bluuebunny/crossref_metadata_2025 huggingface dataset:
Cellular Heterogeneity of the Luteinizing Hormone Receptor and Its Significance for Cyclic GMP Signaling in Mouse Preovulatory Follicles
Authors: Baena Valentina , Owen Corie M , Uliasz Tracy F , Lowther Katie M , Yee Siu-Pok , Terasaki Mark , Egbert Jeremy R , Jaffe Laurinda A
Published: May 2020

Meiotic arrest and resumption in mammalian oocytes are regulated by 2 opposing signaling proteins in the cells of the surrounding follicle: the guanylyl cyclase natriuretic peptide receptor 2 (NPR2), and the luteinizing hormone receptor (LHR). NPR2 maintains a meiosis-inhibitory level of cyclic guanosine 5′-monophosphate (cGMP) until LHR signaling causes dephosphorylation of NPR2, reducing NPR2 activity, lowering cGMP to a level that releases meiotic arrest. However, the signaling pathway between LHR activation and NPR2 dephosphorylation remains incompletely understood, due in part to imprecise information about the cellular localization of these 2 proteins. To investigate their localization, we generated mouse lines in which hemagglutinin epitope tags were added to the endogenous LHR and NPR2 proteins, and used immunofluorescence and immunogold microscopy to localize these proteins with high resolution. The results showed that the LHR protein is absent from the cumulus cells and inner mural granulosa cells, and is present in only 13% to 48% of the outer mural granulosa cells. In contrast, NPR2 is present throughout the follicle, and is more concentrated in the cumulus cells. Less than 20% of the NPR2 is in the same cells that express the LHR. These results suggest that to account for the LH-induced inactivation of NPR2, LHR-expressing cells send a signal that inactivates NPR2 in neighboring cells that do not express the LHR. An inhibitor of gap junction permeability attenuates the LH-induced cGMP decrease in the outer mural granulosa cells, consistent with this mechanism contributing to how NPR2 is inactivated in cells that do not express the LHR.
SAT-131 Asymptomatic Severe Hypoglycemia with Lactic Acidosis in a Case of Non-Hodgkin’s Lymphoma - an Unusual Phenomenon of Hyper-Warburgism
Authors: Goyal Itivrita , Karadsheh Oday , Pandey Manu Raj , Sharma Rajeev , Chaudhuri Ajay
Published: May 2020

INTRODUCTION

Hypoglycemia in malignancy is well known with several etiologies; impaired liver function, insulin receptor autoantibodies, production of insulin-like substance by malignant cells or large tumor burden. Another possible mechanism is the Warburg effect where metabolism shifts towards glycolytic pathways over oxidative phosphorylation even under aerobic conditions leading to excess lactate production. This leads to glucose consumption due to shunting of glucose away from normal cells to cancer cells. Very few cases of lactic acidosis and severe hypoglycemia in Non-Hodgkin’s Lymphoma have been described in the literature. We report such an unusual case here.

CASE DISCUSSION

A 52-year-old, African-American male was admitted for severe malnutrition with 80 lb. weight loss, severe hypoglycemia and progressively increasing right chest wall mass. On arrival, he had no classic symptoms of hypoglycemia. Physical exam revealed persistent tachycardia, white patches on oral mucosa and posterior tongue, and an indurated mass on right chest wall with extensive swelling of right upper limb. Lab work was significant for blood glucose (BG) of 41 mg/dL (60–100), lactate 16 mmol/L (0.5 to 2), anion gap 26 mEq/L (3–10), albumin 2.3 g/dL (3.4 to 5.4) and normal renal and liver function tests. Fingerstick sugar readings were persistently in the 20s with no response to multiple boluses of dextrose and glucagon. He was started on dextrose 5% (D5) drip and intravenous solumedrol. Solumedrol was weaned off and D5 titrated down to investigate causes of hypoglycemia. BG dropped to 39 and corresponding labs showed insulin level of < 2 mcUnit/mL (2–20), C-peptide of 0.2 ng/mL (0.8–6.0) and ketone level of 0.2 mmol/L (<0.4). IGF-1 and IGF-2 were both low at 26 ng/mL (61–200) and 113 ng/mL (333–967) respectively. A CT torso with contrast showed bilateral pleural effusions, moderate pericardial effusions and a large ill-defined heterogeneous mass along anterior chest wall. He underwent ultrasound guided biopsy of the chest wall mass and diagnosed with diffuse large B-cell lymphoma. He also tested positive for HIV/AIDS and Hepatitis C. PET scan showed diffuse FDG (fluorodeoxyglucose) uptake consistent with advanced disease. He was started on chemotherapy and lactate and BG normalized soon after 1st cycle.

CONCLUSION

In our case; suppressed insulin, low C-peptide and IGF-2 levels indicate non-insulin mediated hypoglycemia due to rapid glucose utilization by cancer cells. Severe hypoglycemia with lack of neuroglycopenic symptoms suggests use of lactate (rather than glucose) as an alternative metabolic fuel for brain, thus preserving its function. Our patient presented with an exaggerated Warburg effect (hyper-Warburgism) as evident by extreme glucose consumption, severe lactic acidosis and large tumor burden on FDG/PET. Chemotherapy must be instituted timely to correct these abnormalities.
SAT-427 Quality of Life Following Treatment for Graves’ Disease: A Comparison of Radioactive Iodine Ablation and Surgery
Authors: Rowe Christopher W , Blefari Nicholas D , Rutherford Natalie , Bendinelli Cino , O’Neill Chris
Published: May 2020

Introduction: Quality of Life (QoL) is reduced in patients with Graves’ disease, however the impact of treatment modality is unclear, with conflicting evidence from recent studies (1–3). We hypothesized that surgery would have a greater impact than radioiodine on QoL in Graves’ disease, especially with regard to the physical-symptom subdomain.

Methods: Patients treated with thyroid surgery for benign disease (n=425) or radioactive iodine for hyperthyroidism (n=1637) at a single tertiary institution between 2000 and 2017 were invited to complete a validated thyroid-specific QoL instrument (City of Hope), reporting scores 0–10, where higher scores are associated with greater QoL. Responses were received from 307 patients, of whom 114 (37%) had Graves’ disease, treated with total thyroidectomy (n=23) or doses of 15mCi (550MBq) radioiodine (n=91, including 19 patients receiving 2 or more doses). The results of patients with Graves’ disease are reported here. Medians [interquartile ranges] are compared with the Mann-Whitney test (alpha 0.05).

Results: 85% of respondents were female, with no difference in gender between groups (p=0.11). Thyroidectomy patients were more likely to be younger (36 [31–49] vs 50 [39–59] years, p=0.004); and have a shorter duration between treatment and survey (5.9 [2.4–9.6] vs 7.6 [4.9–11.6] years, p=0.04). No overall QoL deficit was seen in patients treated with surgery compared to radioiodine (6.8 [5.2–7.3] vs 7.0 [5.8–8.1], p=0.08). However, patients treated with surgery reported reduce QoL in psychological (6.6 [4.7–7.5] vs 7.0 [5.9–8.2] p=0.05) and social (7.9 [6.4 – 8.9] vs 8.9 [7.4–9.8] p=0.01) subdomains compared to radioiodine-only treated patients. Within the social subdomain, the QoL detriment was driven by lower scores relating to questions regarding impact on personal and family relationships, support, and isolation (p<0.001), and not by impact on activities of daily living or employment concerns. Interestingly, there was no between group difference in the physical symptom subdomain (p=0.16). QoL differences between treatment modalities were preserved when patients receiving multiple doses of radioiodine were excluded.

Discussion In this non-randomised cross-sectional study from a tertiary-hospital population in Australia, a QoL deficit was demonstrable in subdomain scores for patients with Graves’ disease treated with surgery compared to radioiodine, although the overall result was not significantly different. Better understanding of patient experiences is required to guide treatment strategies and appropriately counsel patients.

References (1) Torring et al. Thyroid. 2019;29(3):322–31. (2) Abraham-Nordling et al. Thyroid. 2005;15(11):1279–86. (3) Ljunggren et al. Thyroid. 1998;8(8):653–9.
SAT-379 Giant Parathyroid Adenoma
Authors: Saberi Sima , Wasco Matthew J , Behjatnia Ramin , Kimball Beth
Published: May 2020

Giant parathyroid adenoma

Background: Primary hyperparathyroidism is the most common cause of hypercalcemia. On ultrasound PTH adenomas are typically homogenous, hypoechoic, oval or bean-shaped with peripheral vascularity.

Clinical Case: A 60 year old woman with a history of calcium oxalate nephrolithiasis presented with fatigue, worsening depression, body aches of 3 months duration. Labs showed a serum calcium 11.1 mg/dl (normal range 8.5–10.1 mg/dl), PTH 114.3 pg/ml (normal range 12–88 pg/ml), 25 OH Vitamin D 11 ng/ml (normal range above 29 ng/ml), alkaline phosphatase 137IU/L (normal range 27–120 IU/L), spot urine calcium 34.8 mg/dl, spot urine creatinine 92.1 mg/dl (estimated 24 hour urine calcium 415 mg/dl). She was started on Vitamin D 1000 IU daily. A PTH scan with SPECT/CT showed a right parathyroid adenoma and possible thyroid nodules. A neck ultrasound demonstrated a left 1.5 cm thyroid nodule and a right 3cm lesion. She underwent FNA of the left thyroid nodule and pathology was suggestive of a benign follicular nodule. She underwent parathyroid gland exploration with resection of the right lesion which was a 3.5 x 2.5 x 1.4 cm right superior 5.68 gm PTH adenoma. Postoperatively her serum calcium normalized to 10.1 mg/dl, PTH was 8.4 pg/ml, 25 OH vitamin D was 15 ng/ml. Her Vitamin D dose was increased.

Clinical Lessons: A normal parathyroid gland typically weighs 30–60 mg and is 3–4 mm in size. The differential diagnosis for large parathyroid lesions is parathyroid carcinoma vs giant parathyroid adenoma. Although there is not a definitive size cutoff to define giant parathyroid adenomas, a size greater than 3.5 gm has been used (1). On ultrasound giant parathyroid adenomas are homogenous with smooth borders whereas parathyroid carcinomas are large lobulated heterogeneous hypoechoic lesions (2). A depth/width ratio on ultrasound may be the ultrasound parameter with greatest discriminatory capacity as a depth/width ratio greater than or equal to 1 had 94% sensitivity and 95% specificity for parathyroid carcinoma (2). Whether vitamin D deficiency is a risk factor for the development of large parathyroid glands is controversial as there has been conflicting data on this (1,3). Because there is no serum calcium level that distinguishes parathyroid carcinoma from a parathyroid adenoma neck ultrasound may be a helpful tool in evaluating these patients.

References:

1. Spanhemier PM, Stoltze AJ, Howe JR, et al. Do giant PTH adenomas represent a distinct clinical entity? Surgery. 2013 Oct; 154(4):714–719.

2. Hara H, Igarashi A, Yano Y, et al. Ultrasonagraphic features of PTH carcinoma. Endocr J. 2001 April 48(2):213–217.

3. Rao DS, Honasoge M, Divine GW, et al. Effect of vitamin D nutrition on PTH adenoma weight: pathogenetic and clinical implications. J Clin Endocrinol Metab. 2000 Mar 85(3): 1054–1058.
OR29-03 The Effects of Hormone Therapy on Premature Ovarian Failure Following Allogenic Hematopoietic Stem Cell Transplantation: A Single-Center Experience
Authors: Ha Jeonghoon , Han Je-Ho , Kang Moo-Il
Published: May 2020

Background: With increasing survival rates after hematopoietic stem cell transplantation (HSCT), it has become important to evaluate methods of improving patients’ quality of life. Most female patients of childbearing age experience premature ovarian failure after transplantation, which results in decreased quality of life and an increase in fracture risk due to rapid bone loss. We analyzed the effects of hormone therapy (HT) on serum follicle stimulating hormone (FSH), serum estradiol, and bone mineral density (BMD) in young female HSCT recipients. Methods: This retrospective cohort study included 234 female patients who underwent allogenic HSCT between April 2009 and April 2018 at our center. The maximum age at the time of transplantation was 40 years, and patients were followed up for at least 3 years. Of the 734 patients who were initially screened, 360 patients aged <18 years and 8 who were transferred to another institution after transplantation were excluded from the study. There were 93 patients who died within 3 years of transplantation, while 30 were lost to follow-up, and 9 were followed-up for less than 3 years. Changes in hormone levels and BMD, according to HT regimen, were evaluated in 234 patients. Results: The mean age at transplantation was 30.47 ± 6.55 years. Out of 234 patients, 170 (72.6%) patients received HT, starting treatment at a mean of 15.1 ± 8.2 months after transplantation. A significant increase in estradiol level was observed in patients receiving HT (p < 0.001); no difference was observed between the 3 different types of HT regimen (p = 0.534). After 2 years of HT, BMD was significantly increased at all measurement sites: lumbar spine 5.8 ± 6.26% (p < 0.001), femoral neck 3.4 ± 17.78% (p = 0.037), total hip 2.1 ± 7.15% (p = 0.001). Again, there was no difference in changes between the HT regimens (p = 0.646 for lumbar spine, p = 0.840 for femoral neck, and p = 0.855 for total hip). These changes were significant even in patients with graft versus host disease (GVHD) or steroid exposure. Conclusion: In patients with premature ovarian failure following allogenic HSCT, HT effectively lowered serum FSH and increased serum estradiol levels. HT significantly increased BMD regardless of the history of GVHD or steroid exposure. These changes in hormones and BMD were independent of the HT regimen.
OR02-01 Gene Dosage Changes in RBFOX-2 Can Affect Upper and Lower Tract Genitourinary Development
Authors: O’Neill Marisol A , White Jeffrey T , Lamb Dolores J
Published: May 2020

Searching for genetic and genomic alterations in patients with genitourinary (GU) birth defects can aid in the identification of genes that are important for normal GU development. Using data in DECIPHER, RBFOX-2, located at 22q12 was identified as one such candidate gene and the effect of haploinsufficiency in humans and a mouse model (Rbfox-2α/+) assessed. RBFOX2 is an RNA-binding protein regulating alternative splicing. It also impacts steroid receptor transcriptional activity. RBFOX family members are thought to affect different developmental programs via isoform-specific localization and splicing activities. RBFOX-2 plays a vital role in multiple developmental processes including heart, brain, muscle and testis development. “Non-syndromic” patients with congenital GU anomalies were more likely to harbor RBFOX-2 CNVs (2.4%; hypospadias, 21% cryptorchidism, 29% vesicoureteral reflux and 29% ureteropelvic junction obstruction) relative to the general population (0.11%) indicating that 22q12 is a hotspot genetic locus for GU anomalies. CNVs (microdeletions and microduplications) spanning RBFOX-2 were identified in twenty-seven humans with a wide range of birth defects(intellectual disability, CNS, cardiac, genitourinary, facial, hearing, vision, growth and stature anomalies) and the phenotype of the haploinsufficient Rbfox-2α/+mouse model closely correlated with the human phenotype, although Rbfox-2α/+ andRbfox-2α/α are neonatal lethal. By E18.5 day of development 100% of the Rbfox-2α/+ and null fetuses exhibited hypospadias, megacystis (50%) and bilateral hydroureteronephrosis. RNA Seq was performed on genital tubercles from three Rbfox2fl/fl, Gdf9 icre+ and three Rbfox2fl/fl P1 males. 377 genes were differentially expressed between the two groups including 212 genes which were upregulated and 165 genes which were downregulated. Hallmark gene set analysis revealed downregulation of Wnt/β-catenin signaling and hedgehog signaling, both pathways which are well defined in genital development. Gene ontology (GO) analysis further defined downregulation of pathways (fibroblast growth factor, retinoic, androgen, estrogen and G-protein receptor signaling) including those involving negative regulation of embryonic development, epithelial development, morphogenesis of epithelial tube, renal, ureter, limb and several other developmental pathways. These results support the hypothesis that loss of Rbfox2 during development leads to hypospadias through impaired development of the urethral epithelium.
OR24-03 GRK2 Mediates Beta-Adrenergic Receptor Crosstalk to Enhanced Adrenocortical AngII-Dependent Aldosterone Production
Authors: Lymperopoulos Anastasios , Pollard Celina M , Pereyra Janelle M , Desimine Victoria L , Wertz Shelby L , Perez Arianna , Ferraino Krysten E , Cora Natalie
Published: May 2020

Aldosterone is produced by adrenocortical zona glomerulosa (AZG) cells in response to hyperkalemia or angiotensin II (AngII) acting through its type I receptors (AT1Rs). AT1R is a G protein-coupled receptor (GPCR) that induces aldosterone synthesis and secretion via both G proteins and the GPCR adapter proteins βarrestins. AZG cells express all three subtypes of β-adrenergic receptor (AR) and respond to catecholamines by producing aldosterone. Being GPCRs, both activated βARs and AT1Rs are phosphorylated by GPCR-kinases (GRKs), followed by βarrestin binding to initiate G protein-independent signaling. Herein, we investigated whether the major adrenal GRKs, GRK2 and GRK5, are involved in catecholaminergic regulation of AngII-dependent aldosterone production. We used the human AZG cell line H295R, in which we measured aldosterone secretion via ELISA and synthesis via real-time PCR for steroidogenic acute regulatory (StAR) protein and CYP11B2 (aldosterone synthase) mRNA levels. Isoproterenol (Iso, a βAR full agonist) treatment significantly augmented AngII-dependent aldosterone synthesis (2.2+0.8-fold CYP11B2 & 1.6+0.5-fold StAR mRNA inductions over AngII alone; p<0.05, n=4), as well as secretion (2.3+0.8-fold of vehicle with Iso; 3.2+1.1-fold of vehicle with AngII; 7.4+1.1-fold of vehicle with Iso+AngII, p<0.05 vs. either agent alone; n=5) in H295R cells. Importantly, GRK2, but not the other major GRK isoform expressed in human adrenals GRK5, was indispensable for the catecholamine-mediated enhancement of aldosterone production in response to AngII in H295R cells. Specifically, GRK2 inhibition with the small molecule Cmpd101 abolished Iso effects on AngII-induced aldosterone synthesis and secretion (Iso+AngII-induced aldosterone secretion: 8.1+2.3-fold of vehicle without Cmpd101; 2.8+0.8-fold of vehicle with Cmpd101; p<0.05, n=5). In contrast, GRK5 knockout via CRISPR/Cas9 did not affect the synergism between isoproterenol and AngII in stimulating aldosterone production. Mechanistically, βAR-activated GRK2, but not GRK5, phosphorylated and activated the Ca2+-activated chloride channel anoctamine-1 (ANO1), also known as transmembrane member (TMEM)16A, ultimately increasing aldosterone production in H295R cells (Iso+10–6 M [Ca2+]-induced ANO1 activity of Cmpd101-pretreated cells: 55+15 % of non-Cmpd101-pretreated cells; p<0.05, n=5). AngII alone failed to stimulate GRK2 in H295R cells. In conclusion, GRK2 mediates a βAR-AT1R signaling crosstalk at the level of ANO1 activation, which results in enhanced aldosterone production in H295R cells. This finding suggests that adrenal GRK2 may be a molecular link connecting the sympathetic nervous and renin-angiotensin systems in the adrenal cortex and that GRK2 inhibition might be therapeutically advantageous for aldosterone suppression.
SAT-371 Severe Hypocalcemia Secondary to Pseudohypoparathyroidism
Authors: Ghanta Neelima , Adams Derick
Published: May 2020

Introduction: Pseudohypoparathyroidism (PHP) is a rare disorder characterized by PTH resistance due to a mutation in the GNAS gene causing decreased cyclic AMP generation. The 5 subtypes of PHP include type 1a, 1b, 1c, 2, and pseudo-PHP with type 1a being the most common. Patients with PHP present with hypocalcemia, hyperphosphatemia, appropriately elevated PTH, and suppressed calcitriol levels. PHP type 1a patients have characteristic features including obesity, short stature, round facies, and shortened metacarpals. PHP patients should be evaluated for other endocrinopathies as mutations in the GNAS gene may result in resistance to other hormones like TSH, GHRH, and gonadotropins.

Case Report: This patient is a 25 year old male who presented to clinic for evaluation of hypocalcemia. He denied any personal or family history of calcium disorders, thyroid disease, or parathyroid disease. He admitted to severe fatigue and muscle cramps for over one year leading to a car accident. He was sent to the emergency room and diagnosed with hypocalcemia requiring IV calcium gluconate. He was then seen by his family physician and was found to have elevated intact PTH and low 25-hydroxy vitamin D levels. He was placed on cholecalciferol 5000 international units (IU) daily, ergocalciferol 50,000 IU once weekly, calcium carbonate 500 mg (6 tablets daily), and referred to endocrinology. The physical exam was unremarkable. The laboratory values tested were an intact PTH of 645 pg/mL (10–65 pg/mL), ionized calcium of 4.2 mg/dL (4.6–5.08 mg/dL), magnesium of 2.1 mg/dL (1.5–2.3 mg/dL), 25-OH vitamin D of 31.7 ng/mL (20–100 ng/mL), and creatinine of 0.81 mg/dL (0.7–1.3 mg/dL) four months after starting the above mentioned calcium and vitamin D supplementation. Further testing revealed a phosphorus level of 4.8 mg/dL (2.3–4.7 mg/dL), calcitriol level of 55.8 pg/mL(19.9–79.3 pg/mL), TSH of 10.46 uIU/mL (0.4–4.2 uIU/mL) and free T4 of 1.5 ng/dL (0.8–1.7 ng/dL). His labs were consistent with PHP. Although unknown which PHP subtype, it is likely not type 1a as he lacks its characteristic phenotype. His abnormal thyroid function tests may be secondary to TSH resistance associated with the GNAS gene mutation. He was told to continue the current dose of calcium carbonate but to discontinue ergocalciferol and cholecalciferol. He was placed on calcitriol 0.5 mcg daily. He will have repeat levels of his ionized calcium, calcitriol, TSH, and free T4 in two weeks. If TSH is still above 10 uIU/mL, we will start levothyroxine replacement.

Conclusion: Although a rare disorder, clinicians should have a high index of suspicion for PHP to prevent complications of hypocalcemia (tetany, arrhythmias, seizures) and metabolic bone disease from PTH resistance.

References: Mantovani, G. Pseudohypoparathyroidism: Diagnosis and Treatment, The Journal of Clinical Endocrinology & Metabolism, Volume 96, Issue 10, 1 October 2011, Pages 3020–3030.
MON-438 Papillary Thyroid Carcinoma Arising in a Thyroglossal Duct Cyst: A Case Report
Authors: Zuniga Gabriela , Fortuna Gliceida Galarza , Guzman-Davant Alejandro , Paramo Juan , Pagacz Michael
Published: May 2020

Introduction: Thyroglossal duct cysts (TGDCs) are uncommon benign congenital entities. Rarely, thyroid carcinoma can arise from a TGDC; the most common being papillary thyroid carcinoma (PTC). Similar to TGDC, carcinomas originating within them can present as an asymptomatic midline neck mass. Signs of malignancy include dysphagia, dysphonia, weight loss, and rapid growth. Given the rarity of TGDC carcinomas, clinical management remains controversial, particularly regarding the requirement for total thyroidectomy.

Case: A 52-year-old female with history of an anterior central neck mass initially noted in 2017. A 0.3-cm left lobe mid-segment cyst and a complex thyroglossal avascular simple cyst measuring 2.4 × 1.1 × 1.8 cm was observed during ultrasound (US). She presented to the endocrinology clinic in April 2019 due to progressive enlargement of the mass.

Repeat thyroid US revealed that the cystic structure had become complex with a peripheral solid component and measured 3.3 × 2.1 × 2.2 cm. FNA was performed and found to be suspicious for PTC (Bethesda category V) and positive for the BRAF V600E mutation.

Patient was referred for surgical evaluation. Physical examination revealed a midline anterior 10-cm, painless, and fixed mass above the thyroid that moved with deglutition and tongue protrusion. Contrast computed tomography scan showed a large multiloculated cystic structure measuring 4.1 × 4.4 × 5.9 cm. A lobulated soft tissue mass measuring 2.2 × 2.4 × 3.0 cm was noted internally along the inferior margin of the cyst. She underwent en-block resection of the TGDC in addition to a total thyroidectomy. Histopathological examination identified a 7.5 × 5.5 × 5.0 cm cystic mass with fluctuation and a firm, solid area in the lower portion measuring 2.6 × 2.4 cm. Thyroid gland examination was otherwise unremarkable. No areas of extension of the mass into the thyroid tissue were clearly identified and no other gross lesions were observed. The solid area within TGDC contained a tumor with findings characteristic of PTC. Postoperatively, she was placed on thyroid hormone replacement therapy.

Conclusion: The main difficulty encountered with cancer developing from TGDC is that the diagnosis is usually made during surgery and from definitive pathological samples. The most common surgical procedure used is the Sistrunk procedure. Some studies have suggested that this procedure alone is an adequate therapy, but others advocate the need for total thyroidectomy. The Sistrunk procedure is considered to be appropriate for low-risk patients, but high-risk patients must undergo total thyroidectomy. The decision to perform a total thyroidectomy in this patient was based on her high-risk classification due to: age, sex, cyst size, and a positive FNA for malignancy. Follow-up includes an annual physical examination, thyroglobulin levels, and an US every 6 months during the first year and annually thereafter.
SUN-170 Adrenal Insufficiency Due to Adrenal Hemorrhage
Authors: Bansal Rashika , Nath Priti V , Hoang Thanh Duc , Mai Vinh Q , Shakir Mohamed K M
Published: May 2020

Introduction: Antiphospholipid Syndrome (APS) can involve multiple organ systems but endocrine manifestations are rare. In most cases adrenal insufficiency (AI) is the first endocrine manifestation of APS. The prompt diagnosis of adrenal insufficiency is critical. We present a case of AI associated with antiphospholipid syndrome who was managed successfully. Case presentation: A 50-year-old man was admitted with deep venous thrombosis of the distal left femoral vein extending to the popliteal vein and was started on xarelto, but he developed pleuritic chest pain and dyspnea in 48 hours. CT scan confirmed a pulmonary embolism and patient was treated with heparin drip. Two days following heparin drip patient developed acute bilateral flank pain and hypotension; and CT abdomen showed 2 masses replacing the adrenal glands that were concerning for hematomas. Laboratory results: serum potassium 4.9 mmol/L, serum cortisol 3.3 mcg/dL (reference 7.2–19.4), ACTH level 319 pg/mL (reference 7–53), aldosterone <1.0 ng/dL (reference 0.0–3.0), and plasma renin activity 7.17 ng/ml/hr (reference, 0.15–3.95). Serum antiphospholipid antibody testing showed cardiolipin Ab Ig 140 GPL/mL (reference 0–14), cardiolipin Ab IgM 100 MPL/mL (reference 0–12) and cardiolipin Ab IgA >150 APL/mL (reference 0–11). Further testing showed beta-2 glycoprotein 1 Ab IgG 103 GPI units (reference 1–20), IgM 94 GPI units (reference 0–32), and IgA 150 GPI units (reference 0–25). His hypotension dramatically improved upon administration of IV hydrocortisone and the abdominal pain resolved in 3 days. Upon discharge he was placed on hydrocortisone and continued warfarin therapy. At a 6-week follow-up visit, patient was asymptomatic. Additional lab tests revealed normal plasma renin activity and aldosterone levels. Two years later an ACTH stimulation test confirmed persistent AI. Basal plasma ACTH level was 230 pg/mL (ref 5–50). Additionally plasma renin activity and serum aldosterone levels indicated no mineralocorticoid deficiency. An adrenal CT scan revealed significant long-term interval decrease in size of bilateral adrenals with hypo-attenuating focus in the right adrenal gland, favored to represent post hemorrhage changes without convincing evidence of underlying neoplasm especially given decrease in size compared to 4-years prior. Presently, patient is doing well on hydrocortisone and warfarin treatment. Conclusion: In all cases of adrenal hemorrhage and infarction with unknown etiology, screening with lupus anticoagulant and anticardiolipin antibodies is imperative. Recognition of this high mortality condition will allow for appropriate screening and confirmatory tests leading to prompt diagnosis and timely management.
SAT-578 A Rare Case of Laboratory Hypertriglyceridemia: Glycerol Kinase Deficiency
Authors: Ueda Masako , Wolska Anna , Sampson Maureen , Burke Frances M , Rader Daniel J , Dunbar Richard L , Remaley Alan T
Published: May 2020

Background: Hypertriglyceridemia (HTG) is common; however, pseudo-HTG due to high glycerol in glycerol kinase deficiency (GKD, MIM: 307030) is a rare cause of HTG that need to be delineated for appropriate management. GKD is an X-linked recessive disorder characterized by hyperglycerolemia and glyceroluria. Two of three GKD subtypes are known as “isolate” GKD due to a mutation in GK gene alone: (1) symptomatic juvenile form, and (2) benign adult form, associated with an incidental finding of HTG.

Since most commercial laboratories determine triglyceride (TG) levels by a glycerol measurement, TG-backbone, patients with GKD are mistakenly labelled as having HTG. Glycerol-blanking is required to reveal the actual TG, but it is costly. Since usual TG-lowering medications are ineffective or even harmful, novel methods to screen for individuals with GKD or pseudo-HTG are necessary.

Objective: Through identification of a clinical case of GKD that was diagnosed by glycerol-blanking, we are proposing two potential methods to screen for pseudo-HTG, and presenting their reliability.

Methods: The patient was recruited into an IRB-approved study investigating etiologies of dyslipidemia at the University of Pennsylvania. Patient provided consent for medical record review.

Results: A 49-year-old man was referred for HTG management. His reported TG levels ranged between 490 and 559 mg/dL without any other adverse lipid levels for several years without a history of pancreatitis or diabetes mellitus. Intriguingly, he reported a family history of HTG.

Since TG-lowering medications (fibrates and fish oil) had not reduced his TG levels, specialized lipid analyses were obtained: a non-blanked TG level of 521 mg/dL and a glycerol-blanked TG of 66 mg/dL, consistent with pseudo-HTG or hyperglycerolemia. Repeat glycerol blanked TG levels were 68 and 69 mg/dL, confirming the previous result, and the likely diagnosis of GKD.

With two methods, estimated TG levels were calculated, using some of his laboratory values: (1) modified Friedewald equation to solve for TG with a direct LDL (dLDL) value, and (2) the application of a newly developed formula derived from a collection of 17,545 patient samples, to calculate the absolute TG-gap, using apolipoprotein A and B, estimating TG levels (% deltaTG), and determining whether a TG mesurement might be falsely deviated from the “plausible” TG value.

Although neither methods showed perfect concordance, the calculated TG-valued derived by the two methods were significantly lower than the non-glycerol blanked TG values. The difference was statistically significant (p<0.05).

Conclusion: The patient was clinically diagnosed with GKD, and was taken off of fibrate and the recently added niacin. These two methods can be used quickly to screen for pseudo-HTG or patients with GKD. Currently, it is unknown whether high glycerol levels are associated with high cardiovascular risks.
SAT-018 Androgen Actions in Adipose Tissue and the Brain Are Key Mediators in the Development of Polycystic Ovary Syndrome
Authors: Cox Madeleine J , Edwards Melissa C , Aflatounian Ali , Paris Valentina Rodriguez , Ledger William L , Gilchrist Robert B , Handelsman David J , Walters Kirsty A
Published: May 2020

Polycystic ovary syndrome (PCOS) is a complex disorder characterised by endocrine, reproductive and metabolic abnormalities. Despite PCOS being the most common endocrinopathy affecting women of reproductive age, its etiology is poorly understood so there is no cure and symptom-oriented treatment is suboptimal. Elucidation of the underlying mechanisms involved in the pathogenesis of PCOS would pave the way for the development of new interventions for PCOS. Hyperandrogenism is the most consistent feature observed in PCOS patients, and recently aberrant neuroendocrine signalling and adipose tissue function have been proposed as playing a pathogenic role in the development of experimental PCOS. To investigate the role of adipose tissue and the brain as potential key sites for androgen receptor (AR)-mediated development of PCOS, we combined an adipocyte and brain-specific ARKO knockout (AdBARKO) mouse model with a dihydrotestosterone (DHT)-induced mouse model of PCOS. Wildtype (WT) and AdBARKO prepubertal mice were implanted with a blank or DHT implant and examined after 12 weeks. In WT control females, DHT exposure induced the PCOS reproductive traits of cycle irregularity, ovulatory dysfunction and reduced follicle health. In contrast, these reproductive features of PCOS were absent in DHT-treated AdBARKO females. The PCOS metabolic characteristics of increased adiposity, adipocyte hypertrophy and hepatic steatosis were induced by DHT in WT females. Despite DHT treatment, AdBARKO females displayed normal white adipose tissue weight, and adipocyte hypertrophy and hepatic steatosis were not evident. However, as with WT mice, DHT treatment induced increased fasting glucose levels in AdBARKO females. These results demonstrate that adipose tissue and the brain are key loci for androgen-mediated actions involved in the developmental origins of PCOS. These findings support targeting adipocyte and neuroendocrine AR-driven pathways in the future development of novel therapeutic strategies for PCOS.
SUN-496 A Challenging Diagnosis of Thyrotoxic Periodic Paralysis
Authors: Mroueh Gabriela , Chemitiganti Ramachandra Rahul V
Published: May 2020

Thyrotoxic Periodic Paralysis (TPP) is a rare but potentially lethal manifestation of hyperthyroidism which is characterized by muscular weakness due to intracellular shift of potassium and subsequent hypokalemia. The muscular weakness may range from mild weakness to complete flaccid paralysis. It is predominantly seen in Asian young men. Graves’ disease has been described as the most common cause of TPP. Other rare causes of hypokalemic periodic paralysis include inherited disorders and acquired cases due to drug abuse, specifically cocaine. It is important to recognize and diagnose TPP to provide appropriate treatment and prevent serious cardiopulmonary complications.

A 26 year old Hispanic male with past medical history of cocaine abuse presented to the emergency department with profound lower extremity weakness since that morning. Laboratory studies on initial evaluation revealed hypokalemia. He was admitted to the intensive care unit (ICU) for IV potassium replacement and cardiac monitoring. Upon obtaining further history, the patient had suffered a similar episode of weakness and hypokalemia two months prior. At the time, he had a positive urine toxicology for cocaine. He was treated with IV potassium with resolution of his weakness and was told the reason for the episode was cocaine induced periodic paralysis. No further work up was done due to patient leaving Against Medical Advice. The patient stopped recreational drug abuse after this diagnosis.

During current hospitalization, further laboratory studies revealed hyperthyroidism. TSI and TPO antibodies were elevated and thus patient was diagnosed with Graves’ disease. On questioning, patient was asymptomatic and clinically euthyroid. He was treated with IV potassium, methimazole and propranolol with quick resolution of weakness. He has been followed in an out-patient basis and he has had no further exacerbations.

In this case, we present a case of TPP that was initially diagnosed as cocaine induced periodic paralysis which is an extremely rare disorder with only a couple of described cases in the literature. Diagnosis was initially missed as the patient was clinically euthyroid and had history of recreational drug abuse. Restoration of euthyroidism eliminates attacks of TPP. It is important to recognize and diagnose these patient to prevent further attacks.
SUN-901 A Case of Coexisting Insulinoma and Islet Cell Hyperplasia
Authors: Chin Yun Ann , Koh Huilin , Kek Peng Chin , Lim Shao Ting Dawn , Bee Yong Mong
Published: May 2020

Introduction

Insulinoma is the most common neuroendocrine tumour of the pancreas and cause of endogenous hyperinsulinemia hypoglycaemia. Islet cell hyperplasia is a rare cause of hypoglycaemia in adults.

Clinical Case

A 42-year-old lady presented with hyperphagia, giddiness, decreased concentration and weight gain of 10 kg over one year. Her symptoms occurred both during fasting and postprandial. She did not have any medical conditions and did not take alcohol.

A 72-hour fast confirmed the presence of endogenous hyperinsulinemia; serum glucose of 2.4 mmol/L paired with insulin 8.14 mU/L and C -peptide 0.71 nmol/L occurring after 16 hours of fasting. Screening for sulphonylureas and meglitinides was negative. Serum beta-hydroxybutyrate was 0.1 mmol/L with a 1.6 mmol/L rise in serum glucose post 1 mg glucagon administration. Computed tomography (CT) of the abdomen showed a 13 X 11 X 15 mm exophytic lesion at the superior aspect of the pancreatic body and another exophytic projection measuring 9 X 8 X 6 mm arising from the tail. In view of possible multifocal insulinoma, a 68Ga-DOTATATE scan was performed and it showed an intensely DOTATATE-avid exophytic nodule arising from the pancreatic body and a second indeterminate DOTATATE-avid nodule close to the pancreatic tail. In addition, there was diffuse DOTATATE uptake in the tail of pancreas.

She underwent enucleation of pancreatic body nodule and spleen-saving distal pancreatectomy as the pancreatic tail nodule was not seen intra-operatively. Histology showed an insulinoma; a well-differentiated neuroendocrine tumour (Grade 1, pT1 N0 Mx) that was positively stained for synaptophysin, CD56, insulin, SSTR2 and SSTR5. The pancreatic tail nodule and distal pancreatectomy specimen showed islet cell hyperplasia; the pancreatic parenchyma showed multiple foci of well-circumscribed nests of bland islet cells with similar morphology to those seen in the insulinoma. She did not have further hypoglycaemia episodes post-operatively.

Concomitant presence of fasting and postprandial hypoglycaemia may suggest underlying dual pathology. Clinical and biochemical differentiation between insulinoma and islet cell hyperplasia is difficult. Therefore, imaging for diagnosis and precise preoperative localisation is important for successful resection of suspected lesions. 68Ga-DOTATATE scan can be as useful as 68Ga-DOTANOC and 68Ga-DOTATOC scan and is better than CT scan in localising not only insulinoma but also islet cell hyperplasia. In this case, islet cell hyperplasia-induced hyperinsulinemic hypoglycaemia may have persisted if distal pancreatectomy was not performed.

Conclusion

Adult-onset endogenous hyperinsulinemia hypoglycaemia can be caused by concurrent insulinoma and islet cell hyperplasia. 68Ga-DOTATATE scan may be a useful, non-invasive investigation, especially in cases where CT imaging suggests multifocal disease.
SUN-250 Effects of Anti-Mullerian Hormone on the Expression of Gonadotropin Subunits in Pituitary Gonadotroph Cell Models
Authors: Kanasaki Haruhiko , Oride Aki , Tumurbaatar Tuvshintugs , Tumurgan Zolzaya , Kyo Satoru
Published: May 2020

Aim: We examined the effect of anti-Müllerian hormone (AMH) on the expression of gonadotropin subunits in pituitary gonadotrophs.Methods: The mouse pituitary gonadotroph cell line LβT2 was stimulated with AMH and the expression levels of gonadotropin subunits were determined by real-time PCR. We also examined the involvement of the Kiss-1 gene (encoding kisspeptin) and the kisspeptin receptor (Kiss-1R) in LβT2 cells. Results: A significant increase was observed in the expression level of the FSHβ subunit with AMH but not in the expression levels of gonadotropin α and LHβ subunits. A significant decrease was observed in the expression of Kiss-1 and Kiss-1R genes in LβT2 cells with AMH stimulation. Kiss-1 gene knockdown by siRNA did not alter the basal expression of gonadotropin subunits. When LβT2 cells overexpressing Kiss-1R were stimulated with kisspeptin, there was a significant increase in the gene expression levels of the gonadotropin subunits α, LHβ, and FSHβ. This inductive effect of kisspeptin was almost completely inhibited by AMH pretreatment. The GnRH-induced increase in gonadotropin subunit genes was unchanged in the presence of AMH. Conclusions: AMH can increase FSHβ subunit gene expression in pituitary gonadotroph cells. However, AMH decreases Kiss-1 and Kiss-1R gene expression within the gonadotrophs. Because AMH pretreatment abolishes kisspeptin-induced expression of gonadotropin subunit genes, AMH may control kisspeptin-regulated gonadotropin expression by inhibiting the expression and function of Kiss-1R within gonadotrophs.
SAT-593 Sex-Specific Modifications in MicroRNAs Contained in Exosomes of Astrocytes in Response to Palmitic Acid
Authors: Chowen Julie Ann , Guerra-Cantera Santiago , Collado-Perez Roberto , Argente Jesús , Frago Laura M
Published: May 2020

Communication between astrocytes and neurons is fundamental for correct functioning of the brain, in both physiological and pathophysiological situations. It is clear that astrocytes play an active role in metabolic control, but much is yet to be learned regarding how these glial cells and the neurons involved in energy intake/expenditure communicate to regulate energy homeostasis. We hypothesized that miRNAs contained in exosomes are an important means of cross-talk between these cells. Our objectives here were to determine whether the miRNA content of exosomes released by hypothalamic astrocytes changes in function of nutrient signals and if these signals are similar between males and females. To this end, primary hypothalamic astrocyte cultures were prepared from 2-day old male and female mice, using a standard protocol, and treated with palmitic acid (PA, 0.5 mM) or vehicle for 24 hours. The exosomes secreted into the culture media were purified and next generation sequencing analysis of the miRNAs contained in these microvesicles performed. Over 200 known miRNAs were identified in the samples. Heat map analysis of the 50 miRNAs most highly expressed across all samples showed significant differences based on sex and PA exposure, as well as differential changes between sexes in response to PA. Of the 25 most highly expressed miRNAs, 24 were significantly different between males and females (Benjamini-Hochberg FDR corrected p-values, between p<0.05 and p<0.0001). In response to PA, 190 miRNAs changed significantly in female astrocytes, but only 92 in male astrocytes; hence, after exposure to PA, 59 miRNAs were identified to be differentially expressed in exosomes of male and female astrocytes. Gene ontology enrichment analysis indicated that modifications in the miRNAs identified here could be related to biological processes such as response to cell injury, as might be expected, but also protein polymerization, receptor trafficking, intracellular signaling, microtubule polymerization, vasodilation, and cytoskeleton organization. Our results suggest that astrocytes communicate changes in nutrient availability to other cell types through miRNAs. Verification and determination of the specific responses to the modification in these miRNAs are now necessary.
SAT-174 Adrenal Incidentalomas: Prevalence and Referral Patterns in a UK University Hospital Using Real-Life Data
Authors: Hanna Fahmy W F , Hancock Sarah , George Cherian , Issa Basil George , Powner Gillian , Waldron Julian , Golash Anurag , Fryer Anthony
Published: May 2020

The estimated prevalence of adrenal incidentaloma at abdominal CT scan is 0.5-2% (1). However, from clinical practice, we noticed that incidentalomas are referred from other imaging modalities (eg MRI) and of other sites (eg thorax, spine). We therefore explored the relationship between prevalence rates and (i) imaging modality and (ii) its change over time, in a real world clinical setting from a large UK teaching hospital/trauma centre. We also examined the referral pattern of potential lesions to endocrinology. We extracted data from all radiology reports for all CT and MRI scans from Jan 2018-Oct 2019. We utilised a key phrase search strategy (eg adrenal adenoma/lesion/mass/nodule/incidentaloma, incidental adrenal, indeterminate adrenal). Where possible we excluded false hits (eg no adrenal lesion). These were linked to the referral patterns as identified by a referral logged or an attendance (new or follow-up) to endocrine clinic 3 months post index scan. Preliminary data showed that, from a total of 127878 scans performed, 2604 potential lesions were reported (prevalence 2.0%), comprising 2496/88838 (2.8%) CT scans and 108/39040 (0.3%) MRI scans. The number of scans/month increased in 2019 vs 2018 (6.9% for CT and 12.6% for MRI). Only 9.0% and 15.7% of reported potential lesions detected by CT and MRI, respectively, were referred for endocrine review. Hence, MRI patients were more likely to be referred than those with CT scans (p=0.018). Referral rates were lower in 2019 than 2018 (8.6% vs 14.4%; p less than 0.001). This approach has its limitations but allows efficiently review of large cohorts. Adrenal incidentalomas pose a rising challenge in view of increasing reliance on scanning. Despite a dedicated adrenal multidisciplinary team with a national track record in improving management of incidentalomas (2), the referral rate of potential lesions is worryingly low and not improving, with >90% of cases overlooked. This work is part of on-going innovation to enhance the pick-up rate for these cases whilst addressing the increased endocrine workload in a cost-effective manner. 1. Barzon L, Sonino N, Fallo F, Palu G, Boscaro M. Prevalence and natural history of adrenal incidentalomas. Eur J Endocrinol. 2003;149:273-285. 2. Hanna FWF, Issa BG, Lea SC, George C, Golash A, Firn M, Ogunmekan S, Maddock E, Sim J, Xydopoulos G, Fordham R, Fryer AA. Adrenal lesions found incidentally: how to improve clinical and cost-effectiveness. BMJ Open Quality. 2019;In press.
SUN-186 Case Report: Mifepristone Taper in an Individual with Equivocal Cushing’s Syndrome Screening Tests
Authors: Martin Christopher , Perez-Molinar David , Drake Tyler C
Published: May 2020

We present a 75-year-old male evaluated by the inpatient endocrine service during an admission for hemorrhagic stroke. Approximately 1 year prior to this admission he was started on mifepristone therapy for presumed Cushing’s Syndrome. Initial Cushing’s work-up was equivocal: 1 mg dexamethasone suppression cortisol level of 1.9 and midnight salivary cortisol 167 ng/dl. Random ACTH measurement was not obtained as part of this initial evaluation. Review of prior imaging studies did not demonstrate obvious culprit pituitary nor adrenal lesions. Mifepristone induced hyperaldosteronism, thyroid dysfunction and adrenal insufficiency were demonstrated presumably secondary to cortisol receptor antagonist induced up-regulation of adrenocorticotropic hormone and cortisol. We describe our experience stopping mifepristone and performing re-evaluation. We propose a tapering protocol in the setting of potentially untreated Cushing’s Syndrome and suggest use as a bridge therapy to surgical intervention rather than destination therapy.