼30) 1-0 and CV% (r ¼ -0.50, p¼0.0041, 95% CI -0.7342 to -0.1814). 5.2% Tab. Levipril (500mg) 1-1-1 (8/152) had all three metrices (TIR >70%, TAR < 25%, TBR < Result: PATIENT HAD A GTC. A H/O FEVER WAS THERE, BUT NO 4%) in the target. FEVER AT THE TIME OF ADMISSION and subsequently, TLC - N, LFT- Discussion/Conclusion: FreeStyle Libre Pro appears to be precise N, RFT-N Sr Na 133 mmol/l. HbA1c 18.4, SR. OSMOLARITY ¼ glycemic monitoring tool with the snapshot of the glycemic met- 301.82mOsm/kg (at admission), URINE KETONES ARE ABSENT. MRI rices, that empowers patients and enables physician to decide for BRAIN IS NORMAL AND EEG SHOWING MILD GENERALISED the customised intervention. The parameters of glycemic variability SLOWING. (% CV and SD) addresses the need to modulate the anti-diabetic All this points to hyperosmolar state as a precipating factor for therapy to specifically mitigate the risk and manage the compli- the convulsion. once the hyperosmolar state was corrected there cations due to hyperglycaemia. was no further episode of convulsion. 1 Month later follow up , No seizure https://doi.org/10.1016/j.eprac.2021.04.615 Discussion: PROVOKED SEIZURE DUE TO HYPERGLYCEMIA -NON KETOTIC HYPERGLYCEMIC SEIZURE Abstract #1014339 Uncontrolled Hyperglycemia and associated Seizures and seenmostoftenbeyondthe5thdecadeoflifewiththemean Presenting a Case of Hyperglycemia /Hyperosmolar age of 64 years, ALBEIT few cases have been reported in Induced Seizure children. It tends to present in female patients. The female to male ratio remains controversial, but the literature with a mean age at the onset of 75 years and the female to male Author Block: Sunil Kamble - Surana Sethia Hospital ratio was 1.33 PATHOPHYSIOLOGY OF NON KETOTIC HYPERGLYCEMIC Introduction: 57 y/F, Mrs. X admitted with h/o 2 episode of GTC. SEIZURE:- Patient is a K/C/O DM, HTN, Dyslipidaemia since 14 years on Hyperosmolarility cause cellular dehydraion and subsequent Irregular Treatment. NO P/H Convulsion. Patient had GTC around dysfunction of brain cells. Moreover the plasma hypertonicity can 10am lasted 5-10minutes, had a similar episode around 12 cause a focal reduction in blood flow and SEIZURES noon.she had MILD FEVER & 1 Episode of Vomitting. Another posssible mechanisms are hyperglycemia or hyper- Case Description: At admission patient had a blank/staring look, no osmolarity inhibited Krebs cycle , gamma amino butric acid (GABA) response to verbal commands. after 5-10 mins she became consious metabolism is increased and the levels decreased, thus lowering and cooperative. the threshold of seizure activity Evening patient had episode of seizure , ANTIEPILEPTIC INJ. https://doi.org/10.1016/j.eprac.2021.04.616 LEVEPIL (1GM) bolus then (500MG) BD continued. Patient become stable. O/E P-96/MIN, BP- 160/80mmHg, RS - CVS- NORMAL Abstract #1038612 INVESTIGATION:- HBA1c :- 18.4 RBS- 524 mg/dl ECG e LVH MINOR ST CHANGES I & AVL Transition from Pediatric to Adult Care in Type 1 CBC- Hb- 9.4g/dl, WBC -6400/cmm, Platelet-277000/cmm, ESR Diabetes Mellitus: A Llongitudinal Analysis of Clinical -40mm, Characteristics and Outcomes LIVER FUNCTION :- NORMAL RENAL PROFILE:- SR, CREATININE:- 0.6mg/100ml SR. Na e 133mq/litre, SR. K e 4.1 mEq/litre, SR. CL- 97mEq/litre, Author Block: Diana Soliman - Duke; Alison Manning, MD - co- SR. CALCIUM:- 8.7 author, Duke University; Gary Maslow, MD - co-author, Duke URINE R & M- Sugar e 3 +, Pus cells e 5-6/hpf, Epithelial cells e University; Karen Chiswell, PhD - co-author, Duke University; 4-5/hpf KETONES- ABSENT Aruna Rikhi, MPH - co-author, Duke University; ECG CHANGES : TNI < 0.01 ng/ml, BNP 23,7 pg/ml Matthew J. Crowley, MD, MHS - co-author, Duke University

S70 Diabetes/Prediabetes/Hypoglycemia Endocrine Practice 27 (2021) S24eS71

Objective: As adolescents and young adults (AYAs) with type 1 Centre; Siddhant Trehan, MD - Co Author, Sri Jayadeva Institute of diabetes mellitus (T1DM) transition from pediatric to adult- Cardiovascular Sciences and Research; Rohit Kumar, MD - Co oriented health care systems, they are at an increased risk for Author, North Delhi Diabetes Centre poor health outcomes. The best approach to transition and optimal timing of transition in patients with T1DM are not well understood. Objective: COVID-19 pandemic has rapidly changed the land- Methods: This retrospective, longitudinal study of electronic scape of diabetes care to quickly adapt to continue providing health record data examined 299 AYAs with T1DM who received optimalcaretopatientswithdiabetesinanefficient and care in the pediatric and adult endocrinology clinics at the Duke effective manner. University Health System. We used multivariable regression Methods: We describe a retrospective assessment of patients models to explore the association of comorbidities, health care with diabetes, with and without COVID-19 infection, during the utilization, continuous glucose monitor (CGM) and insulin pump lockdown period March 2020 to February 2021 managed use with gap in care (in months) when transitioning from pe- through a dedicated comprehensive dedicated telehealth plat- diatric to adult care. form. The virtual health applications comprised of telephone Results: The sample was 54.8% female and 73.4% White. The consultations and video telehealth consultations. mean hemoglobin A1c at the last pediatric encounter was 9.4% Results: The total patients who were managed by tele- ± 2.14. The median number of months to transition (Q1 - Q3) consultation were 765 (30 T1DM), (440 males). 250 patients was 14.09 months (4.58 e 43.80). After adjusting for socio- were COVID-19 with type 2 diabetes, and 15 patients were demographic factors, gap in care was significantly associated type 1 diabetes. The mean age (years) was 60 (±14, minimum with certified diabetes educator visit, nutrition visit, and CGM 10, maximum 88, 95% CI 58 to 62). There were 49% (375/765) use prior to transfer. The gap in care was extended by a factor patients with age less than 60 years. The mean number of of 1.83 fold (95% CI 1.10, 3.05, P ¼ 0.02) for those who were teleconsultations per patient were 1.5 (±0.97, minimum 1, not seen by a diabetes educator, 2.30 fold (95% CI 1.53, 3.46, P maximum 6, 95% CI 1.4 to 1.7). There were 235 patients who ¼ < 0.01) for those who were not seen by a nutritionist, and sought at least 1 repeat virtual consultation, of which 145 had 1.67 fold (95% CI 1.03, 2.71, P ¼ 0.04) for those who did not two virtual consultations. The mean number of virtual con- have a CGM prior to transfer. Hemoglobin A1c, insulin pump sultations were comparable in patients with (1.6±0.94, 95% CI use, comorbidities, ED visits per year, and hospitalizations per 1.3 to 1.8) or without COVID-19 (1.4±0.97, 95% CI 1.2 to 1.6), year were not significantly associated with the gap in care. p¼0.41 ns. The mean age was comparable in patients with Discussion/Conclusion: For AYAs with T1DM, a certified diabetes (58±15.5, 95% CI 54.47 to 63.04) or without COVID-19 educator visit, a nutrition visit, or CGM use prior to transfer are (60.45±12.81, 95% CI 57.91 to 62.9), p¼0.47 ns. The mean associated with a shorter gap in care. This association should be number of virtual consultations were comparable in elderly considered when designing transition programs for AYAs with >60 years (1.4±0.78, 95% CI 1.2 to 1.5) and in age group < 60 T1DM. years (1.6±1.1, 95% CI 1.3 to 1.8), p¼0.22 ns. The mean number of virtual consultations were similar in males (1.4±0.77, 95% CI https://doi.org/10.1016/j.eprac.2021.04.617 1.2 to 1.5) and in females (1.6±1.1, 95% CI 1.3 to 1.9), p¼0.11 ns. Discussion/Conclusion: Digital e virtual diabetes clinic has a Abstract #1042697 potential to provide efficient method of consultative service. Virtual electronic consultation mitigated the lockdown Diabetes Care During COVID-19 Pandemic Using a induced disruption in diabetes care activities and appears to Telehealth Approach be a reliable approach. Beyond the pandemic, we suggest that annually per patient, two virtual consultations would com- plement the two in person consultations, that would suffice to Author Block: Rajeev Chawla, MD - Primary, North Delhi Diabetes maintain the continuity of care and deliver optimal diabetes Centre; Shubhaa Chawla, MD - Co Author, North Delhi Diabetes care. Centre; Shalini Jaggi, MD - Co Author, Lifecare Diabetes Centre, Delhi, India; Aastha Chawla, MD - Co Author, North Delhi Diabetes https://doi.org/10.1016/j.eprac.2021.04.618

S71 Endocrine Practice 27 (2021) S72eS75

Contents lists available at ScienceDirect

Endocrine Practice

journal homepage: www.endocrinepractice.org

LIPIDS/CV HEALTH

Abstract #990437 once the offending agent is discontinued. Statin class of drugs, used for hyperlipidemia treatment, has common side effects of gastro- A Rare Case of Statin-Induced Thrombocytopenia in intestinal upset, myopathy, and liver function test derangement, Patient with Hyperlipidemia After a Year of with thrombocytopenia being very rare with no reported incident Rosuvastatin Treatment rate and no clear underlying mechanism. To our knowledge, ac- cording to one study held in 2016, there had been seven cases of DITP described in the literature, and manifestations varied from Author Block: Mariam Agladze, MD - primary author, Internal asymptomatic thrombocytopenia to patients presenting with Medicine, Icahn School of Medicine at Mount Sinai/NYC epistaxis, gingival bleeding, diffuse petechiae of trunk and limbs. Health+Hospitals/Queens; Masoud Amini, MD - co-author, Differential diagnoses of DITP include a number of conditions and Endocrinology, Icahn School of Medicine at Mount Sinai/NYC need a detailed review of each case. Management of DITP includes Health+Hospitals/Queens; Bayan Rassouli, Research Coordinator - drug discontinuation and treatment of bleeding/severe thrombo- co-author, Endocrinology, Icahn School of Medicine at Mount cytopenia as indicated. Sinai/NYC Health+Hospitals/Queens; Isaac Inoyatov, Research Although statin-induced thrombocytopenia is extremely rare and Volunteer - co-author, Endocrinology, Icahn School of Medicine at affects a small fraction of patients, one should have a high index of Mount Sinai/NYC Health+Hospitals/Queens; Issac Sachmechi, MD, suspicion for unexplained thrombocytopenia in patients receiving this FACE, FACP, Professor of Medicine - co-author, Endocrinology, class of medication to avoid potentially life-threatening complications. Icahn School of Medicine at Mount Sinai/NYC Health + Hospitals/ Queens https://doi.org/10.1016/j.eprac.2021.04.622

Introduction: Thrombocytopenia is defined as a platelet count Abstract #995713 below the lower limit of normal level < 150 x 109/L for adults. It may be associated with a variety of conditions as well as medications. Prevention of Cardiovascular Events in Asymptomatic Statins, a class of lipid altering medications, represent one of the Individuals very rare causes of drug-induced thrombocytopenia. We are pre- senting the case of a 65-year-old (yo) male who developed thrombocytopenia after a year of Rosuvastatin treatment (Crestor). Author Block: Julie Giannini, Medical Student - Presenter, Internal Case Description: 65-yo-male with a past medical history of Dia- Medicine/Endocrinology, University of New Mexico School of betes Mellitus Type 2 on Janumet, Hyperlipidemia on Rosuvastatin Medicine; R. Philip Eaton, M.D. - co-author, Internal Medicine/ 10mg daily, Hypertension on Amlodipine and Hyzaar, Erectile Endocrinology, University of New Mexico School of Medicine; fi dysfunction on Cialis, and Vitamin D de ciency on Ergocalciferol Kristen Gonzales, M.D. - Co-author, Internal Medicine/ 9 developed thrombocytopenia of 73 x 10 /L while on this regimen. Endocrinology, University of New Mexico School of Medicine; The patient was started on Rosuvastatin a year before when his Imaneh Fallahi, M.D. - co-author, Internal Medicine/Endocrinology, 9 platelet count was 175 x 10 /L. Physical examination was unre- University of New Mexico School of Medicine; David S. Schade, markable at the time he developed thrombocytopenia. Laboratory M.D., FACE, FCP - Primary author, Internal Medicine/Endocrinology, work up resulted in normal levels of liver function test, hemoglo- University of New Mexico School of Medicine bin, white blood cell counts, creatinine, and creatine phosphoki- nase. CT abdomen revealed no abnormality. Although Rosuvastatin Objective: The majority of asymptomatic cardiovascular disease treatment had been ongoing over a year before developing (CVD) ultimately presents with a catastrophic event resulting in thrombocytopenia, statin-induced thrombocytopenia was sus- either death (50%) or a myocardial infarction, stroke, or congestive pected. Crestor was discontinued. Platelet count recovery was heart failure. We assessed the potential benefit of reducing LDL sustained and improved gradually to 84 x 109/L and then 99 x 109/L cholesterol to < 60mg/dl upon the cardiovascular event rate in at 1 month and 4 months after discontinuation of Crestor, patients with proven asymptomatic cardiovascular disease. respectively. Methods: Between 2015 and 2021, 83 self-referred healthy elderly Discussion: Drug-induced thrombocytopenia (DITP) can be classi- adults (mean age 69), (58% M / 42% F) were evaluated for subclinical fied as immune, caused by drug-dependent antibody-mediated atherosclerosis by coronary artery calcium scanning (CAC). These platelet destruction, or nonimmune, caused by bone marrow sup- patients had Agatston calcium scores between 5 and 2,538 with a pression, or both. Some drugs are more known to cause thrombo- mean of 496, placing many individuals at very high cardiovascular cytopenia (e.g. heparin, antibiotics, phenytoin) than others. Usually, risk (minimal risk ¼ zero score). For the 71 individuals with both a it occurs one to two weeks after starting the new drug and resolves positive CAC scan and a reduction of LDL cholesterol < 60 mg/dl

1530-891X Lipids/CV Health Endocrine Practice 27 (2021) S72eS75 with medical treatment, the number of expected cardiovascular Results: Among 231 patients with STEMI the mean age of the pa- events was calculated for the duration of observation (up to 5 tients being 60 years + 11.8years. Males out numbered females years). The primary outcome was any cardiovascular event, (male¼69%, female 31%). Among ACS patients at least one lipid including myocardial infarction, stroke, and congestive heart fail- abnormality was present in 83.5%, prevalence of low HDL was ure. Secondary outcomes included changes in triglycerides and HDL 52.8%. It is found that three lipid abnormalities were seen in 22% cholesterol. Based upon published data from the MESA research among 16.4% patients lipid profile was normal. population and the Rotterdam study of coronary artery calcium The number of patients with moderate and severe left ventric- scoring with documented cardiovascular events, we determined ular dysfunction were almost the same between low HDL and the expected annualized cardiovascular event rate for each indi- normal HDL group. The percentage of patients with single, double vidual. Medical treatment consisted of rosuvastatin 10 mg/day, and triple vessel disease in coronary angiogram is 35.5%, 39% and ezetimibe 10 mg/day, and a low cholesterol diet. 25.1% respectively. 21 patients had left main coronary artery Results: Unexpectedly, none of the 71 patients with an LDL involvement. cholesterol below 60 mg/dl experienced a cardiovascular event. In Left ventricular dysfunction was seen in 155[67.09%] patients of contrast, the expected number of cardiovascular events in this which 95[41.1%] were in the high hs-CRP group, 157(67.9%) number population was 6.8. The mean LDL cholesterol decreased from 128 of patients had heart failure out of which 93 were in high hs-CRP mg/dl to 42 mg/dl, HDL cholesterol increased from 60 mg/dl to 65 group and 57 were in moderate hs-CRP group which was statisti- mg/dl and triglycerides decreased from 133 mg/dl to 82 mg/dl. Two cally significant. individuals died of non-cardiovascular causes. In the original cohort In our study severity of atherosclerosis was correlated with of 83 individuals, myocardial infarctions did occur in two non- plasma hs-CRP levels and the p value was significant (< 0.05).15 out compliant individuals who did not reduce their LDL cholesterol of 20 patients who expired were in high hs-CRP group, positive below 60 mg/dl. The average cost for medical therapy was $161 per correlation was observed between Hs-CRP and HDL, but no corre- year, covered by most insurance programs. This cost is far below the lation was found with albumin levels and total counts. average direct costs of one myocardial infarction of $30,000 plus Discussion/Conclusion: coronary artery stenting ($22,000) or coronary artery bypass In this cross-sectional study of 231 patients with ACS, nearly 50% ($55,000) if required. of patients had low HDL-c levels. Discussion/Conclusion: Reducing LDL cholesterol in asymptomatic In patients presenting with the first episode of ACS elevated hs- patients with positive calcium scores to < 60 mg/dl utilizing CRP level is associated with severity of LV dysfunction, heart aggressive medical therapy prevents cardiovascular events in pa- failure, higher rate of in hospital complications including mor- tients with subclinical atherosclerosis. The savings in medical costs tality. Hence hs-CRP can be termed as a simple biochemical alone in preventing these events is very significant. marker which helps us to assess the spectrum of the patient presenting with acute coronary syndrome https://doi.org/10.1016/j.eprac.2021.04.623 The inflammatory marker hs-CRP is associated independently with very low HDL levels. However, it is still unclear whether Abstract #1000529 the changes in plasma levels of HDL-Cholesterol are primary events or secondary to the inflammation and need further HDL Cholesterol Along with Biomarkers of Inflammation studies. in Patients with Acute Coronary Syndrome https://doi.org/10.1016/j.eprac.2021.04.624

Author Block: Mukhyaprana Prabhu - Kasturba Medical College Abstract #1003759 Manipal, India; weena M. Stanley, MD MRCP - co author, General Medicine, KMC,MAHE(deemed to be university; Hypertriglyceridemia in Indian Context: A Potential Mounica M. Chekuri, MBBS - co author, General Medicine, KMC, Beneficial Intervention Needed in The High-Risk MAHE (deemed to be university); arpita Chakraborty, Msc - co Modifiable Group (HRMG) author, General Medicine, KMC, MAHE (deemed to be university)

Objective: 7. To study the prevalence of very low HDL-C levels in Author Block: Brijendra Srivastava - MADRAS DIABETES patients admitted with acute coronary syndrome and correlation of RESEARCH FOUNDATION; M. DEEPA, PHD - CO-AUTHOR, MDRF; inflammatory markers with low R.M. ANJANA, MD, PHD, FRCP - CO-AUTHOR, MDRF; 8. To study clinical outcome and in-hospital mortality in patients MOHAN VISWANATHAN, MD, PHD, FRCP, FACE - CO-AUTHOR, with ACS MDRF Methods: Its a prospective, single center, observational study, total of 231 Objective: Hypertriglyceridemia is a common lipid abnormality patients who presented with first episode of ACS were included observed in Indian population. It has been frequently associated after complying with the inclusion and exclusion criteria with other metabolic abnormalities. Lipid lowering trials for tri- following approval by the IEC. glycerides (TG) reduction have shown the beneficial effects of TG The diagnosis of ACS was done on the basis of Clinical presen- lowering interventions in cardiovascular risk reduction in high-risk tation, ECG changes and The extent of coronary artery disease modifiable group of trial subpopulation having high triglycerides was assessed by coronary angiography. (TG) and low HDL cholesterol. This paper deals with the prevalence On the basis of guidelines of the NCEP Adult Treatment of hypertriglyceridemia in high-risk modifiable group (HRMG) and Panel 3, Patients were divided into 3 categories based on its association with various risk factors; so that a potential benefi- their HDL cholesterol levels into Very low HDL (< 30mg/dl), cial intervention can be planned low HDL (30-39.9mg/dl), and normal HDL (>40 mg/dl). Methods: Study subjects (n¼ 1370) were recruited from the Phase 3 Biomarkers of inflammation in the study were Total counts, of the “Chennai Urban Rural Epidemiology Study”, an ongoing Albumin, hs-CRP. population-based study in Chennai, India. Biochemical analysis was

S73 Lipids/CV Health Endocrine Practice 27 (2021) S72eS75 done on a Hitachi 912 Auto analyser (Hitachi, Germany) using kits lumbar spine (L2-L4) to assess the bone mineral density and di- supplied by Boehringer Mannheim (Mannheim, Germany). High agnose osteoporosis. The women were then divided into two risk modifiable group (HRMG) was classified as TG levels 200 mg/ groups. Group 1 consisted of 55 women who had osteoporosis and dl & HDL cholesterol 40 mg/dl; while other study subjects have Group 2 consisted of the same number of women but without been classified as normal. Hypertriglyceridemia was classified as osteoporosis. A correlation between lipid profile and osteoporosis per NCEP ATP III Guidelines. Glycaemic group comprised of subjects was done in both the groups by using various statistical tests. with normal glucose tolerance (NGT), Impaired fasting glucose Results: The two groups showed no significant difference in the (IFG). impaired glucose tolerance (IGT), prediabetes group mean age, parity, BMI and menstrual years. Mean cholesterol and (IFG+IGT), newly detected as well as known diabetic subjects (DM LDL levels were significantly higher in Group 1 (women with group), all classified as per ADA guidelines. Statistical analysis was osteoporosis). The mean Triglyceride and HDL levels were also done by using SPSS software. higher in postmenopausal women with osteoporosis, though not Results: Nearly a quarter of study subjects (23.1 %) falls in HRMG statistically significant. When data were entered into the model of in Chennai Urban Rural Epidemiology Study (CURES) in South multivariate regression, it showed that elevated level of total Asian Indian population, with a gender wise distribution of 33.6 cholesterol was an independent risk factor for osteoporosis in % for males and 16.7 % for females. The category wise distri- postmenopausal women (p¼0.01). bution of TG levels in HRMG group was 9.1 % having borderline Discussion/Conclusion: Preventive measures can be instituted in high TG levels, 13.3 % has high TG levels and 0.7 % had very these women in the form of lifestyle modifications, diet and drugs high TG levels. In comparison to normal group, HRMG subjects so as to improve their quality. had significantly higher BMI, waist circumference, waist to hip https://doi.org/10.1016/j.eprac.2021.04.626 ratio, blood pressure, fasting, postprandial blood sugars, insulin resistance and HbA1c (P< 0.0001). Maximum prevalence of HRMG was observed in the age group of 30 to 39 years (41.1%). Abstract #1037562 With worsening glycaemia, prevalence of HRMG increased from 9% in NGT group, 22.2 % in prediabetes group (IFG+IGT) and 31.9 Effect of Glucose Level in the Frequency of % in DM group. Discordance Apo B-Low Density Lipoproteins (LDL) Discussion/Conclusion: Lipid lowering trials for triglyceride reduction have shown a beneficial effect of cardiovascular risk reduction in specific subpopulation of the trial, mentioned as High- Author Block: Hector Garcia-Alcala - Hospital Christus Muguerza Risk Modifiable Group (HRMG) in this study. As nearly a quarter of UPAEP; Maria Fernanda Garcia-Plata, MD - Co-Author, Medicine our population comes under HRMG, proper interventions must be Faculty, Universidad Anahuac Puebla; Juan carlos A. Marin-Corte, planned to reduce the cardiovascular disease burden in this MD - Co-author, Clinical patology, Laboratorios Clinicos de Puebla vulnerable group. Objective: Background: Apo B determination lets to know the https://doi.org/10.1016/j.eprac.2021.04.625 number of atherogenic particles and is a risk factor, probably as crucial as LDL determination. However, the effect of glucose level in the frequency of discordant results, low or average LDL with high Abstract #1003985 Apo B, is still unknown in our city Aims: Report the effect of glucose in the frequency of discordant Correlation of Lipid Profile with Bone Mineral Density results Apo B-LDL and Apo B levels. in Postmenopausal Women Methods: From our database (2016-2019), we analyzed the results from all patients with a simultaneous determination of total Author Block: sharikant sharma - SMS Medical college and cholesterol (TC), triglycerides(Tg), high-density lipoproteins (HDL), fi hospital jaipur INDIA; sunita Hemani Associate Professor - co- glucose, Hba1c, and Apo B, who attended our laboratory for the rst < author, Gynecology and obst., SMS Medical college; jyoti D. jain time. With these results, we calculated LDL (if TG 200 mg/dl: ¼ > ¼ senior registrar - co-author, Gynecology and obst., SMS Medical LDL (TG/5+HDL, if TG 200 mg/dl : LDL No-HDL-30). According college to their median, we divided LDL and Apo B into high (above) and low (below). We describe the frequency of discordant Apo B-LDL (Apo B high-LDL low) in the total sample and divided by glucose Objective: Menopausal women face multiple problems which level (Hba1c above and below 7%). A Pearson's correlation and adversely affect their mental and physical well being. They are simple linear regression were also performed. prone to develop diabetes, metabolic syndrome, dyslipidemia and Results: We studied 1736 patients, 55.8% women, mean age of osteoporosis. Osteoporosis is often diagnosed late when bone 55.83 years (SD 15.26, range 20-96). We found a positive correlation fragility is increased significantly and resulting fractures cause Apo B-Hba1c (r¼0.128 P< 0.05). The frequency of Apo B-LDL multiple complications. discordance was in total group : 6.7%, in Hba1c < 7% group : 5.8%, Aim- The study was aimed to examine the correlation of lipid and in Hba1c >7% group: 10.1% (p < 0.05 OR 2.05 (95% CI 1.32-3.1)). profile with bone mineral density in post-menopausal women. We found for every 1% increase in Hba1c there was an increase of Methods: This hospital based comparative and cross-sectional 1.83 mg/dl (CI 95% 1.2-2.6) of Apo B. study included 110 post menopausal women who fulfilled the in- Discussion/Conclusion: we found that discordance high Apo B - clusion and exclusion criteria. A proper history was taken and Low LDL is not an infrequent result, especially in those patients clinical examination done. Following this, lipid profile was done with high glucose levels. Apo B is now a significant part of car- after 12 hours of fasting and was considered abnormal if Choles- diovascular risk evaluation. terol was >200mg/dl; Triglycerides 150 mg/dl and HDL 50 mg/ dl. Then, Dual Energy X-Ray Absorptiometry was done at the https://doi.org/10.1016/j.eprac.2021.04.627

S74 Lipids/CV Health Endocrine Practice 27 (2021) S72eS75

Abstract #1041569 LDL-C, HDL, triglycerides, HbA1c, and 25-hydroxyvitamin D were recorded through an average four years after starting Cardiometabolic Risk Factors in Transgender GAHT. Multivariable mixed modelling was performed to Individuals Taking Gender-affirming Hormone determine change in each parameter over time after adjusting for Therapy Through Four Years covariates. Results: Among 129 patients, 60 (47%) were TF; 62% White, 12% Black, 8% Hispanic and 18% other/unknown. The median age was 26 Author Block: Samihah Ahmed - Northwell Health Lenox Hill; years [interquartile range (IQR) 18, 75]; 31 years for TF and 24 years 2 2 Nyein C. Swe, M.D. - co-author, Northwell Health /Lenox Hill; for TM. The median BMI was 25 kg/m (17, 47); 27 kg/m for TF (17, 2 Michael Frenkel, B.S. - co-author, Northwell Health /Lenox Hill; 47) and 25 kg/m for TM (17, 41). Patients were followed for a mean Karina Ziskovich, BBA, CCRC - co-author, Northwell Health /Lenox 48 ± 12 months. Hill; Tungming Leung, PhD - co-author, Northwell Health; Median values for the parameters at baseline for TF: LDL-C 81 Eugenia Gianos, M.D. - co-author, Cardiology, Northwell Health mg/dL (IQR 33, 165), HDL-C 50 mg/dL (25, 87), triglycerides 121 mg/ /Lenox Hill; Minghao Liu, M.D. - co-author, Endocrinology, dL (37, 643), HbA1c 5.5% (4.6, 15.5), 25-hydroxyvitamin D 24.4 ng/ Northwell Health /Lenox Hill; Aren H. Skolnick, D.O. - co-author, ml (9.3, 64.6). Median values for the parameters at baseline for TM: Endocrinology, Northwell Health; Leonid Poretsky, M.D. - co- LDL-C 103 mg/dL (36, 300), HDL-C 49 mg/dL (26, 85), triglycerides author, Endocrinology, Northwell Health /Lenox Hill; 95 mg/dL (33, 432), HbA1c 5.3% (4.5, 8.5), 25-hydroxyvitamin D Natalie E. Cusano, M.D. - co-author, PI, Endocrinology, Northwell 21.5 ng/mL (9, 92.9). Health /Lenox Hill There was a significant decrease in HDL over time in TM; for every year of GAHT, there was a 2.5% reduction in HDL (p¼0.03). fi Objective: There are limited long term data regarding cardiovas- There were no changes in HDL in TF. There were no signi cant cular safety in transgender individuals receiving gender affirming changes in BMI, LDL-C, triglycerides, HbA1c or 25-hydroxyvitamin hormone therapy (GAHT) with mixed changes noted in car- D levels over time in TM or TF. Discussion/Conclusion: fi diometabolic profiles. The aim of this study was to assess the effects Similar to prior studies, a signi cant of GAHT on cardiometabolic risk parameters over time among decrease in HDL was noted in TM on testosterone therapy. The fi transgender males (TM) and transgender females (TF). correlation of this nding with changes in diet and exercise while Methods: This was a retrospective study. Patients 18 years and on testosterone therapy and its clinical impact on cardiovascular older, identified as transgender and receiving GAHT at our endo- events will need to be further studied. There were no other changes crinology clinic were included. TM received testosterone while TF noted in cardiovascular parameters, which may be reassuring for received estradiol; patients received additional therapy as clinically patients and providers. Further long-term data are needed for pa- indicated. Genderqueer patients who received testosterone were tients receiving GAHT to assure that their long-term cardiovascular grouped with TM while those who received estradiol were grouped risk is optimized. with TF. https://doi.org/10.1016/j.eprac.2021.04.628

S75 Endocrine Practice 27 (2021) S76eS84

Contents lists available at ScienceDirect

Endocrine Practice

journal homepage: www.endocrinepractice.org

OBESITY/NUTRITION

Abstract #989896 p< 0.0001; Pbo -0.34 ± 1.04, p¼0.0097). Similarly, more subjects in the OSH group were in the lower risk NFS category at EOT Plenity® Treatment In The Gelesis Loss of Weight (p¼0.004) but not Pbo (p¼0.135). Amongst subjects who lost at (GLOW) Study Is Associated With Improvement In least 10% weight (n¼44 in OSH, n¼25 in Pbo), the absolute Liver Health, As Measured By The NAFLD Fibrosis Score mean change in NFS was greater for OSH (OSH -0.37 ± 0.80, p¼0.0037; Pbo -0.34 ± 0.98, p¼0.0955), and more subjects were in lower NFS category in OSH at EOT (p¼0.0143) but not Pbo Author Block: Christopher D. Still, DO, FACP, FTOS - co-author, (p¼0.2568). Overall safety and tolerability of OSH were similar Geisinger Commonwealth School of Medicine; Elaine Chiquette, to Pbo. PharmD - co-author, Gelesis, Inc; Bryan Jones, PhD - Primary Discussion/Conclusion: In this exploratory analysis of GLOW, OSH- author, Gelesis, Inc; Harry Leider, MD, MBA - co-author, Gelesis, induced weight loss resulted in a statistically significant reduction Inc; Frank L. Greenway, MD - co-author, Pennington Biomedical in NFS score. Research Center https://doi.org/10.1016/j.eprac.2021.04.630 Objective: Nonalcoholic fatty liver disease (NAFLD) prevalence is >50% in people with obesity, and weight loss remains the corner- Abstract #995159 stone treatment. The Gelesis Loss of Weight (GLOW) study inves- fi ® tigated the ef cacy and safety of Gelesis100 (Plenity ), an orally Individualized Anti-obesity Pharmacotherapy Enhances administered superabsorbent hydrogel (OSH), previously shown to Weight Loss in Patients with Diabetes Mellitus Type 2 elicit meaningful weight loss compared to placebo. This exploratory analysis examined the impact of OSH treatment on liver health as measured by the NAFLD fibrosis score (NFS), which predicts the Author Block: Maria Daniela Hurtado Andrade, M.D., Ph.D. - presence of significant fibrosis using common clinical and labora- Primary Author and Presenter, Endocrinology, Diabetes, tory values. Metabolism and Nutrition, Mayo Clinic; Maria L. Ricardo Silgado, Methods: Of the 436 subjects originally enrolled in the 24-week, M.D. - co-author, Gastroenterology and hepatology, Mayo Clinic; randomized, double-blind placebo controlled study, 317 with gerardo Calderon, M.D. - co-author, Internal Medicine, Indiana complete pre-post data were included in this analysis. NFS was University; Alison McRae, M.S. - co-author, Gastroenterology and categorized as either higher (combining intermediate and high hepatology, Mayo Clinic; Andres Acosta C, M.D., Ph.D. - co-author, scores; i.e. score -1.45) or lower (score < -1.45) probability of liver Gastroenterology and hepatology, Mayo Clinic fibrosis. The absolute and categorical scores were calculated at baseline and 6 months for 1) the entire cohort, 2) subjects with Objective: Obesity is among the most important risk factors for prediabetes or diabetes at baseline (DM) and 3) subjects who lost type 2 diabetes mellitus (DM2), hence the term “diabesity”. The 10% weight. 2 OSH and 1 Pbo subjects with NFS > 3 SD from the prevalence of “diabesity” is increasing rapidly and has become a overall mean were excluded. Paired sample t-test was used for public health crisis. Modest weight loss with lifestyle interventions within subject treatment responses, ANCOVA was used for all other results in improved DM2 control. Because sustained weight loss parameters. with lifestyle interventions is challenging, there has been an Results: At baseline, 90/168 (53.6%) subjects in the OSH and 80/ increased need to develop more effective anti-obesity treatment 149 (53.7%) in the placebo (Pbo) had NFS in the higher proba- modalities. Recently, we proposed a classification of obesity based bility for fibrosis category (p¼0.98). More subjects in the OSH on pathophysiological and behavioral phenotypes: 1) abnormal group were in the lower probability risk category (p¼0.016) at satiation, 2) abnormal postprandial satiety, 3) emotional eating, the end of treatment (EOT), while no difference was observed in and 4) abnormal resting energy expenditure. Previous research has Pbo (p >0.99). In the overall cohort, a statistically significant shown that these phenotypes can be targeted pharmacologically to reduction in the absolute mean change in NFS within OSH group enhance weight loss. Phenotype-guided approach was associated occurred (-0.15 ± 0.90; p¼0.030), but not the Pbo (0.02 ± 0.85; with greater weight loss after 12 months: 15.9% vs. 9.0% in the non- p¼0.824). The difference between groups was significant phenotype-guided group. The aim of this study was to assess the (p¼0.043). In the subgroup with DM (n¼64 OSH; n¼65 Pbo), effect of obesity phenotype-guided pharmacotherapy in patients both groups significantly reduced NFS (OSH -0.53 ± 0.88, with “diabesity”.

1530-891X Obesity/Nutrition Endocrine Practice 27 (2021) S76eS84

Methods: This was a subgroup analysis of a 12-month pragmatic pharmacists, and diabetes care and education specialists. Par- trial. A total of 450 participants were phenotyped based on body ticipants in the intervention group met individually with a composition, resting energy expenditure, satiety, satiation, eating member of the care team at each visit to discuss progress and behavior, affect and physical activity. After phenotyping, patients set specific goals.Eleven participants in the control group were randomly assigned to phenotype-guided treatment or non- received the standard of care. The outcomes were based on phenotype-guided treatment with anti-obesity medications: body weight, height, and body fat percentage measured at the phentermine, phentermine/topiramate, bupropion/naltrexone, initial and final visits. Attendance was tracked at each visit. lorcaserin and liraglutide. The primary outcome, percentage of participants who lost 5% Results: A total of 450 patients were phenotyped. Eighty eight of initial body weight, was analyzed using the Fisher's exact patients (20%) had DM2 (mean age 51±2.6 years, 59% female, test. Secondary outcomes were analyzed using the t-test. BMI 43.4 kg/m2, mean HbA1c 7.1±0.3%). 21/88 (24%) patients Results: With regard to the primary outcome, 36.7% of par- were treated with phenotype-guided therapy, and the rest, 67/ ticipants in the intervention group lost 5% of body weight 88 (76%), were treated with non-phenotype-guided therapy. At compared with 16.7% in the control group, but this finding baseline, the two groups had comparable demographic char- was not statistically significantly (P ¼ 0.37). The differences acteristics. Importantly, the non-phenotype-guided therapy between the two groups with regard to secondary outcomes group had a higher baseline HbA1c (7.7% versus 6.5%, were change in body weight from baseline (-6.24 kg, P¼0.02), p¼0.008) and thus patients in this group were more likely to percentage of body weight lost (-5.76%, P¼0.03), change in be treated with liraglutide (60% versus 37%, p¼0.004). Weight BMI (-2.08 kg/m2, P¼0.02) and change in body fat percentage loss at 6 and 12 months was significantly higher in the (-0.32%, P¼0.19). Attendance to the visits did not appear to phenotype-guided therapy group compared to the non- affect the outcomes. phenotype-guided therapy: 9.7±1.4% vs. 5.3±0.7% (p¼0.01) at 6 Discussion/Conclusion: A 6-month shared medical appointment months and 12±1.7% vs. 6.3±1.0% (p¼0.009) at 12 months. intervention provided by an interdisciplinary care team may be There was no difference in the incidence of adverse events beneficial for weight loss in patients with obesity. Several sec- among the two groups. ondary endpoints were statistically and clinically significant. The Discussion/Conclusion: Obesity phenotypes based on biological intervention group lost more weight, lost a higher percentage of and behavioral traits elucidate human obesity’s heterogeneity. body weight overall, and had a larger reduction in BMI In this study, phenotype-guided pharmacotherapy was asso- compared with the control group. Although the primary ciated with a higher weight loss in patients with DM2. Higher endpoint was not statically significant, twice as many partici- weight loss would benefitDM2controlatagreaterextent. pants lost 5% of their body weight compared with the control Long term, this greater weight loss could result in a cost- group, and all participants in the intervention group lost weight effective therapeutic modality in patients with “diabesity”. by the end of the study. Had the sample size been larger, the primary outcome could possibly have been significant as well, https://doi.org/10.1016/j.eprac.2021.04.631 but more research is needed to determine whether or not this is true. It is unknown to the researchers why attendance at the Abstract #996428 visits did not affect the outcomes. Perhaps being part of the intervention group offered a level of motivation and account- Shared Medical Appointments for Weight Loss ability that persisted, despite missed visits, resulting in signifi- cant weight loss in some participants.

https://doi.org/10.1016/j.eprac.2021.04.632 Author Block: Rachel Franks, PharmD, BCACP, CDCES - Primary Author, University of South Florida; Olivia Pane, PharmD, CDCES - Co-author, Family Medicine, University of South Florida; Abstract #997302 Crystal Jacovino, DO - Presenter, General Internal Medicine, University of South Florida; Jerry Brown, DMD, CDCES - Co-author, Real-world Effectiveness of Digital Therapeutics General Internal Medicine, University of South Florida; Towards Achieving Weight Loss in People With Derek Balazy, PharmD Candidate - Co-author, University of South Obesity and Metabolic Syndrome Florida; Ronald Alvarez Martinez, PharmD Candidate - Co-author, University of South Florida; Lucy Guerra, MD, MPH - Co-author, General Internal Medicine, University of South Florida Author Block: Rishi Adhikary - Wellthy Therapeutics Pvt. Ltd; Siddhesh Kolwankar, MD, MHA, MSMIT - Presenter, Wellthy Objective: Obesity rates have risen drastically over the past few Therapeutics Pvt. Ltd; Ritika Verma, BTech, MTech, PhD - Co- decades. More than one-third of adults in the United States are author, Wellthy Therapeutics Pvt. Ltd; Saipranoti Pawar, MSc, RD - obese. The objective of this study was to develop an innovative Co-author, Wellthy Therapeutics Pvt. Ltd; Ratika Agarwal, BTech, model of care utilizing shared medical appointments to assist obese MTech - Co-author, Wellthy Therapeutics Pvt. Ltd; patients with weight loss. Bhargavi M. Naidu, BSc, PGDFST - Co-author, Wellthy Therapeutics Methods: This randomized controlled trial included 23 partic- Pvt. Ltd; Jitesh Bhatt, MBBS, MCGP - Co-author, Wellthy ipants between the ages of 18-74 years with a BMI 30 kg/m2. Therapeutics Pvt. Ltd; Banshi Saboo, MD, MSc , DNB, PhD, FRCP, Twelve participants in the intervention group participated in FACE - Co-author, DiaCare - Diabetes Care & Hormone Clinic 90-minute group visits occurring weekly for 4 weeks, then biweekly for the remainder of 26 weeks and a total of 15 Objective: Obesity is a serious public health concern and a major visits. Each visit focused on intensive lifestyle changes and risk factor for metabolic syndrome, type 2 diabetes mellitus and behavioral therapies. The sessions were conducted by an various cardiovascular diseases. In the present study, we assess the interdisciplinary care team consisting of physicians, clinical real-world effectiveness of a digital therapeutic in influencing

S77 Obesity/Nutrition Endocrine Practice 27 (2021) S76eS84 lifestyle modification to encourage weight loss in patients with Methods: A twenty-three-question survey was administered to obesity and metabolic syndrome. patients (N¼220) with a BMI (kg/m2) 25 that attended an Methods: Wellthy CARE™ Digital Therapeutics (WDTx) Platform endocrinology office encounter at a community-based practice consists of a smartphone application with a 52-week lifestyle location of a large integrated healthcare delivery system (9/1/2019- modification program. It enables artificial intelligence (AI)- 11/30/2019). Continuous variables were summarized using mean ± augmented tracking of health outcomes while providing evidence- SD and categorical variables using N (%). Bivariate analysis was based curated content and personalized remote human health performed using the Chi square test and the Fisher's exact test to coach support. The program is directed towards providing real- determine associations between study variables. time AI- and human-supported guidance on weight, meals, physical Results: The mean age (years) of patients was 53.7 ± 15.1, and the activity, blood sugar, blood pressure, lipid profile and other health majority identified as female (62.3%) and Caucasian (89.1%). The parameters. In the present study, WDTx users who reported a majority of patients (69.1%) reported that their endocrinologist baseline body mass index (BMI) of at least 23 kg/m2 were included. talked about nutrition for a total of 1-3 times (33.2%). Presence of Further subclassification of overweight, obese class I, and obese overweight (BMI 25-29.9), obesity (BMI 30) and diabetes mellitus class II was based on the WHO classification for Asian Adults (2000) (DM) were queried and reported in 42.3%, 37.7% and 48.2%, while the definition of metabolic syndrome was based on the respectively. Patients with overweight or obesity with DM were Consensus Statement for Diagnosis in Asian Indians (2009). The more likely to have seen a registered dietitian (RD) (61.5%) than change in weight and BMI was observed in users as compared to patients with overweight or obesity without DM (34.2%) (P¼< baseline. 0.001). Of the patients with overweight or obesity with DM, 66.2% Results: The present study included 196 users on the WDTx plat- reported having seen a certified diabetes educator. Patients with form (mean age 46.1 years, SD 11.9 years) comprising 38 females overweight or obesity with DM were more likely to attend SMA (19.4%). Amongst all users, there was a significant mean reduction (16.7%) than patients with overweight or obesity without DM (5.1%) in body weight by 1.9 kg (95%CI 1.2-2.7 kg, p< 0.0001) with a cor- (P¼0.003). responding mean reduction in BMI of 0.7 kg/m2 (95%CI 0.4-1.0 kg/ Discussion/Conclusion: Nutrition education appears to be m2,p< 0.0001). The average app interactions recorded per user was underutilized in patients with overweight or obesity, especially 418 over the entire program duration, with the quartile of users among patients without concomitant DM. This is likely, in part, having the highest app interactions showing 2.5 times higher because referral to RDs for patients with overweight or obesity reduction in body weight as compared to users in the lowest (particularly those without DM) is often met with barriers such as quartile. The mean reduction of body weight in users who were lack of insurance coverage as well as providers' under-recognition overweight at baseline was 1.4 kg (n¼44, 95%CI 0.1-2.7 kg, p< of overweight and obesity as chronic medical conditions that 0.0001), in those who were obese class I at baseline being 1.8 kg warrant such interventions. More frequent and thorough discus- (n¼97, 95%CI 0.8-2.8 kg, p< 0.0001) and for those who were obese sions between patients and providers about nutrition, increased class II being 2.6 kg (n¼55, 95%CI 0.8-4.4 kg, p< 0.0001). Among 37 formal nutrition training for providers without nutrition back- patients who were diagnosed with metabolic syndrome, it was grounds, and more consistent RD referrals could help to improve found that the mean reduction in weight was 2.7 kg (95%CI 1.4-3.8 health outcomes and facilitate more sustainable lifestyle changes. A kg, p< 0.0001) with a corresponding mean BMI reduction by 0.9 kg/ tremendous opportunity exists to provide nutrition education to m2 (95%CI 0.5-1.4 kg/m2,p< 0.0001) and with average app in- patients with overweight or obesity both with and without DM. teractions of 734 per user over the entire duration of the program. Providing adequate nutrition education to such patients is a critical Discussion/Conclusion: This study demonstrates the real-world component of treatment. Endocrinology providers are well posi- effectiveness of the Wellthy CARE™ Digital Therapeutics (WDTx) tioned to ensure this patient population is identified and referred platform in achieving weight loss and thus reducing the risk of for appropriate interventions. comorbidities amongst people with obesity and metabolic https://doi.org/10.1016/j.eprac.2021.04.634 syndrome. https://doi.org/10.1016/j.eprac.2021.04.633 Abstract #1002595

Abstract #1002272 Anorexic Girl Presenting with Severe Bradycardia and Amenorrhea: A Serious Presentation of a Medical Patient Nutrition Awareness: Survey of a Community- Condition based Endocrinology Practice

Author Block: Sajjad Ali Khan - Aga Khan university hospital, Author Block: Bhakti Chavan, MBBS, MPH - Co-author, Ohio Karachi, Pakistan; Zafar a. Suchal, n/a - Co-author, Medicine, Aga University Heritage College of Osteopathic Medicine, Ohio, USA; Khan University Hospital; Muhammad M. Mehdi Khan, n/a - Co- Kevin M. Pantalone, DO, ECNU, FACE - Co-author, Department of author, Medicine, Aga Khan University Hospital; asma ahmed Dr - Endocrinology, Cleveland Clinic, Cleveland, Ohio, USA; Co-author, Medicine, Aga Khan University Hospital Kristen T. Ruckstuhl, MS - Primary author, Ohio University Heritage College of Osteopathic Medicine, Ohio, USA Introduction: Anorexia Nervosa is an eating disorder presenting low weight in patients with a fear of gaining weight leading to Objective: To assess nutrition awareness among patients seen by an restriction of intake. Patients with this disorder have a strong desire endocrinology provider and to evaluate referral patterns to nutri- to stay thin, with the psychological stress and nutritional deficiency tion specialists and the utilization of group-based interventions in such patients the symptoms can vary with patients often being such as shared medical appointments (SMA). difficult to diagnose.

S78 Obesity/Nutrition Endocrine Practice 27 (2021) S76eS84

Case Description: A 22-year-old lady presented in the tertiary early administration, but use is not feasible in large inpatient care hospital of Karachi, Pakistan with complaints of loose numbers. motions for two days. At the time of presentation, her blood Vitamin D regulates expression of approximately 11,000 genes pressures were 90/50 mmHg, and despite the low B.P she had spanning many physiologic functions that include regulation of a heart rate of 40 beats /minute, and had the BMI of 14.3 both innate and adaptive immune function, pulmonary cytokine kgm-2. According to the patient, she had her menarche at the release, and induction of autophagy as an immune defense. Hos- age of thirteen years and her menstrual cycle had been pitalized and severely ill patients exhibit high rates of vitamin D completely normal until four months back when it suddenly deficiency. Activation of vitamin D-dependent pathways may pro- stopped. The patient had an amenorrheic since then. The vide clinical benefit to patients with SARS-CoV-2 infection. We patient’s attendant reported a history of weight loss in the investigate potential benefit of calcitriol therapy given to patients patient with a gradual and progressive weight loss of 25 kg hospitalized with COVID-19. in the past 6 months with normal appetite but doing Methods: This is an open label, randomized clinical trial of calcitriol excessive exercise under the peer pressure of looking smart or no treatment given to hospitalized adult patients with COVID19. and healthy. Initial ECG was consistent with sinus brady- Subjects were randomly assigned treatment with calcitriol 0.5 mcg cardia. Further workup revealed that her FSH, LH, and free T4 daily for 14 days or hospital discharge; or no treatment (1:1) at time were reduced. of enrollment. The remainder of treatment was per hospital pro- Treatment course: She was initially kept inward to monitor her tocol and may include remdesivir, dexamethasone, as well as blood pressures with the fluid being given. Dopamine was started supplemental 02. for the symptomatic bradycardia which was tapered off and The primary end point was length of stay. Secondary endpoints stopped later on. After an interview with the patient and her family, include the need for ICU, need for oxygen step up therapy, death, a diagnosis of anorexia nervosa was reached with the patient being and hospital readmission. Patients were excluded if they are started on SSRI treatment. Thyroxine in the low dose was also given admitted directly to the ICU, if they had hypercalcemia, hyper- to bring FT4 to the normal range. phosphatemia on admission, if they had disorders of calcium Discussion: Patient Vitamin B12 was 179 pd/ml (N¼ greater than metabolism, chronic renal insufficiency with glomerular filtration 201 pg/ml), Hemoglobin 11.2g/dl, Calcium 8.6 mg/dl (8.6-10.2), rate < 30 ml/min, or if they are prescribed calcitriol for any reason Thyroid stimulating hormone (TSH) 0.950 uIU/ml (N-0.4-4.2), free outside of the study. T4 (FT4) 0.85 ng/dl (N-0.89-1.76), free T3 (FT3) 1.20 pg/m ( N-l2.1- Results: We enrolled 50 consecutive patients, 25 per trial arm. The 4.4), luteinizing hormone (LH) < 0.07 mIU/ml , follicle stimulating average length of stay was 5.5 (± 3.9) days in the calcitriol group hormone (FSH) 1.07 mIU/ml, Estradiol < 11.80 pg/ml, and folate of compared to 9.24 (± 9.4) in the control group (p¼ .39). The need for 4.78 ng/ml (2.6-12.2). ICU transfer was 8 in the control group and 5 in the calcitriol group. Conclusion: Anorexia nervosa can have a profound impact on There were 3 deaths and 4 readmissions in the control group and endocrine organs. Long-term anorexia can lead to disruption of the 0 deaths and 2 readmissions in the calcitriol group. When hypothalamus-pituitary axis (HPA) and can lead to amenorrhea. comparing the oxygen saturation (sa02/Fio2 ratio) on admission These patients can have thyroid dysfunction which can lead to and discharge between the groups the control group had an diagnostic confusion. Most of the endocrinal disorders improve average increase of +3 on discharge and the calcitriol group had an with nutritional support. increase of +22.8. Peer pressure can lead to adopting an unhealthy lifestyle with Discussion/Conclusion: This pilot study illustrated the potential for dire consequences. A thorough history is very important in calcitriol use in the treatment of COVID-19 and illustrates the need assessing such patients. for a larger randomized clinical trial. Promising results included the length of stay and improvement in oxygenation. Multiple potential https://doi.org/10.1016/j.eprac.2021.04.635 mechanisms through activation of vitamin D responsive pathways warrant further study.

Abstract #1002919 https://doi.org/10.1016/j.eprac.2021.04.636

Endocrine Therapy for COVID19: A Randomized Pilot Study Using Calcitriol Abstract #1003244

The Weight of Time: Achievements and Challenges of a Author Block: Yasmine Elamir - Mount Sinai Beth Israel, Mount Physician-Led Weight Loss Program in a Primary Care Sinai St Lukes, Mount Sinai West; Hajira Amir, MD - co-author, Setting Mount Sinai Beth Israel; Natalia Feliciano, MD - co-author, Mount Sinai Beth Israel; Carolina Gonzalez, MD - co-author, Mount Sinai Beth Israel; William Grist, MD - co-author, St Joseph's University Author Block: Aleksandra Sliwinska - University of Connecticut; Medical Center; Steven Lim, MD - co-author, Mount Sinai Beth Srinath Ramanan, BS - co-author, University of Connecticut School Israel; Ali Omar, MD - co-author, Mount Sinai Beth Israel; Of Medicine; Varalakshmi Niranajan, MD - co-author, University of Yesha Patel, MD - co-author, Mount Sinai Beth Israel; Michael Via, Connecticut; Helen Wu, PhD - co-author, University of MD - co-author, Mount Sinai Beth Israel Connecticut; Fufei Chen, BS - co-author, University of Connecticut; Narinder Maheshwari, MD - co-author, University of Connecticut Objective: The systemic illness associated with SARS-CoV-2 infection results in hospitalization rate of 380.3 hospitalizations Objective: Obesity is a complex condition with multiple asso- per 100,000 population, overwhelming health care systems. ciated comorbidities. Evidence suggests that 5-10% weight loss Some emerging therapies demonstrate modest benefits with has a significant reduction in metabolic complications. With

S79 Obesity/Nutrition Endocrine Practice 27 (2021) S76eS84 limited resources in the primary care setting, efficient coun- University, Chicago, IL, USA; Soo Lim, MD - co-author, Department seling and comprehensive approach at a routine visit can be of Internal Medicine, Seoul National University College of challenging. Referral to a specialized weight loss program may Medicine, Seoul National University Bundang Hospital, Seongnam, result in early intervention, better compliance, and a higher South Korea; Ildiko Lingvay, MD, MPH, MSCS - co-author, success rate. Our program (one day/week) is led by an obesity- Department of Internal Medicine/Endocrinology and Department board certified physician in a primary care setting. Our aim of Population and Data Sciences, University of Texas Southwestern was to examine the effectiveness of a specialized weight loss Medical Center, Dallas, TX, USA; Ofri Mosenzon, MD - co-author, clinic in a primary care setting and validate the current Diabetes Unit, Department of Endocrinology and Metabolism, obesity care model. Hadassah Medical Center, Faculty of Medicine, Hebrew University Methods: We analyzed medical records from patients with a of Jerusalem, Jerusalem, Israel; Signe O. Wallenstein, MSc - co- Body Mass Index (BMI) >29 kg/m2 and aged 18 years and over, author, Novo Nordisk A/S, Søborg, Denmark; Thomas A. Wadden, from Oct 2018 to Jan 2021, in University-based primary care PhD - co-author, Department of Psychiatry, Perelman School of with a weight loss program (one day/week). Reported Medicine, University of Pennsylvania, Philadelphia, PA, USA; comorbidities included pre-diabetes, diabetes, hypertension, Carel W. Le Roux, PhD - co-author, Diabetes Complications hyperlipidemia, cardiovascular disease, sleep apnea, arthritis, Research Centre, Conway Institute, University College Dublin, malignancy, depression, and PCOS. Weight loss interventions Dublin, Ireland included motivational interviewing, dietary and exercise counseling, behavioral training, and pharmacotherapy to treat Objective: To assess weight loss (WL) with once-weekly subcu- obesity and underlying metabolic dysfunction. Outcomes were taneous (s.c.) semaglutide 2.4 mg plus intensive behavioral therapy assessed based on percentage weight change during a time (IBT) in STEP 3 according to participants’ baseline characteristics period of two consecutive visits less than 90 days. Descriptive and weight history (post-hoc analysis). analyses were reported, and chi-square or t-test were per- Methods: STEP 3 was a double-blind phase 3 trial formed when appropriate. (NCT03611582). Adults (N¼611) with overweight/obesity, Results: Among 300 enrolled patients with a mean age of 48 without type 2 diabetes, were randomized 2:1 to IBT, plus years about 51% (n¼158) visited the clinic once, 31% (n¼93) 2- once-weekly s.c. semaglutide 2.4 mg or placebo, for 68 weeks. 3times,8%(n¼23) 4-5 times and 9% (n¼26) 5 times or more. Distribution of WL was evaluated as intervals of categorical Patients with 2-3 visits had 2.2 comorbid conditions; those WL at week 68 (20%, 15e< 20%, 10e< 15%, 5e< 10%, < 5%). with 4-5 visits had 2.6 comorbid conditions and patients with Mean percent WL at week 68 was analyzed by baseline 5 or more visits had 2.6 comorbidities. We found that 57.7%, characteristics (sex [male, female], age [18e< 65, 65 years], 43.3% and 16.1% patients who attended the clinic 5 or more race [White, other], ethnicity [Hispanic or Latino, not Hispanic times, 4-5 times, 2-3 times respectively achieved 5% weight or Latino], body weight [< 90, 90e< 100, 100e< 115, 115 kg]) loss (p < 0.0001).Itwasalsofoundthat42.3%,8.7%,and4.3% and weight history (collected using a self-report question- of patients who attended the clinic 5 or more times, 4-5 naire; age of onset [11, 18 years], maximum pretrial-to- times, and 2-3 times respectively achieved 10% weight loss (p baseline weight [0, >0e5, >5 kg], number of times losing 5 < 0.0001). Moreover, 60% of patients achieved 5% of weight kg [0, 1e2, 3e5, 6], overweight/obesity among 1st-degree loss in about 200 days, and 40% achieved 10% weight loss in relatives); for each parameter, a mixed model for repeated about 350 days. measurements was used, with treatment and subgroup vari- Discussion/Conclusion: Our analysis demonstrated that an effec- ables and the interaction between these as factors and base- tive physician-led weight loss program can be created in a primary line body weight as a covariate, all nested within visit. care setting to achieve 5-10% weight loss. Patients who stay longer Analyses were based on the trial product estimand (treatment in follow-up have a higher chance of success. Ongoing education effect assuming treatment adherence and without rescue and positive reinforcement may improve follow-up rates. A intervention) for the on-treatment period and were not comprehensive approach, including pharmacotherapy, can be adjusted for multiplicity. implemented in the primary care setting meeting current practice Results: Participants had a mean age of 46 years, body weight guidelines. 105.8 kg, body mass index 38.0 kg/m2, and 81.0% were female. The distribution of participants across the weight-history https://doi.org/10.1016/j.eprac.2021.04.637 subgroups was similar for semaglutide and placebo. The observed proportions of participants with 20%, 15e< 20%, e< e< < Abstract #1003901 10 15%, 5 10%, and 5% WL at week 68 were 38.6% vs 4.3%, 21.0% vs 8.5%, 19.8% vs 14.6%, 10.5% vs 22.6%, and 10.2% Once-Weekly Subcutaneous Semaglutide 2.4 mg Plus vs 50.0% with semaglutide vs placebo, respectively. Across the Intensive Behavioral Therapy Produces Clinically weight-history subgroups, semaglutide treatment resulted in Meaningful Weight Loss in Adults with Overweight/ 15.9e18.8% WL at week 68 and 2.7e7.6% with placebo. Mean Obesity Regardless of Baseline Characteristics and percentWLatweek68wassignificantly greater with sem- Weight History aglutide vs placebo in all baseline-characteristic and weight- history subgroups (all p< 0.01). There were no significant subgroup interactions for any parameter analyzed (interaction Author Block: W. Timothy Garvey - University of Alabama at p >0.05 for all). Birmingham; Dan Hesse, PhD - co-author, Novo Nordisk A/S, Discussion/Conclusion: In STEP 3, clinically relevant, significant Søborg, Denmark; Anna Koroleva, MD - co-author, Novo Nordisk A/ WL occurred with once-weekly s.c. semaglutide 2.4 mg vs S, Søborg, Denmark; Robert F. Kushner, MD - co-author, Division of placebo (both with IBT) in all subgroups evaluated. Weight Endocrinology, Feinberg School of Medicine, Northwestern history and baseline characteristics had no significant effects

S80 Obesity/Nutrition Endocrine Practice 27 (2021) S76eS84 on WL with semaglutide, suggesting potential benefits of Discussion: Although secondary causes of obesity are uncommon, this treatment for a wide range of people with overweight/ they should be considered and ruled out. Many patients with severe obesity. obesity do not undergo work up for secondary causes prior to un- dergoing bariatric surgery. Severe unremitting postoperative https://doi.org/10.1016/j.eprac.2021.04.638 weight gain or low percentage of excess weight loss should not always be attributed to noncompliance or surgical failure, and ’ Abstract #1003975 secondary causes such as Cushing s syndrome should be considered. ’ Cushing s Syndrome: A Secondary Cause of Obesity https://doi.org/10.1016/j.eprac.2021.04.639 and Weight Regain After Bariatric Surgery

Abstract #1004191 Author Block: Sabrina Meftali Endocrinology Fellow - Primary author, ST LUKES HOSPITAL; Rebecca Unterborn, Medical Association of CYP1A2, IL-6, and FTO Genetic Student - Co-author, ST LUKES HOSPITAL; Polymorphisms With Weight Loss Response Following mrunalini Deshmukh Endocrinology Attending - Co-author, ST a Low Carbohydrate Diet (LCD), Prospective Study. LUKES HOSPITAL

Introduction: Bariatric surgery has gained wide acceptance as a Author Block: Hazem Ayesh - University of Toledo; Sajida Ayesh, treatment for severe obesity. It can be expected that 20e25% of the MD - co-author, Gene Medical Labs; Suhail Ayesh, PhD - co-author, weight lost after bariatric surgery will be regained over a 10-year Gene Medical Labs period. Weight regain is often related to noncompliance with di- etary and lifestyle instructions, and occasionally to surgical failure. Objective: Many studies reported that FTO genetic poly- Excessive weight regain can be related to an undiagnosed morphism is associated with body mass index (BMI), meta- secondary cause of obesity. We present a rare case of weight regain bolic syndrome (MS), and type 2 diabetes mellitus (DM2). after bariatric surgery secondary to underlying Cushing's CYP1A2 is associated with caffeine metabolism and suscepti- syndrome. bility to DM2. IL-6 genetic polymorphism is associated with an Case Description: A 51-year-old female with morbid obesity, increased risk for developing obesity-related metabolic disor- hypertension, type 2 diabetes, and ambulatory dysfunction ders such as hypertension, dyslipidemia, and insulin resis- was first seen in clinic in 2018 for uncontrolled diabetes. She tance. In this study, we will investigate the association underwent gastric sleeve surgery in 2015. She lost 80 pounds between weight loss and FTO, CYP1A2, and IL-6 genetic but regained 50 pounds, which was attributed to poor polymorphisms. compliance with diet and physical activity. Review of her re- Methods: A random sample of 79 subjects with BMI 25 started on cordsshowednopreviousworkupforsecondarycausesof LCD (daily glucose intake < 150 g) and followed up for six months. obesity prior to her surgery. Her diabetes and hypertension All Subjects genotyped for FTO rs9939609, CYP1A2 rs762551, and were uncontrolled despite multiple medications. She devel- IL-6 rs1800795 SNPs. Triglyceride level (TG), Total cholesterol (TC), oped worsening ambulatory dysfunction that was attributed to and fasting blood sugar (FBS) levels are obtained for all subjects. spinal stenosis. Careful review of systems revealed skin thin- Linear regression analysis controlled for age and BMI performed to ning, easy bruising and worsening proximal weakness. Two evaluate the effect of these genetic polymorphisms on the weekly 24-hour urine free cortisol were elevated to 122 and 224 mcg/ weight loss rate. 24h (6-42 mcg/24h). Morning cortisol after 1 mg dexametha- Results: CYP1A2 minor allele frequency negatively correlated with sone suppression test was 14 mcg/dl (< 1.8 mcg/dl). Midnight weekly weight loss rate (P ¼ 0.04). Homozygous FTO variant salivary cortisol was elevated on 3 consecutive days: 0.55 mcg/ showed a slower weekly weight loss rate when compared with the dl, 0.41mcg/dl, 0.55 mcg/dl (< 0.01-0.09 mcg/dl). ACTH was normal FTO variant group (P ¼0.044). IL-6 minor allele frequency 50.7 pg/ml (7.2-63.3 pg/ml). Prolactin, IGF, FSH, LH, TSH, free didn’t show a statistically significant difference in weekly weight T4 and DHEA-S were all normal. Patient was diagnosed with loss rate (P¼0.135). No statistically significant association between ACTH dependent Cushing’s syndrome. Old records showed a TG, FBS, and TC levels and CYP1A2, FTO, and IL-6 genetic 2.7 cm left adrenal nodule on abdominal CAT scan. Pheo- polymorphisms. chromocytoma was excluded and repeat imaging showed a Discussion/Conclusion: CYP1A2 and FTO genetic polymorphisms stable adenoma. Pituitary magnetic resonance imaging (MRI) showed a statistically significant association with the weekly showed a homogeneous gland with a normal size; but review weight loss rate in response to LCD. These results support the ev- of images showed fullness of the gland on the right side. MRI idence of genes-diet interaction. with 3D and dynamic sequences revealed 2 small areas of Further larger studies such as RCTs are required to confirm the relative hypo enhancement in the right aspect of the gland. association between FTO and CYP1A2 genetic polymorphisms and Patient underwent inferior petrosal sinus sampling that the response to LCD. There is an increase in LCD popularity in the showed lateralization to the right side. She underwent suc- last years, so these results provide a more personalized approach cessful transsphenoidal surgery for pituitary adenoma resec- for LCD. tion. Immunohistochemistry stain was positive for ACTH. She These study results showed a statistically significant association was initially on maintenance dose Hydrocortisone that was between CYP1A2 and FTO genetic polymorphism and weight loss tapered slowly and then stopped. 24-hour urine cortisol has response to LCD, further high-quality studies are required to normalized. She lost 50 pounds. There was slow improvement confirm this association. in ambulatory dysfunction and drastic improvement in dia- betes and blood pressure control. https://doi.org/10.1016/j.eprac.2021.04.640

S81 Obesity/Nutrition Endocrine Practice 27 (2021) S76eS84

Abstract #1004241 L-Carnitine needs to be considered in patients with heredity myopathy syndromes.

Oculocerebrorenal Syndrome (Lowe Syndrome) https://doi.org/10.1016/j.eprac.2021.04.641 Associated With Proteinuria due to Congenitally Reduced Nephron Number and Persistent Weight Loss Successfully Managed With ACE Inhibition and Abstract #1004271 L-Carnitine The Effect of Short-term Energy Restriction on Appetite

Author Block: Josephine Moyo - St. Luke's University Hospital Network; Richard W. Snyder, DO. - co-author, Internal Medicine, St. Author Block: Chinelo C. Okigbo, MD, PhD - Primary author, Luke's Anderson Division of Endocrinology and Metabolism, University of North Carolina Chapel Hill, Chapel Hill, NC, USA; Clinical Research Introduction: Oculocerebrorenal Syndrome (Lowe Syndrome) is Branch, National Institute of Environmental Health Sciences, a rare congenital abnormality characterized by developmental NIH, Research Triangle Park, NC, USA; Joselyne Tessa Tonleu, delay, hypotonia, cataracts, and renal abnormalities including BS - Co-author, Clinical Research Branch, National Institute of Fanconi’s syndrome and tubular proteinuria. The mechanism Environmental Health Sciences, NIH, Research Triangle Park, NC, of proteinuria and subsequent renal decline in the second USA; Skand Shekhar, MD - Co-author, Clinical Research Branch, decade of life is thought to be due to secondary glomerulo- National Institute of Environmental Health Sciences, NIH, sclerosis because of persistent tubular proteinuria. We present Research Triangle Park, NC, USA; Helen F. Leka, BS - Co-author, a patient with Lowe Syndrome in which the proposed mech- Clinical Research Branch, National Institute of Environmental anism of proteinuria and chronic kidney disease may be due Health Sciences, NIH, Research Triangle Park, NC, USA; to hyperfiltration because of congenitally reduced nephron Anne E. Kim, MD - Co-author, Clinical Research Branch, National number. In addition, the patient had an inability to gain Institute of Environmental Health Sciences, NIH, Research weight over two decades which was improved after the Triangle Park, NC, USA; Bona P. Purse, MSW - Co-author, Clinical addition of supplements Coenzyme Q10 and L-carnitine. Research Branch, National Institute of Environmental Health Case Description: A 30 yo male with diagnosed Lowe Syndrome Sciences,NIH,ResearchTrianglePark,NC,USA;KatieR.Hirsch, presented to the kidney clinic to establish care. Past medical PhD - Co-author, Department of Exercise and Sport Science, history included developmental delay, CKD III with persistent University of North Carolina Chapel Hill, Chapel Hill, NC, USA; proteinuria, Vitamin D deficiency, cataracts, recently diagnosed Abbie E. Smith-Ryan, PhD - Co-author, Department of Exercise diabetes and osteoporosis. He has had persistent tubular-range and Sport Science, University of North Carolina Chapel Hill, proteinuria ranging 1500 -1800 mg, baseline protein creatinine Chapel Hill, NC, USA; Janet E. Hall, MD - Co-author, Clinical ratio of 1.3- 1.6 for several years. Kidney biopsy suggested Research Branch, National Institute of Environmental Health nephron hyperfiltration due to congenitally reduced nephron Sciences,NIH,ResearchTrianglePark,NC,USA number. His kidney function and range of proteinuria have remained stable over several years with Lisinopril 2.5 mg a day. Objective: Appetite increases following chronic energy restriction Since childhood, he could not gain weight despite having a (ER) in women but the relationship between appetite and short- liberal diet. To try to better address hypotonia and inability to term ER is not well characterized. We sought to determine the ef- gain weight for many years, he was started on L-Carnitine fect of controlled short-term ER on appetite, cravings, and their 500 mg by mouth and CoQ10 200 mg once daily. Two potential mediators in young women. years after taking both, L- Carnitine was increased to twice Methods: Nineteen healthy women aged 23.36 ± 2.08 years a day due to lack of positive response in muscle tone (mean ± SD) with a BMI of 23.15 ± 2.34 kg/m2 (mean ± sem), un- and mass. He was able to gain weight on this regimen to a derwent two five-day diet and exercise interventions in the early BMI of 25 kg/m2 but was not able to increase muscle tone or follicular phase of two menstrual cycles [neutral energy availability mass. (NEA) ¼ 45 kcal/kg lean body mass (LBM)/day and deficient energy Discussion: Our patient’s clinical manifestations are somewhat availability (DEA) ¼ 20 kcal/kg LBM/day]. On day 5 of both in- atypical. The majority of renal pathology is due to the pres- terventions, the following were measured: visual analog scale ence of Fanconi’s syndrome. It is not known if our patient had (VAS) appetite questionnaire, body weight, and fasting leptin and a minor case of Fanconi’ssyndromeatbirth,however,hewas orexin-A. Paired t-tests compared the VAS questionnaire items, never hypophosphatemic, did not have a metabolic acidosis body weight, and fasting hormone levels. Principal-component and several UA over the years did not demonstrate renal factor analysis categorized VAS scores into appetite, satiety, hunger glucosuria. Rather than the development of secondary glo- and cravings (Cronbach alphas >0.80). Linear regression models merulosclerosis due to persistent proteinuria, in our patient it assessed the effects of changes (D) in body weight, leptin, and was felt on renal biopsy that the cause of his CKD and pro- orexin-A on appetite, satiety, hunger, and cravings. Resultsare teinuria was due to congenital hyperfiltration due to reduced shown as mean ± sem. nephron number. This has been rarely described in the med- Results: From NEA to DEA, the appetite score increased (55% vs ical literature in patients with Lowe syndrome. Our patient is 76%; p< 0.001), satiety score decreased (42% vs 19%; p< 0.01), in his 30s and his kidney function and level of proteinuria hunger score increased (52% vs 71%; p< 0.001), and craving have remained stable with the use of Lisinopril 2.5 mg daily. score decreased (49% to 38%; p< 0.01). DEA was accompanied Individuals with Lowe Syndrome also have carnitine deficiency by weight loss (-1.0 ± 0.22 kg, p< 0.001), reduced leptin which can affect skeletal muscle integrity and inability to (-3.13 ± 0.95 ng/ml; p¼0.002), and increased orexin-A (0.06 ± ability to gain weight. Supplementation with Coq10 and 0.02 ng/ml; p¼0.018). D body weight was positively associated

S82 Obesity/Nutrition Endocrine Practice 27 (2021) S76eS84 with D leptin (p¼0.001) but not D orexin-A. Weight loss was patients with PCM were significantly higher than those associated with increased appetite, controlling for leptin and without (8.31% vs 3.32%); p< 0.0001. Mean LOS and mean HC orexin-A (p¼0.011). D satiety was positively associated with D were also higher in the presence of PCM compared to those in body weight (p¼0.002), independent of D leptin. D leptin without (9.97 vs 5.07 days & $140,186 vs $47,834 respectively). was associated with satiety (p¼0.033), although this associa- When adjusted for patient demographics, comorbidities, and tion was weight dependent. D hunger was positively associ- hospital characteristics, HF patients with PCM had higher risk ated with D body weight (p¼0.043), independent of changes of mortality (aOR¼2.41, 95% CI 2.04-2.84, p< 0.0001), cardiac in orexin-A. D craving did not correlate with D in body weight, arrest (aOR¼1.7, 95% CI 1.16 - 2.5, p¼0.006), stroke (aOR¼1.77, leptin, or orexin-A. p¼0.0616), PE (aOR¼1.42, p¼0.045), sepsis (aOR¼4.63, p< Discussion/Conclusion: Short-term ER led to a dramatic increase in 0.0001), pneumonia (aOR¼1.39, p< 0.0001), and AKI appetite despite a small reduction in body weight. Increased (aOR¼1.53, 95% CI 1.38-1.69, p< 0.0001). When adjusted appetite was mediated through the effect of weight loss-associated similarly, HF patients with PCM had longer LOS by 4.61 days decreased leptin on satiety. Appetite and hunger were not associ- (p< 0.0001) and an additional HC of $89,486 (p< 0.0001). ated with orexin-A, but ghrelin was not measured. Interestingly, However, there was no statistical difference in the risk of specific food cravings were overwhelmed by the overall increase in developing acute respiratory failure (aOR¼1.23, p¼0.15), or appetite. Even with short-term ER, weight loss is confounded by being intubated (aOR¼1.14, p¼0.13) in HF patients with and increased appetite and decreased satiety, indicating the importance without PCM. of these factors in weight loss programs. Discussion/Conclusion: HF patients with PCM had worse out- comes in terms of in-hospital mortality, LOS, HC, cardiac arrest, https://doi.org/10.1016/j.eprac.2021.04.642 stroke, PE, sepsis, pneumonia, and AKI compared to those without PCM. This suggests that PCM is an adverse prognostic Abstract #1004325 marker in this population. Current limitations include the underrepresentation of metabolic derangements due Protein Calorie Malnutrition Is An Adverse Prognostic to inadequate coding within this administrative database. Future Marker In Hospitalized Heart Failure Patients: An models for treating HF exacerbation should consider the po- Analysis of the National Inpatient Sample Registry tential advantage of nutritional supplementation to increase body weight in HF patients who are at risk of malnutrition as a method of reducing mortality and morbidity. Author Block: Ramtej Atluri, MD - Primary Author and https://doi.org/10.1016/j.eprac.2021.04.643 Presenter, Internal Medicine, John H. Stroger Hospital of Cook County; Marcelo Ramirez, MD - Co-author, Internal Medicine, John H. Stroger Hospital of Cook County; Kevin C. Bustos, MD - Co- Abstract #1004340 author, Internal Medicine, John H. Stroger Hospital of Cook County; Hafeez Shaka, MD - Co-author, Internal Medicine, John The Pregnant Service Member. How a Single H. Stroger Hospital of Cook County Pregnancy Impacts Physical Fitness Scores in Active Duty Women Objective: Protein Calorie Malnutrition (PCM) is common among heart failure (HF) patients. The prevalence of malnu- trition among HF patients can be attributed to factors such as Author Block: Michelle N. Lee, MD - primary author, Department reduced caloric intake due to medication-induced anorexia, of Endocrinology, San Antonio Military Medical Center, Fort anxiety, and low energy levels to prepare food. Some chronic Sam Houston, TX; Whitney L. Forbes, PhD - co-author, Diabetes HF patients may even develop cardiac cachexia with skeletal Center of Excellence, Wilford Hall Ambulatory Surgical muscle wasting as a result of entering a catabolic state. Center, San Antonio, TX; Darrick J. Beckman, MD - co-author, However, the impact of metabolic derangements such as PCM Diabetes Center of Excellence, Wilford Hall Ambulatory Surgical on outcomes in HF patients is not well defined. We aimed to Center, San Antonio, TX assess the impact of PCM on outcomes in patients admitted with acute HF exacerbation. Objective: Disclaimer: “The view(s) expressed herein are those of the Methods: A retrospective cohort study was conducted using author(s) and do not reflect the official policy or position of Brooke the Nationwide Inpatient Sample from 2017. About 212,199 Army Medical Center, the U.S. Army Medical Department, the U.S. hospitalizations who had acute HF as their primary diagnosis Army Office of the Surgeon General, the Department of the Army, the were identified and stratified based on the presence of PCM Department of the Air Force and Department of Defense or the U.S. using ICD-10 codes. Outcomes included are inpatient mortality Government.” rates, length of stay (LOS), hospital charges (HC), rates of Obesity rates continue to rise in the United States and military sepsis, cardiac arrest, stroke, pulmonary embolism (PE), population, with women having the additional challenges of pneumonia, and acute kidney injury (AKI). Multivariate hormonal and lifestyle changes that come with pregnancy and regression analysis was used to adjust for confounders such as motherhood. Active duty women are placed on a profile limiting patient demographics, hospital factors, and the Charlson co- their duties and deployability while pregnant. They are exempt morbidity index, as well as to analyze the variables. The se- from taking physical fitness tests (PFT) until a year following lection of covariates was done with a univariate screen and their delivery. With the worsening rates of obesity, this study literature review. was to review how this period affects weight and physical Results: Out of the 212,200 hospitalized patients with HF, fitness in active duty women in the United States Air Force 12,695 individuals had PCM. In-hospital mortality in HF (USAF).

S83 Obesity/Nutrition Endocrine Practice 27 (2021) S76eS84

Methods: Active duty USAF women who underwent a normal Objective: Obesity and diabetes mellitus (DM) have emerged as pregnancy and delivery between January 1st, 2013 to December significant risk factors for poor outcomes in COVID-19 (SARS-CoV- 31st, 2017 were reviewed. Demographics to include age, rank, 2) infection. In this study, we explored the impact of DM and gly- martial status, number of dependents, and race were obtained. cemic control on mortality rates in patients with obesity admitted PFT scores before and after pregnancy were collected. Women to the hospital with COVID-19 infection. with missing data, ectopic pregnancies, or spontaneous abortions Methods: Data from 1477 adults with obesity admitted to the were excluded. Data was analyzed using average percentages and Lifespan hospital system in Rhode Island with COVID-19 chi-squared tests or fisher’s exact test. infection between March 1, 2020 and February 28, 2021 were Results: Between January 1st, 2013 and December 31st,2017, analyzed. Multivariate logistic regression analysis was con- approximately 4,000 active duty USAF women were identified as ducted in SAS software adjusted for age, race/ethnicity, sex, undergoing a normal pregnancy and delivery with comparable PFT renal disease (dz), hypertension (HTN), pulmonary dz, Type 1 scores before and after pregnancy. Majority of women gained 2 DM (T1DM), Type 2 DM (T2DM), stress hyperglycemia (StH) inches on their waist circumference measurement (70.8%) while definedasabloodglucose(BG)> 180 mg/dL on 2 occasions only 5.9% lost 2 inches on their post-pregnancy PFT. Of those that and A1c< 6.5%, hyperglycemia, diabetic ketoacidosis (DKA), got smaller, 47.3% scored excellent compared to 28.8% with stable length of stay (LOS) and mechanical ventilation (MV). waists and 46.9% of those that got larger. Fail rates were also worse Results: The mean (± SD) age was 61.6 (±16.1) years with in the group that increased in waist or stayed the same, 5.6% and 48.8% men, 28.5% Hispanics, 65.1% Non-Hispanic Whites and 13.5% respectively. 1.6% Non-Hispanic Blacks in the cohort. Obesity Class I, II, and Discussion/Conclusion: As expected, most of the women had an III accounted for 50.1%, 26.9%, and 23.0%, respectively. Five increase in their abdominal circumference on their post-pregnancy percent had T1DM, 42.4% T2DM and 22.7% StH. Mean A1c of PFT. Although excellent and fail rates were the best in the women 8.3% (±2.4), BG of 155.2 mg/dL (±72.5) and LOS 8.7 days that had a decrease in abdominal circumference, it was not (±18.9) were noted during hospitalization. MV and mortality significantly different from those that increased in size. Further rates were 6.3% and 15.4%, respectively. Unadjusted model studies are needed to assess whether PFT scores correlate with identified the following risk factors for mortality: older age overall fitness. (OR 0.95 [0.94-0.96]), male sex (OR 1.54 [1.16-2.05]), Hispanic ethnicity (OR 1.87 [1.27-2.80]), HTN (OR 1.87 [1.35-2.6]), pul- https://doi.org/10.1016/j.eprac.2021.04.644 monary dz (OR 1.44 [1.08-1.93]), renal dz (OR 1.75 [1.19-2.58]), T1DM (OR 1.70 [1.0,-2.86]), T2DM (OR 1.74 [1.31-2.32]), StH (OR 4.27 [3.19-5.73]), DKA (OR 12.79 [3.9-41.9]), LOS (OR 0.99 Abstract #1042611 [0.98-0.998]), MV(OR 12.21 [8.63-17.26]), prior A1c (OR 1.23 [1.04-1.46], admission BG (OR 0.99 [0.997-0.999]), mean BG Impact of Diabetes and Glycemic Control on Poor (OR 0.99 [0.99-0.999]), peak BG (OR 0.99 [0.99-0.997]) and Outcomes in Hospitalized Patients with Obesity and hyperglycemia (OR 4.0 [2.98-5.37]). Adjusted model identified COVID-19 Infectionq2 older age (OR 0.95 [0.92-0.97]), male sex (OR 1.69 [1.02-2.82]), Hispanic ethnicity (OR 2.61 [1.27-5.38]), longer LOS (OR 1.04 [1.01-1.06]), MV (OR 5.65 [7.15-34.25]) and hyperglycemia (OR Author Block: Jasmin Lebastchi, MD - Primary author, Division 2.02 [1.15-3.54]) to be independent risk factors for increased of Endocrinology, Diabetes, and Metabolism, Warren Alpert mortality in patients with obesity admitted to the hospital Medical School of Brown University; Filipe Monteiro, PhD - with COVID -19 infection. co-author, Warren Alpert Medical School of Brown Discussion/Conclusion: Hyperglycemia independent of DM status University; Marie E. MCDonnell, MD - co-author, Division of was predictive of increased mortality in hospitalized patients with Endocrinology, Diabetes, and Hypertension, Brigham and obesity and COVID-19 infection. Further studies are needed to Women's Hospital, Harvard Medical School; determine if hyperglycemia is the cause or result of severity of Geetha Gopalkrishnan, MD - co-author, Division of COVID-19 infection. Endocrinology, Diabetes, and Metabolism, Warren Alpert Medical School of Brown University https://doi.org/10.1016/j.eprac.2021.04.645

S84 Endocrine Practice 27 (2021) S85eS106

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Endocrine Practice

journal homepage: www.endocrinepractice.org

PARATHYROID/BONE DISORDERS

Abstract #983057 in significant risk reduction for vertebral, nonvertebral, and major OP fx, and numerical reduction in clinical and wrist fx. ABL was Effect of Abaloparatide on Bone Mineral Density and associated with significant improvements in BMD vs PBO. Result- Fracture Incidence in Postmenopausal Women with sare consistent with those observed in the overall ACTIVE popula- Osteoporosis and Obesity tion, confirmation of these findings is warranted. Resultsfrom this post hoc analysis suggest ABL may provide a valuable treatment option for women with postmenopausal OP and obesity at high risk Author Block: W. Timothy Garvey, MD - Presenter, The University for fx. of Alabama at Birmingham; Elena Nikonova, MD - Co-author, Radius Health, Inc; Yamei Wang, PhD - Co-author, Radius Health, https://doi.org/10.1016/j.eprac.2021.04.647 Inc; Anne Schafer, MD - Co-author, School of Medicine, University of California and the San Francisco VA Health Care System; Abstract #987968 Joanna Rega - Radius Health, Inc Case of Severe Hypercalcemia in a Patient with Latent Objective: In the 18-month Phase 3 ACTIVE study in women with Autoimmune Diabetes of Adulthood and Diabetic fi postmenopausal osteoporosis (OP), abaloparatide (ABL) signi - Ketoacidosis cantly increased bone mineral density (BMD), and decreased the risk of vertebral, nonvertebral, and clinical fractures (fx) vs placebo (PBO), and major OP fx vs teriparatide (TPTD) and PBO. The rela- Author Block: Khulood Bukhari, MBBS - Presenter, Department of tionship between obesity and fx risk is complex, and obese patients Medicine, University of Maryland Medical Center Midtown may have higher fx risk after adjustment for BMD. The objective of Campus; Megan Kristan, MD - Co-author, Division of fi this post hoc analysis was to evaluate the ef cacy of ABL in patients Endocrinology, Diabetes and Nutrition, University of Maryland with high body mass index (BMI) enrolled in ACTIVE. School of Medicine; Marjorie Pennant, MD - Co-author, Division of Methods: In ACTIVE, 2,463 postmenopausal women with OP were Endocrinology, Diabetes and Nutrition, University of Maryland m randomized 1:1:1 to double-blind daily ABL 80 g or PBO, or open- School of Medicine label TPTD 20 mg SC for 18 months. A subgroup of patients with high BMI (27 kg/m2), adjusted by race (24 kg/m2 for Asian), were Introduction: Hypercalcemia is most commonly seen with primary evaluated. hyperparathyroidism and malignancy. Most cases are asymptom- Results: 823 patients with BMI 27 kg/m2 (BMI27) were identified atic and are detected on routine biochemical testing. Here we (ABL: n¼262, TPTD: n¼281, PBO: n¼280). Demographic and clinical present a case of severe hypercalcemia in an individual with latent baseline characteristics were balanced across the treatment groups. autoimmune diabetes of adulthood (LADA) presenting with dia- Both ABL and TPTD were associated with significant reduction in betic ketoacidosis (DKA). new vertebral fx vs PBO (ABL: 2 [0.9%], TPTD: 3 [1.2%], PBO: 11 Case Description: A 50-year-old male presented to the emergency [4.7%]; P< 0.05 both). Significant reduction in nonvertebral and department (ED) with a complaint of nausea, vomiting, epigastric major OP fx were observed with ABL vs PBO (P< 0.05); Kaplan- pain, and diarrhea for 1 week. He had a history of type 2 diabetes Meier estimated cumulative incidence were as follows: non- diagnosed at the age of 43. His regimen included metformin 500 vertebral fx: 2.0%, 3.2%, 5.4%; clinical fx: 3.3%, 5.7%, 6.7%; major OP mg twice daily and insulin glargine 27 units twice daily. He ran out fx: 1.4%, 2.8%, 5.5%; wrist fx: 0.9%, 2.0%, 3.4%; in ABL, TPTD, and PBO of insulin two days prior to the commencement of his symptoms. In groups, respectively. Fx reduction trends were consistent with the ED, labs were consistent with a diagnosis of DKA. He was those of the overall ACTIVE population. Significant BMD increases admitted to the intensive care unit for further management. His from baseline at 6, 12, and 18 months were observed with ABL vs glutamic acid decarboxylase antibody was >250 IU/ml (0.0-5.0 IU/ PBO and TPTD vs PBO at the total hip, femoral neck, and lumbar ml) and islet cell antibody 1:16 (< 1:4) supporting a diagnosis of spine, consistent with the overall ACTIVE population (P< 0.0001). LADA. Additionally, significantly greater BMD gains were observed with His calcium was 17.3 mg/dl (8.4-10.2 mg/dl) with an ionized ABL vs TPTD at the total hip (all timepoints), femoral neck (12 and calcium of 1.97 mmol/L (1.15-1.29 mmol/L). He received 18 months), and lumbar spine (6 months) (P< 0.05). Changes in aggressive intravenous hydration with isotonic saline and 4 mg bone markers and safety parameters were also comparable to the of intravenous zoledronic acid. Laboratory evaluation showed overall study population. parathyroid hormone 5 pg/ml (8-54 pg/ml), parathyroid hormone- Discussion/Conclusion: Among postmenopausal women with OP related protein < 2.0 pmol/L (0.0-2.3 pmol/L), 25 (OH)2 vitamin D enrolled in ACTIVE, in a subpopulation with high BMI, ABL resulted 10 ng/ml (20-80 ng/ml) and 1, 25 (OH)2 vitamin D 17.3 pg/ml

1530-891X Parathyroid/Bone Disorders Endocrine Practice 27 (2021) S85eS106

(19.9-79.3 pg/ml). Computed tomography scan of the chest, subcutaneous daily injections in terms of improvement in serum abdomen, and pelvis with contrast showed no evidence of malig- calcium levels, decreased daily requirements of oral calcium and nancy. Protein electrophoresis showed no evidence of monoclonal vitamin D and improvement in debilitating symptoms of hypocal- protein. His calcium levels improved to 8.6 mg/dl on day 5 and he cemia and overall quality of life. However, in some cases, contin- was discharged home. During a follow-up visit, he admitted to uous injections can lead to the rubber being injected into the body. ingesting large amounts of over-the-counter calcium carbonate The patient should be advised not to stop the injections abruptly (TUMS) to help with dyspepsia. until they speak to their physicians. Discussion: More frequently described in case reports of pediatric Conclusion: According to our findings, Natpara (recombinant patients, hypercalcemia is an uncommon electrolyte abnormality human parathyroid hormone) is highly recommended for man- seen with DKA. Hypercalcemia in this setting is thought to be aging those patients with hypoparathyroidism. It has a good safety related to insulin deficiency mediated inhibition of bone mineral- profile and can alleviate the symptoms with no risk of over-treat- ization. Additionally, in-vitro studies of metabolic acidosis show an ment related complications and also improve the quality of life. increase in osteoclastic bone resorption, a decrease in osteoblastic https://doi.org/10.1016/j.eprac.2021.04.649 bone formation, and an increase in non-cell mediated bone disso- lution leading to a net efflux of calcium from bone. Milk alkali syndrome (MAS) is characterized by the triad of hy- Abstract #991296 percalcemia, metabolic alkalosis, and acute kidney injury. The ingestion of excessive quantities of calcium and absorbable alkali is Hypophosphatemia Secondary to Tumor-Induced a pre-requisite for diagnosis. The postulated mechanism of action is Osteomalacia that kidney injury develops first, inhibiting the body’s ability to properly excrete calcium. Hypercalcemia causes afferent arteriole constriction and has natriuretic and diuretic effects. This leads to Author Block: Neelima Ghanta - University of Kentucky; worsening hypercalcemia and propagates the toxic effects of cal- Derick Adams, D.O. - Co-author, Endocrinology, University of cium on the kidneys. Immobilization hypercalcemia is uncommon Kentucky and is a diagnosis of exclusion. It is seen predominantly in children and adolescents, and the mechanism of action is not entirely Introduction: Tumor-induced osteomalacia (TIO) is a paraneo- understood. plastic condition caused by tumoral production of fibroblast growth https://doi.org/10.1016/j.eprac.2021.04.648 factor 23 (FGF-23). TIO is caused by benign mesenchymal tumors from the soft tissue or bone. TIO is characterized by renal phosphate wasting that leads to hypophosphatemia and normal to low Abstract #989981 1,25-dihydroxyvitamin D with inappropriately normal or elevated FGF-23. A thorough history, physical exam, and biochemical Three Cases of Hypoparathyroidism Treated Successfully workup followed by imaging, such as a Gallium-68 DOTA-Octreo- with Daily Recombinant Human Parathyroid Hormone tate (DOTA-TATE) positron emission tomography (PET) scan is rhPTH (1-84; Natpara) Subcutaneous Injections, with necessary for diagnosis. In this case study, we will discuss a 53 year Improvement in the Quality of Life and Reduction in old male who presented to our clinic with a recent history of severe Daily Calcium and Vitamin D Requirements hypophosphatemia and multiple non-traumatic fractures. Case Description: A 53 year old male with no significant past medical history presented to the endocrine clinic with a recent Author Block: Mohamed Abouzid - Mansoura University Faculty of history of multiple non-traumatic fractures. Over the past one year, Medicine; Mohamed Riad, MBBCh - Primary author and presenter, he was diagnosed with fractures of his vertebrae, feet, and ribs Mansoura University Faculty of Medicine, Egypt; Jassimran Singh, without any antecedent trauma. He also stated that ever since one MBBS - Co-author, Institute of medical sciences, BHU, India; year ago, he has been confined to a wheelchair as he cannot walk syeda zaidi, MD - Co-author, Nishtar Medical College, Multan long distances. He denies any family history of osteoporosis, frac- Pakistan; Ritu Yadav, MBBS - Co-author, Maulana Azad Medical tures, abnormal tooth development, or disorders of calcium and College, New Delhi, India; Maria Rendon, MD - Co-author, phosphate metabolism. He has two children who are otherwise Universidad catolica de Santiago de Guayaquil, Ecuador; healthy. Of note, he was hospitalized approximately one month ago Jose Duenas,~ MD - Co-author, Universidad catolica de Santiago de for severe hypophosphatemia (0.9 mg/dL) requiring intravenous Guayaquil, ecuador Lubna Mirza, Endocrinologist and Diabetes phosphorus replacement. He was discharged on oral phosphorus Specialist e Co-author, Norman Regional Health System supplements. His lab results from clinic are as follows: phosphorus 1.5 mg/dL, magnesium 1.9 mg/dL, calcium 9.8 mg/dL, albumin Introduction: To report three clinical cases of hypocalcemia due to 4.6 g/dL, 25-hydroxyvitamin D 30.1 ng/mL, intact parathyroid hypoparathyroidism that were successfully treated in our Endo- hormone 32 pg/mL and thyroid stimulating hormone 4.84 mU/L. crinology practice with daily Natpara subcutaneous injections with We further ordered a FGF-23 level which was inappropriately improvement in symptoms and quality of life. normal at 164 RU/mL. His clinical and biochemical picture were Case Description: The clinical history, physical examination and consistent with TIO, so we continued the patient on oral phos- laboratory values of three patients with severe hypocalcemia. A phorus supplementation and calcitriol. We proceeded with a FDG- literature search was performed to learn more about the exciting PET/CT scan which unfortunately did not localize the tumor. He was new indication for the human recombinant parathyroid hormone subsequently started on burosumab (human monoclonal antibody drug class to help treat patients with severe symptoms of hypo- against FGF-23) which has now significantly improved his hypo- calcemia due to hypoparathyroidism. phosphatemia to 3.0 mg/dL without further need for oral phos- Discussion: Results: We are pleased to report that 100% of our phorus supplementation and calcitriol. He is now able to ambulate clinic patients with hypocalcemia due to hypoparathyroidism without assistance and denied any recent fractures since starting whether post-surgical or autoimmune responded well to Natpara burosumab.

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Discussion: This case study illustrates a previously healthy male Discussion: Hypocalcemia is a dangerous complication of denosu- who developed hypophosphatemia and multiple non-traumatic mab therapy. This case highlights the importance of screening for fractures in the span of one year and was ultimately diagnosed with and correcting VITD deficiency prior to start of denosumab therapy TIO. Although a rare disorder, clinicians must have a high index of and the need of monitoring calcium and VITD levels during suspicion for TIO. In this case, imaging was not able to localize the treatment. FGF-23 secreting tumor. However, the patient did have a reasonable https://doi.org/10.1016/j.eprac.2021.04.651 clinical and biochemical response after starting burosumab treatment. https://doi.org/10.1016/j.eprac.2021.04.650 Abstract #997023

A 65-Year-Old Man With Parathyroid Independent Abstract #995475 Hypercalcemia Due To Renal Cell Carcinoma And Resolution of Hypercalcemia Following Nephrectomy - Severe Hypocalcemia: A Life-threatening but Proposed Mechanisms of Hypercalcemia With Renal Preventable Complication of Denosumab Therapy Cell Carcinoma

Author Block: L. Maria Belalcazar - University of Texas Medical Author Block: SAI REDDY - Norman Endocrinology Associates; Branch; Nicholas Gore, BS - First author, School of Medicine, LUBNA MIRZA, MD - Co-author, ENDOCRINOLOGY, Norman University of Texas Medical Branch; Deepam Joseph, MD - co- Associates; Sravani Konatham, MBBS - Co-author, author, Medicine, Division of Internal Medicine, University of Texas ENDOCRINOLOGY, Norman Associates Medical Branch Introduction: Among the genitourinary cancers, Renal Cell Car- Introduction: Severe hypocalcemia, a potentially life-threatening cinoma (RCC) has the highest mortality rate, and the incidence electrolyte disorder, may lead to neuromuscular instability with of RCC has increased steadily. Once detected early, RCC is curable tetany, laryngospasm, seizures or cardiac complications including by surgery, although some are at risk of recurrence. It encom- QT interval prolongation with arrhythmias and/or myocardial passes many histological and molecular subtypes. Clear cell va- dysfunction. Denosumab, an osteoclast inhibitor used in osteopo- riety is most common and accounts for most cancer-related rosis, multiple myeloma (MM) and metastatic bone disease, has deaths. The clinical constellation of signs and symptoms termed been associated with an increased risk of severe hypocalcemia. We paraneoplastic is essential to identify as they could be a marker present a patient with bone disease due to MM who developed of cancer recurrence or the first presenting sign of the tumor. severe hypocalcemia in the setting of 25-hydroxy vitamin D (VITD) Hypercalcemia is the most common paraneoplastic manifesta- deficiency. The case highlights the importance of recognizing VITD tion of RCC, accounting for 14-20% of the cases. In a patient deficiency as a modifiable risk factor in the prevention of denosu- presenting with RCC, the presence of a paraneoplastic syndrome mab-induced hypocalcemia. is neither a marker of metastatic disease nor necessarily indic- Case Description: A 47-year-old man undergoing chemotherapy for ative of a poor prognosis. Paraneoplastic syndromes may be MM presented to an outside facility with nausea, vomiting and produced by early, localized, and potentially curable disease. diarrhea. He was found to have hypokalemia and hypocalcemia Proper evaluation and treatment of the tumor often lead to (calcium of 4.4 (8.6-10.6 mg/dL)) and a prolonged QT interval. He improvement or resolution of the paraneoplastic features. was given calcium and potassium replacement and transferred to Case Description: We report a case of a 65-year-old man who our hospital for further care. Upon arrival, the patient complained presented to the Endocrine service for hypercalcemia. He had of abdominal cramps, perioral and digital paresthesias, plus wors- painful joints, muscle aches, joint stiffness and incidentally ening lethargy. He was hemodynamically stable; Chvostek sign was discovered elevated calcium levels on two separate occasions. A negative. Calcium level, corrected for albumin, was low at 4.7 (8.6- lab evaluation indicated non-parathyroid mediated hypercalce- 10.6 mg/dL). Laboratories were also significant for hypokalemia, mia with calcium levels in the range of 10.1-10.5mg/dl. Para- hypomagnesemia and acute kidney injury. EKG showed a pro- thyroid hormone-related peptide (PTHrP) level was undetectable. longed QT interval (QTc of 601 msec; normal < 450 msec). Elec- His Parathyroid hormone (PTH) and 25-hydroxyvitamin D levels trolyte replacement was initiated. After initial calcium boluses, he were normal. But his 1, 25-dihydroxyvitamin D levels were low. was treated with continuous calcium infusion (1 gram elemental Initial imaging revealed a heterogeneously enhancing mass on calcium) for 48 hours, followed by half the dose on the third day, in the posterolateral left kidney. Our patient underwent a left ne- addition to oral calcium citrate 1 gram thrice daily and calcitriol 0.5 phrectomy, and the mass was identified as RCC on surgical ucg twice a day. Records revealed that he had started denosumab pathology. therapy (120 mg every 4 weeks) 10 months earlier but had only Discussion: Hypercalcemia is a common paraneoplastic compli- received 5 doses prior to presentation. Before initiating denosu- cation in patients with RCC, but frequently it is an unusual mab, the patient had a normal calcium level, but his VITD level presenting symptom. One should focus on whether the hyper- had not been checked and no supplementation had been calcemia is parathyroid dependent, malignancy-related, or given. Patient’s VITD level returned very low at < 13 ng/mL (25.0- medication-induced after initial evaluation of corrected calcium 80.0 ng/mL); parathyroid hormone was high at 269.6 pg/mL (12.0- levels, albumin, and magnesium. Necessary lab investigations 88.0 pg/mL) and phosphorous normal at 2.9 mg/dL (2.5-5.0 mg/dL). include PTH, PTHrP, 1,25-dihydroxyvitamin D, Thyroid function Ergocalciferol 50,000 IU once a week was added. Patient’s symp- tests. In cases where the cause of hypercalcemia is unclear, toms of hypocalcemia resolved. He left the hospital 6 days after bone-resorbing cytokines could be present. If the lab findings admission, with a calcium level of 7.96 (8.6-10.6 mg/dL) and a are not diagnostic, PET-CT( Positron Emission Tomography and normal QTc interval, on calcium citrate and weekly ergocalciferol Computed Tomography) and bone scan can be done to evaluate replacement. for lytic lesions or underlying malignancy. Primarily in a patient

S87 Parathyroid/Bone Disorders Endocrine Practice 27 (2021) S85eS106 with hypercalcemia, it is crucial to restore the volume status and preventive measures are taken, severe hypocalcemia can still occur, accordingly treat with antiresorptive agents with constant and it’s prompt recognition and treatment is essential. monitoring of serum electrolytes and albumin levels. Majority of https://doi.org/10.1016/j.eprac.2021.04.653 the cases of paraneoplastic hypercalcemia with RCC resolve with nephrectomy. Thus, We illustrated the differential diagnosis of hypercalcemia and the evaluation of hypercalcemia occurring Abstract #998480 with RCC. This case explains that we need to carefully evaluate, interpret, and review all the data, especially when the patient Sequential Therapy of Abaloparatide Followed by has borderline elevated calcium levels and does not have a Alendronate as Assessed by DXA-Based 3D Modeling in typical presentation of malignancy. Postmenopausal Women with Osteoporosis https://doi.org/10.1016/j.eprac.2021.04.652

Author Block: Renaud Winzenrieth, PhD - Primary author, Galgo Abstract #998460 Medical, Barcelona, Spain; Paul Kostenuik, PhD - co-author, Radius Health, Inc., Boston, MA; John Boxberger, PhD - co-author, Radius Management of Denosumab-induced Hypocalcemia: A Health, Inc., Boston, MA; Yamei Wang, PhD - co-author, Radius Case Study Health, Inc., Boston, MA; Ludovic Humbert, PhD - co-author, Galgo Medical, Barcelona, Spain; Richard J. Weiss, MD - co-author, Radius Health, Inc., Boston MA; Joanna Rega - Radius Health, Inc Author Block: Anne Borja - Cooper University Health Care; Farah Morgan, MD - co-author, Endocrinology, Cooper University Objective: In the ACTIVE study, 18 months (M) of abaloparatide Health Care (ABL) treatment (tx) reduced fracture (fx) risk in postmenopausal women with osteoporosis. Post-hoc analysis by 3D-DXA modeling indicated greater increases in total hip cortical volumetric BMD Introduction: Denosumab is commonly used in patients with (Ct.vBMD) and estimated indices of hip strength for ABL vs placebo prostate cancer with bone metastases. Treatment with denosumab (PBO) and vs open-label teriparatide (TPTD). A 24-month extension is used as a preventative measure for skeletal-related events, such study (ACTIVExtend) showed that 24M of alendronate (ALN) after as pathologic fractures, spinal cord compression, and necessity for 18M of ABL increased areal BMD (aBMD) and reduced vertebral and radiation or surgery to the bone. However, treatment can be asso- nonvertebral fx risk vs 24M of ALN after 18M of PBO. The current ciated with severe hypocalcemia. We present a case of a patient analyses describe 3D-DXA modeling data of the hip for ACTIVE + with metastatic prostate cancer who developed severe hypocalce- ACTIVExtend. mia following denosumab treatment. Methods: Hip DXA scans from 204 subjects receiving ABL/ALN and Case Description: A 57 year old man with a past medical history of 202 subjects receiving PBO/ALN who completed from baseline (BL) metastatic prostate cancer and hypertension, presented to the to M43 underwent 3D modeling via 3D-SHAPER (v2.10.1, Galgo emergency room with complaints of peripheral numbness, jaw Medical, Spain). Measurements were taken at BL, 6M, and 18M in clenching and tightness. He received denosumab 120 mg subcu- ACTIVE, and at the end of ACTIVExtend (18M of ABL or PBO, 1 M for taneously two days prior. Laboratory results were significant for patient reconsent, then 24M ALN for a total of 43M). Changes from calcium 5.2 mg/dL, albumin 3.6 g/dL, PTH 191 pg/mL, magnesium BL were calculated for total hip cortical thickness (Ct.Th), Ct.vBMD, 1.8 mg/dL, phosphorus 2.4 mg/dL, and a vitamin D 25-OH 6 ng/mL. and cortical surface BMD (Ct.sBMD; product of Ct.Th and Ct.vBMD). Several electrocardiograms revealed QTc intervals between 490 and Estimated strength indices including cross-sectional moment of 505 ms. A calcium infusion was immediately initiated. Calcium inertia (CSMI), section modulus (Z), and buckling ratio (BR) were carbonate, ergocalciferol, and calcitriol were also added to his calculated for neck, intertrochanteric, and shaft subregions. BL regimen. The patient’s calcium levels improved with the calcium comparisons were made by paired t-tests; tx group comparisons infusion and his symptoms resolved. However, despite increases in were based on an MMRM model. his oral calcium and calcitriol supplements, he was unable to Results: At 43M, total hip aBMD increased in both groups, with maintain an adequate serum calcium when the infusion was down larger gains for ABL/ALN vs PBO/ALN (6.42% vs 2.88%; p< 0.001). By titrated. Due to use of proton pump therapy, calcium carbonate was 3-D DXA, total hip Ct.Th, Ct.vBMD, and Ct.sBMD increased from BL changed to calcium citrate, a non-formulary medication. His cal- in both groups (all p< 0.001 vs BL), with greater increases for ABL/ cium infusion was eventually titrated off after 19 days, and his ALN vs PBO/ALN (Ct.Th: 2.32% vs 1.14%; Ct.vBMD: 3.41% vs 1.86%; calcium levels remained stable on calcium citrate 1200 mg 3 times/ Ct.sBMD: 5.82% vs 3.0%, respectively; all p< 0.001). The ABL/ALN day, and calcitriol 0.5 mcg 2 times/day. He was discharged in stable group also showed greater increases in CSMI, Z, and BR at all 3 medical condition, and now follows regularly with his subregions vs BL (all p< 0.0001) and vs PBO/ALN (all p< 0.02). endocrinologist. Discussion/Conclusion: 3D-DXA modeling indicates that sequential Discussion: Severe hypocalcemia following denosumab treatment ABL/ALN or PBO/ALN tx improved total hip Ct.Th, Ct.vBMD, Ct.sBMD, is rare; however risk factors and laboratory results need to be as well as estimated strength indices of hip subregions, with signifi- assessed prior to administration in order to reduce the risk of this cantly greater increases at M43 with ABL/ALN vs PBO/ALN. These complication. One key risk factor is active osteoblastic metastasis, findings are consistent with significantly greater nonvertebral fx risk as evidenced by elevated alkaline phosphatase levels and imaging. reduction with ABL/ALN vs PBO/ALN. The results also support the use This patient had an alkaline phosphatase level of 1819, as well as CT of ABL as the initial tx in sequential therapy with ALN in post- and MRI imaging consistent with osseous metastatic disease. In menopausal women with osteoporosis at highest fx risk, a treatment these patients, if feasible, denosumab should be avoided until dis- paradigm consistent with recommendations by AACE, ESCEO, and ease activity is controlled first with chemotherapy and/or androgen other major organizations to consider bone anabolic agents first fol- deprivation therapy. Assessment of vitamin D and magnesium lowed by potent antiresorptives in such patient populations. levels should also be performed, and any deficiencies should be treated and normalized prior to denosumab treatment. Even if all https://doi.org/10.1016/j.eprac.2021.04.654

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Abstract #998765 phosphate reabsorption and decreased 1-alpha-hydroxylase activ- ity leading to decreased phosphorus and calcitriol levels. Patients A Case of Ocular Inflammation Following Zoledronic with TIO present with bone pain, height loss, proximal muscle Acid Infusion weakness and fractures. For decades, phosphate and calcitriol supplements have been the mainstay of therapy. Recently, bur- osumab, a monoclonal antibody against FGF23, was approved for Author Block: Caroline Johns - University of South Florida; the treatment of TIO. We present the case of a patient with TIO who Marla E. Sevilla-Alsina, MD - co-author, USF; Natalia Weare- is being treated with burosumab. Regales, MD - co-author, James A Haley Veterans Hospital Case Description: 74-year-old man who presented with general- ized bone pain, muscle weakness and multiple fractures over the Introduction: Bisphosphonates, a medication class that inhibits the span of eight years. On exam his height was 62 inches. Initial work resorptive action of osteoclasts, represent the most prescribed up revealed low serum phosphorus and 1,25 vitamin D levels. A 24- medications for the management of osteoporosis. They are also hour urine collection revealed increased phosphate wasting. FGF23 used to treat pathologic hypercalcemia, Paget’s disease and bony levels were elevated. Congenital forms of FGF23 excess were ruled metastasis. Oral therapy can be locally irritating and not indicated out with negative PHEX, FGF23 and DMP1 mutation analyses. A in patients with gastrointestinal pathology. For these patients, bone density showed osteoporosis with the lowest T-score of -3.5 at zoledronic acid is preferred as it is given via an annual intravenous the right hip. The patient was diagnosed with TIO. Multiple at- infusion. Common side effects include transient hypocalcemia, tempts to localize an underlying tumor were unsuccessful. acute phase reaction symptoms such as myalgias, arthralgias, and He had been treated with calcitriol and phosphate supplemen- fatigue. Although ocular side effects are uncommon, they have been tation for years with limited success as phosphorus levels remained reported. We present a case of a woman with severe bilateral eye low despite multiple daily doses and frequent titration. Patient pain following zoledronic acid infusion. remained with severe bone pain requiring opioid therapy and his Case Description: Patient is a 72 y/o female with history of acid bone density declined significantly through time. Given recent reflux, gastritis, hypothyroidism, cataracts and chronic dry eyes approval of burosumab for TIO, treatment was initiated at a dose of who presented for management of osteoporosis. She was treatment 30 mg every 4 weeks. His phosphate and calcitriol supplements naïve. Biochemical work up showed Vitamin D level of 44ng/ml and were discontinued 1 week prior to first dose. Phosphorus levels negative work up for secondary causes. She was on calcium and were rechecked and noted to have normalized two weeks after the Vitamin D supplementation. DEXA scan showed T score of -0.3 at first dose of burosumab. Clinically patient is still experiencing bone the lumbar spine, -2.9 at left femoral neck and e 1.6 at total hip. pain. He has not had new fractures. Because of her gastritis, decision was made to start zoledronic acid. Discussion: The diagnosis of TIO is often delayed given nonspecific Day 1 post infusion, patient woke up with bilateral eye pain and symptoms such as weakness along with bone and muscle pain. redness. She endorsed pain with eye movement, denied blurry Clinical clues to the diagnosis include frequent fractures and short vision or vision loss. On day 3, she was seen by ophthalmology after height. TIO is diagnosed after confirming FGF23-mediated hypo- home supportive measures provided no relief. Ophthalmologic phosphatemia in the absence of congenital forms of FGF23 excess. exam showed normal visual acuity and normal visual fields. There TIO is caused by mesenchymal tumors which are commonly not was no intraocular inflammation or anterior scleritis. Corneal exam localized, hence surgical intervention is not feasible. Historically, showed pseudodendrites in bilateral eyes. Patient was treated this condition has been treated with phosphate and calcitriol conservatively with lubricants. She was reevaluated on day 5 with supplementations. However, this regimen involves multiple daily noted improvement in bilateral eye pain and resolution of the doses which can add to the patient’s disease burden and non- pseudodendrites. By day 10, the eye pain had resolved. compliance. Dose titrations are usually limited by renal failure and Discussion: The close temporal relationship between the zole- secondary hyperparathyroidism. Burosumab is a monoclonal anti- dronic acid infusion and the onset of ocular symptoms in our pa- body against FGF23 that was recently approved for the manage- tient are characteristic of bisphosphonate-related ocular ment of TIO. We describe a patient with TIO with persistent inflammation. Although rare, there have been several case reports. hypophosphatemia and worsening BMD despite conventional The presentations include conjunctivitis, scleritis, episcleritis, therapy. After one dose of burosumab, he had correction of hypo- keratitis, anterior uveitis. Of these, keratitis and scleritis have phosphatemia. This is a promising result for this patient in which greater risk of vision loss. Most cases are self-limited with symptom we will continue to monitor his bone pain, BMD and fracture risk in duration of 3-10 days. Physicians should be aware of possible ocular hopes that there is significant improvement with continued side effects in order to avoid treatment delay and should provide therapy. expert ophthalmologic evaluation. https://doi.org/10.1016/j.eprac.2021.04.656 https://doi.org/10.1016/j.eprac.2021.04.655

Abstract #1000149 Abstract #999151 A Qualitative Study to Assess Patient Perspective of Burosumab Treatment For Tumor-Induced Osteomalacia Osteoporosis Treatment

Author Block: Mickael Hiligsmann, PhD - Presenter, Maastricht Author Block: Juan Sarmiento - Ochsner Medical Center; University; Stuart Silverman, MD - A co author, Cedar-Sinai Daniel Englert, MD - Co-author, Endocrinology, Ochsner Medical Medical Center and UCLA School of Medicine; Deborah T. Gold, MD Center - A co-author, Duke University Medical Center; Introduction: Tumor-induced osteomalacia (TIO) occurs as a result Setareh A. Williams, MSc - A co-author, Radius Health, Inc; of excessive fibroblast growth factor 23 (FGF23) production by Rich Weiss, MD - A co author, Radius Health, Inc; mesenchymal tumors. FGF23 excess causes impaired renal Charlotte Beaudart, PhD - Primary author, Maastricht University

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Objective: Given the increasing osteoporosis (OP) disease burden, (14-27 pg/mL). Hypercalcemia was treated with IV fluids, calci- poor acceptability of available treatment options, and increasing tonin, and IV pamidronate. importance of the patient benefit/risk perspective in regulatory Neck ultrasound did not show a parathyroid lesion. CT C/A/P was decisions, we evaluated patients’ consideration and relative significant for a 3 cm well-circumscribed homogeneous nodule in importance of attributes of currently approved anabolics and a the right lower lung. Whole body sestamibi T-99 scan showed no potential new product (novel mode of administration (a solid signs of a parathyroid lesion, but showed moderate uptake in a Microstructured Transdermal System (sMTS)) currently under round mass in the right lower lung and intense uptake in the investigation in a phase III trial. fundus of the stomach. Methods: Three online focus groups with US patients over 50 years She underwent open reduction and internal fixation of the femur. at high risk for fracture eligible to receive anabolic therapies were Biopsy of the lesion was negative for carcinoma. Pathology showed conducted using the Nominal Group Technique. During this exer- bone with increased resorption, peritrabecular fibrosis, and gran- cise, after being shown visual illustrations about 3 modes of ulation-like tissue with hemosiderin, hemorrhage, and giant cells, administration (i.e. sMTS, daily SC self-injection with pen or compatible with bony changes of hyperparathyroidism. Right lower monthly SC-injection in HCP office), patients were asked to (1) lobectomy showed a benign 4 cm well-differentiated intermediate- individually identify attributes important for their treatment grade neuroendocrine tumor with focal necrosis, 3-4 mitoses/ choice, (2) share ideas and discuss perspectives with other patients, 10HPF, and 15% proliferative index with Ki-67, strongly positive for (3) review additional attributes from literature reviews and expert PTH. Intraoperative diluted PTH was 678 pg/mL and postoperative consultation, (4) individually select and rank the top 7 attributes, PTH 51 pg/mL. and (5) report their acceptability and preference ranking between She then developed symptomatic hypocalcemia, with nadir cor- sMTS application, daily self-injection, monthly in-office injection rected calcium 7.7 mg/dL on postoperative day 4. Calcium gluconate by a provider and no treatment. infusion, oral calcium, vitamin D, and calcitriol were used to Results: A total of 27 US patients participated in 3 focus groups. The maintain calcium within range. Alkaline phosphatase (ALP) median age was 65 years with 74% women and 85% non-Hispanic peaked at 1232 U/L (31-125 U/L) on postoperative day 9 and PTH at whites. Eighty-one percent had prior OP treatment and 60% had a 372 pg/mL on postoperative day 14. By postoperative day 30, PTH history of fractures. A total of 24 characteristics were identified and was 29 pg/mL, corrected calcium 9.3 mg/dL, vitamin D 49 ng/mL, further categorized into 4 domains: “efficacy”, “safety/tolerability”, and ALP 521 U/L on high doses of calcitriol, calcium carbonate, and “convenience” and “costs”. Globally, efficacy, safety and out-of- vitamin D. pocket costs were ranked as the most important attributes. In Discussion: This is a rare presentation of a well-differentiated addition, strength of clinical evidence and the option to self- pulmonary neuroendocrine tumor producing extremely high levels administer were considered important. Ninety-six percent of of PTH with resultant severe hyperparathyroidism, PTH-mediated patients were willing to administer a daily sMTS if prescribed by bone changes, and pathological fracture complicated by hungry their doctor. 84%, 4%, and 13% of patients ranked sMTS, daily pen bone syndrome following resection of the source of PTH. To our injection, and in-office monthly injection as their first choice of knowledge, this is the first report of a pulmonary neuroendocrine administration, respectively. tumor producing PTH, as most cases of neuroendocrine tumor- Discussion/Conclusion: This study revealed that efficacy, safety, induced hypercalcemia are PTHrP-mediated. We are evaluating this out-of-pocket costs, and convenience are important treatment at- patient with a gallium Ga-68 DOTATATE scan and endoscopic ul- tributes in this population of US patients with a high acceptability trasound for uptake seen in the fundus of the stomach on sestamibi and preference for sMTS over SC-injections. Additional quantitative T-99 scan. preference data is currently planned to further investigate the https://doi.org/10.1016/j.eprac.2021.04.658 trade-offs between attributes and characterize patients who prefer sMTS vs SC-injections. https://doi.org/10.1016/j.eprac.2021.04.657 Abstract #1000494

A Rare Case of Hypercalcemic Hyperparathyroid Crisis Abstract #1000351 due to Parathyroid Adenoma

Occult Neuroendocrine Tumor Causing Severe Hyperparathyroidism Author Block: Christopher Lesniak, DO - Primary Author, Jersey Shore University Medical Center; Katherine Hu, DO - Co-author, Jersey Shore University Medical Center; Soemiwati Holland, MD - Author Block: Neelam Upadhyaya - Temple University Hospital; Co-author, Jersey Shore University Medical Center; Jennifer Cheng, Kunal Shah, MD - co-author, Temple University; Ajay Rao, MD - co- DO - Co-author, Jersey Shore University Medical Center; author, Temple University; Cherie L. Vaz, MD - co-author, Temple Raquel Ong, MD - Co-author, Jersey Shore University Medical University Center

Introduction: We describe the diagnosis and successful manage- Introduction: Hyperparathyroid crisis is a rare complication of ment of a rare case of occult severe hyperparathyroidism due to a primary hyperparathyroidism (PHPT) that manifests as acutely well-differentiated pulmonary neuroendocrine tumor. While hy- elevated serum calcium and parathyroid hormone (PTH), causing percalcemia improved after tumor resection, the patient developed end-organ damage as well as neurologic, cardiac, gastrointestinal, hungry bone syndrome causing hypocalcemia. and renal disturbances. Highly elevated PTH is usually associated Case Description: A 39-year-old female who presented with right with parathyroid carcinoma rather than a benign process. We leg pain was found to have a 9 x 3 x 3 cm lytic femur lesion, calcium present a unique case of a 70-year-old woman with markedly 17.5 mg/dL (8.6-10.0 mg/dL), non-diluted PTH >2000 pg/mL (19-88 elevated PTH and serum calcium due to a benign parathyroid pg/mL), vitamin D 11 ng/mL (30-100 ng/mL), and PTHrP 17 pg/mL adenoma.

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Case Description: A 70-year-old female with no significant history pelvis, shoulder, radius/ulna, carpal/wrist, hip, other femur, tibia/ presented to the hospital from home after being found in a debil- fibula, ankle) and in pre-specified subpopulations of interest itated state. She had confusion, generalized weakness, unsteady considered to be at high risk for subsequent fx: sex; age 65; age gait, poor appetite, and 40 lb weight loss over 2 months. She denied 80; Type II diabetes mellitus (T2DM), rheumatoid arthritis (RA), polydipsia, polyuria, nausea, vomiting, abdominal pain, con- osteoarthritis (OA), and those with respiratory diseases (asthma/ stipation, or bone pains. She had dry mucous membranes, no chronic obstructive pulmonary disorder). The evaluation period for palpable neck masses, and otherwise unremarkable physical exam. the second fracture started from the index date (first fx event date) Corrected calcium was 21.5 mg/dL (8.5-10.5 mg/dL) and PTH was and was variable based on data availability for different pts. 2012.5 pg/mL (12-88 pg/mL). There were no EKG changes, but she Results: Overall, 755,312 pts met study criteria. Mean age (SD) was did present with acute kidney injury (Cr 1.73 mg/dL). 70.2 (9.4), 69.9% were 65 years, and 71.6% were female. The CT of the neck showed a 4.2 x 2.9 x 1.6 cm soft tissue lesion at the proportion of pts with T2DM, respiratory disease, RA, and OA were level of the thoracic inlet. A 99mTc sestamibi scan showed focal 28.9%, 26.3%, 4.6%, and 27.4% respectively. Almost all pts had a 1- increased radiotracer activity at the level of the inferior thyroid year follow-up data with the mean (SD) of follow-up of 23.8 (6.7) gland in the right parasagittal region. months. Prior to index fx, 11.4% were on an osteoporosis treatment. The patient was treated with aggressive intravenous fluid Over ten percent of pts with an index fx had a second fracture of any resuscitation, calcitonin, cinacalcet, and zoledronic acid before she kind during follow-up: pelvis (18.7%), clinical spine (18.4%), other underwent partial parathyroidectomy with removal of a 4.6 x 3.0 x femur (17.6%), hip (15.9%), tibia/fibula (12.3%), shoulder (12.3%), 1.4 cm right superior parathyroid adenoma weighing 9.97 grams. carpal/wrist (11.1%), ankle (10.9%), and radius (10.1%). Occurrence of Pathology revealed only hypercellular parathyroid tissue and no a second fx at the same site was as follows: clinical spine (12.0%), malignant tissue. Intra-operative PTH was 396.8, followed by 301.1, hip (6.9%) and femur (6.3%), tibia/fibula (5.4%), shoulder (5.4%), then 88.2, and finally 39.2. Post-operative PTH remained normal at pelvis (4.6%), radius/ulna (3.4%), ankle (3.3%) and carpal/wrist 38.5. (2.4%). Secondary fx rates by fx site across all subgroups of interest Discussion: We report an unusual presentation of a benign para- were consistent with the secondary fx rates by fx site for the whole thyroid adenoma causing hyperparathyroid crisis. PHPT usually population. Overall, 102,359 (13.6%) of all pts had a second fx in the presents with mildly elevated calcium and PTH levels; it rarely post index period. Proportion of pts with a second fx in the post causes hyperparathyroid crisis and multi-organ dysfunction. The index period was higher for subgroups of interest with comparable 99mTc-sestamibi scintigraphy is preferred for visualization of the duration of follow-up: women:14.1%; age 65: 14.8%; age 80: hyperfunctional parathyroid gland. Significantly elevated PTH 17.3%; T2DM: 14.9%; respiratory disease: 15.4%; RA: 17.2%; OA: levels and large size is usually indicative of malignancy. While a 16.2%. normal parathyroid gland weighs less than 50 mg and an adenoma Discussion/Conclusion: In summary, a high proportion of pts have a typically weighs 300 mg to several grams, many parathyroid car- second fx following their index fx and the proportion is higher for cinomas can weigh up to 12 g. Emergent medical treatment can older pts, those with index clinical spine fx, and those with chronic lower calcium levels until definitive surgery is performed. conditions associated with increased fx risk and healing. While our patient had significantly elevated PTH and a large https://doi.org/10.1016/j.eprac.2021.04.660 parathyroid lesion, she did not have parathyroid malignancy as initially suspected. Clinicians should be aware that hyper- parathyroid crisis could still present in primary hyperparathyroid- Abstract #1001400 ism caused by large benign adenoma. https://doi.org/10.1016/j.eprac.2021.04.659 Hypercalcemia in Ovarian Clear Cell Carcinoma

Author Block: Abstract #1000585 Imaneh Fallahi - University of New Mexico School of Medicine, Division of Endocrinology, Diabetes, and Metabolism; The Evaluation of Fractures Following a Fragility Patricia Kapnser, Professor of Endocrinology, Diabetes and Fracture in Real-World Setting Metabolism - co-author, University of New Mexico

Introduction: Hypercalcemia of malignancy is categorized into two Author Block: Andrea J. Singer, MD - Primary author, MedStar groups: local osteolytic hypercalcemia due to metastases to bone, Georgetown, University Hospital, Washington, DC, USA; or humoral hypercalcemia of malignancy (HHM) with systemic Setareh A. Williams, PhD - co-author, Radius Health, Inc., Boston, bone resorption due to factors produced by tumor cells, parathyroid MA; Richard J. Weiss, MD - co-author, Radius Health, Inc., Boston hormone related peptide (PTHrP), 1-alpha hydroxylase converting MA; Yamei Wang, PhD - co-author, Radius Health, Inc., Boston, MA; Vit D (25 hydroxyvitamin D) to the active metabolite of Vit D, 1,25- Hily Nichols, BA - co-author, Cobbs Creek Healthcare, Newtown dihydroxyvitamin D (1,25[OH)2D) and PTH (parathyroid hormone). Square, PA; Nick Pyrih, BS - co-author, Cobbs Creek Healthcare, In ovarian clear cell carcinoma, PTHrP is the usual cause of HHM. Newtown Square, PA; Joanna Rega - Radius Health, Inc Case Description: We present an unusual case of HMM in the setting ovarian clear cell carcinoma. A 51-year-old female, status Objective: To evaluate fractures following index fracture (fx) in post hysterectomy in 2017, benign pathology, presented to her real-world setting. Primary Care Physician with nausea, abdominal distension and Methods: A retrospective cohort study was conducted using claims pain, polyuria, polydipsia and brain fog. Evaluation showed calcium data from Symphony Health PatientSource®. Index was defined as (Ca) 14.0 mg/dl (8.4-10.4), albumin (alb) 4.0 g/dl (3.4-4.7), PTH < 6 the date of fx event during identification period (May 1, 2017- pg/ml (18-84), vit D 18 ng/mL(30-100), creatinine 1.16 mg/dl (0.5- March 31, 2019). A previously validated claims-based algorithm 1.4). CT abdomen showed a 9 x 11x 11cm adnexal mass, pelvic ul- was used to identify case qualifying fx. The proportion of patients trasound showed a mixed cystic and solid 9.5 x 10.6 x 10.9 cm (pts) with a second fx was evaluated by index fx site (clinical spine, central pelvic mass, chest x-ray was normal. When seen by

S91 Parathyroid/Bone Disorders Endocrine Practice 27 (2021) S85eS106 endocrinology 4 weeks later, she had progressive symptoms, low intraepithelial lymphocytes suggestive of celiac disease (CD). In back pain and had lost 12 lb. Ca 14.9 mg/dL, alb 3.3 g/dl, PTH < 6 pg/ addition to mineral and vitamin supplementation, the patient was ml, PTHrP 53.2 pmol/L (0-3.4), vit D 42 ng/mL, 1,25[OH)2D 88.9 pg/ treated for right middle lobe pneumococcal pneumonia and mL (18-72). She was admitted and treated with normal saline and Campylobacter diarrhea, and all of her presenting complaints were zoledronate. Ca level normalized. She underwent bilateral sal- resolved at hospital discharge. Due to findings on small bowel bi- pingo-oophorectomy and lymphadenectomy. Pathology showed an opsy, a gluten-free diet was started; however, after six months of ovarian clear cell carcinoma of the right ovary with lympho- adherence, the patient’s vitamin, mineral, and immunoglobulin vascular invasion. She was started on carboplatin apaclitaxel deficiencies persisted. Lack of response to a gluten-free diet was felt chemotherapy. PTHrP decreased to < 2 pmol/L and 1,25[OH)2Dto to indicate CVID complicated by small bowel enteropathy. 54 pg/ml. Vit D remained sufficient and PTH became detectable at Discussion: Patients with CVID may develop a small bowel enter- 52 pg/ml. Ca levels have remained normal. opathy that closely resembles CD and can only be distinguished Discussion: This clear cell carcinoma produced PTHrP which binds from CD by failure to respond to a gluten-free diet. Hypocalcemia to the PTH/PTHrP receptor in bones and kidneys with equal affinity occurs in approximately 5% of CD patients but is uncommonly re- to PTH and causes hypercalcemia. However, PTHrP is not thought to ported in CVID. An all fields PubMed search of “hypocalcemia” and stimulate the production of 1,25[OH)2D as does PTH. Levels are “common variable immunodeficiency” yielded only one English usually low or normal. Our patient had an elevated 1,25[OH)2D language report of severe hypocalcemia due to co-occurring auto- which normalized after surgery. There are case reports of clear cell immune hypoparathyroidism and a Spanish language report of ovarian carcinomas in which the 1,25[OH)2D is elevated in addition tetany as the initial presentation of CVID. Our patient was predis- to PTHrP bringing up the possibility of the tumor producing 1-alpha posed to symptomatic hypocalcemia by severe hypovitaminosis D hydroxylase. This has been shown in a renal clear cell carcinoma in and functional hypoparathyroidism from severe hypomagnesemia. which the hypercalcemia did not resolve with bisphosphonate This case appears to be one of very few in which CVID enteropathy therapy but did after the addition of glucocorticoids. Studies was the cause of severe hypocalcemia. confirmed 1-alpha hydroxylase production by the tumor. One https://doi.org/10.1016/j.eprac.2021.04.662 should consider this a possibility in HHM due to a clear cell carci- noma especially if there is not a response to usual therapy. https://doi.org/10.1016/j.eprac.2021.04.661 Abstract #1002188

Delayed Rebound Hypercalcemia in Severe Abstract #1001822 Rhabdomyolysis-induced Acute Renal Failure

Severe Hypocalcemia as the Initial Presentation of Common Variable Immunodeficiency (CVID) Enteropathy Author Block: Khin Zin - Jersey Shore University Medical Center; Monika Akula, MD - co-author, Endocrinology, Jersey Shore University Medical Center; Katherine Hu, DO - co-author, Author Block: Vanessa Williams, MD - Primary author, Internal Endocrinology, Jersey Shore University Medical Center; Medicine/Endocrinology, Southern Illinois University School of Raquel Ong, MD - co-author, Endocrinology, Jersey Shore Medicine; Noor Wazzan, MD - Presenter, Internal Medicine/ University Medical Center; Soemiwati Holland, MD - co-author, Endocrinology, Southern Illinois University School of Medicine; Endocrinology, Jersey Shore University Medical Center; Anis Rehman, MD - Co-author, Internal Medicine/Endocrinology, Jennifer Cheng, DO - co-author, Endocrinology, Jersey Shore Southern Illinois University School of Medicine; Michael Jakoby, University Medical Center MD/MA - Co-author, Internal Medicine/Endocrinology, Southern Illinois University School of Medicine Introduction: Alteration in calcium metabolism from acute renal failure secondary to rhabdomyolysis can be life-threatening when Introduction: Common variable immunodeficiency (CVID) is a undiagnosed and untreated appropriately. We present a patient primary immunodeficiency with decreased levels of at least two with severe rhabdomyolysis who developed acute renal failure immunoglobulin subtypes. Patients typically present with recur- requiring hemodialysis and delayed hypercalcemia in his recovery rent infections, especially of the respiratory and gastrointestinal phase from renal failure. tracts. However, approximately 15% of patients develop an enter- Case Description: A 66-year-old Caucasian man with no significant opathy that resembles inflammatory bowel disease or celiac dis- past medical history presented to the hospital with altered mental ease. We present a case of symptomatic hypocalcemia leading to a status after being found on the floor by his sister who was unable to diagnosis of CVID enteropathy. contact him for three days. He was alert and awake but not ori- Case Description: A 41-year-old female with no medical or surgical ented. The rest of the physical examination was unremarkable. Lab history presented to the emergency department due to 1-week of results showed significantly elevated creatinine kinase > 82,000 iU/ perioral numbness and carpopedal spasm. The patient reported L (22-232 iU/L), AST 1501 U/L (10-42 U/L), ALT 694 U/L (10-60 U/L), mild, intermittent diarrhea over the prior six months, but she de- BUN 98 mg/dL (5-25 mg/dL), creatinine 5.49 mg/dL (0.61-1.24 mg/ nied other symptoms. Calcium level corrected for low albumin was dL), GFR 10 ml/min/1.73m2 ( > 60 ml/min/1.73m2), corrected cal- 6.2 mg/dL (8.6-10.3). Intact parathyroid hormone (PTH) level was cium 7.5 mg/dL (8.5 -10.5 mg/dL) with normal albumin 3.7 g/dL, 45 pg/mL (12-88), magnesium 0.7 mg/dL (1.9-2.7), phosphorus < potassium 5.0 mmol/L (3.5 -5.2 mmol/L), phosphorus 11.2 mg/dL 1.0 mg/dL (2.5-5.0), and 25-hydroxyvitamin D < 7 ng/mL (30-100). (2.5 -4.6 mg/dL), magnesium 3.5 mg/dL (1.3-2.5 mg/dL), carbon Electrolytes were promptly treated, with intact PTH increasing to dioxide 18 mmol/L (24-31 mmol/L), and anion gap 23 mmol/L (5-13 232 pg/mL after supplementing magnesium. Additional evaluation mmol/L). After two days, hemodialysis was initiated and calcium revealed extensive mineral and vitamin deficiencies and hypo- infusions were administered after his calcium level dropped to 5.7 gammaglobulinemia (all immunoglobulin types undetectable). mg/dL with EKG changes of prolonged QTc interval, creatinine Small bowel biopsies showed severe villous blunting and increased increased to 7.82 mg/dL, potassium increased to 5.3 mmol/L and

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GFR decreased to 7 ml/min/1.73m2. Within the three weeks, involvement) requiring urgent therapeutic intervention to prevent rebound hypercalcemia developed with corrected calcium as high life-threatening complications from severely elevated calcium as 14.5 mg/dL despite the improvement of renal function with levels. PHPT can be due to parathyroid hyperplasia, adenoma or hemodialysis. Intact parathyroid hormone level showed remark- carcinoma. It is difficult to distinguish the etiology of PHPT clinically ably elevation at 608.2 pg/mL, 25-hydroxy vitamin D was low at 26 but when PTH levels are greater than 5 times the upper limit of ng/mL and 1,25-dihydroxy vitamin D was low at 19.1 pg/mL. The normal, it usually suggests parathyroid carcinoma. However, in our ultrasound of the neck was negative for parathyroid adenoma. He case, the inordinate levels of PTH were due to parathyroid hyper- was started on intravenous normal saline infusion, calcitonin, and plasia. Imaging modalities are helpful in localizing the disease but sensipar. Renal dosed bisphosphonate was considered to assist in cannot assess malignancy potential and fine needle aspiration improving calcium further but was not needed. Within five days of cytology (FNAC) is contraindicated due to the risk of seeding. Hence, treatment, his calcium level became normalized. early surgery is the ultimate diagnostic and curative modality. Discussion: In a patient with rhabdomyolysis and acute tubular https://doi.org/10.1016/j.eprac.2021.04.664 necrosis, understanding the mechanism of calcium deposition in damaged muscles during the oliguric phase as well as later release of calcium from injured muscles in the recovery phase is of para- Abstract #1002413 mount importance. Overcorrection of hypocalcemia during the oliguric phase and secondary hyperparathyroidism induced by A Practical Surgical Challenge to Treatment of Primary acute renal failure can all contribute to delayed hypercalcemia. The Hyperparathyroidism Secondary to Ectopic purpose of this abstract is to raise clinical suspicion for rhabdo- Parathyroid Gland myolysis-induced rebound hypercalcemia in the recovery phase of acute renal failure. Author Block: https://doi.org/10.1016/j.eprac.2021.04.663 Elina Shakya - LSU-Ochsner Hospital; Rajini Yatavelli Endocrinologist, Diabetes and Metabolism - Co- author, Endocrinology, Ochsner LSU Health Shreveport-Academic Abstract #1002356 medical center

A Problem So Rare Yet So Serious - Parathyroid Crisis Introduction: Primary hyperparathyroidism (PHPT) is a common cause of hypercalcemia and when indicated, surgery is the main- stay of treatment. However, persistence of PHPT after surgery is a Author Block: Asma Syeda, MBBS - primary author, Internal difficult aspect of treatment. Variable anatomy and small size of Medicine, UCONN Health; Nickolas Coombs, DO - co-author, parathyroid glands can make parathyroid surgery particularly Internal Medicine, UCONN Health; Turab Mohammed, MD - co- challenging. Additionally, ectopic parathyroid glands and their author, Internal Medicine, UCONN Health; Madhuri Manne, MD - missed identification during surgery is an important etiology of co-author, Internal Medicine, Saint Francis Hospital persistence of disease after surgery. We present a difficult surgical case of ectopic parathyroid gland despite availability of preopera- Introduction: Parathyroid crisis (PC) is a very rare yet fatal clinical tive localization by 99mTc-sestamibi scan. condition which mandates urgent intervention. We present a case Case Description: A 61- year- old African American male under- of parathyroid crisis with severe symptomatic hypercalcemia and went surgery for primary hyperparathyroidism. Preoperatively his multi-organ involvement. PTH level was 273.7pg/ml (9-77pg/ml) and corrected calcium was Case Description: A 63-year-old male presented with three days of 11.8 mg/dl(8.7-10.5 mg/dl). generalized fatigue, abdominal pain and vomiting. Review of sys- 99mTc-sestamibi scan localized soft tissue lesion measuring 2.6 x tems revealed constipation and symptoms suggestive of depression 2.0 x 2.0 cm, likely representing enlarged ectopic left parathyroid over the past 6 months. Vital signs were notable for tachycardia gland behind the left proximal clavicular head. Patient underwent with a heart rate of 120 beats/minute. On physical examination, the four-hour long neck dissection surgery exploring parathyroid patient was in mild distress and looked dehydrated. Laboratory glands. Left inferior area which was suspicious on preoperative investigations revealed hypercalcemia with a total calcium of 19.9 imaging was meticulously explored. However, no parathyroid gland mg/dL, ionized calcium of 1.83 mmol/L, phosphorus of 3.2 mg/dL, was identified. Prolonged exploration of all quadrants of neck creatinine of 2.7 mg/dL. Hypercalcemia workup revealed a PTH bilaterally did not find abnormal parathyroid gland. Notably, level of 2472 pg/mL and a normal urine calcium, vitamin D level Intraoperative PTH levels did not fall appropriately. and serum protein electrophoresis. Acute kidney injury, depression Postoperatively patient continued to have hypercalcemia with and gastrointestinal symptoms were explained by severe hyper- hyperparathyroidism. He underwent 4D CT for further localization calcemia. He was promptly treated with aggression fluid resusci- of parathyroid adenoma, which showed a hyper enhancing soft tation, pamidronate and calcitonin. A Technetium 99m sestamibi tissue nodule superolateral and posterior to the sternoclavicular scan demonstrated two large bilateral parathyroid masses which joint measuring 2.7 x 2 x 1.2 cm on left. Patient was started on correlated with the findings on the ultrasound. The patient un- Cinacalcet in the interim prior to re-exploration. He underwent derwent bilateral parathyroidectomy and left thyroid lobectomy as second surgery for neck re-exploration. Left inferior parathyroid the left sided mass was adherent to the thyroid gland. Parathyroid adenoma was removed measuring 30 x19 x 9 mm and weighing carcinoma was ruled out on biopsy and was consistent with hy- 3010 mg. His Intraoperative PTH level dropped from 554 pg/ml to 23 perplastic parathyroid tissue. The PTH level decreased to 125 pg/mL pg/ml. Corrected calcium level after this surgery was maintained at intraoperatively and subsequently normalized. Post-operatively 9.3 mg/dl. the patient developed hungry bone syndrome requiring IV calcium Discussion: Despite availability of advanced diagnostic modalities, therapy and large-dose vitamin D supplementation. parathyroidectomy can be an effortful procedure resulting in Discussion: PC is a rare phenomenon where PHPT manifests as a persistence of disease after surgery. Ectopic adenomas have been hypercalcemic crisis (serum calcium >14 mg/dL and multi-organ reported in 4-16% of patients with Primary hyperparathyroidism

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fi and are thought to be a cause of a signi cant portion of failed Abstract #1002830 surgery. This case reinforces consideration of ectopic parathyroid gland in any case of hyperparathyroidism, utility of application of Juvenile Hereditary Hypophosphatasia diagnosed in complementary imaging techniques and intensifies a broader need an adult male for parathyroid surgical expertise. https://doi.org/10.1016/j.eprac.2021.04.665 Author Block: Monika Akula - Jersey Shore University Medical Center; Katherine Hu, DO - co-author, Jersey Shore University Abstract #1002422 medical center; Khin Zin, MD - Co-author, Jersey shore University medical center; Soemiwati Holland, MD - co-author, Jersey Shore Non Traumatic Fractures In Fabry Disease: A Case Report University Medical Center; Raquel Ong, MD - co-author, Jersey Shore University Medical Center; Jennifer Cheng, DO - co-author, Jersey Shore University Medical Center Author Block: Kenda Alkwatli - University of Connecticut; Sobia Faisal, M.B.B.S - Co-author, Endocrinology, Diabetes and Introduction: Hereditary Hypophosphatasia (HPP) is a rare genetic Metabolism, University of Connecticut; Pooja Luthra, M.D., F.A.C.E. condition that presents with signs and symptoms such as weak- - Co-author, Endocrinology, Diabetes and Metabolism, Uconn ening of bones, premature loss of teeth, bowing of legs, short Health stature, craniosynostosis, poor feeding, and respiratory problems. In adults, symptoms of HPP are often misdiagnosed and confused Introduction: Fabry disease (FD) is a rare X-linked inborn error of with other, more common bone or rheumatologic diseases. This can metabolism resulting from the deficiency of a- galactosidase A. It lead to delayed diagnosis and inappropriate treatment such as high causes multi organ involvement including severe renal and cardiac dose Vitamin D, calcium supplementation, or bisphosphonate manifestations. Bone involvement has been suggested in multiple therapy which can be ineffective or even worsen the symptoms. We studies, with osteoporosis being the leading bone manifestation in present a rare case of juvenile HPP diagnosed in adulthood. FD. We describe here a case of FD with multiple non traumatic Case Description: A 49 year old man, with past medical history of fractures. hypertension, hyperlipidemia, chronic kidney disease stage III and a Case Description: Patient is a 60-year-old male with FD who pre- family history of HPP in his sister was seen for an evaluation of HPP. sented with recurrent non traumatic metatarsal fractures. Patient He had small stature, muscle weakness, bone pain, hip pain, and was diagnosed with FD by an ophthalmologist because of corneal waddling gait as a child. He also had premature loss of teeth at age verticillate at age of 30. He had 0% enzyme activity. Patient has other 2. Of note, no history of seizures, respiratory problems, skull disease complications including cardiomyopathy, atrial fibrillation, changes, or bone fracture as a child. At age 48, he had stress frac- neuropathy and nephropathy which progressed to end stage renal tures of bilateral femurs that required complicated, extensive sur- disease and he underwent a living unrelated kidney transplant at gery. During surgery, the upper part of his left femur broke into age of 52. He is on Agalsidase enzyme replacement therapy for FD, multiple pieces. As a result, he had significant disability. Blood work carbamazepine, coumadin, mycophenolate mofetil and Belatacept showed very low serum alkaline phosphatase level of 8 (36-130 U/ post-transplant. Patient has sustained recurrent non traumatic L) and elevated Pyridoxal 5'- phosphate level of >5000 (20-125 metatarsal fractures over the years. He was diagnosed with osteo- nmol/L). These constellation of signs, symptoms, and blood work porosis at age of 40 based on bone mineral density (BMD). He was confirms the diagnosis of HPP. He was started on Asfotase alfa treated with alendronate for 10 years and has been on drug holiday (STRENSIQ). from 2009 till present. In 2019, he had a left tibial plateau closed Discussion: The diagnosis of juvenile onset HPP was missed during fracture while hiking. He was not on calcium or vitamin D supple- childhood and he ultimately presented as an adult with bilateral mentation. BMD revealed osteoporosis at the left forearm, which femur fractures, significant impairment, and poor quality of life. was stable when compared to prior bone densities. Spine and hip HPP is a genetic abnormality that occurs due to mutations in tissue bone density were normal, although he had significant degenerative non specific alkaline phosphatase enzyme (TNSALP). This leads to disease at the lumbar spine which may have overestimated the low activity of TNSALP enzyme in tissues and accumulation of spine BMD. Biochemical workup revealed normal renal function, inorganic pyrophosphate, pyridoxal phosphate which inhibits bone calcium, albumin, phosphorus levels, 25 OH -Vitamin D levels and mineralization. Severity of symptoms vary widely due to a large protein electrophoresis. He did not have evidence of hypogonadism. number of mutations and can present in perinatal, infantile, juve- Random urine calcium and creatinine ratio was low consistent with nile, and adulthood forms. Perinatal form is usually lethal and his poor dietary calcium intake. Patient was advised to optimize nearly 50% of these patients die in infancy. Juvenile form is char- calcium and vitamin D intake at this time. He was not started on acterized by premature loss of deciduous teeth and waddling gait. antiresorptive therapy since BMD had been stable. FDA has approved Asfotase alfa (STRENSIQ) in 2015, before that, Discussion: FD is a rare disorder with multisystem involvement. HPP was treated by supportive therapy. Asfotase alfa is a recom- Patients with FD often have multiple risk factors for osteoporosis binant TNSALP enzyme replacement therapy which is shown to including use of long-term immunosuppression, carbamazpine use improve bone mineralization. HPP can often be missed or mis- for neuropathy, and decrease mobility and exercise intolerance due diagnosed as it resembles other bone or rheumatologic conditions. to cardiomyopathy. There have also been case reports of accumu- We emphasize that health care providers should be vigilant of HPP lation of globotriaosylceramide (GB3) in bone marrow macro- in context of signs and symptoms and missing diagnosis will lead to phages in patients with FD, causing avascular necrosis of the chronic bone, thigh pain, multiple fractures, and impaired quality of femoral head. We suggest that all patients with FD should have life. Low alkaline phosphatase enzyme levels should prompt diag- early assessment of their BMD followed by long-term monitoring to nosis which can be confirmed with genetic testing. Timely initia- help with early recognition of bone disease and prevention of tion of treatment will strengthen bones and prevent further fractures. morbidity. https://doi.org/10.1016/j.eprac.2021.04.666 https://doi.org/10.1016/j.eprac.2021.04.667

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Abstract #1003085 San Francisco, Fresno; Soe Naing, MD - Co-author, University of California, San Francisco-Fresno Differences in Clinical Characteristics of PHPT between the Elder and Younger Patients Introduction: Denosumab is a novel anti-resorptive agent used for the treatment of osteoporosis. It decreases the risk of fractures by inhibiting the receptor activator of nuclear kappa-b ligand (RANKL) Author Block: Yuling He - Division of geriatric endocrinology and which leads to reduced osteoclast activity and bone resorption. metabolic diseases, the first affiliated hospital of Guangxi Medical Denosumab has also been associated with a compensatory increase University; Chi Su Master - co-author, Division of Endocrinology in parathyroid hormone (PTH) levels during the first few months and Metabolism, Rutgers-RWJMS; lingqiong Meng, PHD - co- after injection, especially in the setting of chronic kidney disease. author, Division of Endocrinology and Metabolism, Rutgers- Here we report notable transitory PTH elevations after denosumab RWJMS; Stanley Z. Trooskin, MD - co-author, Divisions of General administration in two patients. Surgery, Departments of Surgery, Rutgers-RWJMS, New Brunswick, Case Description: Case 1: An 83-year-old female, with past medical NJ 08901, USA; Xiangbing Wang, MD - co-author, Division of history of osteoporosis and hypothyroidism, presented for evalua- Endocrinology and Metabolism, Rutgers-RWJMS tion of elevated parathyroid hormone levels. She had been on Objective: Primary hyperparathyroidism (PHPT) is the third most bisphosphonates for 5 years until she was started on denosumab common endocrine disorder, characterised by hypercalcemia and injections in 2018. One week after receiving her first denosumab elevated or inappropriately normal concentrations of parathyroid injection, her PTH level was noted to be significantly elevated to 418 hormone. As the world’s population ages, diagnosis of PHPT is pg/mL (normal reference range 14-64 pg/mL). Repeat PTH 6 months increasingly being reported in older patients. Little is known about later was at 114 pg/mL. The most recent PTH measured at 6 months elderly patients diagnosed with PTHP. after last dose of denosumab was near normal at 83 pg/mL. Our study is to observe the differences in clinical presentation of Case 2: A 62-year-old female, with past medical history of Roux- PHPT between elder and younger patients. En-Y gastric bypass surgery and osteoporosis, presented for evalu- Methods: In this retrospective analysis of medical records, we ation of elevated parathyroid hormone levels. She had been getting reviewed 384 cases aged 50-74 years(defined as younger group) denosumab injections since 2018. PTH was significantly elevated to and 67 cases aged over 75 years (defined as older group) . The 600 pg/mL in 2019, approximately 2 months after getting her clinical Presentations and laboratory data were compared between second dose of denosumab. The most recent PTH measured at 6 the two groups. iPTH associations were also assessed along with months after last dose of denosumab was normal at 39 pg/mL. several other parameters. Discussion: Both cases demonstrate the transient yet significant Results: Elder PHPT patients had higher incidence of joint and back changes in parathyroid hormone levels that can be associated with pain and fractures (p < 0 05). The frequencies of coronary heart denosumab. Some studies have shown that increased PTH may be a disease/stroke (p < 0 05), Colorectal cancer and skin cancer (p < compensatory response to maintain serum calcium levels since hy- 0 01) in the elder than in the younger group. The elder patients had pocalcemia can occur with antiresorptive treatments. This phenome- higher iPTH (p < 0 05) than younger, but there were no differences non may lead to misinterpretation of laboratory tests and expose in 25-hydroxyvitamin D (25 (OH) D), serum calcium, corrected patients to unnecessary evaluations for primary hyperparathyroidism. serum calcium in the two groups. Serum iPTH level was positively https://doi.org/10.1016/j.eprac.2021.04.669 correlated with serum calcium and serum AKP levels but negative correlated with 25-hydroxyvitamin D (p < 0 01) .The BMDs of < lumbar spine (p 0 05) , hip regions, femoral neck and left 1/3 Abstract #1003217 radius (p < 0 01) were all lower in the elder than in the younger. Discussion/Conclusion: With the aging process, the elderly patients A Case of X-Linked Hypophosphatemic Rickets with with PHPT are increasingly concerned. Our study showed that the Tertiary Hyperparathyroidism elderly patients had a higher prevalence of complications such as coronary heart disease, stroke and rectal cancer, which were all age- related diseases. Compared with the younger group, bone mineral Author Block: Sareen Sandhu - Loma Linda University; density was significantly decreased, which was related to aging, and Mitali Talsania, MBBS - Co-author, Endocrinology, Loma Linda may be related to the high level of PTH. Therefore, the treatment for University elder patients with PHPT should be considered comprehensively. Conclusions: There were distinct clinical and biochemical dif- Introduction: X-linked hypophosphatemic rickets is a disorder ferences between the elder and the younger. Our study revealed characterized by renal phosphate wasting and subsequent bone that the elder PHPT patients had more severe PHPT clinical mani- demineralization. It is caused by a loss of function mutation of the festations, lower bone mineral density, and higher incidence of phosphate regulating endopeptidase gene on the X chromosome accompanied diseases. leading to an increased production of fibroblast growth factor 23 https://doi.org/10.1016/j.eprac.2021.04.668 (FGF23). Increased FGF23 inhibits phosphate reabsorption in the kidney. The resulting hypophosphatemia leads to bone deminer- alization and rickets. Standard treatment includes phosphate sup- Abstract #1003150 plementation which lowers ionized calcium concentration eliciting an upregulation of parathyroid hormone (PTH). Progression to Elevated Parathyroid Hormone Levels Following tertiary hyperparathyroidism due to development of autonomous Denosumab Treatment: A Case Series hyperfunction of the parathyroid glands has been reported. We present a rare case of X-linked hypophosphatemic rickets with tertiary hyperparathyroidism. Author Block: Aye Khine - University of California, San Francisco- Case Description: A 22 year old woman came to clinic for man- Fresno; Mehdia Amini, MD - Co-author, University of California, agement of X-linked hypophosphatemic rickets. She was diagnosed

S95 Parathyroid/Bone Disorders Endocrine Practice 27 (2021) S85eS106 with rickets at age two with bowing of her legs, elevated FGF23 suppressed PTH level of 11.0 pg/mL (8.7-77.1). He had a low Vitamin (2293 RU/mL; reference 44-215 RU/mL), increased urinary phos- D 25-Hydroxy (25OHD) level of 24.5 ng/mL (30-80), an elevated phorus at 185.4 mg/dL ( >100 mg/dL) and low phosphorus levels. parathyroid hormone-related peptide (PTHrP) level of 3.2 pmol/L Her grandmother has a history of short stature. Previous medica- (0-2.3), and a significantly elevated calcitriol level of 136 pg/mL tion regimen included phosphorous supplementation and calci- (19.9-79.3). He was found to have multiple brain lesions and bone triol. Recently, patient has been taking burosumab. Labs were marrow involvement consistent with DH. His fungal cultures grew significant for: calcium 12.2 mg/dL (elevated for 5 years), PTH 316 Histoplasma capsulatum. To avoid amphotericin B-related neph- pg/mL, phosphorous 1.7 mg/dL, creatinine 0.55 mg/dL, vitamin D rotoxicity, he was started on oral voriconazole. Intravenous fluids 25-OH 18 ng/mL, and fractional excretion of calcium 0.32, consis- (IVF), calcitonin, and bisphosphonates lowered his corrected Ca to tent with tertiary hyperparathyroidism as patient previously had 11.2 mg/dL. His symptoms improved and he was discharged home normal calcium and high PTH. Dual-energy x-ray absorptiometry on voriconazole with outpatient infectious disease follow-up. (DXA) showed Z-score of -2.9 at distal 1/3 of radius. A sestamibi Discussion: DH is an unusual cause of hypercalcemia. Activated scan detected right inferior parathyroid adenoma. She had resec- macrophages in granulomatous diseases increase expression of 1 tion of the adenoma with normalization of serum calcium. PTH has alpha-hydroxylase which converts 25OHD to calcitriol independent remained elevated with normal calcium postoperatively indicating of parathyroid hormone feedback. Immunostaining has shown she has four gland hyperplasia. PTHrP expression in granulomas, providing an additional mecha- Discussion: Tertiary hyperparathyroidism is a rare complication of nism for hypercalcemia in this case. Our patient’s Ca levels were X-linked hypophosphatemic rickets and occurs in patients treated corrected with IVF and bisphosphonate therapy but treatment of with phosphate and calcitriol. The resultant decrease in serum the underlying cause with anti-fungal medication was essential to calcium that occurs in response to this therapy causes secondary maintaining normal Ca levels. This case highlights the importance hyperparathyroidism which can progress to autonomous tertiary of considering infectious granulomatous diseases in the differential hyperparathyroidism requiring surgical intervention. Recently, the for hypercalcemia. US Food and Drug Administration has approved burosumab, a hu- https://doi.org/10.1016/j.eprac.2021.04.671 man anti-FGF23 monoclonal antibody, that offers an alternative effective treatment with limited side effects and can be considered in untreated children or those who have received phosphate/cal- Abstract #1003260 citriol therapy with limited benefits or adverse side effects. https://doi.org/10.1016/j.eprac.2021.04.670 Osteitis Fibrosa Cystica (OFC) - An Unusual Presentation of Contemporary Primary Hyperparathyroidism (PHPT)

Abstract #1003234 Author Block: Arti Bhan - Henry Ford Health System; An Case of Severe Hypercalcemia from Progressive Dhanwada S. Rao, MD, FACE - co-author, Henry Ford Health Disseminated Histoplasmosis in an System; Michael Singer, MD, FACE - co-author, Henry Ford Health Immunocompetent Adult System

Introduction: OFC (or brown tumors) among patients with Primary Author Block: Azeen Anjum, MD - primary author, Internal hyperparathyroidism ( PHPT) in the US is very rare; PHPT usually Medicine, Texas Health Presbyterian Hospital of Dallas; presents as asymptomatic hypercalcemia during routine biochem- Gayane Tumyan, MD - Co-author, Internal Medicine, Texas Health ical screening. OFC can sometimes be misdiagnosed as metastatic Presbyterian Hospital of Dallas bone disease, bone cysts, multiple myeloma and osteosarcoma. The differentiating feature is hypercalcemia, with elevated PTH levels. Introduction: Histoplasmosis is a common endemic mycosis in the When a lytic lesion is seen on radiography, in the presence of hy- United States but an uncommon cause of parathyroid hormone percalcemia, evaluation for PHPT should be initiated. (PTH) independent hypercalcemia. Typically seen in immunocom- Case Description: We report a 26-year-old woman, who presented promised patients, this case of disseminated histoplasmosis (DH) in with a 3-month history of worsening, left knee pain, resulting in an immunocompetent adult is an unusual etiology of severe progressive immobility. X-rays of the knee revealed a lytic lesion in symptomatic hypercalcemia. the distal left femur and MRI showed T1 hypointense and T2 Case Description: A 68 year-old male with diabetes, chronic kidney hyperintense lesions in the patella and epicondyle with well disease (CKD) and coronary artery disease presented with one year demarcated borders, suggestive of a brown tumor. Serum calcium of weight loss, fatigue and two weeks of muscle cramps, con- was elevated at 12.4 mg/dl with a concurrent PTH of 731 pg/ml and stipation, and generalized weakness. Six months prior to presen- high urine calcium of 873 mg/vol. BMD was decreased at all sites, tation he was diagnosed with CKD and found to have with Z-scores of e3.8, -4.6 and e6.3 at the spine, femoral neck and hypercalcemia. Worsening hypercalcemia prompted a malignancy 1/3rd forearm respectively. A 2 cm mass at the lower pole of the work-up and CT imaging revealed bilateral adrenal nodules and right thyroid lobe was seen on bedside US, and at surgery, a 2 cm splenomegaly. Adrenal biopsy showed necrotizing granulomatous parathyroid adenoma was found. Histopathology was consistent inflammation with yeast forms suggestive of histoplasmosis. He with an atypical parathyroid adenoma and revealed a high mitotic was HIV negative and had no history of immunocompromise. His index and two areas of capsular invasion. only risk factor for exposure was his occupation as a truck driver Discussion: The presentation of PHPT has changed dramatically with routes in the Midwest and Southeast United States. He pre- over the past several decades in the US, mostly due to routine sented to the hospital with symptomatic hypotension with a blood biochemical screening, so the severe manifestations of PHPT like pressure of 91/55 mmHg. Laboratory testing revealed leukopenia nephrolithiasis/calcinosis and brown tumors are rarely seen in with peripheral eosinophilia. His corrected calcium (Ca) was contemporary PHPT. In addition, the diagnosis of OFC is often significantly elevated at 16 mg/dL (8.4-10.2) with an appropriately delayed because of a mistaken diagnosis of skeletal metastasis in a

S96 Parathyroid/Bone Disorders Endocrine Practice 27 (2021) S85eS106

< patient with hypercalcemia. The worldwide prevalence of OFC is Abstract #1003437 0.1%, mostly confined to endemic areas of vitamin D deficiency. In fact, we have seen only 7 patients among >2500 patients since An Unusual Case of Drug Induced Hypoparathyroidism 1980. Brown tumors are erosive bone lesions caused by intense osteoclastic activity and fibrosis due to excess PTH resulting in Author Block: locally destructive lesions, commonly seen in long bones, pelvis, Vijay G. Eranki, MD - primary author, Endocrinology, TTUHSC; Devi Suravajjala - Texas Tech University of Health ribs, and the skull. It is not a true neoplasm. OFC manifests clinically by bone pain and radiologically by subperiosteal bone resorption, Sciences “salt and pepper” appearance of the skull, and brown tumors. Introduction: Following parathyroidectomy and consequent normalization of Endocrinologists often see patients with hypopara- PTH, OFC heal with sclerosis, but the bone deformity persists. The thyroidism. Evidence exists of the impact of anti-epileptics on bone best way to distinguish OFC of PHPT from malignant bone lesions is health. We note a case in which there may be a possible association to measure serum calcium and PTH levels: in PHPT both serum with the use of Topiramate and a low PTH. Case Description: calcium and PTH levels are elevated, whereas PTH levels are sup- A 23-year-old female with intellectual disability pressed in hypercalcemia of malignancy and seizure disorder presented to us for evaluation of low PTH done for work up of increased ALP (alkaline phosphatase), noted 3 https://doi.org/10.1016/j.eprac.2021.04.672 months prior to our visit. On review of medications, she was on Topiramate and Levetiracetam for more than a year. No history of fractures or bone pain noted. Physical exam was unremarkable. Abstract #1003276 The baseline labs were PTH: 11 pg/ml (15-65), Vitamin D: 41 ng/ ml (30-100), Ca: 9.7 mg/dl (8.7-10.2), ALP: 196 IU/ML (0-32), Mg Increased Fracture Prevalence Among Older Women and Phos not available. Repeat labs at 3 months showed: PTH: 20 with Isolated Osteoporosis at the Forearm pg/ml (15-65), Vitamin D: 23.5ng/ml (30-100), Ca: 10 mg/dl (8.7- 10.2), Phos: 3.6 (3.0-4.3), Magnesium: 2 mg/dl (1.6-2.3), ALP: 303 IU/ml (0-32). As noted above the PTH remained relatively low for Author Block: Tariq Chukir, MD - Presenter and primary author, the low Vitamin D. WCM-Q; Katherine Haseltine, MD - Co author, HSS; Huong Do, Discussion: Topiramate is used for treatment of epilepsy and Director of Clinical data core - co-author, HSS; Donald McMahon migraine. Very little evidence exists on the association between Statistician - co-author, HSS; Emily Stein, MD - Co-author/PI, HSS topiramate and low PTH, effects on calcium level and bone turn- over. Very few cases have been reported in the literature on this. Objective: Patients found to have isolated osteoporosis at the 1/3 Although normal calcium levels have been observed, there is a radius (1/3RO) represent a therapeutic dilemma. As it is unknown consistent elevation of ALP with no clear effect on bone health. whether 1/3RO is associated with an increased risk of fragility Trials are ongoing to try to demonstrate the identified effects of fractures, it is unclear whether these patients should be treated. topiramate. In a study of 36 patients, those on Topiramate had fi This study aimed to investigate the clinical signi cance of isolated higher levels of bone formation markers compared with normal osteoporosis at the forearm and identify the clinical factors asso- subjects or those on anti-epileptics. ciated with fractures in women with 1/3RO. Topiramate is known for its action on many voltage gated ligands Methods: This retrospective study compared medical history, through various mechanisms but one common characteristic iden- fracture prevalence, areal BMD and Trabecular Bone Score in tified was all Topiramate receptors channels and ligands are regu- ¼ postmenopausal women with 1/3RO (n 107), age-matched lated by protein phosphorylation. Topiramate may prevent protein ¼ women with osteoporosis at the hip and/or spine (PMO, n 214), kinases A and C from phosphorylating the channels. The calcium- ¼ and controls without osteoporosis at any site (n 214). We then sensing receptor on parathyroid gland cells is also modulated by compared clinical and densitometric characteristics among women protein kinases A and C. This effect on preventing phosphorylation of with 1/3RO according to fracture history. We hypothesized 1/3RO the calcium-sensing receptor may lead to a reduced PTH secretion. would be related to primary hyperparathyroidism or conditions Topiramate is a weak carbonic anhydrase inhibitor that may lead that foster secondary hyperparathyroidism, lower intake of calcium to metabolic acidosis and have adverse effects on bone health and vitamin D and chronic kidney disease. Women with 1/3RO though it was not associated with significant fracture risk. would have a higher prevalence of fractures compared to controls Conclusion: but similar prevalence of fractures to PMO. A thorough history and evaluation is needed for hypoparathy- Results: ± Of 535 women included, mean age was 71 8 years. 1/3RO roidism and even rare causes such as Topiramate should be ¼ had BMD in the osteopenic range at other sites (spine -1.0, total considered in the differential. More data is needed in this regard to ¼ ¼ hip -1.4, femoral neck -1.7). 1/3RO reported similar calcium and confirm a definitive association. vitamin D intake, prevalence of primary hyperparathyroidism, chronic kidney disease, and other comorbidities compared to other https://doi.org/10.1016/j.eprac.2021.04.674 groups. Osteoporotic fractures tended to be more frequent among PMO (PMO: 31%, 1/3RO: 21%, Controls: 23%, p¼0.07). There was no difference in extremity fractures. Among 1/3RO, fracture preva- Abstract #1003594 lence was related to older age. No other clinical characteristic The Novel Use of Ga-68 Dotatate PET/CT for Skeletal distinguished women with and without fracture. Neither BMD at Lesions of Parathyroid Carcinoma other sites nor TBS differed according to fracture history. Discussion/Conclusion: Among postmenopausal women with 1/ 3RO, those who are older are at an increased risk of fracture. Author Block: Niyoti Reddy, MD - Primary author, Endocrinology, Additional research is needed to confirm our results, which suggest Boston Medical Center; danica M. Vodopivec, MD - Co-author, that these patients may benefit most from treatment. Endocrinology, Boston Medical Center; stephanie L. Lee, MD PhD - https://doi.org/10.1016/j.eprac.2021.04.673 Co-author, Endocrinology, Boston Medical Center

S97 Parathyroid/Bone Disorders Endocrine Practice 27 (2021) S85eS106

Introduction: Parathyroid carcinoma (PC) may metastasize to bone. Samaritan Hospital; Pamela R. Schroeder, MD, PhD - co-author, It is difficult to differentiate PC bone metastasis from a PHPT- MedStar Union Memorial Hospital related brown tumor by conventional imaging. We report a case in which a Ga68-DOTATATE PET/CT scan was able to make this Introduction: Osteoporosis is a ubiquitous disease with a preva- differentiation. lence of over 200 million people worldwide and is a major risk Case Description: A 63-year-old man with a 13-year history of factor for bone fractures, decreased quality of life, and increased recurrent PC requiring 5 operations (parathyroidectomies, thy- mortality. Primary causes account for the majority of cases and roidectomy, and neck dissections) presented with polyuria, include postmenopausal estrogen loss and age-related bone loss. polydipsia, and worsening rib pain. Labs revealed elevated Secondary causes account for 30% of cases in postmenopausal serum Ca 13.1mg/dL (8-10.5mg/dL), albumin 3.8mg/dL, elevated women and 50% in men, with chronic glucocorticoid use being the PTH 1750pg/mL (11-90pg/mL) and elevated serum Cr at 3.34mg/ most common secondary cause. Hyperhomocysteinemia (HHcy) dL (0.5-1.3mg/dL). Neck ultrasound showed 3 hypoechoic masses has been associated with lower bone mineral density and rarely in the left thyroid bed (the largest 1.6 cm), and a 4th mass in may be the cause of osteoporosis as a diagnosis of exclusion. the left central neck (1.1 cm). The degree of PTH/Ca elevation Case Description: A 50-year-old male was referred to the endo- was inconsistent with the small interval growth of the residual crinology clinic for management of osteoporosis diagnosed at 40 locoregional tumor, thus distant metastatic disease was sus- years of age after a left hip fracture from a ground-level fall. He did pected. A CT chest revealed a 3.6cm lytic lesion in the right 6th not have any common osteoporosis risk factors, such as smoking, rib for which the differential was a brown tumor or a PC bone alcohol use, or steroid use. At the time of diagnosis, he took Vitamin metastasis. A F18-fluorodeoxyglucose PET/CT (F18-FDG-PET/CT) D 2000 IU with 2-3 servings of calcium-rich food daily and walked scan revealed that the rib lesion was hypermetabolic (SUVmax of 1-2 miles/day. Treatment with alendronate was initiated but was 5.6). AGa68-DOTATATE PET/CT scan that was performed 6 stopped with treatment failure 5 years later after he sustained months prior to current presentation to evaluate octreotide as a bilateral ankle fracture after a 3-foot fall. DEXA scan at that time possible therapy showed that the right 6th rib lesion (size 1.6cm and 2 years later showed a lumbar spine T score of -3.2. Complete at that time) was tracer avid (SUVmax of 6.5). He was treated for work-up of secondary causes for osteoporosis was unrevealing, acute hypercalcemic crisis and was discharged on cinacalcet. A including parathyroid hormone 24 (14-64) pg/mL, total testos- few weeks later a rib excision was performed. Pre-operative PTH terone 346 (250-827) ng/dL, TSH 2.08 (0.4-4.5) mlU/L, prolactin 7.6 of 2334 pg/dL decreased to 671ng/dL after surgery. Similarly, (2-18) ng/mL, corrected serum calcium level 9.7 (8.6-10.3) mg/dL, serum Ca decreased to 9.3mg/dL off cinacalcet. Pathology alkaline phosphatase 85 (35-144) units/L, phosphorous 2.8 (2.5- confirmed metastatic PC. 4.5) mg/dL, normal serum protein electrophoresis pattern, negative Discussion: Longstanding PHPT may cause a metabolic bone dis- tissue transglutaminase IgA, and 24-hour urine calcium level of 177 ease called osteitis fibrosa cystica, and a localized form is a brown (55-300) mg/24hr with urine Ca:Cr ratio of 133 mg/gm Cr. His tumor. FDG PET/CT scanning is used to differentiate benign and homocysteine (Hcy) level was 11.8 (0-11.4) umol/L, which was 15.1 malignant lesions because of the differentially high glucose meta- umol/L about 5 years before this visit. Vitamin B 12 and folate levels bolism of metastases. However, brown tumors also have a high were 533 (200-1100) pg/mL and 15.8 (2.7-17) ng/mL, respectively. glucose metabolism because of increased cellular (macrophage and He was diagnosed with HHcy-induced osteoporosis after all other giant cell) activity and can be positive on FDG PET/CT scan. There secondary causes were ruled out. are reports of brown tumors mistaken for metastatic disease Discussion: Hcy has been found to be directly involved in activation leading to a biopsy. Ga68-DOTATATE PET/CT binds to the cell surface of osteoclasts, induction of osteoblast apoptosis, and decreased somatostatin receptor subtype 2 and is the preferred functional blood flow to the bone. Several studies have found a close associ- imaging modality for localization of an unknown primary and the ation between HHcy, elevated risk for osteoporosis, and bone diagnosis of neuroendocrine tumors. Ranade et al. reported that fracture, especially in those 59 years or older. HHcy induced oste- metastatic neuroendocrine tumor was positive with Ga68-DOTA- oporosis is a diagnosis of exclusion. It is well known that low TATE PE T/CT while lesions of metabolic bone disease were nega- vitamin B 12 and folate can cause high Hcy. No guidelines exist for tive. Given this, and the fact that our patient’s metastasis was Ga68- this rare entity, but HHcy may be considered in cases where all DOTATATE and FDG scan positive, we conclude that a Ga68-DOTA- other secondary causes have been ruled out. TATE scan may differentiate between the two- positive in PC met- https://doi.org/10.1016/j.eprac.2021.04.676 astatic disease and negative in brown tumors. To our knowledge, this is the first case reported in the literature where this conclusion has been reached. Differentiating between these two radiographi- Abstract #1003631 cally identical bone lesions (osteolytic expansile lesions) is crucial as removal of a PC bone metastasis can result in amelioration of Metastatic Calcinosis Cutis in a Kidney Transplant hypercalcemia. Patient with Normal Calcium and Phosphate https://doi.org/10.1016/j.eprac.2021.04.675

Author Block: Thanh Hoang - Walter Reed National Military Abstract #1003622 Medical Center; Nguyen T. Nguyen, MD - co-author, Endocrinology, Walter Reed National Military Medical Center; Mohamed K. Shakir, Hyperhomocysteinemia and Osteoporisis: Should We MD - Co-author, Endocrinology, Walter Reed National Military Check Homocysteine Levels More Often? Medical Center

Introduction: Calcinosis cutis is an unusual disorder characterized Author Block: Mohammad-ehsan Owrangi - Medstar Union by calcium phosphate deposition into cutaneous and subcutaneous Memorial Hospital; Ling Cui, MD - co-author, MedStar Union tissues. There are 5 subtypes: dystrophic, metastatic, idiopathic, Memorial Hospital; Malek Cheikh, MD - co-author, MedStar Good iatrogenic and calciphylaxis. We report a case of widespread

S98 Parathyroid/Bone Disorders Endocrine Practice 27 (2021) S85eS106 calcification in skin, soft tissue and blood vessels after kidney genes associated with hypoparathyroidism and her results revealed transplant in a setting of normal calcium and phosphate levels. that she is heterozygous for a variant of uncertain significance in Case Description: A 68-year-old Asian woman with a history of the GATA3 gene. hemodialysis-dependent ESRD secondary to IgA vasculitis s/p kid- Discussion: Pathogenic mutations in the GATA3 gene cause a ney transplant presented with peau d’orange and painful indura- rare syndrome called Barakat Syndrome, also known as HDR tion of skin on bilateral legs and evolved to left elbow and right syndrome, which consists of hypoparathyroidism, sensorineural clavicle. Laboratory findings showed stable renal function, normal hearing loss, and renal disease. GATA3 is a transcription factor serum calcium 8.9 mg/dL and phosphate 4.9 mg/dL, with mildly that regulates the expression of genes involved in the develop- elevated serum PTH 100pg/mL. Levels of serum 25-hydroxyvitamin ment of the parathyroid glands, sensory components of the D, 1,25-dihydroxyvitamin D and urine calcium are within normal auditory system, and the kidney. There is a wide phenotypic range. DXA showed osteoporosis. X-rays of bilateral legs showed variability, but the sensorineural hearing loss, which is usually extensive subcutaneous and vascular calcification. Skin excision bilateral, is the most penetrant of the three features. Patients biopsy revealed deep dermal to subcutaneous extravascular and commonly present with early onset bilateral hearing loss. vascular calcification consistent with metastatic calcinosis cutis. However, our patient presented with isolated hypoparathyroid- Patient did not tolerate low-dose cinacalcet due to symptomatic ism. She did not have sensorineural hearing loss or renal disease hypocalcemia nor topical thiosulfate due to skin irritation. Patient that is seen with Barakat Syndrome. It might be that the mu- received oral weekly alendronate for osteoporosis. tation variant observed in this patient is associated with milder Discussion: Calcinosis cutis is a rare condition. Metastatic calcinosis forms of HDR syndrome with isolated hypoparathyroidism only. cutis can be related to ESRD with or without phosphate and calcium This clinical case might add important knowledge to the library metabolism abnormalities. Treatment for calcinosis cutis can be of mutations associated with hypoparathyroidism. challenging. Trauma avoidance, smoking cessation, stress/inflam- https://doi.org/10.1016/j.eprac.2021.04.678 mation/cold exposure reduction should be counseled. Small/local- ized lesions can be treated surgically; however, generalized disease, as in our case, will require medical management such as Abstract #1003673 bisphosphonates, sodium thiosulfate, diltiazem, IV Ig. The out- comes are variable because the condition has no cure. Normocalcemic Primary Hyperparathyroidism Post https://doi.org/10.1016/j.eprac.2021.04.677 Bariatric Surgery

Author Block: Abstract #1003636 Emily Silverman, MD - primary author, University of Nebraska Medical Center; Ilia Bernstein, BMBS - co-author, Heterozygous GATA3 Gene Mutation and Isolated University of Nebraska Medical Center; Padmaja Akkireddy, MBBS Hypoparathyroidism Diagnosed in Adulthood - co-author, University of Nebraska Medical Center

Introduction: Secondary hyperparathyroidism is a well-estab- Author Block: Hadir Mohamed - Albany Medical Center; lished post bariatric surgery complication and is often due to cal- Grace Kim, MD - Co-author, Endocrinology, Albany Medical Center; cium and Vitamin D malabsorption and deficiency. Primary Anna Ziganshina, MD - Co-Author, Endocrinology, Albany Medical hyperparathyroidism post bariatric surgery is rare and often poses a Center diagnostic challenge. We describe a case of normocalcemic primary hyperparathyroidism (NPHPT) in a patient with a history of bar- Introduction: Hypoparathyroidism is a disorder of calcium meta- iatric surgery who was successfully treated with para- bolism that presents with hypocalcemia and hyperphosphatemia. It thyroidectomy. NPHPT is characterized by persistently elevated is caused by a deficiency of parathyroid hormone (PTH). It can be serum PTH levels in the setting of normal albumin-adjusted and seen as an isolated disorder or it can be a component of a syndrome. ionized serum calcium levels, and by the absence of secondary Although genetic causes of hypoparathyroidism are not common, a causes of PTH elevation. number of genes have been identified that can lead to a disorder in Case Description: A 59-year-old female was referred to the clinic parathyroid gland formation or PTH synthesis and secretion. Some for evaluation of an elevated PTH of 101 pg/mL. Her medical history can lead to destruction of the parathyroid gland. We herein present was significant for Roux-en-Y gastric bypass in 2007. The patient a case of isolated hypoparathyroidism diagnosed in adulthood endorsed a one-year history of fatigue, arthralgias, polydipsia, and secondary to a rare genetic mutation in the GATA3 gene. memory issues. Due to fatigue, she was not able to participate in Case Description: A 55-year-old female was diagnosed with idio- exercise which contributed to significant weight regain. She has no pathic hypoparathyroidism in 1993 after presenting with general- history of kidney stones or osteoporosis. She was not on calcium ized seizures two months after giving birth to her son. At that time, supplements. Lab data showed calcium of 9.9 mg/dL (ref 8.6- she reported having a long history of intermittent numbness and 10.2mg/dL) with normal albumin of 4.1 g/dL, PTH of 101 pg/mL (12- tingling in her extremities and face that was not previously eval- 88 pg/ml). Further evaluation showed normal ionized calcium, 25- uated. After she was found to be hypocalcemic, she was started on OH Vitamin D was 49 ng/mL, GFR > 60. Urine studies were obtained calcitriol, which she took for about three years but self-dis- to rule out calcium malabsorption, however her 24-hour urine continued and stopped following up with endocrinology. She calcium came back normal at 255 mg/24hr (ref 100-300mg/24 hr). continued to have occasional symptoms of paresthesia and she was The results indicated good calcium absorption and supported a referred back to endocrinology by her primary care physician in diagnosis of NPHPT. DXA scan showed low T scores consistent with 2019 for hypocalcemia. Endocrinology re-evaluated the patient and osteopenia at lumbar spine and femoral neck. Since the patient was repeat blood work revealed hypocalcemia and hypoparathyroidism symptomatic, we referred her for surgery. Localization studies with calcium corrected for albumin of 8.5 mg/dL (n 8.6-10.4 mg/dL) showed enlarged right parathyroid gland. She successfully under- and PTH of 7 pg/mL (n 12-88). She underwent genetic testing for 15 went right superior parathyroidectomy. Intra-operative PTH levels

S99 Parathyroid/Bone Disorders Endocrine Practice 27 (2021) S85eS106 dropped from 118 to 27 pg/mL, and post-op pathology showed disease-causing gene mutations of CASR reported in medical hypercellular parathyroid tissue measuring 525mg. literature. Discussion: Primary hyperparathyroidism, in particular NPHPT, is a Loss or gain of function mutations of CASR lead to hypercalcemic rare cause of PTH elevation in post bariatric surgery patients. It is or less commonly occurring hypocalcemic disorders respectively. important to recognize NPHPT and differentiate it from secondary Familial hypercalcemic hypocalciuria is an inheritable loss of hyperparathyroidism which is more common in this population. function mutation leading to mild hypercalcemia. Normal serum The patient’s symptoms and urine calcium studies were particu- calcium levels such as in our case might also be due to autoimmune larly helpful in our case to establish a diagnosis of NPHPT. Suc- hypoparathyroidism due to autoantibodies to extracellular portion cessful treatment led to improvement in patient’s symptoms, her of CASR, which can enhance receptor function and decrease PTH energy levels improved, and she was able to participate in exercise secretion. and continue her weight loss pursuits. Medical literature pertaining to the etiology and management of this disorder is scarce. Our case aims to shed light on this rare https://doi.org/10.1016/j.eprac.2021.04.679 variant in order to encourage additional research to better under- stand this condition.

Abstract #1003707 https://doi.org/10.1016/j.eprac.2021.04.680

A Parathyroid Paradox: Hypoparathyroidism without Hypocalcemia Abstract #1003734

Biphasic Response of Calcium Concentrations in Author Block: Samarth Virmani, MBBS - Primary author and Rhabdomyolysis Induced Acute Kidney Injury presenter, Department of Internal Medicine, University of Central Florida College of Medicine, Orlando, FL, USA, University of Central Florida HCA Healthcare GME, Orlando, Florida; Author Block: Claudia Villatoro Santos, MD, PhD - primary author, Gabriela Zuniga Paniagua, MD - Co author, Department of Internal Internal Medicine, Ascension St John Hospital; Margaret Fadanelli, Medicine, University of Central Florida College of Medicine, MD - co-author, Endocrinology, Ascension St John Hospital Orlando, FL, USA, University of Central Florida HCA Healthcare GME, Orlando, Florida; Suzanne Quinn-Martinez, MD - Co author, Introduction: Rhabdomyolysis typically results in acute kidney Department of Internal Medicine, University of Central Florida injury (AKI). Calcium concentrations can have a biphasic distribu- College of Medicine, Orlando, FL, USA, Section of Endocrinology, tion with initial hypocalcemia during the AKI oliguric phase and Orlando VA Medical Center, Orlando, FL later hypercalcemia during the polyuric phase. We present a case of rhabdomyolysis and AKI with a biphasic calcium response. Introduction: Primary hypoparathyroidism is a disorder that is Case Description: A 28-year-old Caucasian male without significant usually characterized by hypocalcemia and hyperphosphatemia medical history presented with sudden, excruciating pain of the associated with low or inappropriately normal levels of parathyroid right lower extremity. The pain was rated 10/10, located in the right hormone (PTH). We present a unique case of a patient with a calf with radiation to the groin associated with edema, skin blisters, variant of hypoparathyroidism which manifests with numbness, tingling, and weakness. He denied recent trauma, normocalcemia. infection, drug use, surgery, or long travel. Laboratory evaluation Case Description: A 53-y/o male presented to the endocrinology showed AKI with creatinine 3.9 mg/dL, hyponatremia, hyper- clinic due to low PTH associated with normal serum calcium levels. kalemia, and CPK 2,417 IU/L. A non-contrast CT of the affected leg Medical history is significant for hypertension and nephrolithiasis showed diffuse myositis. Doppler US was negative for arterial or (calcium oxalate stones). He takes no calcium or vitamin D sup- venous thrombosis. The lateral compartment pressure was elevated plements, has no family history of calcium related disorders, and is (88 mmHg), and he underwent an emergent fasciotomy of the right completely asymptomatic. His physical examination was unre- gluteus muscle, right lateral thigh compartment, and four com- markable. Lab work revealed a corrected serum calcium of 9.7 mg/ partments of the leg. Subsequent lab values showed worsening dl (8.5-10.2 mg/dl), serum PTH of 6 pg/ml (10-55 pg/ml) ,PTHrP of creatinine 4.9 mg/dL, CPK > 22,000 IU/L, potassium 6.8 mEq/L, 10 pg/ml (14-27 pg/ml), serum phosphorous of 2.9 mg/dl (2.5-4.5 calcium 6.7 mg/dL, phosphorus 5.3 mg/dL, AST 5,219 IU/L, ALT 1,061 mg/dl), serum magnesium of 2 mg/dl (1.7-2.2 mg/dl), serum IU/L, and a urine drug screen positive for marijuana. The patient creatinine of 1.2 mg/dl, and urinary calcium of 129mg in 2800 ml developed oliguria and started hemodialysis (HD) on day 2. The collected over 24 hours (50-300 mg/24 hours). Vit D 25-hydroxy CPK peaked at 76,380 IU/L on day 3 and slowly declined, normal- was 38 ng/ml (30-100 ng/ml), and vit D 1,25 dihydroxy was 16 pg/ izing after 30 days. The patient was treated with IV calcium glu- ml (18-64 pg/ml). The angiotensin converting enzyme level was 8 conate boluses and oral calcium acetate to correct persistent u/l (< 40 u/l). CT Chest showed no findings suggestive of sarcoid- hypocalcemia and continued HD three times per week until day 19. osis. Patient remained asymptomatic during follow up visits, but Serum calcium normalized on day 17 at 8.5 mg/dl. On day 20, his lab results showed a persistence of low PTH and normocalcemia. oliguria resolved, but calcium increased to 15 mg/dL. Intact PTH and There are plans to test for Calcium Sensing Receptor (CASR) gene 25-OH vitamin D levels were low. Aggressive hydration with mutations on the next visit as a part of further workup. intravenous 0.9% saline was initiated, followed by IV furosemide Discussion: Cases of hypoparathyroidism not resulting from anterior without improvement. The patient required 5 additional days of HD neck surgery could be due to genetic and autoimmune disorders. for hypercalcemia along with normal saline infusion. Genetic testing is essential in suspected patients, especially in the Discussion: The initial hypocalcemia was caused by calcium bind- absence of family history of related disorders and when other ing in the necrotic muscle tissue. Once the oliguria and muscle common causes have been ruled out. CASR is a family member of necrosis improved, the calcium deposits were released from the G protein coupled receptor which is usually present in the para- tissues, resulting in hypercalcemia and PTH secretion suppression. thyroid gland and kidneys. There are greater than 230 various Importantly, treatment with bisphosphonates, calcitonin, or

S100 Parathyroid/Bone Disorders Endocrine Practice 27 (2021) S85eS106 denosumab may not be effective in lowering the calcium levels in Blood pressure and hypocalciuria. Our case was different as she had this setting. Additionally, calcium supplementation in the hypo- hypocalcaemia & no hypocalciuria. calcemic phase should be judicious. The predominant hypercalce- https://doi.org/10.1016/j.eprac.2021.04.682 mia mechanism is independent of PTH action or osteoclastic bone resorption and postulated to be caused by the dissolution of cal- cium precipitates. Physical removal of calcium through low calcium Abstract #1003860 bath HD is indicated if aggressive hydration fails. https://doi.org/10.1016/j.eprac.2021.04.681 Non-operative Management of Primary Hyperparathyroidism: A Learning Experience

Abstract #1003852 Author Block: Sajjad Ali Khan - Aga Khan university hospital, A Case of Pseudo Gitelman Syndrome Secondary to Karachi, Pakistan; Muhammad M. Mehdi Khan, n/a - Co-author, Cisplatin Therapy Medicine, Aga Khan University Hospital; Aisha Shaikh, Dr - Co- author, Medicine, Aga Khan University Hospital

Author Block: Muhammad Hassaan Pervez - Royal College of Introduction: Primary hyperparathyroidism is a relatively common Physicians Edinburgh; Sath Nag, Consultant Physician Endocrine & disorder. For symptomatic cases, surgical parathyroidectomy is a Diabetes - co-author, Endocrine and diabetes, James Cook treatment of choice. However, if surgery is not possible or not opted for, University Hospital, Middlesbrough, UK medical management is initiated but the patients require strict monitoring to prevent hypercalcemia, bone loss, and renal impair- Introduction: Cisplatin is a platinum based chemotherapeutic ment. Hence, medical management was initiated. Current recom- (alkylating) drug. It is used to treat a number of solid cancers mended medical management includes the use of Cinacalcet, including testicular, ovarian, bladder, cervix, lung, wilm’s tumour, Donesumab, Bisphosphonate, or Alendronate. Recent studies suggest Sarcoma etc. It has many side effects- hepatoxicity, neurotoxicity, focused parathyroidectomy under local anesthesia as the procedure of Ototoxicity and nephrotoxicity to name a few. Pseudo Gitelman choice in patients who are not good candidates for General Anesthesia. syndrome is one of the side effects of Cisplatin therapy. There are Case Description: We report the case of a 61-year-old female only few cases reported in literature. known diabetic (well controlled) with a history of recurrent Case Description: We report a case of 32 years old lady who pre- nephrolithiasis and hyperuricemia. The patient had a prior history sented to AE with two days history of vomiting, carpopedal spasms, of sarcoidosis which was treated with steroid therapy. It was later paraesthesia & palpitations. Her potassium level was 2.8 mmol/L, followed by muscular weakness which was attributed to neuro- Calcium- 1.78 mmol/L & magnesium -0.18 mmol/L. She also had sarcoidosis which had a complete recovery with Methotrexate mild metabolic alkalosis with pH- 7.56 and bicarbonate levels of 30. treatment. Examination findings were unremarkable. Lab tests Her electrolytes were replaced intravenously & later discharged revealed Urine calcium 215.28, Parathormone 225.0, serum Cal- home with oral supplements. She had multiple admissions with low cium 11.5, serum Phosphorus 2.1, uric acid 8.1, Vitamin D 12.5. Dexa Magnesium, Calcium and Potassium levels requiring IV replace- scan of the hip, spine, and Rt. The distal forearm showed osteo- ment. She was seen by the Endocrinologist at this point. She had porosis. Ultrasound neck was done which showed dumbbell-sha- past medical history of Osteosarcoma of spine at age of 5 and treated ped adenoma in the lower pole of right thyroid gland measuring 18 with Cisplatin & Doxorubicin-6 cycles in total along with surgery. x 4.5 mm. Their findings were consistent with the presence of right There was no family history of tubulopathy or kidney disease. She parathyroid adenoma. Benign nodules with no calcifications were had a normal pregnancy and an 8 year old healthy daughter. Her identified in both lobes of the thyroid. Parathyroid scintigraphy urine electrolytes including Calcium, magnesium and potassium with sestamibi was positive for solitary parathyroid adenoma over were within normal range. Her general physical examination was the upper half of the right lobe of the thyroid. unremarkable and her Blood pressure was always in the normal Treatment and Outcome: range. Her ECG was also normal with a normal QT and QTc. Family was educated regarding the need of an invasive proced- It became evident that she had Cisplatin induced tubular dysfunc- ure, but the family refused surgical management due to history of tion which mimics Gitelman’s syndrome. She was referred to tubol- neurosarcoidosis and anesthesia-related risk. Patient was started opathy renal specialist team which also agreed that her tubulopathy on Cinacalcet and bisphosphonates. Patient calcium level improved was secondary to Cisplatin therapy. She is currently stable on two and is under close follow up in the endocrine clinic. tablets of calcichew forte twice a day (4g calcium/day), 4 tablets of Discussion: Surgery is the treatment modality of choice for primary Sando K per day(4 grams of potassium), and 7 tablets of magnesium hyperparathyroidism. However, it cannot be offered to a subset of 500mg per day and is under regular follow up of endocrine team. patients because of underlying comorbidities. Medical therapy in Discussion: About 20% of patients treated with high dose Cisplatin the Cinacalcet and bisphosphonates can be offered to such patients. develop renal side effects. Cisplatin causes renal damage in four https://doi.org/10.1016/j.eprac.2021.04.683 different ways as below: 9. Renal tubular cell injury and apoptosis 10. Renal vasoconstriction and injury to renal vessels Abstract #1003877 11. Inflammatory response causing interstitial cell damage 12. Damage to glomeruli The Lifelong Impact of ENPP1 Deficiency: Outcomes Other drugs including diuretics, aminoglycosides like Capreo- From a Patient and Caregiver Survey mycin can also cause a similar clinical picture. True Gitleman syndrome is an autosomal recessive disorder caused by SLC12A3 or CLCNKB gene mutation. It is characterized by Author Block: Christine O'Brien, MA - Co-author, Co-President hypokalaemia, metabolic alkalosis, hypomagnesaemia, low-normal GACI Global; Beth Leiro, PT - Co-author, Clinical Outcomes

S101 Parathyroid/Bone Disorders Endocrine Practice 27 (2021) S85eS106

Consultant; Gus Khursigara, PhD - Co-author, Inozyme Pharma; Adina Mariana Ghemigian, MD, PhD - co-author, National Institute Catherine Nester, BScN - Presenter, Inozyme Pharma of Endocrinology "C. I . Parhon", Bucharest, Romania

Objective: Pyrophosphate (PPi) acts as a potent inhibitor of Introduction: Paget’s disease of bone (PDB) is a slowly progressive mineralization. Patients deficient in ectonucleotide pyrophospha- skeletal condition of disorganized bone turnover, being character- tase/phosphodiesterase 1 (ENPP1), a protein involved in PPi ized by remodeling and impaired bone integrity. metabolism, have low serum PPi and heterogeneous clinical man- Lynch syndrome (LS), is an inherited disorder associated with ifestations, including arterial calcification; cardiac, neurological, various types of cancer, such as: colorectal, endometrial, ovarian and gastrointestinal (GI) dysfunction; skeletal abnormalities; and etc. hearing loss. This study was intended to characterize the burden of Case Description: A 44-year-old woman was referred to our disease from a patient or caregiver/parent perspective. Endocrinology clinic in 2020 due to suspected PDB because of her Methods: Primary qualitative patient-reported outcomes research suggestive personal and family medical history. under institutional review board approval was performed to The patient was experiencing progressively worsening pain and determine disease burden in patients with ENPP1 deficiency across swelling in the left elbow and proximal extremity of the left fore- all ages. Patients were recruited through GACI Global, social media, arm for the last two years. and health care professionals. Her total serum alkaline phosphatase (ALP) was high 392 U/L (35- Results: Thirty-two respondents from 9 countries who had ENPP1 104 U/L) and the bone scintigraphy showed uptake at left forearm deficiency [infantile (n¼12), pediatric (n¼13), and adult (n¼7)] level. were assessed. Of all patients, 34% (n¼11/32) were deceased; 31% Personal history included rectosigmoidian carcinoma (2010) (n¼10/32) were deceased before 12 months of life. Parents or treated with chemotherapy and radiotherapy which lead to sec- caregivers responded on behalf of patients aged < 18 years (78%; ondary amenorrhea. Her mother and maternal grandmother were n¼25/32). diagnosed with PDB and her father with colorectal cancer. Patients reported a physical health burden related to cardiac Physical examination revealed swelling of the left elbow and (88%; n¼28/32) and GI (50%; n¼16/32) issues; rates were similar tenderness at palpation. Biochemical work-up showed: slightly across the infant, pediatric, and adult cohorts (cardiac: 92%, 85%, elevated serum calcium¼10.3 mg/dL (8.4-10.2 mg/dL) and 24-hour 86%; GI: 50%, 54%, 43%, respectively). Although the onset of these urinary calcium¼0.33g/24h (0.07-0.3 g/24h) with normal phos- symptoms ranged from infancy to adulthood, the burden of disease phorus, renal function, transaminases and parathormone. increased with age. Markers of bone formation were elevated: total ALP¼347 U/L (40- There was an increasing trend of reports of age-related bone/joint 105 U/L), procollagen type 1 N-terminal propeptide¼203.4 ng/mL pain and stiffness among the infant, pediatric, and adult groups (20.25-76.31 ng/mL) and the resorption bone marker C-terminal (pain: 42%, 85%, 100%; stiffness: 25%, 39%, 57%, respectively). Joint telopeptide¼0.67 ng/mL (0.162-0.436 ng/mL). pain impacted movement for both pediatric and adult cohorts. In Arm X-ray showed expended proximal part of left ulna and adults, the age of onset for joint pain was broad (infancy to adult- lucent changes. hood); the pain continued daily regardless of activity in patients Whole Exome Sequencing analysis identified pathogenic muta- with early onset. tions: P392L in SQSTM1 gene associated with PDB and c.2634+1G Impairment of mobility/fatigue was reported in 72% (n¼23/32) of >T in MSH2 gene associated with LS. Her daughter carried the same all patients; this was higher in pediatric (85%; n¼11/13) and adult mutations but neither her sister, brother and their children. groups (86%; n¼6/7) vs infants (50%; n¼6/12). For both pediatric The patient was discharged after receiving a single IV dose of and adult cohorts, specific symptoms were related to fatigue after Zoledronic acid 5mg and genetic counseling regarding the risk of brief activity or immobility due to pain. passing the LS to descendants. Discussion/Conclusion: Patients with ENPP1 deficiency have high At follow-up, we noted clinical improvement and significant mortality early in life and a high burden of disease across the age decrease of serum total ALP but still above upper limit. A second spectrum; reported symptoms reflected multisystem dysfunction, dose of Zoledronic acid 5mg was administered. including cardiac, GI, and bone/joint complications. These symp- Discussion: There is a genetic component of PDB, also seen in our toms were comparable across all age groups suggesting that in case: P392L in SQSTM1 gene, the most common. some patients these dysfunctions have a lifelong burden. Further The mutation c.2634+1G >T in MSH2 gene associated with LS, investigation is necessary to determine if there is a relationship also found in this case, emphasizes the importance of colonoscopy between the impact of joint pain/stiffness and impairment of screening of all members in families with a history of colorectal mobility/fatigue. cancer in case of unavailable genetic testing. Because patient’s serum total ALP was still too high after a https://doi.org/10.1016/j.eprac.2021.04.684 single dose of Zoledronic acid 5 mg, we recommended a second dose, also considering her iatrogenic premature amenorrhea.

Abstract #1003929 https://doi.org/10.1016/j.eprac.2021.04.685

A Case of Paget’s Disease of Bone Associated with Lynch Syndrome Abstract #1003989

A Rare Case of Tumor-Induced Osteomalacia Despite Author Block: Laura-Semonia Stanescu, MD Resident - primary Resection of a Benign Glomangioma author, National Institute of Endocrinology "C. I. Parhon", Bucharest, Romania; Nicoleta Dumitru, MD, PhD - co-author, National Institute of Endocrinology "C. I . Parhon", Bucharest, Author Block: Tiffany Tsang - Rutgers New Jersey Medical School; Romania; Andra Maria Olteanu, MD Resident - co-author, National Lissette Cespedes, MD - Co-author, Endocrinology, Rutgers New Institute of Endocrinology "C. I . Parhon", Bucharest, Romania; Jersey Medical School

S102 Parathyroid/Bone Disorders Endocrine Practice 27 (2021) S85eS106

Introduction: Tumor-induced osteomalacia (TIO), a rare paraneo- Introduction: Brown tumors are focal bone lesions formed by plastic syndrome, ectopically secretes fibroblast growth factor 23 osteoclast and fibroblast proliferation with hemosiderin accumu- (FGF23) and prevents phosphate reabsorption by suppressing renal lation causing the brown color. They occur in 3% of secondary hy- Na/Pi cotransporter and inhibiting 1-a-hydroxylase. Presentation perparathyroidism and 2% of primary hyperparathyroidism (PHPT). resembles the biochemical and mineralization abnormalities of In young patients with PHPT, it is prudent to obtain a thorough hereditary hypophosphatemic rickets. family history and consider genetic testing for multiple endocrine Case Description: A 42-year-old male with a history of left mastoid neoplasias (MEN), hyperparathyroid-jaw tumor (HPT-JT) syn- glomangioma, resected 4 months ago, presented for a second drome, and familial isolated hyperparathyroidism (FIHP), since opinion with widespread, unprovoked fractures associated with preferred surgical management may differ. We present a young back pain and muscle weakness for the past four years. He had a man with bone pain who was found to have brown tumors caused DEXA scan which showed osteoporosis and a bone scan which by PHPT with negative genetic testing. showed innumerable foci of increased activity in the axial and Case Description: A 22-year-old man with history of hypertension appendicular skeleton. Previous workup for multiple myeloma was and nephrolithiasis was evaluated for leg pain and found to have negative. He also had a skull X-ray which showed an indeterminate bilateral tibia and fibula soft tissue masses with associated cortical focal lucency in the calvarium, suggestive of Paget’s disease, for erosion and periosteal reaction, suspicious for malignancy. He was which he was treated with a dose of zoledronic acid. Despite prior planned for open biopsy but was found to have severe hypercal- extensive workup, a phosphorus level was never ordered. On exam, cemia on pre-operative labs. He denied confusion, headache, poor he was of expected stature based on mid-parental height. He had appetite, nausea, vomiting, abdominal pain, constipation, poly- normal dentition, no bony deformities and no skin lesions. There dipsia, polyuria, or prior bone fracture. He reported systolic blood was tenderness to palpation in his forearms and he ambulated with pressures of up to 170 mmHg for years and was started on hydro- crutches. Skeletal survey revealed diffuse subacute fractures and chlorothiazide 2 weeks prior to hospitalization. He reported impending fractures of the femurs. Labs revealed corrected calcium nephrolithiasis 2 years ago. His mother had hypercalcemia and his 8.8mg/dL (8.4-10.2mg/dL), phosphorus 1.9mg/dL (2.5-4.5mg/dL), father had resistant hypertension, nephrolithiasis, and Cushing’s magnesium 2.2mg/dL (1.6-2.5mg/dL), creatinine 0.8mg/dL (0.5- disease status post pituitary tumor resection. Patient had serum 1.0mg/dL), 25(OH)D 52.2ng/mL (30-100ng/mL), 1,25(OH)2D 19.1pg/ calcium 14.2 mg/dL, PTH 622.7 pg/mL, and 25 hydroxy vitamin D 13 mL (19.9-79.3pg/mL), PTH 80pg/mL (15-65pg/mL), alkaline phos- ng/mL. He received intravenous saline, calcitonin, and cinacalcet phatase 183U/L (35-105U/L), bone alkaline phosphatase isoenzyme with serum calcium reaching normal range. Due to patient’s age, 73% (12-68 %), total testosterone 552ng/mL (249-836ng/mL) and C- history, and family history, genetic testing was performed and ruled telopeptide 614pg/mL (34-635pg/mL). Tubular maximum phos- out MEN, HPT-JT, and FIHP. He had a left inferior parathyroidectomy phate reabsorption per GFR (TmP/GFR) was low at 0.43mmol/L and left distal femur biopsy. Serial intraoperative PTH levels were (0.99-1.34mmol/L). Findings were suggestive of osteomalacia due 722.8 pg/mL, 415.5 pg/mL, and 69.1 pg/mL. Post-operative PTH 29.0 to renal phosphate wasting. Intact FGF23 level was elevated to pg/mL and calcium 9.4 mg/dL without further medical therapy. 93pg/mL (< 22pg/mL) and genetic testing for hypophosphatemic Pathology confirmed hypercellular parathyroid gland. Bone biopsy rickets was negative. A 68Ga-DOTATATE CT/PET scan for tumor showed hemosiderin pigment consistent with brown tumor. localization is pending; however, medical management with bur- Discussion: Our case involves a young man with bone lesions osumab was initiated. suspicious for malignancy but was found to have brown tumor Discussion: Our patient likely had TIO from his glomangioma. provoked by PHPT. Brown tumors are not malignant and manage- Despite being potentially curative, 11% of cases have persistent ment of HPT with medications, surgery, or dialysis is the preferred hypophosphatemia after surgery. Due to their small size, TIO tu- treatment for tumor regression. We highlight the importance of mors are difficult to localize or resect. Burosumab, a human anti- genetic screening for familial disorders in young patients present- FGF23 monoclonal antibody, is a therapeutic option in cases of ing with PHPT with suspicious family history. Genetic testing unresectable TIO. Benefits include improved fracture-healing and should be performed before surgery to help determine the best normalization of phosphorus levels. Our case highlights the course of definitive surgery. importance of measuring phosphorus levels as part of any evalua- https://doi.org/10.1016/j.eprac.2021.04.687 tion of metabolic bone disease. https://doi.org/10.1016/j.eprac.2021.04.686 Abstract #1004056

Abstract #1004047 A Case of Familial Hypocalciuric Hypercalcemia: A Diagnostic Dilemma A Young Patient Presenting with Bone Pain from Brown Tumors due to Underlying Primary Hyperparathyroidism Author Block: Shameela Begum - Shadan Institute of Medical Sciences; Syed Wajih Rizvi, MD - Co-author, Endocrinology, R- Author Block: Katherine Hu - Hackensack Meridian Jersey Shore Endocrinology; Muntazir Ali Sayed, MBBS - Co-author, Internal University Medical Center; Khin Zin, MD - co-author, Medicine, R-Endocrinology; Shahnaz Begum, MD - Co-author, Endocrinology, Jersey Shore University Medical Center; GMC/NHS; Hira Akhlaq, MBBS - Co-author, R-Endocrinology; Monika Akula, MD - co-author, Endocrinology, Jersey Shore Ammar Mushtaq, MD - Co-author, AMITA Health; Sadiq Ali Sayed, University Medical Center; Fadi Barkho, BA - co-author, St. George's MBBS - Co-author, National Pirogov Memorial Medical University, School of Medicine; Jennifer Cheng, DO - co-author, Endocrinology, Vinnytsya, Ukraine; Rehan O. Khan, BS - Co-author, UTD Jersey Shore University Medical Center; Soemiwati Holland, MD - co-author, Endocrinology, Jersey Shore University Medical Center; Introduction: Familial Hypocalciuric Hypercalcemia (FHH) is a Raquel Ong, MD - co-author, Endocrinology, Jersey Shore benign autosomal dominant inherited condition causing hyper- University Medical Center calcemia. FHH is caused by inactivating mutation in calcium-

S103 Parathyroid/Bone Disorders Endocrine Practice 27 (2021) S85eS106 sensing receptor (CaSR) gene causing decreased receptor activity in post discharge with new-onset hand cramping, facial tingling, and parathyroid glands and kidneys. The reported prevalence is severely low serum calcium of 5.5 mg/dL. Magnesium was low at 1:78,000 but the true prevalence could be higher due to undiag- 1.5 mg/dL, phosphorus 2.3 mg/dL, creatinine 0.9 mg/dL, alkaline nosed patients. We report a case of FHH in a female presented with phosphatase (ALP) significantly high at 1,140 IU/L, PTH 248 pg/mL, hypercalcemia confirmed by laboratory diagnosis. and 25-hydroxy vit D of 31.4 ng/mL. Due to inadequate improve- Case Description: A 71-year-old female with a past medical history ment of calcium level on oral calcium and magnesium repletion, of Metabolic syndrome and post-menopausal Osteoporosis pre- the patient required 34 g of IV calcium gluconate over six days of sented to our Endocrinology clinic for a routine follow up. During hospitalization along with high doses of calcitriol and oral calcium. the evaluation, the patient reported paresthesia in her hands and The patient was discharged on 1 g calcium/400 IU of vit D 4 times feet, and chronic constipation. A review of her blood-work results daily and 0.1 mcg calcitriol twice daily. She remained diligent with revealed elevated Calcium levels at 10.4 mg/dL. A complete work up her calcium supplementation and was given given a second 120 mg was ordered to evaluate the cause of hypercalcemia. Follow-up DMB dose 2 weeks post discharge. She had a third admission two laboratory investigations 4 weeks later showed elevated Calcium weeks later for abdominal pain when admission serum calcium was levels at 10.7 mg/dL (normal, 8.4-10.3 mg/dL, depressed Phos- normal. Her oral calcium supplements were not continued; how- phorus at 2.9 mg/dL (normal, 3.0-4.3 mg/dL), normal PTH intact at ever by the fifth day of hospitalization she had hypocalcemia 33 pg/mL, normal Magnesium at 1.8 mg/dL, normal Creatinine symptoms and a very low serum calcium of 5.9 mg/dL. Over three Clearance at 91 mL/min, normal calcium urine at 2.3 mg/dL, and weeks of hospitalization she received a total of 112 g IV calcium, depressed Calcium urine 24hr at 35 mg/24 hr (normal, 47-462 mg/ along with high doses of oral calcium and calcitriol which were 24 hr), with a calcium-creatinine clearance ratio (CCCR) at 0.002. continued post discharge. No further treatment with DMB is Investigations to rule out other possible pathologies were non- planned at this time. contributory. Patient reported that her mother had always had Discussion: In comparison to zoledronic acid, DMB is more effec- elevated calcium levels and “some” parathyroid issues which were tive in reducing SRE and has lower nephrotoxicity but carries a undiagnosed. Considering this finding and blood-work results, a higher hypocalcemia risk. High bone turnover, characterized by diagnosis of FHH was made. Patient will be re-evaluated in subse- significantly elevated ALP (as in our patient, likely due to extensive quent encounters. skeletal metastasis), may be an important risk factor and predictor Discussion: FHH is a rare genetic disorder characterised by mild, of DMB-induced hypocalcemia. Impaired kidney function, a com- asymptomatic, long standing hypercalcemia that does not warrant mon risk factor for hypocalcemia, was not seen in our patient. medical or surgical interventions. When presented with hypercal- Typically, hypocalcemia occurs weeks to months after administra- cemia, doctors should consider the likelihood of them dealing with tion of DMB. The exceedingly rapid onset of hypocalcemia as in our FHH. A detailed FHx plays a pivotal role in diagnosis. A 24-hr urine case, is extremely uncommon. This highlights the importance of CCCR aids in differentiating FHH from Primary Hyperparathyroid- risk stratification, immediate proactive monitoring of calcium, as ism (HPT), and a ratio of < 0.01 is highly suggestive of FHH. well as maintenance of oral calcium supplementation even after Moreover, confirmation with CaSR gene testing will facilitate the recovery from DMB-induced hypocalcemia. diagnosis of FHH, and the need for further evaluation of familial https://doi.org/10.1016/j.eprac.2021.04.689 causes of hypercalcemia. Also, patient counseling and reassurance about the benign nature of this disorder is critical. This will help in avoiding unnecessary surgical intervention and associated health- Abstract #1004238 care financial burden. https://doi.org/10.1016/j.eprac.2021.04.688 Can Use of Injectable PTH Analogs Contribute to Overstimulation of Bone Causing Painful Bone Lesions?

Abstract #1004234 Author Block: Alina H. Aasim, MD - Primary author, Endocrinology, Acute, Rapid-onset, Severe and Protracted Denosumab- Medstar Union Memorial Hospital; Pamela R. Schroeder, MD, PhD - Induced Hypocalcemia in a Patient with Intact Kidney Co-author, Endocrinology, Medstar Union Memorial Hospital Function, Skeletal Metastasis and High Bone Turnover Introduction: Injectable PTH analogs are effective in treatment of hypoparathyroidism, but some important safety concerns are risk Author Block: Ailyn Rivero - UF Health Jacksonville; of overstimulation of bone, osteosarcoma, and hypercalcemia. Madeline Fasen, DO - co-author, UF Health-Jackonsville; Case Description: A 43-year-old Caucasian female with chronic Gunjan Y. Gandhi, MD - co-author, Endocrinology, Diabetes, and fatigue syndrome, vitamin D deficiency, and history of multi- metabolism, UF Health-Jacksonville, FL nodular goiter s/p total thyroidectomy with postsurgical hypo- parathyroidism presented with severe fatigue, back pain, and Introduction: Denosumab (DMB) is a monoclonal antibody used to widespread paresthesias in upper and lower extremities. prevent debilitating skeletal-related events (SRE) in patients with For post-surgical hypoparathyroidism, she was initially pre- bone metastases due to solid tumors. We present an unusual case of scribed vitamin D2 50000 IU weekly, calcitriol 0.25mcg 3x/day and rapid-onset and severe hypocalcemia in a patient with normal calcium carbonate 1000mg 2x/day. Despite optimizing the renal function, skeletal metastasis and high bone turnover. regimen, she remained symptomatic so was started on Natpara Case Description: A 72-year-old female with carcinoma of un- (injectable parathyroid hormone) 100mcg SC/day with calcitriol known origin and widespread lytic osseous metastases was dosage decreased to 0.25 mcg/day and vitamin D3 5000 IU daily. admitted for severe anemia. She had received 120 mg of DMB for Her calcium level remained stable with no hypocalcemia symp- SRE prevention that same day. During a two-day hospital course toms. After Natpara was recalled, she was started on Forteo (Ter- she had a low serum calcium of 6.9 mg/dL (albumin 3.3 g/dL) iparatide off-label) 20 mcg/day, vitamin D2 50,000 IU/wk, and requiring IV calcium. She presented for a second admission 2 days calcitriol 0.25 mcg 4x/day.

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A few months later, after a fall, she was found to have lytic and medications, or HD, which likely lead to his ULO. There are only two sclerotic lesions along the spine and pelvis. Laboratory findings other reported cases of ULO causing optic nerve compression. There including lactate dehydrogenase and SPEP with IFE were unre- is no standardized treatment for complications of ULO but para- markable. She was diagnosed with osteodystrophy and Forteo was thyroidectomy and steroids followed by surgical decompression discontinued. Biochemical tests for the etiology of osteodystrophy have been successful. This case highlights the importance early revealed low parathyroid, 11pg/ml(15-65pg/mL). Bone turnover recognition and treatment of secondary hyperparathyroidism. It is markers, C telopeptide, and procollagen type 1 N telopeptide (P1NP) important to consider ULO on the differential for acute cranial were normal. Fibroblast growth factor-23 was elevated, 637 (44-215 nerve palsy in a patient with uncontrolled hyperparathyroidism RU/mL). She underwent tetracycline-labeled bone biopsy which due to ESRD. showed normocellular bone marrow, with trilineage hematopoiesis https://doi.org/10.1016/j.eprac.2021.04.691 and bony trabecula with focal osteoclastic activity. There was no evidence of a plasma cell neoplasm or a lymphoproliferative disor- fi der. Based on the ndings of the biopsy, diagnosis of a bone meta- Abstract #1014122 bolic disorder was suggested. Octreotide scan did not localize any small lesions typically seen in tumor-induced osteomalacia. COVID-19 Associated Hypercalcemia , A Rare Yet Discussion: It is known that patients with hyperparathyroidism can Interesting Case develop bone tumors, and injectable PTH has been associated with osteosarcoma in rat species. A recent case report described a 27- year-old female who underwent treatment with 1-34 for hypo- Author Block: Azka Arif - University of Oklahoma Health Sciences parathyroidism and developed significant bone pain after 3 years of Center; Nabeela Shakir, MD - co-author, Section of Diabetes and therapy. Whole body scan revealed findings suggesting possible Endocrinology, University of Oklahoma Health Sciences Center; overstimulation of bone cells. Therapy with PTH analogs is effective Ahmad Abu-Limon, MD - co-author, Section of Diabetes and in patients with hypoparathyroidism refractory to conventional Endocrinology, University of Oklahoma Health Sciences Center; treatment. However, whether these medications can cause over- Juan A. Cantu Clatza, MD - co-author, Section of Diabetes and stimulation of bone is unclear and needs to be investigated further. Endocrinology, University of Oklahoma Health Sciences Center; https://doi.org/10.1016/j.eprac.2021.04.690 Jonea Lim, MD - co-author, Section of Diabetes and Endocrinology, University of Oklahoma Health Sciences Center; Mary Zoe Baker, MD - co-author, Section of Diabetes and Endocrinology, University Abstract #1004352 of Oklahoma Health Sciences Center

Uremic Leontiasis Ossea Causing Acute Monocular Introduction: Hypercalcemia is a common clinical diagnosis. Hy- Blindness perparathyroidism is one of the most common etiologies. Rarely hypercalcemia is associated with intense inflammation secondary to IL-6 production. Herein we present an interesting case of hy- Author Block: Azeen Anjum, MD - primary author, Internal percalcemia associated with COVID-19. Medicine, Texas Health Presbyterian Hospital of Dallas Case Description: 36-year-old woman with history of Cirrhosis secondary to hepatitis C and alcohol abuse initially admitted for Introduction: Uremic leontiasis ossea (ULO) is a form of renal COVID/ARDS and cryptococcemia without CNS involvement. She osteodystrophy characterized by overgrowth of facial and cranial was initially treated with amphotericin B and continued on flu- bones. This condition can sometimes lead to compression of nerves, conazole. Patient was re-admitted after 2 weeks with abdominal vessels, or the upper airway. This is a rare case of ULO causing pain, constipation and hypercalcemia (Ca 14.2 mg/dl (normal range compressive optic neuropathy leading to acute monocular 8.7-10.1mg/dl). Her ionized calcium was 1.78 mmol/L (normal blindness. range 1.12-1.32 mmol/L). Serum phosphorus was 2.5 mg/dl (normal Case Description: A 36 year-old man with end stage renal disease range 2.5-4.5mg/dl). Intact PTH level was 6.7 pg/ml (normal range (ESRD) due to post-streptococcal glomerulonephritis on hemodi- 6-48pg/ml). Vitamin D 25-OH level was 26.8 ng/ml (sufficient range alysis (HD) for 15 years presented with acute left-sided monocular 32-100 ng/ml); Vitamin D 1,25-OH level was 7.4 pg/ml (normal vision loss. Physical exam was significant for facial deformity with 19.9-79.3pg/ml). PTH-rp was unmeasurable (< 2pmol/l). CRP was bilateral mandibular enlargement. Laboratory analysis revealed elevated at 31.7mg/L (normal range 0.2-8 mg/L). She was not on parathyroid hormone (PTH) level of 2,309 pg/mL (8.7-77.1), calcium calcium, Vitamin D supplementation or thiazide diuretics. Her renal of 8.1 mg/dl (8.6-10.0), vitamin D 25-hydroxy of 16.8 ng/ml (30-80), functions were normal. She was given Intravenous fluids & Intra- inorganic phosphorus of 3.2 mg/dl (2.4-4.4), and serum alkaline venous pamidronate. Steroids were not used due to an ongoing phosphatase of 837 U/L (40-150). CT Head showed diffuse osseous fungal infection. It was proposed that the patient had Interleukin- expansion of the calvarium and facial bones with significant ste- induced hypercalcemia secondary to COVID-19 infection. Her nosis of the bilateral orbital apices and optic canals. Fundoscopic serum calcium normalized with improvement in clinical status exam demonstrated a left-sided pale optic nerve with diffuse nerve Discussion: Recent literature suggests COVID-19 is associated with edema, consistent with optic nerve compression. High-dose ste- inflammatory response with cytokines & interleukins production. roids were started with partial improvement in light perception in IL-6 production is significantly upregulated especially in severe the left eye. He was discharged with follow-up with oculoplastic cases of COVID-19 known as “Cytokine storm”. IL-6 is produced by surgery for surgical decompression evaluation. bronchial epithelial cells. High levels of IL-6 are associated with Discussion: ULO is seen in poorly-managed ESRD patients who worse outcomes and much more severe disease. IL-6 in turn causes have chronic uncontrolled secondary hyperparathyroidism, like our osteoclast activation, bone resorption & hypercalcemia. In our pa- patient. Treatment for renal osteodystrophy is primarily prevention tient other potential causes of hypercalcemia were ruled out. The with dietary modification, medical management, and regular HD. proposed mechanism of her hypercalcemia is an intense inflam- Unfortunately our patient had not been compliant with his diet, matory response associated with COVID-19 infection.

S105 Parathyroid/Bone Disorders Endocrine Practice 27 (2021) S85eS106

Conclusion: We present a rare sequelae of COVID-19 infection Author, Division of Endocrine Surgery and Surgical Oncology, which presents a teaching point for clinicians to consider while Boston Medical Center; Shirin Haddady, M.D. - Co-author, Division managing such novel disease of Endocrinology, Diabetes, Weight Management, and Nutrition, Boston Medical Center; Stephanie Lee, M.D., Ph.D - Co-author, https://doi.org/10.1016/j.eprac.2021.04.692 Division of Endocrinology, Diabetes, Weight Management, and Nutrition, Boston Medical Center; David McAneny, M.D. - Co- author, Division of Endocrine Surgery and Surgical Oncology, Abstract #1030483 Boston Medical Center

Temporal Evolution of its Diagnosis and Treatment in a Peruvian National Hospital Objective: Primary hyperparathyroidism (PHPT) is the most common etiology of hypercalcemia in the outpatient setting. Familial forms of PHTP (F-PHTP) account for approximately 2- Author Block: Jose Paz-Ibarra - HOSPITAL NACIONAL EDGARDO 5% of all cases; however, their detection has significant clinical REBAGLIATI MARTINS - ESSALUD. UNIVERSIDAD NACIONAL value. Patients with F-PHPT present with endocrine and non- MAYOR DE SAN MARCOS. LIMA - PERU; Sofia Saenz, MD - co- endocrine disorders that require attention, treatment, and author, Servicio de Endocrinologia, Hospital Nacional Edgardo long-term surveillance. We describe three patients who were Rebagliati Martins, Lima e Peru; Gerson Siura, MD - co-author, referred to the Endocrine clinic for unrelated conditions from Servicio de Endocrinologia, Hospital Nacional Edgardo Rebagliati 2019-2020 but were later diagnosed with F-PHTP. Martins, Lima e Peru; Victor Garcia, MD - co-author, Servicio de Methods: Case I: A 38-year-old man referred for diabetes Endocrinologia, Hospital Nacional Edgardo Rebagliati Martins, mellitus was found to have hypercalcemia and PHPT. A 6-cm Lima e Peru; Fernando Quinto, MD - co-author, Servicio de pancreatic mass was incidentally demonstrated on chest Endocrinologia, Hospital Nacional Edgardo Rebagliati Martins, computed tomography, and MEN 1 was confirmed with ge- Lima e Peru netic testing. Case II: A 30-year-old women referred for a multinodular goiter was diagnosed with medullary thyroid Objective: To present the temporal evolution of the management of carcinoma based upon fine needle thyroid aspiration and tumor-induced osteomalacia (OIT) in a Peruvian national hospital serum calcitonin. Genetic testing confirmed MEN 2A, and from 1999 to the present. further investigation revealed pheochromocytoma but no PHPT Methods: The clinical and para-clinical characteristics of the pa- at that time. Case III: A 27-year-old man was referred for se- tients treated in a national referral hospital with a diagnosis of OIT vere hypercalcemia. His young age and family histories of neck from 1999 to the present were reviewed and described. operations and jaw tumors led to genetic testing that Results: Four patients were found in the study period (1999, 2011, diagnosed CDC-73 hyperparathyroid-jaw tumor syndrome 2018, 2019). In the first case the tumor was not found, the patient (HTT-JTS). died due to respiratory complications resulting from prostration; In Results: We present three young patients with F-PHPT. In pa- the second and third cases, the tumor was located in the right leg tients with MEN 1, PHPT is the result of parathyroid hyper- and right hemithorax, respectively, with resolution of the condition plasia and subtotal parathyroidectomy may be indicated. As after total resection of both tumors; In the fourth case, despite all often seen in patients with MEN 1, our patient had persistent the examinations and images currently available in Peru, the tumor borderline hypercalcemia. When PHPT manifests in MEN 2, it could not be located, he is receiving medical treatment with is associated with multiple-gland hyperplasia. Our patient did phosphorus salts and calcitriol with improvement in pain and not have PHPT, but three normal parathyroid glands were strength, being able to walk without support. auto-transplanted in the forearm during thyroidectomy. The Discussion/Conclusion: The diagnosis of OIT in our environment is likelihood of PHPT in MEN 2 is determined by specificgenetic difficult; Once the biochemical confirmation of this type of osteo- mutations. Patients with CDC-73 mutation are at risk of PHPT, malacia and the topographic location of the phosphaturic tumor is although the parathyroid disease affects multiple glands and considered as a diagnostic alternative, it depends on the availability may show up as hyperplasia, adenoma or malignancy. Our of laboratory tests and imaging equipment in the environment. The patient underwent neck exploration, in which two parathyroid resolution of the cases will depend on the capacity of the team of adenomas were removed, normalizing PTH level, although he surgeons when the tumor is located. has no jaw tumor. Discussion/Conclusion: Surgical approaches of patients with F- https://doi.org/10.1016/j.eprac.2021.04.693 PHPT may differ from that in sporadic PHPT. Therefore, it is important to maintain high level of suspicion for F-PHPT in young patients, especially with contributory family histories. Abstract #1040290 Close communication among endocrinologists, endocrine sur- geons and genetic counselors is essential for the management The Importance of Detecting Familial Forms of Primary of F-PHPT. Clinicians must understand that MEN 1 and 2 are Hyperparathyroidism to Determine Management typically associated with hyperplastic glands, while CDC-73 may involve constellation of parathyroid pathology, both Author Block: Pooja Bhargava, D.O. - Primary author, presenter, benign and malignant. Division of Endocrinology, Diabetes, Weight Management, and Nutrition, Boston Medical Center; Fredrick Drake, M.D. - Co- https://doi.org/10.1016/j.eprac.2021.04.694

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Endocrine Practice

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PITUITARY DISORDERS/NEUROENDOCRINOLOGY

Abstract #974563 prolonged course of the disease, many clinical specialties may need to be involved prior to accurate diagnosis. Isolated Central Diabetes Insipidus and Multisystem Langerhans Cell Histiocytosis https://doi.org/10.1016/j.eprac.2021.04.696

Abstract #986866 Author Block: Ola-Oluwakiti Alabi - Reading Hospital; Rodney Jamil, MD - Co-author, Hematology and Oncology, Tower Resistant Hypertension in Acromegaly Health; Vasudev Magaji, MD - Co-author, Endocrinology, Tower Health Author Block: Jimmy Mao - Mayo Clinic; Catherine D. Zhang, MD - Introduction: Initial clinical manifestations of Langerhans cell co-author, Endocrinology, Diabetes, Metabolism, and Nutrition, histiocytosis (LCH) are typically musculoskeletal. The likeli- Mayo Clinic; Natalia Lazik, MD, PhD - co-author, General Internal hood of central nervous system (CNS) involvement at the time Medicine, Mayo Clinic; Eddie L. Greene, MD - last author, fi ofdiagnosisislow.LCHismarkedbythein ltration of het- Nephrology and Hypertension, Mayo Clinic erogeneous cell types in certain organ tissues, with resultant parenchymal destruction. Here we discuss a unique patient with LCH that presented with diabetes insipidus (DI) as the Introduction: Acromegaly is a rare pituitary disorder with high initial symptom. rates of concomitant hypertension. Therapy of acromegaly and its Case Description: A 39-year-old female with history of Sjogren’s related clinical manifestations improve long-term cardiovascular disease and hypothyroidism presented to the endocrine clinic outcomes. with complaints of six months of polydipsia, polyuria, and Case Description: A 48-year-old woman with resistant hyperten- headaches. Review of systems was negative for trauma or sion of nearly 10 years duration was referred to our tertiary medical reproductive dysfunction. Urine osmolality was low at 139 center. She reported blood pressures (BPs) up to 200/120 mm Hg mOsm/K and urine volume in 24 hours was elevated at 9750mls. that did not improve despite the use of 3 different classes of anti- Central DI was diagnosed with subsequent water deprivation hypertensives and lifestyle modifications. The patient also noted test and she was started on desmopressin 50mcg oral daily. worsening anxiety, excessive sweating with minimal exertion, and Pituitary MRI revealed normal pituitary size, normal signal in- increases in her shoe and ring size. Physical examination revealed tensity, and a loss of the posterior pituitary bright spot. Inci- enlargement of her nasal and frontal bones. dentally, a right-sided parietal extra-axial mass was also noted. Diagnostic work-up revealed a thyroid stimulating hormone level Later, the patient began to experience left sided hearing loss and of 1.6 mIU/L (ref. 0.3-4.2 mIU/L), plasma aldosterone concentration vertigo. Subsequent brain MRI revealed bilateral extra-axial of 14 ng/dL (ref. < 21 ng/dL), 24-hour urinary aldosterone of 24 mcg masses and fluid opacification in the left mastoid. She under- (ref. 2-20 mcg), and plasma renin activity of < 0.6 ng/mL/hr. went left mastoidectomy by ENT and surgical pathology diag- Doppler-based renal ultrasonography was negative for renal artery nosed LCH. PET scan confirmed multisystem disease in the stenosis, and computed tomography of the abdomen revealed cervical lymph nodes and other osseous sites. She failed initial normal adrenal glands. Echocardiography demonstrated normal vinblastine and prednisone therapy but achieved appropriate left ventricular size and thickness, but a severely enlarged left response on cytarabine and denosumab. atrium. Growth hormone (GH), insulin-like growth factor-1 (IGF-1), Discussion: LCH is a rare neoplastic disorder with unvalidated and insulin-like growth factor-binding protein 3 levels were incidence and developing pathogenesis. Studies have identified elevated to 32 ng/mL (ref. 0.01-3.61 ng/mL), 545 ng/mL (44-227 ng/ that only 4% of patients present with DI prior to the diagnosis of mL), and 7.6 mcg/L (ref. 3.3-6.7 mcg/mL), respectively. Prolactin LCH, as seen with this patient. CNS involvement can manifest as level was within normal limits. Pituitary magnetic resonance im- diabetes insipidus. MRI may show loss of the posterior bright aging revealed a 1.8 cm right hypo-enhancing mass, consistent with spot on the pituitary gland, but this finding is not diagnostic. a GH-producing macroadenoma. Furthermore, there is an infrequent association between auto- She was initiated on a multimodal antihypertensive regimen immune disease and LCH that may have played a role in the with amlodipine 10 mg daily, carvedilol 12.5 mg daily, and spi- disease development in this case. In summary, LCH must be ronolactone 25 mg daily. Her BPs improved significantly over included in the differential for patients who present with isolated several weeks, allowing for successful transsphenoidal pituitary symptoms of diabetes insipidus. Given the often indolent and resection. Postoperatively, GH and IGF-1 levels normalized. Three

1530-891X Pituitary Disorders/Neuroendocrinology Endocrine Practice 27 (2021) S107eS132 months later, BPs remained well-controlled without the need for Identifying different mutations and their resultant phenotypes additional changes to her anti-hypertensive regimen. helps us further understand the pathogenesis of MEN1 syndrome. Discussion: We discuss a case of acromegaly presenting with The importance of vigilance for small, but often difficult to localize resistant hypertension. While current guidelines recommend that neuroendocrine tumors (NETs) is underscored by the fact that the choice of anti-hypertensives be similar between those with or malignant NETs are the primary cause of morbidity and mortality in without acromegaly, our patient experienced significant improve- patients with MEN 1 syndrome. A diagnosis of MEN 1 syndrome is ment in BPs with the addition of the mineralocorticoid receptor of vital importance for patients and their families, who must be antagonist (MRA), spironolactone. This finding is consistent with referred for genetic counseling. prior studies suggesting that epithelial sodium channels may act as https://doi.org/10.1016/j.eprac.2021.04.698 key mediators of GH-induced sodium retention. MRAs should be considered in the treatment of hypertension in acromegaly, particularly if there are no contraindications and BPs are non- Abstract #989420 responsive to multiple other agents. https://doi.org/10.1016/j.eprac.2021.04.697 A Novel CHD7 Mutation, Described as a Variant of Uncertain Significance, is Found in a Patient Diagnosed with Kallmann Syndrome Abstract #988443

Primary Hyperparathyroidism and Persistent Peptic Author Block: Mohamed Abouzid - Mansoura University Faculty of Ulcers: A Prelude to a Diagnosis of MEN1 Caused by a Medicine; Mohamed Riad, MBBCh - Primary author and presenter, Novel Gene Mutation Mansoura University Faculty of Medicine, Egypt; syeda zaidi, MD - Co-author, Nishtar Medical College, Multan Pakistan; Jose Duenas,~ MD - Co-author, Universidad catolica de Santiago de Guayaquil, Author Block: Tamaryn Fox - Einstein Medical Center; ecuador; Maria Rendon, MD - Co-author, Universidad catolica de Catherine Anastasopoulou, MD, PhD, FACE - co-author, Santiago de Guayaquil, Ecuador; Ritu Yadav, MBBS - Co-author, Endocrinology and Metabolism, Einstein Medical Center; Maulana Azad Medical College, New Delhi, India; Jassimran Singh, Nissa Blocher, MD, FACE - co-author, Einstein Medical Center MBBS - Co-author, Institute of medical sciences, BHU, India; Lubna Mirza, MBBS - Endocrinologist and Diabetes Specialist e Co- Introduction: Multiple Endocrine Neoplasia 1 (MEN1) is a rare author, Norman Regional Health System syndrome characterized by a propensity for pituitary, parathyroid, pancreatic, and adrenal tumors. Over 200 pathologic mutations Introduction: Reporting a novel mutation in chromodomain-heli- have been reported. Penetrance is high, but presentation can be case-DNA-binding protein 7 (CHD7) gene in the case of Kallmann variable making its diagnosis at times difficult. syndrome, which has been classified as a Variant of Uncertain Case Description: The patient is a 36-year-old male with type 1 Significance. diabetes mellitus complicated by chronic kidney disease and gas- Case Description: We present a case of a 25-year-old male patient troparesis, primary hyperparathyroidism, and severe peptic ulcer who was admitted to the Endocrinology Clinic with a complaint of disease. His only known family history is type 1 diabetes in his delayed puberty. He presented with hypogonadotropic hypo- mother. Regarding his primary hyperparathyroidism, at diagnosis gonadism and anosmia in addition to a past medical history of his calcium was 11.9mg/dL (ref: 8.4-10.3mg/dL), PTH 126.7pg/mL unilateral undescended testis, bimanual synkinesia and social (ref: 9-73pg/mL) and 24-hour urine calcium elevated at 332mg/24 anxiety disorder. Laboratory investigations revealed very low levels hours (ref: 100-300mg/24 hours). He never had symptoms of hy- of FSH, LH and testosterone. Genetic mutational analysis by invitae percalcemia nor evidence of nephrolithiasis. His peptic ulcer dis- platform was done. The patient has responded well to treatment ease history was characterized by multiple ulcers spanning from with 200 mg intramuscular testosterone cypionate every two the esophagus to the jejunum with 2 episodes of ulcer perforation. weeks, and additional infertility treatment may be required. Given the multiple widespread ulcers, suspicion was raised for Discussion: Invitae test result identified a Variant of Uncertain Zollinger Ellison syndrome. A gastrin level was found to be elevated Significance, c.8595G >A (silent) in CHD7, exon 38. It is a silent at 553pg/mL (ref: < ¼100pg/mL), however, this was done whilst on change, meaning that it does not change the encoded amino acid a proton-pump inhibitor and no gastric pH was checked. A so- sequence of the CHD7 protein. This variant is present in population matostatin scan was negative. Regardless, the index of suspicion databases (rs757002335, ExAC 0.001%) and has not been reported remained high, and in conjunction with his diagnosis of primary in the literature in individuals with CHD7 related conditions such as hyperparathyroidism, MEN1 syndrome became a diagnostic pos- Kallmann syndrome or CHARGE syndrome. sibility. He underwent genetic testing which turned positive for (arr Further studying of CHD7 gene as a culprit of Kallmann syndrome [hg19] 11q13.1 (64573363_64575254)X1) deletion encompassing a through additional case reports or clinical trials is necessary, as this region in exon 4-7 of the MEN1 gene. Workup for other manifes- novel mutation has expanded the number of mutations on CHD7 tations of MEN 1 syndrome was negative, including normal pro- gene in particular and the overall genetic mutations that can lactin level and adrenal imaging. contribute to the pathogenesis of Kallmann syndrome. Discussion: Clinical suspicion of MEN 1 syndrome is based on https://doi.org/10.1016/j.eprac.2021.04.699 recognition of associated tumors and confirmed with genetic testing. A family history of the disorder is typical, but 10% of cases ’ fi arise from de novo germline mutations. Our patient s speci c mu- Abstract #993208 tation has not been previously described in the literature; however, similar mutations have established pathogenicity. Most germline Pituitary Apoplexy Secondary to GnRH Agonist, mutations in MEN1 syndrome are small insertions, deletions or Leuprolide, for Breast Cancer: A Case Study and Review substitutions. Large deletions such as this are extremely rare. of The Literature

S108 Pituitary Disorders/Neuroendocrinology Endocrine Practice 27 (2021) S107eS132

Author Block: Mihail Voica, Endocrinology Fellow - Primary Introduction: we report here a case of cushing disease secondary to author, Endocrinology, Allegheny Health Network; Maryam Tetlay, pituitary micro adenoma with diagnostic challenges due to Resident - Co-author, Internal Medicine, Allegheny Health discrepancy in radiologic and IPSS findings. Network; Farhad Hasan, Attending endocrinologist - Co-author, Case Description: A 27 year old male presented at endocrine clinic Endocrinology, Allegheny Health Network of jinnah post graduate medical centre, Karachi, pakistan with history of weight gain, cutaneous striae and uncontrolled hyper- Introduction: Pituitary apoplexy (PA) is most often caused by tension for 6 years.Examination showed BP of 190/150mm Hg, spontaneous bleeding into a pituitary macroadenoma (PM). PA has moon like face with prominent striae overs limbs and abdomen. A rarely been reported as an adverse effect of GnRH agonists. We 24 hour urinary cortisol levels were significantly raised with an report the first case of PA following leuprolide adjuvant therapy for ACTH level of 29.18pg/m1 corroborating the ACTH dependent na- breast cancer. ture of tumor. Serial pituitary MRI scans performed during this Case Description: A 53 y.o. female was evaluated for recurrence period failed to reveal the tumor. High dose dexamethasone sup- of nonfunctioning PM. PMHx included breast cancer and obesity. pression test showed positive result validating the tumor localiza- She was originally diagnosed with PM at the age of 37 y during tion to brain. Ectopic foci were rule out via chest and abdominal workup for chronic headaches. Evaluation showed a nonfunc- Imaging. Moreover, Inferior petrosal sinus sampling was performed tioning PM with compressive symptoms. She underwent trans- showing gradient difference of 24.94 on the right side as compare sphenoidal surgery after which she was lost to follow up. She to 12.40 on the left side .However a repeat MRI pituitary showed presented to our clinic at the age of 52 because of worsening tumor on the left side. He was then planned for trans-sphenoidal headaches and fatigue. A pituitary MRI (Fig. 1) showed recur- tumor resection. Pre-operative Blood pressures were controlled rence of PM measuring 1.5 x 1.5 x 1.5 cm with suprasellar with triple drug regimen. Histopathology confirmed the pituitary extension and abutment of the optic chiasm. Examination was origin of tumor. Post operatively, patient's symptoms markedly remarkable for obesity (BMI 34) and no VF deficits. Endocrine improved with systolic blood pressure falling in normal range and evaluation showed anterior pituitary hormones within reference weight reduction in three months follow-up. His post op ACTH is range, free T4 0.7 ng/dl (0.8-1.8), and normal cortisol. Patient 38.5 (0 -46 pg/ml) and costisol is 18.30 (4.3 e 224 ug/dl) was started on LT4 50 mcg daily. Tumor surveillance was Discussion: Bilateral inferior petrosal sinus sampling plays a sig- planned in 6m. Regarding breast cancer history, she had partial nificant role in the diagnosis of Cushing disease having the sensi- mastectomy followed by adjuvant therapy. She received the first tivity and specificity of 96% and 100% respectively. However, it is dose of adjuvant GnRH agonist, leuprolide (11.25 mg IM), on not the accurate method for localizing the side of pituitary having June 8th, 2020. On June 12th (4 days later) she presented with adenoma. There might be a discrepancy in the tumor localization acute onset severe headache associated with photophobia, between the IPSS and radiological findings which could be due to phonophobia, nausea, emesis, and blurriness in the right eye. PA anatomical differences and technical issues. The best treatment was suspected and the patient was referred to the ER. Pituitary option in such cases with discrepancy in radiology is always sur- MRI confirmed PA (Fig. 2) and endocrine work up revealed gical removal of the adenoma. anterior panhypopituitarism. Patient was hospitalized and https://doi.org/10.1016/j.eprac.2021.04.701 received IV glucocorticoids after drawing labs. Ophthalmologic evaluation revealed mild bilateral impairment in visual acuity (20/30) and scotomas in the right eye. Conservative treatment Abstract #994705 was elected and patient was discharged on HC 15 mg/day and LT4 50 mcg daily. Repeat pituitary MRI in 3m showed a partial The High Prevalence of Coronary Calcification and empty sella (Fig. 3). Increased Risk for Coronary Heart Disease in Patients Discussion: We identified 22 reported cases of PA in patients with Sheehan’s Syndrome receiving GnRH agonists for prostate cancer, and 2 cases in patients receiving GnRH agonists for infertility. To our knowledge, this is the first reported case of PA in a patient receiving leuprolide as adju- Author Block: JAVAID AHMAD BHAT - Sher i Kashmir Institute of vant therapy for breast cancer. The exact mechanism of this Medical Sciences, Srinagar, Jammu and Kashmir, India; complication is unknown. It is presumed to be due to the initial Mehak Afroze, M.D, Medicine - Co-author, Deptt. of Medicine, pituitary stimulation caused by GnRH agonist action that in return Deptt. of Medicine, GMC, Srinagar, Jammu and Kashmir, India; causes the underlying adenoma to become more active and to Hardeep Singh, M.D, Medicine - Co-author, Deptt. of Medicine, outgrow its blood supply, eventually causing necrosis and hemor- Deptt. of Medicine, GMC, Srinagar, Jammu and Kashmir, India; rhage. Physicians should be aware of this rare complication of GnRH Shahnaz A. Mir, DM Endocrinology - Co-author, Deptt. of agonist therapy in patients with known PM. Endocrinology, Superspeciality Hospital, GMC, Srinagar, https://doi.org/10.1016/j.eprac.2021.04.700 Superspeciality Hospital, GMC, Srinagar, Jammu and Kashmir, India

Objective: Sheehan's syndrome (SS) is one of the most important Abstract #994648 causes of hypopituitarism in developing countries with patients having varying degrees and severity of anterior pituitary hormone Cushing Disease; A Diagnostic Puzzle. deficiency including growth hormone deficiency (GHD). SS is characterized by Increased clustering of metabolic and pro-in- flammatory risk factors predisposing them to increased cardio- Author Block: Urooj lal Rehman - jinnah postgraduate medical vascular morbidity and mortality. Coronary calcium deposits (CCD), centre; RUKHSHANDA JABEEN, MBBS, FCPS - co author, medicine a marker for significant coronary atherosclerosis, is used for eval- and endocrinology, jinnah postgraduate medical centre; uation in asymptomatic individuals of global cardiac risk to develop sidra mumtaz, MBBS - co author, medicine and endocrinology, events related to coronary heart disease (CHD). The present study jinnah postgraduate medical centre was designed to evaluate the prevalence of coronary calcium

S109 Pituitary Disorders/Neuroendocrinology Endocrine Practice 27 (2021) S107eS132 deposits in patients with SS appropriately replaced for pituitary an incidental cystic macroadenoma, the patient was discharged hormones deficiencies but untreated for GHD. from the emergency department after unremarkable neurological Methods: Thirty patients previously diagnosed with SS and stable and ophthalmic evaluation. The patient returned from an outpa- on conventional replacement treatment for at least 6 months tient follow-up MRI brain three weeks later for new onset fever before the study and thirty age, sex and body mass index (BMI) (101.1 F), hypotension (76/50 mmHg), and syncopal episodes. MRI matched controls were enrolled in this observational study. The brain demonstrated a 1.9 x 1.4 cm centrally necrotic sellar mass subjects underwent detailed clinical, biochemical, and hormone with suprasellar extension and a thick enhancing wall. She was analysis. Coronary multidetector computed tomography was per- started on broad spectrum antibiotics and pressor support for formed in 19 SS patients and 19 healthy participants by 16-row sepsis secondary to superimposed infection of sellar cyst versus multislice scanner. Noncontrast acquisitions were performed to abscess. Her workup included WBC 2.4x10E3/uL, INR 1.5 seconds, detect coronary calcifications. Calcium was quantified by the TSH 0.03 mIU/L, free T4 0.3 ng/dL, cortisol 5.0 mcg/dL, ACTH< 1.5 Agatston score (AS) in all subjects. AS >10 indicates increased CHD pg/mL, prolactin 2.9 ng/mL, IGF-118 ng/mL, FSH 1.3 mIU/mL, LH 0.6 risk. mIU/mL and negative urine, blood, and CSF studies (including Results: The mean (±SD) age of patients and healthy controls was syphilis and toxoplasmosis). She required hydrocortisone, levo- comparable (38.30 ±10.73 vs. 40.6 ±8.46years; P¼0.78) and diag- thyroxine and eventually DDAVP for diabetes insipidus. TSS was nostic delay for patients was 11.35 ±4.74 years. Patients with SS had deferred in light of clinical instability, AIDS, leukopenia and risk for significantly higher mean triglyceride, total cholesterol and low bleed. Repeat MRI brain after seven days of medical management density lipoprotein cholesterol and lower high density lipoprotein and stabilization showed a decrease in size of the lesion to 1.3 x 0.7 cholesterol concentrations on conventional replacement therapy. cm confined to the sella, favoring pituitary abscess as final The prevalence of CCD was significantly higher in patients of SS diagnosis and positive treatment response. After six weeks compared to controls (42.1% vs. 5.3%; P ¼ 0.023). The presence of of vancomycin, cefepime and metronidazole final MRI brain CCD and AS >10 were detected in 42.1% and 31.6% of patients showed resolution of the pituitary abscess with no residual masses. respectively. The presence of significant calcification (Agatston Today she has no neurological deficits and remains on levo- score > 10) was documented in 75% of patients (Left anterior thyroxine and hydrocortisone until reevaluation of her descending, 1; left circumflex, 2; right coronary artery, 2 and pos- panhypopituitarism. terior descending, 1) of the SS patients with CCD compared to none Discussion: The diagnosis and treatment of PAs often occur in the control group (P ¼ 0.019). simultaneously during surgical intervention and are uncommonly Discussion/Conclusion: In conclusion, our study demonstrated that diagnosed preoperatively. Specific radiographic features may the patients with SS have higher prevalence of significant coronary improve preoperative diagnosis and allow for timely treatment. In calcium deposits and AS >10. Since coronary artery calcium has the presented case, follow-up imaging supported both pituitary been found to be an independent predictor of increased risk of CHD abscess as diagnosis and medical management as effective events; the significant prevalence of CCD in patients with SS treatment. compared to healthy matched controls, undermines the impor- https://doi.org/10.1016/j.eprac.2021.04.703 tance of early risk stratification of SS individuals with plethora of conventional cardiovascular risk factors, to avoid the adverse vascular consequences. Abstract #996232 https://doi.org/10.1016/j.eprac.2021.04.702 A Rare Case Of Actinomyces Infected Prolactinoma

Abstract #994803 Author Block: Amy Shah - University of Vermont Medical Center; A Conservative Approach to an Aggressive Anthony Tran, DO - Co-author, Westchester Medical Center; Presentation: Nonsurgical Treatment of a Pituitary Matthew Gilbert, DO, MPH - Co-author, UVMMC; Sree Garapati, Abscess in an Immunocompromised Patient MD - Co-author, UVMMC

Introduction: BACKGROUND: Pituitary abscesses are rare and can Author Block: Madeline Fasen, DO - Primary author, University of be dire. During MRI (the preferred imaging modality for prolacti- Florida College of Medicine; Aleem Ali, MD - co-author, University nomas) they present as a solid tumor displaying an intrasellar or of Florida College of Medicine; Kent Wehmeier, MD - co-author, suprasellar mass with attenuation similar to the brain, demon- University of Florida College of Medicine strating moderate contrast enhancement. Here we present a patientwho had transsphenoidal resection of a prolactinoma and Introduction: Pituitary abscesses (PAs) are rare but detrimental pathology revealed a gram positive filamentous bacteria. entities that comprise less than 1% of all pituitary disease. The Case Description: CASE: A 41-year-old female with untreated diagnosis of PAs prior to surgery is a challenge due to this rarity and prolactinoma diagnosed in 2004 presents in 2019 with headache similar presentation to other pituitary diseases, both clinically and and visual disturbances. MRI reveals a sellar/suprasellar 3cm radiographically. Prompt surgical treatment with transsphenoidal hypoenhancing solid mass with cystic components invading the surgery (TSS) and antibiotics is standard therapy. To demonstrate left cavernous sinus and optic chiasm compression. PRL 1,356. that medical management can be an effective and alternative op- Cabergoline was started, but the dose reduced due to patient tion we describe the successful treatment of a pituitary abscess in a intolerance. After 1 month, repeat MRI showed minimal size high-risk surgical candidate with HIV. decrease. Medication intolerance led to intervention by trans- Case Description: A 46 year-old female presented with generalized sphenoidal resection, which drained mucoid-like fluid, not headache after a head injury from a domestic dispute. History cultured. Pathology revealed a prolactinoma with large bacterial included HIV (CD4 92 cells/UL) on no medications. CT head growth. Staining showed positive filaments on Brown and Brenn revealed a 1.4 x 0.7 cm hypodense sellar mass lesion. Deemed to be and negative AFB-FITE consistent with Actinomyces. Given

S110 Pituitary Disorders/Neuroendocrinology Endocrine Practice 27 (2021) S107eS132 potential outcomes without treatment, patient was given IV peni- 2.4 mIU/ml [0.6 - 12.1mIU/ml], Follicle-stimulating hormone: 5.25 cillin for 1 mo followed by oral amoxicillin for 6 mo. mIU/ml [1.4-13.6 mIU/ml], Insulin-like growth factor: 16 ng/ml Discussion: Surgery for prolactinomas has a limited role due to the (reference range for age and sex: 35-215 ng/ml). The patient un- usual success of medical therapy alone. In this case and in literature derwent transnasal-transsphenoidal resection of the tumor, which review of pituitary abscess, we found certain radiologic findings had invaded deep into the CS. Pathology showed a pituitary ade- that may suggest a superimposed infectious process. Although pi- noma with total hemorrhagic necrosis. He had an uneventful tuitary abscess are rare, the potential fatal outcome gives impor- postoperative hospital course but with no improvement in ocular tance in considering an approach to differentiate an infectious symptoms. He was discharged on hydrocortisone 10 milligrams in process within pituitary lesions. Commonly there are no clinical the morning and 5 milligrams in the evening and levothyroxine 25 symptoms or signs of pituitary abscess and it is indistinguishable mcg with outpatient endocrine follow-up. clinically of other pituitary lesions. Actinomyces, a bacteria that can Discussion: Pituitary adenomas tend to grow upward into the colonize the mouth, digestive, and genital tract, is even more suprasellar cistern, but when an adenoma expands laterally, it may indolent than other organisms previously reported in pituitary erode the sellar turcica and compress the adjacent CS and its abscess, with similar potentially devastating outcomes. Super- contained structures. Our case highlights a rare constellation of a imposed infections of pituitary lesions characteristically showed pituitary adenoma with CS invasion complicated by PA during HD. cystic pituitary masses with isointense/lower signal intensity on T1, Patients undergoing HD are at increased risk of pituitary adenoma absence of normal high signal intensity of neurohypophysis, and hemorrhage due to variability in hemodynamics and intracranial direct extension to cavernous sinus or other sinuses, some of which pressure. Furthermore, the use of anticoagulants such as heparin were seen in our case. Hemorrhage and rim enhancing character- during dialysis can be a predisposing factor for pituitary hemor- istics with previous findings increase suspicion of infectious pro- rhage and PA. There are only three cases of PA during HD in the cess. We suggest a multidisciplinary approach if the imaging literature, and to our knowledge, this is the first reported case of characteristics described are present despite initial response to simultaneous PA and CSS during HD. Prompt recognition of PA in a medical therapy as is common in this and other reported cases of patient presenting with CSS, particularly in the HD setting, is pituitary lesions with superimposed infections. essential to ensure appropriate care is provided for this endocrine emergency. https://doi.org/10.1016/j.eprac.2021.04.704 https://doi.org/10.1016/j.eprac.2021.04.705

Abstract #996661 Abstract #999903 A Case of Pituitary Apoplexy and Cavernous Sinus Syndrome During Hemodialysis Evaluation of Cardiovascular Risk Factors in Sheehan’s Syndrome

Author Block: Yusra Jamal, MBBS - Primary Author, Endocrinology, Westchester Medical Center; Yudi Camacho, M.D - co.author, Author Block: MAYUR AGRAWAL - SGPGI, Lucknow; Westchester Medical Center; Jamie A. Mullally, Board Certified SUBHASH YADAV, MBBS, MD MEDICINE DNB ENDOCRINOLOGY - Endocrinologist, MD. - Co.author, Endocrinology, Westchester CO-AUTHOR, ENDOCRINOLOGY, SGPGI Medical Center Objective: Hypopituitarism has an increased prevalence of con- Introduction: Pituitary apoplexy (PA) is a clinical syndrome of pi- ventional cardiovascular risk factors like obesity, dyslipidaemia, tuitary hemorrhage or infarction and can result in hypopituitarism and insulin resistance. Sheehan syndrome caused by postpartum and compression of adjacent brain structures. Cavernous sinus necrosis is not well studied in this respect. We evaluated the sur- syndrome (CSS) occurs when a pituitary adenoma extends into the rogate markers of cardiovascular risks by various clinical, cavernous sinus (CS), causing CN III, IV, V1, V2, and VI compression. biochemical, and radiological tests including hsCRP, IL-6, CIMT, We describe a case of a patient with an undiagnosed pituitary FMD and echocardiography. macroadenoma who presented with acute PA and CSS during he- Methods: In this cross-sectional study, we studied 45 patients with modialysis (HD). Sheehan’s syndrome (SS) on standard replacement therapy and Case Description: A 77-year-old male with end-stage renal disease compared with healthy age, gender and BMI matched controls. SS (ESRD) presented to an outside hospital with acute headache and was diagnosed by history of post-partum hemorrhage or amenor- ophthalmoplegia of the left eye during HD. A MRI of the brain rhea following childbirth or lactational failure, hormonal evalua- revealed a 2.5 x 1.5 x 1.8 cm pituitary adenoma with invasion into tion suggestive of loss of pituitary hormone reserve and MRI the left CS. He was started on steroids due to hypotension with a imaging was done to rule out other causes of hypopituitarism. blood pressure of 90/55 and transferred to our hospital, where he Anthropometric measurements and hormonal evaluation including was hemodynamically stable. His physical exam showed left eye Adrenocorticotropic hormone (ACTH), 8am cortisol, stimulated ptosis, fixed and dilated left pupil, left eye vision 20/100, normal cortisol (1 hr after synacthen), Insulin-like growth factor-1 (IGF-1), afferent pupillary reflex, and complete palsy of left CN III, IV, and Thyroxine (T4), Follicle-stimulating hormone (FSH), Luteinizing partial palsy of CN VI. Visual fields were full to confrontation. The Hormone (LH), Estradiol (E2) and Prolactin and serum Insulin level, remainder of the physical and funduscopic examination was un- Interleukin-6 (IL-6) and high sensitivity C reactive protein (hsCRP) remarkable. The hormonal profile was consistent with pan-hypo- were measured on chemiluminescence assay (Immulite1000, pituitarism with Cortisol: 2.1 mcg/dl [3.7-19.4mcg/dl], Siemens, Germany). Carotid intima-media thickness (CIMT), flow- Adrenocorticotropic hormone: 7.0 pg/ml [7.2-63 pg/ml], Thyroid- mediated dilation (FMD) and echocardiography with colour stimulating hormone: 0.053 mIU/l [0.350-4.700 mIU/L], Free doppler (GE vivid E9 XD, Wisconsin, USA) were also performed. thyroxine: 0.7ng/l [0.7-1.9 ng/l], Prolactin: 1.9 ng/ml [2.6 e 181 ng/ Results: Mean age and BMI of Sheehan patients was 48.11±10.0 ml], Testosterone < 7.0 ng/dl [240-950 ng/dl], Luteinizing hormone: years and 24.34±4.30 kg/m2 while that of controls was 44.58±12.0

S111 Pituitary Disorders/Neuroendocrinology Endocrine Practice 27 (2021) S107eS132 years and 24.63±3.18 kg/m2. Waist hip ratio was significantly decisions were made by independent non-blinded endocrinolo- higher in SS controls (0.95±0.08 vs.0.88±0.07, p¼0.000). All SS gists until W12. All pts received osilodrostat from W12 to W48 patients were hypothyroid and all except one were hypo- (max 30mg bid). Efficacy/safety were assessed for pts during osi- cortisolemic. Triglycerides levels were significantly higher lodrostat treatment (excluding data from periods that the pt (165.60±83.28 vs. 117.16±56.08, p ¼0.001) but no difference in received P) until primary analysis cut-off date. prevalence of metabolic syndrome was found (32.5% vs. 27.9%, Results: Median (IQR) osilodrostat exposure was 75W (48e117) p¼0.4). hsCRP (15.25±20.3 vs. 2.12±2.4, p¼0.000) and IL-6 [4.9(3.7- and 70W (49e87) in LINC3 and LINC4 (median [IQR] dose 7.1 7.2) vs. 3.06 (2.0-4.1), p¼0.000] was significantly higher. CIMT was [3.8e14.0] and 5.0 [3.8e9.2] mg bid). Median (95%CI) time to first significantly increased (0.624±0.107 vs. 0.566±0.136, p< 0.01) as mUFCULN was 41 (30e42) and 35 (34e52) days in LINC3 and but no difference in FMD was found (19.96±9.93 vs.19.43±6.56, LINC4. AEs potentially related to hypocortisolism occurred in more p¼0.97). Echocardiography revealed no significant difference in LV pts in LINC3 than LINC4 (51% [n¼70] and 27% [n¼20]). Among this dimensions, interventricular thickness, posterior wall thickness, category of events, the most commonly reported preferred term ejection fraction, LV mass and diastolic function. was adrenal insufficiency (AI), which comprised events of gluco- Discussion/Conclusion: Our study demonstrated that SS patients on corticoid deficiency, adrenocortical insufficiency, steroid with- standard replacement therapyexcept GH replacement have increased drawal syndrome, and cortisol decreased. AI was mostly grade 1e2 cardiovascular risk including hypertension, dyslipidemia, central and managed with dose interruption and/or concomitant medica- obesity, inflammatory markers like hsCRP and IL-6 and atheroscle- tion. In LINC3, most hypocortisolism-related AEs emerged by W26 rotic markers like CIMT and may lead to increased mortality. (77% [n¼54/70]); in LINC4, 25% (n¼12/48) of pts randomized to osilodrostat had a hypocortisolism-related AE, 58% (n¼7/12) of https://doi.org/10.1016/j.eprac.2021.04.706 whom during the P-controlled period (W1e12). Hypocortisolism- related AEs were not associated with mUFC levels or specific osi- Abstract #999926 lodrostat dose. Discussion/Conclusion: More gradual increases in osilodrostat dose Effect of Dosing and Titration of Osilodrostat on Efficacy (every 3W vs 2W), from a starting dose of 2mg bid, may reduce the and Safety in Patients With Cushing's Disease (CD): occurrence of hypocortisolism-related AEs without compromising Results From Two Phase III Trials (LINC3 and LINC4) mUFC control. CD pts should initiate osilodrostat at a low dose, with incremental dose increases based on disease severity and individ- ual response/tolerability aimed at normalizing cortisol levels. Author Block: Maria Fleseriu, Professor of Medicine and https://doi.org/10.1016/j.eprac.2021.04.707 Neurological Surgery - Primary author and presenter, Oregon Health & Science University; Richard J. Auchus, Professor of Internal Medicine and Pharmacology - Co-author, University of Abstract #1000028 Michigan; Peter J. Snyder, Professor of Medicine - Co-author, Perelman School of Medicine, University of Pennsylvania; Injection Site Reactions and Their Impact in Patients Andre Lacroix, Professeur Titulaire - Co-author, Centre hospitalier With Acromegaly Receiving Injectable Somatostatin de l’Universite de Montreal; Anthony P. Heaney, Associate Receptor Ligands in the Phase 3 MPOWERED Trial Professor - Co-author, David Geffen School of Medicine, University of California, Los Angeles; Eliza B. Geer, Medical Director - Co- author, Memorial Sloan Kettering Cancer Center; Author Block: Murray B. Gordon, MD - Primary Author, Allegheny James W. Findling, Clinical Professor of Medicine and Surgery - Co- General Hospital; Maria Fleseriu, MD - Presenter and Primary author, Medical College of Wisconsin; Julie Silverstein, Associate Author, Oregon Health & Science University; Irina Bondar, MD - Professor of Medicine and Neurological Surgery - Co-author, Co-Author, Novosibirsk State Medical University; Elena Isaeva, MD, Washington University School of Medicine; Alberto M. Pedroncelli, PhD - Co-Author, Interregional Clinical Diagnostic Center; Global Medical Director - Co-author, Recordati AG; Mark E. Molitch, MD - Co-Author, Division of Endocrinology, Andrea Piacentini, Senior Statistician - Co-author, Recordati SpA; Metabolism & Molecular Medicine, Department of Medicine, Beverly M.K. Biller, Professor of Medicine - Co-author, Northwestern University Feinberg School of Medicine; Massachusetts General Hospital Djuro P. Macut, MD, PhD - Co-Author, University of Belgrade; Nina Leonova, MD, PhD - Co-Author, Antrium Multidisciplinary Objective: Two Phase III studies (LINC3 NCT02180217; LINC4 Medical Clinic; Gerald Raverot, MD, PhD - Co-Author, Hospices NCT02697734), showed that osilodrostat, a potent oral 11b-hy- Civils de Lyon; Yossi Gilgun-Sherki, PhD - Co-Author, Chiasma, Inc; droxylase inhibitor, is an effective treatment for CD. Reductions in William H. Ludlam, MD, PHD - Co-Author, Chiasma, Inc; cortisol levels during osilodrostat therapy can lead to hypo- Gary Patou, MD - Co-Author, Chiasma, Inc; Asi Haviv, DMD - Co- cortisolism, which may be mitigated by slow dose uptitration. We Author, Chiasma, Inc; Nienke Biermasz, MD, PhD - Co-Author, assessed the effect of the different dose titration schedules in LINC3 Leiden University Medical Center (LUMC); Shlomo Melmed, MB, and LINC4 on hypocortisolism-related AEs. ChB, FRCP, MACP - Co-Author, Cedars Sinai Medical Center; Methods: In LINC3, 137 CD patients (pts) with mean urinary free Christian J. Strasburger, MD - Co-Author, Charite Campus Mitte cortisol (mUFC) >1.5xULN (baseline [BL] median 3.5xULN) started open-label osilodrostat 2mg bid, with dose increases (max 30mg Objective: Injectable somatostatin receptor ligands (iSRLs) are used bid) every 2 weeks (W) until W12 if mUFC >ULN, then every 4W to treat acromegaly. However, injection site reactions (ISRs) are until W24. At W26, eligible pts were randomized to osilodrostat or common and impact patient activities of daily living and quality of ® placebo (P) for 8W, followed by osilodrostat until W48 (max 30mg life (QOL).1-3 Recently, oral octreotide capsules (OOC; MYCAPSSA ) bid). In LINC4, 73 CD pts with mUFC >1.3xULN (BL median 2.5xULN) were approved in the United States as a new treatment option for were randomized to osilodrostat 2mg bid (n¼48) or P (n¼25). Dose adult patients with acromegaly previously responding to iSRLs was increased (max 20mg bid) every 3W until W12 if mUFC >ULN; (octreotide or lanreotide). MPOWERED is a phase 3 trial assessing

S112 Pituitary Disorders/Neuroendocrinology Endocrine Practice 27 (2021) S107eS132 maintenance of response to OOC compared to iSRLs in patients with mild TBI. Symptoms of GHD are often nonspecific and can acromegaly. Here we report ISR-related data from patients encompass decreased quality of life, muscle mass, and physical receiving iSRLs in the randomized controlled treatment (RCT) capacity; increased visceral fat; poor growth; and impaired cogni- phase of the MPOWERED trial. tive function. Methods: Eligibility criteria for MPOWERED included acromegaly Methods: Panels of pediatric and adult endocrinologists, neurolo- diagnosis, biochemical control of acromegaly (insulin-like growth gists, physical medicine and rehabilitation specialists, and brain factor I < 1.3 upper limit of normal; mean integrated growth injury medicine specialists convened in February and October 2020 hormone, < 2.5 ng/mL) and 6 months’ iSRL (octreotide or lan- as part of advisory boards (sponsored by Novo Nordisk Inc.) to reotide) treatment. Eligible patients entered a 26-week Run-in discuss ongoing challenges and provide strategies for detection and phase to determine the effective OOC dose; responders at week 24 optimal management of patients with mild TBI and GHD. then entered a 36-week RCT phase receiving OOC or iSRLs. Inci- Results: Advisors identified challenges with the diagnosis and dence of ISRs was assessed throughout the RCT phase using adverse treatment of GHD in patients with mild TBI, including the role of event (AE) reporting, acromegaly directed physical examination primary care physicians, and obtaining GH replacement therapy. (ADPE), and as part of the validated patient-reported outcome Difficulties with diagnosis include suboptimal screening tools, (PRO) measure for acromegaly, the Acromegaly Treatment Satis- limited availability of GHD testing, issues with insurance reim- faction Questionnaire (Acro-TSQ).1 bursement, and a lack of consensus on when to test for GHD in Results: Ninety-two patients were eligible to enter the RCT phase, these patients. In addition, there is an absence of referrals to en- of which 55 were randomized to receive OOC and 37 were ran- docrinologists from other specialists who often are not aware of the domized to receive iSRLs. ISRs were reported in 32.4% of patients need for GHD testing. Moreover, a large community of clinicians (12/37) in the iSRL arm: as an AE in 10 patients and as part of the believe that concussions (ie, mild TBI) are a benign condition; ADPE in the remaining two. ISRs reported as AEs included injection however, literature suggests that 15% to 50% of concussed patients site nodules (16.2%), injection site pain (10.8%), pain (5.4%), injec- may have residual cognitive symptoms at 1 year. The belief that all tion site erythema (2.7%), and injection site pruritus (2.7%). Using mild TBI cases with persistent symptoms are benign contributes to Acro-TSQ responses collected as a PRO, assessments of ISRs during the lack of referrals for GHD diagnostic testing. Advisors varied treatment demonstrated that in the iSRL arm, 47% of patients (17/ broadly in how they would identify patients with mild TBI who 36) reported ISRs, and of those, 81.2% reported that the ISRs need screening for potential GHD and other deficiencies, recog- interfered with their daily activities. nizing that pituitary hormone abnormalities are difficult to Discussion/Conclusion: In this study population, 32.4% of patients confirm. experienced ISRs while receiving iSRL treatment, through sponta- Recommendations from the panel for managing such patients neous reporting. However, 47% of patients reported ISRs as a soli- included multidisciplinary guidelines on the diagnosis and man- cited response to PROs. Recently approved OOC is an oral option for agement of post-TBI GHD and additional education on long-term maintaining biochemical response in patients with acromegaly metabolic and probable cognitive benefits of GH replacement with the advantage of avoiding or eliminating ISRs that could therapy in both pediatric and adult patients. interfere with daily activities and thereby impair QOL. Discussion/Conclusion: Patients of all ages with mild TBI may also have GHD and/or other pituitary deficiencies. A multidisciplinary https://doi.org/10.1016/j.eprac.2021.04.708 approach to provide education to both endocrinologists and non- endocrinologists and guidelines for the early identification and Abstract #1000170 management of GHD related to mild TBI are urgently needed. https://doi.org/10.1016/j.eprac.2021.04.709 Growth Hormone Deficiency in Patients With Mild Traumatic Brain Injury: Insights From a US Advisory Board Abstract #1000208

Crooke Cell Adenomas in Patients with Cushing’s Author Block: Kevin Yuen - Barrow Neurological Institute; Disease: A Tertiary Care Center Experience Brent Masel, MD - co-author, University of Texas Medical Branch, Galveston, TX, USA; Michael S. Jaffee, MD - co-author, University of Florida, Gainesville, FL, USA; Gregory O'Shanick, MD - co-author, Author Block: Erica A. Giraldi, MD - primary author, Department of Center for Neurorehabilitation Services, Richmond, VA, USA; Medicine, Division of Endocrinology; Department of Neurosurgery, Kent Reifschneider, MD - co-author, Children’s Hospital of The Emory University School of Medicine; Stewart G. Neill, MD, MS - King’s Daughters, Norfolk, VA, USA; Randall J. Urban, MD - co- co-author, Department of Pathology, Emory University School of author, University of Texas Medical Branch, Galveston, TX, USA; Medicine; Pia R. Mendoza, MD - co-author, Department of Sophie Hoang, PharmD - co-author, Novo Nordisk Inc., Plainsboro, Pathology, Emory University School of Medicine; NJ, USA; Nicky Kelepouris, MD - co-author, Novo Nordisk Inc., Nelson M. Oyesiku, MD, PhD - co-author, Department of Plainsboro, NJ, USA; Andrew R. Hoffman, MD - co-author, Stanford Neurosurgery, Emory University School of Medicine; University Medical Center, Stanford, CA, USA Adriana G. Ioachimescu, MD, PhD - co-author, Department of Medicine, Division of Endocrinology; Department of Neurosurgery, Objective: Approximately 2.5 million children and adults in the US Emory University School of Medicine experience traumatic brain injury (TBI) annually, and most of these injuries (85%) are considered “mild.” Many events, including motor Objective: Crooke cell adenomas (CCA) are a rare subtype of cor- vehicle and bicycle accidents, sports injuries, and falls, can cause ticotroph adenomas characterized by the majority of cells exhibit- TBI. TBI can have long-term consequences on pituitary function, ing ring-like deposition of cytokeratin. CCAs were identified as a including growth hormone deficiency (GHD), although this has clinically aggressive pituitary adenoma subtype by the WHO in been more commonly identified in moderate-severe cases than in 2017. Two surgical series published before the updated WHO

S113 Pituitary Disorders/Neuroendocrinology Endocrine Practice 27 (2021) S107eS132 classification reported a prevalence of CCA among functioning Case Description: Case presentation. ACTH-adenomas of 6.8% and 4.9% respectively. Discussion: 86-year old female presented with one week of general Presentation and clinical course of CCAs in Cushing’s disease (CD) weakness, decreased appetite, sleep, and polyuria. Initial serum has been poorly delineated, mostly by case reports. sodium was 128 mmol/L (136-146), and plasma and urine osmo- Methods: Retrospective review of 59 Cushing’s disease consecutive larities were 271mOsmol/kg (285-305) and 592 mOsmol/kg (50- cases operated from the implementation of WHO 2017 classifica- 1400), respectively. Her urine sodium was elevated at 126 mmol/L tion at our institution in 10/2017 until 11/2020. CCA diagnosis was (n< 20), suggestive of a clinical picture of a syndrome of inappro- confirmed by 2 neuropathologists. We evaluated their clinical, priate secretion of antidiuretic hormone (SIADH). The patient did biochemical and radiological presentation, as well as postoperative not respond to < 1L/day fluid restriction alone. The initial dose of outcomes. furosemide did not improve the sodium level; thus, the dosage was Results: The prevalence of CCA among CD patients operated over 3 raised and salt tablets were added, which improved sodium level years was 8.5% (5/59). steadily. Meanwhile, her thyroid profile showed TSH 0.07uU/mL Patients were predominantly women (80%, 4/5) with a mean age (0.3-4.2), free T4 0.9 ng/dL (0.8-1.8), demonstrating central hypo- at surgery of 46±11 years. Clinical presentation consisted of man- thyroidism while taking levothyroxine as a home medication. ifestations of hypercortisolism in 3 cases, vision loss in one and Further pituitary workup revealed an abnormally low level of FSH incidental detection in one. All patients had elevated ACTH levels 4.95mIU/mL (16.7-113.5) and LH 2.33mIU/mL (10.8-58.6), consid- (mean 151±53 pg/ml), i.e. 2.7± 1.1 above upper limit normal (ULN). ering the post-menopausal state. Prolactin was elevated at 39ng/ All patients had elevated urinary free cortisol (mean 830 ± 796.5 mL (3.3-26.7). The rest of the hormone labs including cortisol, mg/day), and late night salivary cortisol. Tumors were 60% (3/5) ACTH, and GH were normal. Blood sugar and serum triglyceride macroadenomas and 2 had cavernous sinus invasion. The maximal levels were within the normal range. Per history and physical, the tumor diameter ranged between 0.7-4.0 cm. The ki67 proliferation patient neither exhibited hypervolemic nor hypovolemic features. index and mitoses were not increased in the 5 CCA tumors. No home medications would have likely caused SIADH. Her MRI of All 5 patients achieved biochemical remission at 3 months post the brain in 2016 reported a sellar mass uplifting the optic chiasm operatively (3 hypo- and 2 normocortisolemic). The male patient and its extension of the right cavernous sinus. Latest outpatient with a preoperative giant pituitary adenoma had a residual tumor record from October 2020 documented pituitary macroadenoma and underwent fractionated radiation therapy 5 months with secondary hypothyroidism, secondary hypogonadism, and postoperatively. hyperprolactinemia due to the stalk effect. Finally, ADH returned as Length of follow-up ranged from 3.1-31.0 months. The 4 patients < 0.8 pg/mL (0-4.7), ruling out SIADH as the most likely etiology. who were followed >1 year did not show evidence of radiological Conclusion: Treating hyponatremia in the elderly is a challenge. or biochemical recurrence. Starting with a broad differential list and effectively ruling out each Discussion/Conclusion: The CCA prevalence among functioning diagnosis is critical to find the most likely etiology and prevent a ACTH-adenomas at our center is higher compared to the literature, premature diagnosis. Instances of such diagnoses and subsequent which can be related to the implementation of 2017 WHO classi- inappropriate treatments invariably lead to poor patient outcomes. fication in clinical practice. All our CCA patients had a significant It is, therefore, crucial to keep an open mind and consider all pos- ACTH elevation, which is not typical for CD. The majority of our CCA sibilities when approaching a hyponatremic elderly patient. patients had macroadenomas, unlike most CD patients who exhibit https://doi.org/10.1016/j.eprac.2021.04.711 microadenomas. Postoperative biochemical outcomes were excel- lent with remission in all patients, but longer follow-up is needed to determine tumor behavior over time. Abstract #1000674 https://doi.org/10.1016/j.eprac.2021.04.710 A Rare Case Of Hemorrhagic Rathke’s Cleft Cyst Presenting With Severe Hyponatremia Abstract #1000245

A Case of Panhypopituitarism, Resembling the Picture Author Block: Peggy N. Amoakohene, MD - Primary author, of SIADH Diabetes, Endocrinology and metabolism, University Of Virginia; Gregory Hong, MD PhD - Co-author, Diabetes, Endocrinology and metabolism, University Of Virginia Author Block: Andrew Jung - Larkin Community Hospital Palm Springs Campus; Eugenio Angueira-Serrano, Endocrinology Introduction: Rathke’s cleft cysts(RCCs) are benign sellar/supra- Fellowship Director, MD - co-author, Larkin Community Hospital sellar epithelium-lined, fluid-filled cysts arising from the remnants Palm Springs Campus; Noreen Shaaban, Endocrine Fellow, MD - of Rathke’s pouch. RCCs are usually small, asymptomatic and inci- co-author, Larkin Community Hospital Palm Springs Campus; dentally found on brain imaging. Hemorrhage into RCC is very Novera Shahid, Resident physician, DO - co-author, Larkin unusual and may present with headaches, visual field deficits and Community Hospital Palm Springs Campus pituitary dysfunction. Central adrenal insufficiency (AI) with severe hyponatremia is a potential consequence which can be life- Introduction: Hyponatremia is a common medical condition in the threatening. elderly. When encountering hyponatremia in the clinical setting, it We present a rare case of severe hyponatremia due to central AI is important to start with a broad differential list, and then work from a hemorrhagic RCC. through all the different possibilities before arriving at the correct Case Description: A 40-year-old male with a history of a 9mm RCC diagnosis. Treatment guidelines recommend starting with broad presented to the Emergency room(ER) with altered mental status. A differentials in order to avoid premature conclusions, reach the week prior, he had presented to the ER with a severe headache and correct diagnosis, and avoid suboptimal treatment or inappropriate vomiting. On that visit, serum Na was 135(nl 136-145mmol/l) and K workup. 3.1(nl 3.4-4.8mmol/l). He was managed with IV fluids, ibuprofen,

S114 Pituitary Disorders/Neuroendocrinology Endocrine Practice 27 (2021) S107eS132 and anti-emetics. At home, he continued to feel ill, with polydipsia - 4.500 m[iU]/L), and Free T4 0.84 (0.89 - 1.76 ng/dL). No clinical or and fatigue. He became confused and lethargic, and returned to the biochemical signs of diabetes insipidus were noted. Patient was ER. He denied visual changes, seizures or head trauma. On exam, he started on hydrocortisone prior to discharge and she completed a was normotensive and ill-appearing. Labs showed Na 108, K 3.7, full course of antibiotic therapy for meningitis. A follow-up MRI serum osmolality 250(low), urine Na 70 and urine osmolality 235. approximately one month from injury showed interval resolution Further work up revealed early morning cortisol of 3.5(low), TSH of intrasellar/pituitary abscess and improvement of osteomyelitis of 0.35(low), fT4 0.9(NL), prolactin 3.2 and IGF-1 96(z-score -0.8). An posteroinferior wall of the sella. Repeat serology approximately 6 ACTH stimulation test showed baseline cortisol 0.8, 30 min 10.9 and months following original injury showed LH 2.5, FSH 2.7, Estradiol 60 min 14.7. ACTH was 3(low). An interval increase in size of the 155, Prolactin 8.1, IGF-1 243, morning cortisol 7.7, TSH 8.69 and Free RCC to 2.2cm with intrinsic T1 hyperintense foci likely representing T4 1.1. blood products was seen on MRI brain. Visual field testing was Discussion: Infections of the hypothalamic pituitary region are rare unremarkable. He received IV hydrocortisone with gradual reso- and account for less than 1 percent of all pituitary lesions. Risk lution of hyponatremia. Neurosurgery recommended conservative factors include meningitis, paranasal sinusitis, head/neck surgery, management as visual fields were intact and he was improving and an immunocompromised host. Most events have been reports clinically. He was discharged on hydrocortisone; 20mg in the am in case reports or small case series. Symptoms and deficiencies can and 10mg in the afternoon. MRI brain 3 months later showed a range from isolated pituitary hormones to panhypopituitarism. residual RCC measuring 8mm in size. Subsequent pituitary labs Some reports have possibly seen more of an effect on anterior pi- were unremarkable except an ACTH stimulation test which tuitary hormones, though, some have reported diabetes insipidus. revealed a 60min cortisol of 16.0, with baseline ACTH of 17. He is In the majority of reported cases, endocrine dysfunction has currently on hydrocortisone 15mg daily, without hyponatremia. been irreversible and, should recovery occur, one needs to Discussion: Hypo-osmolar, euvolemic hyponatremia in this setting monitor for inflammation, bleeding and infraction as recurrence is occurs mainly from loss of cortisol feedback inhibition on ADH possible. In our patient, endocrine dysfunction improved with release from the posterior pituitary, resulting in free water reten- treatment of infectious etiology. Repeat MRI will be done to tion, and corrects with hydrocortisone replacement. In the absence document stability. of visual deficits, RCC hemorrhage can be managed conservatively https://doi.org/10.1016/j.eprac.2021.04.713 with appropriate hormone replacement and serial brain MRI. Central AI may be transient as reported in some cases, but can also persist for more than 6 months, as seen in our patient. Abstract #1000905 https://doi.org/10.1016/j.eprac.2021.04.712 Pituitary Apoplexy Presenting in a COVID-19 Positive Patient as Ophthalmoplegia Abstract #1000694

A Case of Graves’ Thyroiditis followed by Infective Author Block: Christopher Lesniak, DO - primary author, Hypopituitarism Department of Medicine, Jersey Shore University Medical Center; Katherine Hu, DO - co-author, Department of Medicine, Jersey Shore University Medical Center; Monika Akula, MD - co-author, Author Block: Preethi Gogineni - Temple University Hospital; Department of Medicine, Jersey Shore University Medical Center; Imali Sirisena, MD - Co-author, Lewis Katz School of Medicine at Khin Zin, MD - co-author, Jersey Shore University Medical Center; Temple University Raquel Ong, MD - co-author, Department of Medicine, Jersey Shore University Medical Center; Soemiwati Holland, MD - co-author, Introduction: We present a case of uncontrolled Graves’ hyper- Department of Medicine, Jersey Shore University Medical Center; thyroidism complicated by agranulocytosis ultimately requiring Jennifer Cheng, DO - co-author, Department of Medicine, Jersey thyroidectomy and the subsequent occurrence of hypopituitarism Shore University Medical Center due to meningeal infection. Case Description: 31 year old female with history of depression Introduction: Pituitary apoplexy (PA) involves infarction or hem- presented with complaints of nausea and vomiting and noted orrhage of a pituitary adenoma with symptoms including head- progressively worsening palpitations, tremor, weight loss, heat ache, nausea, decreased visual acuity, temporal visual field deficit, intolerance, dizziness and shortness of breath. Exam was pertinent ophthalmoplegia, and altered mental status. We present a 38-year- for lid lag, proptosis, and enlarged thyroid gland with no palpable old female with acute headache and ophthalmoplegia who was nodules. Thyroid function tests were consistent with uncontrolled found to have COVID-19 and PA. hyperthyroidism and ultrasound with diffusely increased vascu- Case Description: A 38-year-old female patient who was found to larity. Methimazole was started and quickly discontinued due to be COVID-19 positive on admission presented to the hospital with agranulocytosis. She ultimately required thyroidectomy and she severe headache, nausea, vomiting, blurry vision, and oph- was discharged on levothyroxine. Nine days following thyroidec- thalmoplegia for 4 days. She reported an unintentional 50 lb weight tomy patient is readmitted with sepsis likely due to bacterial gain over 2 months, hot flashes, and increased frequency of men- meningitis thought to be due to an oral source. Acute Streptococcal strual cycles to 3 per month. Exam revealed right eyelid ptosis, right meningitis was diagnosed and hospital course was further third and sixth cranial nerve palsies, and bilateral temporal complicated by seller abscess and sphenoid osteomyelitis/abscess hemianopia. noted on imaging. Dental extractions and endoscopic sinus MRI brain showed a 3.6 x 2.6 x 2.4 cm mass in the pituitary fossa, drainage was performed along with intravenous antibiotic therapy. right greater than left cavernous sinus extension, and mass effect On serology LH was 0.3 (0.5 - 76.0 m[iU]/mL), FSH 2.2 (1.5 - 33.4 m on the prechiasmatic optic nerves and optic chiasm. MRI pituitary [iU]/mL), Estradiol < 15 (pg/mL), Prolactin 0.8 (2.8 - 29.2 ng/mL), later revealed a hemorrhagic mass with extra-axial blood IGF-1 65 (53 - 331 ng/mL), Cortisol 0.90 (ug/dL), TSH < 0.005 (0.400 products. Biochemical workup revealed low FSH, LH, and estradiol

S115 Pituitary Disorders/Neuroendocrinology Endocrine Practice 27 (2021) S107eS132 in follicular phase, inappropriately normal ACTH and suppressed the study. Quantitative variables were shown as Mean ± Standard TSH while on steroids, normal free T4, low prolactin, and normal Deviation while qualitative variables were shown as frequency and IGF-1. percentages. The patient was initially treated with dexamethasone for COVID- Results: Data of 126 IHH patients were reviewed with Mean Age ± 19 infection then required increased dosing for pituitary apoplexy. SD being 24.2 ± 7.5 years. Clinically 94 (74.6%) presented with small She underwent endoscopic transnasal transsphenoidal surgery for genitalia, 75 (59.5%) had absent secondary sexual characteristics, pituitary macroadenoma with apoplexy. Pathology confirmed an 78 (61.9%) presented with infertility, 66 (52.5%) had not attained infarcted hemorrhagic pituitary adenoma with CAM 5.2, synapto- puberty, 71 (56.3%) had erectile dysfunction, 60 (47.6%) with loss of physin, chromogranin. Her course was complicated by a CSF leak libido, 14(11.1) had a positive family history, 33 (26.3%) had gy- which required surgical repair and graft, and transient central necomastia, 17 (13.5%) had undescended testes and 8 (6.3%) had diabetes insipidus treated with desmopressin. hyposmia or anosmia. The mean serum testosterone level of the Discussion: Pituitary apoplexy is a rare condition that develops patients was 26.3 ± 60 hg/dL while mean FSH and LH level were 2.7 when a pituitary tumor spontaneously hemorrhages or outgrows ± 5.0 and 1.3 ± 2.4 respectively. its blood supply. Symptoms include headache due to meningeal Discussion/Conclusion: It was observed that the primary com- irritation, vision changes, and oculomotor palsies due to mass ef- plaints of patients presenting with IHH were small genitalia, fect. Hormonal disturbances due to pituitary stalk compression can infertility, and absence of secondary sexual characteristics with a cause sexual problems, menstrual disturbances, galactorrhea, and low serum testosterone level. fatigue. CT scan can detect a mass and rule out other hemorrhage, https://doi.org/10.1016/j.eprac.2021.04.715 but MRI is more sensitive for PA. Treatment includes conservative management with steroids if there are no neurologic deficits to surgical resection for more symptomatic tumors and hormone Abstract #1001394 replacement therapy. Our patient presented with acute onset of neurological deficits A Rare Endocrine Complication of the COVID-19 Vaccine and symptoms of hormone disturbances. CT scan revealed a pitui- tary mass, but MRI was needed to visualize hemorrhage. Clinicians should order appropriate imaging so pituitary apoplexy can be Author Block: Shirin Jaggi - Thomas Jefferson University Hospital; addressed in a timely manner. Serge Jabbour, MD - Co-Author, Thomas Jefferson University https://doi.org/10.1016/j.eprac.2021.04.714 Hospital

Introduction: Pituitary adenomas are a common, asymptomatic Abstract #1001080 finding in the general population. They are usually diagnosed incidentally on imaging studies. Rarely, pituitary adenomas can Characteristics of Male Idiopathic Hypogonadotropic progress to pituitary apoplexy, defined as hemorrhage and/or Hypogonadism (IHH) Patients; an Experience from a infarction and are often associated with a triggering event. Developing Country Case Description: A 44 year old man with a history of hypo- gonadism presented to the hospital for fevers, chills and blurry vision that started after he received his second COVID-19 vaccine Author Block: Sajjad Ali Khan - Aga Khan university hospital, three days prior. The day following his vaccine, he initially devel- Karachi, Pakistan; SALEEM NOORALAM, Dr - Co-author, Medicine, oped subjective fevers, chills and myalgia which he self-treated Aga Khan University Hospital; nANIK. RAM, Dr - Co-author, with over the counter analgesics at home. Three days after the Medicine, Aga Khan University Hospital; Muhammad M. Mehdi vaccine, he developed blurry vision along with change in mental Khan, n/a - Co-author, Medicine, Aga Khan University Hospital; status which brought him to the hospital. When he initially pre- Zafar a. Suchal, n/a - Co-author, Medicine, Aga Khan University sented to an outside hospital, vital signs showed hypotension with Hospital MAP of 57 and fever of 103 degrees fahrenheit. MRI of the head showed a 4.7cm sellar and suprasellar mass with optic chiasm Objective: Idiopathic Hypogonadotropic Hypogonadism (IHH) is a compression and left sphenoidal extension. Labs at the time condition caused by deficiency or insensitivity to gonadotropin- showed FSH 10.5 IU/L, LH 3.3 IU/L, Prolactin 1.2 ng/mL, Cortisol 9.3 releasing hormone where the pathology behind the mechanism is ug/dL at 5am, ACTH 7 pg/mL, TSH 2.90 uIU/mL, free T4 1.33 ng/dL unknown and no secondary causes of hypogonadotropic hypo- and free T3 3.88 ng/dL. Due to the patient's hypotension and gonadism are present. The condition not only affects sexual char- findings on imaging studies, there was concern for adrenal insuf- acteristic but can affect the physical and psychosocial development ficiency and the patient was started on stress dose steroids. He was of a patient, therefore, making its prompt diagnoses and treatment transferred to a tertiary care center and vitals at the time were necessary. The purpose of this study was to determine the clinical significant for a temperature 105.9 degrees fahrenheit but other- symptoms and laboratory parameters of the male IHH patients wise hemodynamically stable. He underwent an endoscopic presenting in a tertiary setting. transsphenoidal resection of the pituitary tumor given compres- Methods: This cross-sectional study was carried in Aga Khan Uni- sion of the optic chiasm. Pathology report was consistent with pi- versity on male patients presenting with IHH to the Endocrinology tuitary adenoma with focal hemorrhage and necrosis of pituitary clinic from December 2000 to December 2020. The patients pre- adenoma cells. Patient currently remains on maintenance dose senting with signs or symptoms of hypogonadism, an associated steroids and levothyroxine. low sex steroid hormone, and inappropriately low or normal go- Discussion: Pituitary apoplexy can occur either spontaneously or nadotropins with absent expansive hypothalamic or pituitary le- due to a stressful trigger. There have been no case reports showing sions or multiple pituitary hormone defects were included in the the novel COVID-19 vaccine leading to pituitary infarction or study. Those with a BMI < 18.5 kgm-2, those who exercised > 5 hemorrhage. Although the pathophysiology is not entirely clear, hours in a week, or those with chronic illnesses were excluded from our patient may have developed a robust immune response that

S116 Pituitary Disorders/Neuroendocrinology Endocrine Practice 27 (2021) S107eS132 could have potentially been a trigger leading to a pituitary of adjusting further to the restrictions of quarantine have added apoplexy. significant burden to these patients. Social isolation and post- ponement of needed tests and procedures in particular have https://doi.org/10.1016/j.eprac.2021.04.716 contributed to a decreased quality of life for CS patients during the COVID-19 pandemic.

Abstract #1001609 https://doi.org/10.1016/j.eprac.2021.04.717

COVID-19 Response in the Cushing's Community: A Report from the Membership of the Cushing's Support Abstract #1002103 & Research Foundation (CSRF), a Patient Advocacy Organization A Rare Case of Pituicytoma Submitter: Leslie Edwin - Cushing's Support and Research Foundation Author Block: Pushyami Mikkilineni, MD - Primary author, Henry Ford Hospital; Simon Rebecca, DO - Co-author, Henry Ford Hospital Author Block: Adriana G. Ioachimescu, MD, PhD, FACE - co-author, Endocrinology and Neurosurgery, Emory University Hospital; Introduction: Pituicytoma is a rare, low grade glioma arising from Amy Dahm, n/a - co-author, Cushing's Support & Research pituicytes of the posterior pituitary. It presents as a suprasellar Foundation mass and is often difficult to distinguish from pituitary adenomas. Diagnosis is based on histopathology, positive staining for thyroid Objective: Cushing’s syndrome (CS) is a rare neuroendocrine disease transcription factor 1 (TTF-1).Surgical resection is the main stay of caused by persistent, excessive cortisol secretion. Many patients treatment. We are reporting this case of pituicytoma to add to suffer significant co-morbidities, and most experience delays in current literature for future research and better understanding diagnosis and treatment. During active CS through at least the short- Case Description: We report a 42-year-old female with headaches term post-surgical period, patients are at increased risk of infections and galactorrhea. MRI brain revealed 10X11.1X10.7 mm enhancing and, frequently, poorly managed hypertension and glucose intoler- lesion within the suprasellar cistern posteriorly causing mass effect ance / insulin resistance. The COVID-19 pandemic thus presented of the optic chiasm and involving the pituitary stalk. Hormonal this rare patient population with an unprecedented challenge to assay showed elevated prolactin level, 45.1 ng/ml (reference range mitigate. We examined self-reported pandemic-related behaviors of < 27 ng/ml). TSH, cortisol, FSH,LH,ACTH, and IGF-1 levels were CS patients who are members of the US-based patient advocacy normal. Humphrey’s visual field testing was normal. She under- organization Cushing’s Support & Research Foundation (CSRF). went craniotomy with radical subtotal resection of the lesion due to Methods: An online survey analyzing behaviors related to CS status, progressive symptoms and increase in size of suprasellar mass on adverse effects of quarantine, and adaptive measures engaged as a repeat imaging. Postoperative course was complicated by triphasic result of the COVID-19 pandemic was designed and shared with diabetes insipidus and hypopituitarism. members of CSRF. Discussion: Pituicytoma is a rare, low-grade glioma which arise in Results: Of 274 total responses, 91.2% (n¼250) of members indi- the posterior pituitary. So far 120 cases were described in the cated that they had not become infected with COVID-19 as of the literature. It is commonly seen in adults, with mean age of 46.9 time of survey completion, whereas 8.8% (n¼24) had caught the years at the time of diagnosis. The most common clinical presen- virus. The majority of respondents (78.5%, n¼215) are post-surgical tation is headache and bitemporal hemianopsia. Panhypopituitar- and in remission; the remaining 21.5% (n¼59) are experiencing ism and hyperprolactinemia frequently occur. Only 5% of cases recurrence, diagnosed but not yet treated, or still in the diagnostic presented with diabetes insipidus. Common histological features phase. About two-thirds of respondents (66.4%, n¼182) reported include rounded to spindled nuclei, eosinophilic cytoplasm, and making changes to their routine immediately or within the first minimal mitotic activity. TTF 1 is the most reliable immunostain. week of hearing about the pandemic. Most (89.8%, n¼246) have Surgical resection is the mainstay of treatment. Total resection can habitually worn a mask throughout 2020 and into 2021, but in be difficult due to highly vascular nature of these tumors and their some cases it has taken adverse experiences to alter behaviors. potential for infiltration. Some authors recommend craniotomy due Among the patients diagnosed with COVID, five reported not to the vascularity, and adherence of tumor to surrounding struc- wearing a mask before getting the virus, but four of those began tures. The role of radiotherapy in the management of pituicytoma is wearing a mask after getting infected with the virus. Some patients well established. It should be performed if the tumor is not surgi- reported postponing labs (38.7%, n¼106), postponing MRIs or other cally resectable and increases in size. Tumor recurrence is 29.2% in radiology appointments (21.2%, n¼58), and testing for the virus incomplete resections and current treatment is repeat surgery in (13.5%, n¼37) based solely on concern for potential increased risk of curative intention or radiation therapy. However, repeat surgery infection / severity of infection due to their history with CS. About a poses significant risks and may even lead to fatal outcome. As the third of respondents (34.7%, n¼95) also have temporary or per- majority of tumors are not completely resectable and recurrence manent adrenal insufficiency (AI) due to CS, and a notable 38.9% after partial removal is high, targeted therapies may be a possible (n¼37) of these patients reported shortages of their regular option in the future. The most common postoperative complica- cortisol-replacement medication at their regular pharmacy. tions are diabetes insipidus, hypopituitarism, visual impairment, Changing dosage and/or cutting pills is another response to and hypothyroidism. These complications were thought to be sec- shortages reported by 13.7% (n¼13) of those experiencing AI. ondary to iatrogenic trauma to contiguous structures. Our patient Discussion/Conclusion: Quarantine restrictions are at times underwent craniotomy and subtotal resection of tumor. Histopa- extreme and difficult to manage. Rare disease patients such as thology revealed low grade glioma with spindle cell morphology those with CS already adapt their conditions daily to a world that and fascicular pattern with diffuse TTF e 1positivity consistent with often doesn’t readily support or understand those adaptations. The pituicytoma. Postoperative course was complicated by triphasic results of this survey confirm that the added stress and uncertainty diabetes insipidus treated with desmopressin as well as

S117 Pituitary Disorders/Neuroendocrinology Endocrine Practice 27 (2021) S107eS132 hypopituitarism. Close follow up is recommended to monitor for dopamine agonists (Bromocriptine or Cabergoline) is preferred. recurrence in our patient Cabergoline was chosen for our patient as it is more tolerable in terms of side-effects if compared with Bromocriptine. Dopamine https://doi.org/10.1016/j.eprac.2021.04.718 agonists subsequently decrease the serum prolactin levels, and can also reverse secondary hypogonadism, which improves gyneco- mastia, as seen in our patient. With patients with Hyper- Abstract #1002232 prolactinemia associated with Hypogonadism, it is recommended Drug Induced Severe Hyperprolactinemia in a Male with to consider the HPA axis (especially in the setting of persistent Persistent Erectile Dysfunction and Hypogonadism testosterone deficiency). Further reporting of similar cases is encouraged.

https://doi.org/10.1016/j.eprac.2021.04.719 Author Block: Muntazir Ali Sayed - RCSM Government Medical College Kolhapur, India; Syed Wajih Rizvi, MD - Co-author, Endocrinology, R-Endocrinology; Anum Khan, MD - Co-author, Abstract #1002280 Internal Medicine, R-Endocrinology; Shameela Begum, MD - Co- author, Internal Medicine, R-Endocrinology; Hira Akhlaq, MBBS - Pituitary Macroadenoma Without Pituitary Apoplexy Co-author, Internal Medicine, R-Endocrinology; Shereen Naccour, Presenting as Isolated Unilateral Cranial Nerve III Palsy MD - Co-author, Internal Medicine, R-Endocrinology; and Altered Mentation: A Case Report Summaiya Nazneen, MBBS - Co-author, Internal Medicine, R- Endocrinology; Meenakshi R. Kotcherlakota, BS - Co-author, Endocrinology, R-Endocrinology; Sadiq Ali Sayed, MBBS - Co- Author Block: Tiffany Purewal - Jersey Shore University Medical author, Internal Medicine, National Pirogov Memorial Medical Center; Katherine Hu, DO - Co-author, Jersey Shore University University, Vinnytsya, Ukraine Medical Center; Monika Akula, MD - Co-author, Jersey Shore University Medical Center; Khin Zin, MD - Co-author, Jersey Shore Introduction: Hyperprolactinemia is a common and underappre- University Medical Center; Raquel Ong, MD - Co-author, Jersey ciated consequence of the treatment with various anti-psychotic Shore University Medical Center; Soemiwati Holland, MD - Co- and anti-depression medications. Our objective is to report a case of author, Jersey Shore University Medical Center; Jennifer Cheng, DO a 21 year old male presenting with persistent erectile dysfunction - Co-author, Jersey Shore University Medical Center (ED) in the setting of testosterone deficiency, who was subse- quently found to have drug-induced severe hyperprolactinemia. Introduction: Pituitary adenomas account for about 10-25% of Case Description: A 21-year-old male with a history of testosterone intracranial tumors and can present with visual disturbance. Cra- deficiency, and ED was referred to the Endocrinology clinic with nial nerve palsy is fairly rare and has mainly been demonstrated in concerns about bilateral breast tenderness since a month. The pa- pituitary macroadenomas with apoplexy. We present a patient tient has a history of gender congruency since puberty and wanted with altered mentation and hyponatremia who was evaluated for to transition. He has always had low testosterone and ED since adrenal insufficiency by inpatient endocrinology and subsequently then. Patient started to transition to female 3 months before this diagnosed with pituitary macroadenoma without apoplexy after appointment with Estradiol 2mg (PO x OD) and Spironolactone evaluation of right eye ptosis and cranial nerve III palsy. 25mg (PO x BID) but stopped the process within a month due to a Case Description: A 78-year-old male with a history of coronary strong feeling of reluctance and jeopardy with his health. The pa- artery disease, hypertension, and hepatitis C presented to the tient simultaneously experienced daily headaches with right sided hospital with hypothermia and altered mental status for un- blurred vision. Bilateral breast tenderness presented 3 weeks later. known duration. Review of systems was difficult to obtain due He also endorsed severe fatigue and a weight gain of 10lbs. The to altered mentation. Endocrinology was consulted to evaluate referring physician investigated his hypothalamic-pituitary-adre- for hyponatremia of 120 mmol/L and morning serum cortisol of nal (HPA) axis. His follicle-stimulating hormone (FSH) was low 3.8 ug/dL. Primary adrenal insufficiency was not present with an whereas luteinizing hormone (LH) was within normal limits. His appropriate serum cortisol level of 21.9 ug/dL after cosyntropin total testosterone and free testosterone levels both were low at 21 stimulation. The patient had right eye ptosis with a nonreactive ng/dL (normal, 190-780 ng/dL) and 5.5 pg/mL (normal, 9.3-26.5 ng/ right pupil measuring 7mm due to cranial nerve III palsy. CT of dL) respectively. His serum prolactin level was greater than 101 ng/ the head without contrast revealed supra-tentorial chronic mL (normal, 2.5-17.4 ng/mL). On referral, we proceeded with a ischemic changes. Further evaluation of altered mentation and brain MRI, which showed normal findings. Patient reported taking cranial nerve III palsy with MRI of the brain revealed promi- Sertraline 100mg (PO x OD), Buspirone 5mg (PO x OD), Perphena- nence of the region of the pituitary gland. MRI of the pituitary zine 2mg (PO x BID), and Paliperidone IM injection for his psychi- revealed a cystic pituitary adenoma without evidence of hem- atry concerns. With patient’s denial to transition, we placed him on orrhage measuring 2.0 x 0.9 x 1.2 cm with bilateral extension Depo-Testosterone 200mg/ml Injection (IM x Q2weekly), and into the cavernous sinus with normal optic chiasm and supra- Cabergoline 1mg (PO x twice a week). On consult with his psy- sellar cistern. Pituitary hormone evaluation revealed normal FSH, chiatrist, respective medications were discontinued and necessary LH, ACTH, TSH, Free T4, Prolactin, and IGF-1 levels. CT of the adjustments made. The patient is tolerating his newly prescribed chest, abdomen, and pelvis revealed multiple pulmonary nod- medications well, along with mild improvements in his gyneco- ules. The patient had an IR guided lung biopsy to rule out un- mastia, and respective reported symptoms of hyperprolactinemia. derlying primary lung malignancy, but pathology was Subsequently the Prolactin levels have considerably reduced (levels inconclusive. The patient was treated conservatively with dexa- at 41.3 ng/mL) after 8 weeks. Patient will be routinely assessed. methasone to reduce vasogenic cerebral edema and mentation Discussion: Drug-induced Hyperprolactinemia is a rare but improved while ptosis remained stable. Transsphenoidal resec- possible event. The condition can cause hypogonadism, resulting in tion of the pituitary adenoma was placed on hold until further galactorrhea, gynecomastia, or ED. Medical management with evaluation of a possible pulmonary malignancy.

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Discussion: Our case highlights a rare presentation of a pituitary identified in our patient, heterozygous for cDNA, c.202T >C (p. macroadenoma with altered mental status and isolated unilateral Ser68Pro) has not been reported in the literature or online data- cranial nerve III palsy. No evidence of pituitary apoplexy was bases before as pathogenic variant, location of it and diagnosis of evident on imaging. Cranial nerve dysfunction remains an unusual pheochromocytoma in her cousin at age 16 years makes it highly presenting symptom found in pituitary adenomas without evi- suspicious to be a pathogenic rather than a benign variant. We have dence of apoplexy. A high index of clinical suspicion and thorough offered targeted genetic testing to first degree family members and physical examination is crucial in early diagnosis, which can allow her cousin with h/o pheochromocytoma, hoping we can get more for prompt medical treatment with steroids and potentially defin- useful information following these tests. itive treatment with resection to preserve vision and prevent long- https://doi.org/10.1016/j.eprac.2021.04.721 term sequela. https://doi.org/10.1016/j.eprac.2021.04.720 Abstract #1002321

Abstract #1002284 Nephrolithiasis in Cushing’s Disease

Case Report of Paraganglioma with a New SDHC Mutation of Undetermined Significance Author Block: Sandhya Bassin - Rutgers Robert Wood Johnson Medical School; Najaf Asrar, MD - Co-author, North Brunswick Medical Associates; Steve Khalil, MD - Co-author, Nephrology, Author Block: Rajani Gundluru - University of Missouri, Columbia; Rutgers Robert Wood Johnson Medical School; Payal Parikh, MD - Uzma Khan, MD - CO-AUTHOR, DIVISION OF ENDOCRINOLOGY, Co-author, Internal Medicine, Rutgers Robert Wood Johnson METABOLISM AND DIABETES, University of Missouri, Columbia Medical School; Louis Amorosa, MD - Co-author, Endocrinology, Rutgers Robert Wood Johnson Medical School Introduction: All patients with paragangliomas and pheochromo- cytomas should ideally be tested for germline mutations in SDH. Introduction: Cushing’s Disease (CD) results from an ACTH- While there are well identified pathogenic variants associated with secreting pituitary adenoma where augmented steroid production hereditary pheochromocytoma and paraganglioma syndromes, leads to a variety of physical, mental, and biological changes. with increasing frequency of genetic testing, newer variants in Nephrolithiasis is an understated complication, occurring in 20- known genetic locations are being identified. 50% of patients. Case Description: 33 YO Caucasian female was referred to endo- Case Description: A 25-year-old male recently diagnosed with CD crinology for management of hypothyroidism. Hypothyroidism presented to the emergency room due to hypertensive emergency. diagnosed at age 25 years, she ran out of her levothyroxine few Over the preceding 1.5 years he developed hypertension, decreased months prior, was found to have significantly elevated TSH of 731 libido, abdominal striae, and gained 100 pounds. While admitted, mcunit/ml (normal 0.27-4.2), low free T4 0.16 ng/dl (normal 0.93- Cushing’s syndrome was confirmed with positive overnight low- 1.7). In review of her medical history patient reported h/o para- dose dexamethasone suppression test, 8am cortisol 18.6mcg/dL ganglioma diagnosed 2 years prior when she was being evaluated (normal < 1.8), as well as two positive urinary free cortisol mea- for kidney donation. CT abdomen showed incidental finding of surements, 2798 ug/24hr and 4396ug/24hr (normal 5-64). Pituitary 2.3x2.9x2.7 cm hyper enhancing left para-aortic mass at the level of MRI showed a 3mm pituitary adenoma and ACTH levels were kidneys.MRI abdomen with/without contrast confirmed retroperi- elevated, 145pg/mL (normal 7.2-63). Patient’s hospital course was toneal left periaortic 2.1x2.8x3.3 cm heterogenous lobulated mass. complicated by acute flank pain with CT imaging showing multiple Labs showed elevated 24-hour urinary normetanephrines 1185 bilateral renal calculi which spontaneously passed after intrave- mcg/24 hr (normal 111-419), elevated norepinephrine 198 mcg/24 nous fluids. He completed inferior petrosal sinus sampling (IPSS), hr (normal 15-80), elevated metanephrine 1281mcg/24 hr (normal confirming the diagnosis of CD, and underwent transsphenoidal 149-533). Patient was started on alpha blockade with doxazosin, resection of the pituitary adenoma with improvement in his underwent surgical resection of paraaortic mass 4 weeks later. symptoms over the next 10 months. Surgical pathology showed pheochromocytoma. Subsequently had Discussion: This case highlights the prevalence of nephrolithiasis in normal plasma metanephrines and nor metanephrine twice, most CD. Though the precise mechanism of action is not known, patients recent being couple days prior to endocrine clinic visit. MIBG scan with active CD, like other nephrolithic patients, have higher levels from nine months prior was normal. of calcium and uric acid in the urine and lower levels of citrate Family history positive for cousin (maternal uncle’s daughter) compared to the general population. One study identified increased with pheochromocytoma at age 16 , father with postsurgical hy- uric acid excretion and hypertension as independent associations pothyroidism (cause of thyroid surgery unclear), mother with pri- with risk for nephrolithiasis, identifying a role for diet modification mary biliary cirrhosis and lichen planus and blood pressure control in preventing stones. Nephrolithiasis is Our patient was offered genetic testing for hereditary pheo- a prevalent complication of Cushing’s disease which endocrinolo- chromocytoma / paraganglioma at the time of Endocrine visit. gists should recognize and understand how to prophylactically Genetic test performed using next generation sequencing through manage. Mayo lab. She was found to have heterozygous SDHC mutation, https://doi.org/10.1016/j.eprac.2021.04.722 variant C.202 T >C, with amino acid change from serine to proline at position 68 on short arm of chromosome 1. This was reported as variant of uncertain significance. Abstract #1002771 Discussion: SDHC gene encodes a subunit of the succinate dehy- drogenase complex (complex II) of mitochondria. Mutations in Effects of Jet Lag on Hormones: Case Report of the SDHC predispose to parasympathetic head and neck para- Impact of Circadian Change on Thyrotropin (TSH) and gangliomas and sympathetic paragangliomas. While the variant Prolactin (PRL) Secretion

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Author Block: Robert Dons - Lawndale Christian Health Center, Introduction: Gynecomastia is characterized by a benign prolifer- Chicago, IL; Roger A. Piepenbrink, DO - Author, Endocrinology, ation of glandular breast tissue in men. Non-physiologic causes of American Red Cross Nevada Utah Endocrinology Consultant gynecomastia are a result of various medical conditions, medica- tion use, or substance use. We report a case of a 31-year-old male Introduction: Loss of sleep is an endemic problem-with conse- presenting with gynecomastia in the setting of hyperprolactinemia quences. In jet lag, desynchronization of the circadian clock is and elevated ACTH with no underlying pathological condition. exacerbated by the number of time zones crossed, eastward travel, Case Description: A 31-year-old male with no PMH was referred loss of sleep and availability of local time cues. Factors altering TSH to our Endocrinology clinic for diagnostic workup for pro- and PRL in a jet lag-affected individual are illustrated here. nounced gynecomastia with onset six years ago. Patient Case Description: A healthy 35-year-old male returned to a Uni- endorsed pain and tenderness of breast that was sharp in na- versal Time Coordinated (UTC) zone +/- 0, from a trip to UTC-08, ture, localized, and 8 out of 10 on a scale of severity. He denied after a 10-hour non-stop flight. Symptoms of daytime fatigue, discharge from nipples bilaterally, sexual dysfunction, family headache, nausea, poor concentration, daytime sleepiness, diffi- history of gynecomastia, steroid, and illicit drug use. He reported culty falling asleep and remaining asleep were noted to be much no delay in puberty or irregularities in timing of stages of pu- worse on arrival in UTC +/- 0 than those experienced after west- berty. He is not on any current medication and has no history of ward journey to UTC-08. Alcohol intake during travel was minimal, pharmacotherapy. His current weight is 198 lbs and height is 5’ but conversations with fellow passengers obviated his getting any 8.5” cumulating to a BMI of 29.7 kg/m2. Referring physician sleep on the plane despite taking zolpidem. ordered a mammogram of the bilateral breast which revealed Labs obtained within 2 hours of arrival revealed an elevated TSH asymmetric prominent glandular right breast parenchyma as of 9.1 mIU/L (0.3 e 40) and PRL of 16.3 ng/mL (3.0 e 14.7); free compared to the left breast. There was no evidence of a domi- thyroxine (FT4) of 1.23 ng/dL and free triiodothyronine (FT3) of 3.12 nant mass lesion, area of architectural distortion or suspicious pg/mL were in reference range (RR). On day 2 and 6 after arrival, all calcification of the either breast. On referral, we proceeded with hormones were in RR: [TSH] 3.0 and 2.8 mIU/L, [FT3] 2.93 and 2.86 blood work which revealed total and free testosterone, estradiol, pg/mL, respectively with [FT4] unchanged, and [PRL] < 10 ng/mL. LH, FSH, hepatic transaminase, serum creatinine, TSH levels, Discussion: Elevation of both TSH and PRL was unexpected based serum beta hCG, and DHEA-Sulfate within normal range. His on known near-opposite contribution of the two sleep controlling prolactin levels were mildly elevated at 19.2 ng/mL (normal, 4.0- processes: sleep-wake homeostasis (S) and circadian (C) effects. 15.2 ng/mL) along with elevated plasma ACTH at 137.0 pg/mL TSH is affected by C primarily via retinal light exposure and the (normal, 7.2-63.3 pg/mL). His cortisol level was within normal hypothalamic suprachiasmatic nucleus (HSN), while S affects PR range measuring at 18.2 ug/dL (normal, AM 6.2-19.4 ug/dL). We secretion via adenosine concentrations accumulating during proceeded with a chest radiograph which revealed no pathology. wakefulness, independent of the HSN. The temporary rise in TSH Additionally, an MRI of the brain and pituitary with and without and FT3 with sleep deprivation is followed by normalization in the contrast showed that the pituitary gland is normal in size but recovery phase as FT3 falls and FT4 remains stable. Zolpidem is microadenoma could not be excluded. Further assessment is known to increase PRL levels by 400% at 2 hours after ingestion required via ultrasound of the breast bilaterally in order to with a persistent elevation in PRL to about 200% above baseline 8 assess the increased glandular tissue found by mammogram, and hours later. a repeat blood work to assess ACTH furthermore. A parallel rise and fall in TSH and PRL after 10 hours of eastward Discussion: Gynecomastia in young adult males, in the absence of intercontinental air travel results from two different mechanisms. medication or substance use, warrants extensive investigation for Sleep deprivation alone accounts for the increased TSH while the its etiology. Our patient's thorough workup did not reveal active PRL increase is probably zolpidem related. Both medication and pathology but Prolactin and ACTH-secreting microadenoma could recent travel history are key to correct interpretation of pituitary not be ruled out as MRI frequently fails to identify microadenomas hormone test results. that are smaller than 3 mm across. Not much is known on the co- expression of ACTH and prolactin as it is very rare in pituitary ad- https://doi.org/10.1016/j.eprac.2021.04.723 enoma. Repeat blood work to assess ACTH is thus necessary to rule out laboratory error. Studies have shown that there is no definite cause in around 25% of patients who develop gynecomastia. With Abstract #1002789 non-physiologic gynecomastia, treatment is directed toward Idiopathic Hyperprolactinemia and Elevated improving the underlying illness or discontinuing use of causative fi Adrenocorticotropic Hormone (ACTH) in a Male with agents. As no underlying illness was identi ed, monitoring with Gynecomastia biannual follow-up is appropriate, especially if the patient is un- troubled by symptoms and has no features that suggest underlying disease or malignancy. Author Block: Anum Khan - Windsor University School of https://doi.org/10.1016/j.eprac.2021.04.724 Medicine; Syed Wajih Rizvi, MD - Co-author, Endocrinology, R- Endocrinology; Samir Beso, MD - Co-author, Emergency Medicine, Windsor University School of Medicine, St. Kitts & Nevis; Abstract #1002927 Shanaz Ahmad, MD - Co-author, Internal Medicine, University of Medicine and Health Sciences, St. Kitts & Nevis; Cowthar Shurie, An Atypical Presentation of Sheehan Syndrome with MD - Co-author, Family Medicine, Windsor University School of Symptomatic Hypoglycemia Medicine, St. Kitts & Nevis; Muntazir Ali Sayed, MBBS - Co-Author, Internal Medicine, R-Endocrinology; Sadiq Ali Sayed, MBBS - Co- author, Internal Medicine, National Pirogov Memorial Medical Author Block: Jessica Watari - Thomas Jefferson University University, Vinnytsya, Ukraine Hospital

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Introduction: Sheehan syndrome, or pituitary infarction in the and histologic findings of islet cell hypertrophy/hyperplasia, setting of postpartum hemorrhage, has a broad clinical presenta- enlarged and hyperchromatic nuclei. tion that is based on the extent of hormone deficiency. We present a Case Description: A 21-year-old woman with a history of restrictive case of Sheehan syndrome in a patient with no history of major anorexia presented with repeated episodes of severe hypoglycemia postpartum hemorrhage that presented subtly with symptoms of with associated seizures. She was treated before for restrictive hypoglycemia four months after delivery. anorexia and symptoms improved with cognitive behavioral ther- Case Description: A 23-year-old female with no past medical his- apy 6 weeks prior. tory presented to the emergency department for numbness and During admission, she was persistently hypoglycemic with a tingling in her extremities for three days. She reported having an serum glucose nadir of 32 mg/dL, requiring continuous dextrose, uncomplicated pregnancy and vaginal delivery four months prior octreotide, and diazoxide infusions. Laboratory findings on a sam- to presentation. She noted difficulty with lactation and oligome- ple showing glucose of 40 mg/dL revealed raised insulin, C-peptide norrhea following delivery. On initial presentation, vital signs were and proinsulin levels, sulfonylurea/meglitinide screens were normal and physical examination was unremarkable. Laboratory negative. Imaging of the pancreas was negative for lesions. Endo- analysis showed a blood glucose of 49 mg/dL. Morning cortisol was scopic ultrasound was negative for malignancy. A selective arterial < 0.2 mcg/dL (normal 6-18 mcg/dL). Cosyntropin stimulation test calcium stimulation test with hepatic venous sampling showed showed a cortisol level of 0.5 mcg/dL collected at 60 minutes. excess insulin production in the superior mesenteric and distal Further lab testing was consistent with hypopituitarism with splenic arteries localizing the abnormality to the distal pancreas. adrenocorticotrophic hormone (ACTH) < 9 pg/mL (normal 9-46), After medical management failed to control hypoglycemia, the thyroid stimulating hormone (TSH) 2.06 uIU/mL (normal 0.3-5.0), patient underwent distal pancreatectomy. Histologic examination free thyroxine (FT4) 0.4 ng/dL (normal 0.7-1.7), and prolactin < 1 showed islet cell hyperplasia, enlarged neuroendocrine islets with ng/mL (normal 0-29). Interestingly, estradiol was normal with focal nuclear enlargement, and absence of neuroendocrine tumor. follicle stimulating hormone (FSH) 2.1 mIU/mL and luteinizing Post operatively, she maintained euglycemia for one month, with hormone (LH) 3.7 mIU/mL (normal for luteal phase). She was glucose values ranging 90-100mg/dl, without pharmacologic initially treated with stress dose steroids and titrated down to intervention. prednisone 5 mg daily. She was also started on levothyroxine 88 Discussion: This case presented a challenging diagnostic dilemma. mcg daily. Magnetic resonance imaging of the brain showed a NIPHS typically presents in infancy, found in males, or occurs after partially empty sella turcica with a homogenous pituitary gland. GI surgery, none of which applied in our patient without surgical The patient’s paresthesias improved and she had no further hy- history. Our patient also exhibited both fasting and postprandial poglycemic episodes. hypoglycemia, while NIPHS typically features only postprandial Discussion: The incidence of Sheehan syndrome has declined with hypoglycemia. There is sparse data about management of NIPHS. advances in obstetrical care. Pituitary infarction in the absence of Successful resolution of hypoglycemia is seen after partial or sub- obvious hemorrhage is rare but has been reported. Clinical pre- total pancreatectomy in refractory cases such as ours. However, sentation includes failure to lactate, amenorrhea, and fatigue. Hy- recurrent hypoglycemia may also occur requiring total pancrea- poglycemia, secondary to ACTH deficiency, is a rare presenting tectomy. Our case illustrates a rare incidence of NIPHS with a symptom of Sheehan syndrome. Imaging may show a small pitui- favorable outcome, and emphasizes the importance of maintaining tary resulting in the appearance of an empty sella. Treatment in- a broad differential in approaching patients with hypoglycemia. volves hormone replacement depending on the degree of https://doi.org/10.1016/j.eprac.2021.04.726 hypopituitarism. Adrenal insufficiency secondary to Sheehan syn- drome is an important differential diagnosis to maintain in the evaluation of hypoglycemia. The presentation of Sheehan syn- Abstract #1003264 drome may be nonspecific and a high clinical suspicion must be maintained even in patients without a history of postpartum A Rare Case of Reversible Panhypopituitarism Secondary hemorrhage. to Cavernous Internal Carotid Artery Aneurysm https://doi.org/10.1016/j.eprac.2021.04.725 Successfully Treated with Pipeline Embolization

Author Block: Abstract #1002957 Aisha R. Saand, MD - Primary author, Internal Medicine, Cleveland Clinic; Sura Alqaisi, MD - Co-author, Internal A Rare Case of Nesidioblastosis Medicine, Cleveland Clinic; Tarini N. Gunaratne, MD - Co-author, Internal Medicine, Cleveland Clinic; Sana Hasan, MD - Co-author, Endocrinology, Cleveland Clinic Author Block: Wazhma Nasiri-Ahad - Stony Brook University Hospital; Jane Hand, MD - Co-author, Stony brook University Introduction: Large cavernous aneurysms are a rare cause of Hospital; Carolyn Maxwell, Attending Physician - Co author, Stony pituitary dysfunction (< 0.2%) due to mass effect and can mimic brook University Hospital pituitary tumors. We present a case of hypopituitarism secondary to left Internal Carotid Artery (ICA) aneurysm treated with pipeline Introduction: Hypoglycemia not induced by diabetic medications embolization, leading to complete recovery of pituitary function in is a medical challenge. Hyperinsulinemic hypoglycemia is mostly 18 months. caused by insulinomas, but a smaller number can be due to non- Case Description: An 81-year-old female with past medical history insulinoma pancreatogenous hypoglycemia syndrome (NIPHS) or of long-standing primary hypothyroidism was referred for evalua- nesidioblastosis. NIPHS is a rare disorder usually identified in in- tion of suppressed TSH (0.007 uU/mL (0.400- 5.50)). Further fancy, mostly in males, and seen in those with prior upper gastro- biochemical evaluation revealed hyperprolactinemia (173.4 ng/mL intestinal (GI) surgery or gastric bypass. Patients experience (4.5 - 26.8)) and inappropriately low gonadotrophins for a post- postprandial hypoglycemia, have negative radiologic localization, menopausal woman (FSH 4.4mU/mL (20-100), LH 0.8mU/mL

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(>20)) and low basal cortisol level of 2.8 ug/dL (5.3-22.5). Although except for the presence of mild hypochromic microcytic anemia cortisol level 60 minutes post ACTH stimulation was optimal (20.8 and HbA1c of 5.8%. Hormonal evaluation showed raised serum IGF- ug/dL ( >18)), low basal cortisol level was concerning for secondary 1 whereas, estimation of other pituitary hormones was normal. Her adrenal insufficiency. Therefore, she was started on prednisone thyroid-stimulating hormone, free thyroxine and free triiodothy- 5mg daily and continued levothyroxine 50mcg daily. MRI/MRA ronine were raised. Thyroid receptor antibody was positive with brain revealed a large left ICA aneurysm measuring 13x17x16mm, high titer; anti- thyroid peroxidase and anti-thyroglobulin were completely filling the sella with suprasellar extension. The patient negative. Thyroid scan showed cold nodule in the left lobe; FNAC was referred to Neurosurgery and underwent elective pipeline advised but refused. MRI of the pituitary revealed pituitary hy- embolization of cavernous aneurysm with no significant compli- perplasia and no evidence of adenoma. CT imaging of chest, cations. At 6 months follow up, she was noted to have marked abdomen and pelvis did not show any tumor. Dotatoc PET scan improvement in her pituitary function, TSH was no longer sup- revealed hyperplastic left adrenal gland with increased radiotracer pressed (8.15uU/mL), FSH trended up (18.3mU/mL) and prolactin uptake compared to right and no evidence of neuroendocrine tu- decreased (103.8 ng/mL). Her levothyroxine dose was increased to mor (NET). Echocardiography was normal. As tumor source was not 75mcg daily and prednisone dose was reduced with a slow taper obvious so she was started on octreotide long-acting release 20 mg over 8 weeks. At 12 months follow up, prolactin level reduced (67.3 monthly therapy. There was marked improvement in her acrome- ng/mL), FSH continued to trend up (19.2mU/mL) and basal cortisol galic symptoms following octreotide therapy. She received Inject- was normal (18.5ug/dL). At 18-months follow up, her pituitary able Methylprednisolone 500mg once weekly for 6 weeks followed function had completely recovered with normalization of TSH and by 250mg once weekly for 6 weeks, Mycophenolate mofetil 500mg prolactin levels. twice a day and Selenium 200mcg once daily for the control of Discussion: ICA aneurysms are a rare cause of pituitary dysfunc- orbitapathy. tion, it is eminent to promptly diagnose and treat them to prevent Discussion: Based on the history, examination & Investigations, fatal complications. Although endocrine abnormalities are usually patient had active acromegaly. However, pituitary imaging only irreversible requiring permanent hormone replacement therapy showed gland hyperplasia. No NET could be localized in PET/CT even after treatment of aneurysm, our patient had complete re- imaging of cervical, thoracic, abdominal and pelvic region. Excessive covery of pituitary function after successful aneurysm treatment. peripheral production of GHRH by a tumor source would be ex- pected to cause somatotroph hyperstimulation, increased GH https://doi.org/10.1016/j.eprac.2021.04.727 secretion and eventually acromegaly. Whereas GHRH estimation is possible in several centres in developed world, we are unable to Abstract #1003298 measure this in our labs. GHRH secretion has been reported in several tumors, including NET, pancreatic tumors, lung tumors, ad- Grave’s Disease with Orbitopathy in Association with renal adenomas, and pheochromocytomas. Localization of extra- Active Acromegaly Secondary to Ectopic Growth cranial source of GHRH secretion is extremely important to affect Hormone Releasing Hormone and Adrenal Hyperplasia cure and requires re-investigation after an interval. Once euthyroid, thyroidectomy is planned as she has compressive symptoms.

https://doi.org/10.1016/j.eprac.2021.04.728 Author Block: Tasnim Ahsan - Medicell Institute of Diabetes Endocrinology and Metabolism; Paras Imran, Consultant Physician & Fellow Endocrinology - Presenter, Medicell Institute of Diabetes, Abstract #1003398 Endocrinology and Metabolism, Karachi, Pakistan; Saeeda Fouzia Qasim, Consultant physician & Fellow Diabetic Ketoacidosis Leading to the Diagnosis of Endocrinology - co-author, Medicell Institute of Diabetes, Acromegaly Endocrinology and Metabolism, Karachi, Pakistan; Rakshanda Jabeen, Consultant Endocrinologist - co-author, Jinnah Postgraduate Medical Centre Karachi, Pakistan; Wasfa Aijaz, Author Block: Makarem Abu Limon, fellow - Presenter, Primary Consultant physician & Fellow Endocrinology - co-author, Medicell author, endocrinology, SIU school of medicine; michael Jakoby, Institute of Diabetes, Endocrinology and Metabolism, Karachi, Chief, Division of Endocrinology - co author, endocrinology, SIU Pakistan school of medicine; Mariam Ali, Assistant Professor - co author, endocrinology, SIU school of medicine; Sonaina Imtiaz, Assistant Introduction: We describe a rare case of Grave’s Disease (GD) and Professor - Co Author, endocrinology, SIU school of Medicine; Orbitopathy along with acromegaly attributed to ectopic produc- Sanober Parveen, Assistant Professor - co author, endocrinology, tion of growth hormone releasing hormone (GHRH) with adrenal SIU school of medicine; Anis Rehman, Associate Program Director - hyperplasia. co author, endocrinology, SIU school of medicine Case Description: A 40 Year-old female, single, known case of GD and Orbitopathy for 4 years. She presented with Increase in size of Introduction: Secondary diabetes mellitus due to increased insulin hands and feet with coarsening of facial features and blurring of resistance from growth hormone (GH) excess is a well-established vision for 6 months. There was no history of headache, weight complication of acromegaly. However, diabetic ketoacidosis (DKA) changes or similar complaints in any of her family members; her in acromegaly is rare. We report a case of DKA as the event that led menstrual cycle was regular; no regular medications other than to the diagnosis of acromegaly. Neomercazole. Examination revealed normal vital parameters and Case Description: A 27-year-old Congolese female presented to the classical acromegalic features. She had a body mass index of 23.8 emergency department with polydipsia and polyuria of two weeks kg/m2; was anaemic with a slate grey skin pigmentation, grade III duration. In the two years before seeking medical attention, she multinodular, non-tender goiter; significant orbitopathy with experienced oligomenorrhea, mild coarsening of facial features, clinical activity score of 5. Systemic examination and visual peri- and enlargement of her hands and feet. Unusually large hands and metry assessment was normal. Complete blood count was normal wide feet were noted on examination, and facial features were

S122 Pituitary Disorders/Neuroendocrinology Endocrine Practice 27 (2021) S107eS132 changed compared to a picture taken three years earlier. Plasma body hair, and normal testicular volume bilaterally. In September glucose on admission was 496 mg/dL (60-100), bicarbonate 15 mM 2020, labs showed prolactin 302.4 ng/ml [reference range (RR) 4- (21-32), anion gap 13 ( 10), and beta-hydroxybutyrate 4.3 mM 15.2 ng/ml], confirmed by dilution to eliminate hook effect, (0.0-0.3). The patient was hydrated and managed with parenteral testosterone 119 ng/dl [RR 250-110 ng/dl], FSH 2.0 mIU/ml [RR 1.6-8 insulin before being started on basal/bolus insulin for hospital mIU/ml], and LH 1.7 mIU/ml [RR 1.5-9.3 mIU/ml], confirming glycemic management. IGF-1 level measured after resolution of hyperprolactinemia and central hypogonadism, though prolactin DKA was 578 ng/mL (63-373); FSH and LH were undetectable and was lower than expected given the size of the pituitary mass. prolactin level was low (1.2 ng/mL. 2.2-30.3). TSH (1.67 mIU/L, Cabergoline was started with goals to shrink the adenoma, alleviate 0.358-3.740) and free T4 (1.04 ng/dL, 0.76-1.46) were unremark- optic chiasm compression and restore gonadal function. able, and random cortisol level on admission was 24.6 mg/dL (3.4- By October 2020, the patient’s prolactin normalized and he was 16.8). MRI of the sella turcica revealed a 4.8 cm pituitary lesion tolerating cabergoline. By December, there was marked reduction exerting mass effect on adjacent structures and causing obstructive in the size of the pituitary mass on MRI to 2.1 cm in height. He had hydrocephalus. Initial transsphenoidal surgery failed to relieve significant improvement in visual fields, improved visual acuity, hydrocephalus, and a craniotomy and transcallosal resection of slightly less prominent afferent papillary defect, and improving residual tumor was then performed. Tumor stained strongly for Pit- libido. 1, and this was interpreted to indicate a GH adenoma in light of the Discussion: This case illustrates the classic presentation of a patient’s clinical presentation and IGF-1 level. IGF-1 did not patient with a large prolactinoma with hormonal and mass ef- improve after surgery (787 ng/mL), and depot lanreotide was fects. It highlights the role of primary dopamine agonist therapy started. Though fasting C-peptide level before starting lanreotide to treat large prolactinomas causing visual impairment with was somewhat low (0.73 ng/mL, 0.80-3.85), hyperglycemia even- lower than expected prolactin given the size of the pituitary tually responded well to metformin and low dose insulin glargine mass. In this case, the pituitary adenoma may have been an (HbA1c 6.6%). inefficient prolactin secretor due to being poorly differentiated Discussion: Secondary diabetes complicates 20-50% of acromegaly or partially cystic, but treating medically was effective in quickly cases, and symptomatic hyperglycemia is the initial presentation in shrinking the mass and improving his vision, thus avoiding the approximately 5% of cases. However, there are few case reports of need for surgery. DKA occurring in acromegaly, with some cases appearing to occur https://doi.org/10.1016/j.eprac.2021.04.730 as a complication of treatment with somatostatin analogs. In this patient’s case, DKA occurred well before medical treatment for acromegaly. High grade insulin resistance due to GH excess may Abstract #1003638 rarely predispose to ketoacidemia by creating a state of significant relative insulinopenia. Diabetes Insipidus and Third Cranial Nerve Palsy https://doi.org/10.1016/j.eprac.2021.04.729 Associated with a Pituitary Macroadenoma

Author Block: Abstract #1003567 Thanh Hoang - Walter Reed National Military Medical Center; Benjamin Wilson, MD - Primary author, Internal The Prolactinoma Predicament; To Treat Medically Or Medicine, Walter Reed National Military Medical Center; Surgically Mohamed K. Shakir, MD - Co-author, Endocrinology, Walter Reed National Military Medical Center

Author Block: Adam Cadesky - Pennsylvania Hospital; Introduction: We present a case of central diabetes insipidus un- Ramya Punati, MD - Co-Author, Endcorinology, Pennsylvania covered during the work up of a non-functional pituitary macro- Hospital adenoma. This case is unique due to the rarity of the association of diabetes insipidus with a relatively small pituitary macroadenoma Introduction: Hormonal effects of prolactinomas include central and the absence of nocturnal polyuria. hypogonadism, infertility, and breast symptoms. When the mass is Case Description: A 24-year-old man presented with an incidental large enough to abut or compress the optic chiasm, prompt treat- finding of a 2.5cm sellar mass with upward displacement of the ment is critical to preserve vision. Prolactin secretion is usually optic chiasm during the work up of a new-onset headache and right proportional to the size of the adenoma. This case describes a pa- third cranial nerve palsy. No evidence of hypophysitis or infiltrative tient who presented with prominent vision changes and was found disease was identified on MRI. He was previously in excellent to have a large pituitary macroadenoma with lower than expected health. He was referred to our clinic for further evaluation where prolactin elevation, highlighting the dilemma between medical his initial symptoms had improved. He was identified as having versus surgical treatment. daytime polyuria without nocturia. Physical examination was Case Description: A previously healthy 32 year old male first normal, including ophthalomological and neurological exam. Vi- noticed vision changes in October 2019 when he was unable to see sual field testing was normal bilaterally. Fasting morning laboratory the dots to focus a camera. Due to the COVID-19 pandemic, he results showed: Prolactin 16.9 ng/mL, FSH 5.8 mIU/mL, LH 5.21 delayed seeking care. When he visited a neuro-ophthalmologist in mIU/mL, total testosterone 505.7 ng/dL, IGF-1183 ng/mL, ACTH 19.5 September 2020, he was noted to have dense left eye and mild right pg/mL, cortisol 11.7 mcg/dL, TSH 0.949 mcIU/mL, FT4 1.26 ng/dL, eye temporal defects, left afferent pupillary defect, and left greater serum sodium 146 mmol/L, serum osmolality 309 mOsm/kg, urine than right optic disc pallor suspicious for a sellar lesion. MRI in osmolality 262 mOsm/kg, 24-hour urine volume 3975 ml. A water September 2020 showed a sellar and suprasellar mass measuring deprivation test and copeptin level (< 2.8 pmol/L) confirmed cen- 3.4 cm tall with left greater than right optic chiasm compression. tral diabetes insipidus. A follow-up MRI one month later demon- He was referred to endocrinology, where further history revealed strated reduction in the size of pituitary macroadenoma to 1.5cm low libido. Physical exam showed BMI 38.7, lipomastia, normal with resolution of mass effect on the optic chiasm, and he had rapid

S123 Pituitary Disorders/Neuroendocrinology Endocrine Practice 27 (2021) S107eS132 improvement of his serum sodium and symptoms with DDAVP after adjustment of glucocorticoid therapy to a less potent steroid therapy. (Hydrocortisone). Discussion: This case highlights a unique presentation of a complex Discussion: Normalization of GH secretion does not always happen disorder (1) association of central diabetes insipidus with a rela- after surgery for CD and its deficiency could lead to metabolic de- tively small non-functional pituitary macroadenoma, (2) absence of rangements, increased cardiovascular risk and loss of bone mass as nocturnal polyuria, (3) spontaneous resolution of headaches and seen in this case. Adequate postoperative monitoring and hormone third cranial nerve palsy along with reduction of the pituitary tu- supplementation following successful CD surgery is warranted. mor size. This case illustrates that an individual could benefitofGH replacement therapy regardless of the time factor. It is never to late https://doi.org/10.1016/j.eprac.2021.04.731 to make an impact in quality of life.

https://doi.org/10.1016/j.eprac.2021.04.732 Abstract #1003643

Never is Too Late for Growth Hormone Replacement Abstract #1003690 Therapy??? The Unfortunate Constellation of MEN

Author Block: yineli ortiz, n/a - primary author, internal medicine, n/a; gabriel Mora, n/a - co-author, n/a; alegyari figueroa, n/a - co- Author Block: Samarth Virmani, MBBS - Primary author and author, n/a; jOSEm. gARCIA, n/a - co-author, n/a; Emily Leon, n/a - presenter, Department of Internal Medicine, University of Central co-author, n/a Florida College of Medicine, Orlando, FL, USA, University of Central Florida HCA Healthcare GME, Greater Orlando, FL, USA; Introduction: Treatment options for Cushing’s disease (CD) include Ramses Ramirez Damera, MD - Co author, Department of Internal transsphenoidal surgery, which may lead to post surgical pituitary Medicine, University of Central Florida College of Medicine, hormone failure including growth hormone (GH) deficiency. The Orlando, FL, USA, University of Central Florida HCA Healthcare rate of pituitary insufficiency is higher for patients undergoing GME, Greater Orlando, FL, USA; Hilda Merino-Chavez, MD - Co surgery for CD. Factors that may account for this insufficiency are: author, Department of Internal Medicine, University of Central long-term need for glucocorticoids postoperatively, a larger pitui- Florida College of Medicine, Orlando, FL, USA, University of Central tary manipulation during surgery, and frequent localization of ad- Florida HCA Healthcare GME, Greater Orlando, FL, USA; renocorticotropic hormone secreting pituitary adenomas. GH Mustafa Kinaan, MD - Co author, Department of Internal Medicine, deficiency can last months to years after successful treatment or University of Central Florida College of Medicine, Orlando, FL, USA, may even be permanent. University of Central Florida HCA Healthcare GME, Greater Case Description: This is a case of a 55-year-old man with history of Orlando, FL, USA CD, dyslipidemia, and arterial hypertension who presented to the clinic for evaluation of hypopituitarism for over 30 years after Introduction: Multiple endocrine neoplasia type 2A (MEN2A) is a transsphenoidal surgery. He complaint about muscle weakness, rare medical disorder characterized by medullary thyroid carci- decreased libido, and weight gain associated with discriminatory noma (MTC), pheochromocytoma and primary hyperparathyroid- features suggestive of Cushing's syndrome, such as moon facies, ism (PHPT). This case highlights the clinical presentation of this rare buffalo hump, and truncal obesity. Examination was significant for disorder and the genetics of RET proto-oncogene. blood pressure of 159/98 mm Hg, a younger appearance, the Case Description: A 27-year-old African American woman pre- presence of acanthosis nigricans, and thick-branched abdominal sented to emergency department with complaints of chest pain,- striae. Patient was not treated postoperatively with growth hor- palpitations and generalized pruritis. She was incidentally found to mone therapy. Further assessment demonstrated biochemical evi- have hypercalcemia of 11.8 mg/dL. Lab evaluation was consistent dence of hypopituitarism including hypocortisolism with morning with PHPT with PTH levels of 329.7 pg/ml, normal urine calcium, cortisol < 1.0ug/dl after holding previous evening glucocorticoid and increase vitamin D activation. Incidentally, the patient was also dose , correlating with Cushing’s syndrome secondary to excess found to have a large right adrenal mass on coronary CT angiog- steroid supplementation. Patient was clinically and biochemically raphy. The mass had features highly suspicious of pheochromocy- eugonadic with testosterone: 796 ng/dl. Also, euthyroid with a FT4: toma and measured 6 x 8 x 7.7 cm. Hormonal workup revealed 1.02 ng/dl. Subsequent tests showed dyslipidemia with total plasma metanephrines of 4,622.7 pg/ml and urinary meta- cholesterol: 267 mg/dl, triglycerides: 375 mg/dl, LDL: 165 mg/dl, nephrines of 8,579 mcg/24 hour. Based on the constellation of impaired glucose tolerance with Fasting Blood Sugar (FBS) of 108 pheochromocytoma and primary hyperparathyroidism, a neck ul- mg/dl and HbA1c of 6%. Insulin-like growth factor-1 of 25.1 ng/ml trasound was performed which showed a heterogenous thyroid was consistent with adult GH deficiency. A Brain MRI to rule out gland with a calcified sub centimeter nodule in the left lobe. Fine pituitary adenoma demonstrated no abnormalities. However, bone needle aspiration of the thyroid nodule was consistent with med- densitometry was diagnostic for osteopenia with T-score: -1.49, ullary thyroid carcinoma. Serum calcitonin and carcinoembryonic most likely induced by glucocorticoids. Patient was started on GH antigen were elevated at 586 pg/ml and 14.7 ng/ml respectively. therapy with somatotropin 0.45 mg subcutaneous injection once There were no signs of local or distant metastases on imaging daily despite the fact that his surgery was performed more than 30 studies. Gene testing revealed a RET proto-oncogene mutation years ago. The benefit of GH replacement was given to this patient (C634W mutation), suggestive of MEN2A syndrome with Cuta- and he showed significant improvement of symptoms and meta- neous Lichen Amyloidosis. The patient was started on alpha bolic derangements on follow up laboratory tests with cholesterol: blockade and scheduled for adrenalectomy. She was referred to a 151 mg/dl, triglycerides: 169 mg/dl and LDL: 65.2 mg/dl, compared genetic counselor and was advised to seek immediate pediatric to previous results. FBS of 93 mg/dl and HbA1c: 5.6% also improved endocrinology care for her three children for prophylactic

S124 Pituitary Disorders/Neuroendocrinology Endocrine Practice 27 (2021) S107eS132 thyroidectomy evaluation. Unfortunately, the patient was lost to Discussion: We present a patient with macroprolactinoma causing follow up in our institution. visual defect as well as significant pituitary hormonal compromise Discussion: MEN2A is a rare autosomal dominant disorder with a who developed psychosis in the setting of cabergoline therapy, but prevalence of 1:30,000, occurring due to germline mutations in the was subsequently treated successfully with a combination of TPS, RET proto-oncogene. Different genotypes have varying risks of stereotactic radiotherapy, and hormonal replacement with serial malignancy. Our patient has an aggressive mutation involving exon monitoring. 11 of the RET proto-oncogene. This mutation results in changes in https://doi.org/10.1016/j.eprac.2021.04.734 the cysteine-rich domain which causes unregulated dimerization of the RET tyrosine kinase receptors and continued stimulation of downstream pathways. This mutation is also associated with Abstract #1003739 cutaneous lichen amyloidosis, a rare dermatologic condition asso- ciated with pruritic lesions. Patients with the C634W mutation are Adipsic Hypernatremia without DIabetes Insipidus at about a 100%, 50% and 10-30% risk of developing MTC, pheo- chromocytoma and PHPT respectively. This syndrome can pose diagnostic, therapeutic, and even ethical dilemmas. Our case will Author Block: Angela Calimag - Advocate Christ Medical Center; highlight some of these challenges and will educate about this rare Husna Khan, DO - Co-Author, Internal Medicine, Advocate Christ and aggressive subtype of MEN2A. Medical Center; Tahira Yasmeen, MD - Co-Author, Endocrinology, https://doi.org/10.1016/j.eprac.2021.04.733 Advocate Christ Medical Center

Introduction: Adipsic hypernatremia (AH) is a rare disorder that Abstract #1003713 has been described in only approximately 100 patients. It is a condition where an individual has a deficient or absent thirst Cabergoline Induced Psychosis During Medical response to hyperosmolarity and is usually associated with hypo- Therapy of Macroprolactinoma tonic polyuria caused by central diabetes insipidus. We report a rare case of AH without DI. Case Description: A 45-year-old male with a significant past Author Block: Samuel Dengler - Cooper University Hospital; medical history of hypertension, hyperlipidemia, uncontrolled Warren Goldman, MD - Co-author, MD Anderson Cancer Center; diabetes mellitus, COPD, Vitamin D deficiency, atrial fibrillation, Thomas Holdbrook, MD - Co-author, Cooper University Hospital; and congestive heart failure presented to the emergency depart- Gregory Kubicek, MD - Co-author, MD Anderson Cancer Center; ment after his primary care physician noted hypernatremia on Farah H. Morgan, MD - Co-author, Cooper University Hospital; routine laboratory workup. Interestingly, the patient was also noted Alan R. Turtz, MD - Co-author, MD Anderson Cancer Center to be hypernatremic during his previous admission for Fournier’s gangrene that required surgical intervention a month prior to the Introduction: Dopamine agonist (DA) treatment is the mainstay of current admission. Upon ED workup, his sodium was 170, and therapy for prolactinomas and in many tumors can result in sig- blood glucose was 425, corrected sodium for hyperglycemia was nificant decreases in tumor size. DA therapy is not without its risks 175. On further questioning, the patient endorsed a feeling of however, with some patients reporting adverse effects such as generalized fatigue and some confusion for some days prior to nausea, lightheadedness, and rarely increased impulsivity or even admission. He had not felt thirsty in the past 2 years but had noted a psychosis. Here we present a case involving a patient with mac- dry mouth. He denied polyuria. Further workup revealed that he roprolactinoma on DA therapy with cabergoline (CBG) who devel- was appropriately concentrating urine with Urine osm 704, Urine oped psychosis requiring discontinuation of CBG, and eventually Na 219, serum Na 152, and Serum osm 336. IGF-1 was normal at transsphenoidal surgery (TPS) as well as stereotactic radiotherapy 79.8. MRI was negative for hypothalamic or pituitary lesions. At this time Rheumatology was also involved in the patient’s care and no (STRT) to diminish the effects of his giant prolactinoma. Case Description: A 43 yo man with a history of hypercholester- evidence of sarcoidosis was found on imaging, history, or exam. He was treated with IV fluids and serum sodium improved to 148. The olemia and oligospermia (diagnosed in setting of infertility work up) with no psychiatric history who initially presented with patient was eventually discharged home with instructions for strict water intake of at least 3 liters per day and close follow up with worsening visual field cuts over several months. He was referred to ophthalmology who diagnosed his syndrome as bitemporal hem- Endocrinology and Nephrology. Discussion: A review of the literature revealed that most cases of ianopsia, prompting an ER visit in March 2018, with an urgent pi- tuitary MRI revealing a macroadenoma measuring 6 x 3.29 x 3.77 autoimmune adipsic hypernatremia occur as a sequela of anterior communicating artery aneurysm rupture with post-surgical clip- cm, and a serum prolactin level of > 3,707 ng/mL. The patient was seen by endocrinology and started on CBG 0.25 mg twice weekly, ping using a frontal craniotomy approach, intracranial defects such as corpus callosum defects, craniopharyngioma, neurosarcoidosis, which was increased to 0.5 mg twice weekly on week 2. The patient experienced anxiety and trouble sleeping, which progressed over hypothalamic or pituitary tumors. In a few reported cases, patients have a negative MRI usually associated with GH deficiency, obesity, the next 24 hours to paranoia and frank psychosis, prompting hospital admission and psychiatric evaluation. CBG was stopped and autonomic failure. Also, the reported case of sarcoid hypotha- lamic involvement resulted in chronic hypernatremia and partial during his hospital stay, and he underwent TPS to reduce tumor fi burden. Given the inability to receive DA therapy post-operatively, hypopituitarism with GH and gonadotropin de ciencies. Most of the reported cases of adipsic hypernatremia with negative MRI the decision was made to pursue STRT, and the patient underwent fi cyber knife radiotherapy. The patient had panhypopituitarism after ndings of hypothalamic lesions were among patients less than 13 the initial surgery, requiring hormonal replacement for central years old. Our patient is a rare case of adipsic hypernatremia in an fi adrenal insufficiency, central hypothyroidism, central hypogonad- adult patient with negative MRI ndings of any intracranial lesions ism, and partial central diabetes insipidus. There has been a steady and no evidence of Diabetes Insipidus. decline in his prolactin levels, stabilizing around 262 ng/mL. https://doi.org/10.1016/j.eprac.2021.04.735

S125 Pituitary Disorders/Neuroendocrinology Endocrine Practice 27 (2021) S107eS132

Abstract #1003773 Abstract #1003917

Sheehan’s syndrome uncovered by COVID 19 infection Challenges in Diagnosis and Treatment of Pediatric Growth Hormone Deficiency: One More Illustration

Author Block: Rajani Gundluru - University of Missouri, Columbia; Uzma Khan, MD - CO-AUTHOR, DIVISION OF ENDOCRINOLOGY, Author Block: Jayalakshmi Thimmaiah, MBBS, FEDM, CDE - METABOLISM AND DIABETES, UNIVERSITY OF MISSOURI- Primary Author, Endocrinology Diabetes Medicine, Samatvam COLUMBIA; Joseph Theressa Nehu Parimi, MD - Co-Author, Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital Division of Endocrinology and Metabolism, University of and Medical Center; Mandyam D. Chitra, MBBS, FEDM, CDE - Co- Missouri,Columbia; Carlton Homan, BS in Cell &Molecular Biology author, Endocrinology Diabetes Medicine, Samatvam with a minor in Chemistry - Co-author, MU School of Medicine-M1, Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital UNIVERSITY OF MISSOURI-COLUMBIA and Medical Center; siddhartha dinesha, MBBS, FEDM CDE - Co Author, Endocrinology Diabetes Medicine, Samatvam Introduction: Sheehan’s syndrome results from severe postpartum Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital hemorrhage resulting in pituitary necrosis. Here we are presenting and Medical Center; Apoorva Govind, MBBS, FEDM CDE - Co a case of Sheehan’s syndrome that was uncovered by COVID 19 Author, Endocrinology Diabetes Medicine, Samatvam infection. Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital Case Description: 38-Year-old women presented to outside ER and Medical Center; Prateek Hongal, MBBS, FEDM CDE - Co Author, with c/o SOB, cough, fever of few days’ duration in late October Endocrinology Diabetes Medicine, Samatvam Endocrinology 2020. She was hemodynamically unstable with altered mental Diabetes Center, Jnana Sanjeevini Diabetes Hospital and Medical status, hypotension, and tachycardia. She was tested for COVID Center; Chandrika K, MBBS, FEDM, FACE - Co Author, 19 infection given worldwide pandemic going on at the time of Endocrinology Diabetes Medicine, Samatvam Endocrinology her presentation and tested positive. Dexamethasone was given Diabetes Center, Jnana Sanjeevini Diabetes Hospital and Medical as part of COVID 19 treatment protocol. Patient showed Center; Kavitha Muniraj, MBBS, FEDM, FACE - Co Author, remarkable improvement within few hours after receiving first Endocrinology Diabetes Medicine, Samatvam Endocrinology dose of steroids Upon further review patient’s family reported Diabetes Center, Jnana Sanjeevini Diabetes Hospital and Medical patient had delivered twins 17 years ago, had massive bleeding Center; Pushpa Ravikumar, MBBS, FEDM, FACE - Co Author, postpartum, needed 8 units of blood transfusion. Treating team Endocrinology Diabetes Medicine, Samatvam Endocrinology at outside hospital suspected diagnosis of Sheehan’s syndrome. Diabetes Center, Jnana Sanjeevini Diabetes Hospital and Medical Patient was discharged home on prednisone and scheduled for Center; Muralidharakrishna C. S, MBBS, FEDM, FACE - Co Author, follow up in Endocrine clinic. Endocrinology Diabetes Medicine, Samatvam Endocrinology She presented to Endocrine clinic 4 weeks later. She had Diabetes Center, Jnana Sanjeevini Diabetes Hospital and Medical stopped taking Prednisone few weeks after her hospital Center; Lakshmi Reddy, MBBS, FEDM, FACE - Co Author, discharge as she noticed she was constantly hungry when taking Endocrinology Diabetes Medicine, Samatvam Endocrinology prednisone. She reported chronic fatigue, absence of menses for Diabetes Center, Jnana Sanjeevini Diabetes Hospital and Medical several years,not clear whether she had menses after her child Center; Chandraprabha siddalingappa, MBBS, FEDM, FACE - Co birth, was only able to partially breast fed her twin children. She Author, Endocrinology Diabetes Medicine, Samatvam was given oral contraceptive pills by PCP several years ago, Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital which she did not tolerate because of severe nausea. Pituitary and Medical Center; babitha devi T, MBBS, FEDM, FACE - Co Author, hormone work up showed low free T4 level of 0.62 ng/dl Endocrinology Diabetes Medicine, Samatvam Endocrinology (normal 0.93-1.7), inappropriately normal TSH of 2.46 mcunit/ Diabetes Center, Jnana Sanjeevini Diabetes Hospital and Medical ml(normal 0.27-4.2), random cortisol 0.94 mcg/dl ,ACTH 15 pg/ Center; Reshma B. Vijay, MBBS, FEDM, FACE - Co-author, ml, FSH 6.8 munit/ml, LH 3.4 munit/ml, estradiol < 5 pg/ml, Endocrinology Diabetes Medicine, Samatvam Endocrinology prolactin 7.6 ng/ml, IGF 1 level of 10 ng/ml. Standard Cosyn- Diabetes Center, Jnana Sanjeevini Diabetes Hospital and Medical tropin stimulation test following 250 mcg synthetic ACTH Center; Sathyanarayana Srikanta, MBBS, MD, FEDM, FACE, FRCP - resulted in 60-minute cortisol of only 2.87 mcg/dl. MRI pituitary Co Author, Endocrinology Diabetes Medicine, Samatvam showed partial empty sella with small pituitary and no space Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital occupying lesion. and Medical Center - Endocrinology Diabetes Study Group, Patient was started on Prednisone 5 mg daily first, followed by Endocrinology Diabetes e Co Author, Endocrinology Diabetes Levothyroxine 75 mcg daily 3 days later, followed by Oral contra- Medicine, Samatvam Endocrinology Diabetes Center, Jnana ceptive pills after 4 weeks. She reported significant improvement in Sanjeevini Diabetes Hospital and Medical Center her energy levels shortly after and is having menstrual bleeding every 4 weeks while on oral contraceptives. Introduction: While availability of recombinant DNA-derived hu- Discussion: Symptoms of Sheehan’s syndrome can be nonspecific man GH (rhGH) is no longer a problem [for the affordable], there and vary widely in degree of severity, often contributing to diag- still remains a number of difficulties with the diagnosis of GHD, nostic delay. Sometimes it can take a major stressor like severe resulting mainly from the lack of appropriate tools to make (or ’ infection, trauma that leads to the diagnosis. Cases of Sheehan s exclude) the diagnosis reliably. An accurate diagnosis is essential fl syndrome diagnosed after in uenza infection have been reported before recommending rhGH therapy. Most paediatric endocrinol- in the literature. This case illustrates importance of taking thorough ogists agree that the foundation for diagnosis of GHD in childhood history, broadening the differential diagnosis when the treatments is based on a comparison of the child's growth pattern with ’ and outcomes don t match. established norms. A consensus view concluded that clinical https://doi.org/10.1016/j.eprac.2021.04.736 assessment of the growth-retarded child is the single most useful

S126 Pituitary Disorders/Neuroendocrinology Endocrine Practice 27 (2021) S107eS132 parameter in diagnosing growth disorders and challenged the Neuroendocrinology, Republican Specialized scientific Practical status of GH measurements as the diagnostic "gold standard". Medical Center of Endocrinology named after Academician Case Description: Birth: 2008 FTCS Birth Weight 2.9 kg Y.K.Turakulov, Tashkent; Shokhsanam Safarova, none - co-author, Age 11: Very healthy young boy. Short stature - decreased growth Neuroendocrinology, Republican Specialized scientific Practical observed by mother [vs peers] x 2 years Medical Center of Endocrinology named after Academician Growth chart: No significant decrease in growth velocity. Normal Y.K.Turakulov, Tashkent; Ozoda Azimova, none - co-author, bone age; no bone age delay. Boy growing at 5% since age 7; now Neuroendocrinology, Republican Specialized scientific Practical also 5th %; MPH¼ Mid Parental Height 170.5 cm 10 to 25%; Genetic Medical Center of Endocrinology named after Academician short stature; paternal grandmother [4’9”]; maternal and paternal Y.K.Turakulov, Tashkent; Saodat Issaeva, none - co-author, great grandmothers short. No chronic childhood diseases. Euthy- Neuroendocrinology, Republican Specialized scientific Practical roid; Prepubertal; Haematology and Biochemistry Normal. Medical Center of Endocrinology named after Academician Age 12: 2020 Oct: GH stimulation test: Y.K.Turakulov, Tashkent Dopa Arginine Stimulation (USA): Objective: Acromegaly is a rare chronic disease caused by hypersecretion of growth hormone and characterized by 0min 60min 90min 120min 150min excessive tissue growth leading to significant burden of com- < HGH 0.1 0.1 0.5 0.8 0.2 ng/ml plications and associate pathologies such as cardiovascular, S Cortisol 14 28 31 32 33 ug/dl musculoskeletal, respiratory, endocrine, and metabolic dis- S IGF1, IGFBP3, FT4, TSH, LH, FSH, Testosterone: All Normal; eases.The objective of our research was to study interrelation MRI: Pituitary slightly decreased in size of acromegaly musculoskeletal complications development Diagnosis: Complete GH Deficiency. Advised rhGH therapy dependent on age, gender of patients, and the duration of the Age 12: 2020 Dec 12 years 9 months: Sought second opinion from disease. our Center. Methods: The subject of the study were 110 patients with GH Endocrine Evaluation: pituitary adenoma, who applied to the RSSPMCE within the Weight: 45 kg Height: 138.2 cm BMI: 24.0 kg/m2 BP: 117/76 period from 2000 to 2020 and were registered as patients with mmHg Pre-Pubertal; Acanthosis Nigricans axilla and neck++; no acromegaly in the RUz. Among them there were 40 (33.37%) microphallus; Forehead hypertrichosis ++. Repeat Bone Age: No men and 70 (63.63%) women. The mean age of the patients was delay (CA¼BA) 43±8.7 years old.According to the age the patients were After Priming with Inj Testosterone 100 mg IM: distributed to three groups: I group under 30, II group 30- Exercise Test: GH 20 min¼ 3.8, 40 min¼ 0.59 ng/ml 44 years old, and the III group of patients of 45 years old and Clonidine Stimulation Test: GH 60 min¼ 6.88, 90 min¼ elder. 4.74 ng/ml Results: In young age there was higher prevalence rate of Basal 17 OH Progesterone: 347 ng/dl (< 100) osteoarthritis (49% versus 10.5%, р< 0.001) and osteopenia Basal S Cortisol 8 AM: 26.1 mcg/dl; Hypercortisolism; P ACTH: (33.9% versus 13.2%, р< 0.01). Patients with acromegaly had a 67.3 pg/ml high rate of musculoskeletal complications, in the structure of 24-hour urine Cortisol: 131 mcg/day (2.6-37) which a significant part is attributed to osteoporosis (60.9%) and S Cortisol: < 0.90 mcg/dl post overnight 1 mg Dexamethasone osteoarthrosis (58.2%), with prevailing osteoarthrosis among fe- FP Glucose: 107 mg/dl, Prediabetes. Euthyroid male patients (60.5% versus 46.8%, р< 0.05), and compression MRI: Adrenals normal. vertebral fractures among males (12.8% versus 5.5%, р< 0.001 ). Plan: Growth and Puberty monitoring. ACTH stimulation test for With the aging of patients lesions of skeletal system become non-classic congenital adrenal hyperplasia due to 21-hydroxylase more severe developing to osteoporosis, osteoarthrosis, and deficiency. fractures. With the increase in the duration of the disease hy- Discussion: A very unusual patient with two recessive endocrine persecretion of GH caused deterioration of MSC and growth of diseases: non-classic congenital adrenal hyperplasia modifying the osteoarthrosis (92.5% with duration 10-19 years, р< 0.001 and classical GH deficiency phenotype has been reported with 94.3% with duration 20 years and more, р< 0.001) and osteo- advanced bone age - Genetic diagnosis: homozygous mutation in porosis (91.2% with duration 10-19 years, р< 0.001and 98.3% GHRHR (p.Leu144His), homozygous CYP21A2 mutation (p.Val282- with duration 20 years and more, р< 0.001) prevalence rate. Leu) and CYP21A1P pseudogene duplication [Arch Endocrinol Discussion/Conclusion: Thus, patients with acromegaly have high Metab. 2017 Dec;61(6):633-636]. prevalence rate of musculoskeletal complications, in the struc- ture of which the most prevalent was osteoporosis and osteo- https://doi.org/10.1016/j.eprac.2021.04.737 arthrosis with osteoarthrosis more often observed in female patients and compression vertebral fractures in male patients. Patients’ aging resulted in deterioration of bone-articulate sys- Abstract #1003957 tem lesions due to the rise of prevalence rate of osteoporosis, Correlation of Acromegaly Musculosceletal osteoarthrosis and fractures With the increase of the term of GH Complications Development with Gender, Age of hypersecretion the severity of skeletal system lesion increased Patients and Term of Disease resulting in the rise of prevalence rate of osteoarthrosis and osteoporosis. These findings confirm the necessity of early aggressive therapy of both basic disease and initial complications in musculoskeletal system, as alterations in joints and cartilages Author Block: Zamira Khalimova, none - primary author, become irreversible with aging of the patients and increase of Neuroendocrinology, Republican Specialized scientific Practical the disease duration. Medical Center of Endocrinology named after Academician Y.K.Turakulov, Tashkent; Adliya Kholikova, none - co-author, https://doi.org/10.1016/j.eprac.2021.04.738

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Abstract #1004125 clinicopathologic characteristics of PAs requires close and careful follow-up even if total resection is achieved.

Prognostic Factors in Acromegaly: A Case Series https://doi.org/10.1016/j.eprac.2021.04.739

Author Block: Roxana Ioana Dumitriu, Carol Davila University of Abstract #1004277 Medicine and Pharmacy - Primary author, Pituitary and Neuroendocrine Disorders Department, C. I. Parhon National Persistently Elevated VIP Levels in the Setting of e Institute of Endocrinology; Iulia Florentina Burcea, Carol Davila Pancreatic Neuroendocrine Tumor Resection University of Medicine and Pharmacy - Co-author, Pituitary and Potential Testing Limitations Neuroendocrine Disorders Department, C. I. Parhon National Institute of Endocrinology,; Roxana Dusceac, Carol Davila Author Block: Joseph Cataline, MD - Primary Author, Internal University of Medicine and Pharmacy - Co-author, Pituitary and Medicine, Cleveland Clinic Foundation; Nabil Z. Madhoun, DO - Co- Neuroendocrine Disorders Department, C. I. Parhon National author, Endocrinology, Cleveland Clinic Foundation; Institute of Endocrinology,; Valeria Nicoleta Nastase* - Co-author, Adam McShane, PhD - Co-author, Endocrinology, Cleveland Clinic Pituitary and Neuroendocrine Disorders Department, C. I. Parhon Foundation; Jay Morrow, MD - Co-author, Endocrinology, National Institute of Endocrinology; Catalina Poiana, Carol Davila Cleveland Clinic Foundation University of Medicine and Pharmacy - Co-author, Pituitary and Neuroendocrine Disorders Department, C. I. Parhon National Introduction: Institute of Endocrinology, A VIPoma is a subtype of pancreatic endocrine neoplasm that reflects the systemic overproduction of VIP. This report describes the case of a patient with elevated VIP levels both Introduction: Immunohistochemical staining is an important before and after resection of a small, distal pancreatic neuroendo- parameter in predicting the behavior of pituitary adenomas (Pas), crine tumor. especially through anterior pituitary hormones, but also through Case Description: A 45-year-old female presented to a GI clinic transcription factors. These, along with the clinical and biochemical with a long history of intermittent diarrhea, bloating, and bright red characteristics of the patients can be integrated in a risk stratifi- blood per rectum. EGD, colonoscopy, and gastric emptying tests cation system, which helps the therapeutic management. were unremarkable. After failure to respond to empiric dietary and Case Description: We present 5 cases of acromegaly due to GH pharmacologic treatment she was evaluated by functional medi- secreting PAs, with ages between 48-75 years old, with male:female cine who ordered serum VIP which was repeatedly elevated to 162, ratio 4:1, who underwent surgical treatment. Four patients were 135, and 114 pg/mL (0-60 pg/mL) at 1, 3, and 6 months respectively. diagnosed with macroadenomas and 1 patient had a microadenoma. MRI revealed a stable hypervascular 0.6 cm lesion within the All patients had transsphenoidal resection (one patient had two in- pancreatic tail and was subsequently confirmed by EUS. DOTATATE terventions) and one of them had also gamma-knife radiosurgery. PET/CT was done and the lesion demonstrated elevated SUV. Three tumors were considered invasive, according to Knosp classi- Laparoscopic distal pancreatectomy revealed a 0.6 cm well- fication (grade 3-4). Four patients had tumor remnants and residual differentiated neuroendocrine tumor, WHO grade 1, with epithe- hypersection which was controlled only in two cases under therapy lioid cells strongly positive for chromogranin and synaptophysin with somatostatin analogues, growth hormone receptor antagonist and Ki-67 proliferation index of < 3%. Immunohistochemistry for and dopamine agonists, in different associations. The male patient pancreatic hormones was not performed. VIP remained compa- with microadenoma had remission of the disease following surgery rably elevated postoperatively, and MRI of the abdomen and pelvis alone. In all 5 cases, specimens obtained were stained with routine 7 months postoperatively revealed no abnormal lesions. Genetic hematoxylin and eosin method and vimentin for quality-control. testing for MEN was negative. The patient was evaluated by Histologically, all tumors were acidohilic, with diffuse growth endocrinology for the persistence of her symptoms. Repeat VIP pattern in 3 cases and alveolar in 2 cases. Immunohistochemistry measurement was 190 pg/mL. In the absence of typical VIPoma showed 3 mixed mammosomatotroph PAs (GH/PRL) and 2 pluri- symptoms and lack of improvement of serum VIP levels after hormonal Pas with unusual immunohistochemical combinations resection, assay interference was considered a likely cause of the (GH+ACTH and GH/PRL/TSH/LH). All of them showed intensive re- persistently elevated VIP. Serum VIP levels were sent to a separate action for GH (3+) and a ki-67 ranging from 0.05% to 3%. reference lab, which manufactures their own rabbit antibody, and Discussion: Both patients with uncontrolled disease presented the patient’s VIP level was 59 pg/mL (< 75 pg/mL). Several studies, with the largest diameter (35 mm and 29 mm, respectively) and including molecular weight cutoff filtration and polyethylene glycol Knosp grade 3. One of them, a female patient, presented immu- (PEG) precipitation, were attempted to identify the cause of the nohistochemical intensive reaction for ACTH (3+), the other one discrepancy (e.g. a macro-complex); however, all VIP activity was had a mixed mammo-somatotroph PA. The microadenoma had an removed with a standard sample. high positivity for GH (3+), medium for PRL and TSH (2+) and low Discussion: There is relative instability of VIP in plasma, which adds for LH (1+). The pathogenesis of plurihormonal tumors is hypoth- difficulty in sample collection and assay of this hormone. Causes of esized to be as a result of neoplastic transformation of two different falsely elevated VIP may be other neurogenic tumors, small-bowel cell lines or transdifferentiation of a once tumor cell line into a resections, inflammatory bowel disease, or prolonged fasting. Our different hormone-producing cell line, but we do not have a clear patient lacked typical features of VIPoma. Also, her symptoms did correlation with the prognosis. Predicting the evolution of pituitary not improve after pancreatic mass resection pointing away from adenomas can be challenging, but the clinicopathological classifi- this diagnosis. This case highlights the importance of history when cation can offer valuable information. Unusual cell combinations interpreting laboratory data. As the VIP level normalized with the that produce hormones unrelated histogenetically, biochemically, use of a different antibody, interfering substance in the patient’s or throughout regulatory mechanisms can appear, but these un- serum was the most likely cause of the spurious VIP elevation. usual combinations are characterized by aggressive beahviour, persistence of disease and high recurrence. Understanding the https://doi.org/10.1016/j.eprac.2021.04.740

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Abstract #1004314 Abstract #1004343

Rare Association of Empty Sella Syndrome with Assessment of Quality of Life in Patients with Central Diabetes Insipidus Syndrome: A Case Report Cushing's Syndrome

Author Block: Sonika Malik, MD - Primary Author, Endocrinology, Author Block: Ozoda Azimova - Republican Specialized diabetes and metabolism, Texas Tech University Health Sciences Scientific medical center of Endocrinology, named after Center; James Burks, MD - Co-author, Endocrinology, diabetes and acad.prof. Turakulov.Ya.X; Gulchekhra Narimova, none - primary metabolism, Texas Tech University Health Sciences Center author, Neuroendocrinology, Republican Specialized scientific Practical Medical Center of Endocrinology named after Introduction: Empty sella syndrome refers to radiological Academician Y.K.Turakulov, Tashkent; Shakhnoza Ergasheva, description of an enlarged sella turcica that is not completely none - co-author, Neuroendocrinology, Republican filled by the pituitary tissue. This results from intrasellar hernia- Specialized scientific Practical Medical Center of tion of the subarachnoid space through a congenital defect of the Endocrinology named after Academician Y.K.Turakulov, diaphragma sellae resulting in flattening of the pituitary gland. Tashkent Incidence is rare with 12% patients found to have empty sella syndrome on neuroimaging. Patients are usually asymptomatic. However, endocrine dysfunction in the form of hypopituitarism Objective: Cushing's syndrome (CS) is a rare, severe, multi- has been described in about 30% cases. We report a case of pos- symptomatic endocrine disease associated with excessive produc- terior pituitary dysfunction in the form of central diabetes tion of cortisol. Chronic exposure to hypercortisolism determines insipidus associated with empty sella syndrome in a young hypertension, hyperglycemia, osteoporosis, delayed wound heal- female. ing, muscle weakness and depression, which affect quality of life Case Description: Our patient was a 32-year old female who was (QoL) - physically, mentally and emotionally. Our purpose is to referred to our endocrine clinic for management of central dia- study the QOL of patients with CS depending on the duration of betes insipidus diagnosed at age 3 years. At the time of our hypercortisolemia and disease activity evaluation, she was on intranasal desmopressin (DDAVP) since Methods: The features of the quality of life in 20 patients with atleast 10 years. On review of medical records, she was diagnosed CS examined and treated at the Republican Specialized Sci- with diabetes insipidus with presence of hypernatremia (sodium entific and Practical Medical Center for Endocrinology (Tash- 150 mEq/L), polyuria (6L/day), high plasma osmolality (350 kent, Uzbekistan) in 2020 were studied. All patients mOsm/kg) and low urine osmolality (250 mOms/kg). Utilization underwent general clinical, hormonal tests (blood and urine of water deprivation test for diagnostic purpose was unclear. cortisol). To assess the QoL of patients, we used the Cush- Further work up for anterior pituitary hormone deficiency was ingQoL questionnaire. un-revealing. Interestingly, subsequent MRI of the pituitary Results: The average age of patients was 31.4±3.53 years. The revealed a predominantly empty and slightly expanded sella majority were patients aged 18 to 44 years. Blood cortisol at turcica. There was absence of high signal on T-1 weighted images diagnosis (according to the register) and after treatment was in the region of posterior pituitary. This could be a sign of pos- the following 848.71 and 320.98 (respectively) (P0.001). terior pituitary abnormality, but can be purely incidental. Urine cortisol at diagnosis (according to register data) and Clinically, the patient was asymptomatic with infrequent dizzi- after treatment was 298.2 and 150.6 (respectively) (P0.001). ness and headaches. She did not have visual field defects. She did 9 of 20 patients (45%) had an active period of the disease (in 2 not have intra-cranial hypertension. We continued desmopressin it was detected initially, in 7 it was relapsing), and in 11 (55%) and continue to follow up with her in our clinic. there was a remission of the disease. The analysis of the QoL Discussion: There is limited literature on association of central revealed: 30.2(50.5%) at the time of diagnosis of CS, diabetes insipidus with empty sella syndrome. Few case reports 25.5(42.5%) in patients with a primary diagnosis, 33.7(56.2%) have been described so far on posterior pituitary dysfunction, with in patients with remission and 33.7 in relapse (56.2%). in the the first case described in 1973 by Matisonn. This was a 43-year old last admission-40.5(67.5%), in patients with remission and woman who had DI with post-partum galactorrhea. Similar to our relapse it was 40.7(67.8) and 40.5(67.5%), respectively.It was case, Marano et al described posterior empty sella in two children found that the QoL depends on the duration of hyper- with central diabetes insipidus. Overall, the incidence is rare. In our cortisolemia in 11 patients (55%) with hypercortisolemia for 1- patient, the diagnosis was made at age 3 years. She denied family 2 years, before treatment in 31.2(52.1%) and 47 patients history of similar disease. (68.3%) after treatment, in 4 patients with hypercortisolemia The pathogenesis is not clear. In our patient, the anterior pi- within 3-5 years before treatment 30.7(51%) and 44(73.3%) tuitary hormones were all normal. Her reproductive capacity after treatment, more than 5 years 5(25%), in a patient before was normal. She presented as a case of isolated posterior pi- treatment 37(61.7%) and 34 after treatment (56.7%) (p0.05). tuitary deficiency and empty sella. The association could be Discussion/Conclusion: In CS, the relationship between the dura- purely co-incidental. Lambert et al described similar case but tion of hypercortisolemia and the level of QoL was assessed using with both anterior and posterior pituitary dysfunction. It has the Pearson method, which revealed a moderate negative rela- been hypothesized that an empty sella represents necrosis of a tionship.At the same time, the relationship between hyper- prior pituitary adenoma, most frequently a prolactinoma, but cortisolemia and QoL before treatment has an average negative again, in our patient, we did not suspect this based on clinical relationship and the degree of hypercortisolemia and QoL after presentation. treatment has a low positive relationship. https://doi.org/10.1016/j.eprac.2021.04.741 https://doi.org/10.1016/j.eprac.2021.04.742

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Abstract #1004357 purulent complications of diabetes mellitus - 9 ( 2.8%), Covid 19-1 (0.31%).

Analysis of Deaths in Patients with Cushing's Syndrome https://doi.org/10.1016/j.eprac.2021.04.743 in the Republic of Uzbekistan According to the Register

Abstract #1040637 Author Block: Ozoda Azimova - Republican Specialized Scientific medical center of Endocrinology, named after acad.prof. Effect of Osilodrostat on Clinical signs, Physical Turakulov.Ya.X; Zamira Khalimova, none - primary author, Features and Health-related Quality of Life (HRQoL) by Neuroendocrinology, Republican Specialized scientific Practical Degree of mUFC Control in Patients with Cushing’s Medical Center of Endocrinology named after Academician Disease (CD): Results from the LINC3 Study Y.K.Turakulov, Tashkent; Gulchekhra Narimova, none - co-author, Neuroendocrinology, Republican Specialized scientific Practical Medical Center of Endocrinology named after Academician Author Block: Rosario Pivonello, Professor of Endocrinology - Y.K.Turakulov, Tashkent; Gavhar Zhabborova, none - co-author, Primary author and presenter, Dipartimento di Medicina Clinica e Neuroendocrinology, Republican Specialized scientific Practical Chirurgia, Universita Federico II di Napoli; Maria Fleseriu, Professor Medical Center of Endocrinology named after Academician of Medicine/Endocrinology and Neurological Surgery - Co-author, Y.K.Turakulov, Tashkent Pituitary Center, Departments of Medicine and Neurological Surgery, Oregon Health & Science University; John Newell-Price, Professor of Endocrinology - Co-author, Department of Oncology Objective: Purpose of the study is to analysis of deaths in patients and Metabolism, The Medical School, University of Sheffield; with Cushing's syndrome (CK) in the Republic of Uzbekistan ( RUz ) Akira Shimatsu, Director - Co-author, Advanced Medical Care according to the register. Center, Kusatsu General Hospital; Richard A. Feelders, Associate Methods: fi According to the etiologic classi cation of the Re- Professor of Endocrinology - Co-author, Department of Internal public of Uzbekistan from the period 2002 to 2021 established Medicine, Endocrine Section, Erasmus Medical Center; 317 patients with the following clinical forms of Cushing's Pinar Kadioglu, Assistant Professor - Co-author, Division of С Н syndrome: A T -dependent CS - 258 (81.3% ) of patients are Endocrinology, Metabolism and Diabetes, Cerrahpasa Medical women -174 (54.8%), men-84 (26 .4%), ectopic CS -8 patients Faculty, Istanbul University; Antoine Tabarin, Chef du service (2.5%) women-5 (1.5%), men-3 (0.94%); ACTH independent Endocrinologie - Diabete et Nutrition - Co-author, CHU de Cushing's syndrome - 51 patients (16.08%) women - 41 Bordeaux; Thierry C. Brue, Professor of Endocrinology - Co-author, (12.9%), men - 10 (3.15%). Aix-Marseille Universite, Marseille Medical Genetics, and Centre Depending on the stage of the disease, patients with ACTH de Ref erence des Maladies Rares de l’Hypophyse; Eliza B. Geer, dependent CS : women in the stage of relapse - 19 (5.9%), active Medical Director - Co-author, Pituitary & Skull Base Tumor Center, phase - 30, without radical treatment (9.4%), remission - 109 Memorial Sloan Kettering Cancer Center; Andrea Piacentini, Senior (34.3%); men in the stage of relapse -6 (1.8%), active phase - 14 Statistician - Co-author, Recordati SpA; Alberto M. Pedroncelli, (4.4%), remission - 46 (14.5%). Global Medical Director - Co-author, Recordati AG; ACTH independent CS in remission: 36 women (11.3%), 8 men Beverly M.K. Biller, Professor of Medicine - Co-author, (2.52%). Neuroendocrine and Pituitary Tumor Clinical Center, ACTH ectopic CS in the stage of remission: women - 2 (0.6%), in Massachusetts General Hospital the active phase - 2 (0.6%) ; men in remission-1 (0.01%). Performed methods of therapy: Transsphenoidal adenomec- tomy of the pituitary gland (TPAEG) was performed in 92 Objective: LINC3 (NCT02180217), a Phase III, multicenter, double- (35.6%) patients with ACTH dependent CS , in the form of blind, randomized withdrawal study, showed osilodrostat (a potent monotherapy, 11 patients (4.26%) underwent repeated TPAEG; oral 11b-hydroxylase inhibitor) to be an effective treatment for CD 29 patients (11.2%) received combined treatment; Radiation by normalizing mUFC in most patients. Here we assessed the effects therapy - 4 patients (1.5%), bilateral adrenalectomy was per- of osilodrostat on signs, symptoms and HRQoL of CD by degree of formed in 12 patients with ACTH dependent CS and one pa- mUFC control. tient with ACTH ectopic CS (3.7%), 85 patients ( 32.9%) are on Methods: 137 adults with CD and mUFC >1.5xULN enrolled in drug therapy , Unilateral adrenalectomy - in 60 patients (18.9 LINC3 and received open-label (OL) osilodrostat for the 48-week %) embolization and electrocoagulation vessel adrenal - 3 core phase. Patients started treatment at 2mg bid with dose in- (0.9%) patients refusing treatment - 9 (2.8%); removing ectopic creases every 2 weeks (W) until W12 (max 30mg bid) based on focus - 3 ACTH ectopic CS patients (37.5%), chemotherapy mUFC and safety, then continued at the therapeutic dose to W24. At surround formation performed 2 patients (25%). W26, eligible patients (mUFCULN at W24 without uptitration Results: It was found that among these groups 41 (12.9%) deaths after W12) were randomized to osilodrostat (n¼36) or placebo were registered over the 19 year period , of which 36 (11.3%) were (n¼35) in an 8-week double-blind phase (ineligible patients with ACTH dependent CS -19 women (5.9%), 17 men (5.3%) ; ACTH continued OL osilodrostat; n¼47). All patients then received OL independent CS -2 (0.6%) 1 woman (0.3%), 1 man- (0.3%); ACTH osilodrostat up to W48. mUFC (average of three samples by liquid ectopic CS -3 patients (0.9%) of them women - 1 (0.3%), men - 2 chromatography-tandem mass spectrometry, normal range 11‒138 (0.6%). nmol/24h [4‒50 mg/24h]), cardiovascular-related metabolic pa- Discussion/Conclusion: The causes of death in patients with CS rameters, physical features (rating: 0¼absent; 1¼mild; were mainly cardiovascular accidents, of which myocardial infarc- 2¼moderate; 3¼severe) and CushingQoL and Beck Depression In- tion was established in 11 (3.4%), acute cerebrovascular accident-10 ventory (BDI) scores were evaluated at baseline (BL), every 2, 4 or (3.15%), pulmonary embolism(PE)-10 (3.15%), the consequences of 12W (depending on study phase) and at W48. mUFC was defined at

S130 Pituitary Disorders/Neuroendocrinology Endocrine Practice 27 (2021) S107eS132

W24 and W48 as controlled (C) if ULN, partially controlled (PC) if growth hormone [GH], < 2.5 ng/mL) and 6 months’ iSRL treat- >ULN but 50% reduction from BL, and uncontrolled (UC) if >ULN ment. Eligible patients entered a 26-week Run-in phase to deter- and < 50% reduction from BL. mine the effective OOC dose, followed by a 36-week randomized Results: At W24, 93 (67.9%) and 20 (14.6%) patients had C and PC controlled treatment (RCT) phase receiving OOC or iSRLs. Eligibility mUFC, respectively; 24 (17.5%) were UC. At W48, 91 (66.4%), 13 for the RCT was based on response (defined as IGF-I < 1.3 ULN (9.5%) and 33 (24.1%) were C, PC and UC, respectively. Patients with and mean GH < 2.5 ng/mL) at week 24 of the Run-in. This analysis C or PC mUFC at W24 had the greatest change from BL in mean [95% evaluated proportion of patients who were biochemical responders CI] systolic BP (e7.1 [e10.3,e3.9], e7.2 [e14.0, e0.4] and 2.0 [e9.7, (defined as time-weighted average [TWA] IGF-I < 1.3 x ULN) 13.7] mmHg in C, PC and UC groups, respectively) and diastolic BP throughout the RCT or at end of RCT (defined as IGF-I < 1.3 x ULN (e4.9 [e7.1, e2.7], e5.2 [e9.8, e0.6] and 5.3 [e3.3, 13.9] in C, PC and based on average of measurements at end of RCT and 4 weeks prior UC groups). At W48, improvements in systolic/diastolic BP occurred to end of RCT, landmark analyses) subdivided by type and dose of irrespective of mUFC control. Other cardiovascular risk factors prior iSRL. Least squares mean (LSM) change from baseline (CFB) of (weight, BMI, waist circumference, fasting plasma glucose, HbA1c, IGF-I levels at the end of treatment in the RCT was also evaluated. total cholesterol, triglycerides), CushingQoL and BDI scores, and Populations assessed were the full analysis set (FAS; all randomized physical features of hypercortisolism (facial rubor, striae, fat dis- patients) and the population meeting response criteria at week 26 tribution, bruising, hirsutism [females], muscle atrophy) progres- (RCT baseline responders). sively improved from BL to W24 and W48, irrespective of mUFC Results: Of 146 enrolled patients, 92 were eligible to enter the RCT. control. The 55 patients randomized to receive OOC are assessed here. Rate Discussion/Conclusion: Improvements in clinical signs, physical of response in the FAS (N¼55) was 90% (26/29) in those previously features and HRQoL of CD patients occurred soon after osilodrostat receiving injectable octreotide and 92% (24/26) in those previously initiation and were sustained until end of core study at W48. In receiving injectable lanreotide. In RCT baseline responders (n¼48), most cases, improvements were seen even in patients without response rates increased to 93% (25/27) and 100% (21/21), respec- complete mUFC normalization. tively. Based on landmark analyses, the response rate in the FAS was 86% (25/29) in those previously receiving octreotide and 92% (24/ https://doi.org/10.1016/j.eprac.2021.04.744 26) for lanreotide. These rates increased to 93% (25/27) and 95% (20/21) in RCT baseline responders, respectively. Responses were Abstract #1041607 also similar for all prior iSRL doses. Prior iSRL use did not affect change in IGF-I level in the RCT for the FAS (LSM CFB of IGF-I: Effects of Prior Injectable Somatostatin Receptor Ligand octreotide, 0.003; lanreotide, e0.003; P¼0.89) or RCT baseline re- Type and Dose in Patients With Acromegaly Receiving sponders (LSM CFB of IGF-I: octreotide, e0.004; lanreotide, 0.03; Oral Octreotide Capsules in the Phase 3 MPOWERED Trial P¼0.55). Discussion/Conclusion: Biochemical response to OOC in patients with acromegaly is not determined by the type or dosage of prior Author Block: Murray B. Gordon, MD - Primary Author, Allegheny iSRL therapy.

General Hospital; Maria Fleseriu, MD, PhD - Co-author, Pituitary https://doi.org/10.1016/j.eprac.2021.04.745 Center, Oregon Health & Sciences University; Nienke Biermasz, MD, PhD - Co-author, Leiden University Medical Center; Alexander Dreval, MD, PhD, Prof - Co-author, M.F. Vladimirsky Abstract #1022216 Moscow Regional Research Clinical Institute; Yulia G. Pokramovich, MD, PhD - Co-author, M.F. Vladimirsky Moscow Regional Research MAX Gene Mutation: New Marker for Multiple Clinical Institute; Irina Bondar, MD - Co-author, Novosibirsk State Endocrine Neoplasia Syndrome? Medical University; Elena Isaeva, MD, PhD - Co-author, Interregional Clinical Diagnostic Center; Mark E. Molitch, MD - Co- author, Northwestern University Feinberg School of Medicine; Author Block: Jesse Sundar, MS-4 - Co-author, WVU; Djuro P. Macut, MD, PhD - Co-author, University of Belgrade; Anusha Kothapalli, MS-4 - Co-author, WVU Medicine; Yossi Gilgun-Sherki, PhD - Co-author, Chiasma Inc; Adnan Haider, MD - Co-author, WVU Medicine; Oksana Symczyk, William H. Ludlam, MD, PhD - Co-author, Chiasma Inc; Gary Patou, MD - Co-author, Presenter, WVU Medicine MD - Co-author, Chiasma Inc; Asi Haviv, DMD - Co-author, Chiasma Inc; Christian J. Strasburger, MD - Co-author, Charite- Introduction: The novel germline MAX (MYC-associated factor X) Universitatsmedizin,€ Campus Mitte; Shlomo Melmed, MB, ChB, gene mutation is a known cause of hereditary paraganglioma- FRCP, MACP - Co-author, Cedars-Sinai Medical Center pheochromocytoma syndrome. Here we describe a novel case suggesting a link between Multiple Endocrine Neoplasia and MAX ® Objective: Oral octreotide capsules (OOC; MYCAPSSA ) are mutation. approved in the US for treating adults with acromegaly previously Case Description: We present a case of a 40 year old male who responding to and tolerating injectable somatostatin receptor li- initially was diagnosed with a pituitary macroadenoma at age 11 as gands (iSRLs). MPOWERED is a phase 3 trial assessing maintenance part of an evaluation of headaches, vision changes, and sinus of response to OOC compared to iSRLs in acromegaly. Here we pressure. Further testing of the previously healthy 6 foot 6 inches report outcomes in patients receiving OOC based on their prior iSRL tall boy confirmed the diagnosis of gigantism. Biochemical remis- treatment (octreotide or lanreotide). sion was achieved following initial transsphenoidal resection. Four Methods: Eligibility criteria for MPOWERED included acromegaly years later, he developed acral enlargement and excessive sweat- diagnosis, current biochemical response (insulin-like growth factor ing. Repeat transsphenoidal resection followed by gamma knife I [IGF-I] < 1.3 upper limit of normal [ULN], mean integrated radiation resulted in biochemical remission. A year later, he began

S131 Pituitary Disorders/Neuroendocrinology Endocrine Practice 27 (2021) S107eS132 experiencing recurrent headaches, excessive sweating, and palpa- Medical University; Elena Isaeva, MD, PhD - Co-author, tions. Plasma normetanephrines showed a greater than 5-fold Interregional Clinical Diagnostic Center; Mark E. Molitch, MD - Co- elevation and an abdominal MRI revealed a 1.9 cm left adrenal mass author, Northwestern University Feinberg School of Medicine; with 50 Housenfield Units. Pathology confirmed the diagnosis of a Djuro P. Macut, MD, PhD - Co-author, University of Belgrade; pheochromocytoma. After surgical resection, biochemical remis- Yossi Gilgun-Sherki, PhD - Co-author, Chiasma Inc; sion was achieved. Five years later, he presented with the same William H. Ludlam, MD, PhD - Co-author, Chiasma Inc; Gary Patou, symptoms. Workup was notable for a 4-fold elevation in plasma MD - Co-author, Chiasma Inc; Asi Haviv, DMD - Co-author, Chiasma normetanephrine and MIBG scan showed uptake in the right ad- Inc; Christian J. Strasburger, MD - Co-author, Charite- renal bed with pathology confirming right adrenal pheochromo- Universitatsmedizin,€ Campus Mitte; Shlomo Melmed, MB, ChB, cytoma. Following bilateral adrenalectomy and initiation of FRCP, MACP - Co-author, Cedars-Sinai Medical Center hydrocortisone and florinef the patient attained symptomatic relief. Five years later, an incidental finding of left adrenal bed Objective: Patient-reported outcomes (PROs) are a key treatment nodules on abdominal CT done for trauma evaluation was noted objective in acromegaly. Validated PROs were used to assess disease and plasma normetanephrines were once again found to be and treatment burden in the MPOWERED phase 3 trial comparing ® elevated. MIBG scan did not show uptake in the incidental oral octreotide capsules (OOC; MYCAPSSA ) to injectable SRLs nodules. A clonidine suppression test failed to suppress the (iSRLs). plasma metanephrines. Surgical resection of the left adrenal bed Methods: Eligibility criteria for MPOWERED included acromegaly nodule due to suspected recurrence of pheochromocytoma was diagnosis, current biochemical response (insulin-like growth factor confirmed on pathology. On follow-up, while on sertraline for I < 1.3 upper limit of normal; mean integrated growth hormone, anxiety, plasma normetaphrine were once again found to be < 2.5 ng/mL), and 6 months’ iSRL treatment (octreotide or lan- elevated (1.4 ng/dL, normal < 0.9 ng/dL) and a Gallium DOATATE reotide). Eligible patients entered a 26-week Run-in phase in which scan showed 1.4 cm uptake medial to the left kidney. A 0.3 mg all patients received OOC to determine effective OOC dose; re- clonidine suppression test was preformed and resulted in 42% sponders then entered a 36-week randomized controlled treat- suppression in plasma normetanephrine from baseline. Initial ment (RCT) phase receiving OOC or iSRLs in a 3:2 ratio. EuroQol-5 gene testing including RET, NF1, SDHB, SDHC, SDHD, VHL was Dimensions-5 Levels (EQ-5D-5L) and Work Productivity and Ac- negative. A 14 gene panel subsequently found the patient was tivity Impairment Questionnaire: Specific Health Problem heterozygous for MAX Exon 4 c.228del variant. (WPAI:SHP) were collected at baseline (reflecting outcomes on Discussion: A handful of cases in previous literature have described iSRLs), end of Run-in (reflecting outcomes on OOC), and end of RCT the association between pheochromocytomas (often bilateral) and (OOC or iSRLs). Resultsof the Acromegaly Treatment Satisfaction pituitary tumors with germline MAX mutations. Ganglioneuromas, Questionnaire were reported elsewhere. neuroganglioma, and kidney tumors have also been associated Results: Of 146 enrolled patients, 92 were randomized to the RCT with MAX gene mutations. Most recently cases of pancreatic phase. Baseline EQ-5D-5L and WPAI:SHP results were similar be- neuroendocrine tumors and GIST tumors have been reported with tween the 2 treatment groups. Among randomized patients, sig- this mutation. It will be interesting to see if in this case, the 1.4 cm nificant improvements were observed in EQ-5D-5L Index scores mass proves to be a case of recurrent pheochromcytoma vs para- (mean change from baseline, 0.053; 95% CI, 0.0130e0.0922) ganglioma or a separate tumor associated with this new MEN gene. comparing end of Run-in (OOC) to baseline Run-in (iSRL). Signifi- cant improvements on the WPAI:SHP were also demonstrated https://doi.org/10.1016/j.eprac.2021.04.746 comparing end of Run-in (OOC) to baseline Run-in (iSRL) for Pre- senteeism (impairment at work/reduced on-the-job effectiveness; least squares mean [LSM], e6.65; 95% CI,e12.39 to e0.90; P¼0.024), Abstract #1041639 Work Productivity Loss (LSM, e6.92; 95% CI, e12.83 to e1.02; P¼0.022), and Activity Impairment (LSM, e4.94; 95% CI, e9.17 to Improved Quality of Life and Work Productivity in e0.71; P¼0.022) among randomized patients. EQ-5D-5L Index Patients With Acromegaly Receiving Oral Octreotide scores and WPAI:SHP domain scores were comparable at the end of Capsules in the Phase 3 MPOWERED Trial the RCT phase between patients receiving OOC (N¼55) and iSRL (N¼37). Discussion/Conclusion: PROs, including quality of life (QoL) and Author Block: Nienke Biermasz, MD, PhD - Primary, Leiden work productivity, were all significantly improved in the Run-in University Medical Center; Maria Fleseriu, MD - Co-author, phase in patients transitioning from iSRL to OOC. As patients served Pituitary Center, Oregon Health & Sciences University; as their own control, the analysis was highly sensitive in the Run-in Murray B. Gordon, MD - Co-author, Allegheny General Hospital; phase. Significant differences between treatment arms were not MD, PhD Alexander Dreval, Prof - Co-author, M.F. Vladimirsky observed during the RCT phase, potentially due to sample size and Moscow Regional Research Clinical Institute; Yulia G. Pokramovich, variability of the measures. MD - Co-author, M.F. Vladimirsky Moscow Regional Research Clinical Institute; Irina Bondar, MD - Co-author, Novosibirsk State https://doi.org/10.1016/j.eprac.2021.04.747

S132 Endocrine Practice 27 (2021) S133eS140

Contents lists available at ScienceDirect

Endocrine Practice

journal homepage: www.endocrinepractice.org

REPRODUCTIVE ENDOCRINOLOGY

Abstract #973797 significant increase in BMI over the first year of treatment. As treatment for CPP generally continues for several years, it is 6-Month Subcutaneous Leuprolide Acetate Effectively anticipated that attenuation in the rate of skeletal maturation will Suppressed Rate of Bone Maturation and Increased continue, leading to further improvement in adult height out- Predicted Adult Height Without Significant Increase in comes. These results support the use of a new product with the BMI in Children with Central Precocious Puberty beneficial features of subcutaneous administration, small injection volume, and twice a year dosing.

Author Block: Matthew Benson, MD - Presenter, Nemours https://doi.org/10.1016/j.eprac.2021.04.749 Children's Hospital and Nemours Children's Health System; Stuart Atkinson, MD - Co-Author, Tolmar Pharmaceuticals, Inc; Abstract #984062 Deborah Boldt-Houle, MD - Co-Author, Tolmar Pharmaceuticals, Inc; Karen Klein, MD - Co-Author, Rady Children's Hospital A Case of Ovarian Hyperthecosis in a Postmenopausal Female with Incidental Findings of Unilateral Renal Objective: The first small-volume, long-acting, subcutaneously Cell Carcinoma and Bilateral Adrenal Adenomas administered GnRHa treatment for central precocious puberty (CPP) was approved for use in 2020. Subcutaneous leuprolide ac- etate (45 mg) administered at a 6-month interval effectively sup- Author Block: Zaina Alamer - hamad medical corporation; pressed pubertal hormones and stopped or caused regression of M.D. gowri karuppasamy - Co-Author, endocrine, Hamad Medical pubertal progression. Eighty-seven percent of children achieved corporation; M.D. samir Al Hyassat - Co-Author, Hamad Medical < fi LH 4 IU/L at Wk24 in a Phase III trial evaluating the ef cacy and corporation; kHALED. BAAGAR, MBBCH, MRCP(UK), FACE - Co- fi safety, and 7/8 children who did not achieve the primary ef cacy Author, Hamad Medical corporation endpoint achieved LH< 5 IU/L by Wk48 and showed signs of effective clinical suppression. We present secondary analyses of Introduction: Ovarian Hyperthecosis (OH) is associated with bone age (BA) advancement, weight, BMI, growth rate, and pre- slowly progressive virilization, and it mainly affects post- dicted adult height (PAH). menopausal females. We report a postmenopausal female who Methods: Sixty-two children (60 girls, 2 boys) with CPP (naïve to presented with hyperandrogenism and found to have OH with treatment) received 2 doses of 45 mg subcutaneous leuprolide coexisting renal cell carcinoma and bilateral adrenal adenomas. acetate at 24-Wk intervals. Mean (±SE) for BA, weight, BMI, and Case Description: A 54-year-old postmenopausal woman pre- growth rate were assessed pre-treatment and at Wks24 and 48. sented with hirsutism, frontal balding, and deepening of voice for a Radiographs of the left hand and wrist were obtained pre-treat- year. No history of vaginal bleeding. She had controlled hyperten- ment and at Wks24 and 48 to determine BA using the Greulich and sion on valsartan, and type 2 diabetes on metformin and sitagliptin. Pyle method. Rate of advancement in BA was determined by the On examination, she looked masculine and her vital signs were ratio of BA to chronological age (CA) (BA/CA). PAH was calculated normal. She had hirsutism over her face, chest, and shoulders. pre-treatment and at Wk48. Laboratory workup revealed testosterone 10.32 nmol/L, repeated Results: Mean age at onset of treatment was 7.5±0.1 years. BA/CA 9.41 (normal: 0.69 - 2.78), and DHEAS 1.8 umol/L (normal: 1.5 e 77). declined or remained consistent throughout treatment, from CT scan showed bilateral adrenal adenomas and a suspicious left 1.4±0.02 at baseline, to 1.3±0.02 at Wk24 (p< 0.001) and 1.3±0.02 renal pelvic mass. Transvaginal ultrasound and MRI pelvis showed at Wk48 (p< 0.001), similar to what was previously reported for enlarged ovaries (7 ml) with no definite lesions. The 1 mg dexa- BA-CA. Although mean weight increased 8.7% from screening to methasone suppression test excluded Cushing’s syndrome (cortisol Wk24 (34.8 kg vs 37.7 kg) and 16.9% from screening to Wk48 (40.4 < 22 nmol/L), and DHEAS was suppressed to 1.1 umol/L. Also, pri- kg), as expected, mean BMI remained stable throughout the study: mary aldosteronism and pheochromocytoma were excluded by 18.56±0.4 kg/m2 at baseline, and 19.71±0.4 kg/m2 at Wk48. Mean normal levels of aldosterone (275 pmol/L, normal:49-645), plasma growth rate decreased to normal pre-pubertal levels throughout renin activity (3.7 ng/mL/hr, normal: 0.06-4.7), and 24h-urine treatment: 6.9±0.4 cm/year from baseline to Wk24, and 5.8±0.3 metanephrines (0.13 umol, normal: 0-1.4) and normetanephrines cm/year from Wk24 to 48. PAH increased, from 157±1.0 cm at (0.21 umol, normal: 0-3.45). This workup denoted an ovarian origin baseline, to 160±1.0 at Wk48 (p< 0.001). of her hyperandrogenism, most likely secondary to OH. She un- Discussion/Conclusion: Six-monthly 45 mg subcutaneous leupro- derwent left radical nephrectomy and histopathology showed clear lide acetate is a promising treatment for CPP. It effectively sup- cell renal cell carcinoma. Later, she had an abdominal hysterectomy pressed rate of bone maturation, increased PAH, and did not cause with bilateral Salpingo-oophorectomy. Histopathology confirmed

1530-891X Reproductive Endocrinology Endocrine Practice 27 (2021) S133eS140 bilateral OH with inactive endometrium. Thereafter, testosterone should be counseled about this potential drug-related adverse was normal with improvement of the patient’s virilization. event and be routinely evaluated by their healthcare worker for Discussion: Rigorous assessment of high testosterone levels in early diagnosis and treatment of gynecomastia. This could poten- postmenopausal females is warranted. OH should be considered in tially reduce the burden of surgical management of gynecomastia the differential diagnosis as testosterone level in OH overlaps with as well as reduce the future risk of development of male breast malignant androgen-producing ovarian or adrenal tumors. The cancer. patient had bilateral adrenal adenomas, which increased the https://doi.org/10.1016/j.eprac.2021.04.751 diagnostic complexity. However, the workup was indicative of OH. Bilateral oophorectomy is the definitive treatment of OH, alterna- tively, a long-term GnRH agonist with careful follow-up can be used Abstract #998544 if surgery is not desired or risky. Hysterectomy can be done for OH cases, as there is a risk of endometrial atypia secondary to exposure Ectopic Cushing Syndrome due to Lung Carcinoid, to estrogen produced by aromatization of the high testosterone. Up presenting as a case of PCOS. to our knowledge, this is the first reported case of OH with inci- dental findings of renal cell carcinoma and bilateral adrenal adenomas. Author Block: Vaishali Deshmukh - Deshmukh Clinic and Research https://doi.org/10.1016/j.eprac.2021.04.750 Centre; Paulami Deshmukh, M.B.B.S Student- Medical writer - co- author, SKN Medical College/ Deshmukh Clinic and Research Centre; Anand Nadkarni Consultant Cardiothoracic Surgeon - co- Abstract #996159 author, Cardiothoracic surgery, Deenanath Mangeshkar Hospital and Research Centre Chronic Risperidone Use Leading to Gynecomastia in Young Adult Male Introduction: PCOS is a very common etiology for secondary amenorrhea. However, we present here, a case of secondary amenorrhea, who was eventually diagnosed to have Ectopic Author Block: Rishi Raj - Pikeville Medical Center; Pavitri Dwivedi, Cushing's Syndrome due to a Lung Carcinoid. MD - co-author, Family Medicine, Pikeville Medical Center; Case Description: A 28-year old lady, presented to a gynecologist Ghada Elshimy, MD - Co-author, Endocrinology, Diabetes and with oligomenorrhoea since 4 years and weight gain since a year. Metabolism, Augusta Univeristy She had PCOS on ultrasound and was treated with oral contra- ceptive pills. She responded initially but developed complete Introduction: Risperidone, an atypical antipsychotic, is the most amenorrhea after 6 months. Meanwhile she complained of commonly prescribed antipsychotic medication in the US. It acts as anasarca and hence was referred to a physician, who diagnosed her a D2 receptor antagonist and may elevate prolactin levels and to have BP of 160/100 mmHg and random glucose of 428 mg/dl, reduce gonadotropin secretion. Long-term use of risperidone is hypokalemia (serum K + 2.8 meq/L) and treated as a case of renal associated with gynecomastia with an incidence of 2.3%. We hereby tubular acidosis with hypokalemia, T2DM, hypertension with PCOS. report a case of a young adult male who developed gynecomastia Her potassium was corrected and diabetes was controlled with due to prolonged use of risperidone for bipolar disorder. premix insulin, 80 units per day and Tab. Metformin 1500mg daily. Case Description: A 23-year-old Caucasian male presented with Hypertension was controlled with spironolactone 100 mg and swelling and discomfort in his right breast slowly growing in size amlodipine 5 mg daily. She reported worsening of diabetes, over the last six years. His past medical history was significant for weakness, anasarca, weight gain, fungal infection patches on the bipolar disorder treated with risperidone between the ages of 7-15 skin all over her body, new striae on the abdomen, amenorrhea .She years. He denied any nipple discharge, galactorrhea, nausea, vom- was referred to us with raised BP (140/110 mm Hg), and blood iting, headache, or visual field defects. He denied any use of glucose (fasting: 245mg/dl, post prandial: 392mg/dl), HbA1c 9.8% anabolic steroid use. BMI was 21 kg/m2.On physical examination, and serum potassium was 3.2 meq/L. She had depression, proximal vital signs were stable. Breast examination showed a 4 cm retro- muscle weakness, patches of ringworm infection and was hence areolar lump on the right side without any nipple distortion. investigated for Cushing’s Syndrome. Genital examination revealed normal-sized testes. He had normal Her serum 11:00 pm ACTH was 233pg/dl (n¼10-46pg/dl), base- adrenarche. There was no family history of breast cancer and he line cortisol was 20.4mcg/dl (n¼10-20mcg/dl).Her ODS (overnight had one biological child. Laboratory workup revealed Total testos- dexamethasone suppression) Cortisol was 18.2 mcg/dl, LDDS terone 702 ng/dL (241e827 ng/dL), LH 3.4 mIU/ml (1.7-8.6 mIU/ml), Cortisol was, 9.1mcg/dl and HDDS Cortisol was 1.7mcg/dl, S.FSH FSH 3.8 mIU/ml (1.5-12.5 mIU/ml), HCG < 1 mIU/ml, prolactin 8.1 was 2.1 IU/ml ,S.LH was 1.4 IU/ml, S. Estradiol was 35.3pg/dl. ng/ml ( 4.0e15.2 ng/ml), TSH 1.25 mIU/ml (0.36-3.74 mIU/ml), free In view of non suppression of the HPA axis, the diagnosis of T4 0.90 ng/dL (0.76-1.46 ng/dL), estradiol 17.6 pg/ml ( 0-367.2 pg/ Ectopic Cushing’s Syndrome was made. PET-CT scan revealed ml), hemoglobin 14.9 g/dl (11-17.8 g/dl) and hematocrit 43.5 % (32- bilateral adrenal hyperplasia with a nodule in the lower lobe of the 51.6%). The comprehensive metabolic panel was normal. Ultra- left lung. A cardiothoracic surgeon’s opinion was sought. Removal sound of bilateral breast showed retroareolar glandular densities of the lung nodule was suggested. bilaterally, right greater than left without any suspicious zone of Her blood glucose was controlled with Tab Metformin (1500mg microcalcification. A mammogram showed BI-RADs category 2 daily) and Tab Glimepiride (6mg daily) and 30 units of insulin lesion and ruled out any underlying malignancy. Due to the chro- Glargine at bedtime. Hypertension was controlled using Tab nicity of the condition, surgery was recommended. The patient is Amlodipine (10 mg daily), Tab. Telmisartan (80mg daily) and Tab. currently awaiting evaluation by plastic surgery for further Spironolactone (100mg daily). management. She underwent an anterior basal segmentectomy of the left lung, Discussion: Chronic use of risperidone can lead to gynecomastia in uneventfully. Histopathology was suggestive of Carcinoid of the adolescent and young adult males. Patients on chronic risperidone Left Lung (Low Grade Neuroendocrine Tumor). Tumor cells

S134 Reproductive Endocrinology Endocrine Practice 27 (2021) S133eS140 expressed Cytokeratin CK (weak, focal), Chromogranin A (weak) glucose metabolism, lipid metabolism, gut microbiota diversity, and Synaptophysin (strong). analyzed the correlation between clinical data and gut microbiota, At 3 months , patient’s requirement for drugs reduced to Tab analyzed the differences in gut microbiota between groups, and Amlodipine 5mg daily and Tab. Glimepiride 0.5mg daily. Her blood predicted the function of different gut microbiota and the meta- glucose ,BP and S. Potassium normalized (fasting: 116mg/dl; post bolic pathways that may be involved. prandial: 168mg/dl;BP:130/84 mmHg; S.K+ :3.9 meq/L) with Methods: 18 healthy premenopausal women (group CON ), 20 PCOS spontaneous resumption of menses and a weight loss of 8 kg and women with low low-density lipoprotein cholesterol (LDLC)(group resolution of striae, anasarca and fungal infection. L_LDLC), and 16 PCOS with high LDLC(group H_LDLC) were enrolled Discussion: Although PCOS with metabolic syndrome is a common according to ” Guidelines for prevention and treatment of dyslipi- cause of secondary amenorrhea, one must not forget the possibility demia in Chinese adults”.PCR amplification technology was used to of a rare and curable cause, like Ectopic Cushing’s Syndrome, as a collect the purified amplicons at the same molar concentration, and possible differential diagnosis of the same. terminal sequencing was performed on Illumina Miseq PE300 platform to complete fecal DNA extraction and sequencing. The https://doi.org/10.1016/j.eprac.2021.04.752 clinical data were calculated by SPSS statistical software package 20.0. All statistical tests were double-tailed. When p < 0.05, the difference was statistically significant. Alpha diversity and beta Abstract #1002545 diversity were used to describe the change of gut microbiota be- Prediction of Gut Microbial Community Structure and tween groups.Spearman correlation coefficient was used to eval- Function in Polycystic Ovary Syndrome with High uate the potential correlation between gut microbial community Low-density Lipoprotein Cholesterol and clinical parameters.ROC Curve was made to reveal the rela- tionship between sensitivity and specificity of gut microbiota. COG, KEGG and Phylogenetic Investigation of Communities by Recon- Author Block: Xuping zhu, MD - primary author, Department of struction of Unobserved States (PICRUSt) were used to predict the Endocrinology, The Affiliated Wuxi People’s Hospital of Nanjing functional profile of gut microbial communities. Medical University, Nanjing Medical University; Yanyu Li, MD - Results: Our study showed that the gut microbial community of primary author, Department of Endocrinology, The Affiliated Wuxi PCOS with high low-density lipoprotein cholesterol (LDLC) has a People’s Hospital of Nanjing Medical University, Nanjing Medical noticeable imbalance, mainly manifested by the decrease of a-di- University; yanmin Jiang, MD - primary author, Department of versity, the change of b-diversity, the increase of pro-inflammatory Endocrinology, The Affiliated Wuxi People’s Hospital of Nanjing bacteria and the decrease of healthy symbiotic bacteria. We can Medical University, Nanjing Medical University; Jisheng Zhang, MD distinguish healthy people from PCOS patients or PCOS subtypes - primary author, Department of Good Clinical Practice (GCP), The using characteristic gut microbiota. In PCOS with high LDLC, car- Affiliated Wuxi People’s Hospital of Nanjing Medical University; bohydrate, lipid, amino acid metabolism, and inflammation-related Ru Duan, MD - primary author, Department of Good Clinical pathways were most significantly changed, suggesting that gut Practice (GCP), The Affiliated Wuxi People’s Hospital of Nanjing microbiota may participate in the disease's occurrence and devel- Medical University; Lin Liu, MD - primary author, Department of opment through these pathways. Endocrinology, The Affiliated Wuxi People’s Hospital of Nanjing Discussion/Conclusion: In conclusion, this is the first report on the Medical University, Nanjing Medical University; Chao Liu, MD - gut microbiota of PCOS with high LDLC, suggesting that in the drug primary author, Department of Endocrinology, The Affiliated Wuxi development or treatment of PCOS patients, the difference of gut People’s Hospital of Nanjing Medical University, Nanjing Medical microbiota in PCOS patients with different LDLC levels should be University; Xiang Xu, MD - primary author, Department of fully considered. fi ’ Endocrinology, The Af liated Wuxi People s Hospital of Nanjing https://doi.org/10.1016/j.eprac.2021.04.753 Medical University, Nanjing Medical University; Lu Yu, MD - primary author, Department of Endocrinology, The Affiliated Wuxi ’ People s Hospital of Nanjing Medical University, Nanjing Medical Abstract #1003169 University; Qian Wang, MD - primary author, Department of Endocrinology, The Affiliated Wuxi People’s Hospital of Nanjing A case of "Autoimmune Progesterone Induced Medical University, Nanjing Medical University; Fan Xiong, MD - Dermatitis" primary author, Department of Endocrinology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Nanjing Medical University; Chengming Ni, MD - primary author, Department of Author Block: Tasnim Ahsan - Medicell Institute of Diabetes Endocrinology, The Affiliated Wuxi People’s Hospital of Nanjing Endocrinology and Metabolism; Wasfa Aijaz, FCPS (medicine) - Medical University, Nanjing Medical University; Lan Xu, MD - co- Presenter, Medicell Institute of Diabetes Endocrinology author, Department of Endocrinology, The Affiliated Wuxi People’s Metabolism; Bharta Khem, FCPS (medicine) - co-author, Medicell Hospital of Nanjing Medical University, Nanjing Medical Institute of Diabetes Endocrinology Metabolism; Paras Imran, FCPS University; Qing He, MD - co-author, Department of Good Clinical (medicine) - co-author, Medicell Institute of Diabetes Practice (GCP), The Affiliated Wuxi People’s Hospital of Nanjing Endocrinology Metabolism; Syeda F. Qasim, FCPS (medicine) - co- Medical University author, Medicell Institute of Diabetes Endocrinology Metabolism

Objective: Gut microbiota has been proved to be involved in the Introduction: A case of recurrent skin eruptions with blistering occurrence and development of many diseases, such as type 2 secondary to Autoimmune Progesterone Induced Dermatitis (AIPD) diabetes, obesity, coronary heart disease, etc. It provides a new idea Case Description: A 19-year-old single girl, with no significant for the pathogenesis of polycystic ovary syndrome (PCOS).Our medical history & no prior exogenous hormone use, presented with purpose was to collect the data of sex hormone metabolism, a 5-month history of recurrent skin eruptions with blistering at the

S135 Reproductive Endocrinology Endocrine Practice 27 (2021) S133eS140 same site & oral ulcers. She had been attending multiple der- and Medical Center; Prateek Hongal, MBBS, FEDM CDE - Co Author, matologists for this problem. The lesions were localized to Endocrinology Diabetes Medicine, Samatvam Endocrinology supraorbital region of right eye and redness at infraorbital re- Diabetes Center, Jnana Sanjeevini Diabetes Hospital and Medical gion of left eye. These skin eruptions waxed and waned for 5 Center; Reshma Harsha, MBBS, FEDM, FACE - Co Author, months, recurring on the 1st day of menstruation with reso- Endocrinology Diabetes Medicine, Samatvam Endocrinology lution after cessation of menses, eventually leaving some post- Diabetes Center, Jnana Sanjeevini Diabetes Hospital and Medical inflammatory pigmentation. She had no history of fever, alo- Center; Muralidharakrishna C. S, MBBS, FEDM, FACE - Co Author, pecia, hypersensitivity dermatitis, or symptoms of arthritis, or Endocrinology Diabetes Medicine, Samatvam Endocrinology photosensitivity. She was not using any cosmetics. She had Diabetes Center, Jnana Sanjeevini Diabetes Hospital and Medical menarche at14 and reported 28 days regular menstrual cycles. Center; Sumathi K, MBBS, FEDM, FACE - Co Author, Endocrinology Drug history was insignificant and there was no family history Diabetes Medicine, Samatvam Endocrinology Diabetes Center, of similar illness. She was vitally stable with a BMI of 15.4 kg/ Jnana Sanjeevini Diabetes Hospital and Medical Center; m2. She had post-inflammatory pigmentation on right upper Kavitha Muniraj, MBBS, FEDM, FACE - Co Author, Endocrinology eyelid and a superficial ulcer on left labial angle and right side Diabetes Medicine, Samatvam Endocrinology Diabetes Center, of tongue. Baseline investigations including complete blood Jnana Sanjeevini Diabetes Hospital and Medical Center; count, creatinine, inflammatory markers ESR & CRP, autoim- vasanthi Nath, MBBS, FEDM, FACE - Co Author, Endocrinology mune profile ANA, AMA, Anti-Ds-DNA, Anti-CCP, RA factor & all Diabetes Medicine, Samatvam Endocrinology Diabetes Center, hormonal workup including TSH, LH and FSH were normal. Jnana Sanjeevini Diabetes Hospital and Medical Center; Based on clinical history, as these lesions were synchronous Pushpa Ravikumar, MBBS, FEDM, FACE - Co Author, Endocrinology with menstruation, and physical examination, a diagnosis of Diabetes Medicine, Samatvam Endocrinology Diabetes Center, AIPD was made. She was treated with short 6 days courses of Jnana Sanjeevini Diabetes Hospital and Medical Center; steroids & antihistamines, starting with the onset of menstru- Chandraprabha siddalingappa, MBBS, FEDM, FACE - Co Author, ation. The symptoms & lesions have resolved with this treat- Endocrinology Diabetes Medicine, Samatvam Endocrinology ment protocol. Diabetes Center, Jnana Sanjeevini Diabetes Hospital and Medical Discussion: AIPD is a rare autoimmune cyclic premenstrual Center; babitha devi T, MBBS, FEDM, FACE - Co Author, hypersensitivity reaction to progesterone during the luteal Endocrinology Diabetes Medicine, Samatvam Endocrinology phase. Skin lesions develop 3-10 days before menstruation & Diabetes Center, Jnana Sanjeevini Diabetes Hospital and Medical persist up to 1-2 days after cessation of menses, & correlate Center; Sathyanarayana Srikanta, MBBS, MD, FEDM, FACE, FRCP - with serum progesterone levels. The clinical features of AIPD Co-author, Endocrinology Diabetes Medicine, Samatvam vary & thus far, about 80 cases have been reported in the Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital literature. The most common clinical manifestations were ur- and Medical Center, Endocrinology Diabetes Study Group, ticaria, angioedema & erythema multiforme. Intradermal test Endocrinology Diabetes e Co-author, Endocrinology Diabetes with progesterone can be used to confirm AIPD. It can be Medicine, Samatvam Endocrinology Diabetes Center, Jnana treated mainly by suppressing ovulation, initial therapy is Sanjeevini Diabetes Hospital and Medical Center combined oral contraceptives. To control simple cutaneous le- sions, an antihistamine combined with a systemic steroid may Introduction: Few cases of In-Vitro Fertilizationeinduced be helpful. In conclusion, it is a rare autoimmune response to Hypertriglyceridemia with secondary Acute Pancreatitis have progesterone & may present with diverse manifestations, been reported. This is a serious and life-threatening compli- resulting in a delayed/misdiagnosis. This case highlights the cation. In high-risk patients (diabetes, PCOS, obesity, dyslipi- importance of possibility of AIPD in patients with cyclical skin demia[DLP] family/personal history) DLP screening before lesions coordinated with menstruation. initiating IVF and subsequent monitoring are mandatory. Case Description: Age 28: Primary Infertility, PCOS https://doi.org/10.1016/j.eprac.2021.04.754 Age 30: HTG ( >1000), Hypercholesterolemia; Rx Statin+Fibrate. No family history of DLP, IHD or AP Abstract #1003231 Age 33 [2020 Aug]: IVF Cycle 1 [Estradiol 2 mg tid; Prednisolone 10 mg bid; Dydrogesterone 10 mg x 1 month]. Hospitalised for pain Genetic Hypertriglyceridemia [HTG], Assisted abdomen and vomiting; IV Fluids; ? AP [not documented]; ?? Reproduction e In-Vitro Fertilisation [IVF] and Acute Ovarian hyperstimulation Pancreatitis [AP] Age 33 [2020 Dec]: IVF Cycle 2 [Estradiol 2 mg tid; Prednisolone 10 mg bid; Dydrogesterone 10 mg x 1 month] 10 Dec: Statin+Fibrate stopped. Embryo Transfer done; failed Author Block: Mandyam D. Chitra, MBBS, FEDM, CDE - Primary 28 Dec: Hospitalised for severe acute epigastric pain, vomiting, Author, Endocrinology Diabetes Medicine, Samatvam ileus; S amylase 220 U/L; CT Abdomen: Acute pancreatitis; S Tri- Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital glycerides: 1707 mg/dl. Statin restarted and Medical Center; Jayalakshmi Thimmaiah, MBBS, DNB, FEDM, 2021 Jan 10: S Amylase 225 [U/L], S Triglycerides: 504 mg/dl;S CDE - Co-author, Endocrinology Diabetes Medicine, Samatvam Cholesterol: 125 mg/dl; LDLc: 44mg/dl; HDLc: 21mg/dl. FP Glucose: Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital 94. HbA1c: 6.1. TSH: 1.08. Ref Endocrinology and Medical Center; Apoorva Govind, MBBS, FEDM CDE - Co Assessment: Acute Pancreatitis due to potential multiple mech- Author, Endocrinology Diabetes Medicine, Samatvam anisms: (a) Hypertriglyceridemia, both genetic and drug [high dose Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital estrogen, glucocorticoids] induced; (b) Direct pancreatotoxic effect and Medical Center; siddhartha dinesha, MBBS, FEDM CDE - Co of drugs [Estrogen, Prednisolone] Author, Endocrinology Diabetes Medicine, Samatvam Plan: Diet Rx, lipid lowering medicines [omega 3 fatty acids/ Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital fibrates/ niacin/ statin] permanently. Possibility of “gentle” and safe

S136 Reproductive Endocrinology Endocrine Practice 27 (2021) S133eS140 ovulation induction, followed by surrogate pregnancy has been referred to genetic counseling and reproductive endocrinology recommended in literature to explore fertility options. Discussion: Drug-induced pancreatitis: Accounts for 0.1-2% of AP. Discussion: ROBT are common chromosomal defects that occur Potential mechanisms for drug-induced AP include pancreatic in 1/1000 births. ROBT carry reproductive risks that are duct constriction, cytotoxic and metabolic effects, accumulation dependent on the chromosomes involved and the sex of of a toxic metabolite or intermediary, and hypersensitivity re- the carrier. Translocation (13;14) is one of the most frequent actions; Negative effects of drugs, such as hypertriglyceridemia, form with an approximate 75% among ROBT. 45,XY,der chronic hypercalcemia, localized angioedema effect in the (13;14)(q10;q10) karyotype is a rare cause of male infertility pancreas and arteriolar thrombosis [Culprit Drug Classes Ia, Ib, II, and is associated with severe oligospermia in adults. In addi- III, IV] tion, 45,XX,der(13;14)(q10;q10) karyotype carries reproductive Clomiphene induced severe hypertriglyceridemia and pancrea- risks such as miscarriage or infertility in female adults. ROBT titis: Rarely reported in patients with baseline hypertriglyceridemia; carriers can pass translocations to the offspring. Therefore, pre- mechanism similar to tamoxifen. implantation genetic diagnosis (PGD) should be offered. In vitro Fenofibrate-induced “nonlithogenic” recurrent pancreatitis: fertilization (IVF) and intracytoplasmic sperm injection (ICSI) Single case reported with monotherapy [very few with simva- are used as fertility options for these couples. A multidisci- statin combination therapy]; mechanism unclear e related or plinary approach with reproductive endocrinology, OB-GYN, unrelated to enhanced gall stone formation. In 7 fibrate trials and geneticists is recommended and can lead to better fertility with 40162 participants conducted over 5.3 years, 144 partici- outcomes. pants developed pancreatitis (84 assigned to fibrate therapy, 60 https://doi.org/10.1016/j.eprac.2021.04.756 assigned to placebo) (RR, 1.39 [95% CI, 1.00-1.95; P ¼ .053; I2 ¼ 0%]). However, in our case, we opine that Fenofibrate was a “ ” “ ” saviour than a villain Abstract #1003803 https://doi.org/10.1016/j.eprac.2021.04.755 Case of Six Sisters: Two with Androgen Insensitivity Syndrome and Four with Primary Ovarian Insufficiency Abstract #1003543

Male Infertility Secondary To Robertsonian Author Block: Tasnim Ahsan - Medicell Institute of Diabetes Translocation e A Case Study And Literature Review Endocrinology and Metabolism; Saeeda Fouzia Qasim Consultant Physician & Fellow Endocrinology - Presenter, Jinnah Postgraduate Medical Centre Karachi, Pakistan; Paras Imran Consultant Author Block: Ali Tipu - Allegheny General Hospital; Farhad Hasan, Physician & Fellow Endocrinology - co-author, Jinnah Postgraduate MD - Co-author, Endocrinology, Allegheny Health Network Medical Centre Karachi, Pakistan; Rakshanda Jabeen Consultant Physician & Consultant Endocrinologist - co-author, Jinnah Introduction: Translocations are the most common structural Postgraduate Medical Centre Karachi, Pakistan; Wasfa Aijaz chromosomal abnormalities in the general population. Rob- Consultant Physician & Fellow Endocrinology - co-author, Jinnah ertsonian translocations (ROBT) can be associated with infertility Postgraduate Medical Centre Karachi, Pakistan and pregnancy loss. We present a case of der(13;14)(q10;q10) karyotype ROBT in a phenotypically normal adult male who Introduction: Rare case series of six sisters, with simultaneous presented with infertility and severe oligoasthenozoospermia occurrence of androgen insensitivity syndrome (AIS) in two and (OAS). Reports on the phenotype of this karyotype are rare. We premature ovarian insufficiency (POI) in four sisters. summarize the relevant literature. Case Description: Six sisters, offsprings of a non-consanguin- Case Description: 35-year-old healthy White male was referred eous marriage, presented to our endocrine clinic; five of them, to our clinic for evaluation of endocrine causes of infertility. aged 18, 22, 28, 31 & 33 years had primary amenorrhea; 6th The patient and his female partner had been trying to conceive one, 30 years old, married, had secondary amenorrhea, primary for the 2 years, and the partner’s workup had been unre- subfertility, Type II diabetes and hypothyroidism. Two had beta markable. Patient went through normal puberty around age 13- thalassemia trait. On examination all sisters had normal female 14 years. He had no history of gynecomastia, sexual dysfunc- habitus, normotensive; Tanner V breast and pubic hair. The tion, or testicular injury. He denied using recreational drugs or youngest one had prominent jaw bone and prominent Adam’s anabolic androgenic steroids. Family history was notable for apple, heavy voice and stage II clitoromegaly. The youngest mother with history of trisomy 13 and multiple miscarriages, sister had an Estradiol of 74.14pg/ml, LH and FSH of 23.40 mIU/ as well as maternal aunts with fertility problems. On physical ml and 5.38mIU/ml respectively. Testosterone (T) was raised at examination the patient was 5’9” tall, healthy appearing, viri- 1146.0 ng/dL and so was Dihydrotestosterone (DHT) at 989.6 lized male with normal hair distribution, and normal testicular pg/ml. Her AMH was >23.0 ng/ml. Another 22 years old had volume. He had no gynecomastia or eunuchoid habitus. His Estradiol of 38.6 ng/dL, LH of 23.4 mIU/ ml, FSH of 5.37 mIU/ml semen analysis showed severe OAS on two separate specimens and raised T of 394 ng/dL and low sex hormone binding (sperm count 0.2 and 0.4 x 106 per mL, respectively). Endocrine globulin of 15.31nmol/L. Her DHT level was normal at 602.31 biochemical workup was unremarkable, including normal pg/ml Karyotyping of both showed 46XY chromosomes. The testosterone, E2, FSH, prolactin, and thyroid function. Testicular other four had very low Estradiol and markedly elevated LH US was negative for obstructive pathology grossly. Chromo- and FSH, consistent with POI. Karyotyping was also done for somal analysis showed 45,XY,der(13;14)(q10;q10) karyotype, one of these four, as a prototype of the POI group, and was consistent with male ROBT carrier karyotype. Patient was 46XX. Ultrasound (USG) and MRI of pelvis in the two sisters

S137 Reproductive Endocrinology Endocrine Practice 27 (2021) S133eS140 with elevated T, showed the absence of uterus and ovaries, ng/dL) after 90 days of therapy. Mean T concentrations presence of prostate gland and testicles, located in the inguinal remained in the eugonadal range throughout Trial 2. There canals bilaterally. The four POI patients had normal USGs were no persistent clinically significant changes in liver func- except one, in whom ovaries were not visualized. Genetic tion tests e ALT (28.0 ± 12.3 to 26.6 ± 12.8 U/L), AST (21.8 ± testing could not be done due to financial constraints. 6.8 to 22.0 ± 8.2 U/L), or bilirubin (0.58 ± 0.22 to 0.52 ± 0.19 POI sisters were counselled about the necessity of long term mg/dL) during treatment. The only report of an LFT elevation hormone replacement therapy and fertility constraints. was at d270. One subject has ALT 227 U/L, > 4x the ULN (ULN Sisters with AIS were counselled for affirmation of gender for ALT ¼ 45 U/L). Despite continued use of oral TU, ALT identity in keeping with their wishes, surgical removal of testes dropped to 87 U/L on d279, < 2x ULN. There was a modest followed by estrogen replacement and future referral for initial increase in prostate-related growth endpoints (i.e., PSA vaginoplasty. and prostate volume) that stabilized over time. There were no Discussion: Based on history, examination, laboratory and significant changes in prostate function (IPSS total score: -0.06 radiological workup two sisters had complete AIS and other ± 3.9 vs BL). Modest increases in mean HCT (+2.52 ± 3.7% vs four siblings had POI. Simultaneous occurrence of POI and AIS BL, p < 0.001) and cuff systolic BP (+5.6 ± 15.0 mmHg vs BL, p in one family has not been reported so far. This is a set of ¼ 0.006). The change in prostate-related growth variables and siblings with four being normal in all respects, and two with CV endpoints changed initially and stabilized throughout the 2 very different genetic disorders of gonadal dysfunction pre- trials. For example, systolic BP consistently showed a mean senting together in the six of the same family. Case series of increase from BL between 3 e 6mmHg. AIS and POI siblings, occurring separately in different families, Discussion/Conclusion: This oral TU formulation is an effective has been reported in literature. This case series highlights the long-term therapy for hypogonadal men and has a safety importance of carefully assessing each member of a family profile consistent with other approved T products. Notably, no presenting with similar complaints, so as to not miss an evidence of liver toxicity was observed. The long-term efficacy alternative diagnosis. and safety profile of oral TU may provide a treatment option that avoids issues associated with other TRTs, such as injection https://doi.org/10.1016/j.eprac.2021.04.757 site pain or transference to partners and children.

https://doi.org/10.1016/j.eprac.2021.04.758 Abstract #1004071

Safety Analysis of an Oral Testosterone Undecanoate Abstract #1004144 (TU) Formulation Following 2 Years of Administration in Hypogonadal Men Imatinib Induced Gynecomastia- A Rare Endocrine Facet of Anti Cancer Therapy

Author Block: Ronald Swerdloff, MD - Presenter, Lundquist Institute at Harbor-UCLA; Christina Wang, MD - co-author, Author Block: Swayamsidha Mangaraj - IMS and SUM Medical Lundquist Institute at Harbor-UCLA; John K. Amory, MD - co- College and Hospital, Bhubaneswar; Priyanka Samal, MD, DM - Co author, University of Washington; Marc Gittelman, MD - co-author, author, Hematology, IMS and SUM Medical College and Hospital, UroMedix and South Florida Medical Research; B. Woun Seo, PhD - Bhubaneswar co-author, Clarus Therapeutics; Nestor Rohowsky, MA - co-author, Integrated Data Consultation Services, Inc; Robert Dudley, PhD - co-author, Clarus Therapeutics Introduction: Tyrosine kinase Inhibitors(TKI) are now commonly used in management of different cancers. Imatinib(a member of TKI family) is a commonly used drug to treat chronic myeloid leukemia Objective: An oral testosterone replacement therapy (TRT) would and gastrointestinal stromal tumors. We intend to report a rare be the preferred choice for many hypogonadal men. Until recently, endocrine side effect(gynecomastia) associated with imatinib the only oral TRT approved in the US was methyl-T which has been therapy. associated with hepatotoxicity. The safety of a novel oral T unde- Case Description: A 60 year old male presented for evaluation canoate (TU) formulation was evaluated in hypogonadal men for up of bilateral breast enlargement. He was diagnosed with chronic to 2 years. myeloid leukemia for last 8 months. The patient was taking Methods: Two open-label, multicenter, dose-titration trials were tablet Imatinib mesylate 400mg once daily as per advice of conducted in hypogonadal men (serum T 300 ng/dL) age 18- treating hematologist. He noticed gradual enlargement of 75 years. Trial I was a randomized, active-controlled, 2-arm, 12- bilateral breasts for last 3 months. There was no history of any month study. Trial 2 was a long-term extension of those who other associated medical illness or chronic drug intake apart completed Trial 1. Statistical analyses were only conducted with from Imatinib. There was no history of decreased libido. He did the subjects who completed Trial 1 and continued treatment in not smoke or consume alcohol. On evaluation, his vitals were Trial 2, thus providing up to 2 full years of data. Safety was stable. There was no goitre. On local examination, around assessed by physical exam, AE reporting, and routine clinical 3cmx3cm bilateral breast discs were palpable which were firm laboratory measurements. and slightly tender. Bilateral testes were normal in size(around Results: 81 subjects participated in both studies. Average T 20 ml) and consistency. Ultrasonography of the breasts concentrations increased from 208.3 ± 102.4 ng/dL (Mean ± confirmed presence of glandular tissue in bilateral breasts. SD)atbaseline(BL)to470.1± 396.5 ng/dL after 24 mo of oral Hepatic function tests, renal function tests, serum electrolytes TU, and 84% of men achieved T in eugonadal range (300-1000 and glycaemic parameters were within normal limits. Serum

S138 Reproductive Endocrinology Endocrine Practice 27 (2021) S133eS140 markers for human immunodeficiency virus, hepatitis B viral trials each in Turkey (n¼198) and Egypt (n¼520) and one each antigen and hepatitis virus were negative. Hormonal analysis in Italy and France. Mean number of participants being enrolled showed normal levels of thyroid hormones, luteinizing hor- is 145 (SD ± 130, maximum 400, minimum 50, range 350, 95% mone (6.2mIU/ml), follicle stimulating hormone(7.8mIU/ml), CI 8.4 to 281). Two trials enrol exclusively females (n¼198) and total testosterone(4.38ng/ml) and estradiol (28.80pg/ml). Serum one trial only evaluates males (n¼50), with highest age 80 years beta human chorionic gonadotropin titres were not detectable and longest evaluation planned for one year. Interventions (< 0.1mIU/mL). Based on above findings, a diagnosis of imati- include questionnaire-based evaluation and diagnostic work-up. nib-associated gynecomastia was made. The patient was started Established tools including IIEF-5, IPSS, SECRET questionnaire, on a brief course of tamoxifen therapy for symptomatic Male Sexual Health Questionnaire (MSHQ), FSFI (Female Sexual management. Function Index), dyspareunia scale are utilised. SARS-CoV 2 RNA Discussion: Chronic use of TKIs has been associated with many PCR evaluation in urine and semen and interleukin assessment endocrine related adverse events including thyroid dysfunction, in semen are being done. alteration in bone metabolism, alteration in glucose metabolism Discussion/Conclusion: The utilisation of validated tools across and hypogonadism. The precise mechanism through which TKI varied spectrum of participants, for evaluation for impact of causes gynecomastia is still speculative. Testicular tissue expresses contagiousness of the virus to confinement due to lockdown is a receptor tyrosine kinases c-Kit and platelet-derived growth-factor collective strength of ongoing observational studies. Varied novel receptors alpha (PDGFRa). These are believed to be involved in the approaches are being explored to understand the implications of bio-synthesis of testosterone. As Imatinib mesylate inhibits both COVID-19 on sexual health and function. c-Kit and PDGFRa, hence the production of testosterone may be https://doi.org/10.1016/j.eprac.2021.04.760 decreased during its use. Some authors have reported low testos- terone levels in such patients. However, others have reported normal testosterone along with normal/increased estradiol levels Abstract #1041967 in subjects who developed gynecomastia during chronic imatinib therapy. Our patient had normal testosterone and estradiol levels. Effects of Gender Affirming Hormone Therapy on the Knowledge about this entity among physicians caring for such Metabolic Profile and Body Composition in patients would be helpful for early identification and appropriate Transgender Individuals management. https://doi.org/10.1016/j.eprac.2021.04.759 Author Block: Hari Kiran Baratam - MS Ramaiah Medical College; Pramila Kalra Professor of Endocrinology, MD DM(Endo) FACE Abstract #1004372 MNAMS - co-author, Endocrinology, MS Ramaiah Medical College, Bengaluru, India Systematic Review and Meta-analysis of the Observational Trials Evaluating the Functional Impact of COVID-19 on Sexual Health Objective: Gender affirming therapy has been shown to have pos- itive physical and psychological effects on the transgender in- dividuals. There is paucity of data in our country about the changes Author Block: Ghufran l. Ismaeel, phd - Co Author, College of in the metabolic profile and body composition in transgender in- Pharmacy, University of Al-Ameed, Karbala, Iraq; Shashank Joshi, dividuals receiving gender affirming hormone therapy. Here we DM - Co Author, Lilavati Hospital, Mumbai, India; Abhishek Jumani, present our results of a cross-sectional study investigating the MD - Co Author, Consultant, My Best Doctor Clinic, Mumbai; same. Deepak Jumani, MD - Presenter, Senior Sexual Health Physician Methods: This study was conducted over a period of 6 months. and Counsellor, JJ Group of Govt Hospitals and Grant Medical A total of 17 transwomen and 21 transmen who came to the College and My Best Doctor Clinic, Mumbai, India Endocrinology OPD were included in the study. The in- dividuals who were on hormone therapy for more than 3 months were taken as cases, while individuals who were Objective: Natural disasters resulting in psychosocial stress and treatment naïve or received treatment for less than 3 months endocrine imbalances are implicated for impacting sexual health. were taken as controls. Body composition was assessed using We postulate COVID-19 for its longer duration and global lockdown BIA (Bioelectrical impedance analysis) using Omron HBF 375 has implications on the sexual health. Karada Scan in both cisgender (cis) and transgender (trans) Methods: We analysed contemporary protocols of six ongoing settings for each participant. The glucose tolerance, lipid trials through WHO International Clinical Trials Registry Platform profile, thyroid function, and body composition were studied and www.clinicaltrials.gov trials registry database. The latest in both groups. evaluation was done on September 27, 2020 for trials registered Results: In the transwomen group, 4 (23.5%) were cases, and 13 from April to June 2020, evaluating the impact of COVID-19 on (76.5%) were controls, while in the transmen group, 17 (80.95%) sexual health. Two researchers independently analysed the study were cases and 4 (19.05%) were controls. The relevant data designs. were compared between cases and controls within each group Results: The trials evaluate female sexual behavior, marital and using unpaired t-test. In the transwomen group, differences in sexual health problems, sexual fantasies, postpartum sexual the values of Thyroid Stimulating Hormone (TSH), Fasting Blood function, sexual function among healthcare workers, qualitative Glucose (FBG), Glycosylated Hemoglobin (HbA1c), Total and quantitative aspects for fertility, urinary function, and STD. Cholesterol (TC), Triglycerides (TG), High Density Lipoprotein Six trials are cumulatively recruiting 868 participants; with two Cholesterol (HDL-C), Low Density Lipoprotein Cholesterol (LDL-

S139 Reproductive Endocrinology Endocrine Practice 27 (2021) S133eS140

C), Very Low Density Lipoprotein Cholesterol (VLDL-C), whole normally virilized 46XY males. It is rare type of male hermaphro- body fat% (cis), whole body fat% (trans), visceral fat% (cis), ditism caused by deficiency in anti mullerian hormone or defect in visceral fat% (trans), subcutaneous fat% (cis), subcutaneous fat% its type II receptors. (trans), skeletal muscle% (cis) and skeletal muscle% (trans) were The first noted signs and symptoms in males with PMDS are not significant (p¼NS). Among the transmen, differences in the usually undescended testes (cryptorchidism) or soft out- values of TG (p¼0.004), VLDL-C (p¼0.007), TSH (p¼0.022) were pouchings in the lower abdomen (inguinal hernias). The found to be significant, though the other parameters like FBS, uterus and fallopian tubes are typically discovered when sur- HbA1c,TC,HDL-C,LDL-C,andbodycompositionwere gery is performed to treat these conditions. The testes and not(p¼NS). female reproductive organs can be located in unusual posi- Discussion/Conclusion: Gender affirming hormone therapy in tions in PMDS. Occasionally both testes are undescended transmen was observed to cause lipid abnormalities with an in- (bilateral cryptorchidism) and the uterus is in the pelvis. More crease in triglyceride and VLDL-C levels and mild elevation in TSH often, one testis has descended into the scrotum normally, and values which were significant. Hormone therapy in transwomen one has not. Sometimes, the descended testis pulls the fallo- did not cause any significant changes in terms of metabolism and pian tube and uterus into the track through which it has body composition. This study's limitation is a relatively small descended. This creates a condition called hernia uteri ingui- sample size, and further data needs to be collected and analyzed nalis, a form of inguinal hernia. In other cases, the unde- before concluding the above results. scended testis from the other side of the body is also pulled into the same track, forming an inguinal hernia. This condi- https://doi.org/10.1016/j.eprac.2021.04.761 tion, called transverse testicular ectopia, is common in people with PMDS. Other effects of PMDS may include the inability to father children Abstract #1015220 or blood in semen (hematospermia). Also the undescended testes may breakdown or degenerate or develop cancer if left untreated. Rare Case of a Young Male with Persistent Mullerian Case Description: The current study reports the clinical data Duct Syndrome and results of 19 years old male boy who was diagnosed with PMDS. The patient was presented with right iliac fossa pain. Author Block: Nazish Fatima - Dow University of health sciences He was investigated for acute appendicitis and on imaging ojha campus; Zareen Kiran, FCPS medicine, FCPS endocrine, MRCP studies he was diagnosed to have bilateral cryptorchidism UK - Co-author, National Institute of Diabetes Endocrine, DOW with rudimentary uterus. CT scan pelvis followed by pelvic University of Health sciences, Ojha campus Karachi; Khalil Sheikh, ultrasonography indicated two testes in abdomen and soft FCPS medicine, FCPS endocrine - Co-author, National Institute of tissue density structure i.e. rudimentary uterus located pos- Diabetes Endocrine, DOW University of Health sciences, Ojha terior to urinary bladder. CT scan findings were further campus Karachi confirmed by MRI pelvis. karyotyping detected 46XY chro- mosomes pattern. Laproscopic gonadectomy with removal of Introduction: Persistent mullerian duct syndrome (PMDS) af- rudimentary uterus was advised along with long term endo- fects the development of sexual organ in male. This condition crinological and reproductive survelliance for future. is inherited in an autosomal recessive pattern. Male with Discussion: PMDS is a rare genetic disorder.it is caused by PMDS have normal testes and normal external genitalia. defects in genes that encode anti mullerian hormone or its However they also have uterus and fallopian tubes. PMDS can receptor. Treatment aims to correct cryptorchidism and ensure present in one of three ways: bilateral cryptorchidism, uni- appropriate scrotal placement of testes in scrotum. lateral cryptorchidism with contralateral hernia and transverse Failing early surgical correction, gonadectomy must be testicular ectopia. offered to prevent malignancy. Malignant transformation is as Male differentiation is driven by two hormones, testosterone and likely as the presence of abdominal testes in an otherwise anti mullerian hormone (AMH), which is responsible for the normal man. regression of mullerian ducts in male fetuses. Mutations inacti- vating AMH or its receptor AMHR-II, leads to PMDS in otherwise https://doi.org/10.1016/j.eprac.2021.04.762

S140 Endocrine Practice 27 (2021) S141eS188

Contents lists available at ScienceDirect

Endocrine Practice

journal homepage: www.endocrinepractice.org

THYROID

Abstract #973571 matched controls. This issue of cognitive impairment in elderly subjects with SCH is of importance in clinical practice as SCH is Assessment of Cognitive Functions Among The Elderly more prevalent in older subjects and many of them may already Indian Subjects with Subclinical Hypothyroidism be having age related cognitive decline. Therefore the potential benefit of LT4 therapy if used with an aim of improving cogni- tive functions in this vulnerable group becomes doubtful. Author Block: Vipan Talwar, MD, FACE - Presenter or primary author, Endocrinology, Golden hospital; Gourav Talwar, https://doi.org/10.1016/j.eprac.2021.04.765 Department of Endocrinology - co-author, Golden hospital

Abstract #974205 Objective: The consequences of overt hypothyroidism on CNS are well known. In contrast, there is less evidence regarding the Secondary Hypothyroidism Following Recovery from effects of subclinical hypothyroidism (SCH) on cognitive func- Graves’ Disease: A Rare Case Report tions particularly in the elderly subjects. Studies from various countries including India have shown a variable association be- tween SCH and cognitive dysfunction. This study was done with Author Block: Yakubu Lawal - Federal Medical Center Azare, an aim to assess the prevalence of cognitive impairment among Bauchi State; Ibrahim Abdullahi, MBBS, FMCP - co-author, Internal elderly Indian subjects (Age >60 years) with subclinical Medicine, Federal Medical Center Azare; Umar Dahuwa, MBBS, hypothyroidism. FWACP - co-author, Internal Medicine, Federal Medical Center Methods: The participants were 125 elderly subjects (age >60) Azare with SCH and similar number of age matched euthyroid con- trols. Subclinical hypothyroidism was defined as serum TSH level Introduction: This is the case report of a 39-year old lady who more than 4.0 mIU/L with normal FT3 and FT4. Participants presented with clinical and laboratory features of secondary hy- were interviewed by a single observer. Cognitive function was pothyroidism two (2) years after achieving clinical and biochemical assessed by Mini Mental State Examination (MMSE) and clock euthyroid state and cessation of carbimazole used to treat Graves' drawing test (CDT). MMSE has maximum score of 30 and scores disease. 24 are indicative of cognitive impairment. For CDT a score of Though there were previous reports of primary hypothyroidism 3 represents a cognitive deficit, while a score of 1 or 2 is several years following treatment and recovery from Graves' dis- considered normal. Data was analysed by using SPSS and p value ease, we have not encountered reports of secondary hypothyroid- of < 0.05 was significant. ism following recovery from Graves' disease. Results: The mean age of patient group was 67.4 years, and BMI Case Description: Clinical features include excessive weight gain, 26.1kg/m2 which were comparable to controls who had a mean age cold intolerance, dry coarse skin, constipation, menorrhagia, of 68.1 years (p-0.16) and mean BMI 25.9 kg/m2 (p-0.25) . All other recurrence of exophthalmos. baseline variables including sex ratio, co-morbidities, family history Thyroid function test showed: T3¼1.33ng/ml (0.8-1.7ng/ml), of dementia, smoking, alcohol use, education and exercise were T4¼2.92ug/dl (4.5-12.0ug/dl), TSH¼0.2mIU/ml (0.5-5.0mIU/ml). also comparable in both the groups. The mean TSH was 7.8 in pa- Brain imaging was normal. tient group and 2.7 in control group (p-< 0.05).The mean MMSE Thyroid-related autoantibodies could not be assayed due to score was 26.3 in patient group and 27.6 in controls (p-0.34) The financial constraints. However, pointers to the autoimmune nature patients had mean CDT of 2.32 and controls 2.42 (p-0.68). Cognitive of the hypothyroidism include the recurrence of exophthalmos, impairment by MMSE (score 24 ) was found in 28.3% of patients relative lymphocytosis, and moderate elevation of erythrocyte and in 26.54% of controls (p-0.64), also the cognitive impairment by sedimentation rate (ESR). CDT (score of 3) was present in 31.2% of patients and 29.9% of Patient was treated with levothyroxine and low dose steroid. At controls (p-0.49). sixth month follow up, there was resolution of hypothyroidism Discussion/Conclusion: Hypothyroidism is known to cause features, recession of exophthalmos, normalization of TFT, hema- decline in cognitive functions. Studies have addressed the as- tological indices, and ESR. sociation of cognitive impairment with subclinical hypothyroid- Discussion: It becomes imperative to report this case to alert cli- ism with variable results specially in elderly subjects. In the nicians to the possibility of autoimmune disease of the hypothal- present study we have found that the prevalence of cognitive amus-pituitary axis coexisting with or occurring following recovery impairment in elderly subjects with SCH is similar to the age from Graves' disease.

1530-891X Thyroid Endocrine Practice 27 (2021) S141eS188

And to highlight the maximal use of clinical acumen and limited Medicine-Jacksonville; Russell Fung, MD - co-author, laboratory resources to diagnose and treat endocrine patients in Endocrinology, UF College of Medicine-Jacksonville resource-constraint setting. Introduction: The Ewing Sarcoma family (ESF) includes many types https://doi.org/10.1016/j.eprac.2021.04.766 including bone-specific tumors, extraosseous, and Askin’s tumors. Approximately 5% of Ewing Sarcomas (ES) involve the head and Abstract #976662 neck. Sarcomas are less than 1% of thyroid cancer cases. ES is sus- pected when sheets or nests of cells are seen on microscopy. To our Sociodemographic Disparities in the Treatment of knowledge, there are only 8 cases of primary ES of the thyroid Hypothyroidism: NHANES 2007-2012 described in literature. We present a case of primary Ada- mantinoma-like Ewing Sarcoma of the thyroid gland. Case Description: Patient is a 60-year-old male who presented with Author Block: Matthew Ettleson - University of Chicago; an 8-week history of a painless neck lump with occasional neck Antonio C. Bianco, M.D., Ph.D. - co-author, University of Chicago; fullness. Physical exam was significant for left sided large thyroid Neda Laiteerapong, M.D., M.S. - co-author, University of Chicago; nodule. There was no tenderness to palpation of the nodule or Mengqi Zhu, M.S. - co-author, University of Chicago bruits on auscultation of the thyroid gland. Thyroid ultrasound revealed a 7.2x3.3x6.0 cm heterogeneous, hypoechoic nodule with Objective: Both undertreatment and overtreatment of hypothyroid- increased vascularity. Fine needle aspiration revealed atypia of ism with thyroid hormone are associated with adverse clinical out- undetermined significance, categorized as Bethesda III. Patient comes. Disparities in the treatment of hypothyroidism may lead to a underwent a left thyroid lobectomy. Pathology report showed higher risk of adverse outcomes for certain sociodemographic groups. Adamantinoma-like Ewing Sarcoma, limited to the thyroid lobe The objectives of this study were to identify sociodemographic dis- without any lymphovascular invasion or extrathyroidal extension. parities between those with treated and untreated hypothyroidism, Microscopically, the neoplasm consisted of small blue round cells, and to identify sociodemographic disparities between those on organized in sheets and cords. The neoplastic cells had increased treatment who are adequately and inadequately treated. Ki-67 proliferation index. The cells were sparsely positive for Methods: This is a cross-sectional study of the National Health and epithelial markers cytokeratin AE1/AE3, CK8/18, and MOC 31. Nutrition Examination Survey (NHANES) database from years Markers for thyroid origin like TTF-1, thyroglobulin and PAX-8 were 2007-2012. The study population was a representative sample of negative. The tumor was diffusely positive for CD99. Molecular US non-pregnant adults aged 20 years and older with hypothy- pathology report identified EWSR1-FLI1translocation. Patient un- roidism (n ¼ 698). The primary outcome measures were gender, derwent a right thyroid lobectomy. Pathology showed nodular age, race/ethnicity, education, income and healthcare access dif- hyperplasia, without evidence of malignancy. CT chest, abdomen, ferences among those with treated hypothyroidism and untreated and pelvis with contrast showed post-surgical changes in the thy- hypothyroidism. roid bed, but no evidence of metastasis. PET scan showed hyper- Results: Of those with hypothyroidism, women were more likely metabolic foci in the thyroid bed, likely post-surgical changes given than men to be taking thyroid hormone (OR 2.66 [95% CI 1.42 e no correlates on CT. Patient was assessed by radiation oncologist 499]), as were older participants (45 - 69 years old vs. 20 e 44 years and radiotherapy was deemed unnecessary. Patient was evaluated old: OR 7.25 [95% CI 4.15 e 12.67]; 70 years of age and older: OR by medical oncologist but chemotherapy was not started due to 11.00 [95% CI 5.30 e 22.79]). Healthcare access was strongly asso- indolent course of disease, but yearly PET scan was recommended. ciated with thyroid hormone use (OR 14.32 [95% CI 3.63 e 56.58]). Discussion: Ewing sarcoma tumors are a group of small-, round- When those with untreated subclinical hypothyroidism (defined as celled tumors, with different degrees of neuroectodermal differ- thyroid-stimulating hormone level < 10 mIU/L, free thyroxine level entiation. Majority of patients with ES, including our patient, have a within normal limits) were excluded from the analysis, female t(11,22)(q24;q12) translocation, producing a protein that is thought gender was no longer a predictor of thyroid hormone use (OR 1.17 to be an aberrant transcription factor. CD99 marker was positive in [95% CI 0.35 e 3.84]). Amongst those on treatment, Hispanic race/ all cases of ES involving the thyroid gland, making it an important ethnicity was associated with inadequate treatment compared to marker for diagnostic confirmation. Diagnosing thyroid ES can be non-Hispanic whites (OR 2.42 [95% CI 1.14 e 5.14]). challenging as it may present like other more common thyroid Discussion/Conclusion: Male gender, younger age, and lack of malignancies. FNA did not obtain correct diagnosis in any reported healthcare access were associated with untreated hypothyroidism, cases. Due to scarcity of cases, no guidelines exist for treatment of and Hispanic race was associated with inadequate treatment of hy- primary thyroid ES. NCCN guidelines recommend neoadjuvant pothyroidism. Clinicians should be aware of these sociodemographic multiagent chemotherapy prior to local therapy, but lack of disparities in the hypothyroid population, and consider strategies to confirmed diagnosis prior to surgical treatment in thyroid cases is a improve the quality of treatment of hypothyroidism in men, younger barrier to neoadjuvant therapy. Lymph node dissection is recom- adults, Hispanics, and those that lack routine healthcare access. mended and frequent imaging is needed for monitoring. https://doi.org/10.1016/j.eprac.2021.04.767 https://doi.org/10.1016/j.eprac.2021.04.768

Abstract #977910 Abstract #977955

Primary Ewing Sarcoma of the Thyroid Presenting as a Lenvatinib use Associated with Multi-organ Adverse Neck Mass Events in Hurthle Cell Thyroid Cancer

Author Block: Firas Warda - UF College of Medicine-Jacksonville; Author Block: Muhammad Butt - King Faisal Specialist Hospital; Joe Chehade, M - co-author, Endocrinology, UF College of Abdulmohsen M. Bakhsh, MD - co-author, King Faisal Specialist

S142 Thyroid Endocrine Practice 27 (2021) S141eS188

Hospital & Research Centre; Quaid J. Nadri, MD - co-author, King dysuria or neck pain and stiffness. Patient denied recent viral illness Faisal Specialist Hospital & Research Centre and/or taking iodine containing medications, supplements or recent iodine contrast studies. Past medical history unremarkable. Introduction: The management of metastatic progressive radio- On physical examination patient appeared acutely ill, was febrile iodine-resistant differentiated thyroid cancer has remained a with temperature of 103.4F; blood pressure of 143/85 mm Hg; challenge for clinicians. The availability of tyrosine kinase inhibitors heart rate of 129 beats/min. Physical exam of note for mildly tender (TKIs) within the last decade has expanded the treatment options, thyroid gland of 35 gms. Lab data noted for ESR 118 mm/hr (0-20) but these come with significant adverse effects that may curtail and CRP 43.1mg/L (< 3.0), TSH 0.005mIU/mL (0.35-5.50), Free T4 their use. 2.93 ng/dL (0.90-1.70) and T3 of 81.20 mg/dL (84-202). All anti- Case Description: We report a 47-year-old female with Hurthle cell bodies including TSI were negative. ER non-contrast CT scan of the thyroid cancer who was treated with total thyroidectomy followed chest did not reveal any parapharyngeal abscess. Thyroid US by radioactive iodine ablation. During the follow-up period, she showed heterogeneous thyroid gland with increased vascularity of developed metastases in the lungs and kidney. These metastases the peripheral area of the gland. Thyroid scan showed 1% uptake at were non-iodine avid and FDG avid. In the context of pre-existing 24 hours (10-25%), consistent with thyroiditis. Patient continued to diabetes, hypertension and significant polycystic kidney disease, spike fever up to 105F. The work up did not revealed infectious the tumor board decided against the surgical treatment of renal etiology or malignancy. Blood cultures and urine cultures remained metastasis as it carried a significant risk of future renal decline without growth. Based on clinical presentation, lab tests and im- requiring renal replacement therapy. aging studies patient was diagnosed with subacute thyroiditis with We used a TKI (Sorafenib, Bayer Pharmaceuticals, Germany) for high suspicion for thyroid storm, scoring 55 points on Wartofsky the treatment of metastatic disease, which provided initial stability scale. At this point treatment with NSAIDs was initiated. The followed by a progression of the disease within a year. We switched symptoms improved in the next 48 hours and steroid therapy was to Lenvatinib (Eisai Co. Ltd., Tokyo Japan), which provided disease considered but not given. In the following few days the fever control followed by regression of the disease. However, the patient completely resolved. Vitals normalized and diarrheal episodes experienced severe adverse effects including cardiomyopathy, bi- ceased while ESR and CRP improved. NSAIDs were tapered down cytopenia, renal impairment, and rarely reported nephrotic and eventually stopped. One month after discharge labs revealed a syndrome. TSH of 20 mIU/mL and free T4 of 0.53 ng/dL, consistent with the Metastasis to the kidney is a rare manifestation of Hurthle cell hypothyroid phase of subacute thyroiditis. Thyroxine was initiated thyroid cancer with two reported cases. We share the first case and at one year follow up patient was still in need of thyroxine experience of its treatment with Sorafenib followed by Lenvatinib. replacement, suggestive of permanent hypothyroidism. This case serves a reminder of the adverse drug reactions associated Discussion: Subacute thyroiditis is a disorder that usually causes with the use of TKIs. mild to moderate self-limited hyperthyroidism. However, in very Discussion: This unique case study presents widespread metasta- rare cases this disorder can present with thyroid storm. The ses despite a low-risk pathology, prolonged overall survival absence of clinical signs and symptoms of thyrotoxicosis can approaching two decades despite the non-iodine avid distant me- obscure the diagnosis and lead to treatment delays. Misdiagnosis tastases, and a confluence of multi-organ adverse events with the can lead to unnecessary investigations and can delay otherwise use of Lenvatinib. We advocate close follow-up examination of straightforward treatment of this condition. patients treated with Lenvatinib, which includes monitoring their https://doi.org/10.1016/j.eprac.2021.04.770 haematological and renal profile and using an echocardiogram to access their cardiac status. https://doi.org/10.1016/j.eprac.2021.04.769 Abstract #991725

Lack of Pathology Data as a Source of Misclassification of Abstract #990240 Thyroid Microcarcinoma Risk: An Algerian Observation

Subacute Thyroiditis Masquerading as Thyroid Storm Author Block: Nadjib Kaouache - University hospital of Constantine; Nassim Azzouz, MD - Co author, Endocrinology Author Block: Todor Zlatanski - Coney Island Hospital; Department, University hospital of Constantine, University of Silvia Bercovici, MD, FACE - co-author, Coney Island Hospital Constantine 3 Faculty of Medicine, Algeria; Ryma Boulefkhad, MD - co author, Endocrinology Department, University hospital of Introduction: Subacute thyroiditis is a self-limited inflammatory Constantine, University of Constantine 3 Faculty of Medicine, thyroid disease that usually follows a viral URI and is characterized Algeria; Mohammed Chaib, MD - co author, Endocrinology by neck pain and constitutional symptoms such as fatigue, malaise Department, University hospital of Constantine, University of and fever. Patient may also present with mild transient thyrotoxi- Constantine 3 Faculty of Medicine, Algeria; Soumia Grari, MD - co cosis. Thyroid storm on the other hand is a life-threatening con- author, Endocrinology Department, University hospital of dition, manifested by severe thyrotoxicosis and associated with Constantine, University of Constantine 3 Faculty of Medicine, substantial morbidity and mortality. Although subacute thyroiditis Algeria; Chahinaz Habi, MD - co author, Endocrinology can only cause mild to moderate hyperthyroidism, rare cases of Department, University hospital of Constantine, University of simultaneous thyroid storm have been reported. Constantine 3 Faculty of Medicine, Algeria; Alkassem Lezzar, MD - Case Description: A 63-year-old Caucasian male presents to ER Co author, Endocrinology Department, University hospital of with intermittent fever of 101F for 3 weeks, associated with profuse Constantine, University of Constantine 3 Faculty of Medicine, night sweats, tiredness and malaise and fever of 103F on the day of Algeria; Sami Menaceur, MD - co author, Endocrinology presentation. Review of systems is significant for headache, diar- Department, University hospital of Constantine, University of rhea and 10 lbs. weight loss but no upper respiratory symptoms, Constantine 3 Faculty of Medicine, Algeria; Samira Merabet,

S143 Thyroid Endocrine Practice 27 (2021) S141eS188

MD - Co author, Endocrinology Department, University hospital of Results: Sixty-three patients met inclusion criteria between 2007 Constantine, University of Constantine 3 Faculty of Medicine, and 2018. Among these, 25 patients underwent OCC total thy- Algeria; Nassim nouri, MD - co author, Endocrinology Department, roidectomies and 9 received RAI treatments OCC. Tracking the University hospital of Constantine, University of Constantine 3 composite outcome of OCC total thyroidectomy or RAI, cumulative Faculty of Medicine, Algeria; Bilal Zouraghen, MD - co author, sum revealed an inflection point corresponding to overall Endocrinology Department, University hospital of Constantine, improvement from June 2015 onward. Rates of OCC total thyroid- University of Constantine 3 Faculty of Medicine, Algeria ectomy (23.5% vs 50%, p ¼ 0.018) and RAI (9.5% vs 16.7%, p ¼ 0.445) decreased by roughly half in the recent era. There were no Objective: Thyroid cancer prevalence especially microcarcinoma locoregional recurrences in either time period. The average cost has increased significantly in recent years, including in Algeria. Risk savings attributable to these institutional practice changes was stratification based on pathology and clinical characteristics is the $1,381 per patient. cornerstone for clinical decision. We aim to describe pathology Discussion/Conclusion: This study captured real-world practice characteristics and difficulties of risk stratification of thyroid changes reflective of evolving consensus guidelines in thyroid microcarcinoma in a series from eastern Algeria. cancer. Improvement in surgery and RAI stewardship leads to cost Methods: A descriptive retrospective study including patients fol- containment without sacrificing locoregional control. lowed and monitored in the thyroid cancer register in the endo- https://doi.org/10.1016/j.eprac.2021.04.772 crinology department of Constantine University Hospital during the period between January 2015 and December 2018. Results: Of 70 cases of thyroid microcarcinomas, mean age was 44 Abstract #994791 years [17-84 years] and 94% were women. 94% of the cases were papillary micro carcinomas. Moltifocality and bilaterality were re- An Unusual Presentation of Amiodarone-Induced ported in 27% and 5.71% of cases respectively. Average size was Thyroid Hormone Dysregulation 6.17mm and 55% of whom had a size < 5 mm. concerning lymph node invasion, 12% were N1, distant metastases were reported in two patients. On pathology report, the presence of vascular inva- Author Block: Joseph Hsiao - UCLA; Shalini Bhat, MD - co-author, sion and their number were not documented in 58% and 42% of Endocrinology, Division of Endocrinology, Diabetes and patients, while the invasion of the thyroid capsule was not was not Hypertension, Department of Medicine, David Geffen School of noted in 42% of patients. 28% were not classified due to insufficient Medicine at UCLA and VA Greater Los Angeles Healthcare System; data. Anna Milanesi, MD - co-author, Endocrinology, Division of Discussion/Conclusion: Better collaboration between pathologist Endocrinology, Diabetes and Hypertension, Department of and clinician could improve thyroid microcarcinoma management. Medicine, David Geffen School of Medicine at UCLA and VA Greater https://doi.org/10.1016/j.eprac.2021.04.771 Los Angeles Healthcare System

Introduction: Amiodarone is a common antiarrhythmic with both Abstract #992010 inhibitory and stimulatory effects on the thyroid. This duality is attributable to inhibition of T4 to T3 conversion, direct toxicity to Practice Patterns and Cost Implications of Surgery and follicular cells, suppression of gene expression, and Iodine loading. Radioactive Iodine for Papillary Thyroid Carcinoma Depending on the underlying thyroid background, hyperthyroid- ism or hypothyroidism may result. Amiodarone-Induced Thyro- toxicosis (AIT) is classically delineated into two types based on Author Block: Christina Paluskievicz, MD - Presenter, University of inflammatory (AIT2) vs stimulatory predominance (AIT1). Howev- Maryland Medical Center; Jessica Wimbush, BA - Co-author, er, these distinctions can often become difficult to elucidate. We University of Maryland Medical Center; Kashif M. Munir, MD - Co- present a case of thyroid hormone disruption due to Amiodarone author, Endocrinology, University of Maryland Medical Center; that does not fit into the usual pathological designations. Douglas J. Turner, MD - Co-author, Surgery, University of Maryland Case Description: A 69-year-old male with atrial fibrillation on Medical Center; John A. Olson, Jr., MD, PhD - Co-author, Surgery, chronic Amiodarone was admitted for heart failure. He did not University of Maryland Medical Center; Yinin Hu, MD - primary endorse any hyperthyroid symptoms. Labs 2 years prior showed author, Surgery, University of Maryland Medical Center TSH of 2.7 mIU/L (nl 0.6-4.8). He then started Amiodarone and 3- month interval labs showed TSH 3.9 mIU/L, fT4 3.1 ng/dL (nl 0.7- Objective: The American Thyroid Association (ATA) provided 1.7), TT3 97 ng/dL (nl 60-181 ng/dL). These remained stable on guidelines in 2015 for radioactive iodine (RAI) and extent of subsequent checks without intervention. On this admission, labs resection for low-risk papillary thyroid cancer. The objective of this showed TSH 0.05, fT4 5.9, TT3 88, TPO ab < 15, TSI 206. His thyroid study was to describe the evolution of institutional practice pat- ultrasound was unremarkable. He was started on Prednisone for terns over time and estimate the cost implications of these trends. presumed AIT2. Two weeks post discharge, labs showed TSH 1, fT4 Methods: Patients with T1-T2N0 papillary thyroid cancer were 2.3, TT3 39.4. Steroids were then tapered off. One month later, labs identified via institutional tumor registry. Based on 2015 ATA showed TSH 5.6, fT4 2, TT3 58. guidelines, accepted criteria for total thyroidectomy with or Discussion: This case exemplifies the impact of Amiodarone on without RAI were defined as margin positivity, vascular invasion, thyroid physiology. Initially, inhibition of T4 to T3 conversion or multifocality. Incidences of total thyroidectomy or RAI per- resulted in elevated fT4 and relatively low TT3, causing a formed outside of consensus criteria (OCC) were tracked longi- compensatory rise in TSH from lack of fT3 feedback on the pituitary. tudinally using cumulative sum. Excess costs per patient related On hospital presentation, this pattern persisted as fT4 was very to OCC total thyroidectomy or RAI were estimated using national high, but TT3 remained in the low-normal range and TSH was only Medicare reimbursement rates and National Inpatient Sample mildly suppressed. The TSH decrease may have been due to a cost data. concurrent nonthyroidal-illness and was not consistent with the

S144 Thyroid Endocrine Practice 27 (2021) S141eS188 very elevated fT4. The low-normal TT3 was less consistent with week 36. Patient had vaginal delivery of viable female infant that AIT1 despite elevated TSI. This patient’s fT4 elevation was driven weighed 2.49 kg. Infant had no signs or symptoms of hyperthy- primarily by inhibition of fT4 to fT3 conversion, which preserved roidism but her labs were consistent with hyperthyroid state. low-normal TT3 and maintained a relatively euthyroid state. His fT4 Patient was discharged on methimazole 30 mg daily and meto- reduction during steroid therapy can be secondary to known effects prolol succinate 75 mg daily in a stable condition. of corticosteroid-induced TSH reduction. Outpatient labs off corti- Discussion: Graves’ disease accounts for 85% of hyperthyroid cases costeroids show return to his previous pattern of mildly elevated during pregnancy. Oligohydramnios is a well-established compli- TSH and fT4 with low-normal TT3.This is an important case to cation and can be detrimental on fetal health. TSI can cross the remind physicians that sometimes, abnormal TFTs in the setting of placenta and stimulate fetal thyroid tissue, leading to fetal hyper- Amiodarone therapy do not require pharmacological intervention, thyroidism. TSI titers that are 2-3 times the upper limit of normal and thus we can avoid unnecessary treatment by recognizing these correlate with higher chance of fetal thyroid dysfunction regardless patterns. of the mother’s treatment status. It is essential to ensure maternal and fetal euthyroidism using antithyroid medications and beta https://doi.org/10.1016/j.eprac.2021.04.773 blockers as those agents will cross the placenta and aid in clinical improvement.

Abstract #995684 https://doi.org/10.1016/j.eprac.2021.04.774

Oligohydramnios Complicating Pregnancy in a Patient with Uncontrolled Hyperthyroidism Abstract #995915

Active Versus Inactive Thyroid Eye Disease: Symptom Author Block: Firas Warda - UF College of Medicine-Jacksonville; and Quality of Life Comparison in US Patients Madeline Fasen, DO - co-author, UF Health Jacksonville College of Medicine; Ailyn Rivero, MD - co-author, UF Health Jacksonville College of Medicine; Leena Shahla, MD - Faculty mentor, UF Health Author Block: Yao Wang, MD - primary author, Cedars Sinai Jacksonville College of Medicine Medical Center; Lissa Padnick-Silver, PhD - Presenter, Horizon Therapeutics plc; Megan Francis-Sedlak, PhD - co-author, Horizon Introduction: Clinical management of Grave’s disease (GD) is Therapeutics plc; Robert J. Holt, PharmD, MBA - co-author, Horizon challenged by the physiological changes in pregnancy. Patients Therapeutics plc; Colleen Foley, MS - co-author, Horizon with thyrotoxicosis are typically advised to continue medications in Therapeutics plc; Raymond S. Douglas, MD, PhD - co-author, order to prevent effects on mother and fetus. Poor control of GD is Cedars Sinai Medical Center associated with pregnancy loss, premature labor, low birth weight, stillbirth, oligohydramnios and maternal congestive heart failure. Objective: To examine and compare clinical characteristics and Excessive maternal thyroid hormone transmission to the fetus can physician-reported quality of life (QOL) of US patients with active cause seizure and neurobehavioral disorders. The presented case and inactive moderate-to-severe thyroid eye disease (TED). describes the uncommon development of thyroid storm and oli- Methods: Physicians provided clinical data on patients with mod- gohydramnios complicating pregnancy after self-cessation of erate-to-severe TED via online survey in late 2018 (prior to the therapy. approval of teprotumumab). Clinical activity score (CAS) was Case Description: A 36-year-old G2P1, 35W2D pregnant female calculated for each patient using 6 of 7 available CAS measures with history of asthma and Graves’ disease diagnosed in 2015, (caruncle status not noted) and patients were categorized as having who presented with worsening shortness of breath for 3 days active (CAS 3) or inactive (CAS ¼ 0 or 1) disease. Physicians also despite albuterol use, associated with heart racing and anxiety. rated the impact TED had on patient QOL on a 7-point scale (1 ¼ She denied any recent illness and reported no pregnancy-related “not at all impacted”,7¼ “extremely impacted”). In patients with complications. She was prescribed methimazole 3 months prior inactive TED, the effect of disease duration on TED signs/symptoms to presentation but only took one dose. Physical exam showed an and QOL were also examined. acutely distressed female with tachypnea, tachycardia, bibasilar Results: 307 patients had active TED and 281 patients had crackles, gravid uterus, and moderate lower extremity pitting inactive TED. Groups were comparable in age (active: 50.0±13.3 edema bilaterally. Labs were significant for thyroid stimulating years, inactive: 48.3±13.8 years), gender (65.8% female, 64.4% hormone (TSH) of < 0.005 mIU/L, free T4 of 5.2 ng/dL, free T3 of female), TED duration (4.0±4.9 years, 4.6±5.5 years), and smok- 22.3 pg/mL, thyroid stimulating immunoglobulin (TSI) of 73.3 IU/ ing status (current smoker: 14.7%, 11.0%), but the active group L, and thyroid peroxidase antibody (TPO) of >600 IU/mL. Chest X- had more severe TED patients (24.8% vs. 5.0%). Active patients Ray showed mild interstitial opacities and left small pleural most commonly had ocular dryness/grittiness (91.9%), soft tissue effusion. Transthoracic echocardiography showed mild global swelling (91.9%), conjunctival redness (89.6%), eyelid redness hypokinesis and ejection fraction of 40%. Patient was admitted to (79.5%), proptosis (78.2%), and excessive tearing (71.7%). medical intensive care unit for management of thyroid storm, Decreased vision was reported in 62.9% of patients, with diplopia where she was started on methimazole 20 mg twice daily, in 42.0%. Anxiety and/or depression was reported in 38% of metoprolol tartrate 12.5 mg twice daily, and hydrocortisone 50 active patients and overall QOL impact averaged 4.7±1.4. All TED mg every 8 hours. Fetal monitoring was implemented by the signs/symptoms occurred less often in the inactive group, but obstetric team, revealing no concerning decelerations. Abdominal ocular dryness/grittiness (77.2%) and proptosis (55.5%) were also ultrasound revealed oligohydramnios with amniotic fluid index highly reported. Decreased vision was reported in 23.8% of pa- (AFI) of 2.9. Patient’s condition continued to improve with near tients, with diplopia in 14.2%. Despite fewer TED signs/symptoms resolution of tachycardia on day 4 of hospitalization, resolution of in inactive patients, anxiety and/or depression prevalence (36%) fluid overload, and improvement in mood. Given patient’s ultra- and overall QOL impact (3.6±1.5) remained high, similar to active sound findings, delivery was recommended at the beginning of patients.

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Discussion/Conclusion: Ocular signs and symptoms of TED often Abstract #996608 persist in inactive disease, particularly proptosis and ocular dry- ness/grittiness. QOL and mental health were markedly impacted by Rapidly Enlarging Neck Mass Progressing to Acute both active and inactive TED. US patients with inactive TED Respiratory Failure and Death: A Case of Anaplastic continue to have symptoms of the disease after inflammation Thyroid Carcinoma subsides with mental health and QOL impact similar to those with active disease. Author Block: https://doi.org/10.1016/j.eprac.2021.04.775 Angela Richter - University of Florida-Jacksonville; Gunjan Gandhi, M.D., M.Sc. - Co-author, Endocrinology, Department of Medicine, University of Florida Abstract #996582 Introduction: Anaplastic thyroid carcinoma (ATC) is rare Computer-Assisted Interpretation of Thyroid Function (1-2% of thyroid malignancies) with a survival rate of only Test (TFT) Result Patterns 10-20% at 12 months. Distant metastasis is seen at diagnosis in 50%, primarily to the lung, adrenals, liver, bone, and brain. Author Block: Robert Dons - Lawndale Christian Health Center, Case Description: A 59-year-old male with hypertension and a Chicago, IL; Roger A. Piepenbrink, DO - coauthor, Nevada Utah 40-pack-year smoking history presented to the emergency Endocrinology Consultant, American Red Cross room (ER) with a 1 week history of neck pain, dysphagia, hoarseness, respiratory stridor and hemoptysis. Computed to- Objective: Appropriate interpretations of thyrotropin (TSH) and mography (CT) neck showed a 6.4cm necrotic mass encom- free thyroxine (FT4) test data (TFT) can be complex. Making avail- passing the left thyroid lobe and isthmus, invading into the able interpretative descriptions of TFT available relative to their left tracheoesophageal groove and superior mediastinum, reference interval patterns via a computerized data base may causing marked right lateral tracheal deviation. CT chest decrease this complexity and facilitate a more complete and ac- without contrast showed innumerable pulmonary nodules, a curate assessment of thyroid status. 4.8cm right adrenal mass with irregular borders (suspected Methods: Descriptive texts that interpret or might explain the 9 TFT metastasis), and bulky necrotic cervical lymphadenopathy data patterns were interactively grouped under 18 clinical sub- invading the left internal jugular vein. Of note, 19 months types. Nine subtypes encompassing effects of congenital, common, prior the patient had CT chest showing a 4.3cm left thyroid or rare metabolic thyroid disorders, brain, pituitary or adrenal nodule, but the patient was lost to follow up. One month prior surgery, inflammation, ischemia or trauma, thyroid hormone to admission he finally had a thyroid ultrasound revealing a binding protein abnormalities, critical non-thyroidal illness and 3.5cmleftlobenoduleanda1.6cmisthmusnodule.IntheER, aging, autoimmune, neoplastic, psychiatric, nutritional, and his symptoms improved minimally with racemic epinephrine, gastrointestinal disorders, as well as testing artifacts and appar- IV dexamethasone, and CPAP; he had emergent cricothyrotomy ently normative data, were identified independent of drugs or after he became unresponsive with respiratory failure. Pa- medication. Nine subtypes encompassing effects of drugs or med- thology from FNA of the thyroid mass at the time of crico- ications were identified including those containing T4, triiodothy- thyrotomy indicated undifferentiated ATC (cells were ronine, iodine, or radioiodine, as well as those affecting the immunoreactive for PAX-8 and CK5/6; negative for TTF-1 and gastrointestinal absorption of T4, thyroid hormone binding pro- thyroglobulin); BRAF V600E mutation was identified. CT teins, the metabolism, secretion, or assay of TSH and T4, individu- abdomen 1 week into admission showed the right adrenal ally or both together. mass was 7.5cm, mixed density from interval hemorrhage. A Results: Alphanumeric coding of 60 interpretive texts of TFT test subsequent core biopsy of the thyroid mass had the same results independent of the 55 texts related drug or medication cytology stain and tumor markers as the FNA, consistent therapy effects was done in a structured manner in preparation for with ATC with squamous differentiation. Patient remained retrieval by electronic health record programs and handheld de- ventilated with tracheostomy for 3 weeks, was given 1 vices. Cases which illustrate the use of the interactive data base in cycle of external beam radiation therapy (RT), but developed diagnosis of thyroid status in context of Sheehan’s versus advanced septic shock and tumor lysis syndrome. Given his rapid aging, altered circadian versus diurnal rhythms, thyrotropinoma clinical decompensation, he was a poor candidate for further versus thyrotrope hyperplasia, tyrosine kinase versus checkpoint surgery, RT, or chemotherapy, and expired on admission day inhibitor therapy, and biotin versus alemtuzumab therapy on TFT 30. are to be presented. Discussion: Differential diagnoses for clinicians to consider for a Discussion/Conclusion: Study of the behaviors of clinicians with a rapidly enlarging thyroid mass include ATC, poorly differentiated wide spectrum of experience in thyroid disease management is thyroid carcinoma, thyroid lymphoma or sarcoma, metastasis to the required to determine if better differential diagnoses and man- thyroid, and abscess. Even with timely diagnosis and treatment agement of a patient’s thyroid status results when an interactive (surgical resection, RT, and/or chemotherapy) of ATC, the majority computer-based, information retrieval program with a full range of survive to merely 6 months. More recently, mutation-specific TFT data interpretations is utilized. While the interpretive data base chemotherapy has yielded more promising results, some targeting devised cannot replace clinical judgement, it will assist in making a the BRAF V600E mutation. Unfortunately, many patients do not more complete assessment of a patient's thyroid status based on have access to adequate health care, rendering them a poor TFT data. prognosis. https://doi.org/10.1016/j.eprac.2021.04.776 https://doi.org/10.1016/j.eprac.2021.04.777

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Abstract #996726 value of detecting the key pathogenetic biomarker of GD for accurate diagnosis and long-term follow-up of the disease Clinical Efficacy of Thyroid-stimulating Immunoglobulin course. The initial FT4 and TSI levels can be used as predictors of Detection for Diagnosing Graves’ Disease and Predictors the responsiveness to methimazole in patients with newly of Responsiveness to Methimazole diagnosed GD. https://doi.org/10.1016/j.eprac.2021.04.778

Author Block: KunY. Liu, NO - Co-author, Department of fi Endocrinology and Metabolism, the First Af liated Hospital of Abstract #997055 Nanjing Medical University; Yu Fu, NO - Co-author, Department of Nuclear Medicine, the First Affiliated Hospital of Nanjing Medical Metastatic Papillary Thyroid Carcinoma without University; TianT. Li, NO - Co-author, the First Affiliated Hospital of Identifiable Primary Tumor Nanjing Medical University; SunQ. Liu, NO - Primary author, Department of Endocrinology and Metabolism, the First Affiliated Hospital of Nanjing Medical University; DouD. Chen, NO - Primary Author Block: Resham Poudel - Louisiana State University Health author, Department of Endocrinology and Metabolism, the First Sciences Center Shreveport; David E. Scarborough, MD - co-author, Affiliated Hospital of Nanjing Medical University; ChenC. Zhao, NO Endocrinology, Louisiana State University HSC-Shreveport - Primary author, Department of Endocrinology and Metabolism, the First Affiliated Hospital of Nanjing Medical University; Yun Shi, Introduction: Papillary Thyroid Carcinoma (PTC) with clinically NO - Primary author, Department of Endocrinology and apparent lymph node metastasis, but without an identifiable pri- Metabolism, the First Affiliated Hospital of Nanjing Medical mary carcinoma lesion, is rare but can occur. We report such a case University; Yun Cai, NO - Primary author, Department of of occult PTC presenting as a cystic cervical lymph node metastasis. Endocrinology and Metabolism, the First Affiliated Hospital of Case Description: A 36-year-old-female with no significant Nanjing Medical University; Tao Yang, NO - Primary author, medical history had a neck ultrasound (US) for dysphagia and Department of Endocrinology and Metabolism, the First Affiliated choking of several weeks duration. US revealed a 3.6 cm com- Hospital of Nanjing Medical University; XuQ. zheng, NO - plex cyst on the left thyroid lobe. Fine needle aspiration (FNA) Corresponding author, Department of Endocrinology and cytology of the nodule was benign, however she chose to have Metabolism, the First Affiliated Hospital of Nanjing Medical the left thyroid lobe removed due to her symptoms. The final University pathology on her left hemithyroidectomy reported no cancer, and her compressive symptoms resolved. Four years later, she has a CT scan for evaluation of headache which revealed a 1.6 Objective: As thyroid-stimulating immunoglobulins (TSI) are a sign cm cystic lesion of the right neck. US of the neck also demon- of Graves' disease (GD), measuring TSI titers is becoming increas- strated 1.6 cm cystic lesion on the right. FNA of the cystic lesion ingly important for GD diagnosis. Only a few studies have assessed was performed twice. On the first FNA results were benign, but the efficacy of TSI detection for diagnosing GD in a Chinese popu- on the repeat FNA were suspicious for PTC. She underwent a lation. This study evaluated the diagnostic accuracy of a new fully completion right thyroidectomy. Surgical pathology revealed PTC automated TSI immunoassay (ImmuliteTM TSI assay) in GD patients in one of 10 level IV lymph nodes; the right thyroid lobe, and compared it to a thyroid-stimulating hormone receptor anti- isthmus and 17 other lymph nodes were negative for malig- body (TRAb) immunoassay (ELiATM TRAb assay). Additionally, nancy. The solitary metastatic lymph node was 4 mm, the clinical characteristics associated with responsiveness to methi- presence of extra-nodal extension could not be assessed owing mazole in patients with newly diagnosed GD were preliminarily to the fragmented nature of the specimen. She was then treated explored. with a 70 mCi ablation dose of I-131, with a stimulated with- Methods: This study involved 324 subjects, comprising patients drawal TSH of 62. Thyroglobulin level was 12 (presurgical), with untreated GD (GD-UT), Graves’ ophthalmopathy (GO) pa- down to 2.2 (stimulated, TSH 62) post right lobectomy, down to tients, GD patients who had been treated for >12 months (GD-T), < 0.1 (TSH 25) three weeks post I-131. A post I-131 Whole Body autoimmune thyroiditis (AIT) patients, and healthy subjects (HS). Scan showed foci of intense uptake in the thyroid bed, but no Serum samples were obtained and the ImmuliteTM TSI and ELiATM increased activity consistent with functioning thyroid tissue TRAb assays were performed on all 324 samples. According to their elsewhere. responsiveness to methimazole, the GD-UT patients were divided Discussion: PTC with clinically apparent nodal or distant metastasis into rapid and slow responder groups, and their clinical charac- but lacking a primary cancer in the thyroid is sometimes referred as teristics were compared. occult PTC (different definitions of occult PTC in literature: ‘not Results: A receiver operating characteristic (ROC) curve analysis of manifest or detectable by clinical methods alone’, ‘not present in GD-UT patients showed that the area under the curve (AUC) was macroscopic amounts’, ‘unknown primary malignancy that is 0.992 (95% confidence interval: 0.971e0.999), leading to a sensi- symptomless, which first manifests itself as metastases or sec- tivity of 99.3% and a specificity of 99%. The optimal TSI cut-off value ondary paraneoplastic phenomena’, etc.). Hypotheses for how this was 0.57 IU/L. Regardless of the initial methimazole dose, initial might occur include that a small microcarcinoma might not be FT4, TRAb, and TSI titers were higher in the rapid responder group detected under routine pathologic examination; or that the host than the slow responder group (P< 0.05). Logistic regression response might have resulted in tumor regression. Nodes of this revealed that age and initial FT4 and TSI levels in the middle-dose type are classified as N1b in the Union for International Cancer methimazole group were related to a rapid response, while the Control (UICC) classification. The prognosis of such cancers de- initial FT4 level, but not TSI, in the high-dose group was also pends on the extent of metastasis. They usually have a favorable associated with a rapid response. prognosis when disease is confined to the lymph node, and worse Discussion/Conclusion: The clinical diagnostic performance of prognosis with extra-nodal extension. the ImmuliteTM TSI assay for diagnosing GD was comparable to that of the ELiATM TRAb assay, and the former has the clinical https://doi.org/10.1016/j.eprac.2021.04.779

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Abstract #997062 Abstract #998651

Methimazole Induced Agranulocytosis in a Patient Follicular Thyroid Lymphoma: A Rare Differential of with Amiodarone Induced Thyrotoxicosis Neck Mass

Author Block: Resham Poudel - Louisiana State University Health Author Block: Ashna Grover - Mount Auburn Hospital, Cambridge, Sciences Center Shreveport; Kamal Bhusal, MD - co-author, MA; Skand Shekhar, MD - co-author, Clinical Research Branch, Endocrinology, Louisiana State University HSC-Shreveport; National Institute of Environmental Health Sciences (NIEHS), NIH, David E. Scarborough, MD - co-author, Endocrinology, Louisiana Bethesda, MD; Ana Rivadeneira, MD - co-author, Internal Medicine, State University HSC-Shreveport Mount Auburn Hospital, Cambridge, MA; Zuha Pandit, MD - co- author, Internal Medicine, Mount Auburn Hospital, Cambridge, Introduction: Methimazole induced agranulocytosis is a rare (0.1- MA; Chuanyun Gao, MD - co-author, Endocrinology, Mount 0.5 %) but serious complication, with approximately 10 times Auburn Hospital, Cambridge, MA increased risk in patients with Amiodarone induced thyrotoxicosis (AIT). We report such a case. Introduction: Primary thyroid lymphoma (PTL) is an extremely Case Description: A 55-year-old man with history of atrial fibril- rare malignancy constituting 1% to 2% of all thyroid cancers. Most lation, heart failure, hypertension, diabetes, sleep apnea, and hy- PTLs are diffuse large B-cell lymphomas with follicular thyroid perthyroidism presented to the ED complaining of a fall due to leg lymphoma (FTL) constituting only 3-5% of all cases. PTL is chal- weakness. He was found to have WBC of 600/uL (3900 e 12700/uL) lenging to diagnose pre-operatively due to the high frequency of an with granulocytes of 1% (38.0 - 73.0 %). He had been on amiodarone inconclusive aspiration cytology. for approximately one year (most recent dose 200 mg twice daily), Case Description: A 49-year-old male was found to have an which had been discontinued six weeks prior due to a new incidental 5 cm right-sided thyroid mass on his annual wellness thyrotoxicosis, TSH < 0.01 (0.400 - 4.000 uIU/mL), free T4 5.51 (0.71 visit. A small thyroid nodule was detected 15 years prior to pre- - 1.51 ng/dL), free T3 7.6 (2.3 - 4.2 pg/mL). Methimazole was started sentation, but he did not have interim follow up and felt no to treat thyrotoxicosis (10 mg TID x 5 days, 15 mg TID x next 5 days change in nodule size. He did not report any obstructive symp- and 20 mg daily x next 1 month), until being discontinued due to toms such as neck pressure, dysphagia, or dyspnea, or systemic the agranulocytosis, at which time TSH was 0.11 uIU/mL, free T4 symptoms such as fever, night sweats, or weight loss and had no 2.59 ng/dL free T3 3.9 pg/mL. Two weeks later, WBC improved to family history of cancer. Laboratory work-up showed TSH 3270/uL with granulocytes 33%. Thyroid peroxidase antibody and elevated at 34.6 uIU/mL (nl: 0.465 - 4.68 uIU/mL) with free T4 Thyroid Stimulating Immunoglobulin were not elevated. Ultra- 0.82 ng/dL (nl: 0.64 - 1.79 ng/dL), elevated anti-TPO and anti-TG sound of the thyroid gland was normal with normal vascularity. antibody titres. Subsequent thyroid ultrasound revealed a 5.5 x Presumptive diagnosis was Type 2 AIT and he was started on 1.8 x 2.6 cm hypoechoic solid nodule with smooth margins Prednisone 20 mg daily. Thyroid function normalized within 4 within the right thyroid lobe without suspicious lymph nodes. weeks with TSH 3.2 uIU/mL, free T4 1.39 ng/dL, and free T3 2.8 pg/ Pharmacotherapy with levothyroxine was started for a working mL. diagnosis of primary hypothyroidism due to Hashimoto’s Discussion: A 200 mg amiodarone tablet contains about 75 thyroiditis. After 8 weeks of treatment, there was no change in mcg iodine, and a standard maintenance treatment provides > the size of the nodule despite normalization of his thyroid 100 times the daily iodine requirement. The side effects can be function tests. Hence the nodule was biopsied by fine needle abnormal thyroid function tests, overt thyrotoxicosis, or overt aspiration (FNA). Cytology was non-diagnostic but revealed hypothyroidism. AIT develops in 3% patients taking amiodar- predominantly small mature-appearing lymphocytes, favoring oneinNorthAmerica(upto10%inlowiodineareas).Type1 chronic thyroiditis. Unfortunately, the flow cytometry from the AIT occurs in patients with underlying thyroid disease, fea- thyroid aspirate was not performed. One month later the patient tures may include: multinodular goiter, Graves, positive anti- underwent right thyroid lobectomy due to the development of bodies, T4/T3 < 4, and detectable radioactive iodine uptake. neck pressure symptoms. Surgical pathology was consistent with Type 2 AIT occurs in patients without underlying thyroid WHO grade 3A follicular lymphoma with no diffuse component. disease and has a clinical picture of subacute thyroiditis. Type The malignant cells were CD10 negative, BCL-6 weakly positive, 1 AIT is usually treated with Methimazole, whereas type 2 AIT and had a high Ki-67 score of 80% on immunochemistry. Cyto- is treated with glucocorticoids. There is no immediate benefit genic analysis revealed a BCL-6 rearrangement but no IGH/BCL2 of stopping amiodarone as it has a very long half-life (100 or MYC rearrangement. Post-operative staging PET-CT showed days). Methimazole induced agranulocytosis occurs in 0.1-0.5% intense uptake in the residual left thyroid lobe but no involve- patients with approximately 10 times increased risk in pa- ment of other sites. After a multi-disciplinary discussion, tients with AIT. This adverse effect appears to be dose related. chemotherapy with rituximab, cyclophosphamide, doxorubicin, Propylthiouracil is also contraindicated due to frequent cross- vincristine, prednisone (R-CHOP), and radiation therapy was reactivity. Discontinuation is the mainstay of treatment, along initiated. with treatment of AIT, which may be difficult in the event of a Discussion: This case reiterates the importance of serial follow-up Type 1 AIT moderate or severe. This case reiterates the need of incidental thyroid masses. PTLs commonly present at an to be careful in initiating a thionamide before making sure advanced stage due to minimal/subtle symptoms initially; In our which type of AIT we are dealing with. This case was type 2 patient, the nodule insidiously increased in size over several years. AITwhichwoulddofine without Methimazole. Also, the PTL frequently occurs in the milieu of Hashimoto’s thyroiditis - an importance of WBC monitoring in patient taking thionamide established risk factor for PTL. FNA alone has limited diagnostic forAITcannotbeoverstatedasitisassociatedincreasedrisk value because of the overlapping cytological features of autoim- of neutropenia than in other cases of hyperthyroidism. mune thyroiditis and PTL. Flow cytometry can assist in diagnosis. Since the stage of diagnosis is a significant prognostic marker of https://doi.org/10.1016/j.eprac.2021.04.780

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PTL, its timely diagnosis and treatment will likely improve out- carcinomas, but not follicular or medullary carcinomas. ALK comes in patients with this rare tumor. gene rearrangements are mutually exclusive with all the other driver mutations and therefore it represents a diagnostic https://doi.org/10.1016/j.eprac.2021.04.781 marker and potential therapeutic target in rare aggressive cancers. There is a need for more research on the true inci- dence and clinicopathologic features of this fusion oncogene in Abstract #999392 PTCtounderstanditsimpactonprognosis.

A Rare Case of Papillary Thyroid Cancer with EML4- https://doi.org/10.1016/j.eprac.2021.04.782 ALK Oncogenic Fusion

Abstract #1000162 Author Block: Mangaiyarkkarasi Sivakumar - Rutgers Robert Wood Johnson Medical School; Sara Lubitz, MD - Co-Author, Rutgers A Severe Case Of Hypothyroidism: Immunotherapy Robert Wood Johnson Medical School Induced

Introduction: Papillary thyroid cancer(PTC) is associated with a variety of genetic alterations. Recent advances in molecular Author Block: Srivani Chunchulu - Cameron Regional Medical genetics have demonstrated the presence of Echinoderm Center microtubule-associated protein-like 4 (EML4) and Anaplastic Lymphoma Receptor Tyrosine Kinase (ALK) fusion oncogene on Introduction: Immune check point inhibitors are playing a crucial Chromosome 2p in PTC, especially progressive tumors. Mo- role in the treatment of many cancers. Their primary role is to lecular diagnostics help determine prognosis and choice of reactivate anti tumor cytotoxic T cells. Programmed cell death 1(PD treatment. Great progress has been made in understanding the 1) is a transmembrane protein expressed on T cells, B cells and RET-RAS-BRAF of the mitogen-activated protein kinase Natural killer cells. PD 1 ligand is expressed in many tumor cells cascade. However, there has been relatively little experimental along with hematopoietic cells and their interaction directly in- validation of the signaling pathways mediated by EML4-ALK. hibits apoptosis of the tumor cell. Pembrolizumab binds PD1.FDA We present a rare case of aggressive PTC with EML4-ALK approved pembrolizumab initially for nonsquamous cell lung fusion in a young female. cancer and metastatic melanoma that express PD1 ligand which Case Description: A 20-year-old female with no family history showed improved survival compared to standard therapy. Addi- of thyroid cancer or history of radiation exposure presented tionally it has been used in several others tumors with more than with left neck swelling. Ultrasound showed a 4.1x2.9cm left 50% PD L1 expression. Although well tolerated, these agents can lymph node. CT demonstrated a 1.5x1.5cm left thyroid nodule cause immune related adverse events. Thyroid dysfunction is re- with left neck adenopathy. FNA of the thyroid nodule showed ported to range between 3.2-10.1% patients receiving rare clusters of atypical follicular cells read as Bethesda III pembrolizumab FLUS/AUS. FNA of the left superior jugular chain lymph node Case Description: 86 year old Caucasian female with past medical showed follicular epithelial cells suspicious for malignancy. history of hypertension and osteoarthritis was diagnosed with The thyroid sample was sent for ThyGeNEXT® Oncogene panel stage III metastatic colon cancer in the hepatic flexure and under- whichreportedanEML4-ALKoncogenicfusionandtheThyr- went hemicolectomy. Pathology showed 6.5cm mass and 2/30 aMIR® molecular test was “positive". Total thyroidectomy and lymph nodes positive. Due to fear of side effects from chemo- left neck dissection pathology showed a 6.8cm PTC infiltrative therapy, patient refused further treatment. Her follow up labs follicular variant with extensive lymphovascular invasion. showed elevation of carcinoembyronic antigen (CEA).Her oncolo- Metastasis was present in 4/6 lymph nodes with largest de- gist suggested Pembrolizumab, immunotherapy. She was started posit of 1cm in the thyroid bed and 4/20 lymph nodes with on 5 cycles every 3 weeks. She had fatigue and fell twice after first largest deposit of 4.7 cm in the lateral neck: T3aN1b. cycle, but her CEA levels were improving, so it was decided to Discussion: ALK is a receptor tyrosine kinase, activated in continue treatment. Soon after fifth cycle she became extremely neoplastic cells by formation of a fusion protein with a partner weak, lethargic, and unable to do any ADLS and was exhausted all through genomic rearrangements. ALK fusion is seen in thy- the time. Her labs showed TSH 137, free T4 0.4. At that point de- roid (1-2%), renal, colorectal, and ovarian cancers. EML4-ALK cision was made to stop pembrolizumab. She was started on lev- fusionsformedbytheinversiononChromosome2phavebeen othyroxine 25mcg by her oncologist and referred to me few months reported in lung adenocarcinomas (5%) and few cases of pe- later. She complained of tiredness, low energy. On exam Pulse 78, diatric neuroblastomas. EML4-ALK fusion serves as the driver Blood pressure 152/77 .Her labs showed TSH 106 and Free T4 for cancer by initiating auto-phosphorylation which activates 0.45.Her levothyroxine dose was increased to 75mcg and followed the tyrosine kinase. However, full understanding of the her 6 weeks later. Her energy levels improved significantly and she oncogenic pathway in PTC remains unclear. In a study by Chou is back to her normal self. Her thyroid function was normal. At this et al. (2015) analysis of 498 aggressive thyroid cancers found point patient has decided not to undergo any treatments for colon 2.2% of unselected PTC and 13% of diffuse sclerosing variant cancer. with ALK translocations. All 14 (2.8%) cases reported in young Discussion: Immune related thyroid events are increasingly females were not associated with aggressive clinicopathologic noticed with wide use of pembrolizumab.There is insufficient evi- features. However, Demeure et al. (2014) identified an EML4- dence to suggest the cause of these events. Reversible destructive ALK translocation of a TRAPP oncogene mutation in a 62-year- thyroiditis and overt hypothyroidism are the common clinical old male with very aggressive disease. ALK translocations have presentations. It is important to recognize patients at high risk for also been identified in poorly differentiated anaplastic these adverse events so these highly efficacious agents can be safely

S149 Thyroid Endocrine Practice 27 (2021) S141eS188 used in patients. Thyroid has been a frequent target for anti PD 1 conventional treatments with thionamides and iodine are treatments, further research can be of benefit to use against thyroid contraindicated. cancers. https://doi.org/10.1016/j.eprac.2021.04.784 https://doi.org/10.1016/j.eprac.2021.04.783

Abstract #1000475 Abstract #1000275 Papillary Carcinoma of Thyroid Origin and Life Saving Plasmapheresis in the Treatment of Hyperthyroidism: A Rare Presentation of a Rare Thyrotoxicosis with Acute Heart Failure Condition

Author Block: Sean Mccalmon, DO - primary author/co-author/ Author Block: Sajjad Ali Khan - Aga Khan university hospital, presenter, UMKC/Truman Medical Center; Peminda K. Cabandugama, Karachi, Pakistan; Sohaib S. Khan, Dr - Co-author, Medicine, Patel MD - co-author, UMKC/Truman Medical Center Hospital Karachi; Matiullah Khan, Dr - Co-author, Medicine, Shifa International Hospital; AZRA RIZWAN, Dr - Co-author, Aga Khan Introduction: Thyrotoxicosis is a potentially life-threatening University Hospital condition requiring urgent treatment. Standard therapy is Methimazole (MMI) or Propylthiouracil (PTU) with a beta- Introduction: Concurrent thyroid cancer and hyperthyroidism is a blocker. However, antithyroid drugs (ATD) are contraindicated in rare finding. The incidence of this association is highly variable. the setting of liver dysfunction, defined as 3x the upper limit of Here we report a rare case of papillary thyroid cancer associated normal (ULN). Plasmapheresis is an alternative treatment that is with hyperthyroidism. effective by the removal of circulating autoantibodies and im- Case Description: A 49-year-old male presented to our outpa- mune complexes. We present a patient treated with plasma- tient clinic with complaints of a painless left-sided anterior pheresis as a final recourse for the treatment of severe neck swelling for the past eight months. He also reported thyrotoxicosis and acute heart failure in the setting of acutely weight loss for the same duration. The anterolateral swelling elevated transaminases. was non-tender, asymmetrical, mobile, and rubbery. Case Description: 37 year old male with atrial fibrillation and Biochemical testing confirmed hyperthyroidism. Ultrasound hyperthyroidism, noncompliant with ATD for three months, neck showed a well-defined, solid, and cystic lesion in the left presented with shortness of breath, palpitations, orthopnea, lobe and isthmus of the thyroid gland. The solid portion had and lower extremity edema for two weeks prior. He also re- fewspecksofcalcification. A radioactive thyroid scan showed ports unexplained 100lb weight loss in the past year. Work up increased tracer uptake in the left lobe. Fine needle aspiration reveals EKG with atrial fibrillation, rate 140 bpm. Labs showed of the left anterior cervical lymph node showed papillary AST 814 U/L, ALT 432 U/L, TSH < 0.01uIU/mL,FreeT43.66ng/ carcinoma of thyroid origin. After preparation, a total thy- dL,FreeT310.3pg/mL,TSI323,BNP6,076pg/mL,viraland roidectomy was done. Histopathological examination autoimmune hepatitis panels negative, urine toxicology nega- confirmed papillary thyroid carcinoma. Following radioactive tive. Transthoracic echocardiogram showed ejection fraction < thyroid ablation, the patient was started on suppressive doses 20% with severe global hypokinesis of left ventricle, pulmo- of thyroxine daily. Although thyroid cancer with hyperthy- nary artery systolic pressure 50mmHg. Abdominal ultrasound roidism is a rare finding, it should not be disregarded. A revealed a heterogeneous 16cm liver without a mass. Thyroid thorough history and physical examination should be done, ultrasound showed enlargement with diffuse heterogeneity. and all the necessary investigations should be sent in order ICU care included intravenous hydrocortisone 100mg q8h, nottomissthisrarebutuncommonfinding. propranolol 40mg q8h, lasix 80mg twice daily. Plasmapheresis Discussion: Complete blood count was normal. Thyroid function was performed daily for 3 consecutive days. The day following test revealed a thyroid-stimulating hormone (TSH) of 0.010 mU/L completion of plasmapheresis course, labs showed freeT4 1.83 (normal range : 0.4-4.0 mU/L) and a Free T4 of 2.6 ng/dl (normal ng/dL, freeT3 2.7 pg/mL, AST 84 U/L, ALT 93U/L. Once labs range :0.7-1.8 ng/dL). Ultrasound neck showed a well-defined confirmed AST/ALT less than 3x ULN, MMI was initiated. The cystic and solid lesion in the left lobe and isthmus of the thyroid patient was discharged in stable condition on MMI 10mg daily gland, measuring 21 * 11* 16 mm. The solid portion measured and Propranolol 30mg three times per day in anticipation of 9*6mm with few specks of calcifications. Sub-centimetre lymph outpatient thyroidectomy. nodes were noted in levels 1,2,4 and 5 of the neck bilaterally. The Discussion: This case shows severe thyrotoxicosis contributing to largest lymph node was seen on the left side which measured 9 the finding of rapid atrial fibrillation with cardiogenic pulmonary mm. edema, requiring immediate therapy of underlying thyroid disease. As the thyroid function tests were consistent with hyperthy- Standard medications of MMI or PTU could not be used due to roidism, a radioactive scan was requested to assess for thyroid acutely elevated AST/ALT ~20x ULN. Iodine therapy was not an functionality. The scan showed increased tracer uptake in the left option due to his cardiac compromise making him ineligible for lobe. The patient was subsequently started on neomercazole and urgent thyroidectomy. propranolol. Fine needle aspiration of the left anterior cervical Plasmapheresis provided a safe and effective treatment op- lymph node revealed metastatic papillary carcinoma of thyroid tion for this patient. We hope to illustrate with this case, the origin. importance of incorporating plasmapheresis into the standard Histopathological results showed multicentric characteristic of care for treatment of severe hyperthyroidism when oval nuclei with grooving confirming papillary thyroid carcinoma.

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One lymph node in left cervical level III was involved by the tu- Abstract #1000765 mor. The size of the nodal metastasis was 0.1 cm with no extra- nodal extension. All the other lymph nodes were negative for Seeing Through the Fog: Characterizing “Brain Fog” in metastasis. Those Treated for Hypothyroidism https://doi.org/10.1016/j.eprac.2021.04.785

Author Block: Matthew Ettleson - University of Chicago; Abstract #1000501 Ava Raine, Undergraduate student - Primary author, presenter, Carleton College, Northfield, MN; McAninch A. Elizabeth, M.D. - co- Impact of Diabetes on Thyroid Eye Disease in US author, Endocrinology, Rush University Medical Center; Patients: A Claims-Based Study Miriam O. Ribeiro, Ph.D. - co-author, Developmental Disorders Program, Center for Biological Sciences and Health, Mackenzie Presbyterian University, Sao Paulo SP, Brazil; Jacqueline Jonklaas, Author Block: Vishal K. Patel, PhramD - co-author, Horizon M.D. - co-author, Endocrinology, Georgetown University Medical Therapeutics plc; Lissa Padnick-Silver, PhD - Presenter, Horizon Center; Antonio C. Bianco, M.D., Ph.D. - co-author, Endocrinology, Therapeutics plc; Rajib K. Bhattacharya, MD - co-author, Horizon Diabetes, and Metabolism, University of Chicago Therapeutics plc; Megan Francis-Sedlak, PhD - co-author, Horizon Therapeutics plc; Robert J. Holt, PharmD, MBA - co-author, Horizon Objective: Despite normalization of thyroid-stimulating hor- Therapeutics mone levels with thyroid hormone replacement therapy, many patients with hypothyroidism remain dissatisfied due to Objective: Thyroid eye disease (TED) is a rare, debilitating autoim- persistent symptoms. A common complaint is cognitive mune condition most often associated with Graves’ disease (GD). dysfunction, referred to by some as “brain fog,” although this Recent literature reports indicate that diabetes may be a risk factor for label has been associated with other disorders. Our primary TED development and/or increased TED severity. However, this as- objectives were to characterize the prominent symptoms of sociation has not been examined in a large, population-based study. A brain fog associated with treated hypothyroidism, measure the large US insurance claims database provided the opportunity to correlation between symptom severity and patient satisfaction examine the relationship between TED and diabetes in GD patients. measures, and catalog factors that improve and/or worsen Methods: These analyses (2010e2015 Symphony database, Pearl- brain fog symptoms. Diver, Inc. software) included patients with 1GDand1TEDICD-9 Methods: An online survey was distributed via hypothyroid sup- code (in database 2 yrs). The TED code algorithm included proptosis, port groups and the American Thyroid Association. Patient satis- diplopia, lid retraction, strabismus, exposure keratopathy (corneal faction and symptom severity questions were scored using a 4- damage from a dry ocular surface), and optic neuropathy (ON) in point Likert scale. Subject responses concerning factors that patients with existing GD. Patients were stratified based on presence/ improve or worsen brain fog were manually reviewed, categorized, absence of diabetes codes and TED codes of interest for comparison. and ranked by frequency. In an effort to isolate the symptom Further, patients with sight-threatening (ST) TED (defined as 1ONor pattern of brain fog unique to hypothyroidism, a secondary analysis exposure keratopathy code) were identifiedandexaminedineach was performed on the subset of subjects with onset of symptoms group (severity assessment), along with TED-related surgery rates. weeks/months after undergoing thyroid surgery and/or radioactive Results: 51,220 TED patients were identified. 2,618 (5%) had iodine (RAI) therapy. Kendall’s rank correlation coefficients (tau-b) type 1 diabetes and 12,846 (25%) had type 2 diabetes. were used to measure the association between symptom severity Compared to non-diabetic (ND) TED patients, diabetics were and patient satisfaction scores. older at first TED diagnosis code (59.0 yrs [type 1], 59.6 [type Results: Of the 5282 survey respondents included in the analysis, 2]vs.51.4[ND])andmoreoftenmale(30%,29%vs.21%);type 905 (17.1%) reported onset of brain fog symptoms weeks/months 1vs.non-diabetic:p< 0.001, type 2 vs. non-diabetic: p< 0.001. after diagnosis of hypothyroidism; of which, 432 (47.8%) underwent Proptosis was less prevalent in diabetics (42%, 46% vs. 59%), thyroid surgery and/or RAI therapy. Lack of energy, forgetfulness, but strabismus (25%, 23% vs. 20%) and diplopia (39%, 38% vs. and feeling sleepy were the most frequent symptoms. The severity 30%) were more prevalent (all p< 0.001). More diabetics than scores of difficulty focusing, mental confusion, and difficulty mak- non-diabetics with TED had ST disease (13%, 13% vs. 11%; both ing decisions had the strongest correlation with the patient satis- p< 0.001). Examining ST-TED codes separately, more TED pa- faction score (tau-b: 0.431, 0.382, 0.367, respectively; p < 0.001 for tients with diabetes had ON codes (4%, 4% vs. 3%, both all). Amongst all subjects, modifications to behavior, diet, and p0.003), but keratopathy was similarly coded (10%, 9% vs. 9%; thyroid hormone replacement were the most frequently p ¼ 0.114, p¼0.304). A similar proportion of type 1 and non- mentioned factors that improved or worsened symptoms. diabetic patients had 1 TED surgery code (both 10%), but Discussion/Conclusion: Complaints of brain fog from treated hy- surgical rates were slightly lower in patients with type 2 pothyroid patients have previously had vague descriptions and diabetes (9%, p< 0.001). unclear implications. While those with brain fog endorse a range Discussion/Conclusion: This unique insurance claims study sug- of symptoms, the cognitive symptoms appear to have the most gests TED patients with diabetes have less proptosis, but more eye marked impact on patient satisfaction, which may differentiate muscle dysfunction as compared to those without diabetes. Sight- hypothyroid brain fog from other forms. Our findings point to threatening TED was also identified more often in diabetic patients, behavior and thyroid hormone modification as potential strate- possibly due to a more vulnerable optic nerve resulting from dia- gies to ameliorate symptoms. Further investigations into the betes-induced vasculopathy. However, TED surgical rates were lifestyle and medication changes which help to relieve symptoms similar (9-10%) in diabetic and non-diabetic patients. These data are of brain fog, as well as role of serum thyroid hormone levels in hypothesis generating and findings need to be confirmed in more contributing to the severity of brain fog symptoms, are controlled case-based analyses and clinical studies. warranted. https://doi.org/10.1016/j.eprac.2021.04.786 https://doi.org/10.1016/j.eprac.2021.04.787

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Abstract #1000821 Endocrinology, Westchester Medical Center; gayotri goswami, MD, Board Certified Endocrinology - Third, Endocrinology, Westchester Misleading FT4 and FT3 Due to Immunoassay Medical Center Interference Introduction: Enlargement of a multinodular goiter is a common finding which can result in compression of structures in the vicinity. Author Block: Travis Goettemoeller - Cleveland Clinic; A rare example is arterial compression by a large substernal goiter Adam J. McShane, PhD - co-author, Cleveland Clinic; Pratibha Rao, that can compromise cerebral blood flow. We present a unique case MD, MPH - co-author, Cleveland Clinic of an enlarged thyroid, which caused substantial compression of the left common carotid artery leading to ischemic stroke. Introduction: Immunoassays used to measure total and free Case Description: A 90-year-old female from Ecuador with a past thyroxine (T4 and FT4) and total and free triiodothyronine (T3 and medical history of multinodular goiter and bilateral hearing loss FT3) can provide inaccurate results due to interference from presented with symptoms of acute stroke, including right-sided endogenous antibodies. We present a clinical case of a patient with weakness and dysarthria. History revealed that the patient had a a previous diagnosis of hypothyroidism with frankly elevated FT4 progressively enlarging goiter for 13 years with compressive symp- and FT3 levels due to assay interference. toms of dysphagia. However, she never followed up for these symp- Case Description: A 74-year-old woman with a history of hypothy- toms. She denied cold or heat intolerance, tremors, palpitations, or roidism presented for abnormal results of thyroid function tests and weight changes. On admission, the patient’s vital signs were stable. weight loss. She had been treated with a stable dose of levothyroxine Physical examination revealed an asymmetrically enlarged non-ten- for many years and was noted to have elevated TSH 6.375 mIU/L (N: der thyroid gland approximately three times the size, and negative 0.465 e 4.68 mIU/L), FT4 >6.99 ng/dL (N: 0.78 e 2.19 ng/dL), and FT3 bruit. Pemberton sign could not be assessed due to right arm weak- 9.76 pg/mL (N: 2.77 e 5.27 pg/mL). Due to concern for hyperthyroid- ness. Neurological exam was difficult to evaluate as patient was not ism, levothyroxine was stopped while further workup was performed. following commands, but right arm and leg weakness were present. MRI of the brain revealed a 3 mm pituitary microadenoma, how- The rest of the physical exam was unremarkable. Laboratory studies ever, her alpha subunit was normal at 0.84 ng/mL (N: < 3.56 ng/mL). showed a suppressed thyroid-stimulating hormone (TSH) level 0.045 Ultrasound of the thyroid was unremarkable. Further labs revealed mIU/L, free thyroxine 1.2 ng/dL, and total tri-iodothyronine 102 ng/dL. elevated microsomal antibody 5,362 IU/mL (N: < 5.2 IU/mL) and Other causes of stroke including atrial fibrillation or thrombus were elevated thyroglobulin antibody 9,815 IU/mL (N: < 14 IU/mL). ruled out by electrocardiogram, telemonitoring, and transthoracic While off levothyroxine, the patient developed worsening fatigue echocardiography. CT Brain significant for acute left frontal middle and cold intolerance. Her TSH increased significantly to 58.674 cerebral artery infarcts. CTangiogram of the brain and neck revealed a mIU/L while FT4 and FT3 remained elevated. There was suspicion thyroid with multiple calcifications causing left common carotid ar- that the immunoassays for FT4 and FT3 were inaccurate, so they tery occlusion due to its mass effect. Subsequently, the patient un- were measured by equilibrium dialysis/liquid chromatography- derwent a total thyroidectomy. Her symptoms of right sided weakness tandem mass spectrometry (LC-MS/MS) and were found to be resolved. Post-operative thyroid pathology showed diffuse heteroge- significantly lower: FT3 1.54 pg/mL (N: 1.81 neous nodularity with multiple nodules ranging from 0.5-1 cm 4.06 pg/mL) and FT4 1.2 ng/dL (N: 1.1 e 2.4 ng/dL). In order to consistent with multinodular goiter. She was eventually discharged determine the cause of immunoassay interference, additional testing on Levothyroxine 50 mcg oral daily and calcium supplements. was performed. Testing using heterophile antibody blocking reagents Discussion: Although non-toxic multinodular goiter is mostly benign, followed by immunoassay testing (Roche Diagnostics) revealed no its substantial growth can invade surrounding structures resulting in significant differences from the original immunoassay testing. Sample obstructive symptoms. A patient presenting with stroke due to artery pretreatment using polyethylene glycol (PEG) precipitation followed compression from thyroid mass effect is rare. Our case is distinctive due by immunoassay testing revealed results similar to the equilibrium to the fact that patient had no risk factors of stroke. Thrombotic and dialysis LC-MS/MS method. These results suggested that the most embolic causes of stroke were ruled out however she developed a likely cause of interference was autoantibodies to both T4 and T3. reversible ischemic stroke as a complication of her untreated thyroid Discussion: In this case, FT4 and FT3 levels measured via immu- disease. As the patient was from a poor rural area in Ecuador, iodine noassays were falsely elevated. Endogenous antibodies known to deficiency and lack of appropriate medical care are most likely the cause cause interference in immunoassays are heterophile, anti-animal, of her massive multinodular goiter with such emergent complication. To and autoantibodies. In our case, the most likely cause of interfer- our knowledge, this is the first reported case of reversible ischemic ence was autoantibodies to T4 and T3. When there is discrepancy stroke caused by a giant thyroid goiter. Acknowledging stroke as a grave between clinical findings and laboratory results, it is imperative to complication of a large multinodular goiter is crucial for the timely and work with the laboratory to repeat the analysis with another appropriate management and to avoid serious consequences. method and ideally compare against equilibrium dialysis which is https://doi.org/10.1016/j.eprac.2021.04.789 the gold standard for measuring FT4 and FT3. https://doi.org/10.1016/j.eprac.2021.04.788 Abstract #1000854

Abstract #1000835 Hyperthyroidism Times 2: Dual Cause of Thyroid Hormone Excess Ischemic Stroke as a Rare Complication of Multinodular Goiter Author Block: Yineli Ortiz, n/a - Primary author, Internal Medicine, n/a; alegyari figueroa, n/a - co-author, n/a; Jose m. gARCIA, N/A - Author Block: Yudi Camacho, MD - Primary, Endocrinology, CO-AUTHOR, N/A; Gabriel Mora, n/a - co-author, n/a; angela torres, Westchester Medical Center; Yusra Jamal, MBBS - second, n/a - co-author, n/a

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Introduction: The most common etiology of Hyperthyroidism is Objective: Propylthiouracil (PTU) is a thioamide drug, which is due to circulating antibodies that are directed against the thyroid- commonly used for the treatment of hyperthyroidism. A serious but stimulating hormone (TSH) receptor, known as Grave’s Disease less frequent side effect of PTU is vasculitis. Many organ systems (GD). Another cause is an autonomously functioning thyroid nodule like renal, cutaneous, hematological, respiratory, gastrointestinal, over-producing hormones or Toxic Adenoma. The mechanism of neurological, and musculoskeletal are affected by PTU-induced these two pathologies are very distinct, but the question that arises vasculitis. The purpose of this study is to evaluate the epidemiology is, can they coexist? of vasculitis associated with PTU use reported to the FDA. Case Description: This is a case of 44-year-old female who comes to Methods: We used the Food and Drug Administration Adverse the clinic referred by her ophthalmologist after been diagnosed Event Reporting System (FAERS), a database that contains with severe thyroid-associated orbitopathy currently on steroid adverse events reports, medication error reports, and product therapy. Thyroid ultrasound has done previously showed enlarged quality complaints reported to the FDA. It is a voluntary post- homogenous thyroid gland with a single isoechoic nodule of marketing pharmacosurveillance database maintained by the 2.2x1.6x1.9cm with faint peripheral calcifications and vascularity. FDA. We identified all adverse events (AEs) associated with The patient was presenting with palpitations, heat intolerance, Propylthiouracil (PTU) between 2010 and 2020. We investigated sweating, and discriminatory features such as double vision and the number of vasculitis cases associated with PTU reported to left eye exophthalmos. On physical examination, there was no the FDA. goiter or palpable thyroid nodules, but it was remarkable for left Results: We identified 642 adverse events related to PTU that were eyelid lag retraction and mild proptosis. Evaluation showed clinical reported to the FDA, out of which 45 (7%) were reported as and biochemical hyperthyroidism with TSH: 0.068 mU/ml (n:0.5- vasculitis. Among these 45 patients, 28 were hospitalized and 1 5.0mU/ml), FT4: 1.39ng/dl (n:0.87-1.85ng/dl), TSH receptor anti- died. It was noted that 93% of these cases were females compared to body: < 1.10IU/L and thyroid-stimulating immunoglobulin: 0.54IU/ 2% being males. Additionally, 53% of the cases were between age L (borderline high). The patient was placed in antithyroid drugs and 18-64 and 40% between age 65-85. Interestingly, 19 (42%) of these B-blockers for disease control. Afterward, the patient underwent a 45 vasculitis cases were reported in 2019. thyroid uptake scan reporting toxic adenoma on the left lobe, Discussion/Conclusion: In the FAERS database, we described the however even when the biochemical workup of GD is inconclusive, prevalence of vasculitis as an immune-related adverse event patient clinical findings are highly suggestive of it. Due to the risk of associated with the use of Propylthiouracil. Vasculitis accounted for worsening orbitopathy with radioactive iodine therapy, patient was 7% of the total adverse events reported with PTU between 2010 and referred for surgical excision of toxic adenoma and total thyroid- 2020. Moreover, our study showed a high hospitalization rate ectomy was decided since residual thyroid tissue may expose the (62.22% ) but a low mortality rate (2.22%) associated with PTU- patient to circulating thyroid-stimulating immunoglobulin leading Vasculitis. to hyperthyroidism recurrence and put her at risk of associated https://doi.org/10.1016/j.eprac.2021.04.791 thyroid excess detrimental complications. Surgical specimen gross pathology biopsy reported the thyroid gland with hyperplastic ’ changes of Grave s Disease. Severe thyroid-associated orbitopathy Abstract #1000874 was managed with decompression surgery but did not improve, for which an alternative therapeutic approach is decided with novel Comparative Study of Diagnostic Accuracy Between immunomodulatory agent and recent approved therapy, Teprotu- the Fine Needle Aspiration and the Surgical Pathology mumab. A monoclonal antibody that works on TSHR/IGF-1R of Patients with Thyroid Nodules at Calmette Hospital, signaling complex involved in Thyroid Eye Disease. Phnom Penh, Cambodia Discussion: Is unusual to see two different superimposing thyroid pathologies, but disease presentations can be atypical and can be present concomitantly. In this scenario, several factors must be Author Block: Satha Sum - Calmette Hospital; Senghak Han, taken into consideration when choosing an adequate therapy Endocrinologist - Co-author, University of Health Sciences; approach. Our case is an example that we need to individualize Linat Kong, Endocrinologist - Co-author, Calmette Hospital; management options based on guidelines recommendations, pa- Sophanara Min, Endocrinologist - Co-author, Calmette Hospital; tient's clinical settings and decreased risks of future complications. Hokban Sor, Endocrinologist - Co-author, Calmette Hospital; https://doi.org/10.1016/j.eprac.2021.04.790 Michel Pluot, Pathologist - Co-author, Calmette Hospital

Objective: Thyroid nodules are very common in Asian population. Abstract #1000858 Fine Needle Aspiration (FNA) is a very useful screening method to diagnosis the malignancy of thyroid nodules. According to FNA Association between Vasculitis and Propylthiouracil series in Calmette hospital, there are 12.2% of patients who have Use: Analysis of the FDA Adverse Events Reporting malignant results. Based on the results of FNA, clinicians could System (FAERS) make a proper therapeutic decision and also could minimize the unnecessary surgery. However, the surgical pathology is the most precise technique to finalize the diagnosis of the thyroid nodules. Author Block: Areeba Altaf, MD - Primary Author/Presenter, The purpose of this study is to compare the diagnostic accuracy University at Buffalo-CHS; Numra A. Tunio, MBBS - co-author, between Fine Needle Aspiration and Surgical Pathology of thyroid Ziauddin University; Sameer A. Tunio, MBBS - co-author, Aga Khan nodules at Calmette Hospital. University Hospital; Meer R. Zafar, MD - co-author, University at Methods: We conducted a retrospective study among thyroid Buffalo-CHS; Hafiz M. Fazeel, MD - co-author, University at Buffalo- nodules patients who received FNA and surgical operation with CHS; saher Aslam, MD - co-author, University at Buffalo-CHS pathology examination at Calmette hospital. Cytologies results

S153 Thyroid Endocrine Practice 27 (2021) S141eS188 were given according to the Bethesda system for reporting thyroid prior antibiotics, she received a 14-day course of IV Ceftriaxone. cytology (5 diagnosis categories). From June 1st 2018 to June 1st Outpatient follow-up eight weeks later showed she was euthyroid 2020 there were 18 medical records of patients. on Levothyroxine 75 mcg with ultrasound revealing small thyroid Results: In our study the patients were relatively young. The gland with resolution of the abscess. average age was 37.11 (±13.33) years old. Among 18 cases of FNA Discussion: Hyperthyroidism in the setting thyroid abscess is reported as benign (Bethesda II) 44.44%, as intermediate 16.67% secondary to destructive thyroiditis. As there is no increase in (Bethesda III) and as malignant 38.89% (Bethesda V and VI). All the thyroid hormone synthesis, there is no role for treatment with 8 cases which were diagnosed as benign by FNA were found benign antithyroid medication. Symptomatic control with beta-blocker, lesions in the final histopathology. And all the 7 cases which were surgical drainage, and IV antibiotics are recommended for cases diagnosed as malignant by FNA were found malignant lesions in the of thyroid abscesses. If infection persists or extensive necrosis final histopathology. All malignant cases were papillary carcinoma develops, thyroidectomy may be indicated. Hypothyroidism can in this study. be a consequence of destructive thyroiditis as was seen in this However, among 3 cases classified as intermediate by FNA, 2 patient. were found benign and 1 malignant. We found almost identical https://doi.org/10.1016/j.eprac.2021.04.793 results between FNA and final surgical histopathology. Discussion/Conclusion: FNA is a safe, simple and cost-effective method. But it requires proper pathological interpretation. The Abstract #1001117 correlation between FNA and surgical pathology is globally good. https://doi.org/10.1016/j.eprac.2021.04.792 Sudden Onset Ocular Myasthenia Gravis as The Presenting Complain in Patient with Thyrotoxicosis

Abstract #1000892 Author Block: Farheen Saeed - Texas Tech University Health Thyroid Abscess Presenting As Destructive Thyroiditis Sciences Center at Permian Basin Odessa Tx; With Subsequent Hypothyroidism Ramachandra Chemitiganti, Regional Chairman, Dept Of Internal Medicine, Chief, Division of Endocrinology and Metabolism - Co- author, Texas Tech University School Of Medicine at Permian Basin Author Block: Ahl Jeffrey Caseja - HCA Healthcare Sunrise Health Graduate Medical Education Program; Richard L. Wang, M.D. - co- Introduction: The coexistence of other autoimmune diseases in author, HCA Healthcare Sunrise Health Graduate Medical Myasthenia Gravis (MG) is well recognized including the as- Education Program; Samer Nakhle, M.D. - co-author, Palm Medical sociation with autoimmune thyroid disease (AITD). The inci- Group dence of myasthenia gravis in patients with autoimmune thyroid disease is unusual. Ocular myasthenia gravis in Introduction: Due to its rich vascular supply and high iodine con- conjunction with Graves’ disease, although is rare. This asso- tent infection of the thyroid gland is rare and is uncommonly ciation when present is attributed to either a common auto- associated with hyperthyroidism. We report a case of a thyroid immune mechanism or a peculiar genetic background. We abscess presenting with hyperthyroidism with subsequent hypo- present a patient who presented with unilateral ptosis related thyroidism in an immunocompetent patient. to ocular myasthenia gravis that was in fact thyrotoxic due to Case Description: A 34-year old female with no past medical his- new onset Graves’ disease. tory presented with an enlarging neck mass associated with Case Description: A 22-year-old Hispanic male, nonsmoker, pre- worsening, non-radiating throat pain of three-week duration sented with a 3-day history of right eye ptosis and diplopia for few associated with dysphagia. She reports 15-lb weight loss and pal- weeks. Patient while being evaluated for a cerebrovascular event in pitations. On presentation vital signs were within normal range. the emergency department was found to have abnormal thyroid Physical examination revealed a diffusely tender anterior neck function test. At consultation patient endorsed hyperdefecation, mass. Her thyroid function tests revealed TSH 0.01 uIU/mL (0.358- insomnia, tremors, palpitations, heat intolerance in addition to the 3.74), FT4 2.4 ng/dL (0.76-1.46), TSI < 0.10 IU/L (0.00-0.55), TPO 12 presenting complaints. He denied dysphagia, dyspnea, dysarthria. IU/mL (0-34). Laboratory workup was also significant for leukocy- Family history was negative for any thyroid disorder or neuro- tosis, thrombocytosis, and hyponatremia. Thyroid ultrasound muscular disease. On physical exam there was mild bilateral revealed a large, irregularly shaped, multiloculated fluid collection proptosis, right eye complete ptosis, diffuse enlargement of thyroid involving both lobes measuring 6.4 x 4.8 x 2.0 cm. She was started gland with bruit, normal sensation and reflexes. His ptosis was on Vancomycin and Ampicillin/Sulbactam, Metoprolol, and constant. Laboratory findings consistent with hyperthyroidism Methimazole. Needle aspiration of 30 cc of purulent material was from Graves’ disease {TSH < 0.001 mIU/ml (nl 0.340 - 5.300), free T4 performed with culture showing a heavy growth of streptococcus > 4.99 ng/dl (nl 0.7 -1.4), total T3 575 ng/dl (nl 80 - 200), thyroid constellatus sensitive to penicillin. After a 4-day inpatient stay, she stimulating immunoglobulin 40 IU/L (nl < 0.54)}. The hematolog- was discharged with Amoxicillin/Clauvanate as well as Methima- ical and other biochemical investigations were all within normal zole 10mg BID. limits. CT and MRI orbits were unremarkable for extraocular muscle Ten days after being discharged, the patient again presented to thickening. CXR was unremarkable of any mediastinal mass. Given the emergency department with complaint that the neck mass had thyrotoxic status, patient was started on propylthiouracil 100 mg increased in size. CT neck showed a 5.1 x 2.8 x 0.8 cm lobulated fluid TID, hydrocortisone 50 mg TID, propranolol 20 mg TID. Neurology collection. CT-guided drainage was performed, cytology and wound was consulted for possibility of ocular myasthenia gravis. culture were found to be unremarkable. Thyroid function tests Neurology evaluation, radiology and CSF analyses were unre- revealed she was hypothyroid with TSH 31.157 uIU/mL and FT4 of markable. He did have elevated Acetylcholine receptor antibodies 0.72 ng/dL. Upon discharge, Methimazole was discontinued and (AchRab) 13.7 nmol/L (nl 0.0 - 0.4). A trial of pyridostigmine was she was started on Levothyroxine 75 mcg daily. Due to failure of given with mild improvement in symptoms. Patient was discharged

S154 Thyroid Endocrine Practice 27 (2021) S141eS188 with methimazole 20 mg BID, propranolol 10 mg BID and pyrido- elements, and foci of papillary or follicular thyroid carcinoma are stigmine with outpatient endocrinology and neurology follow up. observed on cytology and histopathology. High Ki-67 index ( > 30%) Discussion: MG associated with autoimmune thyroid disease and is reported in all cases of ATC; tumors also tend to stain for PAX8, usually has a mild clinical presentation with preferential ocular p53, keratin, and vimentin, with thyroglobulin undetectable. Next- involvement. These patients do not typically have either Thymic generation DNA sequencing in one case series found BRAF and TP53 disease or AchRab’s. Our case illustrates an important teaching mutations in the majority of tumors. Though accumulated evidence point. It is imperative that clinicians distinguish and differentiate indicates that ATC transforms from preexisting differentiated thy- between two similarly presenting autoimmune illnesses when eye roid carcinoma, the events leading to anaplastic transformation disease is present. Ptosis is not a symptom related to graves oph- remain unclear. Surgery is indicated when tumors are operable, and thalmopathy. The two pathologies may coexist or can precede one external beam radiation and chemotherapy are also used to slow another. This case also highlights that when both conditions coexist tumor progression. Early end-of-life planning is important given in active form, successful treatment is possible if timely diagnoses the poor prognosis for ATC. are accomplished. https://doi.org/10.1016/j.eprac.2021.04.795 https://doi.org/10.1016/j.eprac.2021.04.794

Abstract #1001407 Abstract #1001399 Adherence to Guideline-Based Management and Anaplastic Thyroid Carcinoma as the Etiology of a Monitoring of Patients with Differentiated Thyroid Rapidly Enlarging Neck Mass Cancer

Author Block: Noor Wazzan, MD - Primary author/presenter, Author Block: Teresa Sciortino - University of Kansas; Internal Medicine/Endocrinology, Southern Illinois University Sujata Panthi, MBBS - co-author, University of Kansas; School of Medicine; Edem Agamah, MD - Co-author, Internal Rudruidee Karnchanasorn, MD - co-author, University of Kansas Medicine/Oncology, Southern Illinois University School of Medicine; Nassim Banisaeed, MD - Co-author, Pathology, Objective: Differentiated thyroid cancers (DTC) are becoming Pathology Associates of Central Illinois; Michael Jakoby, MD/MA - increasingly prevalent, in part due to advanced imaging and Co-author, Internal Medicine/Endocrinology, Southern Illinois detection techniques1. The American Thyroid Association (ATA) has University School of Medicine; Sanober Parveen, MD - Co-author, released evidence-based clinical practice guidelines regarding the Internal Medicine/Endocrinology, Southern Illinois University management and post-surgical surveillance of DTC2. In this study, School of Medicine we examined practitioner adherence at our institution to estab- lished ATA guidelines by identifying the frequency of documenta- Introduction: Anaplastic thyroid cancer (ATC) is an undifferenti- tion of initial risk stratification (IRS), clinical response to therapy ated tumor of the thyroid follicular epithelium representing (CRT), and goal TSH in outpatient clinic notes. We also compared approximately 0.5% of clinically recognized thyroid cancers. We patients’ documented goal TSH, when present, with current TSH lab present a case of ATC as the cause of a rapidly enlarging neck mass. values to identify the number of patients that were currently at goal Case Description: A 74-year-old female reported a rapidly TSH. enlarging neck mass over two months. She experienced hoarse- Methods: This was a retrospective chart review of 200 unique pa- ness, shortness of breath, night sweats and weight loss. Computed tients with a diagnosis of DTC seen at the University of Kansas tomography (CT) of the neck and chest revealed a 5.4 x 8.1 x 13 cm Medical Center endocrinology outpatient clinic between January 1, thyroid mass extending into the carotid and submandibular spaces, 2019 and December 31, 2019. The quality measures were selected larynx, anterior neck musculature, and left submandibular gland. based on recommended ATA clinical practice guidelines, and Cytopathology from a core biopsy showed cells with pleomorphism included documentation of initial risk stratification, clinical and areas of spindle formation consistent with undifferentiated response to therapy, TSH goal, and most recent TSH lab values. carcinoma of the thyroid. Cells stained for vimentin, PAX8, AE1/ Variables are expressed in percentages, and the Chi-square test was AE3, and CK7. Ki-67 index was 70%, and no thyroglobulin was used for comparison analysis. detectable. The patient received parenteral glucocorticoids, and Results: 200 outpatient visits were reviewed in total. The age range shortness of breath improved. She was diagnosed with inoperable of patients was 18-86 years old, with a mean age of 52. 78% of ATC and started on chemotherapy with doxorubicin and docetaxel. patients were female. IRS was documented in 36% of patients, and Follow up CT of the neck after two months of treatment showed CRT was documented in 16%. TSH goal was documented in 64% of decrease in size of the neck mass, though multiple pulmonary patients. Of these patients, there was no significant difference in nodules were present on CT of the chest and extensive retroperi- patients at goal TSH whose IRS was documented compared to no toneal and right external iliac lymphadenopathy was demonstrated IRS documentation (36.1% vs. 33.6%, P 0. 721). However, patients on CT of the abdomen. Findings of chest and abdominal imaging with CRT documented were more likely to be at goal TSH compared were interpreted to indicate distant metastases from the patient’s to no CRT documentation (62.5% vs. 28.9%, P < 0.001). ATC. Discussion/Conclusion: We identified a gap at our institution be- Discussion: ATC is one of the most aggressive solid tumors. Median tween current patient care and clinical practice guidelines for the survival documented in the Surveillance, Epidemiology, and End management of thyroid cancer. Documentation was lacking, with Results(SEER) Program is four months. The diagnosis is suggested the majority of clinic notes not identifying the patient’s IRS and CRT. by a rapidly enlarging neck mass that is found to be large and This could reflect physicians’ unfamiliarity with the guidelines involve adjacent structures on neck imaging. Spindle cells in a themselves, or simply inadequate documentation practices. Pa- sarcoma-like pattern, pleomorphic and osteoclast-like giant cells, tients were more likely to be at TSH goal if CRT was documented in areas of squamous differentiation, rhabdoid and chondroid their clinic note. Enhancing knowledge of the current guidelines,

S155 Thyroid Endocrine Practice 27 (2021) S141eS188 and ensuring documentation of the clinical thought process behind Abstract #1001797 medical decision making could improve appropriate care of the patient with thyroid cancer. A Case of Atezolizumab- Associated Thyroiditis https://doi.org/10.1016/j.eprac.2021.04.796

Author Block: Mona Abouzaid, Endocrinology Registrar/SPR - Abstract #1001450 Primary author and presenter, Department of Endocrinology, Department of Endocrinology, Royal Victoria Infirmary, Newcastle A Case of Thyroiditis Following Severe COVID-19 Upon Tyne, UK, NE1 4LP; Mudassir Ali, Endocrinology Registrar/ Infection SPR - Co-author, Department of Endocrinology, Department of Endocrinology, Royal Victoria Infirmary, Newcastle Upon Tyne, UK, NE1 4LP; Simon Pearce, Endocrinology Consultant - Co-author, Author Block: Kwan Cheng - Hoftra Northwell; Rifka C. Schulman- Department of Endocrinology, Department of Endocrinology, Royal Rosenbaum, MD - Co-author, Long Island Jewish Medical Center Victoria Infirmary, Newcastle Upon Tyne, UK, NE1 4LP; Anna Mitchell, Endocrinology Consultant - Co-author, Department Introduction: The ongoing COVID-19 pandemic has been devas- of Endocrinology, Department of Endocrinology, Royal Victoria tating the United States since early 2020. As time went on, its extra- Infirmary, Newcastle Upon Tyne, UK, NE1 4LP pulmonary manifestations became further elucidated. Here we present a case of suspected thyroiditis from COVID-19 or intrave- Introduction: The immune checkpoint inhibitors, including anti- nous (IV) contrast. CTLA4 and anti-PD1 agents, have revolutionised the manage- Case Description: 34 year old man with schizoaffective disor- ment of some cancers, improving survival and prognosis. How- der, bowel obstruction with subsequent colectomy and co- ever, they commonly induce autoimmune endocrinopathies, lostomy, and recent COVID-19 ICU admission in May 2020 including thyroid dysfunction, hypophysitis and adrenalitis. presents in July with fevers and chills from group home. Pa- More recently, check point inhibitors targeting Programmed Cell tient had no history of lithium or amiodarone use. He did have Death Ligand 1 (PD-L1) have been introduced. We report the first a CT abdomen with IV contrast in May. He had symptoms of case, to our knowledge, of thyroiditis associated with the PD-L1 increased output from the colostomy and abdominal discom- inhibitor Atezolizumab. fort but denied any symptoms of neck pain, dysphagia, Case Description: A 51-year-old male, was diagnosed with dysphonia, heat intolerance, palpitations, or tremors. On T3N1M1b lung cancer with a solitary brain metastasis. The tumour admission, the patient received an abdominal CT scan with histology showed mixed small cell and adenocarcinoma. He intravenous contrast for his gastrointestinal symptoms which completed third cycle of Carboplatin, Etoposide and Atezolizumab was unremarkable. Lab studies showed TSH < 0.10 mU/L(0.27 in August 2020. He presented with new onset atrial fibrillation (AF) e 42 mU/L), TT3 108 ng/dl(80-200 ng/dl), and FT4 3.21 ng/ requiring hospital admission. Clinically he was thyrotoxic without dl(0.7-1.8 ng/dl). Thyroid ultrasound found no evidence of goitre or signs of thyroid eye disease. Biochemically, he was thy- nodules. Burch Wartofsky score was 60 from temperature of rotoxic with a fully suppressed TSH, a fT4 of 53.9 pmol/L (10.0 -22.0) 102.9 ºF, sinus tachycardia to 130 beats/min and mild and fT3 of 18.3 pmol/L (3.1-6.8). He was given beta blockers and abdominal discomfort with increased output from colostomy. digoxin for symptom relief and AF rate control, and was anti- Though the Burch Wartofsky score was suggestive of thyroid coagulated. His thyrotoxicosis was initially treated with a combi- storm, his FT4 was not severely elevated, therefore he was nation of Carbimazole 40 mg once daily and Prednisolone 30 mg started on methimazole 20 mg daily with metoprolol tartrate once daily. 12.5 mg twice a day. TSH receptor antibody and thyroid His thyroid autoantibodies were subsequently found to be stimulating immunoglobulin came back negative. Given high negative (TPO 13 ku/L, TSH receptor antibody < 1.0 iu/L) and a suspicion for thyroiditis from either COVID-19 or IV contrast, pertechnetate thyroid uptake scan showed no uptake at 20 methimazole was discontinued. Patient was subsequently dis- minutes in keeping with a diagnosis of thyroiditis. His Carbi- charged on metoprolol tartrate 12.5 mg twice a day. His follow mazole was then stopped and his steroids tapered down over 3 up labs in September during an admission for aspiration weeks. One week later, he was more thyrotoxic (fT4 79.5 and fT3 pneumonia revealed TSH < 0.10 mU/L(0.27 e 4.2 mU/L), TT3 16.7 pmol/L) but over the following 4 weeks, his thyroid func- 67.9 ng/dl(80-200 ng/dl), and FT4 1.28 ng/dl(0.7-1.8 ng/dl) tion tests improved (fT4 33.8 then 13.7 pmol/L; fT3 8.5 and 3.9 suggesting resolving thyroiditis. pmol/L). 1 month after his initial presentation, his TSH was 3.88 Discussion: There are a handful of cases of subacute thyroiditis miu/L with a fT4 of 9.3 pmol/L and a fT3 of 2.6 pmol/L sug- caused by COVID-19 viral infection described in literature. Our gestive of an evolving hypothyroid phase. He remains in rate- patient’s thyroiditis is further complicated by recent IV controlled AF. contrast use, which is commonly used. Both IV contrast and Discussion: Endocrinopathies commonly complicate checkpoint COVID-19 can cause thyroiditis, though post-viral thyroiditis inhibitor therapy, with approximately one third of patients devel- typically presents with anterior neck pain. Treatment options oping an endocrinopathy after treatment, with thyroid dysfunction have beta blockers in common but painless thyroiditis from IV being the most commonly reported. contrast usually does not require prednisone or nonsteroidal The spectrum of primary thyroid dysfunction reported with anti-inflammatory drugs. Our case helps raise the awareness of immune checkpoint inhibitors ranges from thyrotoxicosis due COVID-19 and IV contrast as possible causes of thyrotoxicosis to thyroiditis or Graves’ disease, to hypothyroidism which can during this pandemic. Thyroiditis should always be part of the be transient or permanent. Rarely, thyroid storm has been differential in the workup of thyrotoxicosis in a patient reported. The time of onset for thyroid dysfunction is variable, recently diagnosed with COVID-19 in the last couple of but often occurs after 3 cycles of therapy. Thyroid autoanti- months. bodiesandthyroiduptakescanscanbeusefulinrefining the https://doi.org/10.1016/j.eprac.2021.04.797 diagnosis. Treatment focuses on management of the primary

S156 Thyroid Endocrine Practice 27 (2021) S141eS188 disorder, and symptom control. Given that thyroid dysfunction Abstract #1002106 can be transient, a trial off therapy is often appropriate. https://doi.org/10.1016/j.eprac.2021.04.798 Functional Struma Ovarii Associated with Hyperthyroidism and Thyroid Antibodies

Abstract #1001910 Author Block: Preethi Padmanaban, M.D., M.B.B.S - Primary author, Brain-Lung-Thyroid Syndrome (BTLS) Diagnosed in an Department of Endocrinology, George Washington University; Adult and Caused by a Newly Recognized Pathogenic Sabyasachi Sen, M.D. - Co-author, Department of Endocrinology, Variant of Thyroid Transcription Factor-1 (TTF-1) George Washington University

Introduction: Struma ovarii, also known as “goiter of the ovary”,is Author Block: Makarem Abu Limon, MD - Presenter, Primary a rare teratomatous tumor constituting less than 1% of all ovarian Author, Internal Medicine/Endocrinology, Southern Illinois tumors. It is defined by the presence of mature thyroid tissue University School of Medicine; Sanober Parveen, MD - Co-author, occupying at least 50% of the entire tumor mass. Hyperthyroidism Internal Medicine/Endocrinology, Southern Illinois University in this circumstance may be associated with ascites, abdominal School of Medicine; Anis Rehman, MD - Co-author, Internal discomfort or irregular menstrual bleeding and occurs in about 5- Medicine/Endocrinology, Southern Illinois University School of 15% of all Struma ovarii cases. Most of these patients are asymp- Medicine; Michael Jakoby, MD/MA - Co-author, Internal Medicine/ tomatic and diagnosis is usually delayed due to non-specific Endocrinology, Southern Illinois University School of Medicine symptoms associated with over or underactivity of thyroid gland. Case Description: We report a case of 34-year-old clinically Introduction: Brain-Lung-Thyroid Syndrome (BLTS), also known asymptomatic female who had been followed for 6 years for hy- as benign hereditary chorea, is a rare autosomal dominant dis- perthyroidism with TSH < 0.006 uIU/ml, FreeT4 1.98 ng/ml, FreeT3 order caused by mutations in the NK2 Homeobox 1 (NKX2-1; 5.3 pg/ml, elevated TSI 1.70 IU/L, TPO 38IU/ml, anti-thyroglobulin TTF-1) gene located on chromosome 14q13. The gene codes for antibody 9.3 IU/ml. Radioiodine thyroid scan showed minimal thyroid transcription factor-1 (TTF-1) expressed in the devel- uptake in both thyroid lobes (24-hour uptake was 0.3%). She sub- oping brain, lung, and thyroid. The major manifestations of BLTS sequently underwent evaluation for lower abdominal pain and are generalized chorea, recurrent respiratory infections, and menstrual irregularities which revealed a large left ovarian cyst hypothyroidism, with the diagnosis typically made in infancy or around 15cm and small right sided ovarian cyst. Laparoscopic early childhood. We present a case of BLTS diagnosed in an bilateral ovarian cystectomy was performed and the final pathology adult. revealed Struma ovarii of the left ovarian cyst with the entire Case Description: A 23-year-old female was referred for hypo- ovarian tumor made up of benign thyroid tissue. Thyroid function thyroidism. History was notable for chorea that worsened after tests performed 3 months after surgical removal of Struma ovarii birth of the patient’s daughter two years before referral. The showed euthyroidism. daughter had been diagnosed with congenital hypothyroidism, Discussion: Although hyperthyroidism from Struma ovarii is rare, it chorea, and neonatal respiratory distress syndrome despite full should be considered as a differential diagnosis in individuals with term delivery. Neither of the patient’s parents had a move- suppressed TSH, elevated thyroid hormones and low thyroid gland ment disorder, hypothyroidism, or pulmonary diseases. radioiodine uptake. We present a rare case with detailed laboratory Choreiform movements of the extremities and trunk were and immunological data before and after ovarian extirpation with observed, though no thyroid enlargement or discrete nodules resolution of hyperthyroidism associated with functional Struma were appreciated on direct neck examination. TSH was ovarii. elevated at 12.13 mIU/L (0.45-5.33), and ultrasound revealed a https://doi.org/10.1016/j.eprac.2021.04.800 normalsize(rightlobe4.7x1.7x1.6cm;leftlobe4.1x1.2x 1.3 cm), slightly heterogeneous thyroid with an 8 mm, hypo- echoic left lobe nodule. Sequencing of TTF-1 by GeneDx Abstract #1002305 (Gaithersburg, MD) revealed the patient and her daughter were heterozygous for a previously unreported nonsense A Rare Coexistence of Secondary Hypothyroidism, mutation, c.664 G >T (p.Glu222Ter), in exon three predicted to Stargardt Disease, and Ehlers-Danlos Syndrome (EDS) be a pathogenic variant due to loss of protein function from premature truncation. Discussion: This case is notable for three reasons. First, BLTS is Author Block: Muntazir Ali Sayed - RCSM Government Medical rare; though epidemiological studies are limited, the estimated College Kolhapur, India; Syed Wajih Rizvi, MD - Co-author, population prevalence is ~1:500,000. There appears to be a Endocrinology, R-Endocrinology; Anum Khan, MD - Co-author, modest female predominance (1.4:1). Second, manifestations Internal Medicine, R-Endocrinology; Shameela Begum, MD - Co- of BLTS occur in infancy or early childhood, and diagnosing author, Internal Medicine, R-Endocrinology; Hira Akhlaq, MBBS - the condition in an adult is very unusual. Third, a new path- Co-author, Internal Medicine, R-Endocrinology; ogenic mutation of TTF-1 has been identified, extending the Summaiya Nazneen, MBBS - Co-author, Internal Medicine, library of known pathogenic TTF-1 variants and providing a R-Endocrinology; Shereen Naccour, MD - Co-author, Internal genotype-phenotype correlation for the mutation in this newly Medicine, R-Endocrinology; Sadiq Ali Sayed, MBBS - Co-author, recognized BTLS kindred. The patient’s case also illustrates Internal Medicine, National Pirogov Memorial Medical University, that adult endocrinologists need to be vigilant for the occur- Vinnytsya, Ukraine rence of endocrinopathies in rare syndromes that may have escaped diagnosis in childhood. Introduction: Ehlers-Danlos syndrome (EDS) is used to describe https://doi.org/10.1016/j.eprac.2021.04.799 multiple diverse connective tissue disorders that vary in their

S157 Thyroid Endocrine Practice 27 (2021) S141eS188 underlying genetic sources and clinical presentations. Stargardt Introduction: Ectopic thyroid tissue can be found anywhere along disease, also called Stargardt macular dystrophy (STGD), charac- its embryological path of decent from the base of tongue into the terized by the loss of photoreceptor cells in the macula, is a rare mediastinum. Thyroid cancer in ectopic thyroid tissue is extremely autosomal recessive disease resulting in scotoma. We present a rare. We present a unique case of thyroid neoplasm incidentally case of a female patient who had both these syndromes, resulting in found in a mediastinal mass, but benign pathology in the orthotopic secondary hypothyroidism. thyroid gland. In addition, it was not entirely clear whether the Case Description: A 31-year-old Caucasian female with a PMHx pathologic diagnosis from the mediastinal mass was noninvasive of EDS, and Stargardt disease was referred to our out-patient follicular thyroid neoplasm with papillary like nuclear features Endocrinology clinic for hypothyroidism. Patient reported me- (NIFTP) versus follicular variant papillary thyroid carcinoma dium energy levels, weight gain, constipation, decreased appe- (FVPTC). tite, and dry skin. She denied any symptoms of difficulty Case Description: 66-year-old man presented with an incidental swallowing, heat intolerance, and problems with concentration mediastinal mass on chest CT. The mass was resected and pathol- or memory. Patient had a PMHx of acute Lyme disease, chronic ogy revealed thyroid tissue described as well-circumscribed parotitis and STGT, the last of which was diagnosed at the age of follicular patterned thyroid neoplasm with papillary-like nuclear 13 years. Her symptoms that led to the diagnosis of Stargardt features. The differential diagnosis was NIFTP versus FVPTC; an syndrome included photophobia since the age of eight years official determination was unable to be rendered as the entire which caused her frequent headaches, night blindness, and capsule was not submitted for examination. Further evaluation increased difficulty in adapting to the dim light. During further revealed a substernal multinodular goiter with mild tracheal years, she also experienced central blindness which deteriorated compression. Thyroid labs were normal and fine needle aspiration her vision accuracy to 20/100. She was then diagnosed with EDS of representative thyroid nodules were benign. Thyroidectomy was at the age of 19 years. Physical examination exhibited joints performed and pathology was benign. The diagnosis was meta- hypermobility. Laboratory evaluation revealed Free T4 of 1.59 ng/ static thyroid cancer vs. thyroid neoplasm in ectopic thyroid tissue. dL, and TSH of 4.23 uIU/mL. Provided the combination of her Postoperatively, Thyroglobulin level (Tg) was 0.3 ng/ml [1.4-29.2] biochemistry and symptomatic hypothyroidism, the decision was and Thyroglobulin antibody level was < 1.0 IU/ml [0-0.9]. After made to increase the dose of her thyroid hormone replacement extensive discussion at our multi-disciplinary conference, RAI therapy from Cytomel 5mcg (PO x QID) and Levothyroxine ablation was recommended. Whole body I 123 scan showed 4 foci 112mcg (PO x Qam) to Cytomel 15mcg in the morning and 10 of uptake in the neck and he was treated with 75 milliCuries I 131. mcg in the evening, and Levothyroxine 125 mcg (PO x Qam). Discussion: This is an extremely rare case of NIFTP vs FVPTC found This further normalized her Free T4 and serum TSH values to in ectopic mediastinal mass, and benign pathology in orthotopic 1.14 ng/dL and 2.94 uIU/mL respectively, and significantly thyroid gland. Another differential diagnosis is that mediastinal improved her respective symptoms of hypothyroidism in the mass could be metastasis with undetectable primary in thyroid follow-up appointment 8 weeks later. gland. NIFTP has features of FVPTC except it has no capsule or Discussion: The presence of secondary hypothyroidism, Stargardt lymphovascular invasion and no aggressive histology such as high disease, and EDS simultaneously has not been discussed previously mitotic rate and necrosis. NIFTP has very low risk of recurrence and in the literature. The mechanism of a possible association between is treated conservatively, whereas FVPTC may need an aggressive the three conditions is unknown. Potential causes for her hypo- approach based on tumor characteristics such as lymphovascular thyrdoisim were considered, such as post-infectious hypothyroid- invasion, extrathyroidal extension and lymph node metastases. Our ism, endocrine dysfunction and autoimmune attack, and secondary patient’s unique clinical presentation created a treatment dilemma. hypothyroidism due to CNS injury. It is probable that she developed In our case, the decision was made to treat aggressively, given the a descending infection after parotitis, which subsequently led to patient’s initial mediastinal mass pathology of NIFTP vs. FVPTC, the thyroiditis and post-infectious hypothyroidism. Moreover, given detectable postoperative Tg, and the multiple foci of I 123 uptake in the history of her Lyme disease, which involved the central nervous his neck. The complexity of this case illustrates the importance of a system (CNS), her hypothyroidism could be secondary to CNS multi-disciplinary approach for treatment. injury. In addition to that, a simple autoimmune phenomenon as an https://doi.org/10.1016/j.eprac.2021.04.802 origin of hypothyroidism, cannot be overlooked as well. However, further investigations are being performed to find the origin and pathophysiology of her hypothyroidism. In summary, this case ex- Abstract #1002386 emplifies a very rare coexistence of secondary hypothyroidism, Stargardt disease, and EDS. A Challenging Case of Severe Bilateral Graves’ https://doi.org/10.1016/j.eprac.2021.04.801 Orbitopathy (GO) Involving the Prosthetic Eye, in a Patient with History of Hypothyroidism

Abstract #1002367 Author Block: Mir Mudassir Ali - Royal Victoria Infirmary; A Complicated Case of Ectopic Thyroid Neoplasm in Mona Abouzaid, MRCP - Co-author, Royal Victoria Infirmary; Mediastinal Mass with Benign Pathology in Orthotopic Lucy Clarke, FRCS, FRCOphth - Co-author, Royal Victoria Infirmary; Thyroid Gland Gordon Lau, FRCS, FRCOphth - Co-author, Royal Victoria Infirmary; Anna Mitchell, FRCP, PhD - Co-author, Royal Victoria Infirmary; Catherine Napier, FRCP, PhD - Co-author, Royal Victoria Infirmary; Author Block: Monika Akula - Jersey Shore University Medical Simon Pearce, FRCP, MD - Co-author, Royal Victoria Infirmary Center; Tiffany Purewal, MD - co-author, Jersey Shore University Medical Center; Jennifer Cheng, DO - co-author, Jersey Shore Introduction: Graves' disease (GD) is one of the commonest auto- University Medical Center; Danielle Lann, MD - co-author, Jersey immune conditions, which is frequently associated with inflam- Shore University Medical Center matory changes around the eyes (Graves’ orbitopathy; GO). GO

S158 Thyroid Endocrine Practice 27 (2021) S141eS188 frequently results in significant functional visual impairment, and Introduction: The Bethesda classification system utilized for cate- in the most severe cases, it can result in permanent loss of sight. gorizing thyroid cytopathology and molecular marker testing Rituximab (RTX) is a therapeutic anti CD-20 monoclonal antibody, platforms are useful tools to help determine subsequent manage- which is normally reserved for refractory cases of GO. It depletes ment of the thyroid nodule that has undergone fine needle aspi- circulating B lymphocytes and can improve active GO. ration (FNA). We present a patient diagnosed with Stage IV We present a challenging case of Graves’ thyrotoxicosis associ- Follicular Thyroid Cancer (FTC) that preoperatively had multiple ated with severe bilateral GO, in a patient with an anophthalmic FNAs that showed Bethesda III cytology and molecular testing socket. reclassifying the nodule as benign. Case Description: A 54 years old lady with past history of hypo- Case Description: 51-year-old woman with a history of Hashimo- thyroidism (Dec 2017) and ex-smoker, was referred to the endo- to's disease and multinodular goiter underwent FNA of dominant crine team in November 2019 with clinical and biochemical right lower pole 1.3x0.8x0.5 cm nodule which was benign. After 5 evidence of thyrotoxicosis and new onset fast atrial fibrillation. Her years, repeat thyroid ultrasound (US) showed increase in nodule GP had stopped levothyroxine in August 2019. Her left eye was size to 2.4x1.9x2.3 cm. Repeat FNA showed Bethesda Category III enucleated in 1999 for symptomatic relief of a painful blind eye with molecular markers indicating nodule was benign. One year following previous trauma. She had a primary orbital implant and later, the nodule increased to 2.8x2.5x2.3 cm and showed internal wears an artificial eye prosthesis. When seen in the endocrine clinic vascularity and irregular border posteriorly. The cytology was in October 2019 her TSH receptor antibody (TRAb) was 33.2 IU/L Bethesda III with molecular markers that again reclassified nodule (normal range: < 1.0 IU/L), TSH was suppressed at 0.05 mU/L (0.3- as benign. Six months later, nodule measured 3.11x2.48x2.78 cm. 4.5 mU/L), FT4 and FT3 were 32.4 (10-22 pmol/l) and 18.1 pmol/l Given the nodule growth and suspicious sonographic characteris- (3.1-6.8 pmol/l) respectively. She had soft tissue signs of GO in her tics, the patient underwent thyroidectomy. Final pathology right eye with clinical activity score (CAS) of 4/7. revealed 3.1cm angioinvasive encapsulated FTC with multifocal She was started on carbimazole 40 mg and levothyroxine 100 areas of transcapsular invasion and one focus of vascular invasion mcg was started 6 weeks later. On review, she reported a change in and multiple papillary microcarcinomas. Postoperatively, Thyro- the appearance of her left eye prosthesis, which she described as globulin (Tg) was 43 ng/ml (1.3-31.8) and Thyroglobulin antibody ‘’tilted upwards’’. Her MRI orbits showed bilateral GO including (TgAb) was 1.5 IU/ml (0-4). Neck US, Neck Computed Tomography enlargement of the inferior and medial recti behind her prosthesis (CT), Brain Magnetic Resonance Imaging, Spine and Pelvis X rays which explains the change in position she had noted. Due to were unremarkable. CT chest revealed multiple subcentimeter worsening GO and the fact she had only one functioning eye, a pulmonary nodules, suspicious for metastases. She underwent decision was taken to offer her immunomodulatory therapy. She Radioactive Iodine ablation (RAI) with 150 milliCuries I-131. Post repeatedly refused methylprednisolone as she was concerned therapy whole body scan showed abnormal uptake in the mid to about weight gain. She eventually agreed to have a RTX infusion lower neck and bilateral pulmonary nodules compatible with the (received 500 mg iv), which resulted in a transient improvement in lung metastases. CT chest 6 months later showed decrease in size her right eye. When she was reviewed in June 2020, the right eye and number of lung nodules. Eight months post RAI, Tg decreased lagophthalmos remained a problem, hence she was given botuli- to 0.1 ng/ml. num toxin injection She is soon planned for right upper eyelid Discussion: Molecular marker testing platforms are useful in blepharotomy and has been referred to national artificial eye ser- assisting with surgical planning and possibly avoiding unnecessary vice. Treatment for active GO is ongoing. thyroid surgery. However, this case illustrates that molecular Discussion: This was a rare and unique case of Graves’ thyrotoxi- markers can give healthcare providers a false sense of reassurance cosis associated with severe GO, involving even the prosthetic eye in thyroid nodules that have highly suspicious sonographic fea- in a patient with background history of hypothyroidism likely tures. Thyroid nodules with Bethesda Category III or IV cytology related to inhibitory TSH receptor antibody.In Graves’ disease, with benign molecular marker testing still require ongoing moni- conversion of hypothyroidism to hyperthyroidism is rare, yet toring. If repeat US show features suspicious for malignancy such as important to recognize, clinical phenomenon. increase in nodule size, irregular borders, nodule taller than wide, The observation of muscle manifestations of GO in an enucleated calcifications, hypervascularity, extrathyroidal extension or lymph orbit emphasizes that the pathogenic immune response is directed node involvement, we suggest thyroidectomy despite benign at antigens in the soft tissues (extraocular muscles, fibroblasts, cytology and/or molecular marker testing. orbital fat/adipocytes) rather than in the globe of the eye. Treat- https://doi.org/10.1016/j.eprac.2021.04.804 ment of the condition in a uniocular patient necessitated a reduced threshold for intervention. https://doi.org/10.1016/j.eprac.2021.04.803 Abstract #1002477

Association of Insulin Resistance with Thyroid Abstract #1002416 Hormones in Euthyroid Individuals

Delayed Diagnosis of Metastatic Follicular Thyroid Cancer in a Patient with Multiple Benign Fine Needle Aspirations Author Block: Swati Srivastava, M.D, FRCP (Edin), FICP - Primary author, SMS Medical College; Megha Agrawal, Resident M.D - Co- author, SMS Medical College; Shubham Agrawal, M.D - co-author, Author Block: Monika Akula - Jersey Shore University Medical SMS Medical College; Prasun Bhaskar, Resident M.D - Co-author, Center; Tiffany Purewal, MD - co-author, Jersey Shore University SMS Medical College; Mukesh K. Chopra, Resident M.D - Co-author, Medical Center; Jennifer Cheng, DO - co-author, Jersey Shore SMS Medical College; Mangi Lal, Resident M.D - Co-author, SMS University Medical Center; Danielle Lann, MD - co-author, Jersey Medical College; Rakesh Kumar, Resident M.D - Co-author, SMS Shore University Medical Center Medical College; Gunja Jain, M.D - Co-author, SMS Medical College

S159 Thyroid Endocrine Practice 27 (2021) S141eS188

Objective: Insulin resistance is an established predisposing deter- Case Description: A 54-year-old male presented with intermittent minant to the cluster of metabolic syndrome and related cardiac dizziness of three weeks duration. The patient also reported dys- morbidity. The influence of thyroid function on energy equilibrium pnea on exertion and a pressure sensation with swallowing food or and insulin resistance has been studied with varied results in the water. Upon raising his arms, he noted erythema of the face, a past. Recent studies suggest that high thyroid hormone levels even choking sensation, and difficulty breathing. Exam revealed a within the euthyroid range may influence insulin resistance. diffusely enlarged goiter with substernal extension and a positive The present study was designed to study the association of thy- Pemberton’s sign. CTA of the head and neck revealed a large MNG roid hormone levels (FT3, FT4, FT3/FT4 ratio), TSH with insulin with substernal extension causing severe compression and mod- resistance in euthyroid patients. erate displacement of the adjacent trachea and upper esophagus. Methods: We conducted an observational cross-sectional study in The patient was found to be clinically and biochemically euthy- the Department of Medicine SMS Medical College, Jaipur. 300 roid. Due to the clinical and imaging findings demonstrating thy- euthyroid individuals aged 18-60 years were included in the study roid compression of adjacent structures, he underwent after giving informed consent. Patients with thyroid dysfunction thyroidectomy with subsequent resolution of his symptoms. Sur- and thyroid medications were excluded. Participants were cate- gical pathology revealed multiple foci of papillary thyroid carci- gorized in tertiles (low, intermediate, high) according to their TSH, noma of both the right and left lobes, ranging in size from 0.2 cm to FT3, FT4 levels, FT3/ FT4 ratio. For estimation of insulin resistance 0.8 cm with AJCC 8th edition stage I pathology and ATA low risk for we have used Homeostasis model assessment for insulin resistance, recurrence. Post-operative monitoring revealed undetectable HOMA-IR, calculated as fasting insulin (Mu/litre) times fasting thyroglobulin and the patient was treated with levothyroxine to a glucose (mmol/litre) divided by 22.5. The study population char- target TSH of 0.5 e 200 uIU/mL. acteristics were compared using a two-way analysis of variance Discussion: Pemberton’s sign, often seen in non-toxic MNGs with (ANOVA) test for continuous variables. substernal extension, is a useful physical exam maneuver to help Results: We observed elevated HOMA-IR in high normal FT3tertile establish reversible obstruction through the thoracic outlet that can (3.07 + 0.97) compared to low (1.63+ 0.37) and intermediate be seen with large goiters. In patients undergoing thyroidectomy, (2.74+0.89) FT3 tertile (p-value< .001). Low normal FT4 was asso- surgical pathology has demonstrated that 4 e 17% of MNGs have ciated with elevated HOMA-IR but this association was not statis- been found to contain microscopic papillary carcinoma. Although tically significant (p-value< 0.321). HOMA-IR was elevated in high counterintuitive that a large goiter would have microscopic papil- tertile of FT3: FT4 ratio (2.94+1.03) as compared to low (1.93+0.72) lary thyroid carcinoma, this is an important association that clini- and intermediate (2.55+0.95) (p< 0.001). No significant association cians should be aware of when evaluating these patients. was found between TSH and HOMA-IR. https://doi.org/10.1016/j.eprac.2021.04.806 Discussion/Conclusion: Insulin sensitivity is harmonized by the thyroid hormone FT3, which synchronizes the expression of GLUT 2 and glucokinase in the beta islets of the pancreas. Abstract #1002849 Transit of GLUT 4 to the plasma membrane in skeletal muscle and adipose tissue is promoted by FT3 which leads to better Treatment of Hypothyroid Patients with Nonalcoholic glucose tolerance. Increased adipose tissue volume and unfav- Fatty Liver Disease with Resmetirom, a Selective ourable metabolic profile are associated with increased leptin Thyroid Hormone Receptor Beta Agonist level which results in alteration of deiodinase 1 and deiodinase 2 activity. This leads to higher conversion of F4 to FT3. Elevated FT3 values and FT3/ FT4 ratio represents an adaptive process to Author Block: Rebecca Taub - Madrigal Pharmaceuticals; maintain adequate insulin homeostasis and improve insulin Jeannie Lucas, Endocrinologist - Presenter, Member; sensitivity in peripheral tissue. Manal Abdelmalek, Hepatology - co-author, Duke University Conclusion: In euthyroid individuals, increase in FT3 levels and FT3:FT4 ratio is positively associated with insulin resistance. Objective: Evidence suggests that non-alcoholic steatohepatitis https://doi.org/10.1016/j.eprac.2021.04.805 (NASH) may be a condition of hepatic hypothyroidism character- ized by elevated plasma reverse T3 (RT3) and low T3/RT3 ratio compared with healthy controls. The incidence of clinical and Abstract #1002672 subclinical hypothyroidism is higher in patients with NAFLD/NASH. Resmetirom (MGL-3196) is a liver-directed, orally active selective Microscopic Papillary Carcinoma in a Substernal thyroid hormone receptor-b agonist that reduced NASH and MRI- Goiter with Pemberton’s Sign PDFF (magnetic resonance proton density fat fraction (MRI-PDFF) in phase 2. MAESTRO-NAFLD-1 is a 52-week 1200 patient phase 3 randomized double-blind placebo-controlled NASH clinical trial to Author Block: Travis Goettemoeller - Cleveland Clinic; study the effect of resmetirom on non-invasive biomarkers and David Broome, MD - co-author, Endocrinology, Cleveland Clinic imaging (NCT04197479). This study includes an open label 100 mg active treatment arm in patients, with 43% on concomitant Introduction: Pemberton’s sign, originally described in 1946, thyroxine therapy. described a “useful sign given by a submerged goiter.” Pemberton’s Methods: An evaluation of baseline characteristics, imaging, bio- sign is said to be present when elevation of both arms “until they markers and safety was conducted in patients enrolled in the open touch the side of the head” elicits “after a minute or so, congestion label active treatment arm of MAESTRO-NAFLD-1, including hypo- of the face, some cyanosis, and lastly distress.” In this case, we thyroid patients on thyroxine replacement and euthyroid controls. report of a patient with a non-toxic multinodular goiter (MNG) Trial eligibility requires at least 3 metabolic risk factors, with substernal extension and a positive Pemberton’s sign who fibroscan kilopascals (kPa) consistent with F1 fibrosis stage, and underwent thyroidectomy with pathology demonstrating micro- MRI-PDFF8%. The primary and key secondary endpoints of scopic papillary thyroid carcinoma. MAESTRO-NAFLD-1 include safety, relative percent reduction of

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MRI-PDFF (week 16), LDL cholesterol (LDL-C) (week 24), apolipo- subsequent development of overt hypothyroidism requiring thy- protein B and triglycerides. All open label patients received 100 mg roid hormone supplementation. daily oral dose of resmetirom. Discussion: Different to recent evidence of Lenvatinib induced Results: Baseline characteristics in the hypothyroid arm (n¼76) thyrotoxicosis where 80% of patients developed thyrotoxicosis include mean (SD) age 58.9 (11.0), 82% female, BMI 36.2 (6.3), within the first 2 weeks of treatment and return to euthyroid state. diabetes 54%, hypertension 71%, dyslipidemia >70%, mean ASCVD Our patient developed thyrotoxicosis after 20 weeks of therapy and score 13.4% (14.4%), fibroscan kPa 8.3 (4.5)), MRI-PDFF 18.3% (8.1%), subsequently developed overt hypothyroidism requiring thyroid MRE kPa 2.97 (1.0), and euthyroid arm (n¼100) age 53.2 (11.0) 56% hormone replacement after re-initiation of Lenvatinib. For this female, BMI 36.1 (6.1), diabetes 45%, hypertension 67%, dyslipide- reason, is important to monitor thyroid function test every 4 weeks mia >70%, ASCVD score 10.7% (10.7%), fibroscan kPa 7.3 (2.5), MRI- while on Lenvatinib due to risk of thyroid dysfunction during any PDFF, 17.3% (5.9%), MRE 2.61 (0.7), with significant differences in stage of therapy. age, sex, fibroscan, and MRE, both groups consistent with fibrosis https://doi.org/10.1016/j.eprac.2021.04.808 stage 2 NASH. In hypothyroid compared to euthyroid patients baseline FT4 and RT3 were higher (p< 0.0001) while FT3 and FT3/ < fl RT3 were lower (p 0.0001) re ecting greater hepatic hypothy- Abstract #1002925 roidism in thyroxine-treated patients. TSH was not different. The difference in RT3 was partially corrected by treatment with Myxedema Coma or Uremic Coma? resmetirom. At week 16, cohorts had equivalent mean reductions in MRI-PDFF (51 and 52%, respectively). Statistically significantly re- ductions (all p< 0.0001) from baseline were observed in LDL-C Author Block: Manasa Veluru, MBBS - Primary author, Temple (-23% (2.3% (SE)), apolipoprotein-B (-22% (2.3%)), triglycerides University hospital; Kayla Ostiller, MD - Co-author, Temple (med, -32(7.8)), and lipoprotein(a) (-39% (4.6%)) in both pop- University hospital; Cherie L. Vaz, MD - Co-author, Temple ulations. No safety flags were identified, including no adverse University hospital events consistent with hypothyroidism or hyperthyroidism. Discussion/Conclusion: In this 52-week phase 3 open label study, Introduction: Myxedema coma is a life threatening, endocrine concomitant treatment with resmetirom and thyroxine was safe emergency with a high mortality rate. It poses a diagnostic chal- and resulted in pharmacodynamic measures of efficacy. lenge due to its rarity and its overlapping presentation with other https://doi.org/10.1016/j.eprac.2021.04.807 commonly seen critical conditions. We report a case of myxedema coma whose diagnosis was confounded by untreated ESRD thought to be causing uremic encephalopathy and discuss implications of Abstract #1002859 hypothyroidism in ESRD. Case Description: A 60-year-old female with PMH of ESRD on Delayed Lenvatinib Associated Thyrotoxicosis: A Case of Hemodialysis(HD), autoimmune hypothyroidism and seizure dis- Destructive Thyroiditis after 20 Weeks on Lenvatinib order presented with shortness of breath and swelling of legs. On exam, she was lethargic with pedal and peri-orbital edema with vitals significant for bradycardia and hypothermia. Laboratory work Author Block: Max Sosa-Pagan, MD - Primary Author, Ochsner up showed BUN 121 mg/dl [8-20 mg/dl], creatinine 16 mg/dl [06- Clinic Foundation; Susan Karam, MD - CO author, Endocrinology, 1.2 mg/dl], potassium 7 mmol/l [3.5-5.2 mmol/l]. EKG showed QTc Ochsner Clinic Foundation prolongation. Her presentation was attributed to missed HD causing uremic encephalopathy for which she underwent emer- Introduction: Thyroid dysfunction is a well described adverse ef- gent HD followed by repeat HD the next day. BUN and creatinine fect of Lenvatinib. Hypothyroidism is the most common thyroid improved significantly, however mental status worsened. Thyroid dysfunction associated to Lenvatinib with an incidence of 16% - 52%. function testing showed TSH 151 m(iU)/L [0.4-4.5 m(iU)L], total T3 Although less common, recent case reports have evidenced an 16 ng/dl[60-180 ng/dl], freeT4 0.49 ng/dl [0.89-1.76 ng/dl]. Random increased risk for thyrotoxicosis during early treatment with Len- cortisol was 8 mcg/dl. It was unclear if she was compliant with vatinib. The entirety of thyrotoxic cases were associated to Levothyroxine(LT4) at home. Myxedema score was 60 (1). She was destructive thyroiditis presenting within the first 8 weeks of treated with 100 mg IV Hydrocortisone followed by 200 mcg IV LT4. treatment and with 80% of cases occurring within the first two Mental status improved to baseline over the next few days. She was weeks of treatment. discharged on 200 mcg oral LT4 and Hydrocortisone 15 mg AM/10 Case Description: Here we present a case of a 58 year old Female mg PM with planned outpatient ACTH stimulation test. with history of metastatic Renal cell carcinoma on Lenvatinib who Discussion: Hypothyroidism is highly prevalent in ESRD patients as developed destructive thyroiditis after 20wks on treatment. The the metabolism of thyroid hormones is altered in kidney disorders patient had normal thyroid function test and no prior history of (2). Hypothyroidism is a plausible cardiovascular risk factor thereby thyroid dysfunction prior to Lenvatinib initiation. Thyroid function causing increased mortality in ESRD patients (3). Myxedema coma test were monitored every 4 weeks while on treatment. On week 21 presents with decreased mental status, hypothermia and symptoms patient developed palpitations, tremors, insomnia, heat intolerance related to slowing of function in multiple organs. Diagnosis can be and neck tenderness. Thyroid function test and initial blood work challenging as the presenting symptoms are also seen in common showed; TSH < 0.01uIU/mL, FT4 1.97ng/dL, ESR 65mm/Hr and CRP critical conditions such as sepsis, stroke, shock, intoxication or renal 12mg/L that was consistent thyrotoxicosis from destructive failure as in our case. While myxedema coma is primarily a clinical thyroiditis. Lenvatinib was stopped and Metoprolol 50mg BID for diagnosis, diagnostic scoring criteria can assist with predicting the symptom relief was initiated. Thyroid function test normalized over probability of the diagnosis (1). Myxedema coma should be a 8 week period. Lenvatinib was resumed after 10 weeks with considered in the differential diagnosis of a critically ill patient with

S161 Thyroid Endocrine Practice 27 (2021) S141eS188 renal failure who is not improving. Thyroid function testing at pre- Abstract #1003008 sentation can be critical to a patient's prognosis. https://doi.org/10.1016/j.eprac.2021.04.809 A Curious Case of Anaphylaxis to Synthetic Thyroid Hormone

Abstract #1002999 Author Block: Jessica Lucier - Houston Methodist; Laila Tabatabai, Difficulty Monitoring Thyroid Cancer Recurrence With MD - co-author, Houston Methodist Thyroglobulin Antibody In Patients Receiving Immunoglobulin Therapy Introduction: Anaphylaxis secondary to thyroid hormone replacement is a very rare side effect. An anaphylactic reaction in these cases is usually secondary to inactive additives found in the Author Block: Manthan Pandya - Rutgers - Robert Wood Johnson thyroid hormone pill. Synthroid uses different additives than Ar- Medical School; Sara Lubitz, ENDOCRINOLOGIST - Co-Author, mour thyroid formularies. In theory, patients should not have Endocrinology, Rutgers - Robert Wood Johnson Medical School allergic reactions to both formularies. Case Description: A 73 year old female with a PMH of multinodular Introduction: Measuring serum thyroglobulin (Tg) levels and anti- goiter s/p left thyroid lobectomy in 1997 and history of anaphylaxis Tg antibody is an important modality to monitor patients for to Synthroid presented for complete thyroidectomy secondary to recurrence in the follow up of DTC. High anti-Tg antibody levels multinodular goiter. She had her completion thyroidectomy on day could make interpretation of Tg levels unreliable and a trend to- one of admission, with no complications. On post-op day one she wards increasing anti-Tg antibody levels should prompt additional was started on a replacement dose of Armour thyroid by the investigations and potentially additional therapies. It is estimated Endocrine Surgery team. Prior to the surgery, the team had decided that up to 10% of the general population can have detectable anti-Tg on Armour thyroid replacement to avoid any possible allergic re- antibodies. Immunoglobulin therapy such as Octagam®, are sterile action, given her history of anaphylaxis. Shortly after being given preparations of highly purified immunoglobulin G (IgG) derived her first dose of Armour thyroid, she developed shortness of breath from large pools of human plasma which leads to passive transfer of and throat swelling. She was determined to be in anaphylaxis and antibodies including anti-Tg antibody. Here we present two cases of given epinephrine and high dose steroids, with resolution of her patients with PTC on IVIG injections with fluctuating anti-Tg anti- symptoms. Endocrinology was consulted for recommendations on body levels, making monitoring extremely challenging. thyroid replacement in the setting of known anaphylaxis to exog- Case Description: The first case is of a 60-year-old female with a enous thyroid hormone. On post-op day 2 and 3, thyroid hormone history of Myasthenia Gravis (on weekly subcutaneous immune replacement was held. Daily thyroid function labs were obtained globulin Hizentra®,) who had undergone total thyroidectomy with her free T4 trending down on a daily basis. She began devel- following FNA of a 7 mm isthmus nodule. Pathology demon- oping cold intolerance, mental fogging, and fatigue. As she had strated multifocal follicular variant of papillary thyroid cancer anaphylaxis to both synthetic thyroid hormone and animal product and a second 0.4 cm micropapillary cancer in the right lobe with thyroid hormone, it was determined that she would need desen- no lymphovascular invasion and margins free of tumor. She sitization to a replacement medication. Tirosint was chosen as it received 50 mCi I-131 and her post treatment scan showed had the least amount of additives. She underwent desensitization uptake within the thyroid bed only. Serial ultrasounds have been on post-op day 4 of her hospital stay and tolerate a full dose of negative for recurrence. Her Tg levels by LCMS have remained < 100mcg Tirosint on hospital day 5. She had no further episodes of 0.2 ng/mL. Anti-Tg antibodies have trended up and down anaphylaxis. She was followed outpatient in our clinic, with no ranging from 17 to 168 IU/mL. further allergic reactions while on Tirosint. The second case is of a 75-year-old male with a history of CLL (on Discussion: There are no documented allergies to the active monthly IVIG Octagam ® injections) who had total thyroidectomy ingredient in thyroid replacement medications. Allergies to the following FNA of a 1.7 cm left lobe nodule. Pathology was consistent additives in these medications have been seen. This patient was with papillary thyroid cancer with lymphovascular invasion. He unique in having anaphylaxis to both synthetic and animal product was treated with 99.3 mCi I-131 and post treatment scan showed thyroid hormone replacement. Knowing alternate replacement uptake only in the neck. Since the RAI, serial ultrasounds have been options and what additives are in each formulary can be helpful in unremarkable for recurrence. Tg levels by LCMS have also remained these situations. The use of desensitization is also a helpful tool to < 0.2 ng/mL, however his anti-Tg antibody levels have ranged from allow the use of an essential medication. 8 to 17.6 IU/mL. https://doi.org/10.1016/j.eprac.2021.04.811 Discussion: Immunoglobulin therapy can affect the surveillance of patients with PTC due to passive transfer of antibodies including anti-Tg antibody. Here we present cases of two patients with sup- Abstract #1003023 pressed Tg and negative imaging, with fluctuating anti-Tg anti- bodies due to immunoglobulin therapy. Per ATA guidelines, a rising A 62 Year-old Female with Thyroid Cancer and Spine anti-Tg antibody would categorize the response as “biochemical Metastasis: A Case Report incomplete”, while a declining anti-Tg antibody would deem the response as “indeterminate”. This is especially important as the patient’s TSH goal is based on their response to therapy. Hence, Author Block: Michiya Nishino, MD - co-author, Pathology, Beth these cases highlight the importance of a more robust method of Israel Deaconess Medical Center; John Parker, MD - co-author, surveillance in patients with PTC on Immunoglobulin therapy due Nuclear Medicine, Beth Israel Deaconess Medical Center; to varying anti-Tg antibodies. Runhua Hou, MD - primary author, Medicine, Division of https://doi.org/10.1016/j.eprac.2021.04.810 Endocrinology, Beth Israel Deaconess Medical Center

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Introduction: About 7%-23% of patients with thyroid cancer (ANCA) in a patient who presented a previous adverse reaction to develop distant metastases over time. Prognosis is poor when MMI. metastasis occurs. Bone metastasis can pose a treatment challenge Case Description: This is a 64-year-old Hispanic female with pri- as a combination therapy including surgery, radioactive iodine, and mary hyperthyroidism secondary to toxic multinodular goiter chemoradiation are often needed. Despite aggressive treatment, (TMNG), treated with radioiodine therapy which failed hyperthy- many patients may still die of thyroid cancer. We present a case to roidism, and subsequently treated with MMI. The patient was illustrate the difficulty in management of bone metastatic lesion. subsequently hospitalized for atrial fibrillation associated with Case Description: A 62 year-old female had total thyroidectomy for thyrotoxicosis, as she had self-discontinued MMI because of severe a 2.8 cm encapsulated angioinvasive follicular cancer in 2003. She pruritus. Work up done confirmed hyperthyroidism. A plain neck received 150 mCi of I-131 for remnant ablation and post therapy CT revealed a diffusely enlarged thyroid gland with multiple solid whole body scan (WBS) showed no distant metastasis. She did well and cystic masses, and I123 thyroid uptake and scan revealed patchy for about 5 years while on suppressive dose of Levothyroxine. areas of hot and cold uptake. PTU was initiated, which lead to Routine monitoring showed gradually increased thyroglobulin partial biochemical control. Over the following weeks, the patient levels which led to further imaging evaluation. Multiple neck ul- developed gradually expanding skin plaques with induration and trasounds, diagnostic thyrogen I-131 WBS and a PET-CT were all necrosis over her upper and lower limbs and earlobes, without any negative between 2009 and 2012. A withdrawal RAI-WBS in constitutional symptoms. A course of amoxicillin-clavulanate and December 2012 showed intense uptake in the spine. A lytic ciprofloxacin combination did not confer resolution of these le- metastasis centered in L3 measuring 1.6x2.2x2.0 cm was subse- sions. A punch biopsy performed by dermatology revealed features quently identified on CT, for which she received 200 mCi of I-131. of vasculitis with thrombosis of medium-sized vessels. Further After treatment her thyroglobulin reduced to 14 ng/ml from a ancillaries showed P-ANCA > 1:1280 (< 1:20), MPO 101.1 (< 20 U) pretreatment level of 1570 ng/ml. During the following 3 years she and proteinase-3 55.9 (< 20 U). ESR was 58 and the Antinuclear received 2 more doses of radioactive iodine totaling 250 mCi for antibody was negative. For this reason, PTU was discontinued and increasing Tg levels. After each dose of I-131, her Tg level decreased an 8-week course of prednisolone was initiated at 60 mg daily with but never became undetectable. In 2016, she developed worsening a tapering dose schedule. The lesions started to improve and back pain and MRI of the spine showed enlarging bone tumor eventually resolved completely, parallel to the gradual normaliza- causing pathologic fracture of the L3. Her non-stimulated thyro- tion of ANCA and MPO titers. Interestingly, several months after globulin went up to 2,880 ng/ml. Due to persistent pain and discontinuation of PTU and corticosteroids, the patient remained concern of spine instability, emergent spine debulking surgery was clinically and biochemically euthyroid. performed. Post-op thyroglobulin did not improve but increased to Discussion: Vasculitis is commonly associated with both anti-thy- 21500 ng/ml. Additional 200 mCi of I-131 was given and post roid medications but is more frequently reported with PTU than therapy WBS again showed marked uptake in the spine. Cyberknife with MMI. It is often MPO-ANCA positive type, although the exact radiation to L3 was given as well and follow up Tg reduced to 6250 mechanism remains unclear. Switching from MMI to PTU has been ng/ml. However, new metastatic lesions in her thoracic spine, lung reported as one of the risk factors for the development of such and adrenal gland were soon discovered. Despite zolendronic acid, vasculitis. Patients treated with PTU should be closely monitored lenvatinib and local radiation treatment, she passed away 1 year for the potential complication of MPO-ANCA positive vasculitis, as later. its early detection should lead to discontinuation of PTU and the Discussion: Most thyroid cancers have excellent prognosis. How- initiation of immunosuppressive treatment, in addition to estab- ever, once distant metastasis develops, prognosis is bleak. In this lishing an alternative treatment for hyperthyroidism. patient, despite iodine avidity, cancer continued to grow and https://doi.org/10.1016/j.eprac.2021.04.813 spread. The lesson learned from this case is to consider other treatment modalities at an earlier time for iodine refractory thyroid cancer. Abstract #1003208 https://doi.org/10.1016/j.eprac.2021.04.812 A Patient-Centered Assessment of Preconception Counseling Regarding Thyroid Hormone Replacement Abstract #1003107 Therapy in Women of Reproductive Age with Hypothyroidism Propylthiouracil-Induced ANCA-Positive Vasculitis: A case Report Author Block: Alexandra Solomon, MD - Primary Author, Internal Medicine, Boston University Medical Center; Sun Y. Lee, MD, MSc - Author Block: Ahmed Elmaaz, MD - Primary Author, Internal Co-author, Endocrinology, Boston University Medical Center; Medicine, New York Medical College, Metropolitan Hospital; Alan Farwell, MD - co-author, Endocrinology, Boston University Julian Santos, MD - co-author, Internal Medicine, New York Medical Center; Elizabeth Pearce, MD, MSc - Co-author, Medical College, Metropolitan Hospital; Alberto Franco, MD - co- Endocrinology, Boston University Medical Center author, Endocrine, New York Medical College, Metropolitan Hospital; Regina Belokovskaya, DO - co-author, Endocrine, New Objective: Adequate thyroid hormone in pregnancy is critical for York Medical College, Metropolitan Hospital normal fetal development. However, it is unclear whether patients are adequately counseled regarding hypothyroidism in pregnancy. Introduction: Thionamides, including propylthiouracil (PTU) and We conducted a survey of women of reproductive age with hypo- methimazole (MMI), are used in the treatment of hyperthyroidism. thyroidism to assess patients’ perspectives on management of MMI is preferred as first-line, due to PTU’s higher risk of toxicity. thyroid hormone replacement therapy (THRT) in pregnancy. We present a rare case of PTU-induced vasculitis with positive Methods: An anonymous online survey was distributed to sub- Myeloperoxidase (MPO) and anti-neutrophil cytoplasmic antibody scribers of the Friends of the American Thyroid Association (ATA)

S163 Thyroid Endocrine Practice 27 (2021) S141eS188 newsletter, a resource for patients. Women 18-50 years of age with Case Description: 64 year old female with past history of hypo- a diagnosis of hypothyroidism were included. Demographics thyroidism, on 2L of home O2, was admitted with hypoxic respi- including age, race, and region of residence were collected. Infor- ratory failure. Symptoms positive for tachypnea, hoarseness, mation on type of treating clinician, type of THRT used, and man- dysphagia for past few months. On physical exam, was noted to agement and discussion of THRT in pregnancy were collected. have left lateral neck mass. CT chest showed large left sided pleural Univariate associations were used to assess whether the reported effusion, pleural nodules and extensive mediastinal lymphade- presence of counseling regarding THRT in pregnancy differed by nopathy. Pleural fluid analysis showed malignant cells, with a clinician type. Multivariable associations were used to determine preliminary diagnosis of lung cancer. Also noted on chest CT was predictors of discussion and management of THRT in pregnancy. prominently enlarged left thyroid lobe, virtually absent right thy- Results: 166 eligible responses were received. The majority of roid lobe. TSH 4.02 UIU/ml, FT4 1.4 ng/dl were normal. Thyroid women were >30 years of age (84%) and white (81%). The Northeast ultrasound showed replacement of left thyroid lobe by (32%) was the most common region of residence. 20 (13%) were 5.3x2.x2.9cm mass with normal right thyroid & multiple enlarged currently pregnant, 68 (44%) previously pregnant, and 68 (44%) cervical lymph nodes. An IR guided biopsy of the left neck mass never pregnant. Hypothyroidism was managed by endocrinologists resulted as adenocarcinoma of thyroid origin. Immunophenotyping (36%), primary care providers (26%), a combination of clinicians of pleural fluid was repeated & found to be positive for thyroid as (33%), obstetricians (1%), or another specialist (3%). A total of 91 the primary cancer causing pleural effusion. She had total thy- (55%) women reported receiving counseling regarding THRT in roidectomy with bilateral central & radical neck dissection. Post-op pregnancy (18 currently pregnant, 48 previously pregnant, and 25 period was complicated by hypocalcemia, recurrent laryngeal never pregnant). All pregnant and 88% of previously pregnant nerve injury. Histological diagnosis was PTC with tall/columnar women reported taking LT4 monotherapy in pregnancy, consistent variant. She is on suppressive thyroid hormone therapy with a goal with ATA and ACOG guidelines. All currently pregnant and 85% of TSH of < 0.1 UIU/ml for ATA high risk category (American Thyroid previously pregnant women reported an increase in THRT dose Association). She is due for radioiodine treatment. during pregnancy. Whether THRT in pregnancy was discussed Discussion: Tall cell variant PTC tends to be large, invasive, have differed by the type of provider (p¼0.002). Region of residence and local & distant metastases at the time of diagnosis. 2-10% have age were predictors of discussion of THRT (overall model p< 0.001). metastases beyond the neck at the time of diagnosis, of which 2/ Region of residence was a significant predictor of checking thyroid 3rds have pulmonary metastases. Surgery is primary mode of hormone levels in early pregnancy in multivariable analysis therapy, followed by assessing need for radioiodine therapy based (overall model p¼0.003). on ATA risk stratification. Most patients do have residual disease Discussion/Conclusion: The majority of currently pregnant and after initial therapy with a 5-year mortality rates higher than in previously pregnant women with hypothyroidism reported patients with classic papillary cancers. receiving counseling regarding THRT in pregnancy. Most of these https://doi.org/10.1016/j.eprac.2021.04.815 women were treated with LT4 monotherapy, consistent with cur- rent guidelines. However, only 37% of never-pregnant women with hypothyroidism reported receiving counseling regarding THRT in Abstract #1003222 pregnancy, which demonstrates an important gap in patient education. Case Report: Medullary Thyroid Cancer as Part of the https://doi.org/10.1016/j.eprac.2021.04.814 MEN2B Syndrome in an 8-year-old Male Patient

Author Block: Abstract #1003213 Maria P. Sarmiento, MD - Primary author, Pediatric Endocrinology Fellowship Program. Universidad de Antioquia. An Interesting Case of Metastatic Malignant Pleural Medellín, Colombia; Judith S. Garcia, MD - Co-author, Effusion - Initial Presentation of an Aggressive form of Endocrinology Fellowship Program Universidad de Antioquia; Primary Thyroid Cancer Susana gomez, MD - Co-author, Endocrinology Fellowship Program Universidad de Antioquia; Pilar Pereira, MD - Co-author, Pediatric Endocrinology Fellowship Program. Universidad de Antioquia. Author Block: Sudha Nandala - Creighton University Medical Medellín, Colombia; Nora Zuluaga, MD - co-author, Pediatric Center; Shumail Syed, MD - co-author, Endocrinology & Endocrinologist, Hospital San Vicente Fundacion, Medellín, Metabolism, Creighton University School of Medicine; Colombia; Adriana C. forero, MD - Co-author, Pediatric Mohsen Zena, MD - Co-author, Endocrinology & Metabolism, Endocrinologist, Hospital San Vicente Fundacion, Medellín, Creighton University School of Medicine Colombia

Introduction: Papillary thyroid cancer (PTC) is a subtype of differ- Introduction: Medullary thyroid cancer (MTC) accounts for 5% of entiated thyroid cancer (DTC) derived from thyroid follicular all thyroid cancers. MTC originates from the parafollicular of the epithelial cells, which constitutes ~ 85% of DTC. Out of all variants of thyroid, which derive from the neural crest. In children, more than PTC, tall cell is more aggressive & accounts for 1% of papillary 95% cases of MTC are inherited as part of the multiple endocrine cancers. Poor prognostic factors are age > 55, gross local invasion, neoplasia syndromes (MEN2A and MEN2B) or familial MTC. MEN2B distant metastases and positive BRAF V600E mutation. We have a only represents 5% of MEN2 cases and is associated with a mutation rare case of PTC presenting as malignant pleural effusion , initially in the M918T of the RET oncogene. MEN2B is characterized by thought due to primary lung cancer, was later noted to have tall cell specific phenotypic features, including a marfanoid habit, a prom- variant of PTC. Pulmonary metastases in PTC are well known. Pre- inent jaw, ocular abnormalities, ganglioneuromas and mucosal vious such reported cases are due to recurrence of PTC, whereas our neuromas. patient had a rare initial presentation. Indolent thyroid enlarge- Case Description: 8-year-old boy with a history of primary hypo- ment added to diagnostic challenge. thyroidism diagnosed at age 18 months in the setting of generalized

S164 Thyroid Endocrine Practice 27 (2021) S141eS188 hypotonia and failure to meet his neuro-developmental milestones. Repeat antibody testing and thyroid sonography were consis- During regular follow ups, additional findings included micro- tent with Graves’ disease. cephaly, short stature, genu valgus, joint hypermobility and a Based on her presentation, she was diagnosed with thyroid storm marfanoid habitus which prompted an exoma trio analysis. A de and admitted to the intensive care unit. Thionamide therapy was novo M918T heterozygous pathogenic variant in the RET gene was withheld due to neutropenia. She was given hydrocortisone, detected. Neck imaging revealed a right paratracheal mass cholestyramine, potassium iodine (SSKI), antibiotics, intravenous extending into the upper mediastinum. Metastatic medullary thy- hydration and granulocyte colony stimulating factor. By day 7, she roid carcinoma was strongly suspected based on an elevated was discharged home and underwent total thyroidectomy a month calcitonin level. A total thyroidectomy with central neck dissection later without any complications. was planned. During the surgical procedure, a locally advanced Discussion: Thyroid storm occurs in 1-2 percent of patients with thyroid tumor was noticed and based on aggressive findings, the hyperthyroidism. Treatment includes b-blocker, anti-thyroid drugs surgical intervention was aborted. After a tumor board meeting, (ATD), inorganic iodine, and corticosteroids. In our patient, its management with the tyrosine multi-kinase inhibitor sorafenib presence with agranulocytosis which is also rare occurring in 0.3 % was initiated. of cases, made the treatment challenging since ATD were contra- Discussion: Most cases of pediatric MTC are hereditary as part of indicated and the presence of sepsis secondary to tonsillitis was the MEN2 syndrome or familial MTC. The mainstay of treatment is worsening her tachycardia requiring high doses of corticosteroids extensive surgical resection. Prevention is achieved by performing to be continued discharge until the day of thyroidectomy. a prophylactic thyroidectomy in pre-symptomatic patients. In cases https://doi.org/10.1016/j.eprac.2021.04.817 of advanced MTC, the tyrosine kinase inhibitors vandetanib and cabozantinib can be used, based on improvement in progression- free survival in adult patients. Abstract #1003297 https://doi.org/10.1016/j.eprac.2021.04.816 A Case of Hashimoto’s Encephalopathy Presenting with Cognitive Impairment and Visual Hallucinations Abstract #1003261

A Prodigious Storm Author Block: Sai Bhuvanagiri - Louisiana State University, Shreveport; Kamal Bhusal, Program Director - co-author, Endocrinology, Louisiana State University, Shreveport Author Block: Tania Al Shamy, MBBCh - primary author, Endocrinology, Diabetes and Metabolism, Icahn School of Medicine Introduction: Hashimoto's encephalopathy (HE) is a rare immu- at Mount Sinai, Beth Israel Program; Michael Via, MD - Co-Author, neemediated complication of Hashimoto thyroiditis. It is presented Endocrinology, Diabetes and Metabolism, Icahn School of Medicine as subacute onset of altered mental status with confusion, seizures at Mount Sinai, Beth Israel Program and myoclonus. It is a diagnosis of exclusion and requires that all other possible causes of cognitive impairment are excluded with a Introduction: Thyroid storm is a rare and life-threatening response to steroid therapy and evidence of thyroid autoimmunity condition and its presence along with Thionamide induced agran- in a patient. Here, we present a case of HE in a patient who pre- ulocytosis in our patient made the management challenging given sented with altered mental status and visual hallucinations despite high mortality rate and limited treatment options. no history or symptoms of thyroid disorder. Case Description: We report a case of a 24-year-old female given Case Description: A 77 year old male with past medical history of Thionamides therapy for Graves’ disease who subsequently pre- hypertension presented with altered mental status, lethargy, and sented with thyroid storm and agranulocytosis. visual hallucinations. Per patient’s wife, patient started to get The patient was initially diagnosed with hyperthyroidism in somnolent and was having memory problems six weeks prior to March 2018 as she presented with mild thyrotoxicosis symptoms. presentation. His mental status gradually deteriorated, and he Laboratory testing showed undetectable TSH levels and free started to have visual hallucinations. He was somnolent and noted thyroxine (T4) of 2.28 ng/dL. Serum levels of thyroid peroxidase to have myoclonus and twitching on admission. Magnetic reso- antibodies at 47.5 IU/ml (0-5.6 IU/mL), and thyrotropin receptor nance imaging (MRI) of the brain with gadolinium showed chronic antibodies at 27.9 IU/mL (0-1.75 IU/mL). She was treated with a microvascular changes with no acute intracranial pathology or b-blocker and methimazole 30 mg daily. Methimazole was then masses. Electroencephalogram (EEG) showed no signs of epilepti- reduced to 20 mg. Due to rash and hand swelling it was switched to form activity. Infectious disease work up, including complete blood Propylthiouracil (PTU) 50 mg daily as she declined radioactive count, urinalysis, sexually transmitted diseases, and cerebrospinal iodine. fluid (CSF) analysis, was negative. Blood glucose levels, serum In December 2019, she presented to the ED with 3 days of electrolytes, liver function tests, blood urea nitrogen, and creatinine sore throat, fever, cough, odynophagia, heat intolerance, were normal. Coronavirus disease 2019 (COVID-19) was negative. tremors, diarrhea, and a 33-pound weight loss over the last 3 CSF analysis for autoimmune encephalopathy and Creutzfeldt- months. She had self-discontinued PTU approximately 3 Jakob disease was negative. Thyroid function tests were normal. months prior but resumed one month prior due to return of Thyroid peroxidase antibody (TPOAb) was negative (8.6 IU/mL her symptoms, then stopped again prior to presentation. She [reference range (RR): < 9.0 IU/mL]) and TgAb was positive (8.2 ng/ was alert and oriented, had tremors of outstretched arms, mL [RR: < 4 IU/ mL]). With suspicion of Hashimoto's encephalop- tachycardia, diffuse thyromegaly, fever, and hyperreflexia. Vital athy, he was started on intravenous Solu-Medrol 1 g for five days. signs showed sinus tachycardia 169 beats/min, fever 102.7 F, He was then switched to oral prednisone 60 mg daily, which he BP 123/74 mm Hg. Serum TSH was suppressed at < 0.008 uIU/ received for ten days. His mental status improved upon day 14 of mL, free T4 2.92 ng/dL, total triiodothyronine 191 ng/dL (87- admission. On day 17 of admission, he was discharged on oral 178 ng/dL), and undetectable absolute neutrophil count (ANC). prednisone 40 mg daily with taper for five weeks. He was evaluated

S165 Thyroid Endocrine Practice 27 (2021) S141eS188 in the clinic few months after discharge. His mental status had Abstract #1003374 improved significantly, and he was back to his baseline in about two months after discharge as per his wife. Repeat thyroid function SARS-CoV-2-related Atypical Thyroiditis is Likely tests, TPOAb, and TgAb were negative. Under-diagnosed Discussion: The incidence of Hashimoto’s encephalopathy (HE) is 2.1 per 100,000 individuals in the general population, and is more common in women than men. This case highlights that HE should Author Block: Jayalakshmi Thimmaiah, MBBS, DNB, FEDM, CDE - be considered in patients with subacute presentation of neuro- Primary Author, Endocrinology Diabetes Medicine, Samatvam logical problems, which cannot be explained with other possible Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital diagnosis, despite no symptoms of thyroid disease such as the pa- and Medical Center; Mandyam Chitra, MBBS, FEDM CDE - Co tient in this case study. Therefore, HE should be evaluated for in Author, Endocrinology Diabetes Medicine, Samatvam patients with cognitive impairment for prompt diagnosis and Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital treatment with steroid therapy in order to improve the prognosis in and Medical Center; C.S. Muralidharakrishna, MBBS, FEDM, FACE - these patients. Co Author, Endocrinology Diabetes Medicine, Samatvam https://doi.org/10.1016/j.eprac.2021.04.818 Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital and Medical Center; siddhartha dinesha, MBBS, FEDM CDE - Co Author, Endocrinology Diabetes Medicine, Samatvam Abstract #1003327 Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital and Medical Center; Apoorva Govind, MBBS, FEDM CDE - Co Weekly Levothyroxine Therapy for Severe Author, Endocrinology Diabetes Medicine, Samatvam Hypothyroidism in Pregnancy Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital and Medical Center; Reshma Harsha, MBBS, FEDM, FACE - Co Author, Endocrinology Diabetes Medicine, Samatvam Author Block: Siva Kumar Kasina - University of Iowa Hospitals Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital and Clinics; Amal Shibli-Rahhal, MD, MSc - Co-author, University and Medical Center; Prateek Hongal, MBBS, FEDM CDE - Co Author, of Iowa Hospitals and Clinics Endocrinology Diabetes Medicine, Samatvam Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital and Medical Introduction: Hypothyroidism is one of the common thyroid dis- Center; k Chandrika, MBBS, FEDM, FACE - Co Author, orders affecting women of reproductive age. Untreated hypothy- Endocrinology Diabetes Medicine, Samatvam Endocrinology roidism in pregnancy can lead to pre-eclampsia, miscarriage, low Diabetes Center, Jnana Sanjeevini Diabetes Hospital and Medical birth weight, still birth and possible developmental delays in the Center; Thummala Kamala, MBBS, FEDM, FACE - Co Author, offspring. In patients who are non-adherent with daily levothyr- Endocrinology Diabetes Medicine, Samatvam Endocrinology oxine replacement, weekly levothyroxine is a safe and effective Diabetes Center, Jnana Sanjeevini Diabetes Hospital and Medical treatment approach. Here we describe the use of weekly levo- Center; vasanthi Nath, MBBS, FEDM, FACE - Co Author, thyroxine in a pregnant patient with hypothyroidism. Endocrinology Diabetes Medicine, Samatvam Endocrinology Case Description: A 28-year-old female G6P4105 at 12 weeks Diabetes Center, Jnana Sanjeevini Diabetes Hospital and Medical gestation was referred for severely elevated TSH of 299 mIU/mL Center; Pushpa Ravikumar, MBBS, FEDM, FACE - Co Author, (0.27-4.20), and undetectable free T4 and T3. She had a long Endocrinology Diabetes Medicine, Samatvam Endocrinology standing history of primary hypothyroidism, with TSHs ranging Diabetes Center, Jnana Sanjeevini Diabetes Hospital and Medical between normal and 560 over the years. She reported mild diffi- Center; Lakshmi Reddy, MBBS, FEDM, FACE - Co Author, culties with concentration, hypersomnia, cold intolerance and hair Endocrinology Diabetes Medicine, Samatvam Endocrinology loss. Her prescribed dose of levothyroxine was 200 mcg daily and Diabetes Center, Jnana Sanjeevini Diabetes Hospital and Medical she insisted she was taking it regularly. Testing for celiac disease Center; Chandraprabha siddalingappa, MBBS, FEDM, FACE - Co and human anti-mouse antibodies (HAMA) was negative. We Author, Endocrinology Diabetes Medicine, Samatvam contacted her pharmacy and learned that she had not filled her Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital levothyroxine prescription for several months and that her refills and Medical Center; Sathyanarayana Srikanta, MBBS, MD, FEDM, had been chronically irregular. When we shared this information FACE, FRCP - Co Author, Endocrinology Diabetes Medicine, with the patient, she admitted to non-adherence. She was admitted Samatvam Endocrinology Diabetes Center, Jnana Sanjeevini to the hospital for intravenous (IV) levothyroxine to rapidly Diabetes Hospital and Medical Center - Endocrinology Diabetes normalize the thyroid levels. She received 200 mcg daily for 4 days Study Group, Endocrinology Diabetes e Co Author, Endocrinology and free T4 and free T3 increased to 0.90 ng/dL (0.8-1.8) and 1.83 Diabetes Medicine, Samatvam Endocrinology Diabetes Center, pg/mL (2.57-4.43) respectively. We then treated her with oral lev- Jnana Sanjeevini Diabetes Hospital and Medical Center othyroxine 850 mcg every week under direct nursing supervision. TSH levels normalized to 2.62 mIU/mL and free T4 1.19 ng/dL 2 Introduction: Subacute thyroiditis is a rare complication of the weeks after discharge, and a TSH < 2.5 mIU/mL was achieved by 12 “novel” disease COVID-19, and it should be considered especially in weeks. She has presented to treatment appointments regularly and the setting of persistent tachycardia without any suggestion of has tolerated treatment well. She is now close to term. Fetal progression of COVID-19 and other common cardiorespiratory monitoring has shown intrauterine growth retardation, possibly causes. Anterior neck pain, which can be taken as an upper respi- due to the initial severe hypothyroidism, but no other ratory tract symptom, especially in the setting of COVID-19, should abnormalities. not be dismissed and warrants further examination and investi- Discussion: Weekly levothyroxine under direct supervision might gation as required. offer a safe and effective approach to address non-adherence to Case Description: Age 73: 2020 Nov: Referred to Samatvam levothyroxine during pregnancy. Endocrinology Diabetes Center e Telemedicine Clinic for manage- ment of Thyrotoxicosis e “Supressed TSH”. Amidst the Covid https://doi.org/10.1016/j.eprac.2021.04.819

S166 Thyroid Endocrine Practice 27 (2021) S141eS188 pandemic in India, he developed fever and cough of 6 days duration controversial and the association between diabetes and thyroid [treated with Azithromycin, Oseltamir and Paracetamol e home cancer is probably weak. Proposed mechanisms for such a possible care]. During the work up of this “viral” respiratory illness, he e link between diabetes and thyroid cancer include elevated levels of scientist - himself “self” obtained a very wide battery of blood tests, thyroid-stimulating hormone, insulin, glucose and triglycerides, which “incidentally” revealed suppressed TSH 0.03, next day repeat insulin resistance, obesity, vitamin D deficiency, and antidiabetic 0.02 uIU/ml with increased Free T4 1.96 ng/dl [0.89-1.76], increased medications such as insulin. We present the case of a female patient Free T3 4.7 pg/ml [2.3-4.2], Total T4 9.43 ug/dl, Total T3 140 ng/dl, S with type-1 diabetes mellitus who subsequently developed papil- Cortisol 18.2 ug/dl. Height 5 feet 5 Inches, Weight 66 Kg. PR 100/ lary thyroid carcinoma. min; SPO2 95 to 98. ESR 55: There was no history of neck or throat Case Description: A 14-year-old female patient with type 1 dia- pain or dysphagia. There was history of weight loss, palpitation and betes mellitus subsequently developed a goiter. Thyroid ultrasound muscle cramps. Isotope Thyroid Scan was obtained, which was revealed a solid left thyroid oval nodule, with diffuse contours with consistent with thyroiditis. Age 69: Prediabetes [FP Glucose 123 peripheral microcalcifications of heterogeneous echogenicity, mg/dl; HbA1c 6.4%] and Dyslipidemia on statin and aspirin. measures 6.3x8.3x7.6mm. Thyroid peroxidase antibodies were Assessment: Possible Covid Atypical Subacute Thyroiditis [Pain- negative. Fine needle aspiration biopsy of the nodule was consis- less variant], with thyrotoxicosis transient. tent with PTC. The patient was then scheduled for a total thyroid- Discussion: Retrospective data from Italy Intensive Care Units in- ectomy and central lymph node resection. dicates that patients with COVID-19 commonly had low or sup- Discussion: Type 1 diabetes mellitus is characterized by selective pressed serum thyroid stimulating hormone, with and without autoimmune destruction of pancreatic b-cells, resulting in insulin elevated free thyroxine concentrations. Possibilities included: (a) deficiency and associated autoimmune disorders such as thyroid- Critical illness related alterations of thyroid function tests [non- itis. Nevertheless, there is a lot of controversy regarding the role of thyroidal illness syndrome] and (b) SARS-CoV-2 direct infection of diabetes mellitus in the pathogenesis of thyroid cancer and further the thyroid gland [unrelated to underlying thyroid autoimmunity]. studies are necessary to confirm their relationship. Patients with Also, the mild “thyrotoxicosis” in these patients was not associated type 1 DM should be examined for thyroid diseases, and patients with neck pain (consistent with silent thyroiditis); they did not with suspected thyroid disease should be evaluated with a thyroid have leucocytosis, but had lymphopenia, as observed with COVID- ultrasound. 19 infection. Besides this, classic subacute thyroiditis, characterised https://doi.org/10.1016/j.eprac.2021.04.821 by a pathognomonic infiltration of giant cells (congregates of lymphocytes, histiocytes, and colloid), with swelling of thyroid follicles, stretching of the thyroid capsule, and consequent neck Abstract #1003565 pain, has also been reported. Angiotensin-converting enzyme 2 (ACE2), the host-cell entry receptor for both SARS-CoV and SARS- Opportunity and Challenges of Using Novel Therapies CoV-2, might be partly responsible for a common pathogenic in a Case of Anaplastic Thyroid Carcinoma pathway. ACE2 is more highly expressed in thyroid cells than in lung cells, and in women such expression negatively correlates with signatures of immune cell enrichment. This expression profile Author Block: Malek Mushref, MD - Primary Author, has been suggested to explain why the most severe forms of COVID- Endocrinology, Medical University of South Carolina; 19 pneumonia and associated thyroid dysfunction has been pre- Matthew Bridges, Medical Student - Co-author, Medicine, Medical dominantly observed in men in the ICU retrospective study [but not University of South Carolina; Denise Carneiro-Pla, MD - Co-Author, in women, as in classic viral subacute thyroiditis]. Endocrine Surgery, Medical University of South Carolina; https://doi.org/10.1016/j.eprac.2021.04.820 Jyotika Fernandes, MD - Co-Author, Endocrinology, Medical University of South Carolina; John Kaczmar, MD - Co-Author, Hematology/Oncology, Medical University of South Carolina; Abstract #1003488 Mahsa Javid, MD, PhD - Co-Author, Endocrine Surgery, Medical University of South Carolina Possible Association Between Type 1 Diabetes and Thyroid Cancer Introduction: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive and lethal of all cancers. Multimodal therapies including surgery, when feasible, and chemoradiation are utilized Author Block: Susana Gomez, MD - Primary author, Pediatric but median survival remains short at around six months. Genetic Endocrinology Fellowship Program. Universidad de Antioquia. sequencing is increasingly used to identify mutations that can be Medellín, Colombia; Pilar Pereira, MD - co-author, Pediatric targeted by immunotherapy, especially in patients with distant Endocrinology Fellowship Program. Universidad de Antioquia. metastases and unresectable disease. We describe a challenging Medellín, Colombia; Maria P. Sarmiento, MD - Co-author, Pediatric case treated with resection, chemoradiation and a combination of Endocrinology Fellowship Program. Universidad de Antioquia. checkpoint and multikinase inhibitors. Medellín, Colombia; Judith S. Garcia, MD - co-author, Pediatric Case Description: A 72-year-old man initially presented at an Endocrinology Fellowship Program. Universidad de Antioquia. outside facility with a 3-month history of a rapidly growing neck Medellín, Colombia; Nora Zuluaga, MD - co-author, Pediatric mass. A CT neck and ultrasound showed a 5 cm right thyroid nodule Endocrinology Faculty. Universidad de Antioquia. Medellín, with central and right lateral lymphadenopathy. FNA of the thyroid Colombia; Adriana C. Forero, MD - co-author, Pediatric mass reported a malignant process possibly poorly differentiated Endocrinology Faculty. Universidad de Antioquia. Medellín, thyroid cancer versus ATC. Metastatic ATC was confirmed at our Colombia institution following repeat FNA of the mass and a lateral node with appropriate staining. No distant metastases were noted at pre- Introduction: The relationship between thyroid cancer and dia- sentation (Stage IVB). The patient underwent total thyroidectomy, betes has not been extensively studied. Trials results are right central neck and right modified radical neck dissection.

S167 Thyroid Endocrine Practice 27 (2021) S141eS188

Pathology confirmed 6.7 cm ATC with muscular invasion and can- For the purposes of this study, TED was identified by concomi- cer in all 31 nodes excised. Next generation sequencing showed no tantly occurring ICD 10 codes of thyroid disease and ICD-10 codes BRAF mutation but >50% PDL-1 expression. He subsequently for eye manifestations of thyroid eye disease. The coding algo- received 7 cycles of weekly paclitaxel and carboplatin with con- rithms were developed by consensus of three ophthalmic surgeons. current radiation. He tolerated chemoradiation well but developed Results: In 2017, there were 3494 Emergency department visits and lung and mediastinal metastases one month following the last 1870 hospitalizations with primary or secondary diagnosis of thy- chemotherapy cycle. PET scan confirmed diffuse distant metastases roid eye disease. There were 50 hospitalizations and 552 ED visits and local recurrence with increasing risk of laryngotracheal with primary diagnosis of thyroid eye disease. obstruction requiring prophylactic tracheostomy. The patient was In 2017 the mean age for ED visits was 51.8 (95% CI 50.4-53.2) and then commenced on salvage targeted immunotherapy, PD1-in- for hospitalizations was 56.1 (95% CI 54.3-57.9). Women comprised hibitor (pembrolizumab) combined with lenvatinib, but unfortu- 71% of the ED visits and 72% of hospitalizations visit. Medicare and nately passed away due to complications from the tracheostomy Medicaid paid for 59.5% of ED visits and 72.6% of hospitalizations. one month after starting the combination, seven months after his The mean charges for ED visits and hospitalizations were, respec- initial diagnosis. tively $ 6,018 (95% CI $ 5,115- $6,922) and $ 59,103 (95% CI $50,106- Discussion: The use of a pembrolizumab/lenvatinib in the treat- $58,100). Aggregate annual national charges were over 135.5 ment of ATC remains investigatory. It should be considered for million dollars. BRAF-negative tumors with high PDL-1 status. Our patient had a Discussion/Conclusion: While thyroid eye disease is an orphan good initial response on traditional chemoradiation, however, disease with a limited prevalence, and resultant emergency room progressed shortly after. He declined referral for a clinical trial but visits and hospitalizations are relatively infrequent, there are sig- opted for the combination pembrolizumab/lenvatinib therapy nificant economic consequences of these visits. Strategies to reduce which has shown promise in early trials. This case illustrates the resource intense health care utilizations would be beneficial. aggressiveness of ATC despite newer therapies and the challenge of https://doi.org/10.1016/j.eprac.2021.04.823 deciding optimal timing for their use. Future research is needed to confirm efficacy, timing and selection of patients who would most fi bene t from this therapy for this devastating disease. Abstract #1003609 https://doi.org/10.1016/j.eprac.2021.04.822 Sarcoidosis Masquerading as a Multinodular Goiter

Abstract #1003588 Author Block: Anna Melissa Lo - Thomas Jefferson University Thyroid Eye Disease in the United States: Data from Hospital; Lubna Zuberi, MD - Co-author, Thomas Jefferson Emergency Department Visits and Hospitalizations University Hospital

Introduction: Sarcoid involvement of thyroid gland is rare, re- Author Block: Gurkirpal Singh, MD - Presenter, Stanford ported in 1 to 4 % of those with systemic sarcoidosis. We report here University; Maanek Sehgal, BS - co-author, University of California, a case of a patient who was being managed for nodular goiter, and Los Angeles; Alka Mithal, MD - co-author, ICORE; Andrea Kossler, then diagnosed with sarcoidosis of thyroid. MD - co-author, Stanford University Case Description: 63-year-old African American woman was diagnosed with nontoxic multinodular goiter 10 years prior to Objective: Thyroid eye disease (TED) is an autoimmune disorder of presentation. Previous ultrasound guided FNA reported benign the retrobulbar tissue associated with Graves’ disease and presents nodules. Nodules showed progressive increase in size, which led to with a spectrum of signs and symptoms ranging from mild to se- endocrine referral. A repeat US guided FNA of enlarging nodule(s) vere symptoms such as corneal ulceration and compression optic showed inflammatory cells, epithelioid histiocytes, and multinu- neuropathy in 5% of cases. There is little nationwide data on clinical cleated giant cells. A year prior, she developed cutaneous lesions, and economic consequences of this disease. This study examined biopsy of which showed sarcoidosis. She also underwent pulmo- TED hospitalizations and emergency department visits at a recent nary evaluation, which showed mild restrictive lung disease. database timepoint, in 2017 (the latest data available at the time of Additionally serum calcium was 10.4 mg/dL, normal iPTH of 16 pg/ analyses), in the US and estimated their clinical and economic mL, normal 25-hydroxy vit Dlevel29 ng/mL, high normal 1,25 di-OH aspect. vit Dlevel66.2pg/mL (19.9-79.3pg/mL), and undetectable TPO and Methods: The Nationwide Inpatient Sample (NIS) is a stratified TG antibody. Serum ACE level was normal. A diagnosis of thyroid random sample of all US community hospitals. It is the only US sarcoidosis was made, given presence of multinucleated giant cells, national hospital database with information on all patients, negative thyroid antibodies and pre-existing diagnosis of cuta- regardless of payer, including persons covered by Medicare, neous sarcoidosis. Medicaid, private insurance, and the uninsured. Detailed informa- Discussion: Sarcoidosis of lung, skin, eyes, and lymph nodes is well tion including clinical and nonclinical data elements on each hos- recognized. Involvement of thyroid gland is rare and not often pital stay including International Classification of Diseases (ICD) 10 considered to be a differential diagnosis of nodular thyroid. Most diagnosis and procedure codes, age, gender, length of stay, payer, cases reported in the literature were diagnosed with core needle charges, comorbidities etc. is available. biopsy and surgical pathology. It may present with associated hy- The Nationwide Emergency Department Sample (NEDS) is the pothyroidism or hyperthyroidism, as cold nodules or nodular largest all-payer emergency department (ED) database in the goiter. Presence of multinucleated giant cells, in the absence of United States, yielding national estimates of hospital-owned ED underlying thyroid autoimmunity, should raise suspicion of thyroid visits. Unweighted, it contains data from over 30 million ED visits sarcoidosis. Presence of previously diagnosed cutaneous sarcoid- each year. Weighted, it estimates roughly 145 million ED visits. osis, mild non-PTH mediated hypercalcemia and mild underlying

S168 Thyroid Endocrine Practice 27 (2021) S141eS188 restrictive lung disease, coupled with thyroid nodule cytology screening guidelines we do not have sufficient data on co-existing findings led us to the diagnosis of thyroid sarcoidosis in our patient. Graves and Hashimoto’s thyroiditis. We recommend to check titers This case suggests that thyroid sarcoidosis may be more preva- for both the diseases (TSI /TRAB and anti-TPO/anti-Tg) in cases with lent than reported. It should be considered as an important dif- brittle and fluctuating TFT to avoid the misdiagnosis and subse- ferential of thyroid nodules with epithelioid multinucleated giant quent inappropriate management. cell on cytology, particularly in a patient with known sarcoidosis. https://doi.org/10.1016/j.eprac.2021.04.825 https://doi.org/10.1016/j.eprac.2021.04.824

Abstract #1003650 Abstract #1003610 Carbamazepine: An Under-recognized Cause of Synchronous Graves and Hashimoto’s Disease Hypothyroidism in Patients Receiving Levothyroxine

Author Block: Sandesh Dewan - Saint Peters University Hospital; Author Block: Radwa Osman - Eastern Virginia Medical School; Hongxiu Luo, MD - co-author, Endocrine, ST PETERS UNIVERSITY David Lieb, MD, FACE, FACP - co-author, Eastern Virginia Medical HOSPITAL School

Introduction: Graves' disease presents with symptoms of hyper- Introduction: While many orally ingested substances can affect the thyroidism due to overstimulation of thyroid receptors by stimu- bioavailability of levothyroxine, other medications may affect its lating antibodies (TSI, TRAB) whereas Hashimoto’s is the most protein binding and metabolism. This can lead to the need for an common cause of hypothyroidism due to chronic lymphocytic increase in the levothyroxine dose to achieve a euthyroid state. We infiltration in thyroid by antibodies against thyroid peroxidase report a case of a well-described yet under-recognized cause of (anti-TPO) and thyroglobulin (anti-Tg). Although these two diseases hypothyroidism in a patient on levothyroxine replacement. are common in our practice, concurrence of them in one patient is Case Description: A 55-year-old male with primary hypothy- rare, and in such cases, it can become challenging for clinicians to roidism, type 1 diabetes mellitus, and peripheral arterial disease manage thyroid function. We will present a case with synchronous was admitted for sepsis and an iliac stent infection requiring a Graves' disease and Hashimoto's thyroiditis. prolonged hospitalization. The patient had been stable for years Case Description: 25-year-old Female was referred to our Endo- on levothyroxine 125 mcg daily. Three months into hospitaliza- crine clinic due to abnormal thyroid function. She initially pre- tion the patient reported symptoms of fatigue, depressed mood sented to us with hypothyroidism due to Hashimoto thyroiditis, and unexplained hyponatremia, prompting TSH measurement. and being on replacement therapy with Levothyroxine 25 mcg for Despite appropriate administration of levothyroxine, his TSH was about a year. Eventually she developed hyperthyroidism despite higher than 90 mcU/mL with free thyroxine of 0.6 ng/dL (nl 0.9- being off the treatment for two years. On evaluation she had high 1.8). He was not taking any medications known to affect levo- titers of TSI antibodies (231, Reference level < 140); radioactive thyroxine absorption, and evaluations for pernicious anemia and Iodine uptake scan showed diffuse increased uptake (4-hour up- celiac disease were unremarkable. He denied having diarrhea, take: 86%, normal range:8-23%, 24 hours uptake: 94% normal bloating, or indigestion. It was noted that four weeks prior, he range:15-35%) and thyroid US showed a 18 mm solid hypoechoic had been started on carbamazepine as a mood stabilizer. With thyroid nodule, but toxic nodule was ruled out based on uptake concerns for drug interaction with levothyroxine, he was scan report. She was subsequently diagnosed with Graves' disease, switched to oxcarbazepine, with consequent improvement of his but she refused medical therapy with MMI or RAI ablation and was thyroid function. Levothyroxine dose was also slowly increased lost to follow up. She came for follow up after 2 years with to achieve a euthyroid state with a notable improvement in asymptomatic subclinical hypothyroidism with suppressed TSH, symptoms. normal free T4 and TT3 (TSH< 0.01(0.40-4.50 mIU/L); T4:1.6 (0.8- Discussion: Carbamazepine is a widely used medication, with in- 1.8ng/dl); T3: 163(76-181 ng/dl)). She also had high titers for both dications in treating epilepsy, bipolar disorder and chronic pain antibodies (TSI for Graves, TPO for Hashimoto) and repeat thyroid syndromes. It reduces thyroxine-binding globulin resulting in re- uptake scan showed normal radioactive iodine uptake (4-hour ductions of total T4 levels by 20% to 40%. Increasing the dose of uptake:8 %, 24-hour uptake: 15 %.). FNA of thyroid nodule showed levothyroxine typically restores euthyroid TSH serum concentra- Bethesda category II (benign). Her thyroid function was monitored tion. Carbamazepine also increases extra-thyroidal metabolism of every 2-3 months without any treatment and she eventually thyroid hormone via inducing the hepatic enzyme uridine transitioned from subclinical hyperthyroidism to euthyroid and diphosphate glucuronosyltransferase which is responsible for glu- finally overt symptomatic hypothyroidism with hair loss, fatigue curonidation and plays a role in the metabolic pathway for thyroid and weight gain in a span of one year. She was appropriately started hormones. Although this enzyme is also induced by oxcarbazepine, on thyroid replacement therapy. the risk of hypothyroidism with this drug is not as well established. Discussion: Our patient has both Grave’s disease and Hashimoto Our patient highlights the importance of reviewing patient medi- thyroiditis with fluctuating thyroid function from hypothyroidism cations to encompass drugs that can affect levothyroxine absorp- to hyperthyroidism, and eventually again hypothyroidism requiring tion, protein binding and metabolism. Oxcarbazepine may be an thyroxine replacement in a span of five years. She did not require alternative for carbamazepine in hypothyroid patients taking lev- usual treatment for Grave’s disease like MMI or RAI therapy but othyroxine. Physicians should be aware of this interaction, the need transitioned to hypothyroidism in few years. Due to the natural for regular monitoring, early identification, and a possible increase history of these two diseases (stimulation of thyroxine production in levothyroxine dosing. vs chronic infiltration of gland), patients’ thyroid function is fluc- tuating and very difficult to predict or manage. Due to insufficient https://doi.org/10.1016/j.eprac.2021.04.826

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Author Block: Abstract #1003676 Christine Chiu - LAC + USC Internal Medicine; Jonathan Huang, MD - co-author, LAC + USC Internal Medicine; Hypothyroidism-Induced Hyperammonemia: An Nikhila Janakiram, MD - co-author, Huntington Memorial Hospital; Overlooked Clinical Entity Michael Hashimoto, BS - co-author, Keck School of Medicine, University of Southern California; Trevor E. Angell, MD - co-author, Division of Endocrinology and Diabetes, Keck School of Medicine, Author Block: Ahmed Ahmed - EVMS; Sarah Al Allawi, MBChB - University of Southern California Co-Author, N/A; David C. Lieb, MD, FACE, FACP - Co-Author, EVMS Objective: Multiple specialties teach and perform ultrasound- Introduction: Hypothyroidism-induced hyperammonemia is guided fine-needle aspiration biopsy (USG-FNA) of thyroid nodules, rarely reported. We describe a case of noncirrhotic hyper- including Radiology, Endocrinology, and Pathology. Differences in ammonemia with encephalopathy in the setting of severe cytopathology results may relate to different USG-FNA techniques hypothyroidism. as well as differences in the nodules evaluated. This study aimed to Case Description: A 51-year-old female with eosinophilic perform a detailed analysis of USG-FNA outcomes among these myocarditis and Graves’ disease presented to the hospital with different teaching services at a single academic medical center. worsening dyspnea. She was diagnosed to have an acute heart Methods: We performed a retrospective chart review of patients failure exacerbation and required pericardiocentesis for a large who underwent USG-FNA of a thyroid nodule at a single academic pericardial effusion. Her methimazole dose had been reduced medical center from 2015-2017, excluding patients with hyper- from 20 to 10 mg daily one month prior to admission when her thyroidism. Cytopathology results were categorized according to TSH was noted to be 21.2 mcU/mL. Despite this adjustment, her the Bethesda system and stratified by the performing specialty TSH on admission was 75.80 mcU/mL, and free thyroxine was (Radiology, Endocrinology, and Pathology). Demographic, clinical, 0.1 ng/dL. On exam, she had mild thyromegaly and asterixis and ultrasound variables were also analyzed to further investigate with no stigmata of chronic liver disease. Methimazole was differences between the performing specialties. discontinued, and weight-based intravenous levothyroxine ther- Results: Of the 356 total thyroid nodules examined by USG-FNA, apy was initiated. Her mental status deteriorated with workup 167 nodules were biopsied by Radiology, 119 by Endocrinology, and notable for hyperammonemia (369 mcg/dL; nl 19-65). AST and 70 by Pathology. Onsite cytopathology evaluation was available to ALT were normal, and ultrasound demonstrated hepatomegaly Radiology and Pathology, but not to Endocrinology during this with coarsened increased echotexture suggesting nonspecific period. The distribution of Bethesda results was different between hepatocellular disease. Extensive hepatology workup deemed the the three performing services (p< 0.05). The rate of a Bethesda I hyperammonemia to be noncirrhotic in nature, raising suspicion (non-diagnostic) cytopathology result was 3.6% for Radiology, 10.1% for hypothyroidism-induced hyperammonemia. With continued for Endocrinology, and 11.4% for Pathology (p< 0.05). Differences levothyroxine replacement and the addition of lactulose and between the rate of benign (Bethesda II), indeterminate (Bethesda rifaximin, her encephalopathy resolved, and her hyper- III-IV), or high-risk (Bethesda V-VI) results were not statistically ammonemia improved. significant. The Radiology-performed USG-FNA group included Discussion: The most common cause of hyperammonemia in 58.9% nodules discovered incidentally compared to 43.9% and adults is cirrhosis leading to impaired ammonia clearance with 32.8% for Endocrinology and Pathology, respectively (p¼0.001). A portosystemic encephalopathy. In the absence of cirrhosis, majority of nodules were partially or predominantly cystic in the hyperammonemic encephalopathy may result from conditions Radiology (53.4%) and Pathology (55.5%) groups, but not in the that increase ammonia production and decrease its elimination. Endocrinology group (34.6%), which only reached statistical trend There are fewer than ten reports of hypothyroidism-induced (p¼0.07). No other significant differences were noted in patient hyperammonemia in the literature, and its etiology is unclear. characteristics. Hypothyroidism is associated with decreased urea synthesis, Discussion/Conclusion: Both the distribution of thyroid nodule which may lead to reduced clearance of ammonia. Some have USG-FNA cytopathology results and the nodule characteristics postulated that hypothyroidism may be associated with differed between performing services, highlighting the need to decreased glutamine synthase activity in the liver, muscle, and consider sonographic features when assessing USG-FNA perfor- kidney, which would reduce ammonia metabolism. Decreased mance. Additionally, the frequency of non-diagnostic cytopathol- intestinal motility may also promote bacterial production of ogy of USG-FNA of thyroid nodules differed between specialties at ammonia. this single academic teaching medical center, suggesting opportu- The diagnosis of hypothyroidism-induced hyperammonemia is nities for quality improvement such as multidisciplinary procedural challenging and requires a high index of suspicion given the over- training. lapping similarities between hypothyroidism-associated encepha- https://doi.org/10.1016/j.eprac.2021.04.828 lopathy and hepatic encephalopathy, yet it is of absolute importance given therapeutic implications. Previous case reports have suggested that similar patients will not improve without Abstract #1003741 thyroid hormone. A multidisciplinary approach involving endocri- nology and hepatology is critical for the management of this rare Monitoring implications for Marine-Lenhart complication of hypothyroidism. Syndrome: Rare Case on the Consequences of Loss to Follow-up in this Population of Patients https://doi.org/10.1016/j.eprac.2021.04.827

Author Block: Abstract #1003710 Varundeep Rakhra, DO - Primary Author, University of Missouri-Kansas City; Kaitlin T. Hoff, MS 4 - Co-author, A Comparison of Non-Diagnostic FNA Results for University of Missouri-Kansas City; Peminda K. Cabandugama, MD Thyroid Nodules Among Different Specialties - Co-author, University of Missouri-Kansas City

S170 Thyroid Endocrine Practice 27 (2021) S141eS188

Introduction: Marine-Lenhart (ML) syndrome is a rare thyroid cm substernal right thyroid nodule without evidence of pulmonary disorder in which a patient presents concurrently with Grave's metastases and stable pelvic mass. Pre-operative labs demon- disease and hyperfunctioning thyroid nodules. It can cause symp- strated a TSH of 0.328 (0.350-5.500 ulU/mL) with free T4 of 0.61 toms common to both Grave's disease and toxic multinodular (0.58-1.64 ng/dL) and total T3 of 158 (80-180 ng/dL). She under- goiter. There are a few case reports addressing both the diagnosis went total thyroidectomy. Pathology revealed a 3.4 cm FTC with and management of this condition. However, there is a paucity of evidence of capsular and vascular invasion. Post-operatively, the information about the necessity for close follow-up required on patient’s TSH was 0.052 with a free T4 of 1.06, thyroglobulin of these patients after initial treatment. Here we present a case of a 2367.8 (1.0-35 ng/mL) and thyroglobulin antibody of 21.7 (0.0-60.0 highly symptomatic patient with previous treatment for Grave's u/mL) on levothyroxine 75 mcg daily. Subsequent CT scan identified disease who was lost to follow-up and returned with a radioactive multiple subcentimeter pulmonary nodules and a decrease in size iodine uptake indicative of Marine-Lenhart syndrome. of the pelvic mass. Patient underwent thyroid hormone withdrawal Case Description: A 43 year-old African American female initially protocol in preparation for radioactive iodine ablation (RAI) in 2017. diagnosed with Grave's disease, which was confirmed with Patient’s TSH was 1.517 after 6 weeks of thyroid hormone with- elevated thyroid stimulating antibodies, was treated with radio- drawal indicating she was unable to achieve an optimal rise in TSH. active iodine ablation. After this initial treatment, the patient was Her RAI treatment was postponed and she was subsequently lost to lost to follow-up for several years. follow up for three years. She has been off levothyroxine during this The patient returned to our clinic with symptoms of hair loss, entire time period. Lab work upon reestablishment of care revealed constipation, irregular menstrual periods, proptosis, and palpita- overt hyperthyroidism with a TSH < 0.008, Free T4 2.62, thyroid tions. Evaluation by us included a radioiodine uptake and scan, stimulating immunoglobulin 136% (< 140%), thyroglobulin anti- thyroid ultrasound, and repeat thyroid function tests (TFTs). TFTs body < 1, and thyroglobulin 17,051. She was started on methima- returned with a TSH of 0.01, free T3 of 9.3, and free T4 of 1.9. The zole. Imaging revealed negative neck ultrasound and increase in radioiodine uptake and scan revealed an enlarged multinodular size of pulmonary and pelvic lesions on CT scan. Patient is sched- thyroid gland with hyperactive and hypoactive nodular areas with uled for external beam radiation and radioactive iodine ablation. increased thyroid uptake consistent with Marine-Lenhart Discussion: Based on this patient’s preoperative labs, autonomous syndrome. thyroid hormone production was not obvious. The patient’s free T4 The patient was treated with methimazole and then recom- was also normal postoperatively indicating an appropriate dose of mended for thyroidectomy. She completed the thyroidectomy and levothyroxine. Our patient was unable to mount an appropriate rise is now clinically and biochemically euthyroid on levothyroxine. in TSH prior to RAI despite thyroid hormone withdrawal. She However, the patient has persistence of proptosis due to the con- subsequently developed overt hyperthyroidism off thyroid hor- dition and continues to follow up with ophthalmology for evalua- mone replacement. One should consider the presence of functional tion and treatment. metastases when patients are unable to achieve a sufficient in- Discussion: Marine-Lenhart syndrome is a rare medical disorder crease in TSH after hormone withdrawal. This case highlights that with very few cases reported. As a result, there is very little infor- hormone secreting thyroid cancers are not always functional at mation regarding diagnosis and management. This patient had time of diagnosis and often evolve over time. elevated thyroid stimulating antibodies consistent with Grave's https://doi.org/10.1016/j.eprac.2021.04.830 disease and although she was treated with radioactive iodine ablation, she was later found to have functioning nodules resulting in symptomatic hyperthyroidism with ophthalmopathy. Our case Abstract #1003758 illustrates the questions that still remain regarding recommenda- tions for diagnosis and long-term management and the importance Confounding Elevated TSH in Clinically Euthyroid of close follow-up with this population of patients. Patient Due to Macro-TSH https://doi.org/10.1016/j.eprac.2021.04.829

Author Block: Sura Alqaisi, MD - Primary Author, Internal Abstract #1003749 Medicine, Cleveland Clinic/ Fairview; Nabil Z. Madhun, DO - Coauthor, Endocrinology, Cleveland Clinic; Aisha R. Saand, MD - Functional Metastatic Follicular Carcinoma: An Coauthor, Internal Medicine, Cleveland Clinic/Fairview; Evolving Phenomenon Adam McShane, PhD - Coauthor, Pathology and Laboratory Medicine, Cleveland Clinic; Jay Morrow, MD - Coauthor, Endocrinology, Cleveland Clinic Author Block: Sonya Chaudhari, MD - primary author, Brown Medicine; Sejal Doshi, MD - co author, Brown; Jasmin Lebastchi, Introduction: TSH is the most sensitive marker to assess thyroid MD - co author, Brown; Geetha Gopalakrishnan, MD - co author, function, however it is susceptible to numerous laboratory inter- Brown ference that can impact clinical decision-making. We hereby pre- sent a case of macro-TSH as a cause for falsely elevated TSH levels in Introduction: Autonomous thyroid hormone production from a clinically euthyroid patient. metastatic differentiated thyroid cancer may not manifest on initial Case Description: A 47-year-old female with no significant medical biochemical evaluation and can demonstrate functionality over history was referred to our endocrinology clinic due to an elevated time. TSH to 161.9 (0.400-5.500 mIU/L) discovered during screening for Case Description: 88-year-old female presented with left-sided hypothyroidism. Her FT4 was normal at 1.2 (0.9-1.7 pg/ml). The pelvic pain. MRI revealed a 9.8 cm lytic mass within the medial patient was found to have positive anti-TPO and anti-TG antibodies aspect of the left pelvis. CT-guided biopsy of pelvic lesion was and had a family history of hypothyroidism in her mother. The consistent with metastatic follicular thyroid cancer (FTC) and the patient explicitly denied any symptoms of hypo or hyperthyroid- patient underwent external beam radiation. CT scan identified a 3.5 ism. In light of her lack of symptoms, it was elected to observe the

S171 Thyroid Endocrine Practice 27 (2021) S141eS188 patient versus initiating thyroid hormone replacement therapy. Influenza A and Influenza B by PCR were negative. TSH was low at Repeat TSH 6 months later was 159.7(0.400-5.500 mIU/L) by 0.182 uIU/mL (0.450-5.330 uIU/mL), free T4 elevated at 3.00 ng/dL Roche’s Elecsys TSH immunoassay, and 18.54 (0.4-4.5 mUl/L) by (0.58-1.64 ng/dL), free T3 elevated at 5.24 pg/mL (2.20-4.10 pg/mL). Siemen’s TSH immunoassay. Potential presence of laboratory Her TSH 3 weeks ago was normal at 0.723 uIU/mL. Thyroid stim- interference was suspected given incongruent laboratory assay ulating immunoglobulin negative < 0.10 (< ¼0.54 IU/L). Thyroid results with the patient’s presentation and discrepancies in TSH ultrasound showed normal sized gland, few sub centimeter nod- levels utilizing different immunoassays. FSH and LH were obtained ules bilaterally. NM thyroid uptake and scan showed low uptake since the glycoprotein hormones share a common alpha-subunit and no focal hot or cold nodule. Her workup was consistent with and both were within normal limits. Heterophile antibodies as the thyroiditis. Correlating with the diagnosis of COVID-19, this could cause for persistent TSH elevation was ruled out with TSH con- be most likely COVID-19 related thyroiditis. Repeat labs in a week centration being the same with and without heterophile blocking showed normal TSH 1.138 uIU/mL, normal free T4 1.28 ng/dL and treatment. The patient’s sera was precipitated with polyethylene low free T3 1.93 pg/mL. The patient likely had thyroiditis during glycol (PEG). After PEG treatment, the TSH concentration dropped early course of COVID-19 infection and was caught during the late dramatically to 3.4 mIU/L or 97.9% PEG precipitation. Typically, 50% phase and hence, improvement of thyroid function within a week of TSH will precipitate after PEG treatment, suggesting the presence of biochemical diagnosis. of a high molecular weight interfering substance. Macro-TSH was Discussion: Subacute thyroiditis is a self-limited inflammatory suspected and sera was sent to Roche Diagnostics for gel filtration disorder, characterized by neck pain, general symptoms and thy- chromatography which confirmed the presence of TSH near the roid dysfunction. It has been linked to viral infection like mumps molecular weight of an IgG-TSH complex. Thyroid stimulating virus, coxsackievirus, adenovirus, Epstein-Barr virus, rubella and immunoglobulin index < 1(< 1.3) suggested low bioactivity of the cytomegalovirus. In our patient, SARS-CoV-2 was the likely cause of macro-TSH complex. thyroiditis. A single center retrospective study done in 287 patients Discussion: Our case highlights the importance of the clinician’s hospitalized with COVID-19 in Milan, Italy reported 20% of patients interpretation of the laboratory assay in correlation with the clin- with thyrotoxicosis, 5% with hypothyroidism and 74% with normal ical evaluation to avoid misdiagnosis and unnecessary treatment. thyroid function test. We report this case to alert clinicians that Since FSH and LH were not affected by the interfering antibody it is thyroiditis and resultant thyrotoxicosis should always be consid- likely the antibody was directed against the beta-subunit of TSH. ered as a differential diagnosis in patients with COVID-19. Macro-TSH should be suspected when there is a discrepancy be- https://doi.org/10.1016/j.eprac.2021.04.832 tween clinical and laboratory evaluation. Unfortunately, testing for the presence of an interfering substance is a cumbersome process and no single test is readily available. Collaboration with clinical Abstract #1003853 chemistry in these scenarios is essential. ’ https://doi.org/10.1016/j.eprac.2021.04.831 Diagnostic Confusion Between Graves Disease And Pregnancy-Related Thyroid Function Abnormalities: A Learning Experience for Evolving Endocrinologists Abstract #1003850

Case of COVID-19 Related Thyroiditis Author Block: Sajjad Ali Khan - Aga Khan university hospital, Karachi, Pakistan; Muhammad M. Mehdi Khan, n/a - Co-author, Medicine, Aga Khan University Hospital; Zafar a. Suchal, n/a - Co- Author Block: Chheki Sherpa, MD - Primary author, Endocrinology, author, Medicine, Aga Khan University Hospital; Aisha Shaikh, Dr - Tower Health Reading Hospital; Ilan Gabriely, MD - Co-author, Co-author, Medicine, Aga Khan University Hospital Endocrinology, Tower Health Reading Hospital; Bishow C. Shrestha, MD - Co-author, Endocrinology, Tower Health; Introduction: Maternal hyperthyroidism is a rare disorder and the Vinita Singh, MD - Co-author, Endocrinology, Tower Health most common cause is Graves Disease. The physiological changes Reading Hospital that take place within the body in early pregnancy may alter thy- roid function testing and mimic biochemical hyperthyroidism that Introduction: The severe acute respiratory syndrome Coronavirus does not require therapy. Although, uncontrolled hyperthyroidism 2 (SARS-CoV-2) is a novel enveloped RNA beta-coronavirus poses risk for maternal and fetal complications. Circulating anti- responsible for the Coronavirus disease-19 (COVID-19) ranging bodies can enter the fetal circulation and harm the baby, the anti- from asymptomatic cases to severe respiratory involvement. The thyroid medication itself poses risks for the baby and low levels of SARS-CoV-2 pandemic has spread rapidly worldwide. Few cases thyroid hormone affect the myelination of the brain of the fetus. and case series have been published reporting COVID-19 related Case Description: Here we report a case of a 29-year-old lady subacute thyroiditis. We report a case of COVID-19 related (P1G0) who was 20 weeks pregnant presented with excessive thyroiditis. vomiting for 2 days. The onset was sudden with increased oral Case Description: 73-year-old female presented to the hospital intake and it was relieved with antiemetics. Furthermore, there was with complaint of shortness of breath, fever and weakness. She was an unintentional weight loss of 5-6 kg over 6 months with a normal diagnosed with COVID-19 pneumonia and treated with dexa- appetite. There were no complaints of tremors, sweating, palpita- methasone and convalescent plasma. Patient was discharged home tions, visual disturbance, diarrhea, heat intolerance, or menor- after 10 days. Two days after discharge, she presented with rhagia. The rest of the history was unremarkable. On examination complaint of generalized weakness. She was noted to have thyro- her BP was 120/80 and pulse was 70-85 beats per minute. There toxicosis. Patient was not taking lithium or amiodarone and she did were no signs of palmar sweating, tremors, goiter, skin changes or not receive iodinated contrast. She had no sign or symptoms of exophthalmos. Lab investigations revealed TSH 0.010, T4 22.90, thyrotoxicosis. She denied neck pain or difficulty swallowing. On Anti-TPO 22, Tb 0.3, ALT 48, AST 20, BHCG 27.85659. Ultrasound laboratory evaluation, SARS Coronavirus 2 RNA was positive. RSV, abdomen was normal.

S172 Thyroid Endocrine Practice 27 (2021) S141eS188

Discussion: Based on relevant history, examinations, and investi- these patients. In patients with Alemtuzumab-induced thyrotoxi- gation, this was concluded to be a case of pregnancy-related hy- cosis, thyroid autoantibodies, and in particular TRAb, are key in perthyroidism. A proper assessment of hyperthyroid status and refining the diagnosis. An uptake scan is a useful adjunct if the TRAb management is necessary because both the hyperthyroidism and is negative. the therapy may seriously complicate the course and outcome of https://doi.org/10.1016/j.eprac.2021.04.834 pregnancy. https://doi.org/10.1016/j.eprac.2021.04.833 Abstract #1003897

Abstract #1003875 Physician Induced Psychosis

A Case of Alemtuzumab-induced TRAb-negative Graves’ Disease Author Block: Joseph Parimi - University of Missouri, Columbia; Rajani Gundluru, MD - Co-author, Endocrinology, University of Missouri, COlumbia; Romayne kurukulasuriya, MD - Co-author, Author Block: Muhammad Hassaan Pervez - Royal College of Endocrinology, University of Missouri, Columbia; Sowjanya Naha, Physicians Edinburgh; Anna Mitchell, Consultant Endocrine MD - Co-author, Endocrinology, University of Missouri, COlumbia Physician - Co-author, Royal victoria Infirmary, Newcastle Introduction: The usually dose requirement of Liothyronine for Introduction: Alemtuzumab is a disease modifying medication hypothyroidism, myxedema coma, suppression test or depression used for highly active relapsing-remitting Multiple Sclerosis. It is a is between 25 to 75mcg daily. Supra therapeutic doses of Liothyr- recombinant DNA-derived humanised monoclonal antibody which onine will lead to suppression of hypothalamic pituitary axis (HPA). binds to CD-52 (a cell surface antigen present primarily on T and B Half-life of Liothyronine is relatively short at 0.75 days, hence acute lymphocytes). The actual mechanism is unknown but research discontinuation of Liothyronine can then lead to severe suggests it exerts its effects by immunomodulation via depletion hypothyroidism. and repopulation of lymphocytes. Depletion occurs by antibody- Case Description: A 52-year-old female was admitted for acute dependent, cell-mediated cytotoxicity, complement-dependent onset of altered mentation with auditory hallucinations in cytolysis and apoptosis whereas repopulation occurs by two October 2020. Work-up showed thyroid stimulating hormone mechanisms: (TSH) suppressed at < 0.005 micro unit/mL (range 0.270-4.2), 1. Proliferation of mature lymphocytes that escape depletion free thyronine (T4) low at 0.10 ng/dL (range 0.93-1.7), free 2. Bone marrow/thymic repopulation. Triiodothyronine (T3) normal at 2.4 pg/mL (range 2.0-4.4). A Alemtuzumab reduces the relapse rate in MS by 70%. How- review of the outpatient medications discovered the patient has ever, it can potentiate autoimmune disorders and autoimmune been on Liothyronine 250 mcg daily since May 2019, which was thyroid disease (AITD) has been the most common autoimmune started by her primary care physician (PCP) for fatigue. Records disorder, followed by immune thrombocytopenia (ITP), and from the PCP revealed normal TSH, free T4 and negative thyroid nephropathies. peroxidase antibodies in January and May of 2019 prior to Case Description: We present an interesting case of young lady initiation of the Liothyronine. Unfortunately, follow up labs were with known Relapsing-remitting Multiple Scleroris on alemtuzu- not performed to titrate the dose. The admission lab results mab therapy referred to our rapid access endocrine clinic from were consistent with the suppression of HPA axis due to neurology team with abnormal thyroid functions. She reported supraphysiologic doses of liothyronine, except the Free T3 level weight loss of about 4lbs in last few weeks and suffered from which was not elevated as expected. palpitations on and off. She was commenced on Alemtuzumab last Before the current admission, patient was admitted to another year and was due to have 2nd cycle of alemtuzumab in two weeks. hospital for 10 days for small bowel obstruction for which a On examination, her pulse was regular but tachycardia 110 beats nasogastric tube was placed and she was kept nothing per per minute. She did not exhibit any thyroid eye signs. Her thyroid oral(NPO). Given the preceding clinical condition and short half gland palpation showed smooth goitre. On auscultation, there was life of liothyronine the normal free T3 level on admission was no thyroid bruit. logical. On presentation, her thyroid functions revealed TSH < 0.05 Altered mentation was attributed to severe hypothyroidism. mU/L (normal range 0.3-4.5 mU/L), Free Thyroxine >100 pmol/L Intravenous levothyroxine was used for 3 days which (normal range 9.5 - 21.5 pmol/L) Free T3- 38.3 pmol/L (normal normalized the free T4 and significantly improved her menta- range¼ 3.1-6.8 pmol/L), Thyroid Peroxidase Antibody 7 kunits/L tion. Review of systems revealed 50-pound weight loss, tremors, (normal range¼0-34) TBII (TRAb) < 1.0 IU/L (normal range < palpitations and increased frequency of defecation in months 1.8). With undetectable TRAb levels, it appeared that she was preceding the hospital admission. Patient was discharged likely to be a case of thyroiditis. She was commenced on pro- home on 125 mcg of levothyroxine daily with a plan to fol- pranolol upto 40mg TDS and a Thyroid Technicium Tc-99 uptake low-up every 6 weeks to adjust the dose till the HPA axis scan was arranged. Uptake scan showed a diffuse high 12.18 % recovers. uptake throughout the thyroid gland consistent with Graves’ Discussion: Very few case reports of thyrotoxicosis secondary to disease. acute liothyronine toxicity exist. Two of them were due to Discussion: 40% of patients receiving Alemtuzumab develop thy- medication compounding errors from geometric dilution from roid dysfunction (GD, thyroiditis and hypothyroidism) within 5 the same pharmacy in British Columbia. Another was due to the years. Alemtuzumab-induced AITD has a peak incidence in year 3 contamination of liothyronine in weight loss medication. All 3 after the first course and median onset is about 17 months. Moni- patients had suppressed TSH and elevated T3 levels. Offending toring of thyroid function tests are therefore required routinely for medication was stopped and the patients recovered quickly. My

S173 Thyroid Endocrine Practice 27 (2021) S141eS188 patient had a prolonged suppression of HPA axis for 18 months Abstract #1004011 hence we elected to treat her with levothyroxine. https://doi.org/10.1016/j.eprac.2021.04.835 Thyroid Metastasis to Mandible: A Case Report

Author Block: Abstract #1003958 Rakhee Barai, MD - Primary author, Rutgers New Jersey Medical School; Maya Raghuwanshi, MD - Co-author, Thyroid Storm Caused By Hyperemesis Gravidarum Rutgers New Jersey Medical School; Tiffany Tsang, MD - Co-author, Endocrinology, Rutgers New Jersey Medical School

Author Block: Chelsea Zimmerman, MD - UF Health; Introduction: Metastasis from the thyroid gland to the oral cavity is Bradley Bruggeman, MD - Coauthor, Obstetrics and Gynecology, rare. In this case report, we present a case of mandibular metastasis University of Florida; Brittany Bruggeman, MD - Co-Author, from papillary thyroid carcinoma (PTC). Pediatric Endocrinology, University of Florida; Kristin Dayton, MD - Case Description: 68-year-old woman status post total thyroidec- Co-author, Pediatric Endocrinology, University of Florida; tomy presented with recurrent neck swelling and intermittent Alexandra Ilstad-Minnihan, MD - Co-author, University of Florida, dysphagia, without voice changes, respiratory symptoms or history College of Medicine; Nancy Joseph, MD - Co-author, University of of radiation exposure. There was a firm 3cm nodular left neck mass Florida, Department of Pediatrics; Daniel Moas, MD - Co-Author, on exam. A thyroid ultrasound demonstrated benign-appearing Pediatric Intensive Care, University of Florida; Henry Rohrs, MD - lymph nodes, but no discrete nodules. She initially had a left Co-Author (senior please list as last author), University of Florida hemithyroidectomy in Bolivia 9 years ago with pathology demon- strating high-grade PTC with focal follicular and insular patterns; Introduction: Transient thyrotoxicosis has been documented in immunohistochemistry was positive for thyroglobulin. She subse- the setting of hyperemesis gravidarum (HG) as well as in quently underwent completion thyroidectomy and 101.5mci RAI gestational trophoblastic disease (GTD) with profoundly elevated therapy. Pathology of the remaining right thyroid lobe was benign. human chorionic gonadotropin (hCG) levels. Thyroid storm in Posttreatment I-131 whole-body scan showed 0.2% uptake in the pregnancy is rare and typically associated with Graves disease. lower neck, suggestive of residual thyroid tissue or malignancy, Here we describe thyroid storm in a patient with hCG elevation without evidence of distant metastasis. Over the past 2 years, pa- secondary to HG that spontaneously resolved in the second tient’s thyroglobulin levels increased: 10.7ng/mL / 14.1ng/mL / trimester of pregnancy. 23.8ng/mL / 57.5ng/mL / 69.6ng/mL (ref. range 1.5-38.5ng/mL). Case Description: An 18-year-old female presented at 16 weeks An excisional biopsy of the neck mass was performed and pathol- gestation with vomiting, weight loss, tremor, weakness, dark ogy showed metastatic thyroid carcinoma in dermis and subcutis of colored urine, edema, tachycardia, elevated blood pressure, and skin with tumor cells positive for thyroglobulin and CK7; histo- altered mental status. She was found to be in thyroid storm based morphologic pattern was solid and follicular in a nodular on the Burch-Wartofsky Point Scale with undetectable thyroid arrangement. CT chest demonstrated multiple lung nodules and stimulating hormone (TSH) and free T4 > 6.99 ng/dL with subse- lesions in the liver, concerning for metastasis. PET/CT showed an quent hepatic and renal insufficiency. She was treated with intensely FDG-avid bone lesion in the left mandibular angle with methimazole, Lugol’s solution, propranolol and IV hydration. destructive changes, concerning for locoregional tumor recurrence Graves disease was initially suspected however thyroid stimulating and an intensely FDG-avid lung nodule consistent with metastatic immunoglobulin (TSI) and TSH receptor autoantibodies (TRAb) disease. were negative and her thyroid was of normal size and not hyper- Discussion: PTCs are common and usually nonaggressive tumors vascularized on ultrasound. hCG was obtained and significantly that are commonly detected by slow growing swelling of the elevated at 246,030 mIU/L (9,040-56,451 mIU/L). Obstetrics was anterior neck, as seen in our patient’s case. PTC typically follow an consulted and ruled out gestational trophoblastic disease making indolent clinical course and do not recur or metastasize beyond HG the leading diagnosis. Thyroid function quickly normalized as local lymph nodes; generally, thyroidectomy is curative. However, hCG decreased and all anti-thyroid medications were discontinued. our patient experienced metastasis of her PTC at the mandibular Renal and hepatic function also improved throughout her hospital angle, a common site of oral metastasis from thyroid cancer due to course. She has remained stable off all medications and all symp- the rich blood circulation in the medullary cavity of the region. toms resolved by 19 weeks gestation. Metastasis to the oral cavity is a rare occurrence e they account for Discussion: As hCG and TSH have identical alpha subunits, about 1% of all oral malignancies. Prognosis of patients with distant similar beta subunits, and similar receptors, hCG can bind to the thyroid metastases is generally poor, with an average of 40% of TSH receptor and stimulate thyroxine production. hCG peaks patients alive 4 years after the diagnosis of metastasis. In conclu- around 8-14 weeks gestation, correlating with decreased TSH sion, oral metastasis from PTC is a rare event that usually accom- levels in this same time frame. Higher levels of hCG are required panies a poor prognosis. to induce overt hyperthyroidism however, as this hormone has https://doi.org/10.1016/j.eprac.2021.04.837 less thyrotrophic activity. There are many overlapping symptoms including vomiting, weight loss, dehydration and organ dysfunction, and it is critical to establish the correct underlying Abstract #1004012 diagnosis to determine the appropriate treatment and prognosis. Studies show thyrotoxicosis should resolve by 20 weeks in this Nivolumab-Associated Exacerbation of setting, whereas thyroid dysfunction is expected to be more Hypothyroidism in an Athyreotic Patient prolonged with other etiologies. While transient thyrotoxicosis is well documented in HG, our case illustrates a more severe example of these comorbidities. Author Block: Prathayini Subarajan, DO - primary, presenter, https://doi.org/10.1016/j.eprac.2021.04.836 Internal Medicine, OhioHealth Riverside Methodist Hospital;

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Christopher Alcorn, DO - co-author, Internal Medicine, OhioHealth Introduction: At the annual AACE MEETING IN 2004, Stephanie Lee, Riverside Methodist Hospital; Kim Jordan, MD - co-author, Internal M.D., Ph.D. presented that one thyroid laboratory test, the TSH, was Medicine, OhioHealth Riverside Methodist Hospital; Daryl Cottrell, not a Bell-Shaped Curve. It has a right shoulder with TSH from 2.5-5 MD - co-author, Internal Medicine, OhioHealth Riverside which if accompanied by symptoms of hypothyroidism, may war- Methodist Hospital rant treatment with levothyroxine. In the next fourteen years, one hundred forty-six patients were seen with symptoms of hypothy- Introduction: Immune checkpoint inhibitor therapy (ICI) can cause roidism with elevated TSH. They included 14 women after eighteen various endocrinopathies, including thyroid dysfunction. Hypo- miscarriages who then had 14 full-term, healthy babies with thyroidism following ICI therapy has been reported in individuals treatment with levothyroxine. Usually, each patient had three or with intact thyroid. We present a case of worsening hypothyroid- more visits to change the dose of levothyroxine for best reduction ism in an athyreotic patient following nivolumab therapy. of symptoms, keeping the TSH within normal range. Case Description: A 66 year old female presented with fatigue Case Description: The first man is a M.D. chairman of his depart- and elevated TSH. History was significant for papillary thyroid ment with a TSH of 4.0 and multiple symptoms of hypothyroidism. carcinoma s/p total thyroidectomy and I-131 151.4 mCi, synovial The complete history, physical exam and laboratories revealed sarcoma of lung s/p wedge resection, and esophageal melanoma Subclinical Hypothyroidism and he was treated with levothyroxine metastatic to lung and adrenals. TSH ranged 0.18-0.58 uIU/mL on with resolution of all symptoms. He returned to work at his hospital levothyroxine 150 mcg daily with thyroglobulin < 0.1 ng/mL and in good condition with all symptoms resolved. The second man, a negative thyroglobulin antibodies over the previous 4 years. No fireman with TSH 3.5 was told by his primary doctor that he was thyroid remnant was present on exam or neck ultrasound. depressed, his thyroid was normal and he received an Nivolumab was initiated for metastatic melanoma. TSH was 0.74 antidepressant. uIU/mL one week prior. Over 3 months, she developed pro- By seeking an Endocrinology second opinion, he was found to be gressive fatigue. Blood chemistries, adrenal function and CBC hypothyroid and treated with levothyroxine and also Vitamin D were normal, but TSH was elevated at 13.78 uIU/mL. Repeat TSH deficient. He required Cholecalciferol 50,000 units per week. After was 17.15 uIU/mL, with free T4 of 1.26 ng/dL. She denied med- several weeks of both medicines, his MUSCLE WEAKNESS, FATIGUE, ications or supplements that interfere with assay or absorption, WEIGHT GAIN, COLD INTOLERANCE, MYALGIAS, CONSTIPATION, and was compliant with therapy, supported by in-office review and BRAIN-FOG RESOLVED. In addition to his three twelve-hour, of medication bottles. Levothyroxine was titrated to 250 mcg fireman shifts per week, he was able to start a second job. daily, achieving a TSH of 0.54 uIU/mL. Progressive melanoma Discussion: Both men who were 38 years-old, married and with 2 prompted change of nivolumab to ipilimumab. One month after children were now back to their previous or higher level of func- nivolumab discontinuation, TSH was low, 0.017 uIU/mL and free tion. There were 13 men in the study, all of whom received T4 high, 2.57 ng/dL (normal 0.7-1.7). Levothyroxine was gradu- appropriate levothyroxine. ally reduced to 150 mcg/day, her previous dose. Anti-thyro- In summary 146 out of 150 patients were identified in fourteen globulin antibody remained undetectable. years with subclinical Hypothyroidism and successfully treated Discussion: The mechanism by which nivolumab induces pri- with excellent results. mary hypothyroidism remains unclear. No other cases are re- https://doi.org/10.1016/j.eprac.2021.04.839 ported in post-thyroidectomy patients. Anti-PD-1 ICI can cause painless thyroiditis, with transient thyrotoxicosis often followed by hypothyroidism, which may resolve. Several reports docu- Abstract #1004170 ment patients with high baseline thyroid peroxidase or thyro- globulin antibody, or pre-existing hypothyroidism which Patterns of Thyroid Dysfunction in Metabolic worsened after pembrolizumab or nivolumab, sometimes Syndrome Patients and Its Relationship with requiring doubling of levothyroxine dose. However, other pa- Components of Metabolic Syndrome tients were antibody negative, both at baseline and during acute thyroiditis, raising the question of a different mechanism. Exacerbation of hypothyroidism in this case could not be due to Author Block: Nazma Akter - MARKS Medical College & Hospital, thyroiditis, and resolved after discontinuation of nivolumab, Dhaka, Bangladesh suggesting nivolumab as the cause. It is unknown whether other antigens or immune targets, or interference with levothyroxine Objective: Metabolic syndrome (MetS) consists of a constellation of absorption or action contribute. Close monitoring of thyroid metabolic abnormalities which include central obesity, hypergly- function in patients taking PD-1 ICI is needed even in those post cemia plus insulin resistance, high triglycerides plus low high total thyroidectomy on stable thyroid hormone replacement. density lipoprotein (HDL) cholesterol and hypertension. A growing https://doi.org/10.1016/j.eprac.2021.04.838 body of evidence suggests that metabolic syndrome is associated with endocrine disorders including thyroid dysfunction. Thyroid dysfunction in metabolic syndrome patients may further add to Abstract #1004126 cardiovascular disease risk thereby increasing mortality. This study was done to assess thyroid function in metabolic Remarkable Treatment of Two Thirty-Eight-Year-Old syndrome patients and evaluate its relationship with the compo- Professional Men for Subclinical Hypothyroidism nents of metabolic syndrome. Methods: A cross sectional study was carried out among metabolic syndrome patients at a Hormone & Diabetes clinic in a tertiary care Author Block: Lee A. Goscin, M.D., Ph.D., F.A.C.E. - Primary Author, hospital, Dhaka, Bangladesh during June 2019 to March 2020. We Aiyan Diabetes Center; Erika Marrero, B.S. - co-author, Aiyan recruited 346 patients who fulfilled National Cholestrol Education Diabetes Center; Amanda Edgar, CMA - co-author, Aiyan Diabetes; Program-Adult treatment Panel (NCEP-ATP) III (3 out of 5 criteria Crystal Salvatore, Tech - co-author, Aiyan Diabetes Center positive) criteria. Anthropometric measurements (height, weight,

S175 Thyroid Endocrine Practice 27 (2021) S141eS188 waist circumference) and blood pressure were taken. Fasting blood Methods: This study included a nodular goiter group with 55 per- samples were analysed to measure glucose, triglyceride (TG), high sons and control group with 58 persons. Participants’ gender, age, density lipoprotein (HDL) cholesterol and thyroid hormones [Thy- family history, thyroid function tests, sedimentation, leukocyte, roid stimulating hormone (TSH) and Free Thyroxine (FT4)]. Patients fibrinogen, CRP and pentraxin-3 serum levels were recorded. The were said to be euthyroid if all thyroid hormone levels fell within number of nodüles,the largest nodule diameter, nodular echoge- reference range [TSH: 0.47-5.0 mIU/L; FT4: 0.71-1.85 ng/dL]. Sub- nicity and nodule structures were examined on ultrasonography clinical hypothyroidism (SCH) was considered if TSH >5.0 mIU/L and thyroid biopsy was performed. The relationships between and free T4 is within normal reference value (0.71-1.85 ng/dL).O- these parameters were then statistically evaluated. vert hypothyroidism was defined as TSH > 5.0 mIU/L and free T4 < Results: Female/male ratio of the participants was 3.6 with an age 0.71 ng/dL. range of 21-78 (mean 49.5) years. Nodules were found at both sides Results: The study population consisted of 22.8 % (n¼ 79) males in 47.3% of the patients and the number of nodules was two in most and 77.2 % (n¼ 267) females, with mean age of 42.61 ±9.13 patients (47.3%, n:26). Nodule diameters differed between 3-62 years. Average body mass index (BMI) was 26.37± 3.78 kg/m2. (mean 21) mm, and solid nodules were found in majority of the Most of the female subjects (52.6%) were obese; [p¼0.02] and patients (58.2%). In thyroid biopsy, papillary thyroid cancer was had central obesity (62.7%); [p< 0.001]. Thyroid dysfunction was detected in 25.5% (n:14) of the patients. Female/male ratio was seen in 46.8 % (n ¼ 162) metabolic syndrome patients. Sub- found as 1.6 and age range as 18-84 (mean 46.6) years in the control clinical hypothyroidism (34.1 %) was the major thyroid groups. The number of nodules on ultrasonography increased as dysfunction followed by overt hypothyroidism (12.7 %). Thyroid CRP values increased (p¼0.013). In addition, the number of nodules dysfunction was much common in females (37.0%) than males on ultrasonography decreased as fibrinogen values increased (9.9%) but not statistically significant; [p ¼ 0.21]. HDL cholesterol (p¼0,003). No significant difference was found between the groups showed significant negative correlation with TSH level (r ¼ in terms of sedimentation, leukocyte and pentraxin-3 values. -0.150, p¼ 0.005). Triglyceride showed significant positive cor- Discussion/Conclusion: The number of nodules was positively relation with TSH level (r ¼ 0.168, p ¼ 0.002) and negative correlated with CRP and negatively correlated with fibrinogen correlation with free T4 (r ¼ -0.200, p ¼ < 0.001). levels. This may be important in clinical follow-up. However, there Discussion/Conclusion: The prevalence of metabolic syndrome is was no difference between benign and malignant differentiation. increasing all over the world. Thyroid dysfunction, prominently Further studies with larger series of patients will provide more subclinical hypothyroidism has been observed more frequently in definitive results. metabolic syndrome patients than general population. https://doi.org/10.1016/j.eprac.2021.04.841 The present study identifies thyroid dysfunction in metabolic syndrome patients; subclinical hypothyroidism was the common- est followed by overt hypothyroidism. And thyroid function is Abstract #1004259 associated with some components of metabolic syndrome (high density lipoprotein cholesterol and triglycerides). Further study is An Unusual Case Of Severe Hypokalemic Periodic needed to evaluate the mechanism of this correlation. Paralysis https://doi.org/10.1016/j.eprac.2021.04.840

Author Block: Pooja Jotwani - Crozer Chester Medical Center; Abstract #1004209 Goonja Patel, MD - Co-author, Internal Medicine, Crozer Chester Medical Center; Praveena Gandikota, MD - Co-author, Clinical Significance of Erythrocyte Sedimentation Endocrinology, Crozer Chester Medical Center Rate, Leukocyte, Fibrinogen, C Reactive Protein and Pentraxin 3 Values in Thyroid Nodules Introduction: Thyrotoxic Periodic Paralysis (TPP) is a disorder characterized by abrupt onset of hypokalemia and typically lower extremity paralysis secondary to thyrotoxicosis. Despite a higher _ Author Block: Sabahattin Destek - Sancaktepe S¸ ehit Prof. Dr. Ilhan incidence of hyperthyroidism in women, over 95 percent of TPP Varank Training and Research Hospital; Elif Nur S¸ ahin, cases occur in men, with onset between 20-40 years of age. TPP has Sabahattin Destek - Presenter, Department of general surgery, been most widely reported in Asian populations, in which the Sancaktepe S¸ ehit Prof Dr Ilhan Varank Training and Research incidence among patients with hyperthyroidism is 2 percent. In Hospital; Beyza Bentürk, Sabahattin Destek - co-author, Bezmialem non-Asian populations, this incidence is 0.1-0.2 percent. Vakif University, Faculty of Medicine Hospital; Yunus Yapalak, Case Description: We present a 32-year-old Caucasian man with no Sabahattin Destek - co-author, Patnos State Hospital; significant past medical history who presented with acute onset € € Omer Faruk Ozer, Sabahattin Destek - co-author, Bezmialem Vakif bilateral lower extremity weakness on awakening. He denied loss University, Faculty of Medicine Hospital of consciousness, altered sensation, headache, vision change, dys- pnea, chest pain, palpitations, changes in urinary habit, recent Objective: Thyroid nodules are quite common in the general pop- travel, sick contacts, cold or heat intolerance, recent weight change ulation and remain a problem in clinical practice. Genetic and or vomiting. He endorsed 2-3 bowel movements a day. He denied environmental factors as well as chronic inflammation play a role in history of similar episodes, and family history of thyroid disease or occurance of these nodules. The key point in diagnostic assessment paralysis. Heart rate was 110 bpm, he was afebrile. Exam was is to rule out malignancy. In this study, we evaluate the relationship remarkable for easy distractibility, mild bilateral upper extremity between sedimentation rate, leukocyte, fibrinogen, C-reactive resting tremors, and motor strength 2/5 in bilateral lower ex- protein (CRP) and pentraxin-3 inflammatory markers and charac- tremities. Knee and ankle reflexes were bilaterally intact and teristics and cytology of thyroid nodules. symmetrical. No exophthalmos or goiter was noted on exam.

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Laboratory work demonstrated potassium 1.8 mEq/L, sodium 139 29.6. Most recent lab studies show a normal T4 with a normal TSH, mEq/L, magnesium 1.7 mEq/L, corrected calcium 8.8 mg/dL, phos- indicating apparent resolution of the patient’s central phorus 2.3 mg/dL, hemoglobin 13.9 g/dL, TSH 0.002 uIU/mL, free T4 hypothyroidism. 4.0 ng/dL. CT head was negative for acute pathology. EKG demon- Discussion: Changes in thyroid hormone levels after bariatric strated an accelerated junctional rhythm. Given the clinical pre- weight loss surgery have been observed in patients with primary sentation, the patient was diagnosed with hyperthyroidism and hypothyroidism specifically. In one study, 13.2% of patients with associated TPP. He was begun on treatment with Propranolol and primary hypothyroidism no longer required levothyroxine one year Methimazole. He received a total of 140 mEq of potassium chloride after surgery. To our knowledge, this case is the first to describe initially, with improvement in potassium to 3.8 mEq/L. His weak- similar results in a patient with central hypothyroidism. ness resolved. He was discharged with outpatient follow up and https://doi.org/10.1016/j.eprac.2021.04.843 possible radio-iodine uptake scan. Discussion: We present here an unusual case of TPP in a Caucasian individual. TPP is commonly misdiagnosed in western Abstract #1004262 countries because of similarities to familial hypokalemic periodic paralysis, a more common cause of periodic paralysis in Cauca- A Rare Presentation of Renal Cell Carcinoma Metastasis sians. TPP should be considered in the differential and physi- to the Thyroid Mimicking a Multinodular Goiter cians should look for subtle features of thyrotoxicosis when patients present with new onset weakness in the setting of hypokalemia, as with our patient. Increased awareness of this Author Block: James Kamau, MD - Primary author, St. Luke's condition amongst physicians will result in early suspicion and University Hospital Network; Asim Ali, MD - Co-author, St. Luke's recognition of this entity. This is essential for prompt initiation University Hospital Network; Richard Snyder, DO - co-author, St. of appropriate therapy, preventing the risk of rebound hyper- Luke's University Hospital Network kalemia, and improved outcomes. https://doi.org/10.1016/j.eprac.2021.04.842 Introduction: Multinodular goiter is one of the most common causes of an enlarged thyroid. Thyroid nodules are present in up to 50% of the adult population and are usually benign. Renal cell Abstract #1004261 carcinoma (RCC) makes up 80% of all kidney cancer. 65% of patients have localized disease on presentation, for which surgery is usually Central Hypothyroidism Resolved with Bariatric Surgery curative. About a quarter of these patients develop metastasis. The most common sites of metastatic disease are the lungs, bones, liver, renal fossa, and brain. Metastatic disease to the thyroid is extremely Author Block: Sophia Proschel - Wright State University Boonshoft uncommon. We present a case of metastasis from a RCC to the School of Medicine; Ankur Gupta, M.D., F.A.C.E, E.C.N.U. - Second thyroid mimicking a multinodular goiter. author, Wright State University Boonshoft School of Medicine Case Description: A 69-year-old female status post nephrectomy for RCC diagnosed 20 years ago with no evidence of recurrence Introduction: Described is a case of idiopathic central hypothy- on annual renal ultrasound (US) or urine cytology. She had been roidism resolved after bariatric weight loss surgery. evaluated for suspected gastro-intestinal blood loss due to Case Description: A 45-year-old woman with past medical his- weight loss and iron deficiency anemia. She also had complaints tory of hypertension and obesity presented in May 2016 for of dysphagia, which was chronic and felt to be related to her evaluation and management of central hypothyroidism. Labs goiter. Colonoscopy showed internal hemorrhoids. An endoscopy done by her primary care physician in February 2016 showed a could not be performed due to compression on the esophagus. low free T4 with normal serum TSH. She had been started on CT scan of the neck revealed an enlarged left thyroid with levothyroxine 100 micrograms daily. On initial presentation to extension below the clavicles and deviation of the trachea and the endocrine clinic, her only concern was fatigue and 20 esophagus to the right. A thyroid US showed an enlarged het- pounds of weight gain in the past year. She denied any dizzi- erogeneous left thyroid lobe with scattered microcalcifications ness, headaches, or visual symptoms. but no definitive dominant nodule. She had had several biopsies Physical exam was unremarkable with a normal thyroid and on multiple nodules performed, which were benign. The patient normal vital signs. Her weight was 256 pounds and her BMI was underwent a subtotal thyroidectomy for a presumed multi- 43.9. Repeat blood tests revealed a low-normal free T4 by direct nodular goiter. During surgery, a very large mass with significant dialysis and a normal serum TSH. Magnetic resonance imaging necrosis and inflammatory tissue attached to surrounding (MRI) of the pituitary showed a normal pituitary gland and workup musculature and esophagus was noted. Surgical specimens were of other pituitary hormones was unremarkable. A diagnosis of consistent with metastatic renal cell carcinoma and thyroid idiopathic central hypothyroidism was established. The patient’s goiter on pathology. levothyroxine was increased to 150 micrograms and her free T4 Discussion: Our patient likely had metastatic renal cell carcinoma normalized. to the thyroid for many years that went undiagnosed despite In the following year, the patient was taken off levothyroxine and multiple biopsies due to likely sampling of benign nodules. This started on armour thyroid 60 milligrams daily by her obstetrician. delay in diagnosis likely resulted in inability to achieve complete She returned to our clinic in September 2019 and was switched surgical metastasectomy, which confers a survival benefit in addi- back to levothyroxine 150 micrograms daily. Blood tests done in tion to systemic therapy. Renal cell carcinoma is the most common January 2020 showed a normal free T4 and normal free T3. The non-thyroid cancer found in the thyroid. In patients with a history patient elected to undergo gastric sleeve surgery for weight loss in of RCC and a thyroid mass a high suspicion for metastatic RCC February 2020. should be maintained. Following her gastric sleeve surgery, the patient was tapered off levothyroxine. Her current weight is 172 pounds and her BMI is https://doi.org/10.1016/j.eprac.2021.04.844

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Introduction: Abstract #1004269 FAP is caused by a defect in the adenomatous pol- yposis coli gene. There is an association between FAP and PTC Subacute Thyroiditis in Patients Infected with (papillary thyroid cancer) which occurs in 1-2% of patients, mostly SARS-COV-2 young women. The type of PTC is usually a cribriform morular variant, which carries a good prognosis. In contrast, poorly differ- entiated thyroid carcinoma is a more aggressive tumor. We report a Author Block: Zelija Velija Asimi - Outpatient Clinic with Daily case of PTC with a nidus of poorly differentiated thyroid cancer in hospital; Almira Hadzovic Dzuvo, professor - co-author, Outpatient the setting of FAP and a rapidly progressive course. Clinic "dr Al-Tawil" Case Description: A 26-year-old female with FAP had an ultrasound showing a 3 cm right hypoechoic thyroid nodule and a suspicious 9 Introduction: Subacute thyroiditis (SAT) is an inflammatory dis- mm right lymph node. Fine needle aspiration of the nodule was order of the thyroid gland that causes destructive thyrotoxicosis positive for PTC, and the lymph node was negative. Right thyroid and is attributed to a viral or post-viral response. The Severe acute lobectomy and isthmusectomy was performed. Pathology showed respiratory syndrome coronavirus 2 (SARS-CoV-2) virus enters PTC with morules and a 0.8 mm focus of poorly differentiated human cells through the angiotensin-converting enzyme 2 (ACE2) thyroid carcinoma within the main tumor mass. She underwent a receptor. Thyroid follicular cells express the ACE2 receptor, thus left lobectomy which was negative for malignancy. No suspicious making thyroid tissue a possible target of direct infection by the adenopathy was identified during either procedure. Levothyroxine SARS-CoV-2 virus. The aim was to describe cases of SAT associated suppressive therapy was started. Throughout her course her TSH with SARS-CoV-2 infection to alert physicians that SAT may be a remained suppressed and thyroglobulin was undetectable. She manifestation of SARS-CoV-2 infection. received 106 millicuries of I-131. Post treatment scan showed up- Case Description: We describe clinical, biochemical, and imaging take limited to the thyroid bed. Neck ultrasound 6 months later features of 11 patients with SAT related to SARS-CoV-2 infection. showed a 2.8 cm hypoechoic mass in the right thyroid bed and a Discussion: All patients were female (age, 30-45 years). Neck pain right cervical nodule, suspicious for disease recurrence. An ultra- radiated to the jaw, fatigue, tremors, and palpitations were the sound guided core biopsy of the right cervical nodule was consis- main presenting symptoms and were associated with fever and tent with metastatic poorly differentiated thyroid carcinoma. PET asthenia. Physical examination revealed mild tremors of the ex- scan showed a hypermetabolic soft tissue mass in the right thyroid tremities, a diffuse and painful goitre, and enlarged and tender bed, and mildly hypermetabolic small pulmonary nodules. Addi- cervical and submandibular lymph nodes. At biochemical evalua- tional neck surgery showed lymph nodes with poorly differentiated tion, inflammatory markers were high. Thyroid function tests were thyroid carcinoma and extra nodal extension. A stimulated I-123 suggestive of destructive thyroiditis. TSH was suppressed, free scan showed no iodine avid disease. Follow up chest CT showed thyroxine (FT4) and free triiodothyronine (FT3) levels were progressive pulmonary disease. A transbronchial biopsy confirmed elevated, and serum thyroglobulin was markedly increased (175 ng/ poorly differentiated thyroid carcinoma. Tumor molecular testing ml; referral range 2.68-33.2). Anti-thyroid peroxidase, anti-thyro- did not show any candidates for targeted therapies and lenvatinib globulin, and thyroid-stimulating hormone receptor antibodies was started. were negative. At neck ultrasound the thyroid was enlarged, with Discussion: FAP has been associated with an increased risk for diffuse and bilateral hypoechoic areas and absent vascularization at cribriform morular variant PTC. There have been only three other colour Doppler. Thyroid scintigraphy showed markedly reduced reported cases of cribriform morular variant PTC in FAP progressing 99mTc-perthecnetate uptake in the gland. Reverse transcription- to poorly differentiated thyroid carcinoma. This progression is polymerase chain reaction for SARS-CoV-2 using nasopharyngeal difficult to predict as molecular sequencing and pathogenic mani- and oropharyngeal swabs were positive. Chest X-rays and festations have presented uniquely in each case, with our case computed tomography scanning of the chest were normal. Symp- showing no apparent molecular targets. Further investigation is toms were alleviated a few days after commencement of treatment indicated to develop a more complete and focused approach to (aspirin in 3 patients, prednisone in 2 patients, paracetamol in 3 treating this aggressive form of malignancy. and ibuprofen in 3) together with propranolol for tachycardia and https://doi.org/10.1016/j.eprac.2021.04.846 tremors. Ten weeks after the onset of SAT, all patients were asymptomatic and inflammatory markers had returned to normal range. Eight patients were euthyroid, whereas 3 were with sub- Abstract #1004280 clinical hypothyroidism. Conclusion: Clinicians should be aware of thyroid manifestations potentially associated with COVID-19. Severe Hypothyroidism Associated with COVID-19: A Two Case Presentation https://doi.org/10.1016/j.eprac.2021.04.845

Author Block: Maria Ramos Guifarro - Hospital Escuela; Abstract #1004276 Grace García, Internal medicine resident - Co author, Internal Rapidly Progressive Disease Burden of Metastatic medicine, Hospital escuela universitario; Guillermo Zaldivar, Poorly Differentiated Thyroid Carcinoma in a Patient Internal medicine resident - Co author, Internal medicine, Hospital with Familial Adenomatous Polyposis (FAP) escuela universitario; Nadia Alfaro, Internal medicine Resident - Co author, Internal medicine, Hospital escuela universitario; Eimy y. Barahona, MD - Primary, Hospital escuela universitario; Author Block: Anthony Chuang - University of New Mexico; Daniel A. Guifarro, MD - Co author, G &V Medical Kristen M. Gonzales, MD - Co-Author, Endocrinology, Diabetes, and Metabolism, University of New Mexico; Patricia L. Kapsner, MD - Introduction: In January 2020, a new betacoronavirus strain (SARS- Co-Author (Mentor/Supervisor), Endocrinology, Diabetes, and CoV-2) was identified and established as the cause of the corona- Metabolism, University of New Mexico virus disease 2019 (COVID-19) that started in China. On March

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2020, COVID-19 was declared a global pandemic, affecting millions worrisome, and considered a main cause of cancer-specific mor- worldwide. Patients with COVID-19 have been described to present tality in these patients. We present a case of Hurthle cell thyroid pulmonary and systemic manifestations, including endocrinologic carcinoma with breast metastases. alterations and associations such as altered thyroid function. Case Description: An 87-year-old woman presented with shortness Case Description: We present two female patients, both COVID-19 of breath on exertion and lumps on her neck and right breast. Her positive, with symptoms of severe hypothyroidism. Patient 1 is 36 history is significant for hypertension, renal insufficiency, Hurthle years old and patient 2 is 46 years old, both known for hypothy- cell thyroid carcinoma, postoperative hypothyroidism and tracheal roidism treated with levothyroxine (50 and 100mcg PO/day stenosis. Hurthle cell thyroid carcinoma was diagnosed in 2004. respectively). Both patients assisted to the emergency room with She underwent total thyroidectomy followed by radioactive iodine history of dry cough, ageusia, anosmia, fever and dyspnea, thick and and external beam radiation. She also underwent five years of dry scaly skin, bipalpebral edema and pallor. Patient 1 referred therapy with sorafenib. Thyroglobulin level following surgery was myalgias and arthralgias, while patient 2 referred diarrhea. Patient undetectable. Fifteen years later, she presents with increased 1 was found with slow and slurred speech, requiring oxygen at shortness of breath on exertion and new lumps on her neck and arrival, with bilateral basal crackles, left basal hypoventilation and right breast. Computed tomography (CT) scan of her neck and chest diminished heart sounds; Patient 2 had bilateral lung hypo- showed a large irregular infiltrative soft tissue mass in the right ventilation and asterixis. Both were anemic and presented a posi- thyroidectomy bed consistent with progression of thyroid cancer. tive COVID-19 RT-PCR test. Laboratory results: Patient 1: TSH: 30.5 The mass also infiltrated the subglottic larynx and a metastatic soft IU/ml, FT4: < 0.3 mg/dl, Patient 2: TSH: 55.7IU/ml, FT4: 0.59 mg/dl. tissue nodule was noted along the anterior border of the left ster- Chest CT showed cardiomegaly, pleural and pericardial effusions nocleidomastoid muscle, along with worsening mediastinal aden- with bilateral peribronchial consolidations for patient 1, and car- opathy. Breast ultrasound and mammogram showed solid, sharply diomegaly (at expense of left chambers), bilateral pleural effusion circumscribed, hypoechoic nodules in the far posterior right lower and basal reticular pattern with no shattered glass pattern for pa- breast along the chest wall. Subsequently, she underwent ultra- tient 2. Patient 2 was diagnosed with chronic kidney disease that sound-guided breast biopsy and histologic findings showed com- needed dialysis. Both patients were treated with Levothyroxine plex follicular neoplasm with oncocytic features that were 200mcg PO daily and IV steroids, and patient 1 was diagnosed with immunohistochemically consistent with metastatic hurthle cell myxedematous coma. thyroid carcinoma. Discussion: To this date, there is not enough data to support that Discussion: Hurthle cell thyroid carcinoma metastasizing to the thyroid disease increases the risk of having COVID-19, and COVID- breast represents a very rare occurrence. Only a handful of cases 19 has not been found with a greater prevalence in patients with have been reported in the current literature. Hurthle cell carcinoma thyroid disease. Zhang et al reported a 140-case series of COVID-19 of the thyroid with breast metastasis is associated with a very poor patients, in which 5 patients were known for hypothyroidism (4 prognosis. We presented this case to illustrate the possibility of presented severe disease). Wang et al reported that serum T3 and thyroid cancer breast metastases in a patient with a history of T4 were decreased in these patients, being significantly lower than thyroid cancer presenting with a new breast mass. This may help to in the control healthy group. Our patients were found with low FT4 facilitate both early detection and management. and high serum TSH, with symptoms suggesting myxedematous https://doi.org/10.1016/j.eprac.2021.04.848 coma and severe hypothyroidism respectively. Pituitary insuffi- ciency has been described in COVID-19 patients, which can lead to fi thyroid and adrenal insuf ciency requiring hormonal replacement Abstract #1004294 therapy, describing the case of our patients in which the dose of levothyroxine had to be doubled and quadrupled respectively. A Case of Fetal Goiter Secondary to Overtreatment of https://doi.org/10.1016/j.eprac.2021.04.847 Maternal Graves' Disease

Author Block: Abstract #1004282 James Turner - University of Tennessee Health Science Center Hurthle Cell Carcinoma of the Thyroid Gland with Breast Metastasis Introduction: Background: Fetal Goiter due to Maternal Graves' Disease can be caused by thyroid stimulating immunoglobulin as well as overtreatment of maternal hyperthyroidism. Using fetal Author Block: Marie Krielle Pantino - St. Luke's University Health ultrasound and maternal thyroid function tests can help to guide Network; Jana Havranova, MD - co-author, St. Luke's University treatment. Health Network; Atef Labeeb, MD - co-author, St. Luke's University Case Description: A 29-year-old African American Female with no Health Network; Hammad Liaquat, MD - co-author, St. Luke's PMH was referred to Endocrinology by her Obstetrician for labo- University Health Network; Michelle Andrion, MD - co-author, St. ratory findings consistent with hyperthyroidism. The patient was Luke's University Health Network; James Kamau, MD - co-author, gravida 5 para 3 with a history of one spontaneous abortion, and St. Luke's University Health Network; Subhash Proothi, MD - Co- she was 29 weeks pregnant at the time of her first evaluation by author, St. Luke's University Health Network; Richard W. Snyder, Endocrinology. The patient denies a personal history of thyroid DO - co-author, St. Luke's University Health Network problems prior to her current pregnancy, but she does recall having a first degree relative with Hashimoto Thyroiditis. Her primary care Introduction: Hurthle cell carcinoma is a form of differentiated physician originally checked the patient’s thyroid function tests due follicular thyroid carcinoma and the presence of this histology is a to elevated heart rate. Her initial thyroid function tests were as poor prognostic feature. Hematogenous spread most often involves follows: Thyroid Stimulating Hormone - < 0.01 (0.40 - 4.1 mIU/L), the bone, lung, or central nervous system. Metastases of differen- Free T4 4.35 (0.80 - 1.90 ng/dL), and FT3 18.3 (2.2 - 4.2 pg/mL). tiated thyroid cancer to other sites are extremely uncommon, often Thyroid peroxidase antibody was elevated to 460 (0 e 34IU/mL).

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Thyroid Stimulating Immunoglobulin was elevated to 3.18 (0.00 - abdomen revealed ascending colonic and sigmoid wall thick- 0.55 IU/L). The patient was started on Methimazole 10 mg twice ening. Esophagogastroduodenoscopy revealed esophageal, gastric daily. A thyroid US was performed which showed a diffusely and duodenal ulcers while colonoscopy showed an erythema- enlarged thyroid with no nodules. Fetal Ultrasound was performed, tous and friable mucosa with cobblestoning ulcerations. Stool and the fetal thyroid was found to be at the 98th circumference antigen test was negative for Clostridium difficile. Therefore she percentile. Fetal growth and heart rate were considered normal per was started on intravenous steroids and oral mesalazine. the ultrasound report. Cordocentesis was considered, but the pa- Nevertheless, she continued to have unrelenting complaints and tient decided to continue with expectant management. The ques- a colectomy with ileostomy were performed. She had gradual tion remained whether the fetal goiter was secondary to maternal clinical improvement and was discharged with colestiramine , thyroid stimulating immunoglobulin versus overtreatment of lugol's solution, prednisone and mesalazine. maternal hyperthyroidism. The fetal thyroid size remained in the Discussion: It is unclear whether cases of concomitant autoim- 98th circumference percentile for multiple weekly ultrasounds mune thyroid diseases and Crohn's disease have a common while the maternal FT4 decreased well into the normal range. The immunological basis. Some studies have assessed possible common decision was made to decrease the Methimazole dose to 5 mg once genetic factors between both diseases. Yet, thyroid disorders are daily, which appears to have resulted in a decrease in fetal goiter not classified as an extra-intestinal manifestation of Crohn's dis- size. On the latest available fetal ultrasounds, the thyroid circum- ease. Furthermore the association of Crohn's disease and Graves' ference percentile has decreased to the 50th to 90th percentile and disease can trigger therapeutic issues. An inflammatory bowel has remained stable. disease should be taken into consideration in patients with Graves Discussion: Conclusion: Fetal goiter size may improve in pregnant ‘disease when diarrhea persists despite de favorable course of patients with Graves' disease during pregnancy if anti-thyroid drug Graves' disease. dosage is adjusted based on maternal thyroid function tests. https://doi.org/10.1016/j.eprac.2021.04.850 https://doi.org/10.1016/j.eprac.2021.04.849

Abstract #1004302 Abstract #1004297 COVID-19 Pandemic Collateral Damage in Treatment Graves' Disease in Association with Crohn's Disease Adherence of Chronic Disease: A Case Series of 3 Hyperthyroid Patients

Author Block: Michelle García Gonzalez - General Hospital of Mexico Dr. Eduardo Liceaga; Antonio Segovia-Palomo, Thyroid Author Block: Maria Ramos Guifarro - Hospital Escuela; Clinic - Co author, Endocrinology, General Hospital of Mexico Dr. Luis Guifarro, Md - Co author, Heu; Tania Domínguez, Md - Primary Eduardo Liceaga; Gladys E. Cordova-Hernandez, Thyroid Clinic - Co author, Endocrinology, Hospital escuela univeristario; author, Endocrinology, General Hospital of Mexico Dr. Eduardo Daniel A. Guifarro, Md - Co author, G y V medical Liceaga Introduction: Due to the outbreak of betacoronavirus known as Introduction: The coexistence of Crohn's disease and autoimmune COVID-19 that began in China in December 2019 and spread rapidly thyroid disease in uncommon. The rate of Graves' disease in pa- across the globe, almost every country in the world has been tients with Crohn's disease is unknown in detail. However, the affected, causing 2.23 million deaths. Hospitals and health centers reported prevalence can range between 0.3 % - 0.9%. have been overwhelmed with the care of these patients and other Case Description: A 33- year- old female, nonsmoker, was medical emergencies, postponing attention too patients with admitted to the emergency department with history of fever, chronic diseases. Endocrine disorders are no exception and many odynophagia, hyporexia, abdominal pain and diarrhea for which endocrinologists have found themselves in the frontline against she had been previously given several antibiotics. She had been COVID and away from their usual clinical battlefield. diagnosed with Graves’ disease two years prior but had poor Case Description: We describe a series of 3 pregnant/puerperal adherence to treatment. Four months prior she was re- started hyperthyroid female patients, who in the midst of the COVID-19 on thiamazole 30 mg and propranolol 60 mg because of wors- pandemic were forced to discontinue their follow-up from the ening of symptoms. She had family history of systemic lupus endocrinology outpatient clinic and assisted with acute exacerba- erythematous and rheumatoid arthritis. Upon physical exami- tion of their thyroid disease due to suspension of their treatments. nation blood pressure was 80/50 mm/hg , heart rate 108 bpm, Patient 1 is 24 years old, one day postpartum at the time evaluation, temperature 38.7 C. She had bilateral exophthalmos, aphthous patient 2 is 39 years old with 31.1 weeks of gestation, and patient 3 stomatitis and non tender goiter. Abdominal exam was signifi- is 37 years old with 10.6 weeks of gestation, all university educated. cant for diffuse tenderness. Laboratory workup revealed her Patient 1 and 2 discontinued their treatment in March 2020 (when white blood cell count was 2100 ml with 4.9 % neutrophils and the complete lockdown in Honduras took place) patient 3 93.3 % lymphocytes. Her hemoglobin was 9.90 g/dl , hematocrit continued with her medication without medical supervision since 28.20% and platelet count 655,000. Laboratory results of thyroid lockdown. All were found to have exophthalmos and goiter, patient function tests were as follows: TSH 0.01 mUI/ ml (normal range: 2 being the only one presenting hypoecogenic nodules, the biggest 0.38-5.33 mUI/ ml) free T3 1.72 pg/ml (normal range: 2.39-6.79 one measuring 5x3mm. Two of the patients presented tachycardia, pg/ml) free T4: 0.71 ng/dl ( normal range: 0.58-1.64 ng/dl). hypertension, and resting fine hand tremor. Dizziness, nausea, Thyroid ultrasound demonstrated an enlarged gland with vomiting and abdominal pain were other symptoms referred at heterogenous echotexture and thyroid inferno pattern. She was evaluation. Laboratory results: Patient 1: FT4: 4.5mg/dl (0.89- started on intravenous fluids, antibiotics and a colony stimu- 1.76mg/dl), TSH: 0.001 mUI/ml. (0.4-4.0 mUI/ml), TPO AB: 22.7 IU/ lating factor. Treatment with thiamazole was suspended because ml (0-35) IU/, TgAB: < 20.0 IU/ml (0-40IU/ml), Patient 2: TSH: of antithyroid drug induced agranulocytosis. CT scan of the 0.010mUI/ml, FT4 : >6.0 mg/dL, TPO AB: 29.3UI/ml, TgAB :< 20.0 UI/

S180 Thyroid Endocrine Practice 27 (2021) S141eS188 ml, Patient 3: TSH: < 0.004mUI/ml, FT4 >1.93mg/Dl, T3: 227ng/dL. Studies suggest that color doppler ultrasound (CDU) likely has Patient 1 was treated with Propylthyouracil (PTU), propranolol, advantage over other testing modalities such as Grayscale nifedipine, dexamethasone and lugol; Patient 2 with PTU, pro- Ultrasound (GSU) and MRI and is a reasonable first choice as a pranolol, dexamethasone and lugol, and patient 3 with PTU, pro- diagnostic tool. Early detection of CH and its underlying cause pranolol and deflazacort. is important as early treatment of the condition within first Discussion: In the context of the COVID-19 pandemic, preventive few weeks of life with thyroid hormone is known to have health measures such as social isolation, modified routines and improvement in intellectual and linear growth potential of usual care in chronically ill patients have had repercussion on infants. follow-up and treatment. Services and supply chains were affected, Medical management is normally sufficient for management of depleting resources for chronic disease care. Ensuring good health hypothyroidism in patients with lingual thyroid. Surgical excision control in these patients should be one of the objectives in the of the ectopic thyroid tissue is not normally recommended as the management of the pandemic, since their contagion would put risk of development of carcinoma in the ectopic gland is rare with them at greater risk. Abandonment of self-care habits is another less than 30 cases reported in the literature. cause of disease worsening and has to be assessed as a pillar of https://doi.org/10.1016/j.eprac.2021.04.852 disease prevention and care. https://doi.org/10.1016/j.eprac.2021.04.851 Abstract #1004327

Abstract #1004316 Protein Caloric Malnutrition is Associated with Higher Mortality in Patients Admitted with Thyrotoxicosis: An Thyroid Dysgenesis and Congenital Hypothyroidism: A Analysis of the National Inpatient Sample Registry Case Study and Literature Review

Author Block: Marcelo Ramirez, MD - Primary author, John Stroger Author Block: Zara Z. Alvi, MD - primary author, Allegheny Health Hospital of Cook County; Ramtej Atluri, MD - Co-author, John Network; Hassan Mehmood, MD - co-author, Allegheny Health Stroger Hospital of Cook County; Kevin Bustos, MD - Co-author, Network; Farhad Hasan, MD - co-author, Allegheny Health John Stroger Hospital of Cook County; Shaka Hafeez, MD - Co- Network author, John Stroger Hospital of Cook County

Introduction: Congenital hypothyroidism (CH) is one of the Objective: Protein Caloric Malnutrition (PCM) is common among most common endocrine diseases in newborns with about 1 in hospitalized patients and has been associated with poor out- 3200 being affected. Thyroid gland, the primary site of comes in different medical conditions. However, its impact in thyroid hormone synthesis, descends from the base of the patients admitted with Thyrotoxicosis is not well documented in tongue to the center of the neck below the larynx in the the literature. Our goal with this study is to determine PCMs embryo and CH is caused by either thyroid gland dysgenesis effect in these patients in terms of morbidity, mortality and or dyshormonogenesis. hospital stay Case Description: A 23-year-old female with history of lingual Methods: A retrospective cohort study was conducted using the thyroid and congenital hypothyroidism presented to clinic for Nationwide Inpatient Sample from 2017. About 155964 patients follow up. She was started on treatment within a week of who had Thyrotoxicosis as their primary diagnosis were identified birth by her pediatric endocrinologist. Her labs had shown and stratified based on the presence of PCM using ICD-10 codes. primary hypothyroidism with Thyroid stimulating hormone Multivariate regression analysis was used to adjust for confounders (TSH) significantly elevated at 141.5 mIU/L and Free T4 and analyze the variables. The selection of covariates was done with decreased at 0.16 ng/dL. As an adult she had a thyroid ultra- a univariate screen and literature review. soundwhichshowedabsentthyroidglandandathyroidup- Results: Out of the 155964 hospitalized patients with Thyrotox- take scan which showed no iodine avid tissue at normal icosis, 11325 individuals had PCM. In-hospital mortality in thyroid location and iodine uptake 2.2% at 6 hours and 3.5% at Thyrotoxicosis patients with PCM was significantly higher than 24 hours at the base of the tongue, confirming the presence of those without (4.77 vs 1.57%, p¼0.018). Mean length of stay (LOS) lingual thyroid gland. Most recently, patient was on levothyr- and mean hospital charges (HC) were also higher in the presence oxine 100 mcg and liothyronine 10 mcg. She was gradually of PCM compared to those without (8.8 vs 4.6 days & $92,286 vs tapered off liothyronine and continued on levothyroxine for $51,078 respectively). When adjusted to patient demographics, management of her hypothyroidism. Repeat labs showed comorbidities, and hospital characteristics, Thyrotoxicosis pa- subclinical hypothyroidism with mildly elevated TSH at 6.78 tients with PCM had higher risk of mortality (aOR¼2.3, 95% CI mIU/L and normal Free T4 at 1.1 ng/dL. 1.83-2.94, p< 0.0001), AKI (aOR¼1.57, p< 0.0001), Sepsis Discussion: Thyroid dysgenesis encompasses about 85% of the (aOR¼2.83, p< 0.001), Pneumonia (aOR¼1.69, p< 0.001), and cases of CH, further subdivided into agenesis, hypoplasia, need for mechanical ventilation (aOR¼1.37, p¼0.012). When ectopy, and hemiagenesis; while the remaining 15% are adjusted similarly, Thyrotoxicosis patients with PCM had longer thought to be from dyshormonogenesis i.e., genetic defect in LOS by 3.7 days (p< 0.0001) and an additional HC of $36692 (p< thyroid hormone synthesis. Arrest of descent of thyroid gland 0.0001). However, there was no statistical difference in the risk of along its path of migration can result in ectopic thyroid gland, developing Cardiac arrest, PE or Stroke in Thyrotoxicosis patients a type of dysgenesis. About 90% of these are lingual whereas with and without PCM. 10% occur at other sites. Given the relatively high prevalence Discussion/Conclusion: This study demonstrated that patients of CH in newborns it is reasonable to consider screening for admitted with Thyrotoxicosis had higher mortality, morbidity, LOS thyroid dysgenesis in those presenting with the condition. and hospital cost in the presence of PCM. An early assessment and

S181 Thyroid Endocrine Practice 27 (2021) S141eS188 optimization of nutrition status in these patients could improve Author Block: Saima Manzoor - University of Cincinnati outcomes and decrease healthcare costs. Introduction: Immune check point inhibitors (ICPis) have become a https://doi.org/10.1016/j.eprac.2021.04.853 common treatment for cancer. ICPis are associated with toxicities and endocrinopathies are among the most common and include fi Abstract #1004330 thyroid dysfunction, hypophysitis, insulin de cient diabetes mel- litus and primary adrenal insufficiency. Ipilimumab is anti-CTLA 4 Severe Primary Hypothyroidism Causing Sudden monoclonal antibody. While destructive thyroiditis and hypothy- Cardiac Arrest in a Male: A Case Report roidism are the most common thyroid dysfunction induced by ICPis, autoimmune hyperthyroidism (Graves’disease) is rare although has been reported with ipilimumab but in both the cases Author Block: Zara Z. Alvi, MD - primary author, Allegheny Health thyroid receptor antibody (TRAB) was positive. Antibody negative Network; Kirtivardhan Vashistha, MD - co-author, Allegheny Graves’disease have been reported but with anti-PD4/Nivolumab Health Network; Hassan Mehmood, MD - co-author, Allegheny use only.We describe a case of antibody negative Graves’disease Health Network; Farhad Hasan, MD - co-author, Allegheny Health induced by ipilimumab therapy which rapidly progressed to central Network hypothyroidism due to hypophysitis. Case Description: A 35-year-old woman with metastatic melanoma Introduction: Thyroid hormone in known to have a profound was started on ipilimumab. She had normal thyroid function tests impact on myocardial electrophysiologic conduction which is before starting the therapy.She presented to ER with complains of mediated by both genomic and non-genomic effects. As a result of weight loss, extreme fatigue, heat intolerance, irritability and pal- this significant imbalance in hormone levels can have a negative pitations. She was noted to have hyperthyroidism with an unde- effect on cardiac function. tectable TSH of < 0.006 mIU and elevated FT4 of 2.25 ng/dl (0.61- Case Description: A 67-year-old man with history of Atrial 1.76) with a normal FT3 of 3.6 pg/ml(2.8-5.3). TRAB was normal at Fibrillation (AF), myelodysplastic syndrome requiring weekly 1.31. US thyroid revealed mildly enlarged diffusely heterogeneous blood transfusions and morbid obesity presented after an thyroid. Radioiodine uptake scan (RAIU) was differed due to recent episode of ventricular fibrillation (VF) at an outside hospital. He contrast exposure. She was discharged on beta blocker and pred- was noted to have the arrest soon after receiving a blood trans- nisone taper with assumption of hyperthyroidism due to thyroid- fusion. Return of spontaneous circulation was achieved after 9 itis, given normal TRABs. Upon follow up repeat labs in 4 weeks minutes of CPR, IV Magnesium Sulfate and 1 defibrillator shock. showed TSH of < 0.02,elevated FT4 1.8 and elevated FT3 of 8.9.RAIU Review of his telemetry showed progressive bradycardia punc- was done which showed diffuse uptake of 31.5% in 24 hours (15- tuated by R on T event likely triggering the VF arrest. Post arrest 33%).With thyroiditis one would expect very low to minimal up- labs showed Magnesium 2.4 mEq/L, Potassium 6.1 mEq/L and take. RAIU in high normal range with family history of Graves’, normal Troponin. EKG showed Atrial Fibrillation with no ST and T elevated FT3 / FT4 ratio and ICPis use favored autoimmune etiology wave changes. Transthoracic Echocardiogram showed Left ven- and hence diagnosis of antibody negative Graves’ disease. We tricular Ejection fraction of 55-59% and moderate mitral regur- started methimazole 10 mg daily. One month after initiation of gitation. These findings ruled out an ischemic etiology as a cause methimazole therapy, TSH < 0.02, FT4 of 0.57 & T3 6.5,methimazole for patient’s presentation. Patient was started on anti-arrhyth- dose reduced to 5 mg daily. Follow up TSH < 0.01, (FT4) 0.15 and FT3 mics including Amiodarone and later transitioned to Lidocaine 3.9, methimazole discontinued. Repeat labs in 3-4 weeks with TSH drip. Additional work up revealed significantly elevated TSH 42.7 0.03, FT4 0.07 and FT3 of 2.6. Diagnosed central hypothyroidism mcU/ml with very low Free T4 0.4 ng/dL. Given the overall clinical with panhypopituitarism due to hypophysitis. Started on hydro- picture and labs patient’s cardiac arrest was thought to be sec- cortisone and later levothyroxine. ondary to severe hypothyroidism in the setting of hyperkalemia. Discussion: A correct differential diagnosis between destructive Patient’s Lidocaine drip was stopped, his potassium was cor- thyroiditis and autoimmune hyperthyroidism is crucial for the rectedandhewasputonhighdosethyroidhormonereplace- appropriate treatment. The characteristic features that help ment therapy following which he improved and did not incur any differentiate between two includes duration, RAIU, FT3 / FT4 further episodes of arrhythmias. ratio,TRAB status and US with doppler. Regular monitoring of TFTs Discussion: Severe hypothyroidism very rarely can cause life is crucial. It is also important to differentiate between primary and threatening arrhythmias such as Ventricular Fibrillation, especially secondary (central) hypothyroidism as central hypothyroidism in the setting of electrolyte imbalance. Even though there are some should prompt concern for hypophysitis. Patients with concurrent studies implicating thyroid imbalance in cases of cardiac dysfunc- hypothyroidism and adrenal insufficiency should receive cortico- tion, further investigation is warranted to establish the degree of steroid replacement prior to thyroid hormone replacement to avoid insult that maybe caused to the myocardium by a disturbance in precipitation of adrenal crisis. thyroid hormone levels. https://doi.org/10.1016/j.eprac.2021.04.855 https://doi.org/10.1016/j.eprac.2021.04.854

Abstract #1004339 Abstract #1004335 Thymic Hyperplasia and Graves’ Disease An Unusual Case of Rapidly Evolving Thyroidal Dysfunction from New Onset Antibody Negative Graves' Disease to Central Hypothyroidism Within Few Author Block: Cory DeClue - University of Missouri-Columbia; Weeks of Starting Ipilimumab (Immune Check Point Bhavana Chinnakotla, MD - Co-Author, Diabetes and Inhibitor) Therapy Endocrinology, University of Missouri-Columbia

S182 Thyroid Endocrine Practice 27 (2021) S141eS188

Introduction: Thymic hyperplasia has been noted to be histo- Relationship between thyroid dysfunction and COVID-19 remains logically present in up to 38% of patients with Graves’ disease elusive but multiple case reports ranging from thyroiditis to non- (GD). The etiology of this association is currently unknown, but thyroidal illness syndrome to Grave’s disease have been reported. proposed mechanisms include hyperthyroid-induced cortical Although causal relationship cannot be established, the virus is tissue hyperplasia and autoimmune-activated lymphoid hyper- known to cause immune-inflammatory response and thus one can plasia. Interestingly, both seropositive and seronegative myas- postulate emergence of new autoimmunity post-infection.Here, we thenia gravis (MG) appear to be rarely associated with this present two cases of Grave’s disease diagnosed within a short span autoimmune thyroid disease. The following case report describes of being infected with SARS-COV2 virus. a patient who experienced thymic hyperplasia in the setting of Case Description: 41 year old Caucasian female was referred for GD. evaluation of recently diagnosed hyperthyroidism. She endorsed Case Description: A 20-year-old Caucasian woman with a known symptoms of extreme fatigue, weight loss of 15lbs, palpitations, history of asthma presented to endocrinology clinic for consul- hair loss and tremors 3 months prior to diagnosis. Of note, she tation regarding abnormal thyroid function testing. She reported was diagnosed with COVID-19 infection about 4 weeks before heat intolerance, poor sleep, and palpitations. She had elevated symptom onset. She presented to the ER due to palpitations and free T4 of 2.09 ng/dL (0.93-1.7), elevated free T3 of 6.6 pg/mL was found to have undetectable TSH with freeT4 of 6.36ng/dl (2.0-4.4) and suppressed TSH of < 0.005 mcunit/mL (0.27-4.2). (0.76-1.46). At the time of evaluation in the Endocrine clinic - She was diagnosed with GD due to positive TPO antibodies (597 she exhibited several signs of hyperthyroidism including IU/mL), Thyroglobulin antibodies (63 IU/mL), and TSI (3.2 TSI enlarged thyroid gland with bruit, fine tremors in both hands index, normal < 1.8). She was started on methimazole and and resting tachycardia. Further investigations revealed elevated propranolol, which improved her hyperthyroid symptoms, but Thyroid Stimulating Immunoglobulins(TSI) 291% (< 140) and a she continued to endorse palpitations, anxiety, and orthopnea. diffusely enlarged hyper vascular thyroid gland on ultrasound Her asthma regimen was changed, but her symptoms persisted. without any nodules - confirming diagnosis of Grave’s disease. She eventually underwent CT scan of her chest, showing Patient was started on Methimazole and propranolol and has enlarged lymph nodes and a mediastinal mass. She underwent continued to improve clinically. video-assisted thoracoscopic surgery two months later, which 43 year old African American male with PMH of asthma, revealed benign thymic tissue and lymph nodes. Post-opera- generalized anxiety disorder was diagnosed with COVID-19 tively, she developed generalized muscle weakness that wors- infection. Over the next 3 weeks, he developed fatigue, heat ened at the end of the day and is currently being evaluated for intolerance, excessive sweating, unintentional weight loss of myasthenia gravis. about 15lbs, SOB and palpitations. On further evaluation, he was Discussion: While the association between GD and thymic hyper- found to have high Free T4 of 2.98ng/dL (0.82-1.77) and sup- plasia has been well-established, many general practitioners may pressed TSH of < 0.005mIU/mL (0.45-4.5). Evaluation at the be unfamiliar with this connection, leading to unnecessarily endocrinology clinic showed goiter, fine tremor and tachycardia. aggressive management, including surgical interventions. Thymo- Given positive TSI antibodies (3.4 TSI index, normal < 1.8), a mas are exceedingly rare in cases of GD, with the overwhelming diagnosis of Grave’s disease was made. Patient was started on majority of cases of thymic enlargement representing benign hy- Methimazole and a beta blocker. perplasia. Additionally, thymectomy has been shown to have no Discussion: Review of literature reveals that inflammation further effect on the treatment outcome of hyperthyroidism. In involving interleukins and cytokines following a viral infection can many cases, treatment of the GD resulted in a significant decrease exacerbate thyroid dysfunction. Grave's disease after COVID-19 in the thymic enlargement. To this end, management of thymic infection could have been incidental in the above cases but one is enlargement in the setting of GD should focus on primarily treating left to wonder if in fact this new millennial virus could possibly the hyperthyroidism and avoiding unnecessary thymic biopsies and have unveiled the immune dysfunction. surgeries. It is important to understand the pathophysiology of this https://doi.org/10.1016/j.eprac.2021.04.857 association and familiarize providers with the benign nature of thymic enlargement in patients with GD. https://doi.org/10.1016/j.eprac.2021.04.856 Abstract #1004363

A Bloody Heart due to a Toxic Relation with Thyroid? Abstract #1004348 Spontaneous Hemopericardium & Tamponade Secondary to Apixaban in the Backdrop of Subclinical Grave's Disease after COVID-19 Infection Hypothyroidism

Author Block: BHAVANA CHINNAKOTLA, MD - Primary Author, Author Block: Rahul Pansare - St. Mary Mercy Hospital, Livonia; Endocrinology, University of Missouri, Columbia; Richa Patel, MD - George Roman, Resident Physician - Co-author, Internal Medicine, Primary Author, Endocrinology, Baycare Medical Group; St. Mary Mercy Hospital, Livonia; Sangeetha Nanthabalan, Ana M. Ramirez-Berlioz, MD - Co-Author, Endocrinology, Parkview Transitional Year Program Director - Co-author, Internal Medicine, Medical Center St. Mary Mercy Hospital, Livonia

Introduction: Coronavirus disease 2019 (COVID 19) pandemic has Introduction: Spontaneous hemopericardium is defined as posed unprecedented challenges on healthcare globally. The virus bleeding into the pericardial space in absence of a local pathological is notorious for causing severe respiratory illness as well as wide- lesion. There are 12 cases reported to have occurred in association spread systemic inflammation leading to multiorgan failure. with hyperthyroidism. We describe a case of spontaneous

S183 Thyroid Endocrine Practice 27 (2021) S141eS188 hemopericardium and tamponade in the setting of subclinical hy- autoinmune thyroid disease specially Graves' disease; unilateral perthyroidism after receiving anticoagulation. proptosis occurs rarely in these patients. Almost 20-50% of pa- Case Description: A 77-year-old Caucasian male with a past tients with Graves'disease refer eye protrusion in subclinical and medical history of hypertension, diabetes mellitus type 2, ESRD clinical hyperthyroidism, but it is present unilaterally in only 5- and unclassified thyroiditis returned to the ER with complaints 11% of the cases. of shortness of breath and presyncope only 5 days after Case Description: We present a case series of 3 patients, two of discharge. them without prior diagnosis of hyperthyroidism, all which During prior admission he had presented with new-onset referred subjective asymmetry in their eyes. Patient 1 is a 24- atrial fibrillation with rapid ventricular rate. Echo at that time year-old female, patient 2 is a 39-year-old female and patient 3 showed normal EF without pericardial effusion. Thyroid workup is a 37-year-old female, consulting the endocrinology outpatient revealed TSH < 0.01 uIU/ml, free T4 - 1.19 ng/ml and T3 - 3.0 clinic due to the eye asymmetry. Patient 1 had history of thyroid pg/ml suggestive of subclinical hyperthyroidism.Thyroid ultra- disease, alternating between periods of suppressed and elevated sound showed a largely solid left thyroid nodule measuring 5 x TSH, treated with I121 a year ago, and receiving treatment with 2.5 x 2.4cm. Thyroid peroxidase antibodies were negative. levothyroxine, also with family history of Graves'disease; Patient Radioactive iodine uptake scan confirmed a solitary hot nodule 2 had family history of thyroid nodules and patient 3 has family in the left thyroid but suppressed uptake in the rest of the history of goiter and exophthalmos, both without known thyroid gland. Patient was discharged on eliquis 2.5mg twice daily and disease. Patients 1 and 3 did not refer additional symptoms, but methimazole 5mg daily. patient 2 had history of non-intentional weight loss and heart At second ER visit, vitals showed blood pressure 72/ palpitations. Laboratory results and neck ultrasound were as 38mmhg, pulse 70/min, tachypnea upto 24/min but afebrile. follows: Patient 1: TSH:˂ 0.04 (0.4-4.0 mUI/ml), FT4: 2.14 (0.89- Laboratory revealed baseline BUN, negative troponins and INR 1.76mg/dl), TSI: 5.72 UI/L (0- 2IU/L), Patient 2: TSH: ˂ 0.01, FT4: of 2.4. Echo revealed a large pericardial effusion and right 1.37, TSI: 5.06 IU/L, Ultrasound reports Left tobe:1.5x1.5x 3.7cm, ventricular collapse but no obvious vascular or valvular heart right lobe:1.5x1.1x3.7cm vol 3.1 ml, with an heterogenous gland, anomaly. Eliquis was held. Emergent pericardiocentesis lobulated, with multiple solid hypoecogenic nodules, the biggest drained 590cc of serosanguinous fluid and subsequent analysis measuring 0.5x0.3cm; Patient 3: TSH:< 0.1, FT4: 3.6, ultrasound wasn’t concerning for an infectious or malignant etiology. reported and heterogenous gland with high vascularity, with no Patient was eventually discharged in a hemodynamically sta- nodules. Patient 2 had an MRI that reported lacrimal gland ble condition. asymmetry by 0.5mm. Patient 2 was treated with methimazole Discussion: Spontaneous pericardial effusion have been noted in and propranolol, patient 3 received methimazole, propranolol hyperthyroidism related to Graves Disease as well as toxic and deflazacort, while patient 1 remained only with multinodular goiter. An immunological epiphenomenon similar levothyroxine. to ophthalmopathy was described in Graves Disease but the Discussion: The differential diagnosis of proptosis needs to pathogenesis in toxic nodular goiter is unknown. Furthermore, screen for thyroid function abnormality, being Graves'disease timing of onset of the effusion is likely unrelated to thyroid ophthalmopathy its most common cause. In the cases of uni- hormone levels since late post-treatment presentations when T3 lateral proptosis, orbital and eye pathology like orbital pseu- & T4 had normalised have been described. Levy at al noted that dotumors, orbital cellulitis, cavernous sinus thrombosis and among 204 cases of spontaneous pericardial effusions a TSH< intraorbital neoplasms must also be taken into consideration. 0.3 (p value < 0.0001) was a prevalent positive test among a Exophthalmos can be found in subclinical hyperthyroidism subset of those cases labeled as idiopathic in origin. Although like we described in two of our cases, which can complicate anticoagulation in the presence of kidney disease is a valid risk diagnosis. Imaging studies such as ultrasounds and MRIs factor, eliquis was initiated at a low dose and has the safest are helpful to support the diagnosis. Proper thyroid disease pharmacokinetics for use in ESRD. Thus, it is worthy to inves- treatment with antithyroid drugs, glucocorticoids, surgery or tigate the role of our patient’s hyperthyroid state as a co-exist- thyroid ablation with I121 contribute to the regression of the ing risk factor for spontaneous hemopericardium in the ophthalmopathy. backdrop of existing comorbidities. https://doi.org/10.1016/j.eprac.2021.04.859 https://doi.org/10.1016/j.eprac.2021.04.858

Abstract #1004368 Abstract #1004367 Effect of Novel Patient Characteristics on Risk of Unilateral Thyroid Ophthalmopathy in Autoinmune Thyroid Malignancies Thyroid Disease : A Case Series Presentation

Author Block: Nikhila Janakiram, MD - primary author, Huntington Author Block: Maria Ramos Guifarro - Hospital Escuela; Hospital; Jonathan Huang, MD - primary author, USC; Marlen A. Cruz-Joya, MD - Primary author, Endocrinology, Hospital Christine Chiu, MD - co-author, USC; Michael Hashimoto, BS - co- escuela universitario; Daniel A. Guifarro, Md - Co author, G y v author, USC; Trevor Angell, MD - co-author, USC medical; Luis Guifarro, Md - Co author, G&V medical; Alejandra Paz, Md - Coauthor, Endocrinology, Hospital escuela Objective: As thyroid nodules increase in prevalence, the influence of patient risk factors remains uncertain. The aim of our study was Introduction: Thyroid ophthalmopathy and orbital masses are to evaluate the association between thyroid nodule malignancy and the most common causes of proptosis, and although exoph- patient characteristics, including body mass index (BMI) and thalmos is the most common extrathyroid manifestation of ethnicity.

S184 Thyroid Endocrine Practice 27 (2021) S141eS188

Methods: A retrospective chart review of patients who received took a 600 mcg Levothyroxine dose of Tirosint-Sol® after a 10-hour ultrasound-guided fine needle aspiration biopsy (USG-FNA) at two fast, 15 or 30 minutes before a high-fat high-caloric “FDA type” academic medical centers Center between 2013 and 2018. Patients breakfast. Serum samples were taken at three different times at were classified by BMI as low-normal (BMI < 25) or overweight/ baseline, and at 0.5, 1, 1.5, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 48 and at 72 obese (BMI 25). Benign nodules were characterized as Bethesda hours after dosing. The washout period was at least 35 days. Serum category II while malignant nodules were characterized as concentrations of Levothyroxine were measured using a validated Bethesda category VI as well as V after surgical pathology results LC-MS method. confirmed malignancy. Results: Median tmax was unchanged between the two groups Results: 388 patients with sufficient demographic information at 1.5 h. The three subjects that did not complete the trial did so and FNA results were identified. Median patient age (inter- because of not showing up for COVID19 testing, vomiting within quartile range) was 57.2 (47.0-63.1) years in benign cases and 6 hours after dosing, and not finishing the breakfast. The geo- 49.5 (40.6-59.1) years in malignant cases (p¼0.001). Analysis metric mean ratios and confidence intervals for the baseline showed optimal cut-off of 54 years, with 9.8% of patients 54 adjusted maximum (Cmax, 85%, CI: 80-90%) and extent of years having malignant pathology versus 21.8% of patients exposure (AUC0-72, 92%, CI: 87-97%) were within the recognized < 54 years (p< 0.01). Malignant pathology was found in 18% of equivalence boundaries of 80 to 125%, indicating an absence of patients with Hispanic/Latino ethnicity compared to 11% of meaningful clinical difference between dosing at 15 or 30 mi- non-Hispanic/Latino patients (p¼0.084). There was no nutes before a meal. There were no differences in adverse events observed association between BMI < 25 or 25andriskof between groups. malignancy. Though when stratified by sex, males with BMI Discussion/Conclusion: The data of this randomized study indicate 25 had a two-fold risk of malignancy compared to those that the absorption profile of Tirosint-Sol® is clinically equivalent with BMI < 25, this did not reach statistical significancy. when administered 30 or 15 minutes before a high-fat high-caloric Discussion/Conclusion: Age 54 years old was associated with breakfast. risk of malignancy, providing initial independent verification of https://doi.org/10.1016/j.eprac.2021.04.861 recent data. When sex, ethnicity and MDI were not associated with malignant, trends in these clinical data were consistent with population-based epidemiologic studies, suggesting that Abstract #1038473 further studies are warranted to further evaluate these risk variables as clinically relevant risk factors during thyroid nodule Association of Thyroid Cancer with Cardiovascular assessment. Disease, Atrial Fibrillation and Cardiovascular-specific https://doi.org/10.1016/j.eprac.2021.04.860 Mortality: A Systematic Review and Meta-analysis

Author Block: Abstract #1033492 Wen Hsuan Tsai - Mackay Memorial Hospital; Kuo Liong Chien, professor - co-author, Institute of Epidemiology A Novel Solution of Levothyroxine Results in Clinically and Preventive Medicine, College of Public Health, National Taiwan Similar Maximum and Extent of Exposure Whether University; Shih Ping Cheng, MD, PhD - co-author, Department of Taken 30 or just 15 Minutes Before a High-Fat High- General Surgery, Mackay Memorial Hospital, Taipei, Taiwan (ROC); Caloric Breakfast Chun Chuan Lee, MS degree - co-author, Division of Endocrinology and Metabolism, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan (ROC); Sung Chen Liu, MS Author Block: Murray P. Ducharme, PharmD - presentor, Learn and degree - co-author, Division of Endocrinology and Metabolism, Confirm Inc; Claudia Scarsi, PhD - co-author, IBSA Institut Department of Internal Medicine, Mackay Memorial Hospital, Biochimique SA; Elisa Bettazzi, PhD - co-author, IBSA Institut Taipei, Taiwan (ROC); Po Jung Tseng, MD - co-author, Division of Biochimique SA; Giuseppe Mautone, PhD - co-author, IBSA Institut Cardiovascular Surgery, Department of Surgery, Hsin Chu Armed Biochimique SA; Francesco S. Celi, M.D. - primary author, Force Hospital, Hsinchu, Taiwan; Ming Chieh Tsai, MS degree - co- Department of Internal Medicine, Virginia Commonwealth author, Division of Endocrinology and Metabolism, Department of University Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan (ROC) Objective: Levothyroxine is essential for the treatment of hypo- thyroidism, but unfortunately its absorption when taken as a Objective: To conduct a systematic review and meta-analysis of the tablet has been shown to be significantly decreased with coffee association between thyroid cancer and cardiovascular disease, or food ingestion, particularly if containing calcium or magne- atrial fibrillation and cardiovascular-specific mortality sium. Tablets and soft-gel formulations of levothyroxine are Methods: A search of PubMed (MEDLINE), Embase, and the therefore recommended to be taken at least 30 minutes before Cochrane Library from inception to November 25, 2020, with meals, an inconvenience for patients in the morning. Tirosint- cohort studies for potentially eligible articles was performed. Key- Sol® is a novel solution of levothyroxine that has been shown to words included thyroid cancer, atrial fibrillation, cardiovascular result in an approximate 30 minutes faster absorption process disease and thyroxine. Perspective and retrospective cohort studies than tablets or soft gel formulations. The objective of this trial published in peer-reviewed literature and using objective outcome was to investigate whether Tirosint-Sol® could be administered measures were included. Cross-sectional and case-control studies as late as 15 minutes before a high-fat, high-caloric meal, in were excluded. comparison to 30 minutes. Data extraction and Synthesis: Two authors independently Methods: Thirthy-six (thirty-three completers, 24 males and 9 fe- extracted and verified data and assessed study quality. Estimates males) healthy volunteers participating in the randomized study were pooled using fixed-effects and random-effects meta-analysis.

S185 Thyroid Endocrine Practice 27 (2021) S141eS188

Meta-regression analyses of different study-level characteristics procedure was done in an ultrasound room with the help of a nurse were performed. and sonographer. Main outcomes and measures: The primary outcomes was the Results: 41 patients were treated in the offices of the co- incidence of cardiovascular disease, atrial fibrillation and car- authors.KH treated18 patients. 8/8 with cosmetic issues were diovascular-specific mortality among thyroid cancer patients resolved.18/18 had resolution of symptoms.Average Nodule compared with general healthy population. Secondary out- reduction was 80% at 3 months.1/18 had a second treatment that comes were cardiovascular disease, atrial fibrillation and car- resulted in 85%.reduction at 6 months.No major complications.2/ diovascular-specific mortality among thyroid cancer with or 18 had bruising.1/18 had a hematoma that resolved over time.RG without radioactive iodine treatment. had 21 cases 21/21 had improved cosmetic issues. 21/21 had Results: Among all 197202 patients with thyroid cancer receiving resolved or reduced symptoms. Nodule reduction averaged 52% thyroidectomy enrolled in the 9 studies (mean age 47.4 years, at 6 months.1/21 needed two treatments to resolve symptoms. women 84.2 %). The meta-analysis risk estimates of cardiovascular No major complications.1/21 bruise.No hematoma. No voice disease between patients with thyroid cancer compared with changes. One procedure was canceled on the table due to unre- general health population by 2 studies was significantly increased ported hypertension on the co-morbidity report. (RR 1.15, 95% CI 1.10-1.21). The odds of atrial fibrillation associated Discussion/Conclusion: These results clearly show promise that with thyroid cancer by 3 studies demonstrated significance in fixed office based Thyroid RF for benign thyroid nodules is a potential effect model (RR 1.37, 95% CI 1.15-1.62) but no significant difference game changer.These patients can be spared the hospital surgery in random effect model (RR 1.47, 95% CI 0.96-2.23). Additionally, that was the main treatment of choice in the past. The use of thy- cardiovascular-specific mortality associated with thyroid cancer roid RF is significantly less expensive that surgery. It is also less was insignificant by pooled 3 studies (RR 0.82, 95% CI 0.66-1.01). expensive done in the thyroid physician's office than in the hospital Furthermore, the pooled risk of cardiovascular disease between by radiologists. thyroid cancer patients with or without radioactive iodine ablation https://doi.org/10.1016/j.eprac.2021.04.863 by 3 studies demonstrated no significance (RR 1.01, 95% CI 0.81- 1.26). Discussion/Conclusion: fi Thyroid cancer was signi cantly Abstract #1017450 associated with higher risk of cardiovascular disease, but the hazard risk was not different between patients with and COVID-19 Associated Grave’s Disease Identified in a 45- without radioactive iodine. To our knowledge, this study is year-old Male the first meta-analysis to examine the association of thyroid cancer with cardiovascular disease. These results provide in- sights toward optimizing thyroid cancer strategies that should Author Block: Milad Khoury - Penn state Hershey medical center; consider the potential harms and benefits during cancer Pramod Tripathi, M.D. - co-author, Endocrinology, Diabetes & treatment. Metabolism, Hershey, PA, USA., Penn State health; & https://doi.org/10.1016/j.eprac.2021.04.862 Shyam Narayana, M.D. - Co-author, Endocrinology, Diabetes Metabolism, Hershey, PA, USA., Penn State Health

Abstract #973321 Introduction: Graves’ disease is an autoimmune condition char- acterized by hyperthyroidism due to higher levels of circulating Further Evaluation of Office Based Benign Thyroid autoantibodies that bind to and activate the thyrotropin receptors Nodule Radiofrequency Ablation by Thyroidologists (TSH receptors) on the surface of thyroid follicular cells. We report the first known case of Graves’ disease as a result of the cytokine surge after infection with COVID-19. Author Block: Kathleen Hands, MD, FACE, ECNU - primary, Case Description: A 45-year-old male with a past medical history Interventional thyroidology, Thyroid Center of South Texas; of hypertension presented to the Penn State Health Milton S. Richard Guttler, MD, FACE, ECNU - co-author, interventional Hershey Medical Center, Hershey Pennsylvania on May 5th, 2020 thyroidology, SM thyroid INC after reporting symptoms of palpitations, lightheadedness, and dizziness while gardening. He was diagnosed with COVID-19 Objective: Thyroid RFA has recently been FDA approved. The ability infection on April 18th upon experiencing flu-like symptoms to do these procedures without general or conscious sedation including myalgia, fever, and sore throat for several days. Phys- makes possible Thyroid RFA could be an office procedure. The ical examinations showed, patient to be tachycardiac, with an objective is to study it's use in an endocrine office based outpatient. irregular pulse of 155 beats per minute. The patient had a mild We continue to evaluate this by adding more study cases. We resting bilateral hand tremor but did not have any sign of present data on the first 41 patients treated in our two offices.The Grave’s ophthalmopathy or dermopathy. Electrocardiogram objective is to look at efficacy and safety. The size reduction, tracing showed the heart rhythm in atrial fibrillation, and the symptom and cosmetic score changes were monitored over the first Burch-Wartofsky Point Scale indicated a score of 25 reflecting an 6 months. impending thyroid storm. Laboratory work-up conducted on the Methods: All patients had TSH, FT4, TPO and TGab, neck ultra- same day showed an undetectable TSH level with elevated free sounds, FNA, and molecular testing if Class III cytology. Clotting thyroxine (FT4) and free triiodothyronine (FT3). The patient was screens a check for metal inserts and co-morbidity risk were then started on medical therapy with Propranolol and documented. Under only local Lidocaine injection of the skin and Methimazole. thyroid capsule, a 7 mm long 10mm hot tipped # 18-19 electrode On May 6th,thepatient’s cardiac rhythm returned to sinus, was used. The RFA system used was by RF Medical Korea.The power his tremors and palpitations improved, and his thyroid was 20-50watts and the duration was 20-40 minutes. The hormone levels declined. Laboratory workup showed

S186 Thyroid Endocrine Practice 27 (2021) S141eS188 improvement in thyroid hormone levels, unchanged TSH Results: Laboratory results: TSH: 0.024 mU/ml (n: 0.5-5.0 mU/ml), levels, and elevated antibody levels of thyrotropin binding FT4: 1.10 ng/dl (n:0.87-1.85 ng/dl) and thyroglobulin anti- inhibiting immunoglobulins (TBII), Thyroid stimulating immu- body:1.52IU/L (n: < 20 IU/L). Clinical hypothyroidism was being noglobulin (TSI), as well as Thyroid peroxidase (TPO). On masked by biochemical hyperthyroidism. Further questioning May 18th, he was seen in the outpatient clinic, and his labs revealed patient had been self-medicating with OTC biotin sup- showed normal thyroid hormone levels with a lagging unde- plements for months prior to visit. Biotin interference was sus- tectable TSH level. pected and patient was advised to hold biotin to have tests Discussion: Invitro studies have shown release of cytokines such as repeated. Indeed, results showed TSH of 18.5 mU/ml and Free T4: interferon gamma, Interleukins (IL1, IL6), Tumor necrosis factor 0.83 ng/dl, consistent with her hypothyroid state. Patient was ori- (TNF) by SARS-COV 2 infection. Hence, it is likely that infection of ented and started on thyroid hormone replacement therapy with thyroid cells by the COVID-19 and the concomitant cytokine surge Synthroid. increases expression of MHC in thyroid cells with resultant auto- Discussion/Conclusion: As the use of supraphysiological doses antibody response. of biotin increases, assay interference will be regularly Several studies have investigated the role of risk factors that encountered due to the widespread use of immunoassays. cause Graves’ disease. These include age, genetic background, Despite progress in immunoassays technologies, the problem gender, as well as environmental factors such as bacterial and viral of unwanted interference has not yet been overcome. A thor- infections. (5-6) Here we present a case of a patient who developed ough analysis of the clinical picture and hormone results, graves’ disease after being diagnosed with COVID-19, a highly in- along with an open communication with patients and other fectious viral disease caused by SARS- COV 2. We postulate that the clinicians, remains the best strategy to avoid clinical COVID-19 infection might have triggered an inflammatory response mismanagement due to unsuspected interference. (or maybe cytokine surge) leading to autoimmunity and develop- https://doi.org/10.1016/j.eprac.2021.04.865 ment of graves’ disease. https://doi.org/10.1016/j.eprac.2021.04.864 Abstract #1038809

Abstract #1038067 Hypokalemic Periodic Paralysis as Initial Presentation for Graves’ Disease Clinical Hypothyroidism Masked Biochemically due to Biotin Supplements??? Author Block: Lloyd Petty - University of Utah; Katie Kaput, DO - co-author, University of Utah Author Block: Yineli Ortiz - hospital Damas; Astrid Aviles, MD - co- author, Internal medicine, Hospital Damas; Adriana Torres, MD - Objective: Please let this young endocrinology fellow submit his co-author, Internal medicine, Hospital Damas; Alegyari Figueroa, poster late so that he can attend AACE. It's my only chance of being MD - co-author, iNTERNAL MEDICINE, Hospital Damas; able to attend this conference and I really wanted to go! Please. Gabriel Mora, MD - co-author, Internal medicine, Hospital Damas; Submission for poster presentation. Gretchen Rios, MD - co-author, Medicine, Universidad Autonoma A case on Toxic Periodic Paralysis. de Guadalajara; Jose M. Garcia, MD - co-author, Endocrinology, Methods: Case report Hospital Damas Results: Case Description The patient was a 24-year-old male of Thai descent with a Objective: Biotin( Vitamin B7) is widely available as an over the past medical history of atrial fibrillation s/p ablation and counter supplement for skin, hair and nail health. Many immuno- family history of Hashimoto’s who presented with the assays use the biotin-streptavidin interaction as an immobilizing complaint of weakness. The patient had developed mild system, in which biotin can be readily incorporated into a hormone. generalized weakness 3 days prior which progressed to the Ingestion of high doses of biotin has been reported to cause point that he could not move his lower extremities with sig- abnormal results in thyroid function tests by this assay interfer- nificant weakness in his back and upper extremities. Patient ence. Hereby we describe the case of a patient with clinical hypo- had reported that he had 3 falls due to his weakness and was thyroidism but biochemically hyperthyroid due to biotin unable to lift himself up requiring help from friends to bring supplementation. his to the Emergency Department. When he presented to the Methods: A 60-year-old female patient with past medical his- EDhewasinawheelchairandcouldnotstandupfromhis tory of bronchial asthma was referred for further evaluation chair due to severe weakness. after been found with multiple bilateral thyroid nodules of The patient had been having infrequent episodes of tremors low suspicion on Thyroid Ultrasound (US) by her primary care and heat intolerance; however denied weight changes, palpi- physician. Five months prior, patient had been complaining of tations, diarrhea, skin, hair or vision changes. He denied pain fatigue, cold intolerance, dry skin, and muscle weakness. On in his neck, tenderness in his thyroid, recent fevers or viral initial evaluation, patient reports that her symptoms have illnesses. persisted but she denies having neck pain, cough, hoarseness, Patient had sinus tachycardia with heart rate of 120 bpm, odynophagia, family history of thyroid cancer or head and Temperature 98.8F, BP 140/84 hmmg, respiratory rate 16 bpm, neck radiation exposure. Physical examination did not reveal O2sat 95%, BMI 23. Physical exam was notable for bilateral 4/5 goiter and thyroid nodules were not palpable, strength grossly muscle strength with knee extension, knee flexion, forearm intact and deep tendon reflexes slightly decreased on upper extension, forearm flexion; 2/5 grip strength bilaterally. Absent and lower extremities. patellar and biceps reflex bilaterally. Normal sensation to light

S187 Thyroid Endocrine Practice 27 (2021) S141eS188 touch which is equal on bilateral extremities. Alert and ori- levothyroxine, history of testicular trauma, history of diabetes ented x 4. mellitus, history of hypertension, history of hormonal replacement Laboratory results were notable for potassium of 1.8 mmol/L therapy. (3.3 e 5.0) and magnesium of 1.8 mg/dl (1.6 e 2.6). Otherwise prior to the intervention. CMP, CBC and UA was unremarkable. Patient had TSH of < 0.01, Hormones essayed were FREE TESTOSTERONE, T3,T4,TSH, LH, FT4 of 5.0 nl/dl (0.8 e 1.7), TT3 301 nl/dl (80 e 200), and TSH FSH each before and after the intervention additional ADAMS Receptor Antibody 10.17 iu/dl (< ¼1.75). Initial Creatine Kinase questionnaire was included to evaluate the prevalance of sexual was 890 U/L (20 e 200) Otherwise CMP, CBC, and UA dysfunction. unremarkable. Results: Before the intervention:- Hypokalemia was treated with repletion with IV Potassium. 50% of patients (25/51) had low free testosterone level from the K+ reached 4.0 and patient had resolution of his weakness baseline value when his potassium levels normalized. Patient was started on 10-12% of patients had low LH value (5/51) propranolol 40 mg BID and methimazole 10 mg daily. Patient FSH values were under normal parameters for all the patients was able to ambulate independently after his potassium 60% of the patients had low ADAMS score normalized, and he had marked improvement in weakness. At After 4 months of levothyroxine replacement therapy on resto- 6 month follow up in clinic they patient continued on ration of euthyroidism (the doses were variable for each patient methimazole and remains euthyroid without reoccurrence of based on the TSH value and weight) episodes of weakness. 70% of the hypogonadotropic patients the free testosterone level Discussion/Conclusion: It is important for clinicians to be aware came under normal level of this uncommon presentation of Graves Disease. Initial diag- LH values of all the patients restored to normal values nosis is often delayed due to other etiologies that are more 80% of patients with low ADAMS score improved with common with initially presentation of weakness. Increased parameters awareness of this disorder can help with early recognition and Discussion/Conclusion: The prevalance of hypothyroidism overtly treatment. Several key characteristics of thyrotoxic periodic pa- ranges from 5% to 11%. Though hypothyroidism is more common in ralysis will be discussed in the poster. females than males. Hypogonadism in males with overt hypothy- roidism has not been studied widely, these deficiencies and its ef- https://doi.org/10.1016/j.eprac.2021.04.880 fects are not been discussed openly with the physicians which also leads to less diagnosis of the hypogonadism. There can be several pathophysiological mechanisms which causes hypogonadism in Abstract #1038898 hypothyroidism but one important possible causes could be the direct effect of thyroid hormone out the association of thyroid with Effect of Levothyroxine Replacement Therapy on hypogonadism and its effect after levothyroxine therapy. Testosterone, LH, FSH Levels in Men with Overt After 4 months of levothyroxine treatment in the patients with Hypothyrodism hypogonadism 70% of hypogonadotropic patients their free testosterone level came to normal levels, rest 30% of hypo- Author Block: Abhishek Shrivastava - national hospital; gonadotropic patients were further followed up for 2 months but no change in free testosterone level was seen. Bharat Saboo, diabetologist - co author, endocrinology, prayas diabetes centre 80% of the hypogonadotropic patients who had low ADAMS score showed improvement in their parameters. Conclusion: Thyroid hormone is associated with hypogonadotropic Objective: it is well established that overt hypothyroidism can hypogonadism which is more or less reversible with thyroid hor- cause gonadal dysfunction in womens but prevalance of mone replacement, the same has been studied in our study also hypogonadism in overt hypothyroidism in men is still under- that after levothyroxine therapy there was significant improvement studied. And the purpose of our study was t0 study the effect in free testosterone level, significant improvement in ADAMS score of hypothyroidism in testicular function and effect of post parameters. levothyroxine replacement therapy on gondadal functions and So according to the results we concluded that overt hypothyroidism parameters is associated with a moderate degree of hypogonadism which is Methods: Our study was bicentric and interventional. 51 newly reversible to much extent with full restoration of thyroid function. diagnosed overtly hypothyroid male patients were included, the point of exclusion criteria was previously treated with https://doi.org/10.1016/j.eprac.2021.04.881

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Endocrine Practice

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EDUCATION/QUALITY IMPROVEMENT

Abstract #996733 Abstract #999572 Success of Interactive, Online Education Related to A Case of Secondary Osteoporosis with Latent Application of CVOT Data in Real-World Patient Cases Hypogonadotropic Hypogonadism: Ongoing Undertreatment of Fragility Fractures

Author Block: Amy Larkin - Medscape Education; Michael LaCouture, MA - co-author, Medscape Education; Anne Le, Author Block: Michael Ahlers - UCLA Medical Center; PharmD - co-author, Medscape Education Azadeh Lankarani-Fard, MD - co-author, Internal Medicine, West Los Angeles VA Medical Center Objective: We sought to determine if interactive, case-based, online continuing medical education (CME) could improve the compe- Introduction: Osteoporosis diagnosed by fragility fracture is asso- tence and confidence of diabetologists/endocrinologists (D/Es) and ciated with high morbidity and mortality, particularly in men. cardiologists related to applying new antihyperglycemic CVOT data Despite these findings, literature suggests undertreatment of for both primary and secondary CV prevention in real-world pa- osteoporosis in men following fragility fracture. tient cases. Case Description: A 69-year-old man with medical history of Methods: “ ” Educational design included a test, then teach approach multiple long bone fractures, peripheral neuropathy, tobacco use, to elicit cognitive dissonance, with evidence-based feedback pro- and vitamin D deficiency was brought in by ambulance to the vided following each learner response. A repeated pairs pre-/post- emergency department with left upper and lower extremity pain < assessment study design and chi-square test (P .05 is considered after a ground level fall. Computerized tomography of the pelvis fi ’ signi cant) assessed educational effect, with Cramer s V being used demonstrated comminuted displaced subcapital fracture of the left to assess educational impact (0.06-0.15 is a noticeable effect, 0.16- femoral neck, and x-ray of the left wrist showed comminuted > 0.26 considerable, and 0.26 extensive). The activity launched impacted fracture of the distal radius. The patient underwent left September 22, 2020 and data were collected through December 4, hip hemiarthroplasty and left distal radius open reduction internal 2020. fixation. A workup of osteoporosis was initiated. Spine x-ray was Results: In total, 89 D/Es and 145 cardiologists were included in the significant for a L3 vertebral compression fracture. Dual energy x- fi analysis. Overall, there were competence and con dence im- ray absorptiometry showed T score of -2.4 in the right femoral neck provements seen among all groups from pre- to post-assessment: and -2.0 in the lumbar spine. Laboratory workup demonstrated < ¼ < 13. 28% of D/E (P .01, V .32) and 52% of cardiologists (P .01, normal parathyroid hormone axis and replete serum vitamin D. V¼.48) improved at educating patients about strategies to mitigate Secondary osteoporosis workup was significant for low luteinizing common side effects of GLP-1 receptor agonists hormone (1.2mIU/mL) and low total testosterone (131 ng/dL) 14. 53% of D/E (P< .01,V¼.52) and 59% of cardiologists (P< .01, consistent with hypogonadotropic hypogonadism. He reported ¼ fi V .51) improved at selecting the most appropriate intensi cation normal puberty as a child but did have family history of a brother regimen that includes primary prevention of CV events with many fragility fractures. He was offered testing for osteo- < ¼ < 15. 44% of D/E (P .01, V .42) and 28% of cardiologists (P .01, genesis imperfecta but declined. No pituitary mass was noted on V¼.25) improved at calculating/estimating the patient’s ACC/AHA MRI. Dental examination showed gross decay of multiple teeth. 10-year CVD risk Bisphosphonate therapy was deferred in the acute setting pending 16. 17% of D/E and 28% of cardiologists had measurable increases extraction, which the patient later declined. At six months post- fi in con dence in in applying guideline recommendations for CV risk hospital discharge, the patient had not been started on hormone, reduction in patients who have T2D anabolic, or antiresorptive therapy. Discussion/Conclusion: This study demonstrates the success of Discussion: Multiple studies have reported significant associations interactive, case-based, online CME on improving competence and of serum testosterone levels and bone loss, as well as fragility fi con dence of D/Es and cardiologists related to application of CVOT fracture prevalence. Additionally, despite higher mortality rate data in real-world patient cases. Case-based education with inter- associated with hip fractures in men than in women, men are far active polling questions and detailed explanations related to best less likely to receive antiresorptive therapy. Describing barriers to choices should be employed more often to help clinicians apply men receiving treatment for osteoporosis is also understudied, knowledge/data into practice to improve patient management and although suggested to be related to lack of physician awareness and care. patient education. Initiating osteoporosis treatment in an inpatient https://doi.org/10.1016/j.eprac.2021.04.867 setting after an acute fragility fracture can be difficult. Medical

1530-891X Education/Quality Improvement Endocrine Practice 27 (2021) S189eS195 centers and rehabilitation facilities should develop processes to Abstract #1000316 ensure care coordination from the inpatient to outpatient setting. https://doi.org/10.1016/j.eprac.2021.04.868 Social Determinants of Health Training in US Endocrinology Fellowship Program Curricula: A Comprehensive Review of Program Websites Abstract #1000069

COVID-19: Differential Functioning of an Author Block: Divya Shah Medical Student - Primary author, Indian Multispecialty Centre and the Distinctive University of Maryland; Elizabeth M. Lamos, MD - Co-author, Outcomes of Endocrino-morbid Patients in the University of Maryland; Rana Malek, MD - Co-author, University of Pandemic Era Maryland

Objective: In 2019, the Accreditation Council for Graduate Medical Author Block: Sharikant Sharma - SMS Medical college and Education revised the common program requirements of residencies hospital jaipur INDIA; Mukul Singhal senior registrar - co-author, and fellowships to incorporate an understanding of “the social de- Internal medicine, SMS Medical college; Abhishek Bhargava senior terminants of health (SDH) of the populations they serve and registrar - co-author, Internal medicine, SMS Medical college; incorporate them in the design and implementation of the program Prakash Keswani senior Professor - co-author, Internal medicine, curriculum, with the ultimate goal of addressing these needs and SMS Medical college; Sunita D. Hemani Associate Professor - co- health disparities.” Trainees must recognize that understanding SDH author, Gynecology and obst., SMS Medical college is central in explaining health disparities that exist in the commu- nities they serve and diseases they treat. However, SDH curriculum is Objective: The Covid-19 pandemic proved provocative to the informal. Here we seek to evaluate how programs distinguish their already grieving Indian healthcare infrastructure confronting the SDH curriculum to endocrinology fellowship applicant. ever-growing metabolic epidemic, thereby accentuating the Methods: We performed a comprehensive review of 147 United States morbidity and mortality statistics in overtly obese, diabetics and endocrinology fellowship program websites. We identified how SDH hormonally compromised. Imminent for the existing centres, they training was incorporated into their curricula. The consistency in evolved to consummate the task. relaying the SDH training information within the website was assessed. Aim: How does the distinctive functioning and triage-protocol of Results: Twenty percent (29/147) of programs include SDH training systemically variable co-morbid patients affects within an Indian as part of their curricula. Of the 29 programs, 31% included SDH as multispecialty hospital during the covid-19 pandemic era? To part of the ‘Training and Education’ or ‘Curriculum’ page of their determine prevalence of SARS-CoV-2 infection influence the website, 21% mentioned it under the ‘Diversity’ page and 17% under outcomes? the ‘Mission/Aims'. Also, 14% of programs advertised SDH training Methods: The projected study is an observational retrospective within their ‘Program Overview/Introduction’ and 7% under mono-centric analysis, derived from the medical case records ‘Research.’ Four percent of programs addressed SDH under both and interviews of patients/relatives investigating the clinical ‘Mission’ and ‘Research’,3.5%underboth‘Program Overview’ and outcomes of endocrine patients. The employed protocol segre- ‘Research’ categories and 3.5% only under ‘Program Requirements.’ gated those archiving variable clinico-pathologic expositions Of the 29 programs that included SDH training, 28% were in both the and endocrinal comorbidities triaging into 3 separate wards. Midwest and South, 21% in the Northeast, 17% in the Southwest, and These involved the endocrine patients without respiratory illness 7% in the Northwest. Of the programs, 52% were public institutions. (A), with respiratory difficulty (B) and with confirmed covid Discussion/Conclusion: A comprehensive review of endocrinology infection (C). A separate corona outdoor managed the influx of fellowship program websites identified a significant gap in SDH suspected patients with other ailments as per symptomatic curricula reporting. Also, there were inconsistencies in the pre- severity. Individuals with co-ailments viz. diabetes, hypertension sentation of this information and the regional distribution of these was ascertained clinically and marshalled from non-comorbid programs. This either signifies that programs have not incorporated cases in view of critical care obligation. Each super-speciality SDH into their curricula or do not adequately describe their SDH worked separately providing noteworthy attention towards training on their websites. This study emphasizes the importance of realms embracing renal, pituitary or immune-compromised showcasing required formal curricular activities on websites. A patients. standardized placement of SDH curricula on fellowship websites Results: Out of 2790 patients admitted, 890 endocrinal patients, and training will empower future generations of endocrinologists through dedicated outdoor or emergency were reallocated to demonstrate awareness of SDH and respond effectively to miti- emphasizing 144(Ward A), 411(B) and 335(C) separately. Ward (B) gate the impact socioeconomic disparities on the development and cases highlight-able with hormonal affliction, once recovered (293) management of chronic conditions. or found covid positive (118) on repeat testing were transferred to https://doi.org/10.1016/j.eprac.2021.04.870 ward A & C respectively. 95% cases (136) with predominant dysfunction (A) and 77% ward (B) cases (316) were discharged with ‘ ’ mandatory supplemental steroids. Hospital stay was the Abstract #1000346 maximum in ward C cases averaging 6.3 days owing covid status, with < 4% mortality. 104 suspects (B) and 143 cases (C), majorly Virtual Education in its Prime: New England diabetics were proficiently shifted to critical-care units, as condi- Endocrine Fellows Collaborative Learning Series tion downgraded. during the COVID-19 Pandemic Discussion/Conclusion: This protocol portrayed effective specialty- centred furcation and salient role played by endocrinologists that aided us to achieve positive results. Author Block: Danica M. Vodopivec, MD - Primary author and https://doi.org/10.1016/j.eprac.2021.04.869 presenter, Department of Medicine, Section of Endocrinology,

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Diabetes, and Nutrition, Boston University Medical Center, Boston, Abstract #1001232 MA; Maria Vamvini, MD - co-author, Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Meeting the Needs of the Internal Medicine trainee Harvard Medical School, Boston, MA and Adult Diabetes Clinic, during their Endocrinology Subspecialty Rotation: Joslin Diabetes Center, Harvard Medical School, Boston, MA; Development and Implementation of a Structured Diana Athonvarangkul, MD, PhD - co-author, Department of Curriculum Medicine, Section of Endocrinology, Yale School of Medicine, New Haven, CT; Miguel A. Ariza, MD, FACE - co-author, Diabetes and Endocrine Center, Lowell General Hospital, Lowell, MA; Author Block: Russell Fung - University of Florida in Jacksonville; Nadine E. Palermo, DO - co-author, Division of Endocrinology, Madeline Fasen, DO - Co-Author, Internal Medicine, University of Diabetes and Hypertension, Brigham and Women's Hospital, Florida Jacksonville Department of Internal Medicine; Harvard Medical School, Boston, MA; Alan O. Malabanan, MD - co- Poonam Kapadia, MD - Co-Author, Endocrinology, University of author, Division of Endocrinology, Diabetes and Metabolism, Beth Florida Jacksonville Division of Endocrinology; Angela Richter, DO - Israel Deaconess Medical Center, Harvard Medical School, Boston, Co-Author, Endocrinology, University of Florida Jacksonville MA; Geetha Gopalakrishnan, MD - co-author, Lifespan Center for Division of Endocrinology; Firas Warda, MD - Co-Author, Diabetes and Endocrinology, The Warren Alpert Medical School of Endocrinology, University of Florida Jacksonville Division of Brown University, Providence, RI; Katherine L. Modzelewski, MD - Endocrinology; Gunjan Gandhi, MD - Co-Author, Endocrinology, co-author, Department of Medicine, Section of Endocrinology, University of Florida Jacksonville Division of Endocrinology Diabetes, and Nutrition, Boston University Medical Center, Boston, MA Objective: The waning interest among internal medicine (IM) res- idents in entering a career in endocrinology is predicted to exac- Objective: During the COVID-19 pandemic, endocrine fellowship erbate the current shortage of endocrinologists. A well-developed training was disrupted as fellows and faculty were deployed for subspecialty course designed to complement content within the IM COVID-19 patient care, clinics were converted to telemedicine, and curriculum may improve standardized test scores and impacts educational conferences faced the challenge to shift to virtual resident choice of fellowship. Here we describe a structured sessions. We aimed to develop a fellow-directed virtual learning endocrinology educational framework that objectively identifies series for endocrine fellows in the New England region with sup- knowledge gaps, promotes self-learning, improves patient care and port of program leadership to 1) enhance and expand existing enhances fellow-resident relationships. educational activities, 2) unite the community in a time of need, Methods: We designed a formal curriculum to maximize resident and 3) create professional networks. learning in a two-to-four-week endocrinology consult rotation for Methods: Beginning March 2020, 76 endocrine fellows from the 14 internal medicine residents at our institution. Four distinct cate- New England programs were invited to participate in a weekly 1- gories of learning were identified which include formal teaching hour online lecture series via Zoom. A total of 50 fellows (66%) sessions, informal teaching interactions, core faculty lectures and attended the live virtual sessions, and recordings were available for resident case-based presentations. Formal teaching consist of once those who could not attend live. The series included didactic lec- or twice weekly learning sessions on high-yield endocrinology tures, case-based learning, and board review. Most of the speakers topics, while informal teaching consists of daily case-based brief were from the New England region and volunteered their time fellow-resident discussions focused primarily on practical appli- without receiving honoraria. In June 2020, the participating fellows cations to patient care in endocrinology. Weekly core lectures are were surveyed to assess the educational experience. given by faculty that cover high yield endocrinology topics, while Results: A total of 28 fellows (37%) responded to the survey, with 96% resident commitment consist of one end-of-rotation case-based in favor of the virtual conferences to continue. Most fellows preferred presentation. Additionally, we measured the resident’s knowledge weekly sessions. More than half of respondents (61%) attended more in the subject area, overall experience on the rotation and resident than 75% of the lectures. The main barrier for nonattendance was satisfaction with a pre-and-post rotation survey. Both surveys scheduling conflict. Two thirds of fellows perceived the sessions as consist of fifteen endocrinology board-style questions followed by a supplementing the educational curriculum at their own institutions, questionnaire with Likert-style scale responses in each of the four while 33% felt they replaced internal educational activities. Recorded categories of learning. sessions were watched by 57% of the fellows. The 3 most requested Results: Thus far,18 IM residents have completed the pre-test survey. ABIM endocrine topics for future sessions were lipids, female In the pre-test, an overwhelming majority of residents reported reproduction, and adrenal disorders. In addition to the educational “agree” and “strongly agree” in their confidence in the interpretation benefits, nearly half of the fellows (46%) indicated that the virtual of laboratory data and management of common endocrine disorders program provided a valuable networking experience. and “neutral” or “disagree” for uncommon endocrine disorders. Eight Discussion/Conclusion: We present a fellow-driven educational residents who have completed the post-test reported mostly “agree” series utilizing a virtual platform to enhance education and unite in their confidence of managing common and uncommon endo- endocrine fellows from the New England region for networking and crinopathies in the outpatient and inpatient settings. No resident peer support. Post-intervention survey results from participants reported “disagree” or “strongly disagree” in the post test. Formal were largely positive, and these were shared with program directors and informal teaching sessions were found to be the most helpful from the region to facilitate further collaboration. The program has educational categories. Residents reported an increased overall successfully continued and has been modified based on survey satisfaction in their learning experience. feedback to be more interactive. Lectures are recorded and made Discussion/Conclusion: Preliminary survey data indicate residents available to current fellows and recent graduates for continued note an increased satisfaction with the endocrinology rotation with learning. Our program serves as a model of a successful collaborative implementation of a structured curriculum and increased confi- educational experience for endocrine fellows during and beyond the dence in their ability to manage common and uncommon endo- COVID-19 pandemic to foster both fellow education and community. crine disorders. Thus, a well-rounded and high quality https://doi.org/10.1016/j.eprac.2021.04.871 endocrinology curriculum provides an excellent opportunity to

S191 Education/Quality Improvement Endocrine Practice 27 (2021) S189eS195 identify effective ways in identifying deficits in IM residents’ School of Medicine at Temple University; Kevin Williams, MD - co- knowledge of endocrinology, promote investment in their learning, author, Lewis Katz School of Medicine at Temple University increase confidence in the subject area and hopefully promote endocrinology as an exceptional future career choice. Objective: Before COVID-19, telemedicine had gained traction as a clinical tool, which was reflected by the adoption of new billing https://doi.org/10.1016/j.eprac.2021.04.872 codes. Here we report outcomes in our Endocrine practice, which rapidly switched to exclusively tele-health in March 2020 with no Abstract #1002888 pre-existing systems or protocols for this transition. We hypothe- sized that barriers to care, including patients’ health literacy, access A Patient User Experience Survey Study for Patient to technology/internet, and access to remote monitoring tools such Perception and Satisfaction with Insulin Pump System as blood pressure cuffs and weight scales, would make the transi- tion to tele-health less successful in a low-income urban setting than in the suburbs. Author Block: Muntazir Ali Sayed - RCSM Government Medical Methods: We measured show rates at Temple Endocrinology College Kolhapur, India; Syed Wajih Rizvi, MD - Co-author, outpatient clinic sites using the CPT coding system to compare all Endocrinology, R-Endocrinology; Javaria Mushtaq, MD - Co-author, scheduled appointments with all completed visits. We selected Internal Medicine, R-Endocrinology; Anum Khan, MD - Co-author, periods from April 1st to July 31st of 2019 and the same dates in Internal Medicine, R-Endocrinology; Shameela Begum, MD - Co- 2020, because outpatient visits were exclusively in-person (2019) author, Internal Medicine, R-Endocrinology; Syeda Jaffery, MD - or exclusively tele-health (2020). Appointments included both Co-author, Internal Medicine, R-Endocrinology; Sadiq Ali Sayed, faculty and fellow clinics. Data were stratified by service location MBBS - Co-author, Internal Medicine, National Pirogov Memorial amongst four major clinic sites that serve patients of different so- Medical University, Vinnytsya, Ukraine; Summaiya Nazneen, MBBS cioeconomic and ethnic backgrounds e namely, Temple University - Co-author, Internal Medicine, R-Endocrinology Hospital (TUH) in North Philadelphia, an urban federally designated medically underserved area, Temple Fort Washington (FW) serving Objective: Our primary objective was to assess and evaluate patient a high-income suburban area, Temple Center City (CC) serving a perspectives and satisfaction with the MiniMed 670G insulin pump. high-income urban area, and Temple Jeanes, serving a middle-in- Patients utilizing the automatic feature (auto mode) of the insulin come suburban area. pump were the study participants. Results: Surprisingly, the proportion of completed outpatient visits Methods: Adults with Type I Diabetes Mellitus using the Medtronic at TUH increased from 68.2% (n ¼ 2,965/4,346) in 2019 to 72.9% (n ¼ 670G insulin pump were asked about their experience with the 2,997/4,109) in 2020 (p ¼ 0.00001), with an absolute increase of device using a semi-structured survey and Insulin Treatment 1.01% in our completed encounters. In contrast, at FW, the pro- Satisfaction Questionnaire (ITSQ). portion of completed outpatient visits decreased from 89.8% (n ¼ Results: Eleven participants consented for the study. Overall, partic- 378/421) in 2019 to 79.3% (n ¼211/266) in 2020 (p ¼ 0.00014). At ipants indicated a high level of satisfaction with the insulin pump (08/ CC, 90.2% (n ¼ 342/379) visits were completed in 2019 and 89.5% (n 11) and the auto mode feature (09/11) which was attributed mostly to ¼ 366/409) in 2020 (p ¼ 0.73). At Jeanes, rates were 75.8% (n ¼ 485/ the improvements in blood glucose (BG) control (9/11). The least liked 640) in 2019 and 76.7% (n ¼ 615/802) in 2020 (p ¼ 0.69). features of the insulin pump were its physical design and structure (3/ Discussion/Conclusion: Despite the speed with which we transi- 11), frequency of user input (4/11), alert frequency (3/11), and diffi- tioned to an entirely tele-health-based practice at the start of the culty of use (2/11). The least liked features of the auto mode tech- pandemic, we found that we were equally e if not more able e to nology were persistent elevation in blood glucose levels (4/11) and the complete clinical Endocrinology visits with our population of un- frequency of alerts (3/11). Overall mean (SD) ITSQ scores were high derserved patients in North Philadelphia. In contrast, at our sub- among all respondents regardless of prior treatment: 98.3 (24.2) urban FW campus, the show rates fell. We are currently examining (scale: 0-132). Most (87%) of participants rated the Latest Generation disease acuity, transportation issues related to in-person visits, and Insulin Pump (LGIP) to be better than their previous insulin delivery internet access through smartphones in the populations served by system: "much better" (69%), "a bit better" (21%) regardless of age, and TUH and FW. Overall, our data suggest that tele-health can be a 93% would recommend using the LGIP to others. successful option for Endocrine practice in an underserved urban Discussion/Conclusion: Our study participants indicated a moder- area. ately higher level of satisfaction with the Medtronic 670G insulin https://doi.org/10.1016/j.eprac.2021.04.874 pump and its auto mode featured mostly attributing to improve- ments in their BG control. Additional research is encouraged to further evaluate users' perspectives on this device. Abstract #1003444 https://doi.org/10.1016/j.eprac.2021.04.873 Pandemic Forced and Ultra-Rapid 100% Digital Transformation of a Speciality Endocrinology Diabetes Abstract #1002976 Center and its Group Practice: Experience from India

Harnessing Telemedicine to Improve Access to Care During the COVID-19 Pandemic Author Block: Mandyam D. Chitra, MBBS, FEDM, CDE - Primary Author, Endocrinology Diabetes Medicine, Samatvam Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital Author Block: Preethi Gogineni - Temple University Hospital; and Medical Center; Jayalakshmi Thimmaiah, MBBS, FEDM CDE - Remy Mimms, MD - co-author, Endocrinology, Diabetes, and Co Author, Endocrinology Diabetes Medicine, Samatvam Metabolism, Temple University Hospital; Cherie Vaz, MD - co- Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital author, Endocrinology, Diabetes, and Metabolism, Lewis Katz and Medical Center; Siddhartha Dinesha, MBBS, FEDM CDE - Co

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Author, Endocrinology Diabetes Medicine, Samatvam volunteers who serve as “proxy family” to these patients]. The core Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital strength of Wellzio is the most scientific and advanced, yet most and Medical Center; Apoorva Govind, MBBS, FEDM CDE - Co user friendly EMR e the heart of TM. The high safety, quality and Author, Endocrinology Diabetes Medicine, Samatvam efficiency of medical care at Samatvam has been further enriched Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital by the very timely contribution of Wellzio, strangely stimulated by and Medical Center; Umesh Hiriyannaiah, MSc, PhD - Co Author, the humanity's worst pandemic. Information Communication Technology, Wellzio; Prateek Hongal, Discussion/Conclusion: Resources like Wellzio, in coming years, MBBS, FEDM CDE - Co Author, Endocrinology Diabetes Medicine, will hopefully reach every nook and corner of India and help both Samatvam Endocrinology Diabetes Center, Jnana Sanjeevini the Medical Fraternity and the 130 crore People of India enrich their Diabetes Hospital and Medical Center; Natarajan K, MSc - Co health and welfare, through the power of Digital Health e an Author, Information Communication Technology, Wellzio; inevitable and mandatory societal transformation for the coming Rishi Madhok, MD, MBA - Co Author, Emergency and Internal decade. Medicine; Health Informatics, Wellzio; Kavitha Muniraj, MBBS, https://doi.org/10.1016/j.eprac.2021.04.875 FEDM, FACE - Co Author, Endocrinology Diabetes Medicine, Samatvam Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital and Medical Center; Annadanam Murthy, MSc, Abstract #1003580 MBA - Co Author, Endocrinology Diabetes Medicine, Wellzio; Ramamurthy Suresh, BE, MS - Co Author, Information Sub-Specialty Fellow Education on Managing Communication Technology, Wellzio; Pushpa Ravikumar, MBBS, After-Hours Pages: A Single Institute Survey FEDM, FACE - Co Author, Endocrinology Diabetes Medicine, Samatvam Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital and Medical Center; Balakrishna Adiga, B Tech, Author Block: Niyoti Reddy, MD - Primary author, Endocrinology, MBA - Co Author, Information Communication Technology, Boston Medical Center; Katherine Modzelewski, MD - Co-author, Wellzio; Sathyanarayana Srikanta, MBBS, MD, FEDM, FACE, FRCP - Endocrinology, Boston Medical Center; Sara Alexanian, MD - Co- Co Author, Endocrinology Diabetes Medicine, Samatvam author, Endocrinology, Boston Medical Center Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital and Medical Center - Endocrinology Diabetes Study Group, Objective: Internal medicine sub-specialty fellows, including those Endocrinology Diabetes e Co Author, Endocrinology Diabetes in endocrinology, are often responsible for responding to patients Medicine, Samatvam Endocrinology Diabetes Center, Jnana who call after business hours. They are expected to address patient Sanjeevini Diabetes Hospital and Medical Center concerns, often without attending physician supervision. Very few specialties train fellows to answer these calls. Our aim was to assess Objective: Digital Health implementation is more challenging in fellows’ training and comfort with after-hours calls to determine if low resource and developing nations like India [wide disparity there is an unmet need for more education. between haves and have nots, literate and illiterate etc]. Here we Methods: A 12-question survey was sent to 100 sub-specialty cur- share our experiences on the successful Digital Transformation of a rent fellows and recent graduates from 10 programs at Boston Speciality Endocrinology Diabetes Center [Samatvam] and its group Medical Center (BMC), an academic institution. The response rate practice from India. was 65%, with 58% recording complete responses. Qualtrics survey Methods: Samatvam, has been in the forefront of Electronic Med- software was used to design the survey and for analysis. ical Records [EMR] since 1980s, and in 1994, implemented its own Results: At least one fellow responded from all but one specialty. “home grown” EMR Software e “JS Health”. Telemedicine [TM] Endocrinology fellows comprised 23% of all respondents. An over- services have been delivered by Samatvam Doctors and Physician whelming majority of fellows across specialties (94%) are respon- Assistants over last three decades, predominantly via multiple 24- sible for after-hours calls on weekdays and weekends. Of these, hour helplines [perhaps the world’s longest and busiest; Ref World only 22% received formal education (lecture or handbook) on Diabetes Congress, Dubai 2011], to patients and families from our answering calls. Nearly one-third rated the quality of after-hours city, state and country, and even many overseas [all as totally “free” care provided as either poor or adequate and 75% were not value added service and social responsibility]. However, in April comfortable at all or only somewhat comfortable with answering 2020, Samatvam efforts in Digital Health Care, took a quantum leap after-hours pages. Nearly two-thirds felt that a curriculum on how [converting “crisis” to “opportunity”], with the most precious gift of to answer after-hours calls would be very or moderately effective to “Wellzio”, a made in USA EMR-TM platform, with current focus of improve their comfort and quality of care, while one-third felt it implementation in India. All Telehealth modalities have been suc- would be slightly effective, and 1 fellow said it wouldn’t be effective cessfully implemented including: (a) Synchronous: Real-time at all. Of those who were in favor of more education, 76% preferred telephone or live audio-video interaction, typically with a patient, a digital handbook and 52% desired a live didactic in addition to the using a smartphone or computer; (b) Asynchronous: Non-real-time digital handbook. Fewer fellows (30%) preferred a pocket hand- provider and patient communication [Eg: “store and forward” book. High-yield topics listed by fellows were medication queries messages, images, or data]; (c) Remote patient monitoring: [direct (refills, side effects), peri-procedure queries (preparation and post- transmission of a patient’s clinical measurements from a distance; procedure complaints), hospital specific protocols, patients calling may or may not be in real time) to their healthcare provider. for lab results, outpatient complaints (eg: hyperglycemia), insulin Results: As of November 2020, Samatvam’s health care services pump trouble shooting, and when to refer to ER vs treat at home. became 100% digitized [Database 29979 patients; 14946 patients Discussion/Conclusion: Despite more than 90% of fellows at BMC active] e providing high standards of care at both Clinic Visits and answering after-hours calls, less than 25% receive formal education Telemedicine Visits, not only to the “Computer / IT Literate”, but to prepare them and nearly all respondents felt that additional also to each and every totally “Computer / IT Illiterate” [ie all the resources and training would significantly improve their comfort beneficiaries of our 3 decade old DISHA and DOSTI Free Diabetes and quality of care provided. They preferred a digital handbook Clinic for the Poor - via most creative involvement of our staff and with or without a lecture as a means of education. Despite this

S193 Education/Quality Improvement Endocrine Practice 27 (2021) S189eS195 universal desire for increased training, resources would have to be management of patients has been drastically reimagined and specialty and institution specific with emphasis on practical changed by the COVID-19 pandemic. Health care professionals and knowledge not found in other sources. Fellowship programs across systems have creatively adapted in their own ways for their specific the country should consider whether this is an unmet educational needs. Here we share our experiences related to a Speciality need. This is particularly important in endocrinology given that Endocrinology Diabetes Group Practice [Samatvam] from India. answering outpatient calls is a significant part of our jobs. Methods: Samatvam [Inception 1987], as early as March 2020, swung into action to prepare for protection from COVID -19, at the https://doi.org/10.1016/j.eprac.2021.04.876 same time ensure the best possible uninterrupted Non-Covid Care. The focus has been on providing expert advice and treatment to the many follow up and new patients seeking: (a) routine and emer- Abstract #1003842 gency Diabetes, Endocrinology and Primary Care, and (b) even care Successful and Rapid Adaptation to Telemedicine and for COVID-19 [out of sheer social need and humanitarian duty], either Hybrid Model in a Speciality Endocrinology Diabetes at home or in hospitals [for the latter, emphasis was on prompt day Group Practice - Pandemic catalysed to day acquisition and assimilation of global scientific data, often confusing/conflicting, and delivering the “ideal”]. Results: Samatvam Health Care Team: 18 Endocrinologists, 12 Author Block: Mandyam D. Chitra, MBBS, FEDM, CDE - Primary Physician Assistants Diabetes Educators; 4 IT Staff, 20 Support Staff, Author, Endocrinology Diabetes Medicine, Samatvam spread across the city of Bangalore, with few participating Physi- Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital cians from other cities of India and even overseas. and Medical Center; Jayalakshmi Thimmaiah, MBBS, FEDM CDE - Three service models: (a) Telemedicine [TM] Care: “Virtual Co Author, Endocrinology Diabetes Medicine, Samatvam Endocrinology Diabetes Clinics”; (b) Clinic Visit [CV] Care [not during Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital full lockdowns]; (c) Hybrid [HY] Care: ie TM + CV, as per need. The and Medical Center; siddhartha dinesha, MBBS, FEDM CDE - Co model choice depended on the nature of the care needed, literacy Author, Endocrinology Diabetes Medicine, Samatvam and resources available with the patient/family member, and Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital obviously home e clinic distance etc. Just few examples of infinite and Medical Center; Apoorva Govind, MBBS, FEDM CDE - Co “TM creativity” include: Author, Endocrinology Diabetes Medicine, Samatvam (a) Remote guided self/family physical examination: for goiters, Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital skin and foot lesions [even warmth, tenderness etc], growth and and Medical Center; Prateek Hongal, MBBS, FEDM CDE - Co Author, pubertal staging, hirsutism scoring; Endocrinology Diabetes Medicine, Samatvam Endocrinology (b) Individual “serious/complicated” patient centric “Whats app Diabetes Center, Jnana Sanjeevini Diabetes Hospital and Medical groups” and “email chains”: for 24x7 data gathering, patient Center; Reshma Harsha, MBBS, FEDM, FACE - Co Author, monitoring, therapy guidance and counselling, with both physician Endocrinology Diabetes Medicine, Samatvam Endocrinology [clinic and hospitalist] and patient/family participation and Diabetes Center, Jnana Sanjeevini Diabetes Hospital and Medical posting; Center; Kavitha Muniraj, MBBS, FEDM, FACE - Co Author, (c) Tele-self-care technique trainings for “naïve/new/untrained” Endocrinology Diabetes Medicine, Samatvam Endocrinology patients under home care/quarantine: Eg: Glucose Monitoring, Diabetes Center, Jnana Sanjeevini Diabetes Hospital and Medical CGM, Artificial Pancreas, Insulin/GLP-1 and Heparin Injections, Center; vasanthi Nath, MBBS, FEDM, FACE - Co Author, Wound caree via archived or real time video demonstrations; Endocrinology Diabetes Medicine, Samatvam Endocrinology (d) Endocrinology Diabetes Virtual Case Conferences and Grand Diabetes Center, Jnana Sanjeevini Diabetes Hospital and Medical Rounds: Every Sunday 3 hours on Google Meet. Center; Tejeswini Patil, MBBS, FEDM, FACE - Co Author, Discussion/Conclusion: Necessity is the mother of invention. Con- Endocrinology Diabetes Medicine, Samatvam Endocrinology verting crisis to opportunity is an evolutionary trait e survival of Diabetes Center, Jnana Sanjeevini Diabetes Hospital and Medical fittest. Telemedicine Care, Virtual Clinics, Hybrid Models etc will all Center; Lakshmi Reddy, MBBS, FEDM, FACE - Co Author, have significant values beyond the pandemic, in all fields including Endocrinology Diabetes Medicine, Samatvam Endocrinology Endocrinology Diabetes.

Diabetes Center, Jnana Sanjeevini Diabetes Hospital and Medical https://doi.org/10.1016/j.eprac.2021.04.877 Center; amit sinha, MBBS, FEDM, FACE - Co Author, Endocrinology Diabetes Medicine, Samatvam Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital and Medical Center; Abstract #1003950 Sharda Ardhanareeswaran, MBBS, MD, FEDM, FACE, FRCP - Co Author, Endocrinology Diabetes Medicine, Samatvam Successful Co-management between Primary Care and Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital Endocrinology and Medical Center; Sathyanarayana Srikanta, MBBS, MD, FEDM, FACE, FRCP - Co Author, Endocrinology Diabetes Medicine, Samatvam Endocrinology Diabetes Center, Jnana Sanjeevini Author Block: Elizabeth Lepkowski - AACE; Daniel Hurley, MD, Diabetes Hospital and Medical Center Endocrinology Diabetes FACE - co-author, Mayo Clinic; Archana Sadhu, MD, FACE - co- Study Group, Endocrinology Diabetes e Co Author, Endocrinology author, Houston Methodist Diabetes Medicine, Samatvam Endocrinology Diabetes Center, Jnana Sanjeevini Diabetes Hospital and Medical Center Wellzio Inc Objective: Primary care providers (PCPs) are not always equipped USA INDIA, Digital Health e Co-author, Information to diagnose and manage endocrine disorders, although 75% of pa- Communication Technology, Wellzio Inc USA India tients with endocrine diseases are only being managed by their PCPs. Unfortunately, PCPs often do not have timely access to spe- Objective: “The secret of change is to focus all your energy, not on cialty knowledge directly from the endocrinologists, due to the fighting the Old, but on building the New.” Socrates. Globally, shortage within the specialty. PCPs may have to initiate

S194 Education/Quality Improvement Endocrine Practice 27 (2021) S189eS195 management during the wait time for a referral appointment. To Lifecare Diabetes Centre Kirti Nagar New Delhi; Rajeev Chawla, help address this crisis in care, the American Association of Clinical MD, FRCP(UK), FACE - co-author, Diabetes, North Delhi Diabetes Endocrinology (AACE) and The France Foundation (TFF) developed Centre, Rohini, New Delhi; Dhruvi Hasnani, MD, FRCP(UK) - co- SCOPE: Successful Co-management between Primary Care and author, Diabetes, Rudraksha Hospital Bareja Ahmedabad; Endocrinology. SCOPE, which was delivered via 2, full-day regional Vipul Chavda, MD - co-author, Diabetes, Rudraksha Hospital Bareja meetings, and a 4-part online educational enduring series, was Ahmedabad; Shubhaa Chawla, MBBS - co-author, Diabetes, North designed to provide the primary care team with the necessary Delhi Diabetes Centre, Rohini, New Delhi; Aastha Chawla Trehan, knowledge and skills to care for common endocrine disorders in MD - co-author, Dermatology, North Delhi Diabetes Centre, Rohini, the primary care setting and co-manage conditions with endocri- New Delhi nology colleagues. Methods: A thorough needs assessment was developed to ensure Objective: Medicines form a substantial portion of out-of-pocket that the content presented was learner-centered to address real- expenditure on health in India. COVID-19 has induced a financial world practice needs. The curriculum covered content in areas of constraint driving patients to be inquisitive for the cost of the endocrinology, defined as the BOLD-T curriculum (Bone, Obesity, medicines. We explored the patients’ perceptions towards the cost Lipids, Diabetes, and Thyroid). of the medicines in the COVID-19 era Objectives were to: Methods: We conducted a cross-sectional survey in the outpatients (n¼282) attending the three comprehensive diabetes care centres F020 Identify key aspects of the workup for the given endocrine in December - January 2021, with 17 questions to assess the disorder. contemporary patient perceptions towards the cost of medications F020 Explain aspects of patient presentation and/or course that for diabetes care necessitate referral to an endocrinologist. Results: The study showed that cost of medicines is high ac- F020 Summarize key characteristics of evidence-based treat- cording to 80% (225) of the patients. Most patients (77%) preferred ment options for the given disorder. to be prescribed the cheapest medicine. Majority of patients (86%) F020 Formulate a management plan that includes steps/strate- believed that cost should be considered before a drug is pre- gies supporting optimal Primary Care Physician-endocrinologist scribed. Most patients (71%) accepted economical alternative and collaboration. believed that it can provide significant saving. Surveyed patients (91%) agreed that they should have the option of choosing be- Both the content and the educational design ensured that these tween the drugs based on the pricing. Almost, all agreed that the objectives were integrated into a unique learning experience for the physician should ask for the preference of the medicine (95%). workshop learners. The content explored all areas of the BOLD-T cur- Substantial number of patients (46%) were not in agreement if, the riculum through a multifaceted and interactive learning experience. pharmacist provides a cheaper equivalent alternative. 85% pa- Results: Final outcomes demonstrated significant gains in knowl- tients wanted the substitution from a branded to a generic, edge and impact on over 3,000 total learner’s clinical strategies in exclusively based on their request. 79% patients prefer to be all areas of the BOLD-T curriculum. SCOPE outcomes supported the prescribed a well-known brand. Among 80%, effectiveness was utility of Continuing Medical Education (CME), with significant important irrespective of the brand of the medicine. 62% patients posttest score gains, increased confidence in clinical skills, and were not concerned with the cost, provided the drug was effica- plans to incorporate new information into practice across all areas cious. 65% did not believe that an expensive medicine is always of the BOLD-T curriculum. The program was successful in con- better. 57% opined that cost is the most important reason for necting the primary care team with a comprehensive curriculum. compliance. 55% patients were impacted by COVID-19 to spend on The integration of unique design elements broke down any pre- medicine. 25% discontinued medications due to financial conceived barriers between learners and the content, as well as constraint due to COVID-19. Only 37% of the patients had ever between interdisciplinary learners themselves. discussed with the physician for the cheaper options. The results Discussion/Conclusion: The interactive activities revealed a deeper showed a significant statistical correlation with the monthly in- understanding of where continued gaps need to be addressed. come (p< 0.05). Learners’ response to the game-based and interactive content was Discussion/Conclusion: The results of our study demonstrate rated excellent and will be integrated in future activities. that the patients prefer the most economical drug for diabetes care. However, there was equivocal response for the preference https://doi.org/10.1016/j.eprac.2021.04.878 for a well-known brand, without compromise on the quality. There was a reluctance for the pharmacist led alternative without the patient participation to choose an economical Abstract #1004315 option. Despite, out-of-pocket expense, quality is perceived to be more important than just the cost. During the current Evaluation of the Patient Perceptions towards the Cost COVID-19 era, the economical drugs as alternatives for man- of Diabetes Therapy During the COVID-19 Era aging diabetes, enabled the continuity of diabetes care, with only a small proportion of the patients, discontinued the dia- betes therapy. Author Block: Shalini Jaggi, PG Diploma Diabetes(UK), Diploma Endocrinology (UK), FRCP, FACE - Presenting author, Diabetes, https://doi.org/10.1016/j.eprac.2021.04.879

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