ISSN: 2377-3634 Nawal et al. Int J Diabetes Clin Res 2020, 7:127 DOI: 10.23937/2377-3634/1410127 Volume 7 | Issue 3 International Journal of Open Access Diabetes and Clinical Research CASE REPORT Neuro-psychiatric Manifestations in Multiple Endocrine Neo- plasia - 1: A Unique Presentation CL Nawal, Abhishek Yadav, Abhishek Agrawal* , Radhey Shyam Chejara and Aradhana Singh Department of Medicine, SMS Medical College & Hospital, Jaipur, India *Corresponding author: Dr. Abhishek Agrawal, Department of Medicine, SMS Medical College & Hospital, Check for Jaipur, India, Tel: +91-9829298691 updates hair and genital development. A resting pulse rate of Keywords 114/min and blood pressure of 134/86 mm of Hg was MEN-1, Insulinoma, Prolactinoma noted. No other remarkable physical findings were present. The patient was then kept fasting in the ward Introduction and blood glucose was monitored hourly. She develo- Multiple endocrine neoplasia 1 (MEN1) syndrome ped symptoms of sympathetic over activity and blood is a rare heritable disorder characterized by neoplasia glucose was found to be ≤ 45 mg/dl and critical blood or hyperplasia of the parathyroids, enteropancreatic samples were drawn. She had simultaneously high se- tissues, anterior pituitary and other tissues. Clinical dia- rum insulin 4.65 microU/ml (to diagnose insulinoma, it gnostic criteria for MEN 1 include presence of at least 2 should be > 3 µU/ml at the time of hypoglycemia) and a of the 3 groups of endocrine tumors as mentioned abo- high C-peptide level of 5.0 ng/ml (to diagnose insulino- ve [1]. Here, we are reporting an uncommon presen- ma, it should be > 0.6 ng/ml at the time of hypoglyce- tation with neuropsychiatric symptoms, subsequently mia) despite hypoglycemia [2]. Plasma thyroid stimu- diagnosed with insulinoma along with additional findin- lating hormone (TSH) was within normal limits. Serum gs consistent with MEN 1. cortisol was 9.18 μg/dl (normal range: 4.3-22.4 μg/dl) and growth hormone (GH) was 8.75 ng/ml (normal < Case Report 10 ng/ml in females). Glycated hemoglobin (HbA1C) was A twenty-one years-old Indian female patient pre- 4.33% indicating chronic hypoglycemia. Ultrasound sented with episodes of nervousness, irritability and (USG) examination of the whole abdomen revealed a confused behavior for a period of 20 days, particularly hypoechoic lesion (16 × 14 mm) in the tail of the pan- when a meal was delayed. About two days prior to pre- creas along with a small (4 mm) right renal calculus. sentation she developed an episode of loss of consciou- Contrast enhanced computer tomography (CT) scan of sness which recovered when she was administered dex- whole abdomen showed arterial phase enhancement in trose containing intravenous fluids at a local clinic. She the tail of the pancreas (Figure 1). The CT scan finding was then referred to our department for further eva- along with history of hypoglycemia was suggestive of luation. There was no history of chest pain, dyspnea, a pancreatic neuro-endocrine tumor most likely an in- involuntary movements of body, frothing from mouth, sulinoma. Evaluating the cause of renal calculus, serum tongue bite, urinary incontinence, any discharge from calcium was ordered which was high 11.8 mg/dl (nor- nipples, jaundice or facial puffiness. There was no hi- mal range 8.8-10.2 mg/dl) along with raised PTH 110.6 story suggestive of factitious hypoglycemia. On physi- pg/ml (normal range 11.1-79.5 pg/ml). Serum phospha- cal examination, she was thinly built with a body mass te was 2.61 mg/dl (normal range 2.5-4.5 mg/dl). USG index (BMI) of 22.6 Kg/m2. She was Tanner IV for pubic examination of neck was done to evaluate hyperpara- Citation: Nawal CL, Yadav A, Agrawal A, Chejara RS, Singh A (2020) Neuro-psychiatric Manifestations in Multiple Endocrine Neoplasia - 1: A Unique Presentation. Int J Diabetes Clin Res 7:127. doi. org/10.23937/2377-3634/1410127 Accepted: July 13, 2020: Published: July 15, 2020 Copyright: © 2020 Nawal CL, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Nawal et al. Int J Diabetes Clin Res 2020, 7:127 • Page 1 of 4 • DOI: 10.23937/2377-3634/1410127 ISSN: 2377-3634 Liver Liver Spleen Lt Kidney Figure 1: CECT abdomen showing arterial phase enhancement in the tail of pancreas. Figure 2: MRI brain with sella cuts showing anterior pituitary microadenoma. Nawal et al. Int J Diabetes Clin Res 2020, 7:127 • Page 2 of 4 • DOI: 10.23937/2377-3634/1410127 ISSN: 2377-3634 thyroidism, which revealed a hypoechoic lesion (11 mm MEN-1 mostly are asymptomatic and often pre- × 16 mm) with increased vascularity at inferior angle sent with symptoms of hyperparathyroidism. The neu- of thyroid s/o Parathyroid adenoma. Presence of two ro-psychiatric symptoms due to hypoglycemia are seen endocrine neoplasm warranted further investigation as very rarely. These include a wide range of autonomic re- possibility of MEN was considered. Serum prolactin was sponses like sweating, weakness, hunger as well as neu- high (67.27 ng/ml, normal range: 1.9-25 ng/ml) and GH roglycopenia symptoms as irritability, confusion and loss was normal (8.75 ng/ml, normal range < 10 ng/ml for of consciousness. Often, in non-diabetic persons, these females). Magnetic resonance imaging (MRI) scan of manifestations are misdiagnosed as some underlying sella showed a small eccentric lesion in the right half of neuropsychiatric disorder. Insulinoma, a rare cause of anterior pituitary measuring 2 mm × 2 mm suggestive hypoglycemia is diagnosed with insulin concentrations of a microadenoma (Figure 2). The presence of three of at least 3 μU/ml (18 pmol/l) and c-peptide concentra- endocrine tumors i.e. enteropancreatic tumor - insu- tions of at least 0.6 ng/ml (0.2 nmol/l) when the fasting linoma, parathyroid adenoma and pituitary microade- glucose concentrations are below 55 mg/dl without noma (prolactinoma) established the diagnosis of MEN any detectable oral hypoglycemic agent levels and no type 1. The prolactinoma was managed with dopamine circulating insulin antibodies [5]. Insulinoma in MEN-1 agonist cabergoline. For insulinoma, distal pancreatec- presents in second to fourth decade of life as compared tomy with splenectomy was done after Ga68 Dotatate to sporadic cases which present late. MEN-1 insulinoma positron emission tomography (PET) scan to rule out are often small, may be multiple and may be associated metastasis for insulinoma. Histopathology examination with simultaneous presence of other islet cell tumors. revealed tumor cells positive for synaptophysin (diffuse Other gastro-intestinal tumor in MEN-1 is gastrinoma strong positive) and chromogranin (diffuse strong posi- causing Zollinger-Ellison syndrome (ZES), which is also tive) with Ki-67 of 05% suggested a low grade (grade-2) the most common cause of symptomatic disease in neuroendocrine neoplasm. A parathyroid adenoma was MEN-1. Non-functioning pancreatic tumors may be ma- detected on histopathology examination of excised pa- lignant and can metastasize to liver. Gallium-Dotatate rathyroid gland. She was discharged symptom free and PET/CT scanning has been reported to have especially kept on regular follow up to monitor any possible recur- high sensitivity for detecting neuroendocrine tumors in rence. She is currently taking dopamine agonist caber- MEN-1 [6]. A combination of various pharmacological goline and regular prolactin levels monitoring. and surgical approaches is used in treatment. Discussion Pituitary adenomas are clinically apparent in 15 to 20 percent of patients with MEN-1. Prolactinoma is the The term multiple endocrine neoplasia (MEN) en- most common type of pituitary adenoma, but somato- compasses various clinical inherited syndromes com- troph, corticotroph, gonadotroph, and clinically nonfun- prising of various benign or malignant tumors involving ctioning tumors can also occur in MEN-1. Clinical mani- different endocrine glands. MEN - 1 affects 2-20 per festations of pituitary tumors in MEN-1 are similar to 100,000 individuals. Three main tumor types are reco- those with sporadic tumors, and include those that are gnized: parathyroid adenomas, pancreatic neuroendo- due to hormone excess, and those that are related to crine tumors (NET) and pituitary tumors. MEN 2 are clas- the size of the tumor [6]. Patients with prolactinomas sified into three clinical subtypes: (1) MEN2A: Medullary may present with amenorrhea, galactorrhea and infer- carcinoma of thyroid (MTC) associated with pheochro- tility in women; or erectile dysfunction and infertility in mocytoma and hyperparathyroidism; (2) MEN2B: MTC men. Patients having excessive secretion of GH or ACTH associated with mucosal neuromas, pheochromocyto- may present with the signs or symptoms of hormone ma, marfanoid body habitus, gastrointestinal ganglio- excess e.g. gigantism or acromegaly. Individuals with neuromatosis and myelinated corneal nerves; and (3) enlarging pituitary tumors may experience headaches Familial MTC: Only MTC is present. MEN2B is a more and signs of compression of adjacent structures such aggressive disease than MEN2A or familial MTC [3]. visual field disturbances in the setting of optic chiasm Various cutaneous tumors are commonly found in compression, and/or hypopituitarism. Treatment of pi- MEN1 but are often subclinical. These include multiple tuitary tumors in MEN-1 does not differ from sporadic angiofibromas, collagenomas, and lipomas. In contrast cases and include trans-sphenoidal surgical removal of to tuberous sclerosis the angiofibromas in patients with the tumor. Prolactinomas respond well to therapy with MEN1 are smaller in size and less numerous. In addition, dopamine agonists, which may be used for a long period angiofibromas in MEN1 commonly involve the upper lip of time. and vermillion border of the lip, whereas in tuberous Parathyroid tumor is most common manifestation sclerosis, angiofibroma often spare the upper lip region.