bluuebunny/crossref_metadata_2025 huggingface dataset:
PSUN254 Hirata's Disease - An Unexpected Surprise
Authors: Al-Bahadili Huda , Chang Alan , Nasiri-Ahad Wazhma
Published: November 2022

The diagnosis of hypoglycemia in adults without diabetes mellitus is a medical challenge. Insulin autoimmune syndrome (IAS), also known as Hirata's Disease, is a rare condition characterized by episodes of spontaneous hypoglycemia secondary to hyperinsulinemia in the setting of positive insulin autoantibodies. 380 cases of IAS have been reported worldwide between 1970 and 2009 with majority of cases seen in patients of Asian descent. Here we present a case of a patient who presented with episodes of recurrent hypoglycemia secondary to IAS.85 year old Asian female presented to the endocrinology office for recurrent episodes of presyncope which were associated with presumed hypoglycemia. Patient denied a history of gastric bypass surgery, diabetes, use of oral hypoglycemic agents, change in eating habits, fevers, weight loss, or night sweats. A continuous glucose monitor was placed during the visit due to patient having difficulties using a glucometer and on follow-up, multiple episodes of hypoglycemia were noted, dropping down to 50mg/dL throughout the day. Due to recurrent symptomatic hypoglycemic episodes, she was admitted to the hospital for a workup. Point of care (POC) glucose on presentation to the ED was 166 mg/dL. 4 hours later in the ED, POC glucose was 42 mg/dL with serum confirmation of 44 mg/dL. Last meal was about 6 hours prior to this event and no dextrose containing solutions were used in the ER. Prior to correction of hypoglycemia, blood specimen sent for the following: c-peptide 3.4 ng/mL, beta-hydroxybutyrate 0.12 mmol/L, insulin level 285 µIU/mL, and proinsulin 93.7 pmol/L. Sulfonylurea screen was negative. CT pancreas with IV contrast showed no evidence of pancreatic mass suggestive of insulinoma. Due to recurrent episodes of hypoglycemia in the hospital, the patient was started on Diazoxide 50 mg every eight hours. An insulin antibody level sent from the initial specimen, eventually resulted and was elevated to above 50 U/mL. A comprehensive review of the patient's medications was performed; none were new or were associated with autoantibody formation. Patient denied recent symptoms of viral illness or family history of hypoglycemia. Literature review revealed the possible benefits of acarbose over diazoxide in management of IAS; diazoxide was switched to acarbose 50 mg three times a day before meals. Outpatient follow-up showed drastic reduced frequency of hypoglycemia while on Acarbose.IAS is a rare but important etiology of hypoglycemia in adults without diabetes mellitus. IAS involves the formation of insulin autoantibody complexes, which binds to the insulin receptors and prevents insulin from binding to its receptors in the postprandial phase. Insulin is then released from the complexes irrespective of blood glucose concentrations, therefore inducing postprandial hypoglycemia. Prompt recognition and diagnosis of IAS can allow for appropriate treatment and avoidance of performing unnecessary imaging and invasive procedures.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
PSUN260 Diabetic Myconecrosis: a Rare Complication of Uncontrolled Diabetes Mellitus
Authors: Joseph Marina , Ram Roopa , Ambrogini Elena
Published: November 2022

Introduction

Spontaneous diabetic myonecrosis is a rare and underdiagnosed microvascular complication of long standing and poorly controlled diabetes mellitus. The pathogenesis of this infarction of the skeletal muscle appears to be related to vasculopathic changes without an atheroembolic event or occlusion of major arteries. The factors responsible for the acute onset of symptoms are unknown. Since the initial description in 1965, only 170 cases have been described, including 126 initial episodes and 44 episodes of recurrence, with a mean age at presentation of 45 years (range 20 to 67 years). Most of the patients have other microvascular complications. Characteristic symptoms at presentation include acute onset unilateral lower limb pain and swelling, most often in the thigh, without a history of trauma. Bilateral involvement is present in approximately 30% of the cases. Fever has been reported only in about 10% of cases.

Case Report

A 23-year-old female presented with ten days history of fever, left groin pain and inability to walk. Other than chronic fatigue, her review of symptoms was mostly negative. She denied any trauma. She had a history of poorly controlled type 1 diabetes mellitus (HbA1c 10.5%) with diabetic nephropathy (proteinuria),but no evidence of retinopathy or neuropathy. On examination, her left groin and proximal thigh were warm and tender to palpation without noticeable erythema or swelling. Labs showed elevated inflammatory markers. CT scan showed inguinal and retroperitoneal lymphadenopathy with subcutaneous edema of the visualized left lower extremity. Fevers persisted despite appropriate administration of antibiotics for cellulitis. Infectious workup was negative. A biopsy of her inguinal lymph node showed reactive changes. MRI of her left thigh showed large, confluent areas of intramuscular hypo enhancement compatible with diabetic myonecrosis. Her symptoms improved over the next 3-4 weeks with supportive care.

Discussion

Spontaneous diabetic myonecrosis is a very rare complication of uncontrolled diabetes. Knowledge about his condition is required to make the correct diagnosis and avoid the use of unnecessary laboratory tests and treatments. The presence of the characteristic clinical features such as pain and swelling in typically affected areas such as the thigh, will frequently suggest the diagnosis. MRI with intravenous contrast enhancement is the diagnostic imaging of choice and shows increased signal on T2-weighted images from muscle edema and areas of non-enhancement from myonecrosis. Treatment involves symptomatic management with rest, optimal glycemic control, analgesia, and low-dose aspirin, although the optimal treatment approach is uncertain. The short-term prognosis is good, but the recurrence rate remains high and long-term prognosis is poor given underlying poorly controlled diabetes.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
PSUN285 Use of Continuous Glucose Monitoring in Managing Neonatal Diabetes in a Very Low Birth Weight Infant with a GATA-6 Mutation
Authors: Halpin Kelsee , Metzinger Emily
Published: November 2022

Introduction

Although continuous glucose monitoring (CGM) has increased in patients with Type 1 diabetes, its use in the neonatal population has remained limited. Neonates, particularly preterm infants, are at risk of impaired glucose control. Several studies have looked at the use of these devices in improving care for premature infants without diabetes. We describe a case of a very low birth infant with neonatal diabetes secondary to a GATA-6 mutation.

Clinical Case

This is a late preterm infant with IUGR, truncus arteriosus, and neonatal diabetes. Exome genetic panel showed a mutation in GATA-6. Her neonatal diabetes was challenging to control due to variable blood sugars and sensitivity to insulin. Weight gain remained poor. A CGM (Dexcom G6) was placed when the infant was 1.59kg to optimize her diabetes management and improve weight gain. An insulin titration chart was used to adjust her IV regular insulin infusion according to the CGM glucose levels and trend arrows. The following outcomes were reviewed and analyzed fourteen days before and after CGM placement: glucose levels (238 vs. 177 mg/dL), percentage of glucose levels within target range of 70-180mg/dL (31% vs 51%), average number of daily POC glucose checks (10.2 vs. 6.9), average amount of insulin received per day (0.42 vs 0.52 units/day), and average weight gain (11.4 vs. 20.7 grams/day). The discrepancy between POC and CGM glucose was also analyzed. CGM was within 20% of POC values 44% of the time and within 30% POC values 70% of the time. Adverse side effects of CGM were also noted. The patient was started on antibiotics following a small abscess identified underneath the CGM site. Bruising and skin breakdown were noted at the site, and the patient completed a course of antibiotics for the cutaneous infection. There were no other concerns of infection related to CGM for the first 2.5 months following CGM placement.

Conclusion

This case highlights that CGM can effectively be used to optimize glucose management in neonatal diabetes in a very low birth weight infant. However, the area where the CGM is placed needs to be monitored for signs of infection.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
PSUN336 Dietary sugar and protein differentially regulate the insulin and IGF1 homologs Dilp2 and Dilp6 in Drosophila.
Authors: Suzawa Miyuki , Hilovsky Dalton , McPherson Kyle , Bland Michelle
Published: November 2022

Growth deficits are frequently seen among children in resource-poor settings where malnutrition and chronic enteric infections are common. The insulin/IGF1 signaling pathway promotes cell and organismal growth across the animal kingdom. To better understand how malnutrition and infection impair growth, we investigated insulin/IGF1 signaling under such conditions using Drosophila as a model organism. In Drosophila, seven insulin-like peptides (Dilps) activate the insulin/IGF signaling pathway through a single known insulin receptor. Major circulating Dilps include Dilp2, produced from neurosecretory insulin-producing cells in the brain, and Dilp6, produced by the fat body, a functional analog of liver. Like insulin, mature Dilp2 lacks a C-peptide, whereas this sequence is retained in the IGF1 homolog Dilp6. We previously reported that bacterial infection and innate immune signaling negatively regulate whole-animal growth in Drosophila larvae by reducing circulating Dilp6 but not Dilp2. Here we asked whether Dilp2 and Dilp6 also respond differently to dietary sugar and protein, as secretion of insulin-like hormones is rigidly regulated by dietary nutrients. We used dual-epitope tagged Dilp2 and Dilp6 alleles to measure endogenous, circulating Dilp2 or Dilp6 in larvae. We find that circulating Dilp2 decreased by 60% after six hours of starvation on non-nutritive agar, and we observed a 90% decrease in Dilp2 from fed levels after 24 hours of starvation. In contrast, circulating Dilp6 was only reduced by 33% after 24 hours of starvation. Next, we asked whether Dilp2 and Dilp6 respond to specific dietary nutrients by adding yeast extract (to mimic the wild protein source) and/or sucrose to agar. Hemolymph Dilp2 was recovered to 73% of fed levels by the addition of yeast extract; addition of sucrose did not increase Dilp2 levels above the starved condition. Although the circulating level of Dilp6 was not strongly reduced by starvation, hemolymph Dilp6 was increased 40% by a sucrose-only diet compared with the normal, fed condition. Surprisingly, a yeast extract-only diet led to a 70% inhibition of circulating Dilp6 compared with the normal fed state. Addition of sucrose to the yeast diet led to a dose-dependent increase in Dilp6, suggesting that this hormone responds to the ratio of sugar to protein in the diet. Together, these data suggest that Dilp2 and Dilp6 secretion is controlled by distinct environmental conditions ranging from infection to dietary composition. An open question is how these two hormones carry distinct information to target organs despite binding to the single known insulin receptor encoded in the Drosophila genome.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
RF04 | PSUN298 Loss of β-Cell Glut2 Does Not Affect Systemic Glucose Homeostasis in Mice
Authors: Bathina Siresha , Bainbridge Lauren , Davis Autumn , Chhabra Kavaljit
Published: November 2022

Contribution of β-cell GLUT2 to systemic glucose homeostasis remains controversial in humans. For example, recent publications indicate that GLUT2 is not a major glucose transporter in β-cells in humans and therefore may not be involved in regulating systemic glucose homeostasis, which is in strong contrast to its previously assumed contribution to influencing systemic glucose balance. Although global Glut2 knockout mice develop diabetes, the contribution of β-cell Glut2 toward this phenotype is unknown. To determine the role of β-cell Glut2 in systemic glucose homeostasis, we crossed Glut2LoxP/LoxP mice with INSCreERT2 mouse strain to obtain mice that will potentially lack Glut2 specifically in β-cells (β-Glut2 KO) after administration of tamoxifen (100 mg/kg, i.p., once daily for five days) to induce the Cre-Lox recombination. We measured 6 h fasting blood glucose levels, glucose tolerance, and glucose-induced insulin secretion in the β-Glut2 KO mice. We observed that the KO mice had normal fasting blood glucose levels (male: 194.2 ±9.3 vs 192.0 ±3.5; female: 177.3 ±8.5 vs 157.3 ±9.8 mg/dL, Control vs. β-Glut2 KO). Similarly, the β-Glut2 KO mice exhibited normal glucose tolerance following oral administration of 60 mg glucose (Area under the curve for glucose tolerance, male: 39,911 ±1,632 vs. 39,633 ±1,275; female: 47,321 ±3,294 vs. 43,673 ±2,677 mg/dL*min, Control vs. β-Glut2 KO). Moreover, the KO mice had normal glucose-stimulated insulin secretion (baseline fasting plasma insulin levels: male - 0.84 ±0.14 vs. 0.5 ±0.01; female - 0.45 ±0.09 vs 0.48 ±0.1; plasma insulin levels 20 min. after oral glucose administration: male - 2.39 ±0.13 vs 2.48 ±0.51; female - 1.63 ±0.3 vs 1.11 ±0.12 ng/ml, Control vs. β-Glut2 KO). We had validated the loss of β-cell Glut2 using mRNA in situ hybridization. Altogether, our findings indicate that β-cell Glut2 is not essential for regulating systemic glucose homeostasis in mice, which was also observed recently with human β-cells. Therefore, the currently assumed major role of β-cell GLUT2 in directly influencing blood glucose levels needs to be reexamined to better understand the pathophysiology of impaired glucose homeostasis in diabetes.

Presentation: Saturday, June 11, 2022 1:30 p.m. - 1:35 p.m., Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
RF16 | PSUN177 Predictors of Postpartum Depressive Symptoms in Women with Recent GDM
Authors: Dias Jennifer , Nicklas Jacinda , Shqair Lara , Seely Ellen W
Published: November 2022

Background

Patients with gestational diabetes mellitus (GDM) have an increased risk of developing type 2 diabetes mellitus (T2DM) after delivery and are encouraged to practice behaviors, such as healthy nutrition, physical activity and weight loss to attenuate future risk of T2DM. GDM has been shown to significantly increase the risk for post-partum depressive symptoms, which can impair a woman's ability to engage in and adhere to diabetes prevention efforts. To further inform the development and adapation of lifestyle interventions to prevent T2DM, we sought to identify factors associated with depressive symptoms in the early postpartum period among women with recent GDM.

Methods

Participants are from the baseline cohort of the Balance after Baby Intervention study, a two-year randomized clinical trial of a lifestyle intervention for women with recent history GDM conducted in Boston, MA and Denver, CO between 2016-2019. Prior to randomization, a study visit was scheduled at approximately 6 weeks post-partum. At this visit, weight and height were measured for determination of BMI. We administered the Edinburgh Postpartum Depression Scale (EPDS) and Perceived Stress Scale (PSS-10). We used an EPDS score of ≥9 as depressive symptoms and a PSS score of ≥14 as moderate to high perceived stress. We collected self-reported pre-pregnancy weight, and reviewed medical records to obtain medical history, including GDM diagnosis, mode of delivery, gestational weight gain and insulin use during pregnancy. We conducted bivariate analyses to identify predictors of postpartum depressive symptoms, then modeled the odds of post-partum depressive symptoms using multivariate logistic regression.

Results

Our study included 181 women (mean age, SD 32.6 ± 5.3 years, 51.4% White/14.4% Black/33.7% Latinx, mean pre-pregnancy BMI 29.8 ± 6.0 kg/m2). 19% of women scored ≥9 on EPDS and 53% of women scored ≥14 on PSS at the post-partum visit. Variables included in the bivariate analysis were age, Black/Latinx-identifying, college completion, perceived stress, primiparity, having a partner, pre-pregnancy BMI, gestational weight gain, C-section, insulin use during pregnancy, breastfeeding, 1st GDM pregnancy, exceeding IOM weight gain guidelines and income level. Of those variables, the best fit multivariate model with the lowest Akaike information criterion (AIC) included perceived stress, C-section and 1st GDM pregnancy. Using this model, the regression analysis showed that only perceived stress (4.5 OR, 95% CI [2.6-7.7], p was predictive of post-partum depressive symptoms.

Conclusion

Perceived stress was predictive of post-partum depressive symptoms in women with recent GDM. Addressing perceived stress in the early post-partum period may be an important target for development or adaptations of future lifestyle interventions to prevent T2DM in women with recent GDM.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Sunday, June 12, 2022 1:18 p.m. - 1:23 p.m.
RF16 | PSUN204 Improving Inpatient Insulin Management amongst Internal Medicine Residents with a Multi-Media Structured Educational Program
Authors: Pennant Marjorie , Park Jeayoung , Gothong Chikara , Ceipek Julian , Malek Rana
Published: November 2022

Introduction

Approximately 1 in 4 patients admitted to the hospital carry a diagnosis of diabetes mellitus1 and 1 in 10 patients are admitted due to diabetes complications.2 Although Internal Medicine residents comprise the primary care team for the vast majority of patients admitted to major academic hospitals, there is a paucity of resources and standardized training for inpatient diabetes management, specifically designed for residents.

Methods

We developed a structured resident education program consisting of a mobile/web application ("EndoApp") as an accessible resource combined with a series of short lectures. The EndoApp is comprised of checklists, guidelines, and calculators based on the most recent American Diabetes Association (ADA) and American Association of Family Physicians (AAFP) recommendations. The application addresses five major areas of inpatient insulin management—i) insulin pharmacokinetics, ii) admission dosage calculation, iii) inpatient insulin regimen adjustment, iv) management of diabetic emergencies, and v) equipment and prescription management at discharge. The confidence level of residents for each of the five areas were surveyed at months 0, 1, and 3, after the start of the program on a scale of 1-5.

Results

Our 3-month interim analysis showed that the confidence of residents in all five areas of inpatient insulin management improved over the study period. Increased confidence was seen in post-graduate year (PGY) 1, 2, and 3 residents. The Admission Insulin Dosing Calculator was the most frequently used function (45% of residents), followed by DKA/HHS helper (23% of residents), and Inpatient Dosage Adjustment Guidelines (21% of residents). Residents who used the Admission Insulin Dosing Calculator had greater increase in provider confidence compared to those who did not use the function. Subjective feedback from residents included expanding functions to include hypoglycemia and non-emergent hyperglycemia management, as well as having recordings of supplementary lectures available on the application.

Conclusion

Structured resident education in inpatient insulin management utilizing a mobile/web application and lectures as supplementary material is a promising approach to improve resident education and confidence in inpatient diabetes management.

References

1. Moghissi ES, Korytkowski MT, DiNardo M, et al. American association of clinical endocrinologists and american diabetes association consensus statement on inpatient glycemic control. Endocr Pract. 2009;15(4): 353-369. doi: 10.4158/EP09102.RA

2. Russell LB, Valiyeva E, Roman SH, Pogach LM, Suh DC, Safford MM. Hospitalizations, nursing home admissions, and deaths attributable to diabetes. Diabetes Care. 2005;28(7): 1611-1617. doi: 10.2337/diacare.28.7.1611

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Sunday, June 12, 2022 12:30 p.m. - 12:35 p.m.
ODP276 THYROID CANCER CELLS ARE MORE RESISTANT THAN NORMAL CELLS TO BISPHENOL-A CYTOTOXIC EFFECT
Authors: Sterian Ward Laura , Rabi Larissa Teodoro , Nascimento Matheus , Teixeira Elisangela Souza , Dal’ Bó Cruz Izabela Fernanda
Published: November 2022

Bisphenol-A (BPA) is a well-known endocrine disruptor that produces important effects on thyroid metabolism, can interfere with TSH transcriptional activity, alter the transcription of T3-associated genes and, thus, modulate its activity in different cell lines. However, its direct effects on thyroid cells, especially on mutated thyroid cells, are still poorly understood. We tested 14 different concentrations of BPA, ranging from 0.4µg/mL to 400µg/mL, including LME (Specific Migration Limit =1μg/mL, recommended as acceptable by the Brazilian National Health Surveillance Agency-ANVISA) on two human thyroid cell lines: Nthy-ori 3-1 (from normal thyroid follicular cells) and TPC-1 (from papillary carcinoma). Cell viability analysis was made using the Trypan blue assay on cells exposed to BPA for 24h and 48h in technical and biological triplicate. We observed a non-monotone dose-response curve, characteristic of disruptors’ effect, on both cell lines, with greater cytotoxic effect with higher doses. In fact,100μg/mL already killed almost all Nthy-ori 3-1 cells (99% at 24h and 97% at 48h), whereasthe doses of 0.78µg/mL; 4µg/mL and 12.5µg/mL caused 50% kill. Optical microscopy revealed some irregular cells lost on the plate, and few debris with50μg/mL. Concentrations of 100 to 400µg/mL produced many dark small cells detached from the plate and clumps of dead cells. The SCI dose (1µg/mL - allowed in daily life), resulted in 79% of Nthy-ori 3-1 cell death after 24h of exposure. However, only 7% of the cell were dead after 48h of exposure to the SCI dose. This reduction in death rate after longer exposure to BPA was observed at all concentrations, suggesting a potent cellular recovery mechanism. The TPC-1 strain showed a different behavior, with a much more linear dose-dependent cytotoxic effect and much more resistance to the harmful effects of BPA at low doses. In fact, 0.4μg/mL to 3.125μg/mL produced less than 10% cell death, and microscopy confirmed the maintenance of the integrity of virtually all cells. On the contrary, BPA concentrations from 100 to 400µg/mL killed almost all TPC-1 cells at both 24h and 48h times. We conclude that this thyroid papillary carcinoma cell line is more resistant than the normal thyroid lineage to low BPA concentrations (from 0.4 to 50µg/mL) but this endocrine disruptor is highly cytotoxic at higher concentrations, causing more than 90% cell deaths on both normal and mutated thyroid cell lines.

Presentation: No date and time listed
ODP277 Urinary Concentrations of Polycyclic Aromatic Hydrocarbons and Childhood Obesity
Authors: Kim Shin-Hye , Park Mi Jung , Park Sung Kyun
Published: November 2022

Background

Polycyclic aromatic hydrocarbons (PAHs), primarily produced by incomplete combustion of organic materials, have been suggested as obesogens, but information on PAHs and obesity, especially in children, is limited. We examined the cross-sectional association between urinary concentrations of PAHs and obesity in the Korean pediatric population.

Methods

We analyzed the data of 2286 children and adolescents aged 3–17 years who participated in the Korean National Environmental Health Survey (KoNEHS) 2015–2017. Urinary concentrations of 2-naphthol, 2-hydroxyfluorene, 1-hydroxyphenanthrene, and 1-hydroxypyrene were assayed using gas chromatography-mass spectrometry. Covariate-adjusted standardization method was used for the urinary dilution adjustment. Overweight and obesity were defined as BMI-for-age ≥85th percentile and ≥95th percentile, respectively. Multiple linear and logistic regression models were performed to analyze the relationship of BMI z-score and overweight with urinary concentrations of PAHs after adjusting for age, sex, household income, parental education level, physical activity, fast-food consumption, and ETS exposure.

Results

Obese children showed significantly higher urinary 2-naphthol concentrations than normal-weighted children in the overall population [3.62 µg/L (95% confidence intervals (95% CI): 3.20, 4. 09) vs. 2.88 µg/L (95% CI: 2.62, 3.16)]. Similar findings were observed in the age groups 6-11 and 12-17 years. Significant increases in BMI z-scores for 10 times increase in urinary 2-naphthol concentrations were observed in the age groups 6-11 [0.31 z-score units, (95% CI: 0.13, 0.49), P = 0. 001] and 12-17 years [0.33 z-score units, (95% CI: 0. 05, 0.60), P=0. 02]. A significant but smaller association was observed between change in BMI z-score and 1-hydroxypyrene concentrations in the 6-11 year group [0.14 z-score units, (95% CI: 0. 02, 0.27), P=0. 03]. The multiple logistic regression models for overweight showed significant positive associations with the quartiles of 2-NAP in the overall population [OR (95% CI); 1.14 (0.83-1.55), 1.39 (1. 03, 1.88), 1.46 (1. 08, 1.99) in the 2nd, 3rd, and 4th quartile, respectively, compared with the 1st quartile; P-for-trend=0. 006]. Similar associations between 2-naphthol and overweight status were also observed in the 6-11 year and 12-17 year groups.

Conclusion

This result suggests a possible link between PAH exposure, particularly 2-naphthol, and obesity in the Korean pediatric population. Given the growing obesity rates among Asian children and adolescents, this finding warrants further studies on the impacts of long-term exposure of PAHs on childhood obesity and possible mechanisms for this association.

Presentation: No date and time listed
ODP278 A rare case of Ectopic ACTH secretion associated with Primary Gastric Choriocarcinoma
Authors: Abufaied Mohamad , Khan Adeel Ahmad , Saleh Ahmed Osman , Surchi Haval
Published: November 2022

Background

Ectopic ACTH production contributes to 10-15% of cases of Cushing's syndrome. Most cases are caused by neuroendocrine tumors of the lung, pancreas, or thymus. Other rare tumors causing ectopic ACTH secretion include esophageal tumor, gastric carcinoid tumor and squamous cell carcinoma of the larynx (1). We present a rare case of ectopic ACTH production causing Cushing syndrome due to primary gastric choriocarcinoma.

Case Presentation

A 27-year-old lady, not known to have any chronic illnesses, presented with two days history of epigastric pain. The patient also reported facial puffiness, leg swelling, generalized weakness and oligomenorrhea for the last four months. There was no history of easy bruisability or weight. She was not taking any medications. The patient did not smoke or use alcohol. Physical examination revealed conjunctival pallor, facial acne, wide striae on her thighs and hepatomegaly. The rest of the examination was normal. Lab tests showed microcytic anemia with hemoglobin of 7 gm/dl (12-15 gm/dl), hypokalemia (2.5 mmol/L; normal 3.5-5.3 mmol/L), AST 38 U/L (0-40 U/L) and ALT 45 U/L (0-41 U/L). β HCG was 1,506 mIU/mL (0 -5 mIU/ml). An abdominal ultrasound showed hepatomegaly with multiple echogenic solid mass lesions suspicious of metastatic origin. A CT abdomen showed a solid lesion in the fundal region of the stomach with multiple liver metastases and moderate ascites. An esophagogastroduodenoscopy showed fungating mass originating from the stomach fundus. Biopsy of the gastric mass revealed primary gastric adenocarcinoma, which was positive forCK 7, CK 19, beta hCG, CDX2 and CEA, consistent with the diagnosis of primary gastric choriocarcinoma. Due to widespread metastasis, the patient was started on palliative chemotherapy with dexamethasone 2 mg injection once daily along with capecitabine, cisplatin and pembrolizumab. In view of persistent hypokalemia and physical examination findings, a workup for Cushing's syndrome was performed. Early-morning serum cortisol was 1054 nmol/L (138–689 nmol/L), and plasma ACTH was 174 pg/ml (7.2-63.3 pg/ml) despite the patient being on intravenous 2 mg dexamethasone once daily for more than ten days. An MRI of the brain showed a normal pituitary gland. Based on these findings, the patient was diagnosed with Cushing's syndrome due to ectopic ACTH secretion. Unfortunately, her hospital course was complicated by massive upper gastrointestinal bleeding from the tumor, leading to her demise.

Conclusion

Gastric choriocarcinoma is a rare tumor associated with ectopic ACTH secretion leading to Cushing's syndrome. Reference: Imura H, Matsukura S, Yamamoto H, Hirata Y, Nakai Y. Studies on ectopic ACTH-producing tumors. II. Clinical and biochemical features of 30 cases. Cancer. 1975 May;35(5): 1430-7

Presentation: No date and time listed
PMON14 Estrogen Activity of Supplements Targeted for Post-Menopausal Women
Authors: O’Leary Emily , Davis Connor , Mancheski Molly , Ma Peng , Wiese Thomas
Published: November 2022

A wide variety of dietary supplements are available for the treatment of post-menopausal symptoms in women. Many women choose these supplements to avoid the potential unwanted side effects and long-term complications associated with traditional hormone therapy. In this study, we evaluated the in vitro estrogen activity of extracts from eleven supplements targeted for post-menopausal women to test the hypothesis that some of these supplements will induce estrogen activity in human breast cancer cell bioassays. Ethanol extracts (1 g: 1 mL) were prepared from the supplements: Amberen, Nature's Bounty Black Cohosh, Nature's Bounty St. John's Wort, Swanson Chasteberry Fruit, Nature's Way Red Clover, Promensil Real Health, Estroven, Relizen, Remifemin, and Equelle. Black cohosh, St. John's Wort, Chasteberry fruit, and red clover are standalone products that are not sold under a brand name. Promensil, Estroven, and Equelle contain isoflavones that have been reported to be estrogenic. Estroven and Remifemin contain black cohosh. Relizen contains a purified Swedish flower pollen extract and Amberen contains succinates, amino acids, minerals, and vitamin E. The estrogen activity of each extract was measured using both the T47D-kb-Luc estrogen responsive reporter gene and MCF-7 E3 proliferation estrogen bio-assays. The extracts from Nature's Way Red Clover, Promensil Real Health, and Equelle induced full estrogen agonist efficacy in the MCF-7 proliferation assay and more than full efficacy in the T47D-kb-Luc assay compared to estradiol. The agonist activity of these extracts in both bio-assays was inhibited by fulvestrant. Extracts from Nature's Bounty Black Cohosh, Nature's Bounty St. John's Wort, Swanson Chasteberry Fruit and Relizen induced less than full agonist estrogen activity only in the MCF-7 proliferation assay that was not, or not completely inhibited by fulvestrant. Thus, some supplements in this study likely target the estrogen receptor as agonists while others may be only weak estrogens that may also activate other proliferative pathways. While estrogen therapy is known to provide relief of some post-menopausal symptoms, estrogen use is associated with increased breast cancer risk. Consumers may benefit from information about the estrogen activity of supplements targeted for post-menopausal women. The results of this study may allow women to make more informed decisions about the use of these supplements. This study may be a prototype for evaluating the estrogen activity of dietary supplements for the purpose of informing consumers.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON17 Impaired cortisol regulation in Myotonic dystrophy
Authors: Mittal Ashima , Tipu Ali , Alkhaddo Jamil B , Jaiswal Gayatri
Published: November 2022

Introduction

- Myotonic dystrophy (MD) is the most common cause of adult-onset muscular dystrophy. It has impaired HPA axis regulation with exaggerated ACTH response to CRH mediated stimuli and abnormal cortisol metabolism. We present a case of myotonic dystrophy in a male with elevated cortisol levels. Case report - 54-year-old male with a past medical history of type 1 myotonic dystrophy (MD1) presented for evaluation of hypogonadism with complaints of feeling fatigued, progressive weakness of muscles. During the workup, he was noted to have elevated cortisol levels 30.2 mcg/dL (6-18.4) with elevated ACTH 220 pg/mL (10-48). Other notable lab results included low total testosterone levels of 231, 185 with elevated LH of 17.3 m IU/ml (2-9) and FSH 37.7 m IU/ml (1-12). Prolactin levels were minimally elevated to 21.4 ng/mL (4-15.2). On further inquiry, the patient did not have headaches or vision changes. The patient did not report weight gain, easy bruising, change in facial appearance. Physical exam was significant for bilateral gynecomastia and small testes. No cushingoid facies, abdominal stria, proximal myopathy was noted. Given elevated ACTH and cortisol levels, further laboratory data showed a lack of suppression of cortisol levels with 1 mg dexamethasone - cortisol 2.9 micro g/dL (<1.8), elevated midnight salivary cortisol - 0.130, 0.102 ug/dl (0.010-0.090), and normal 24-hour urine cortisol levels -15 mcg/24 hours.

Discussion

– Even though Cushing's disease is one of the differential diagnoses for the above case, high cortisol levels have been reported in MD. Few mechanisms suggested causing this abnormality are increased ACTH responsiveness to CRH-mediated stimuli and abnormal cortisol metabolism. Patients with MD have high pro-inflammatory (IL-1 and TNF-a) markers, which mediate the increased ACTH responsiveness to CRH-mediated stimuli centrally by stimulating the HPA axis.1 In addition, IL-6 chronically stimulates steroidogenesis from the adrenal gland, whereas TNF-α inhibits ACTH-induced adrenal steroid synthesis and increases 11BHSD1 activity. Along with the impaired HP axis, abnormal metabolism of cortisol also contributes to elevated cortisol levels. Increased activity of 11 BHSD1 has been hypothesized to cause impaired clearance of cortisol.2 Impaired diurnal variation for cortisol is also seen in MD with elevated 24-hour cortisol levels. Elevated cortisol levels as in our case can be a diagnostic dilemma given impaired cortisol regulation as seen in MD.

References

Åsa Johansson et.al. Abnormal Cytokine and Adrenocortical Hormone Regulation in Myotonic Dystrophy, The Journal of Clinical Endocrinology & Metabolism, Volume 85, Issue 9, 1 September 2000, Pages 3169–76.Åsa Johansson et.al. Glucocorticoid Metabolism and Adrenocortical Reactivity to ACTH in Myotonic Dystrophy, The Journal of Clinical Endocrinology & Metabolism, Volume 86, Issue 9, 1 September 2001, Pages 4276–83

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
RF22 | PMON04 Sex- and Dose-Dependent Effects of In Utero Endocrine Disruptor Exposure on Offspring Behavior and Brain Monoamines
Authors: MohanKumar Sheba , Kaimal Amrita , Hooversmith Jessica , Al Mansi Maryam , Holmes Philip , MohanKumar Puliyur
Published: November 2022

Exposure to endocrine disruptors (EDs), including the well-known plasticizers bisphenol A (BPA) and di(2-Ethylhexyl) phthalate (DEHP), during the highly sensitive gestational period, can produce long-lasting behavioral changes in offspring. In this study, we hypothesized that gestational exposure to BPA and/or DEHP at various doses would alter stress-related behaviors and monoaminergic activity in a region-specific manner in exposed offspring. To test this, female Sprague-Dawley dams were orally administered saline (control group - 10 µL/kg BW), BPA (5 µg/kg body weight (BW)), DEHP (5 µg/kg BW or 7.5 mg/kg BW), a combination of BPA and low-dose (LD) DEHP (5 µg BPA + 5 µg DEHP/kg BW), or a combination of BPA and high-dose (HD) DEHP (5 µg BPA + 7.5 mg DEHP/kg BW) during days 6 through 21 of pregnancy. The male and female offspring of these dams underwent a battery of behavioral tests in adulthood. Brains collected from the offspring were microdissected to obtain the medial prefrontal cortex (mPFC), paraventricular hypothalamic nucleus (PVN), and hippocampus (HC), which were analyzed for monoamine and metabolite levels using High-Performance Liquid Chromatography (HPLC). While BPA and B+D (LD) female offspring demonstrated anxiolytic effects in the Open Field Test, DEHP (HD) male offspring showed feminized anxiety-like behavior in the Elevated Plus Maze. The offspring also displayed impaired fear responses in the Shock Probe Defensive Burying (SPDB) test. Males in most ED groups buried less than their control counterparts. Furthermore, low-dose ED treatments led to a robust preference for passive coping strategies in both male and female offspring. Within the brain, male offspring in the BPA, LD and HD DEHP, and B+D (HD) groups had diminished dopamine (DA) levels in the PVN, which corresponded with their reduced SPDB burying levels. Moreover, DEHP (LD) male offspring had elevated DA turnover in the mPFC, whereas B+D (LD) female offspring had enhanced norepinephrine levels in the HC, which may underlie their behavioral outcomes in the SDPB. The findings of this study have implications for sex differences in mood and anxiety disorders following prenatal exposures to BPA, DEHP, and their mixtures.

Presentation: Sunday, June 12, 2022 12:36 p.m. - 12:41 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
ODP279 A Case of Nephrogenic Diabetes Insipidus Diagnosed at an Advanced Age in a Female Patient with an AVPR2 Gene Mutation and Skewed×Inactivation
Authors: Nakata Kento , Kameda Hiraku , Kuwabara Saki , Yasui Ayano , Takahashi Yuka , Miya Aika , Nomoto Hiroshi , Cho Kyu Yong , Nakamura Akinobu , Miyoshi Hideaki , Okada Eri , Nozu Kandai , Atsumi Tatsuya
Published: November 2022

Background

Arginine vasopressin receptor 2 (AVPR2) gene mutationsare the most common cause of congenital nephrogenic diabetes insipidus (CNDI), and they are inherited in an X-linked recessive manner. Women are generally asymptomatic or mildly affected, but atypically severe cases have been reported. Skewed X inactivation, in which the X chromosome is unevenly active, is a cause of this atypical severe case.×chromosome inactivation is a developmental compensation mechanism that results in equal doses of X-linked genes between XX females and XY males and has been reported to be accentuated by aging.

Clinical Case

A 69-year-old woman had no family history of diabetes insipidus. Immediately after undergoing a craniotomy for subarachnoid hemorrhage in July, she showed marked polyuria of approximately 8000 mL/day and hypernatremia of 161 mEq/L. The use of desmopressin (15mcg/kg/day) did not improve herpolyuria. She was referred to our department in September for further investigation and treatment. Her urine osmolality remained hypotonic at approximately 60–80 mOsm/kg/H 2 O (50–1300 mOsm/kg/H 2 O) according to a water restriction test. Her urine osmolality increased slightly to 106 mOsm/kg/H 2 O in a desmopressin test. These results indicated that desmopressin was ineffective, and the patient was diagnosed with nephrogenic diabetes. Her urine output decreased to approximately 2500 mL/day with trichlormethiazide treatment. There was no significant anterior pituitary hypofunction. Genetic examination revealed a heterozygous mutation of the AVPR2 gene (c.656T>G, p. Leu219Arg) in her X chromosome, and her X chromosome activity ratio was 79: 21 in a human androgen receptor assay, indicating skewed X inactivation.

Conclusion

We observed a case of CNDI in an elderly woman with no family history of the disease. In this case, a combination of the skewed X inactivation, presumably accentuated by aging, and the onset of subarachnoid hemorrhage, reduced her drinking water and led to the diagnosis of CNDI. References: (1)K. Kinoshita et al, J. Endocrinol. Invest. 27: 167-170, 2004. (2)Ding C et al, Am J Med Genet Part A. 2020; 182A: 1032–1040. (3)Y. Nomura et al, Journal of Clinical Endocrinology and Metabolism: 3434-3437, 1997.

Presentation: No date and time listed
PMON33 Non-Syndromic SRY Negative 46 XX Testicular Disorder of Sex Development (DSD); A rare cause of Infertility
Authors: Riaz Aiman , Barua Nabonita , Gordner Chelsea
Published: November 2022

Introduction

Male infertility can be categorized as endocrine and systemic disorders, primary testicular defects in spermatogenesis, sperm transport disorders and idiopathic male infertility. Chromosomal abnormalities are one of the primary testicular defects. The overall incidence of chromosome abnormalities in infertile men is estimated to be around 5.8%. XX male is a rare sex chromosomal disorder in infertile men. We present case of a young patient with infertility, azoospermia, hypergonadotropic hypogonadism and classical (46, XX) karyotype with negative FISH and SRY gene.

Case report: 28-Year-old gentleman was referred to adult endocrinology clinic as part of work up for infertility. Initial work up included 2 semen analyses which were consistent with azoospermia. Examination revealed height 180 cm, weight 77 kg, a body mass index 24 kg/m2, normal phenotypic male without gynecomastia and had normal male pattern hair distribution. Genital examination showed normal male phallus without hypospadias, a hypoplastic scrotum, bilateral firm testes, with no varicocele or hydrocele. Labs were suggestive of compensated primary hypogonadism (FSH 47.9 mIU/ml, LH 20.4 mIU/ml, total testosterone 397.9 ng/dl by LC/MS, free testosterone 15.76 ng/dl by equilibrium dialysis, Inhibin B < 10 pg/ml, and anti-Mullerian hormone 0.390 ng/ml. Given normal testosterone levels, he was not started on testosterone replacement. Karyotype analysis revealed 46 XX and FISH was negative for SRY gene. CT imaging of abdomen and pelvis did not reveal any Mullerian structures, prostrate and seminal vesicles reported as normal. Patient met with a Urologist and was informed that testicular sperm extraction will not be a possibility for him. Patient had a detailed consultation with a geneticist for genetic and family counseling. Chromosome microarray analysis was obtained and was normal. Invitae Disorders of sex development (DSD) panel obtained for genetic sequencing of 53 genes including SOX-9, DHH, WNT4, WT1, was found to be non-diagnostic.

Conclusion and Discussion

SRY negative 46 XX male is a DSD and a rare genetic cause of male factor infertility, with a discrepancy between genotype and phenotypic sex. In the case presented, genetic work up for potential etiologies has been unrevealing. Further studies are needed to identify the genetic causes of the SRY negative 46 XX male phenotype. Physicians involved in care of these patients should orient with clinical management and prognosis. For Classical 46 XX Males seeking fertility, the current options include invitro-fertilization with donor sperm or adoption only. Testosterone replacement should be considered to correct hypogonadism for physical and sexual well-being. Genetic consultation should be sought in all these cases.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
LBMON141 Macroorchidism In A Patient With A Functional Gonadotroph Macroadenoma
Authors: Chale-Matsau Bettina , Van Staden Louis P , Kemp Tanja , Pillay Tahir S
Published: November 2022

Background

Functioning gonadotroph adenomas (FGAs) are rare, since most pituitary adenomas of gonadotroph origin are clinically silent or non-functioning. FGAs produce hormones that are adequate to result in clinical syndromes. Clinical case We describe a 38-year-old male who presented with pressure effects from a sellar mass manifesting as persistent and progressive headache. He also complained of swelling of the feet, excessive sweating and coarsening of facial features as well as increased libido. The patient also reported symptoms consistent with obstructive sleep apnoea. His shoe size remained the same and had no features of acromegaly. His visual fields appeared intact on informal assessment. He appeared well virilised and had bilateral macroorchidism, with both testes markedly larger than the largest measurement on the orchidometer (25ml). He was found to have elevated follicle stimulating hormone (FSH) 26.7 to 38.4 IU/L [1.3 -19.3] and testosterone levels from 28.1 to 44.3 nmol/L [6.1 - 27.1] with luteinising hormone (LH) levels being either inappropriately non-suppressed or high, 5.7 - 12.3 IU/L [1.2 - 8.6]. He also had erythrocytosis [Hb 19.5 to 21.7 g/dL (14.3 -18.3) and macroorchidism, owing to high gonadotropin levels. The rest of his pituitary axis appeared intact, including TFT, cortisol levels, and IGF-1, were all within normal limits. Although histology of the pituitary adenoma could not be obtained as the patient declined surgery, clinical and biochemical findings were supportive of FGA diagnosis.

Conclusions

FGAs are rare, can have none or subtle clinical features, and often present late with mass effects. Functional gonadotroph adenoma should be suspected in a patient with a sellar mass, with high or non-suppressed gonadotropins in the presence of elevated gonadal steroids. Clinical features such as macroorchidism and polycythaemia may be easily missed or misinterpreted. Surgical removal should be the therapy of choice, and if successful can lead to reversal of the biochemical and clinical abnormalities.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.