bluuebunny/crossref_metadata_2025 huggingface dataset:
SAT-147 Endogenous Expression of TCF21 by CRISPR/dCas9 System Results in Different Biological Responses in Adrenocortical Carcinoma and Hepatocarcinoma
Authors: Kremer Jean Lucas , Passaia Barbara dos santos , Lotfi Claudimara Ferini Pacicco
Published: May 2020

Transcription factor 21 (TCF21/POD-1/Epicardin) inhibits the expression of SF-1 (NR5A1) by binding to the promoter E-box site in adrenocortical carcinoma (ACC). In contrast, TCF21 promotes increased expression of LRH-1 in hepatocarcinoma cell line, HepG2 cells, by binding to the Small Heterodimer Partner (SHP/NR0B2) promoter region, an LRH-1 negative regulator. Epigenetic alteration induced TCF21 loss of function and has been associated with increased of cellular migration and invasion. In ACC, TCF21 promoter is hypermethylated and less expressed. Our aim was to evaluate the effect of TCF21 by expressing or silencing TCF21 in adrenocortical pediatric adenoma, ACA-T7 cells, in ACC cell lines SW-13 and H295R cell line, and in HepG2 cell line. Were used CRISPR/dCas9/TCF21 and pCMVMycPOD1 or siRNATCF21 to express and silence TCF21, respectively. Increased expression of TCF21 in H295RpCMVMycPOD1 and SW-13CRISPR/dCas9/TCF21 cells resulted in significantly decreased cell migration and invasion (53.2±36.1%/70.8±26.5% and 82.6±4.2%/100%, respectively). In ACA-T7/siRNATCF21 cells, the inhibition of TCF21 resulted in significant increase migration and invasion capacity (45.0±12.7%/33.1±17.4%) compared with ACA-T7 cells. Higher TCF21 expression in HepG2CRISPR/dCas9/TCF21 increased invasion [147.08±16.54% (p<0.0001)]. Analysis of metalloproteinase genes expression showed that TCF21 significantly (p<0.01) increased MMP8 expression in SW-13CRISPR/dCas9/TCF21 and H295R/pCMVMycPod-1 whereas decreased MMP9 and MMP2 (p< 0.0001). The opposite effect was observed in ACA-T7/siRNATCF21. Moreover, in HepG2CRISPR/dCas9/TCF21 cells was observed an increase of MMP2 and MMP9 expression (p<0.001). These results suggest that TCF21 regulate epithelial mesenchymal transition and vice versa (EMT/MET) in tumors depending on cellular context. Supported by Fapesp and Capes.
SAT-210 When Acne, Hirsutism and Menstrual Irregularities Are More Than PCOS
Authors: Rios Paola , Zuniga Gabriela , Manzano Alex
Published: May 2020

Background: Polycystic ovarian syndrome (PCOS) mimics non-classic congenital hyperplasia (NCCAH), presenting with hyperandrogenic symptoms. NCCAH is usually diagnosed later in life, where 21-hydroxylase (21OHD) is the most common deficiency. There are more than 300 mutations in 21OHD, being V281L one of the described mutations.

Clinical Case: 23 y/o female patient G0P0 comes to the office complaining of irregular periods, frontal hair loss, weight gain, acne and hirsutism. She has had noticed these changes since menarche; however, her acne was getting worse. Was seen 2 months prior to presentation by her gynecologist who order a free Testosterone that was elevated (6.4 pg/mL, n<4.2 pg/mL), with normal TSH (1.1 uIU/mL, n,0.45-4.5). She was not taking any medication. Her mother has history of 2 spontaneous abortions and her sister has acne and hirsutism as well. On physical exam BMI was 26, it was noticed comedones and papules on her face, back and shoulders. Ferriman-Gallwey scale was >8. At the initial visit due to the clinical scenario, it was thought that she had hyperandrogenic syndrome, probably secondary to PCOS. Serum blood test were ordered and showed an elevated total testosterone (71 ng/dL, n,8-48ng/dL), free testosterone (8.4 pg/mL, n<4.2 pg/mL), 17- OH pregnenolone performed by liquid chromatography-tendem mass spectrometry (LC-MS/MS) was (429 ng/dL, n, 35-290 ng/dL luteal phase) and androstenedione LC-MS/MS (1941 ng/dL, n, 41-262 ng/dL) which confirmed NCCAH diagnosis due to 21OHD. She had no desire to become pregnant at the time of evaluation; however, was concern about fertility and genetics. Was started on OCPs and genetic testing was positive for V281L mutation in the CYP21A2 gene, being homozygous for this mutation. Three months after, her acne and frontal hair loss were better, and a trial of spironolactone 50 mg daily, was prescribed. For her sister and mother was suggested to consult endocrinology, due to possible same disease.

Conclusion: this case highlights the importance of recognizing NCCAH as a cause of hyperandrogenism. Molecular genetic analysis should be offered with genetic counseling to patients, since they can carry a severe allele which can affect their progeny. Clinicians should be aware of the importance of family history when diagnosing NCCAH on their patients; for detection, treatment and genetic counseling of NCCAH on family members as well, as found in this case.
MON-013 Effect of Poor Circumstance in Utero on Adiponectin Gene Expressions Through Epigenetic Changes in Offspring
Authors: Masuyama Hisashi , Mitsui Takashi , Eto Eriko , Hayata Kei
Published: May 2020

The links between obesity and metabolic syndrome in parents and their offspring and the role of genes and a shared environment are not completely understood. Adipocytokines play important roles in glucose and lipid metabolism. We have already developed the model mice for transgenerational effect of obesity and metabolic syndrome and demonstrated that exposure to a high fat diet in utero might cause a metabolic syndrome-like phenomenon through epigenetic modifications of adipocytokine, adiponectin and leptin gene expressions in offspring of the model mice. In this study, we examined whether poor circumstance in utero affected the adiponectin gene expression and epigenetic changes of this gene using samples from umbilical cord in patients with hypertensive disorder of pregnancy (HDP) and fetal growth restriction (FGR) or gestational diabetes mellitus (GDM) and heavy for date fetus (HFD) compared with normal pregnant women without HDP, GDM and abnormal fetal growth. We observed that the poor circumstance under HDP with HGR or GDM with HFD caused significantly lower adiponectin gene expression and higher methylation level of histone H3 at lysine 9 of the promoter of adiponectin gene compared with normal control. Thus, poor circumstance in utero affected adiponectin gene expressions through epigenetic modifications, which might result in the increased risk for metabolic syndrome of offspring.
SUN-206 A Rare Case of Untreated Congenital Adrenal Hyperplasia Leading to Gender Dysphoria and a Female to Male Transgender
Authors: Awad Dana , Win Htet Htet , Zena Mohsen
Published: May 2020

Background: CAH is a common genetic disorder usually diagnosed in early childhood. However, when it is detected in adulthood, different approach and treatment strategies need to be undergone as their needs are generally different from those of children with CAH.

Case presentation: A 49-year-old male with a past medical history of recurrent urinary tract infections was admitted to the hospital with sepsis and was treated with antibiotics. CT abdomen during admission showed an incidental finding of markedly enlarged bilateral adrenal hyperplasia with an 8x5.5x5.8 cm left adrenal mass, as well as two ovaries and a uterus. Upon further history, the patient said he knew that he was born with abnormal genitalia and had a prolonged stay in the hospital immediately after birth and had surgery of his genitals at the age of six months. He was always told by his family that he is a female, although he never felt it, and he continued to identify himself as a male throughout his life.

He only had one menstrual period at the age of thirteen. He participates in sexual activities as a male but was never able to have a normal sex life. He also gave a history of salt cravings, where he consumes dry salt. He was not taking any home medications.

On examination, the patient had a male voice, a beard, male body hair distribution, no breast. The genital exam revealed labia majora, no labia minora. The rest of his examination was unremarkable.

Work up for CAH revealed normal range plasma metanephrines and DHEA. But ACTH, androstenedione, 17-OH progesterone were all elevated (90.4 pg/ml, 2737 ng/dl, and 24191 ng/dl respectively) and levels were all higher after Cosyntropin stimulation test. He was found to have primary adrenal insufficiency with a maximum cortisol level of 13.3 mcg/dl after the stimulation test.

He was started on oral Hydrocortisone and was closely followed by endocrine after discharge where long-term treatment plans were discussed and our patient decided that he wants to continue his life as a male, and was evaluated by Urology as well as OBGYN for left adrenalectomy and hysterectomy with bilateral Salpingo-Oophorectomy that was successfully performed a month later. Pathology of his left adrenals showed adrenocortical hyperplasia without evidence of malignancy. Patient was educated about lifelong corticosteroid treatment and that he would need to start testosterone replacement therapy to keep his male characteristics.

Conclusion: When children with CAH lose follow up and don’t receive treatment early in life, they can develop gender dysphoria, and their approach as adults become more challenging and it needs a multidisciplinary team to treat, address their needs and detect complications of prolonged adrenal stimulation. Additional research to the natural history and optimal interventions is needed to improve outcomes as these cases are not encountered frequently in clinical practice.
SAT-386 Inconsistent Bilateral Arm Serum PTH Testing in Recurrent Hyperparathyroidism in a Patient Status-Post Parathyroid Auto-Transplantation
Authors: Jenkins Craig , Kemm Matthew , Jenkins Lydia
Published: May 2020

Background: More than 95% of patients with primary hyperparathyroidism will be cured with the initial operation by an experienced surgeon. However, localization of hyperparathyroid recurrences, especially after extensive surgery becomes challenging. For patients with transplanted parathyroid glands into the forearm, there may be utility in bilateral arm serum PTH testing to help with localization.

Clinical Case:

A 65-year-old woman presented to the clinic with primary hyperparathyroidism in 2008. After a localization study, she had a partial parathyroidectomy but continued to have persistent biochemical hyperparathyroidism despite negative localization studies. She was then referred to another institution for further studies. Follow up Sestamibi scans were negative but 4D-CT scans assisted in localizing the presence of a superior parathyroid gland adenoma which was later removed in 2011. During this time, the left inferior parathyroid gland was auto-transplanted into the left forearm. Again, her calcium and PTH levels rose despite negative Sestamibi scans showing no abnormalities in post-operative beds or in the forearm. Review of previous labs revealed elevated PTH levels in the ranges of 80-110 pg/mL since 2012-2019. The patient’s most recent PTH was 2408 pg/mL. At that point, the decision was made to repeat the labs on the left and right forearms simultaneously and labs showed PTH levels of 1283 pg/mL and 118 pg/mL, respectively. Repeat Sestamibi scan following these labs demonstrated evidence of increased radiotracer uptake in the region of the prior transplanted parathyroid tissue with no neck uptake concerning for hyperparathyroidism due to auto-transplanted hyperplastic tissue.

Conclusion:

This case demonstrates the utility of bilateral arm serum PTH testing in the evaluation of recurrent hyperparathyroidism in patient’s status-post parathyroid auto-transplantation.
MON-160 The Burdens of Adrenal Insufficiency: A Survey Study from Two Tertiary Care Centers in the United States
Authors: Genere Natalia , Li Dingfeng , Xhikola Majlinda , Behnken Emma , Abbondanza Tiffany , Vaidya Anand , Bancos Irina
Published: May 2020

Background: Adrenal insufficiency (AI) is a chronic disorder necessitating life-long replacement. Patients’ quality of life and health outcomes depend on knowledge and comfort level with self-management.

Objective: To determine patients’ knowledge in regards to diagnosis and management, estimate burden of disease and to identify predictors of adverse outcomes in patients with AI

Methods: Survey study of patients with AI evaluated at two tertiary medical centers between 2015 and 2019. Collected variables included data on circumstances of AI diagnosis, symptoms, management, burden of disease, and overall well-being.

Results: Among 785 patients (mean age at diagnosis 44.2 ± 18.0, 64% women, and 92% Caucasian), 310 (40%) had primary AI (PAI), 255 (33%) had secondary AI (SAI) not related to glucocorticoid use, and 211 (27%) had steroid-induced AI (SIAI). Patients were diagnosed with AI after presenting with symptoms for a median of 1 year (0-6), 28% with symptoms lasting >2 years, 44% visiting emergency room (ER) at least once prior to diagnosis. A third of patients reported a discordant diagnosis from their medical record.

Baseline glucocorticoid replacement therapy included hydrocortisone (HC) in 447 (59%), median of 20 mg (IQR 15 - 25mg), prednisone in 190 (25%), median of 5 mg (IQR 4 - 7.5mg), other regimens in 38 (5%), and no steroids in the remainder (85, 11%); 197 (26%) patients reported daily equivalent HC dose of >25 mg. Overall, 549 (73%) of patients reported use of stress dose steroids at least once per year, higher in patients taking HC >25 mg/day (3.2 vs 2.7 times per year if HC<25mg/day, p=0.01). Improper use of stress steroids was reported in 193, 25% patients. Patients taking HC>25 mg /day reported a higher number of adrenal crises (1.6 vs 1.3 in patients on HC<25 mg/day, p=0.04). Among 314 (41%) patients who reported ER visits due to adrenal crisis, only a third received prompt glucocorticoids.

One third of patients described their general health as fair or poor. Predictors of negative perceptions of overall health included SIAI (OR 6.2 and 2.5, vs PAI and SAI respectively), poor understanding of diagnosis (OR 2.6), daily HC>25 mg (OR 2.1), and presence of at least one adrenal crisis (OR 2.3) (p<0.001 for all).

Conclusion: Patients with AI experience delay in diagnosis, and a third do not fully understand their diagnosis. In addition to patient education, interventions to improve general health and outcomes may include selecting a physiological glucocorticoid replacement therapy, prevention of adrenal crisis, and improving ER care.
SUN-607 Iron Parameters in Patients with Partial Lipodystrophy and Impact of Metreleptin Therapy
Authors: Boutros Sabine , Akinci Efe Yagiz , Ryan Benjamin , Sargin Pinar , Akinci Baris , Swaidan Mario , Neidert Adam , Hench Rita , Horowitz Jeffrey , Oral Elif A
Published: May 2020

Introduction Intriguing rodent studies and epidemiological data suggest that iron metabolism and adipocytokines crosstalk to regulate glucose metabolism and fuel storage. Iron parameters have not been previously studied in patients with lipodystrophy whereas increased iron stores have been associated with type 2 diabetes. In this study, we sought to investigate the status of iron parameters in patients with partial lipodystrophy (PL) and to interrogate whether the adipocyte hormone leptin can modulate iron metabolism. Methods Serum samples of 19 patients with PL (age: 42, IQR: 34-57, M/F: 3/16) were used from an open-label study previously performed at the University of Michigan evaluating the efficacy of metreleptin in nonalcoholic steatohepatitis (NCT01679197) to measure ferritin, hepcidin, iron, and transferrin soluble receptor levels. High-sensitivity C-reactive protein (hs-CRP) levels were also determined as broader changes in inflammatory pathways may potentially impact circulating ferritin levels. Results were integrated into an existing database of metabolic parameters. Data are presented as median, IQR. Results At baseline, ferritin levels were positively correlated with fasting glucose (r = 0.533; p = 0.023) and HbA1c (r = 0.510; p = 0.031). During the 6 months of therapy period, HbA1c (9.2%, 7.3-10.3 vs. month-3: 8.6%, 7.7-9.6; p = 0.099; and month-6: 8.5%, 6.8-9.5; p = 0.264), triglyceride levels (346 mg/dL, 240-1771 vs. month-3: 346 mg/dl, 237-479; p = 0.047; and month-6: 295 mg/dl, 207-495; p = 0.091), and hepatic fat (12.7%, 9.8-20.6 vs. month-6: 8.9%, 7.0-11.0; p = 0.031)} decreased. Reductions were observed in serum ferritin after metreleptin treatment (83.23 ng/mL, 76.43-178.97 vs. month-3: 73.79 ng/ml, 68.30-78.59; p = 0.007; and month-6: 61.03 ng/mL, 46.45-157.74; p = 0.004). There was a tendency for hepcidin and iron to be decreased, but this did not reach statistical significance. On the other hand, there were notable reductions in hs-CRP levels at 6 months compared to baseline (2.94 mg/L, 1.30-4.80 vs. 1.6 mg/L, 1.00-6.30; p = 0.012). Baseline leptin level was inversely correlated with percent reduction in hs-CRP at month-6 (r = -0.685; p = 0.001). Also, modest correlations were observed between changes in serum iron and triglycerides (r = 0.491, p = 0.033) and hepatic fat (r = 0.412, p = 0.079). Conclusions We observed a significant relationship between ferritin and glucose control in a group of patients with PL. Metreleptin therapy was associated with improvements in triglycerides and hepatic fat and there were also significant decreases in ferritin and hs-CRP levels. These results raise the possibility that metreleptin therapy influences iron metabolism. However, whether the decrease in ferritin indicates a decrease in iron stores or is mediated by an effect on inflammation remains unknown.
MON-207 Validating and Optimizing the Guideline Criterion for Skipping Confirmatory Tests of Primary Aldosteronism
Authors: Hu Jinbo , Wang Kanran , Yang Shumin , Li Qifu
Published: May 2020

Abstract

Background: Confirmatory tests of primary aldosteronism (PA), including saline infusion test (SIT), captopril challenge test (CCT) and fludrocortisone suppression test (FST), are recommended by the Endocrine Society Clinical Practice Guideline. In order to simplifying diagnostic process, a criterion for skipping confirmatory tests was established by the guideline, while the evidence is lacking.

Objective: To validate and optimize the guideline criterion for skipping confirmatory tests.

Design: Prospective diagnostic study.

Setting: Chongqing, China.

Measurements: A total of 501 patients with high risk of PA were retrospectively enrolled. All of them completed at least two confirmatory tests (CCT, SIT, and FST). The guideline criterion is: history of spontaneous hypokalemia, plasma renin concentration (PRC) below detection levels and plasma aldosterone (PAC)>20ng/dl (550pmol/L). An optimized criterion (history of spontaneous hypokalemia, PRC <2.5 uIU/ml and PAC>20 ng/dl) was established based on the guideline criterion. Parameters such as sensitivity, specificity and area under the receiver-operator characteristic curves (AUC) were calculated to compare the diagnostic value of these two criteria.

Results: Using SIT, CCT and FST (cutoffs: PAC post-SIT 10 ng·dl-1; PAC post-CCT 11 ng·dl-1; PAC post-FST 6 ng·dl-1) for PA diagnosis, the specificity of the guideline criterion was 1.00 (0.98–1.00), 1.00(0.98–1.00) and 1.00(0.97–1.00) respectively, while the sensitivity was 0.12 (0.09–0.17), 0.12(0.08–0.16) and 0.09(0.06–0.12) respectively. Compared to the guideline criterion, the sensitivity of the optimized criterion was significantly improved [SIT: 0.42 (0.36–0.49); CCT: 0.41 (0.35–0.48); FST: 0.30 (0.25–0.34), all the P values < 0.001 when compared to the guideline criterion]. However, the specificity of the optimized criterion was similar to the guideline criterion (all the P values>0.05).

Limitation: This study was carried out in a single center.

Conclusions: The guideline criterion shows high specificity but low sensitivity for direct diagnosis of PA. The optimized criterion has greatly improved the sensitivity and may be more suitable for skipping confirmatory tests of PA.
MON-171 Characterization of the Adrenal Gland and Adrenal Rest Tissues in Congenital Adrenal Hyperplasia
Authors: Kolli Vipula , Werneck Isabela , Kim SunA , Mallappa Ashwini , Gaynor Alison , Quezado Martha , Merke Deborah P
Published: May 2020

Background: Adrenonodular hyperplasia and tumor formation are common long-term complications of congenital adrenal hyperplasia (CAH) driven by chronic ACTH elevation. Clinical studies indicate that the majority of males with classic CAH have testicular adrenal rest tumors (TART). Ovarian adrenal rest tumors (OART) are less commonly observed. Little is known about the pathophysiology of adrenal rest, however both adrenal cortex and Leydig cell markers have been described in TART, suggesting a pluripotent embryological cell origin.

Objective: To characterize adrenals and adrenal rest tissues of patients with CAH in comparison with normal tissues.

Materials and Methods: Using immunohistochemistry (IHC) and, real-time qRT-PCR we investigated CAH-affected adrenals (n=5), adrenal rest tissues (n=2; 1 testicular, 1 ovarian), controls [normal adrenal (n=2), testis (n=1), and ovary (n=1)]. Tissue sections prepared from paraffin embedded tissue blocks were immunostained with adrenal [melanocortin 2 receptor (MC2R), delta-like homolog 1 (DLK-1), steroidogenic factor 1 (SF-1), steroidogenic acute regulatory protein (StAR) and other cytochrome P450 genes], inflammatory [interleukin 2 receptor (IL-2R), B-lymphocyte antigen (CD20), cluster of differentiation 3 (CD3), tumor necrosis factor alpha (TNFα), interleukin 6 (IL6)], and gonadal markers [progesterone receptor (PR), androgen receptor (AR), insulin-like 3 (INSL3)]. RNA was isolated and gene expression studies were performed. High-throughput RNA sequencing technology was used to analyze the differential transcriptome profiles between the CAH adrenals, adrenal rest and normal tissues.

Results:

In contrast to the controls, CAH adrenals and adrenal rest tissues showed the following:

(i) IHC studies revealed 95% of tissue positive for adrenal zona-reticularis; (ii) significant nodular lymphocytic infiltration with a predominance of B and T lymphocytes and overexpression of lymphocyte markers IL-2R, CD20, CD3, and inflammatory cytokines TNFα and IL6; (iii) increased expression of adrenocortical specific genes MC2R, DLK1.

Conclusion: CAH-affected adrenals and adrenal rest tissue have similar predominance of zona reticularis and demonstrate lymphocytic infiltration. Active inflammation may play a role in the abnormal development of adrenal and adrenal rest tissue in CAH patients.
OR09-03 Brain Aromatase Is Essential for Regulation of Sexual Activity in Male Mice
Authors: Brooks David C , Zhao Hong , Coon V John , Ercan C Mutlu , Dong Hongxin , Levine Jon E , Bulun Serdar Ekrem
Published: May 2020

Introduction: The biologically active form of estrogen, estradiol (E2), has important organizational roles in brain development and activational roles in adult brain physiology and behavior. It has been proposed that E2 formation in the brain might regulate sexual activity in various species. The mechanisms that link estrogen formation in the brain and sexual behavior, however, remain unclear. Aromatase is the key enzyme that catalyzes the conversion of testosterone (T) to E2 in the testis and brain of male mice. To determine the role of brain aromatase in male sexual activity, we generated a brain-specific aromatase knockout (bArKO) mouse model. Additionally, a newly generated total aromatase knockout (tArKO) mouse model served as a positive control. Methods: We generated the floxed aromatase mice (Aromfl/fl), which flanked the transcription and translation start sites and the common splice acceptor site for the upstream brain promoter I.f of the aromatase gene. We then crossed Nestin-Cre mice with Aromfl/fl mice to generate bArKO mice. Using the same Aromfl/fl mice, we bred tArKO via crossing with ZP3-Cre mice. Circulating and tissue (brain and testis) E2 levels were measured using liquid chromatography-tandem mass spectrometry. We assessed sexual activity in 12-14 week-old bArKO, tArKO and littermate control males over two 30-minute trials. The interactions were monitored and videotaped, and the videotape was scored for the sexual activity. To investigate whether the lack of estrogen production in the brain was causative for altered sexual behavior, 20 bArKO and 20 control mice were castrated at ~nine weeks of age and supplemented with exogenous sex hormone via 60-day time release pellet implantation. Results: E2 levels are significantly decreased in the brain but not the testis of bArKO mice as compared to control mice (P < 0.05, n=6-12). As expected, E2 levels in the brain and testis are significantly lower in tArKO mice compared with their WT littermates (n=6-9). Furthermore, we demonstrate that local aromatase expression and estrogen production in the brain is required for male sexual behavior and sex hormone homeostasis. Male bArKO mice exhibited significantly decreased sexual activity in the presence of strikingly elevated circulating T (n=5). In castrated adult bArKO mice, administration of E2 together with T restored maximum sexual behavior (n=5). Thus, aromatase in the brain is necessary for T-dependent male sexual activity. We also found that brain aromatase is required for negative feedback regulation of circulating T of testicular origin. Conclusion: Our findings suggest T activates male sexual behavior in part via conversion to E2 in the brain and provide the foundation for inhibition or enhancement of brain aromatase enzyme activity and/or utilization of selective estrogen receptor modulators in modifying sexual behavior.

DCB and HZ contributed equally to this work.
SUN-650 Body Composition Assessment in Clinical Practice: Use in Rheumatoid Arthritis and Hypogonadism
Authors: da Silva Marina Sousa , Borges Joao Lindolfo
Published: May 2020

BACKGROUND: DXA is an accessible, non-invasive method, also used for body composition assessment, standing out for regional composition analysis. In clinical practice, the analysis of body composition is relevant by differentiating lean (fat-free) mass from fat mass. The higher the fat to lean mass ratio, the greater the obesity-related comorbidities.

CLINICAL CASE:

Case 1: A 22-year-old male, BMI 21kg/m2, with rheumatoid arthritis (RA) and on chronic glucocorticoid (GC) performed a DXA to evaluated body composition. The first analysis, during GC use, showed 26.1% fat (14.6kg) despite the low BMI. The patient, evolved stable from RA, and was able to stay out of GC for 2 years, with no other interventions. A new DXA showed a decrease in fat percentage to 12.6% (6.2kg), a reduction in total body weight (-7kg) and an increase in lean mass (+1.2kg). Within 16 months of GC reintroduction, the fat percentage increased up to 36.8% (23.8kg), the total weight increased by 15.6kg and the lean mass decreased by 2.1kg.

Case 2: A 40-year-old male with hypogonadism showed 37% fat (33.8kg) on ​​first DXA evaluation. Testosterone replacement was started, and a new DXA was performed after 10 weeks, and although the total weight increased by 3.1kg, there was a decrease in fat mass to 33.5% (31.6kg) and an increase of 5.3kg in lean mass. After 3 years, there was a reduction to 27.1% of fat (24.5kg) and, after 4 years of therapy initiation, the percentage of fat was 26.9% (24.5kg). There was no change in diet or exercise.

CONCLUSION:

The exposed cases highlight the importance of body composition assessment in patients with conditions that interferes with energy metabolism. The patient on chronic GC use, after medication withdrawal, presented a significant decrease in fat mass, more pronounced in the android percentage. The reintroduction of the CG showed an increase in fat percentage, with android predominance. The patient with hypogonadism, in the second evaluation performed with only 10 weeks of treatment with testosterone, evolved with a reduction in fat mass associated with an increase in lean mass, besides a reduction in the android percentage.

The reported cases illustrate everyday clinical situations in which disease vs. treatment significantly changes body composition. Assessment of body composition is essential in patients exposed to conditions that interfere with energy metabolism since obesity is associated with chronic comorbidities and cardiovascular outcomes.
MON-922 Multiple Endocrine Neoplasia Type 1- A Clarion Call for Clarity
Authors: Hashmi Hiba , Fish Lisa
Published: May 2020

A 35-year-old gentleman presented with epigastric pain and bilious emesis. He also endorsed urinary frequency, non-bloody diarrhea and diffuse bone pain. On physical examination he had epigastric tenderness and multiple hyperpigmented skin lesions.

An abdominal computed tomography (CT) scan revealed multiple diverticula with peri-colonic fat stranding in the descending and sigmoid colon, concerning for diverticulitis. He was started on a course of metronidazole and ciprofloxacin. A 3.1 cm mass was incidentally noted in the uncinate process of the pancreas. Bilateral adrenal nodules were also appreciated.

An endoscopic ultrasound (EUS) guided trans-gastric fine needle aspiration biopsy was performed, revealing a well differentiated pancreatic neuroendocrine tumor (pNET - pT3N1Mx, intermediate risk). Chromogranin A was elevated to 108 ng/ml (reference range <93 ng/ml). Serum and urine metanephrine, V-peptide, gastrin, glucagon and parathyroid hormone related peptide were all normal; indicating a nonfunctioning neuroendocrine tumor. He underwent a pancreaticoduodenectomy. Octreotide scan was unrevealing for residual uptake. Adrenal biopsy revealed adrenal adenomas.

Three years later, he presented with severe abdominal pain and a new pancreatic mass was noted on CT. Chromogranin A was elevated to 227 ng/mL. EUS revealed a 0.35 cm mass in the bed of the pancreatic head, encasing the superior mesenteric artery. Pathology was positive for recurrence of the neuroendocrine tumor.

He was hypercalcemic to 11.4 mg/dL and parathyroid hormone was elevated to 319 pg/mL. CT neck revealed a 0.1 cm nodule concerning for parathyroid adenoma. He underwent a subtotal parathyroidectomy.

Genetic testing confirmed Multiple Endocrine Neoplasia Type 1 (MEN1) with a heterozygous mutation of the menin1 gene.

MEN1 is a rare genetic syndrome with affected individuals at increased risk of developing pancreatic, pituitary, parathyroid gland and cutaneous tumors. With a kaleidoscope of presentations, clinicians must maintain a high index of suspicion for MEN1, particularly for cases with nonfunctioning pNETs which present insidiously and are the foremost cause of mortality in MEN1 patients.1

Further clarity is needed on MEN1 associated pNET prognostic risk stratification, surveillance and targeted immunochemotherapy.2 Timely and algorithmic screening for MEN 1 syndrome in patients with pancreatic incidentalomas is essential to improving patient outcomes.

1.

Kamilaris CDC, Stratakis CA. Multiple Endocrine Neoplasia Type 1 (MEN1): An Update and the Significance of Early Genetic and Clinical Diagnosis. Front Endocrinol. 2019;10:339. doi:10.3389/fendo.2019.00339

2.

Yates CJ, Newey PJ, Thakker RV. Challenges and controversies in management of pancreatic neuroendocrine tumours in patients with MEN1. Lancet Diabetes Endocrinol. 2015;3(11):895-905. doi:10.1016/S2213-8587(15)00043-1
MON-287 Expression of Programmed Death-Ligand 1 (PD-L1) in Human Pituitary Neuroendocrine Tumor
Authors: Suteau Valentine , Collin Alexandre , Menei Philippe , Rodien Patrice , Rousselet Marie-Christine , Briet Claire
Published: May 2020

Introduction

Some Pituitary NeuroEndocrine Tumors (PitNET) present an aggressive evolution and are resistant to standard management. Immunotherapy have shown durable efficacy in a variety of malignancies. The aim of this study was to explore the programmed death-ligand 1 (PD-L1) expression in varied subtypes of pituitary adenomas with assessment of their clinical behavior at diagnosis and follow-up.

Methods

We conducted a retrospective monocentric study, including all patients operated a PitNET between 2012 and 2018. PDL-1 immunostaining were performed using an European Conformity-In-Vitro-Diagnostic labeled anti-PDL1 antibody (Clone 22C3). PD-L1 immunostaining was evaluated as the percentage of tumor cell showing positive membrane staining, into four grades: grade 0 = <1%, grade 1 = 1 to 5%, grade 2 = 6 to 49% and grade 3 = ≥ 50%. PD-L1 expression was compared with tumor features (secretion, proliferation, invasion) and outcome.

Results

The study included one hundred and thirty-nine PitNET, including 84 (60%) nonfunctioning adenomas. Twenty-five PitNET were PD-L1 positive (18%), including 3 grade 3, 8 grade 2 and 14 grade 1. PD-L1 expression was not different between functioning and non-functioning adenomas (p=0.26). Among sixteen tumors with proliferative markers (Ki-67 ≥ 3% and p53 positive), only one was PD-L1 positive.

Conclusion

In our series, pituitary tumors rarely exhibit PD-L1 expression and this immune marker did not seem to be associated with any biological characteristic or behavior of the pituitary tumors. Thus, PD-L1 staining is necessary before considering PD-L1 blockage in PitNET, in case of therapeutic impasse.
SUN-292 Life-Threatening Hypernatremia in Partial Diabetes Insipidus with Adipsia Due to Cranial Radiation: Diagnostic and Therapeutic Challenges
Authors: Laghi Franco , Sarkar Sauradeep , Singh Amteshwar , Kaur Arshpreet
Published: May 2020

Background: Anterior pituitary dysfunction is a known, time and dose dependent effect of cranial radiotherapy but central diabetes insipidus (CDI) has been rarely reported. We present a patient with partial CDI (PCDI) and adipsia, months after subtotal resection and radiation therapy for a large anterior cranial fossa meningioma.

Clinical Case: A 53-year-old woman with history of subtotal resection of a 7 cm meningioma ~2 years ago and radiation therapy (54 Gy, completed 15 months ago), was admitted to the ICU with obtundation, tachycardia (120/min), hypotension (87/52 mmHg, on vasopressors in the first 24 hours), severe hypernatremia (serum Na 170 mmol/L), and acute kidney injury (creatinine 2.11 mg/dL; baseline 1.0 mg/dL). Plasma osmolality (pOSM) was 385 mOsm/kg and urine osmolality (uOSM) was 982 mOsm/kg. MRI brain 3 months ago showed frontal lobe encephalomalacia, residual meningioma at the planum sphenoidale (1.8x3.5x2.8 cm) with cavitary lesion compatible with post-radiation necrosis. After receiving 4 litres (L) isotonic fluids and 5 L hypotonic fluids in the first 38 hours, serum Na was 168 mmol/L, creatinine 1.35 mg/dl and uOSM 386 mOsm/kg. Urine output was 2.6 L on day-1 and 1.9 L during first 7 hours on day-2. After an IV dose of 2 mcg DDAVP, uOSM increased to 784 mOsm/kg, and Na decreased to 164 mmol/L, supporting CDI diagnosis. ACTH stimulation test was normal. Levothyroxine 50 mcg daily was started for central hypothyroidism. By day-6, her mental status returned to baseline (alert only to person). DDAVP dose adjustment was challenging due to frequent fluctuation in her serum Na (130s to 150s), adipsia and urinary incontinence. On day-44, she was discharged on subcutaneous (subQ) DDAVP 0.25 mcg every 36 hours, with a serum Na of 145 mmol/L. She was readmitted 3 days later with serum Na of 164 mmol/L, followed by another prolonged hospitalization complicated by acute kidney injury and popliteal DVT. On day-64, she was discharged to a nursing facility on DDAVP 0.25 mcg subQ twice daily.

Clinical Lesson: Delayed PCDI with adipsia is an exceedingly rare but challenging complication of cranial radiation therapy. The initial uOSM (twice as high as pOSM) in our case caused a delay in diagnosis. This could reflect enhanced antidiuretic response to low circulating ADH levels, possibly due to lower rate of solute extraction in dehydration, upregulation of ADH receptors due to chronic hormone deficiency, and to a fall in glomerular filtration rate. Decrease in uOSM after hydration could be due to ADH exhaustion.
MON-906 MULTIPLE ENDOCRINE NEOPLASIA TYPE 2A: Familiar Case Report
Authors: Sousa Barbara K P , Calasans Camila R , Scardua Deborah F , Azevedo Potira A G , Ricardo Gustavo P , Pires Andre D A , Maciel Mirele P , Santos Lucas R , Oliveira Marco A C , Biscolla Rosa P M , Scalco Renata C , Bueno Cristina B F , Scalissi Nilza M , Lima Jose Viana
Published: May 2020

Introduction: Multiple endocrine neoplasia type 2A (MEN 2A) is a autosomal dominant transmission inherited syndrome which oncogenesis is based on germline mutations with RET proto-oncogene function gain. Patients have medullary thyroid carcinoma (CMT) and some develop unilateral or bilateral pheochromocytoma and/or primary hyperparathyroidism, its frequency depends on the inherited RET mutation. We present a case of a mother and daughter with marfanoid habitus and MEN 2A syndrome confirmed by genetic analysis that identified mutation in the RET gene, codon 634.Clinical cases: 35-year-old woman with weight loss, sweating, nausea, hypertensive peaks, syncope episodes and marfanoid habitus, with plasma metanephrines 9.1nmol/L (RV<0.5), bilateral adrenal tumors on MRI (4.7x4.5x3.3 cm left adrenal and 7.4x7.3x6.3 cm) and MIBG scintigraphy high uptake bilateral, with diagnosis of bilateral pheochromocytoma. She also had calcitonin 49.40pg/mL (RV<6.4), calcium 11.9mg/dL (RV 8.6-10.2), PTH 372.7pg/mL (RV15-65) and cervical ultrasound (USG) with solid and hypoechogenic thyroid nodule, diagnosed with CMT and primary hyperparathyroidism with 6 possible parathyroid glands by SPECT CT scintigraphy. Genetic panel by NGS identify germline mutation in RET códon 634 - minsense mutation: c.1900T>C. The patient denied prior family history. In the familiar screening, her 18-year-old daughter has a marfanoid habitus, serum calcitonin 48.8pg /mL (RV<9.8), CEA 3.8ng/mL(RV<3.0), cervical USG shows a thyroid nodule of 0.7x0.5x0.5cm, solid, hypoechoic, with microcalcifications and a central compartiment lymph node, whose puncture calcitonin > 2000pg/mL and 118pg/mL, respectively. She features plasma metanephrines 0.5mmol/L (RV<0.5), normal plasma normetanephrines, MIBG scintigraphy and adrenal MRI without alterations and absence of primary hyperparathyroidism. She has the same mutation as her mother.Conclusion: Although rare, it is essential to know the clinical and laboratory changes in MEN 2A in order to enable early diagnosis and treatment. Also, investigate every first-degree relative is important so complications and mortality of this syndrome can be reduced.
MON-393 Evaluation of Bone Mass in Transgender Women After Gender Affirming Surgery - a Pilot Study
Authors: Fighera Tayane Muniz , da Silva Eliane Dias , Borba Gustavo da Silva , Spritzer Poli Mara
Published: May 2020

Estrogen deficiency is classically associated with bone loss in both men and women. In transgender women, after being submitted to gender-affirming surgery (GAS), the main goal of hormone therapy (HT) is to maintain the female phenotype and prevent the consequences of the orchiectomy-related hypogonadal state. The aim of this study was to evaluate the impact of GAS on bone mass in transgender women. A total of 142 trans women attending the outpatient Gender Identity Program were sequentially enrolled. Patients aged < 20 and > 60 years (n=15), with gluteal silicone prosthesis (n=26) and without FSH dosage after surgery (n=9) were excluded. Anthropometric evaluation, laboratory tests and dual-energy X-ray absorptiometry (DXA) were performed in all patients during the follow-up. In women undergoing CAS (CAS-Y), DXA was performed at least 12 months after surgery and with estrogen therapy. In the other women (CAS-N), tests were performed after at least 3 months of standardized treatment (estradiol plus spironolactone or cyproterone acetate). Patients with testosterone values still above the reference for women were not excluded as long as they were on regular HT. Ninety two trans women were included. Among them, 30 had performed CAS, and had DXA assessment performed 37 months (21-78) after surgery. The mean age and BMI were 37 years (33 - 46) and 24.9 kg/m² (23.1 - 27.5) in patients CAS - Y and 30 years (24 - 36) and 24.3 kg/m² (21.5 - 28.5) in patients CAS - N. Trans women CAS-Y were significantly older (p=0.000). No difference was observed regarding estradiol levels between the groups [105.7pmol/L (48.4-207.8) and 147.5 pmol/L (71.9-284.5), p=0.622]. Free androgen index (FAI) was significantly higher [0.45 (0.17 - 1.63) and 4.47 (0.70 - 36.4), p=0.002] and FSH significantly lower [60.4mIU/ml (37.9 - 75.6) and 2.6mIU/ml (0.6 - 4.4), p=0.000] in trans women CAS - N. BMD (g/cm²) and Z-score of lumbar spine, femoral neck and total femur did not differ significantly between the groups. Considering all participants, the lumbar spine BMD was negatively correlated with FSH levels (r=-0.343, p=0.005), which remained significant even after adjustments for FAI. When only CAS - Y trans women were considered, a negative correlation was found between FSH levels and lumbar spine (r=-0.598, p=0.001) and hip (r=-0.404, p=0.033) BMD. In a multiple regression model adjusted for age and surgery, women with FSH > 35 mIU/ml presented a prevalence rate ratio of 11.79 for low bone mass (p=0.040, IC 95% 1.19 - 124.39). The results of this pilot study in trans women show no difference in bone mass according to GAS status. However, long-term elevated FSH levels observed in some post GAS - trans women, even on HT, presented a negative association with bone mass. Further studies with greater sample sizes are needed to confirm the impact of GAS on bone mass and fracture risk.
MON-119 Osteoporosis Practice: A Pilot Survey of Primary Care Medical Residents
Authors: Yatavelli Rajini Kanth , Craven James , Millar Morgan , Bakian Amanda V , Sundaresh Vishnu
Published: May 2020

Background: Patients with osteoporosis are not adequately managed. This pilot study was aimed at evaluating primary care medical residents’ confidence and knowledge to diagnose and treat osteoporosis.

Methods: A 16-item, a paper-based de-identified survey was administered to all participating primary care medical residents at two independent University programs. Questions collected information on resident demographics, prior endocrinology exposure through a rotation or a didactic in osteoporosis, future career plan, and assessed confidence and knowledge about screening, diagnosis, and management of osteoporosis. Wilcoxon rank-sum tests were used to compare mean ranks and tetrachoric correlations were used to assess the correlation between variables.

Results: A total of 66 (24.4%) residents completed the survey with 59% being male, 64% were in the 1st and 2nd year of training (junior residents) and 36% were in their 3rd and 4th year of training (senior residents). Forty-eight percent had completed endocrinology rotation and 74% had attended a didactic in osteoporosis.

Residents who had an endocrine rotation had significantly higher confidence (p= 0.003) and knowledge (p= 0.04) to diagnose and treat osteoporosis. Residents who attended endocrine didactics had significantly higher confidence (p=0.04) but no difference in knowledge (p= 0.1). Senior residents had a positive correlation between confidence and knowledge (rho= 0.4, p=0.02). There was no difference in confidence level between males and females. Senior residents who had completed an endocrinology rotation were more likely to respond that they feel confident to obtain osteoporosis history and perform a physical exam compared to those who had not completed an endocrinology rotation (p=0.04). Female junior residents who attended didactics were more likely to respond that they have a higher confidence level to screen (p=0.02) and diagnose (p=0.007) osteoporosis compared with female junior residents who did not attend didactics. There was a strong positive correlation between confidence and knowledge for osteoporosis screening among senior residents who attended didactics (rho=0.8, p<0.0001) and for female residents overall (rho=0.75, p<0.0001). Confidence and knowledge for management of osteoporosis were highly correlated among junior residents who had completed endocrine rotation (rho=1, p<0.0001).

Limitation: Limitations of this study include its small sample size and lack of generalizability.

Conclusion: This pilot study provides important insights into the confidence and knowledge among in-training primary care medical residents in two independent University programs. Curriculum development should focus on practical and measurable modules to improve resident knowledge. Findings from this survey need to be replicated in a larger sample size study.
MON-289 Pituitary Metastasis: A Systematic Review
Authors: Parekh Shrina , Kalidas Poonam , Fung Russell K , Hernandez Maria Del Mar Morales , Santhoshi Rupa , Gandhi Gunjan Yogendra
Published: May 2020

Metastatic lesions to the pituitary are uncommon as well as concerning as they do not always have a characteristic radiographic appearance and can be easily missed. We conducted a systematic review of all the published cases and case series of pituitary metastasis to further understand the unique characteristics of these lesions. Using Pubmed and Embase as the primary search engines, we reviewed all cases published from January 1980 to July 2019. A total of 175 unique cases were included in the study. Over 400 cases were collected amongst which a total of 278 cases were included in the study. As part of a challenge with any retrospective study some data points were missing from cases reviewed. Only English language publications were included in the study. The study revealed a predominance of females with 121 cases. Median age was noted to be 61 years. Only 40 patients had previously known metastatic disease. 70 patients were noted have primary cancer arising in the breast which was noted to be the most common primary cancer followed by 64 cases of primary cancer arising from the lungs. Majority of the patients (162 cases) had pituitary hypofunction with deficiency of one or more pituitary hormones. 97 cases were reported to have diabetes insipidus on presentation. Only 40 patients had no visual field deficits whereas 77 patients were reported to have abnormal eye movements. Displacement of the gland superiorly towards optic chiasm was the most common radiographic features in 137 reported cases. Although not commonly reported in most of the published literature, 45 cases were noted to have bony erosion due to expansion of the gland. Only 5 cases were reported to have no contrast enhancement, although many case reports did not specify contrast enhancement of the pituitary. 22 cases were noted to have an aggressive or rapid growth pattern of the pituitary. 13 cases were noted to have edema around the optic chiasm. The pituitary should not be overlooked as a site of metastasis. Many cases can present asymptomatically without biochemical or radiographic characteristics of metastatic lesion. Any biochemical or clinical sign of pituitary pathology in a patient with known cancer should raise suspicion for sellar metastasis. Unique radiographic characteristics should alert the clinicians to consider this possibility. Our study revealed many unique characteristics of metastatic lesions of the pituitary. This should allow clinicians to become aware of the more common findings in these patients allowing prompt diagnosis.