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FALL 2018 FALL

| UPDATE IN | DIVISION OF ENDOCRINOLOGY AND

Inside This Edition Dear Colleagues, 2 Using to Transform the I am pleased to share our latest edition of Update in Endocrinology! While the mission of our Division is Care of Rural Veterans With steadfast, we continue to grow both in knowledge and expertise to better serve the clinical and 4 Psychosocial Aspects of Diabetes academic community. Management Across the Life Span Clinically, we continue to make great strides towards improving care of at-risk patients by providing 6 An Interesting Case of Ataxia and telehealth services to patients outside the reach of quality endocrine care. In this issue,Archana Bandi, MD, Osteosclerotic Bone Lesions clinical co-leader of the Endocrine Telehealth Unit and director of Telehealth Services at the Veterans 8 Sex-Dependent Effect of Steroid Administration Pittsburgh Healthcare System (VAPHS), highlights our use of innovative telehealth on Neurodevelopment, programs to transform the care of rural veterans with diabetes. Our endocrine fellows,Karla Detoya, MD, , and Behavior and Neha Karajgikar, MD, presented the positive impact of these programs on quality and cost of diabetes care at the 2018 Annual Sessions for the and American Diabetes Association, 10 Department News resulting in a first place award at the 2018 Endocrine Society Presidential Poster Competition. Another way we are improving care of at-risk patients is by better understanding the impact of Open Faculty Positions: transitions of care and relationships on clinical outcomes. Our clinical endocrinologists Hussain • Director, Multidisciplinary Center Mahmud, MD, and Mary Korytkowski, MD, in collaboration with Vicki Helgeson, PhD, professor of Psychology at Carnegie Mellon University, discuss how these important psychosocial factors influence • Academic Clinical Endocrinologists across the lifespan. • Academic Research Faculty Given the large endocrine catchment area of UPMC, there is never a shortage of complex cases to Full descriptions and contact information challenge our knowledge and expertise. In this issue, our fellow Mihaela Oprea, MD, and her mentor, on back page. Interested candidates should send a cover letter, curriculum vitae, and contact information for three references to Erin E. Kershaw, MD, Chief of Endocrinology Sue Challinor, MD, present an interesting case of ataxia and osteosclerotic bone lesions in a patient and Metabolism, care of Chelsea Dempsey (email: [email protected]). EEO/AA/M/F/Vets/Disabled. with a longstanding history of central . Can you guess the diagnosis?

CME Credit We continue to the growth of our academic mission through recruitment and development of top talent. In the last interval, we welcomed two young and very talented tenure-stream assistant professors, Disclosures: Drs. Bandi, Challinor, Frahm, Helgeson, Kershaw, Korytkowski, and Mahmud Sadeesh Ramakrishnan, DVM, PhD, and Bokai Zhu, PhD. In this issue, we also highlight the research report no relationships with proprietary entities and career development of Krystle Frahm, PhD, a former postdoctoral scholar on our long-standing producing goods and services. NIH T32 training grant, who has recently transitioned to faculty and received an NIH-funded K01 award to understand sex-dependent effects of steroid hormones on neurodevelopment, physiology, and Instructions: To take the CME evaluation and receive credit, please visit UPMCPhysician behavior. Dr. Frahm recently received the 2018 Endocrine Society Early Investigators Award. Resources.com/Endocrinology, and click on We also celebrate many other interval accomplishments of our faculty and trainees. Sann Mon, MD, UPMC Update in Endocrinology Fall 2018. was promoted to chief of Endocrinology at UPMC McKeesport, where she won the Resident Teaching Accreditation Statement: The University of Award for the third year in a row. Our clinical and research fellows presented their scholarly work at the Pittsburgh School of is accredited by 2018 Annual Sessions of the Endocrine Society and the American Diabetes Association, where several the Accreditation Council for Continuing Medical won awards as noted above. Likewise, several of our faculty were recently recognized as “Best Doctors,” (ACCME) to provide continuing both locally and nationally. Finally, we enjoyed celebrating with our colleagues, alumni, and friends at for . The University our 2018 ADA Annual Reception in Orlando, Florida. We hope to see you at our reception next year! of Pittsburgh School of Medicine designates this enduring material for a maximum of .5 AMA PRA If you would like to be a part of a division that rises to the challenge of providing the best of tomorrow’s Category 1 Credits™. Each should only endocrine care today, I look forward to hearing from you! claim credit commensurate with the extent of their participation in the activity. Other health Best wishes, care professionals are awarded .05 continuing education units (CEU), which are equivalent to .5 contact hours. Erin E. Kershaw, MD Chief, Division of Endocrinology and Metabolism

Affiliated with the University of Pittsburgh School of Medicine, UPMC Presbyterian Shadyside is ranked among America’s Best by U.S. News & World Report. Using Telehealth to Transform the Care of Rural Veterans with Diabetes

“Thanks for coordinating care for my Statistics Report produced by the Centers In addition to the above, evidence supporting father,” said Rachel, fighting back tears for Disease Control and Prevention (CDC) the clinical and cost effectiveness of in her eyes. Rachel is a single mom indicates that diabetes is 17 percent more telehealth services for diabetes is likewise and home health care nurse who had prevalent in rural areas compared to urban growing. A systematic review of RPM of accompanied her father, Mr. Smith, to a areas, and yet the majority of endocrin­ structured self-monitored blood local VA in rural Pennsylvania for a ologists serve metropolitan rather than (SMBG) and its impact on HbA1c showed video visit with an endocrinologist located rural areas. Not surprisingly then, the that the impact was most significant when over one hundred miles away at the VA average wait time for a non-urgent new care providers incorporated specific Pittsburgh Healthcare System (VAPHS). patient visit with an endocrinologist at predefined elements (spanning education, Mr. Smith, a World War II veteran, was the time of the CDC study was 37 days. structured SMBG, and feedback) and 83-years-old when his primary care Clearly, there is a tremendous need for new incorporated computer decision support.5 provider (PCP) from James E. Van models of diabetes care, particularly for RPM platforms for SMBG provide real-time Zandt VA Medical Center in Altoona, patients residing in rural areas. support for improving quality of life (QOL), Pennsylvania, first sought assistance from improving outcomes related to patient Telehealth has emerged as a solution for an endocrinologist for his poorly controlled satisfaction, and reducing ED visits and these escalating challenges. While the diabetes. Being the sole caregiver for his inpatient days of care.6 term telehealth and telemedicine are elderly wife, Mr. Smith was unable to travel often used interchangeably, telehealth The VAPHS has been providing telehealth to Pittsburgh­ where the endocrinology encompasses a wide range of health care diabetes services for more than a decade. team was located. He was, therefore, delivery modalities, as well as health The VAPHS team recently presented offered an initial electronic consultation administrative options such as tumor outcomes data at the 2018 Endocrine and telephonic follow-up visits with an 7

| 2 | UPDATE IN ENDOCRINOLOGY | ENDOCRINOLOGY IN | 2 UPDATE boards and medical education. Tele­ Society Annual Meeting and Expo in endocrinologist at the VAPHS. The medicine refers more specifically to Chicago, IL and the 2018 American endocrinology team then offered him medical care delivery processes and Diabetes Association Annual Scientific continuity of care via clinical video includes: 1) asynchronous modalities, such Sessions in Orlando, FL.8 These data tele­conferencing,­ remote blood as remote patient monitoring (RPM) and demonstrate that, compared to traditional monitoring services, and co-management electronic consultations (e-consults), or face-to-face visits, telephone-based of his diabetes with his PCP. This real-life 2) synchronous modalities, such as virtual e-consultation provides comparable story highlights the potential of emerging visits using clinical videoconferencing reductions in A1c levels (from a baseline technologies and implementation of technology (CVT) or telephonic visits. average of 10.1 percent to 8.9 percent non-traditional collaborative care models Although telehealth implementation at six months with sustained benefits in diabetes management. continues to face many challenges, patients at 12 months), but was able to do so with Approximately 30.3 million people in the are becoming increasingly capable of, sub­stantially improved access to care United States carry a diagnosis of diabetes, and receptive to, these models of care. (27 days sooner), reduced travel distances making it the seventh leading cause of According to the fact-sheet published in (431 fewer miles traveled), and reduced time death.1 Concurrent with the escalating February 2018 by the Pew Research Center, engaged in travel/care (9.4 hours less time).7 prevalence of diabetes, there is an increasing about three-fourths of U.S. adults own a These data demonstrate the potential shortage of physicians and other providers desktop or laptop computer and nearly benefits of telehealth in diabetes care. who are specifically trained to care for half own tablet devices.3 Likewise, the VAPHS is a hub location for specialty care patients with diabetes. According to the proportion of people who own and routinely for veterans enrolled in the western half endocrinology workforce analysis commis­ use smartphones has risen from 35 percent of VISN-4 (Veterans Integrated Service sioned by the Endocrine Society in 2012, in 2011 to 77 percent in 2018.3 Additionally, Network) and serves veterans residing in the shortage of adult endocrinologists is The Associated Press-NORC Center for upstate New York, western Pennsylvania, expected to increase from 1,500 in 2012 to Public Affairs recently conducted a survey eastern Ohio, and adjoining West Virginia 2,700 by 2025.2 Further exacerbating this to evaluate attitudes toward telemedicine and Maryland. The majority of these problem, the 2017 National Diabetes among adults over the age of 40. This veterans reside in rural areas and have a survey revealed that 88 percent of those high prevalence of complex diseases, surveyed would be comfortable using such as diabetes and . telemedicine to receive care, with a comfort level of ~87 percent for caregivers and ~50 percent for patients.4 FALL 2018 | 3 | DIVISION OF ENDOCRINOLOGY AND METABOLISM |

J ­gram ­ologists CMAJ: Can Med J Diabetes Sci Technol. 2014 Sep; 3112-21. 99(9): 2017; E 341-E364. 189(9): Vigersky RA, Fish L, Stewart Hogan A, P, Kutler S, Greenwood DA, HM, Young Quinn CC. Karajgikar N, Detoya K, Beattie J, Lutz-McCain S, https://www.cdc.gov/diabetes/pdfs/data/ 2014; 8(2): 378-389. Effect of Telemedicine on Glycated Hemoglobin in Diabetes: A Systematic Review and Meta- analysis of Randomized Trials. Assoc J. Detoya K, Karajgikar N, Beattie J, Lutz-McCain S, Bourdeaux-Kelly M, Bandi A, et al. Impact of ElectronicConsultationFace-to-faceversus Encounters on Glycemic Control among Veterans with Diabetes. Type-2 Abstract presented at the Endo-2018-Endo Society Annual Meeting and Expo 2018, Chicago, IL. *1st Place in Presidential Competition. Poster Boudreaux-Kelly M, Bandi A, et al. Comparison of E-consults and face-to-face care on costs and glycemic control among veterans with type-2 diabetes mellitus. Abstract presented at 78th Scientific Sessions of the American Diabetes FL. Orlando, Association, statistics/national-diabetes-statistics-report.pdf Ladenson McDermott PW, M, Hupart KH. The Clinical Endocrinology Workforce: Current Status and Future Projections ofSupply and Demand. Clin Endocrinol Metab. care-in-america-increasing-access-to-care/ Telehealth Remote Monitoring Systematic Review: Structured Self-monitoring of Blood Glucose and Impact on A1c. Faruque LI, Wiebe N, Ehteshami-Afshar A, et al. http://www.pewinternet.org/fact-sheet/mobile/ https://www.longtermcarepoll.org/long-term-

6 7 8 process efficiencyfor patients and providers alike. A well-designed telediabetes pro should be nimble and elements have that serve the uniquepopulations needs the of being served. Suchprograms be will increasingly necessary as the gap between the number available of endocrin and the patients requiring endocrine and diabetes care continues rise. to References 1 2 3 4 5

VA PittsburghVA Healthcare System Professor Assistant Clinical Division of Endocrinology and Metabolism University of Pittsburgh Archana Bandi, MD Services Telehealth Director, Clinical Director, E-Consult Services Endocrinology of Division burden on PCPs and puts veterans at risk medicationof errors, often precipitating a need for long-distance travel. For this reason, an additional two half days per month are dedicated specificallyto veterans requiring U-500. In this endocrinologistsway, located at the hub can provide direct care via remote teams that coordinate the and visit long-term care. Technological advances and the innovative application telehealth of hold promise in transforming care delivery and improving than 50 miles from away the hub. Currently, CVT service consists five at the of VAPHS endocrine providers endocrinologists (three and two nurse practitioners) who serve four remote hospitals and more than 15 community-based outpatient . These services are available five half days per week and serve more than veterans 120 per month. Such robust partnerships led to the creation a more of specialized Insulin U-500 CVT clinic in Clarksburg, West Virginia. Complexity care of related to concentrated insulin results in a huge

care for stable complex yet needs of veterans with diabetes who more live specialty care services allows for continuous endocrinologists. Embedding CVT clinics as a part the of between primary care teams and hub telehealth coordinators. Such partnerships led reliablehave to care collaboration for SMBG also are providedfor home discharge, during and/or steroid use or chemotherapy. Alert guidelines for RPM for special circumstances, such as before surgical procedures, following modification and betweenappointments education, and RPM services for SMBG. Incorporation of RPM allows for safe e-consults, CVT clinics, group telediabetes consultations and follow-up care, endocrinologists offer at the VAPHS homes using a variety telehealth of strategies. In addition live, in-person to diabetes care for veterans closer their to service has undergone at the VAPHS a transformation improve access to to Given this acute need, the endocrinology ­ study, whichstudy, adopted an adult distress. 199 of A total couples been have recruited in this study in collaboration with the University Utah. of The investigators are currently in the midst preparing of manuscripts for publication. communal coping. As opposed the to pediatric and adolescent population, few studies been have performed address to how couples cope with during adulthood. The focus on communal coping involves appraisals the by persons with diabetes that the illness shared is (i.e., use relational of language such as “it our is disease” rather than an individual’s disease) and collaborative coping efforts manage to the disease. The data collected through interviews, behavioral observations, and online diary assessments has allowed our investigative measure team to communal coping, diabetes management, distress, stress, and executive function. The study identifyaim to is the daily stressors experienced adults by with type 1 diabetes that poorer are linked to diabetes self- management and distress, examine to the collaborative processes that are associated with better diabetes management and lower distress, levels of and examine to whether executive function abilities modulate the relation collaborative of processes diabetes to management and relationship. Romantic partners are to likely be most strongly affected the by person’s diabetes and most to strongly influence how the personwith diabetes manages his or her disease. study the impactTo the of social environ ment on adults with type diabetes, 1 our collaborative team embarked upon the Diabetes Across Development In Couples (DiADIC) life-span perspective examine to the stressors that diabetes are linked to management and distress during young, middle-aged, and older adulthood. The focus this study of was on the ways that romantic partners may facilitate diabetes management across time through 4

study. Thesestudy. Research on Emerging Adults When compared healthy to 2 An analysis the of transition from the 3 pediatric health care system the to adult health care system showed that an early transition associated is with worse glycemic control ,as well asa host psychosocial of variables (lower social status, nonwhite race, lower likelihood pursuing of college after high school graduation, and lower levels parentalof involvement in their daily lives). year after high school was associated with better adherence, fewer depressive symptoms, and lower risk behaviors among emerging adults with diabetes. In addition, parental support buffered the adverse association between peer conflict and poor glycemic control among young adults with diabetes. controls, those with diabetes did not score higher on depressive symptoms, loneliness, or bulimic symptoms, but did report lower satisfactionlife and lower purpose life over time. study, andstudy, Changing Health (REACH) longitudinal studies revealed that parental involvement in diabetes was a critical determinant self-care of behavior and glycemic control during adolescence — especially for older adolescents. During emerging adulthood, the relationship with parents remained an important influence on health behaviors and psychological well-being. Higher parental support in the the context important of social relationships, most importantly the romantic/marital patients and their families. Self-management diabetes of during adulthood (involving good adherence medication to regimens and behaviors that foster good metabolic control) requires daily self-regulation of emotions,one’s behaviors, and cognitions in the face daily of stressful events dealing both with diabetes one’s (highs and lows in blood glucose) and other domains life of (child-rearing problems, marital conflicts, problems at work, managing other chronic Managingillnesses). daily stress occurs in Because individuals with diabetes are experiencing increasingly longer lifespans, it imperative is understand to use how to support resources enhance to diabetes management and quality in adult life of

, Transition Times , Transition study Teen Health Teen

27 in the27 In order study to these transitions, youth with type 1 diabetes and their nondiabetic peers were recruited and followed until age transitions while also assuming increasing responsibility for their diabetes care and overall health. psychosocial aspects care of delivery betterto understand how young adults with type 1 diabetes navigate these UPMC and CMU realized the need to establish working relationships with experts representing the medical and health care, and shifting relationships with family members, friends, and intimate others. Clinicians and investigators at most youth experience multiple transitions during this developmental period, including changesin lifestyle education, (e.g., occupation, changes living in situation), decline during this period time. of The transition through emerging adulthood is an understudied butimportant period, as important study time to youth with diabetes, as self-care behaviors and glycemic control been have observed to community recognized the multiple challenges facing youth with type 1 diabetes. Adolescence a particularly is investigators at Carnegie MellonUniversity This collaboration(CMU). arose almost two decades ago when the diabetes To address theseTo important and complex issues, UPMC endocrinologists have partnered with Vicki Helgeson, PhD, professor psychology, of and her team of most improve these to likely outcomes remain poorly understood. influence the natural historyof the disease throughout the lifespan, and the yet psychosocial factors that most strongly influence outcomes and the interventions and others with whom they share close relationships. These psychosocial aspects of diabetes the have dramatically potential to Diabetes an is incredibly challenging disease that not only affects those carrying the diagnosis, but also their friends, family, Across the Life Span Life the Across Psychosocial Aspects of Diabetes Management Diabetes Aspects of Psychosocial

| 4 | UPDATE IN ENDOCRINOLOGY | FALL 2018 | 5 | DIVISION OF ENDOCRINOLOGY AND METABOLISM |

Health

2013;

2008; 2014; 33(10): J Soc Person 2018; 52: 228-238. 2013; 30: 610–615. J Pediatric Psych.

J Pediatric Psych. Health Psychology. Health

2016; 35(10): 1047-1058. Ann Behavioral Med. Diabetic Medicine.

2018. Helgeson VS, Palladino DK, Reynolds KA, Becker Van VleetVan M, Helgeson VS, Seltman HJ, Helgeson VS, Reynolds KA, Siminerio L, Escobar couples with :Links mood to and self-care. Korytkowski M, Hausmann LRM. Implications of Supportive and Unsupportive Behavior for Couples with Newly Diagnosed Diabetes. 33(5):497-508. EscobarD, O, Siminerio L. Relationships and health among emerging adults with and without 1 diabetes.Type 1125–1133. Becker Siminerio DJ, LM, Escobar O. Emerging adults with type 1 diabetes: A comparison to peers without diabetes. 38(5): 506–517. Palladino DK, Becker Siminerio DJ, L, Escobar O. Characterizing the transition from pediatric to adult care among emerging adults with 1 Type diabetes. Korytkowski Hausmann MT, LRM. An examination of the communal coping process in couples coping with diabetes. Rel. HausmannMT, LRM. Daily communal coping in Helgeson VS, Mascatelli K, Seltman H, Psychology. O, Becker Parent D. and Adolescent Distribution of Responsibility for Diabetes Self-care: Links to Health Outcomes. Zajdel M, Helgeson VS, Seltman HJ, Korytkowski Palladino DK, Helgeson VS, Reynolds KA, Helgeson VS, Reynolds KA, Snyder PR,

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7 3 4 5 6 References 1

Vicki Helgeson, PhD Director of Graduate Studies Psychology of Professor Carnegie Mellon University Hussain Mahmud, MD Medicine of Professor Assistant Clinical Associate EDM Director Program Mary Korytkowski, MD Professor of Medicine and Improvement Quality of Director ­

study. ­mational support DiADIC among our patients. Likewise, the academic environment at UPMC a fertile is environ ment for multidisciplinary collaborative relationships between clinicians and researchers new create knowledge to that ultimately improves the health and well-being our of patients. after participating in the His hemoglobin had improved over by A1c 1 percent, which he ascribed the to interviews conducted Helgeson’s lab. at Dr. He stated that theinterview process made him and that his wife they realize are in this together and need deal to with his diabetes as a team. Insights gleaned from these studies reveal will novel insights into how addressing stressors, life improving coping skills, and recruiting others in key relationships with patients can improve glycemic control and diabetes outcomes minimizingcontrolling behaviors. an endocrinologist’sFrom perspective, interdisciplinary collaboration with Helgeson’s investigate team to Dr. the psychosocial aspects diabetes of across the lifespan has been very enlightening. It has given collaborating clinical endocrinologists a unique perspective regarding the psychosocial needs our of patient population. This nicely is illustrated a favoriteby anecdote from a patient who returned for an office few a visit months families. Intervention efforts should focus on cultivating emotional support, optimizing more subtle forms infor of that are acceptable patients, to and

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study, and study, looking is In addition, patients who felt 5,6 Communal Health Interactions in with diabetes ought target to couples and aimed at people who are newly diagnosed in preventing complications, these results suggest that early intervention efforts diabetes in the United States and the critical role that self-care behavior plays Given the increasing prevalence type of 2 of theof self) were most affected partner by supportive and unsupportive behavior. unmitigated communion on (focus and involvement with others the to exclusion Furthermore, patients characterized by were identified as being more controlling on a daily basis reported poorer mood. basis, whereas patients whose partners reported a better mood and were more take care to likely themselves of on a daily outcomes. understood and cared for their by partners better psychological and health behavior assessments, it was found that patients who engage in communal coping have consecutive days. Through these all of behavioral observation their of coping, and had them complete daily diaries for 14 partner did not diabetes. have The team interviewed couples in person, conducted a living with a romantic partner, and whose had been diagnosed with type 2 diabetes within the pastyears, five were married or were recruited from the community who diagnosed withtype 2 diabetes, also is being conducted. patients 207 of A total management among adult couples, in which one person recently has been at communal coping and diabetes titled Couples(CHOICE) A parallel study also is being conducted,

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5 6 Mutations at 2 DI a feature is that 4 ECD is a rare is ECD type hematopoietic of 1 V600E mutation encountered in 50 percent cases of proof is an of oncogenic process in this disorder. V600E result in increased kinase activity that enhances cell proliferation and survival activatingby the RAS/RAF/MEK/MAPK Additionalsignaling pathway. mutations in KRAS,NRAS (Q61R), PIK3CA, ARAF, and MAP2K1 been have associated with ECD. Discussion reportWe a rare case non-Langerhans of cell histiocytosis originally described by Jakob Erdheim and William Chester in 1930. neoplasm that characterized is abnormal by proliferation and infiltrationCD68-of positive, CD1a-/S100-negative foamy histiocytescausing xanthogranulomatous inflammation in multiple organs.is It not genetically inherited. Its incidence is unknown, but ~500 cases been have reported in the literature. Although described in all age groups, it most is common in adults with a mean age at diagnosis 53 of years, with a slight male predominance. The discovery BRAF of disease, the endocrinopathy usually persists, as in our patient. This disease can affect any organ system, but the most common clinical manifestation multifocalis cortical osteosclerotic lesions theof diaphyseal and metaphyseal part of long bones percent). Pituitary/ (95 (22 central percent), nervous system pulmonary percent), and percent), (46 (41 cardiovascularpercent) (57 involvement beenhave reported. occurs early in the disease process in ~25 percent patients. of The involvement the of pituitary commonly causes central DI, but it also can cause hyperprolactinemia. and deficiencies whenEven there clear is evidence of radiographic regression the of pituitary

Long segment of medullary sclerosis in

(ECD). He be will treated with vemurafenib.(ECD). and 8th nerve complex, disproportionate enhancement and atrophy, cerebellar along the bilateral cerebellar that folia had progressed compared the to 2012 MRI. A repeat right tibial biopsy at UPMC revealed marrow infiltration with histiocytes(some fibrosis,were lipid laden), and sclerosis trabecularof bone. The histiocytes were highlighted CD163, by CD68, CD14, factor XIIIa, and fascin. scattered A few histiocytes were BRAF V600E immunostain positive. The findingswere consistent with a diagnosis Erdheim-Chester of disease Subsequently, he was seenat UPMC for shoulder pain. noted lesions X-rays theof pedicle the of left shoulder and pelvis, medullary sclerosis in the humeral anddiaphysis (Figure symmetrical 1), lesions in the distal femur and tibia Bonebilaterally. scan and FDG-PET scan showed increased activity in the lesions. A follow-up brain MRI revealed absence theof bright spot, enhancement along the proximal 7th osseous changes in Erdheim-Chester disease. Figure 1. the right humeral diaphysis extending up 15 to cm in length corresponding with increased activity on bone scan. No definite cortical thickening, periosteal reaction, erosive changes, or other aggressive features are seen. The appearance is compatible with

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hospital. His calcium, phosphate, 25 vitaminhydroxy parathyroid D, hormone, and alkaline phosphatase were normal. found on x-ray his tibia, of for which he underwent a bone biopsy with diagnosis atPaget’s a communityof disease (PD) He complained chronic of leg pain since 2005, which became progressively more severe. In 2018, osteosclerotic lesions were mus, dysarthria, gait impairment, and truncal ataxia greater than limb ataxia. The etiology was unclear. duties and lost his job. His brain MRI was reexamined and showed evidence significantof cerebellar midline atrophy. On exam, he exhibited horizontal nystag developed progressive gait instability, slurred speech, and impaired motor coordination. He could not fully perform his work was transient and resolved five later. days A brain MRI was initially interpreted as unremarkable. he months A few later, evaluation lethargy, of confusion, impaired short-term memory, and left lower extremity weakness. The altered mental status resolution the of thickening, his DI never resolved. In 2012, he was admitted the to hospital for DDAVP. He showed no other evidence of DDAVP. anterior pituitary hormone deficiencies. Although subsequent imaging showed CSF examination revealed no evidence infectionof or neoplastic disease. His symptoms DI of were controlled with ologist in 1993 for evaluation DI. of It was concluded that he had lymphocytic infundibulitis based on the findingof a pituitary stalkthickened on MRI, while with bone pain and ataxia. He was initially referred an endocrin to Case Presentation male with a priorA 47-year-old history of central diabetes insipidus presented (DI) Patient with a Longstanding History of Central Diabetes Insipidus Diabetes Central of History a Longstanding with Patient An Interesting Case of Ataxia and Osteosclerotic Bone Lesions in a in BoneLesions and Osteosclerotic Ataxia Case of Interesting An

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2015; 2014 Jul 24; N Engl J Med. Blood. 2017; 10: 501-507. 2010; 49: 1203. 2011; 2778–2782. 117: 2013; 72: 1691. Blood. Case Rep Oncol.

http://erdheim-chester.org/diagnosis/ Dagna L, Girlanda S, Langheim S, at al. Vemurafenib in MultipleNonmelanoma Cancers With BRAF V600 Mutations. 373: 726. faceted Clinical Presentations and Manifestations of Erdheim-Chester Disease: Comprehensive Review of the Literature and of 10 New Cases. Ann Rheum Dis. Chester Disease: Case Report With Aggressive Multisystem Manifestations and Review of the Literature. Erdheim-Chester Disease: Report on a Case and New Insights on Its Immunopathogenesis. (Oxford). et al.Janku Consensus F, Guidelines for the Diagnosis and Clinical Management of Erdheim-Chester Disease. 483-92.124(4): JE, Wechsler B, Perez-Pastor G, Blomberg B, Fuzibet JG, Dubourguet et al. CNS Involvement F, and Treatment With Interferon-alpha Are Independent Prognostic Factors in Erdheim- Chester Disease: A Multicenter Survival Analysis of 53 Patients. docs/label/2017/202429s016lbl.pdf Alotaibi S, Alhaifi O, Nasr H, et al. Erdheim- Cavalli G, Guglielmi B, Berti A, et al. The Multi Diamond EL, Dagna L, Hyman DM, Cavalli G, Arnaud L, Hervier B, Neel A, Hamidou MA, Kahn https://www.accessdata.fda.gov/drugsatfda_ Hyman DM, Puzanov I, Subbiah et al. V,

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Blood. Eur J Intern Virchows Arch Arch Virchows Sue M. Challinor, MD Medicine of Professor Division of Endocrinology and Metabolism Mihaela Oprea, MD Fellow Division of Endocrinology and Metabolism Rheum Dis Clin North Crit Rev Oncol Hematol. 1930; 279 (2): 561–602. 2015 223-9. May; 26(4): 2013; 39(2): 299-311. Haroche J, Charlotte Arnaud F, L, at al. High Haroche J, Arnaud L, Cohen-Aubart et al. F, Chester Lipoid W. Granulomatose. Am. Dagna L. Erdheim-Chester Disease. Med. Cristallo Lacalamita M, Ingravallo G, Silvestris F, Dammacco Erdheim-Chester F. Disease: A Review. Systematic Jul; 95(1): 1-11. Erdheim-Chester Disease. Pathol Anat. Prevalence of BRAF V600E Mutations in Erdheim-Chester Disease But Not in Other non-Langerhans CellHistiocytoses. 120(13): 2700-2703. Campochiaro C, Tomelleri A, Cavalli G, Berti A, Cives M, Simone Rizzo FM, V, Dicuonzo F,

3 4 5 diagnosis of ECD, a multisystemdiagnosis ECD, of hema topoietic neoplasm. His diagnosis was challenging due the to fact rare is that ECD and has features that overlap with other more common medical conditions. References 1 2 Conclusion In summary, report we an unusual case of a young male who initially presented with central DI associated with thickening the of pituitary stalk on MRI, and a presumed diagnosis lymphocytic of infundibulitis. More he than developed 10 years later, ataxia, bone pain, and multifocal osteo sclerotic bone lesions. The bone lesions were initially misdiagnosed but as PD, a repeat bone biopsy led the to correct masses and for palliation boneof pain can also be employed as management options.

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MRI the of brain, 8 9 Surgical debulking large of 11-13 recently approvedfor the these by FDA patients. BRAF vemurafenib, inhibitor, which was for BRAF V600E, such as our patient, the initial recommended treatment with is the For symptomatic patients who are positive have beenhave some have shown to clinical efficacy but provide no survival benefit. V600E mutation, treatment with interferon alpha can improve survival. If symptomatic and without the BRAF no evidence central of nervous system involvement or any organ dysfunction. patients who are asymptomatic and have and some patients can be asymptomatic for decades. not is necessary Treatment for The clinical course variable, is ECD of extremities are recommended for staging in patients with ECD. of chest,of abdomen, pelvis, and distal long bones specifically. cardiac MRI, bone scan, andPET/CT bone lesions are bilateral in ECD and symmetric, and affect the diaphysis the of a feature In in contrast PD. the PD, to abnormalities seen in ECD are characterized osteoscleroticby lesions, which also are of theof for BRAF V600E. The bone of involvedof tissue (bonepreferred) along with genetic testing or immunostaining provided his correct diagnosis. The diagnosis bestis made on histopathologicevaluation biopsywith immunostain for BRAF V600E This patient’s bone lesions were initially misdiagnosed but as PD, a repeat bone Wegener’s granulomatosis, neurosar PD, coidosis, mycobacterial disease,and more. and includes Langerhans cell histiocytosis, The differential diagnosis broad is ECD of ­

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The gene 9

Through an NIH Mentored 10 ­ility broader of and more long-term ­crine function, physiology and During postdoctoral my training at the University Pittsburgh, of I was fortunate be supportedto a well-established by institutional training program and by the NIH. I was initially recruited the to University with the support the of NIH T32 Program Research in Endo Training highly associated with BMI and obesity risk in a specific human population. harboring this variant has been shown to influence glucocorticoidreceptor stability and responses stress to in preclinical models. Research Career Development I amAward, now using background my in neuroanatomy/development, neuro endo sex-differences,behavior, and systems genetics approaches examine to the impact this gene of and its risk variant on action within the hypothalamus in a sex-dependent manner. These studies reveal novel are to likely insights the into interaction between sex and glucocorticoid action in early development and their impact on metabolic outcomes in adulthood. and Collaborative Research Supportive Environment at the Pittsburgh of University These studies also important have implica tions for future research. Specifically, these sex-dependent effects glucocorticoids of on early neurodevelopment and subsequent physiology and behavior support the possib effects on a variety outcomes of in later life. In particular, glucocorticoids are well known profoundhave to effects on energy and metabolic , suggesting that these same processes in early develop may profoundly affect risk obesity of and metabolic disease in adulthood. Researchers at the University Pittsburgh of recently have identified a novel obesity-risk variant thatis ­

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In

­ 7,8 We found that We 5,6 the sexually dimorphic dexamethasone transcriptome in mouse cerebral cortical and hypothalamic embryonic neural stem cells. The results provided insight into the mechanisms fetal of glucocorticoid exposure on hypothalamic neurodevelop ment, as well as their long-term behavioral and physiological consequences in both males and females. These results also highlight the importance sex of as a biological variable in biomedical research. amus, as well as behavioral outcomes extending through early adulthood. gain furtherTo insight the into underlying mechanismsthesefor effects, subsequentlyI joined the laboratory Donald of B. DeFranco, PhD, at the University Pittsburgh of as a NIH T32-funded postdoctoral My scholar. research objective characterize was to how glucocorticoid exposure impacts gene regulation in the developing hypothalamus in a sex-specific using manner, systems- wide molecular genetic approaches. doing so, identified we and characterized dissertation in the laboratory Stuart of A. PhD, at ColoradoTobet, University, State researchmy objective determine was to the sex-specific impactof glucocorticoid excess duringfetal development on the development,vascularization, cellular composition, and function specific of hypothalamic nuclei. glucocorticoid exposure had significantly different effects on male and female fetuses, including on the cellular com position and function the of blood-brain barrier in specific nucleiof the hypothal Sex-Specific Differences Sex-Specific in Neurodevelopment in Pre-Clinical Research researchMy program focuses on sex- dependent effects a variety of factors of on early neurological development and their subsequent impact on physiology and behavior in adulthood. During my

3

Proposed Proposed 4 As such, 1 In 1993, 2 the sexes. Another between

­uation males of fivetimes more impact sex of on normal physiology and disease, thereby ensuring that new knowledge can be translated both to men and women. cost performing of studies. Overcoming these challenges critical is for enhancing our fundamental understanding the of received any formal training in the proper evaluation sex of differences. Finally, evaluating both sexes increases time and a particular outcome in both sexes, they are not necessarily powered detect to differences concern that is many investigators not have are often performed in males with only confirmatory studiesfemales. in Likewise, even if studies are powered evaluate to eval frequently than females. when Even both sexes are included, comprehensive studies a legitimate scientific rationalefor not doing so. Despite these recommendations, preclinical studies continue favor to a biological variable preclinical to research involving cell and animal models. studies are now strongly encouraged to include if not, both include sexes to or, responses across sexes in human research. not until JanuaryHowever, 2016 did the NIH extend similar consideration sex of as women comprise half all participants. of This important achievement has broadened our understanding diversity of in biological priorities, including increased emphasis on sex as a biological variable. the NIH Revitalization Act mandated the inclusion women of in clinical trials, and now the largest supporter medical of research than billion(more $37 per year). the NIH a major is driver research of BiomedicalResearch The National Institutes Health of (NIH) is Neurodevelopment, Physiology, and Behavior Physiology, Neurodevelopment, in Differences Sex Sex-Dependent Effect of Steroid Hormones on Hormones Steroid of Effect Sex-Dependent A Junior Faculty’s Perspective on Career Development at the University of Pittsburgh of the University at on CareerDevelopment Perspective A Junior Faculty’s

| 8 | UPDATE IN ENDOCRINOLOGY | FALL 2018 | 9 | DIVISION OF ENDOCRINOLOGY AND METABOLISM |

2017 Am J Mol Cell 2015 2018 Aug Biol Sex J Endocr Soc. Mol Endocrinol. Brain Struct Funct. Mol Cell Endocrinol. 2016 Sep; 48(9): 1049-1054. 1991 Jun; Suppl): 53(6 1586S-1594S. 2015 Sep 3; 6: 14. Dec; 5140-50. 32(24):

Mauvais-Jarvis Sex Differences F. in Metabolic Frahm KA, Handa RJ, SA. Tobet Embryonic Frahm KA, Waldman JK, Luthra S, Rudine AC, https://www.niddk.nih.gov/health-information/ 2016 Jan; 30(1): 144-54. Monaghan-Nichols Chandran AP, UR, DeFranco DB. A Comparison of the Sexually Dimorphic Dexamethasone Transcriptome in Mouse Cerebral Cortical and Hypothalamic Embryonic Neural Stem Cells. Biol. Differ. Differ. files/NOT-OD-15-102.html Perspective on Its Etiology in Polynesians. Clin Nutr. Exposure Dexamethasone to Affects Non- Neuronal Cells in the Adult Paraventricular Nucleusof the Hypothalamus. Jul; 2225-34. 220(4): AB, Couger MB, et al. Research Resource: The Dexamethasone Transcriptome in Hypothalamic Embryonic Neural Stem Cells. 15; 471: 42-50. Cheng H, et al. A Thrifty Variant in CREBRF Strongly Influences Body Mass Index in Samoans. Nat Genet. Amor TR, McCluggage AR, Liang Turner PV, G, Cai K, Lu R. Luman/CREB3 Recruitment Factor Regulates Glucocorticoid Activity and Is Essential for Prolactin-Mediated Maternal Instinct. health-statistics/-obesity Homeostasis, Diabetes, and Obesity. Dec 28; 2(2): 140-153. Blood-Brain Barrier Within the Paraventricular Nucleus of the Hypothalamus: Influence of Fetal GlucocorticoidExcess. Frahm KA, Peffer ME, Zhang Luthra JY, S, Chakka Minster RL, Hawley NL, Su C, Sun G, Kershaw EE, Frahm KA, SA. Tobet Development of the Martyn AC, Choleris E, Gillis Armstrong DJ, JN, https://grants.nih.gov/grants/guide/notice- McGarvey Obesity ST. in Samoans and a

8 3 4 5 7 9 10 References 1 2 6

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Krystle A. Frahm, PhD Research Instructor in Medicine Division of Endocrinology and Metabolism Metabolism at the University of Pittsburgh and currentlyis funded an NIDDK by Mentored Research Scientist Career Development Award. also received Frahm the EndocrineDr. Society atEarly the Investigator annual Award meeting in March 2018. ology and Metabolism at the University Pittsburghof providesan exceptional environment for career development and research success. I look forward a long to career tackling the most critical questions the related to impact sex-dependent of effect steroid of neurodevelopment, on hormones physiology, and behavior. Krystle A. an is PhD, Instructor Frahm, in Medicine in the Division of Endocrinology and the University Pittsburgh of provides outstanding research infrastructure and core resources that helped drive my research and career development forward. This includes resources for genome-wide studies, DNA and synthesis protein and sequencing, animal care, proteomics, imaging, biostatistics, and metabolic studies. I continue benefit to from ongoing multidisciplinary collaborations with expert researchers in a variety fields, of including , , pharmacology, vascular medicine, bioinformatics, and genetics. Thus, the Division Endocrin of the supportive and collaborative research environment both within and outside the Division Endocrinology of and Metabolism,

­ships provided through the T32 were Development In Award. addition (K01) to Association Postdoctoral Fellowship, and an NIH Mentored Research Scientist instrumental in securing an NIH Loan Repayment an Award, American Diabetes tion postdoctoral experience. I am confident that these consistent and valuable rela- were leaders in their fields and had observed progressionmy from the beginning of my network well-established of researchers who and routine interactions set up through the T32.During grant submissions, I had a I personally benefited from these established would the devote majority time my of to researchmy and career development. meetings. This support ensured that I provided a stipend, research funds, and financial supportto attend scientific career development workshops further to scientificmy development. The T32 also goals, and participated in grantwriting and University, met with committee my annually progress my review to and future sessions other to T32 scholars and faculty from within the Division and across the quarterly during the Research in Progress and a rich environment expand to my knowledge. I presented research my resources acquire to new technical skills, , protected focus time to on newmy research project, structure and Pittsburgh. This opportunity provided me with an instant network experienced of running training grant at the University of This training grant has been in place for more than 40 years and the is longest crinology, Diabetes, and Metabolism. , ,

­standing Continued on 11 Page (Clinical Fellow), under the Fellow), (Clinical Hussain Mahmud, MD received the 2018 Frederick DeRubertisDr. Division Endocrinology of Golden Apple Teaching for outAward achievement in endocrine MD, Sue Challinor, Mary Korytkowski, MD Shane LeBeau, and MD, Susan Greenspan, MD, were selected as Pittsburgh Magazine’s “Best Doctors 2018.” fellow education. Neha Karajgikar, MD

, (left) won First Place in the Presidential Poster Competition , (Clinical (Clinical Fellow) right, and Fellow) (Clinical Hira Ali, MD under the Fellow), mentorship Erin of E. and MD, Kershaw, Iva Miljkovic, PhD, MD, won First Place in the fellow postdoctoral was promoted Chief to Endocrinology of at UPMC McKeesport. Sann Yu Mon,Sann Yu MD Archana Bandi, MD present this work at the 2018 American Diabetes Association Annual Meeting. This work supported is an by Endocrine Fellows Foundation Research Grant. category at the 2018 Pitt Health Disparities Research for her Day research entitled “Wny Pathway Inhibitor DKK1: A Potential Novel Biomarker for Ectopic Skeletal Muscle She was Adiposity.” also invited to Karla Detoya, MD mentorship of in the Healthcare Delivery and Education Category at the 2018 Endocrine Society Annual Meeting for their research entitled “Impact Electronic of Consultation Compared Face-to- to EncountersFace on Glycemic 2 Diabetes.” Control Among With Type Veterans

,

,

, , under Lucas Heller, MD Arslanian, received MD, the 2018 Outstanding Abstract at the Award Joon Kim, Young PhD Postdoctoral (T32-funded under theScholar), mentorship Silva of Healthcare System HealthcareSystem the mentorship Harsha of Rao, received MD, the Investigator Award Young for Clinical Research Pittsburghat the 2018 VA invited to presentinvited to her poster entitled “Readmission and Comprehension of Janya Swami, MD under Fellow), (Clinical the mentorship Mary of Korytkowski, was MD, Faculty), under the Faculty), mentorship Erin of and MD, Kershaw, Don DeFranco, PhD, received the Early Investigators Krystle Frahm, PhD (K01-funded Junior 2018 American Diabetes Association 78th Scientific Sessions. “Glycemic Management and Mortality in Patients Undergoing CABG.” He was also present invited to this work at the Research for his project Day entitled 2018 Endocrine Society Annual Meeting. Diabetes Education at Discharge” at the Inflexibility, Impaired Lipolysis and Diminished Oxidation Fat in Obese Girls with Polycystic Syndrome (PCOS).” 2018 Endocrine Society Annual Meeting for his research entitled “Metabolic Award at the 2018Award Endocrine Society Annual Meeting. Awards and Accomplishments and Awards Department News

| 10 | UPDATE IN ENDOCRINOLOGY | FALL 2018 | 11 | DIVISION OF ENDOCRINOLOGY AND METABOLISM | ,

2018 May. 46(5):369-377. 2018 May. Ingrid Libman DeGordon, MD, PhD 2018 Jul;36(3):244-250. 2018 and Diagn Cytopathol. 2018;7(4):e10009, DOI: 10.2196/10009, 2018;7(4):e10009, Clin Diabetes.Clin JMIR ResJMIR Protoc. 2018; 6(7): e10206. Epub ahead print. of Thomas Songer,PhD, Erin Kershaw, MD, 29610111.

PMID: Li C, Hayes L, J, ChuWang CF, Siminerio L. Diabetes Educators’ Insights Regarding Connecting Mobile Phone – Collected – and Wearable Tracker Self-Monitoring Information a Nationally- to Used for Diabetes System Education: Descriptive Quality Study. MhealthJMIR Uhealth. Second Annual UPMC Alumni and Friends Reception where colleaguesand invited guests enjoyeddrinks and hors d’oeuvres, and had the opportunity network. to University Pittsburgh of faculty Notable Recent Publications RiedlingerMon G, SY, Abbott CE, Seeethala Nikiforova R, MN, Ohori Nikiforov YE, NP, Hodak Cancer Risk and ClinicopathologicalSP. Characteristics Thyroid of Nodules Harboring Thyroid- stimulating Hormone Receptor Gene Mutations. At theAt ADA The UPMC Division Endocrinology of and Metabolism was once again well represented at the 2018 American Diabetes Association Scientific Sessions in Orlando, Florida.Faculty and fellows presented research findings andclinical findings, and servedinvited as speakers and symposia chairs. UPMC and the Division Endocrinology of and Metabolism also hosted their Lutz-McCain SJ, Bandi A, Larson M. Advancing Patient Safety and Access Concentrated to Insulin (U-500 Regular Health in the Insulin) Veterans Administration: A Clinician Education Program in the Primary Care Setting. J, ColemanWang DC, Kanter J, Ummer B, Siminerio L. Connecting Smartphone and Wearable Fitness Data with a Nationally Tracker Used Electronic Health Record for Diabetes System Education Behavioral Facilitate to Goal Monitoring in Diabetes Care: Protocol for a Pragmatic Randomized Multi-Site Trial. (pictured left right, to were all members above) Annual the of ADA Sessions Organizing Committee and hosted the reception.

, received ­crinology and received his DVM atreceived his DVM

pleted his postdoctoral postdoctoral his ­pleted , Biological Sciences with Jeffrey Peters, PhD, at State Pennsylvania University. He then com Bokai Zhu, PhD his PhD in Veterinary and PhD Rajiv Gandhi College of Veterinary and Animal Science and his Masters in Animal Biotechnology from the Indian Veterinary Sadeesh Ramakrishnan, Sadeesh

professor in September 2018. of the Aging Institute at the University of Pittsburgh as a tenure stream assistant He joined the Division Endo of circadian and non-circadian biological clocks that influence metabolism and aging. research program focuses on understanding on focuses program research the molecular mechanisms underlying Biology at Baylor College Medicine. of His fellowship with Bert O’Malley in the Department Molecular of and Cellular professor in August 2018. of Pittsburgh as a tenure stream assistant Endocrinology and the Pittsburgh Liver Research Center at the University of regulation in normal metabolism and disease. He joined the Division of of hypoxia signalingof and transcriptional Physiology at the University Michigan. of His research program focuses on therole Department Molecular of and Integrated Toledo. He thenToledo. completed his postdoctoral Shah,fellowship PhD, with in the Yatrik Najjar, PhD, at theNajjar, Center for Diabetes and Endocrine Research at the University of PhD in Biomedical Sciences with Sonia M. Research Institute. He then received his New Faculty

Continued from 10 Page DepartmentNews 200 Lothrop St. Pittsburgh, PA 15213-2582

OPEN FACULTY POSITIONS

Director, Multidisciplinary Thyroid Center (MTC). Academic Clinical Endocrinologists. The Division Academic Research Faculty. The Division of Endo­- The Division of Endocrinology and Metabolism of Endocrinology and Metabolism at UPMC crinology and Metabolism at the University of Pitts- at the University of Pittsburgh and its affiliated seeks full-time BC/BE Endocrinologists to join burgh seeks MD, MD/PhD, or PhD scientists for medical center, UPMC, seeks an MD or MD/PhD our premier, academic, high-volume outpatient full-time, tenure stream, academic faculty positions board-certified endocrinologist for a full-time and inpatient practices. Our nationally ranked (assistant to full professor) in the fields of obesity, academic faculty position as the Director of its Endocrinology program provides a diverse patient diabetes, metabolism, nutrition, and/or metabolic Multidisciplinary Thyroid Center (MTC). The mix and substantial opportunity for academic and disease prevention. All types of research in these successful candidates should have leadership career growth. Successful candidates will have a areas will be considered (basic, translational, clinical, experience, strong academic expertise in thy­roid- strong foundation in endocrinology and diabetes, epidemiological, health outcomes). Physician scientists ­ology / , and a desire to participate in and a desire to participate in all aspects of the and candidates with cross/multidisciplinary research all aspects of the academic mission (clinical care, academic mission (clinical care, education, and programs are particularly desirable. Successful education, and scholarly work). Candidates with scholarly work). Candidates with an interest in candidates will have a history of academic research research experience/interests/qualifications and telehealth are particularly desirable to help grow scholarship, a strong publication record, and a demon- potential for external funding are highly desirable. our expanding telehealth program. strated capacity to secure external research funding.

Interested candidates should send a cover letter, curriculum vitae, and contact information for three references to Erin E. Kershaw, MD, Chief of Endocrinology and Metabolism, care of Chelsea Dempsey (email: [email protected]). EEO/AA/M/F/Vets/Disabled.

DIVISION OF ENDOCRINOLOGY AND METABOLISM ADDRESS CORRESPONDENCE TO: Division of Endocrinology and Metabolism 200 Lothrop St. Clinical Treatment Areas: Research Areas of Focus: W1055 BST • Diabetes • Healthy Lifestyles and Behaviors Pittsburgh, PA 15213 • Obesity • Diabetes Education and Management Phone: 412-648-9770 • Lipid Disorders • Type 1 Diabetes and Pancreatic Islet/ Biology • and Metabolic • Type 2 Diabetes and Bone Disorders • A $19 billion world-renowned health care provider • Hypothalmic, Pituitary, and • Obesity, , and Adipose Tissue Disorders and insurer, Pittsburgh-based UPMC is inventing new models of patient-centered, cost-effective, Adrenal Disorders • Lipid Disorders accountable care. UPMC provides more than • Reproductive Hormonal Disorders • Muscle Metabolism and Function $900 million a year in benefits to its communities, including more care to the region’s most vulnerable • Thyroid Disorders • Osteoporosis and Metabolic Bone Disorders citizens than any other health care institution. The largest nongovernmental employer in Pennsylvania, • Endocrine Neoplasias • Thyroid Cancer Molecular Diagnosis UPMC integrates 85,000 employees, 40 hospitals, 600 doctors’ offices and outpatient sites, and a 3.4 million-member Insurance Services Division, A Resource for You: UPMC Physician Resources brings world-class physicians and free educational the largest medical insurer in western Pennsylvania. As UPMC works in close collaboration with the opportunities to your computer. Learn new information while watching CME-accredited videos in the University of Pittsburgh Schools of the Health Sciences, U.S. News & World Report consistently convenience of your home or office. Find out more atUPMCPhysicianResources.com/Endocrinology . ranks UPMC Presbyterian Shadyside on its annual Honor Roll of America’s Best Hospitals. UPMC Enterprises functions as the innovation and commercialization arm of UPMC, and UPMC To learn more about the UPMC Division of International provides hands-on health care and management services with partners around the Endocrinology and Metabolism, please visit world. For more information, go to UPMC.com. UPMCPhysicianResources.com/Endocrinology. USNW509004 AS/MP 9/18 © 2018 UPMC