bluuebunny/crossref_metadata_2025 huggingface dataset:
SAT-602 Hypothalamic P75 Neurotrophin Receptor Regulates Homeostatic Feeding and Food Anticipation
Authors: Podyma Brandon , Johnson Dove , Sipe Laura , Battin Katherine , Remcho Parks , Deppmann Christopher D , Güler Ali D
Published: May 2020

Proper circadian alignment of feeding behavior is necessary to prevent metabolic disease, and thus it is imperative to identify the neural circuits and molecular players that coordinate energy homeostasis. Neurotrophin signaling has been implicated in both metabolic and circadian processes, thereby representing a good candidate for regulating neural circuits driving time-of-day dependent feeding and foraging behavior. Here, we demonstrate that mice lacking the p75 neurotrophin receptor, p75NTR, have a behavioral defect in their ability to adequately respond to energy deficit. In response to fasting, p75KO mice (1) decrease their refeeding food intake compared to controls. Furthermore, following several days of restricted feeding, they (2) are unable to develop food anticipatory behavior (FAA), a phenomenon believed to be the output of a food-entrained circadian oscillator that has yet to be anatomically defined. Strikingly, these two phenotypes are observed only during the daytime, and not at night. These defects lead to increased weight loss, but do not appear to be mediated by changes in peripheral hormones. Notably, these effects are also independent of a role of p75NTR in development, as a global, adult-inducible p75NTR knockout recapitulates the feeding behavior of germline knockout mice. Rather, we demonstrate that p75NTR is discretely expressed in two hypothalamic regions known to be important for feeding behavior, the arcuate (ARC) and dorsomedial (DMH) hypothalamus. We find that p75KO mice have reduced fasting-induced activation of ARC, but not DMH, neurons. In addition, we show that ARC AgRP neuron p75NTR is necessary for fasting-induced refeeding and daytime FAA. We further suggest that AgRP-p75NTR is necessary to mediate AgRP neuron phospho-CREB signaling in response to energy deficit. Finally, given previous reports of involvement of the DMH in food anticipation, we asked whether DMH-p75NTR is necessary for feeding behavior and food anticipation. Strikingly, we find that p75NTR in the DMH is also necessary for FAA, but not for the control of homeostatic feeding. These data establish p75NTR as a novel regulator of energy homeostasis that acts to gate behavioral responses to food scarcity. It further posits that p75NTR may functionally link two independent hypothalamic regions to a time-of-day dependence of circadian food anticipation.
MON-165 Utility of Salivary Cortisol After 1 Mg Oral Dexamethasone in the Evaluation of Incidental Adrenal Tumors
Authors: Arregger Alejandro L , Contreras Liliana N , Cardoso Estela M L , Céspedes María E
Published: May 2020

The subclinical Cushing′s syndrome (SCS) is found in 20% of incidental adrenal tumors (AI). The overnight 1 mg oral dexamethasone suppression test (DST) with the measurement of circulating cortisol (F) is a sensitive method to rule out SCS. The assessment of salivary cortisol (SAF) as a surrogate of F became a non-invasive methodological advance. There are few data on the functional evaluation of AI through SAF in DST (SAFdex). The aim of this retrospective study was to investigate the utility of SAFdex for the detection of SCS in patients with AI. Subjects and Methods: 20 subjects with AI (7 male and 13 women; 65.0 ± 11.0 y/o; BMI: 26.5 ± 1.4) were studied. Sixteen had unilateral and 4 bilateral tumors (size: 10.0 - 90.0 mm; density (UH) was <10.0 in 17 cases and ≥ 10.0 in 3). They were not on drugs that may affect the HPA axis. Eight patients (1 male and 7 women; 20.0–60.0 y/o; BMI: 27.0 ± 3.0) with overt non ACTH dependent Cushing Syndrome (CS) were included as the reference group of active hypercortisolism. CS had unilateral adrenal tumors in 6 cases and bilateral in 2 (size: 11.0 -200.0 mm; density (UH) <10.0: n= 7 and >10.0: n=1).All subjects collected 24-hour urine for urinary free cortisol (UFC). After the urine collection, they obtained whole saliva samples at 23 h for cortisol (SAF23). Subsequently, they received 1 mg oral dexamethasone. The following day at 8 h, simultaneous blood (Fdex) and saliva (SAFdex) samples were obtained. F, SAF and UFC were determined by RIA and ACTH by IRMA. Reference values ​​from our laboratory (n= 100): UFC ≤90.0 µg / 24hs; ACTH: 10.0–50.0 pg / ml, SAF23: 0.5–3.8 nM / l; SAFdex: 0.5–2.0 nM; Fdex: 13.8–50.0 nM. Statistics were performed by Mann-Whitney and Spearman tests, p <0.05 was considered significant. In AI: ACTH 22.0 ± 11.0 pg /ml; UF:C 47.0 ± 20.0 µg / 24hs; SAF23: 1.5 ± 0.9 nM); SAFdex: 1.0 ± 0.5 nM and Fdex: 35.6 ± 10.0 nM were normal and significantly different from CS: 5.6±1.8 pg /ml; 391.0 ± 406.0 µg / 24hs; 20.0 ± 32.0 nM; 27.0 ± 24.0 nM and 674.0 ± 339.0 nM, respectively; p <0.05 in all cases. A positive and significant correlation was demonstrated between SAFdex and Fdex in AI (r = 0.830) and CS (r = 0.905); p <0.05 in both. Interestingly, a woman with overt CS and moderate signs of hypercortisolism, had normal SAF23 (1.5 nM) and UFC (76.0 µg / 24hs), while SAFdex (3.0 nM) and Fdex (69.0 nM) showed absence of suppression. Surgical resection of the adrenal tumor (an adrenocortical adenoma) and postoperative hypocorticism confirmed the diagnosis of CS.

Conclusion: SCS was excluded in all AI. The dexamethasone suppression test using saliva as a diagnostic fluid was a sensitive and practical method to rule out hypercortisolism in these patients.
SAT-067 Maternal Transmission of Pituitary Stalk Interruption Syndrome(PSIS)
Authors: Likki Snigdha Reddy , Allen Holley F , Gordner Chelsea
Published: May 2020

BACKGROUND: Pituitary stalk interruption syndrome (PSIS) is a rare entity characterized by thin or absent pituitary stalk, hypoplastic/aplastic anterior pituitary and ectopic posterior pituitary (EPP) on magnetic resonance imaging (MRI). PSIS can be associated with variable degrees of pituitary insufficiency 1. Most cases of combined pituitary hormone deficiency are sporadic, however in familial cases, there can be AD or AR inheritance with more than 30 genes identified in association with combined pituitary hormone deficiency (CPHD). We describe how diagnosis of 2 children with PSIS led to the discovery of the condition in their mother.

Clinical Case: Child 1 presented at age 3yrs with growth failure in 2003 with ht z score -4.24 SD. Subsequent work up revealed low IGF-1 (< 25 ng /mL) and MRI showed EPP, small anterior pituitary gland and absent pituitary stalk. No GH stim test was performed. He was started on GH supplementation and later was diagnosed with central hypothyroidism, central adrenal insufficiency and hypogonadotropic hypogonadism and is doing well on multiple hormone replacement at age 19 yrs.

Child 2, a half-brother to child 1 (same mother), presented at age 1yr with growth failure in 2017 with ht z score -2.06. GH stimulation test with glucagon was abnormal and resulted in a very low GH response (peak GH 0.52 ng/mL). MRI showed EPP with small anterior pituitary gland and interruption of the stalk. Later he was found to have central hypothyroidism and mild central adrenal insufficiency. He is receiving standard hormone replacement at 3 yrs of age.

Mother of above 2 patients presented 6 mos postpartum in 2017 after her 7th and last pregnancy with fatigue and amenorrhea. Laboratory evaluation revealed central hypothyroidism (FT4 0.76 ng/dL) and she was prescribed levothyroxine followed by resumption of her menses. She was unable to breastfeed her children due to lack of supply. There were no concerns for DI, amenorrhea or infertility. She was referred to Endocrinology in 2019 for persistent fatigue with a question of GH deficiency. IGF-1 level was normal 114 ng/mL(z score -0.39) and GH stimulation test (clonidine + glucagon) was abnormal with peak GH 1.85 ng/ml. MRI showed EPP with hypoplastic pituitary stalk. Genetic testing was done for CPHD Sequencing Panel at Prevention Genetics which includes GL12, HESX1, LHX3, LHX4, OTX2, POU1F1, PROP1F1, PROP1, SOX2, SOX3 genes and results were negative. She has 4 other children (21, 12, 11, 10yrs) who are currently being investigated for hormone deficiencies. One child died at 3 months of age due to SIDS.

Conclusion: We present 3 family members with PSIS. This family highlights the variable clinical phenotype of PSIS and importance of careful family history when evaluating children with congenital pituitary abnormalities and supports the need for more extensive gene panels for evaluation of CPHD.

Reference:. Acta Endocrinologica, 2017. 13(1):96–105
SUN-189 A Case of Delayed Hypoaldosteronism Following Unilateral Adrenalectomy for Primary Aldosteronism
Authors: Schommer Julie , Shibli-Rahhal Amal A
Published: May 2020

BACKGROUND: Hypoaldosteronism occurs in 6–30% of patients following unilateral adrenalectomy for primary aldosteronism. The Endocrine Society guidelines recommend discontinuing potassium supplementation and spironolactone postoperatively with repeat renin and aldosterone after surgery to monitor for cure. Clinical Case: A 69-year-old male with a 15-year history of hypertension on amlodipine 10 mg daily, atenolol 100 mg daily, terazosin 5 mg daily, valsartan 160 mg daily, spironolactone 50 mg three times daily, with longstanding hypokalemia on potassium chloride 20 mEq four times daily presented with an ischemic stroke and persistent hypertension (BP 182/79). Following discontinuation of spironolactone, evaluation revealed aldosterone concentration of 214 ng/dL (normal 4.0 - 31) and plasma renin activity of 0.1 ng/mL/hr (normal 0.5 - 4.0), giving an aldosterone-to-renin ratio of 2,140. CT of the abdomen showed a 3 cm right adrenal mass. He underwent uncomplicated right adrenalectomy for primary aldosteronism. Postoperative potassium was 3.4 mEq/L (normal 3.5–5.0) and hypertension persisted, so he was discharged on potassium chloride 10 mEq, losartan 100 mg daily, amlodipine 10 mg daily, and labetalol 200 mg twice daily. Two weeks later potassium level was 5.1 mEq/L and potassium chloride supplement was discontinued. Six months postoperatively, potassium was 5.7 mEq/L with well-controlled blood pressure, so losartan was discontinued. Labs over the subsequent several weeks showed persistent hyperkalemia up to 6.2 mEq/L and new hyponatremia to 128 mEq/L (normal 134 - 150). Repeat plasma renin activity was 0.51 ng/mL/hr and aldosterone concentration <1.0 ng/dL. Morning cortisol concentration was 18.3 ug/dL (normal 6.7 - 22.6) and ACTH 38 pg/mL (normal 6.0 - 50 pg/mL). He was diagnosed with postsurgical hypoaldosteronism. Potassium stabilized at 5.1 mEq/L and sodium stabilized at 134 mEq/L, so he was monitored without treatment for hypoaldosteronism. One year postoperatively his labs showed: potassium 5.1 mEq/L, sodium 135 mEq/L, renin 1.0 ng/mL/hr, and aldosterone 5.7 ng/dL. Conclusion: This patient had primary aldosteronism leading to suppression of aldosterone secretion from the contralateral healthy adrenal gland. This resulted in postoperative hypoaldosteronism once the affected adrenal gland was resected. This case demonstrates the need for continued monitoring of potassium, sodium, renin, and aldosterone following unilateral adrenalectomy for primary aldosteronism, especially in the setting of postoperative angiotensin receptor blocker use or other medications which can affect the renin-angiotensin-aldosterone system.
SAT-021 Effects of E2/P4 Oral Capsules on Bone Turnover in Women with Vasomotor Symptoms
Authors: Constantine Ginger , McClung Michael R , Kagan Risa , Graham Shelli , Bernick Brian , Mirkin Sebastian
Published: May 2020

Menopausal hormone therapy slows bone turnover and reduces the risk of osteoporotic fractures. The objective of this post hoc analysis was to evaluate bone turnover markers (BTM) in the phase 3 REPLENISH trial, which evaluated vasomotor symptoms (VMS) with an oral estradiol/progesterone (E2/P4) in postmenopausal women with a uterus.

Eligible women for this analysis had ≥50 moderate to severe VMS/week, <5 years since last menstrual period, and BTM measurements at baseline, and months 6 and 12. Percent changes for 3 BTM (bone specific alkaline phosphatase [BSAP], C-terminal telopeptide of type I collagen [CTX-1], and N-terminal propeptide of type I procollagen [PINP]) assessed by immunoassay methods were evaluated from baseline to months 6 and 12 for the 1/100, 0.5/100 and placebo groups.

A total of 157 women (40–61 years, 69% White) were analyzed (56 for each 1/100 and 0.5/100; 45 for placebo). Mean baseline values ranged from 14.0–14.3 U/L for BSAP, 0.34–0.39 ng/mL for CTX-1, and 76.9–79.3 ng/mL for PINP. Mean differences in percent change from baseline versus placebo significantly decreased with both E2/P4 doses for all 3 BTM at months 6 and 12. Mean differences from placebo for E2/P4 at months 6/12 ranged from -8.1% to -17.8% for BSAP (all, P≤0.02), -30% to -41% for CTX-1 (all, P≤0.001), and -14% to -29% for PINP (all, P≤0.007).

REPLENISH data provide support for a potential skeletal benefit of E2/P4 when used for the treatment of moderate to severe VMS.
MON-041 Diagnostic Performance of Ovarian Morphology for Anovulatory Conditions in Lean and Overweight Women
Authors: Brink Heidi Vanden , Jarrett Brittany Y , Pereira Nigel , Spandorfer Steven D , Hoeger Kathleen M , Lujan Marla Elaine
Published: May 2020

Introduction: Sonographic evidence of polycystic ovarian morphology (PCOM) is a cardinal feature of polycystic ovary syndrome (PCOS), a condition which reflects a spectrum of phenotypes. The criteria to define PCOM are based on an upper threshold for follicle number and ovarian size in lean, regularly cycling women. Whether ovarian features can be used to distinguish between distinct anovulatory conditions is unclear, as is any impact of body mass index (BMI) on the diagnostic performance of ovarian morphology for anovulatory conditions.

Objectives: To determine whether ovarian morphology can discriminate between women with regular cycles, normoandrogenic anovulation (NA-Anov), and hyperandrogenic (HA-Anov) anovulation. Any impact of BMI-specific thresholds to improve the diagnostic performance of ovarian morphology for anovulatory conditions was determined.

Methods: Women with HA-Anov (biochemical and/or clinical hyperandrogenism and irregular cycles; N=53), NA-Anov (irregular cycles in the absence of hyperandrogenism; N=42), and normoandrogenic women with regular cycles (Controls, N=41) underwent a reproductive health history, physical exam, transvaginal ultrasound scan of their ovaries and fasting blood tests for reproductive hormones. Follicle number per ovary (FNPO, 2-9mm) and ovarian volume (OV) were determined. The diagnostic performance of sonographic markers for anovulatory conditions was tested using receiver operating characteristic curves.

Results: FNPO and OV discriminated between HA-Anov and Controls when all women were considered (area under the curve [AUC]=0.82, sensitivity [Se] 72%, specificity [Sp] 90% and AUC=0.84, Se 77%, Se 81%, respectively). The diagnostic accuracy (AUC = 0.87) and sensitivity (83%) of FNPO improved in lean women (BMI < 25kg/m2), whereas specificity (93%) improved for women with overweight/obesity (BMI > 25kg/m2). By contrast, the diagnostic performance of OV declined when BMI was considered. FNPO discriminated between HA-Anov and NA-Anov in lean women (AUC=0.77) whereas OV discriminated between anovulatory conditions in women with overweight or obesity (AUC=0.76). FNPO, but not OV, differentiated between NA-Anov and controls – albeit thresholds were lower for women in lean (>22 follicles) versus overweight categories (>38 follicles).

Conclusion: Ovarian morphology has diagnostic potential for anovulatory conditions – but its performance is impacted by BMI status. OV differentiated between HA and NA status, whereas follicle counts discriminated anovulatory conditions from controls suggesting differential roles for FNPO and OV in reproductive dysfunction. Consideration of BMI improved diagnostic performance in some cases, however the overlap in morphological features between NA- and HA-Anov is too extensive to propose condition-specific thresholds at this time.
SAT-305 Veldoreotide (COR005) Mechanisms of Action Studies: Comparison to Octreotide and Pasireotide
Authors: Dasgupta Pooja , Schulz Stefan
Published: May 2020

Stable somatostatin analogs (SSAs) are the first choice for medical treatment of pituitary adenomas and other neuroendocrine tumors. The somatostatin analogs octreotide, pasireotide, and veldoreotide primarily have been characterized according to their binding profiles. However, their ability to activate individual somatostatin receptor subtypes (SSTs) has not been directly assessed so far. In this study, we assessed G-protein signaling in human embryonic kidney (HEK293) cells stably expressing G protein-coupled inwardly rectifying potassium (GIRK) channels and SSTs using a novel fluorescence-based membrane potential assay. Dose-response curves obtained for veldoreotide revealed high potency and efficacy in cells expressing SST2, SST4, and SST5. Veldoreotide also inhibited proliferation and chromogranin A secretion in SST4-transfected BON-1 cells. In addition, we assessed G-protein signaling in primary pituitary cultures from SST2 and SST5 knockout mice. Our results show that octreotide mediates its effects selectively via the SST2 receptor. Conversely, pasireotide mediates its effects selectively via the SST5 receptor. In contrast, veldoreotide can activate both SST2 and SST5 receptors under otherwise identical conditions. Thus, veldoreotide is a unique SSA with full agonistic activity at the SST2, SST4, and SST5 receptors.
MON-583 Identifying Active Duty Military Meal Planning Preferences to Maximize Nutrition Therapy for Obesity
Authors: Clerc Philip , Wardian Jana
Published: May 2020

INTRODUCTION: Obesity rates exceed 30% for active duty service members with vitals in the military health system electronic medical records. Although nutrition therapy is a cornerstone of treatment for all individuals with obesity, it is even more important in active duty service members, who have restrictions for obesity medications and are not eligible to receive bariatric surgery. Among nutrition therapy services, online nutritional cooking classes are the most desired intervention by patients at our institution. We currently do not have this resource available. The aim of this survey was to identify meal planning preferences among active duty service members to guide the development of online nutritional cooking classes.

METHODS: Surveys were distributed to active duty service members and/or their spouses at San Antonio Military Medical Center and Wilford Hall Medical Center in the summer of 2019. Data included preferences for time spent cooking each meal, weekly grocery budget, meal size, batch cooking preference, available kitchen equipment, most common meals eaten, and desired features in an online nutritional cooking class.

RESULTS: 141 surveys were collected, 77% of whom were active duty service members and 23% of whom were spouses of active duty service members. Most respondents stated they could spend 15 minutes or less on cooking breakfast (65%) and lunch (69%) on a daily basis. The majority of respondents (84%) were willing to batch cook. Half of respondents (50%) were willing to spend $100-$150 on food per week. Over 90% of respondents had to cook for a household of 4 people or less. Of respondents with children, 78% fed children the same meal that they cooked for themselves. About half of respondents had a food processor (55%) and an electronic pressure cooker (52%). Few respondents (14%) shopped for food at specialty grocery stores or farmer’s markets. Half of respondents (50%) preferred a 5–10 minute duration for each online nutritional cooking class. Of the many highly desired features for the classes, the option to watch on a smart phone was the most desired feature (97%).

CONCLUSION: This sample of active duty service members and their spouses demonstrated a high degree of congruity for meal planning preferences and requested features for online nutritional cooking classes. Development of online nutritional cooking classes targeted to these preferences may lead to a higher success rate of nutrition therapy than current interventions.

DISCLAIMER: The views expressed are those of the authors and do not reflect the official views or policy of the Department of Defense or its Components.
SAT-458 A Case of Cardiac Arrest Due to Hashimoto’s Thyroiditis Associated Cardiac Tamponade
Authors: Krutilova Petra , Patel Sabah , Mir Wasey Ali Yadullahi , Gilden Janice L , Syed Uzma N
Published: May 2020

Introduction: Myxedema coma is currently an uncommon medical emergency. We present a case of undiagnosed Hashimoto’s thyroiditis with myxedema coma and cardiac tamponade leading to cardiac arrest.

Case Presentation: A 35 year-old man with no significant past medical history was brought to the emergency department after being found unresponsive. The patient was hypoglycemic (17 mg/dL), hypothermic (34°C), tachypneic (26/min), hypotensive (84/50 mmHg), and hypoxemic (90% on ambient air). Physical exam showed mild anasarca, jugular vein distention, clear lung sounds, and muffled heart sounds. Laboratory findings showed TSH 168.16 uIU/mL (0.45–5.33 uIU/mL), fT4 <0.25 ng/dL (0.58–1.64 ng/dL), fT3 1.33 pg/mL (2.5–3.9 pg/mL), cortisol 5.7 mcg/dL (3–16 mcg/dL). Chest x-ray demonstrated markedly enlarged, globular heart. ECG revealed sinus rhythm and low voltage of QRS complexes. Echocardiogram was significant for a very large pericardial effusion. Resuscitation was started with intravenous thyroxine and hydrocortisone, during which the patient was found to be in a cardiac arrest with pulseless electrical activity. CPR per ACLS protocol was initiated with return of spontaneous circulation. Clear fluid (2000 ml) was evacuated from the pericardial space. He was diagnosed with Hashimoto thyroiditis (thyroid peroxidase antibody level 355 IU/mL, normal <9 IU/mL). He recovered without neurological deficits and was discharged home with thyroid replacement therapy (levothyroxine 100 mcg).

Discussion: Myxedema coma occurs as a complication of undiagnosed/untreated thyroid disease. It may be precipitated by an event such as infection, drug overdose, or myocardial infarction. The mainstay of treatment is T4 replacement along with supportive therapy, and glucocorticoids to counter possible underlying adrenal insufficiency. Massive pericardial effusion due to hypothyroidism, especially resulting in cardiac tamponade, is extremely rare. The incidence of pericardial effusion in patients with hypothyroidism has significantly decreased from 30–80% to 3–6%, due to early recognition of this common disorder. Our case highlights the importance of prompt recognition of hypothyroidism as a cause of cardiac tamponade, thus allowing rapid life-saving treatment. In patient populations with limited access to health care, it should be remembered that very late and potentially fatal complications of otherwise easily treatable conditions can occur. Awareness of this may help limit morbidity and mortality.

References: Kabadi UM, Kumar SP. Pericardial effusion in primary hyperparathyroidism. Am Heart J. 1990; 120:1393.
SUN-557 Hypertriglyceridemia-Induced Pancreatitis: Experience from a Quaternary Care Center
Authors: Béland-Bonenfant Sarah , Paquette Martine , Baass Alexis , Bernard Sophie
Published: May 2020

Severe hypertriglyceridemia is defined by triglycerides levels reaching 11,3 mmol/L (1000 mg/dL) or when chylomicrons are present in the circulation (1). Severe hypertriglyceridemia increases the risk of acute pancreatitis, a serious complication that can be recurrent and fatal. Severe hypertriglyceridemia is most often caused by an underlying primary chylomicronemia disease, either monogenic of multifactorial. Familial chylomicronemia syndrome is a rare autosomal recessive disease that can result from mutations in lipoprotein lipase in more than 90% of cases. Multifactorial chylomicronemia is an oligogenic or polygenic disorder characterized by a reduction in lipoprotein lipase activity. Primary chylomicronemia should be managed in a specialized lipid clinic before acute pancreatitis occur. However, primary chylomicronemia is underdiagnosed (2). This is why hospitalization for an acute episode of hypertriglyceridemia-induced pancreatitis is a window of opportunity to investigate these patients.

The first objective of our study was to investigate retrospectively the quality of the follow-up of patients hospitalized for hypertriglyceridemia-induced acute pancreatitis, specifically looking at specialized lipid clinic referrals. The second objective was to correlate triglyceride (TG) levels with severity of the pancreatitis.

A total of 1063 patients were hospitalized for acute pancreatitis at our center between 2012 and 2019. Twenty-five patients (2.35%) were diagnosed with hypertriglyceridemia-induced pancreatitis. Of those 25 patients, one died of pancreatitis complications, two were already diagnosed with primary chylomicronemia, and of the remaining twenty-two, 11 (50%) had a referral for an evaluation at a specialized lipid clinic. Those referrals resulted in three diagnoses of primary chylomicronemia, with a multidisciplinary follow-up. Regarding severity of pancreatitis, TG levels were positively correlated with patients being hospitalized in the intensive care unit (ICU) and also having longer stays in the ICU.

Only half of patients hospitalized for a hypertriglyceridemia-induced pancreatitis at our center had a referral for lipid disorder evaluation upon hospital discharge. We believe it is important to raise awareness concerning primary chylomicronemia to avoid recurrent acute pancreatitis preceding diagnosis, seeing this pathology increases morbidity and mortality.

1. Valdivielso et al. Eur J Intern Med. 2014;25(8):689-94. 2. Brown et al. J Clin Lipidol. 2018;12(2):254-263.
SUN-193 A Case of Cushing’s Syndrome Caused by Epidural Corticoidsteroid Injection
Authors: Villanueva Fiorella Sotomayor , Nguyen Huong
Published: May 2020

Introduction: Cushing’s syndrome (CS) is a collection of signs and symptoms caused by hypercortisolism that results from endogenous or exogenous glucocorticoid excess. It is associated with increased morbidity and mortality from musculoskeletal, metabolic, thrombotic, infectious and cardiovascular complications. The most common cause of CS today is the use of corticosteroid medications. It′s reported that more than 10 million American receive pharmacological doses of glucocorticoids each year. Case reports have shown that CS can be caused by non-systemic use of corticosteroids. Clinical case: A 53-year-old patient with past medical history of osteoarthritis who presented to outpatient endocrinology office for new onset facial swelling of 2 months. His PCP had attributed it to adverse effect of recent neck glucocorticoid injections and treated him with prednisone for 7 days without any relief. Subsequently, he was referred to Endocrinology due to concern about Cushing′s syndrome. The patient reported associated easy bruising and decreased libido. On further questioning, patient mentioned he had been receiving several epidural steroid injections in the neck, shoulders and back in the past. Per record review, from June to November 2018, he had received multiple triamcinolone and dexamethasone injections as follows: 10mg dexamethasone in each C4-5, C5-6 and C6-7 facet joints; 5mg triamcinolone injections in the right C4-5, C6-C7, left C4-5, C6 and C7, and 40mg of triamcinolone in C7-T1. The patient also reported he had multiple injections in 2019, but these records were not available. Physical exam showed hypertension, facial plethora, and scattered bilateral arm ecchymosis. Laboratory study showed hyperglycemia. Given suspicion for CS, further workup, including morning serum cortisol, ACTH, and 24-hour urine cortisol were ordered, which were 0.5 ug/dl (6.2-19.4 ug/dl), 4.3 pg/ml (7.2-63.3 pg/ml) and <2 ug/24 hours (5-64 ug/24 hours) respectively, suggesting iatrogenic CS secondary to corticoid steroid injection. Also, given that the patient reported lightheadedness, and decreased libido, cosyntropin stimulation test and free testosterone, FSH and LH were ordered to rule out adrenal insufficiency and hypogonadism respectively. Hypogonadism was ruled out, however, cosyntropin stimulation test showed peak cortisol of 12 and 16 mcg/dL at 30 and 60 minutes (>18 mcg/dL), suggesting adrenal insufficiency, due to suppression of endogenous cortisol production from exogenous glucocorticoid use. Patient was started on hydrocortisone and all glucocoirticoid injections were stopped. Conclusions: Many different non-systemic corticosteroid administrations can cause iatrogenic Cushing’s Syndrome, and therefore, physicians should be thoughtful when prescribing steroids regardless of administration form.
SUN-094 Long-Term Safety and Efficacy of Leuprorelin in Treating Central Precocious Puberty: A Large, Open-Label, Multicenter, Phase IV Study in China
Authors: Luo Xiaoping , Hou Ling , Zhong Yan , Yang Yu , Li Pin , Qiu Wenjuan , Liu Ying , Luo Feihong , Hu Yuhua , Wang Qing , Du Hongwei , Fu Junfen , Wang Winston
Published: May 2020

BACKGROUND: Leuprorelin (Enantone®) is a gonadotropin-releasing hormone (GnRH) analogue used worldwide to treat central precocious puberty (CPP). This clinical trial aimed to evaluate the long-term safety and efficacy of leuprorelin in treating Chinese CPP children.

Methods: This is the first, prospective, open-label, and multicenter study conducted from 2015 to 2018, in China. As a large interventional study, it included a four-week screening period, a 96-week treatment period, and a four-week safety follow-up period. Eligible subjects were treated with leuprorelin subcutaneously once every four weeks for 96 weeks. At the beginning of the study, subjects whose body weight ≥20 kg received a dose of 3.75 mg and those <20 kg received a dose of 1.88 mg and then the dose was allowed to be adjusted during the study based on subject’s condition and investigator’s judgment. The primary endpoint was the incidence of adverse events during treatment, and the secondary endpoint was the percentage of subjects who had regression or no progression in Tanner stage at Week 96 compared with baseline.

Results: A total of 307 CPP patients from 11 Chinese medical centers received leuprorelin, of which 305 (99.3%) were girls and 2 were boys (0.7%), with a mean (±SD) age of 7.95±0.982 years and a mean height of 133.68±7.108 cm. Two hundred eighty-three (92.2%) patients completed the 96-week treatment period. Two hundred fifty-two patients (82.1%) reported treatment-emergent adverse events (TEAEs)—most of which (79.5%) were mild to moderate. Only 33 (10.7%) patients experienced TEAEs that were considered related to leuprorelin. The most frequent (>2%) drug-related TEAEs were injection site induration (4.6%, 14/307) and vaginal bleeding (2.3%, 7/305). After the 96-week treatment period, 83.5% female subjects had regression or no progression in Tanner stage compared with baseline (95% CI: 78.68%, 87.62%) and the 2 male subjects had progression of 1 point in Tanner stage genital score occurred at Week 12 and then remained stable throughout the study. By the end of the treatment period, the majority of subjects had decreased GnRH stimulated peak LH and FSH, as well as reduced sex hormone levels and bone age/chronological age ratio compared with baseline. The subjects also had increased predicted adult height and BMI after treatment.

Conclusions: This Chinese study demonstrated that CPP was effectively treated in most patients who received leuprorelin (Enantone®) for nearly two years. Any drug-related adverse events were reported with low incidence (<5%) and were consistent with the known safety profile of leuprorelin. Leuprorelin was shown to be well tolerated and effective in the management of CPP in Chinese patients.
MON-312 The Effects of Cabergoline in Pre-Surgical and Recurrence Periods of Cushing’s Disease Patients
Authors: Pereira Ana Julia Garcia , Andrade Natália Xavier S , Musolino Nina Rosa de Castro , Cescato Valter Angelo Sperling , da Silva Gilberto Ochman , Fragoso Maria Candida Barisson Villares , Bronstein Marcello Delano , Machado Marcio Carlos
Published: May 2020

BACKGROUND: Dopaminergic agonist cabergoline (CAB) has been used in pharmacological treatment of Cushing’s disease (CD). The effect is attributed to the frequent expression of subtype 2 dopamine receptor in corticotropic tumors. However, in vivo studies demonstrated normalization of urinary cortisol (UC) in about 30-40% of cases over the long term, mainly after surgical failure. Objective: To evaluate the effect of CAB as monotherapy in early preoperative period and on recurrence of Cushing’s disease. Methods. A single-center retrospective study was conducted in a tertiary referral center. Twenty-one patients with confirmed CD were included. Median age was 32 years (13-70), 86% female, 10 with microadenomas, 11 with macroadenomas. They were diagnosed from 1986 to 2016 and used CAB as monotherapy either in the preoperative period (n=7, CABi) or in recurrence, before any other treatment (n=14, CABr). It was considered ‘complete response’ a 24h-UC normalization and ‘partial response’ a 24h-UC reduction >50%. UC was obtained on the last follow-up evaluation. Normalization of nocturnal salivary cortisol (NSC) on CAB was evaluated in most cases, as well as the larger tumor diameter by pituitary MRI, before and after CAB treatment. Results: Complete response was achieved in 29% (6/21) of subjects after 14.9±16.4 months of treatment with a mean dose of 2.2±1.0 mg/wweek. Partial response occurred in 9.5% (2/21). NSC normalized in 35% (6/17) and no variation in tumor diameter before and after CAB use was observed (n=13): 6.8±6.8 vs. 7.2±7.1 mm, respectively. There was no normalization of UC in CABi at the end of the treatment whereas in CABr, 43% (6/14) of patients reached complete response. CABi group was treated for 4.7±1.9 months and CABr was treated for 20.1±18.1 months. Both groups were on similar doses of CAB (CABi 2.1±0.9 and CABr 2.3±1.1 mg/w). Interestingly, the difference between the groups’ complete response was evident early on 3 months of treatment: no cases in CABi vs. 60% (6/10) in CABr (p=0.035) despite a lower dose in CABr (1.0 vs. 1.5; p=0.008). Normalization of NSC occurred in 20% in CABi and 42% in CABr. Conclusion. Normalization of UC and NSC occurred in about 30% of total patients, mainly those who used CAB on recurrence of CD. Due to the small number of subjects in CABi group, the absence of hormone control in this group requires further investigation in order to verify the effectiveness of CAB as primary therapy or as preoperative treatment option.
MON-012 The Direct Effect of Kisspeptin on Human Ovarian Granulosa Cells to Regulate Steroidogenesis
Authors: Qin Lixian , Sitticharoon Chantacha , Sririwichitchai Rungnapa , Keadkraichaiwat Issarawan , Maikaew Pailin , Churintaraphan Malika
Published: May 2020

Kisspeptin has a central role to stimulate the hypothalamic-pituitary-gonadal (HPG) axis. Furthermore, a previous study has suggested that kisspeptin might have a peripheral role in follicular development (1). This study aimed to 1) explore the effect of kisspeptin on CYP19A1 (aromatase) mRNA expression in human granulosa cells and aromatase concentrations in the supernatant; and 2) investigate the effect of kisspeptin on FSHR mRNA expression in human granulosa cells. In this study, human granulosa-like tumor cell line (KGN) (n=3) was incubated for 24 hours with FSH (10-8 M); FSH with IGF-1 (10-8 M); different doses of kisspeptin including 1, 10, 100, 1,000, and 10,000 nM; FSH with different doses of kisspeptin; and FSH with IGF-1 together with different doses of kisspeptin. FSH treatment alone or FSH with IGF-1 did not increase CYP19A1 mRNA expression when compared to control. Interestingly, kisspeptin treatment at the doses of 100 nM (P=0.028), 1,000 nM (P=0.005), and 10,000 nM (P=0.009) in the presence of FSH together with IGF-1 enhanced CYP19A1 mRNA expression when compared with control. Furthermore, FSH or FSH with IGF-1 or FSH with all doses of kisspeptin or FSH with IGF-1 together with all doses of kisspeptin increased aromatase concentrations in the supernatant when compared to control (P<0.01 all). Surprisingly, kisspeptin at the dose of 10,000 nM with FSH or FSH together with IGF-1 statistically increased aromatase concentrations in the supernatant when compared with FSH treatment alone or FSH with IGF-1 treatment (P<0.01 all). FSHR mRNA expression was comparable between control and all treatments. As a result, kisspeptin combined with FSH and IGF-1 could enhance CYP19A1 mRNA expression in human granulosa cells and the high dose of kisspeptin (10,000 nM) might be able to augment aromatase secretion in the supernatant. These results suggest that kisspeptin might enhance aromatase expression and secretion, which probably leads to enhance estrogen synthesis. Further studies regarding kisspeptin treatment on estrogen synthesis or secretion in human granulosa cells should be confirmed. Reference: (1) Fernandois D, et al. J Endocrinol. 2016;228(3):161-70.
OR31-03 Single-Cell Profiling of Adult Human Ovarian Cortex Reveals Six Main Cell Types but No Germline Stem Cells
Authors: Wagner Magdalena , Yoshihara Masahito , Douagi Iyadh , Damdimopoulos Anastasios , Panula Sarita , Petropoulos Sophie , Lu Haojiang , Pettersson Karin , Palm Kerstin , Katayama Shintaro , Hovatta Outi , Kere Juha , Lanner Fredrik , Damdimopoulou Pauliina
Published: May 2020

The human ovary orchestrates sex hormone production and undergoes monthly structural changes to release mature oocytes. The outer lining of the ovary (cortex) has a key role in defining fertility in women as it harbors the ovarian reserve. It has been suggested that oogonial stem cells exist in the ovarian cortex and that these can be captured by DDX4 antibody isolation. Our study aimed at comprehensive characterization of all cell types present in the ovarian cortex, including the previously reported oogonial stem cells. We developed methods to dissociate human ovarian cortex to a viable single cell solution allowing subsequent analysis by single cell transcriptomic profiling and cell surface antigen screening. In all analyses, cells captured by DDX4 antibodies (DDX4 Ab+) were included as a reference. High quality ovarian cortex tissue from gender reassignement and caesarean section patients was used in the analyses. Our single cell transcriptomic analyses based on >24,000 cells revealed the presence of six main cell types in ovarian cortex; oocytes, granulosa cells, immune cells, endothelial cells, perivascular cells, and stromal cells. Surface marker screening showed robust expression of 43 cell surface antigens in ovarian cortex cells. With the help of transcriptomic and cell surface antigen profiles, the DDX4 Ab+ cells were identified as perivascular cells. This finding was validated by immunostaining of ovarian tissue showing DDX4 Ab+ cells lining CD31 positive endothelial cells of blood vessels. To search for germline stem cells on a broader front, we compared our data with human fetal ovary cells including pre-meiotic germ cells (Li et al. 2017) and found no evidence for the presence of germ line stem cells of any kind in adult human ovarian cortex. In summary, we provide the first cell map of human ovarian cortex. Our results demonstrate six main cell types, but cannot provide support to the existence of oogonial stem cells. This dataset will be a valuable tool for studying the role of specific cell populations in ovarian biology, dissecting causes of infertility, and developing novel assisted reproductive technologies or even contraceptives.
SUN-923 Combination Immune Checkpoint Inhibitor Therapy for ACTH-Secreting Pituitary Carcinoma
Authors: de Filette Jeroen M K , Sol Bastiaan , Awada Gil , Aspeslagh Sandrine , Andreescu Corina E , Neyns Bart , Velkeniers Brigitte
Published: May 2020

Introduction

Pituitary carcinoma is a rare yet serious entity with poor prognosis despite multimodal therapies. Cerebrospinal and/or systemic metastases are present by definition, making adjuvant systemic therapy necessary. Novel treatments are urgently needed for refractory cases. Immunotherapy with immune checkpoint inhibitors (ICI) targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4), programmed cell death 1 (PD-1) or its ligand (PD-L1) has been a revolution in multiple malignancies. The expression of CTLA-4 and PD-L1 has been elucidated in pituitary adenomas and could be implicated in pituitary carcinomas as well. Hypophysitis is also a frequent endocrine immune-related adverse event, especially during CTLA-4 blockade (with ipilimumab) or combination ICI. However, the efficacy of ICI in the treatment of refractory pituitary tumors has yet to be established. In 2018, Lin et al. successfully treated a first case of a hypermutated aggressive ACTH-secreting pituitary carcinoma with ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1) combination immunotherapy.

Clinical Case

We report a 40-year old male, diagnosed with an invasive ACTH-secreting pituitary macroadenoma in 2012, initially treated by transsphenoidal and transcranial surgery, followed by adjuvant stereotactic radiotherapy and several courses of ketoconazole. In 2017, he presented to our clinic for a recurrent Cushing’s phenotype despite maximal dosing of ketoconazole. Therapy both with pasireotide and cabergoline was unable to normalize cortisol levels and a bilateral (subtotal) adrenalectomy was performed. In June 2018, he presented to our emergency department with acute diplopia due to a left abducens nerve palsy. Imaging revealed recurrent invasion of the tumor into the sella turcica and cavernous sinus, together with cerebellar and drop metastases at the cervical spine. Temozolomide (TMZ) was initiated for a total of 9 cycles. Progressive disease was observed with development of new onset right oculomotor nerve palsy after the last TMZ cycle, and persistence of elevated serum ACTH-cortisol and urinary cortisol levels, despite the absence of radiological progression. Therefore, he was started in a compassionate use setting with a combination ICI therapy with ipilimumab 3 mg/kg and nivolumab 1 mg/kg (for 4 cycles), followed by maintenance nivolumab therapy (240 mg) every two weeks. He has stable disease (both radiographically and hormonally) five months after the initiation of the immunotherapy.

Clinical Lesson(s) or Conclusion(s)

We report the second case of ACTH-secreting pituitary carcinoma treated with combination ICI therapy. The disease status of the patient is stable up until now, suggesting at least disease control by the immunotherapy. Checkpoint blockade inhibitors are a promising novel treatment modality for refractory pituitary tumors and should be further studied.
SUN-157 Delayed Diagnosis of Cushings Syndrome: Hiding in Plain Sight!
Authors: Jalil Fatima , Taxel Pamela , Mirza Faryal Sardar
Published: May 2020

BACKGROUND: Endogenous Cushing’s syndrome (CS) is rare, with an incidence of 0.7-2.4/million people/year.1 It should be considered in individuals with diabetes (DM), hypertension (HTN), osteoporosis or electrolyte abnormalities.2 We present a patient with DM2 and persistent hypokalemia for 10 years found to have ACTH-independent Cushing’s disease as the cause of metabolic syndrome. Case: 62 y.o. M admitted with abdominal pain, a history of DM2 (2012) on Metformin 500 mg BID, HTN (2010) and on ramipril 10 mg qd, with chronic lymphedema on furosemide 20 mg qd. He reported 3-inch height loss. On exam, had facial plethora, moon facies, supraclavicular fullness, thick violaceous abdominal striae and kyphosis. Past history was significant for abdominal/leg cellulitis, muscle weakness, difficult to heal wounds, easy bruising and recurrent hospitalizations for hypokalemia, despite being on KCl up to 80 mEq/d for 10 years. Labs showed AM cortisol at 22.6 ug/dL, ACTH <5 pg/mL, 24-hour urine free cortisol of 523 ug/d (normal < 60 ug/d). AM cortisol after 1 mg overnight dexamethasone suppression was 36.8 g/dL, ACTH <5 pg/mL. CT abdomen showed right adrenal nodule, 4.0 x 3.5 cm with density of 22 HU. MRI showed lipid-poor adenoma measuring 3.9 x 3.5 cm, raising concern for adrenocortical malignancy. Patient underwent right adrenalectomy. Pathology was consistent with benign adenoma showing no nuclear pleomorphism, lipid rich cells containing eosnophillic cytoplasm. Mib-1 stain <1% cells and positive inhibin. He was maintained on steroids post op due to concern about adrenal insufficiency. Hypokalemia, DM and lymphedema resolved completely 4 months post op with weight loss of ~30 pounds. HbA1c improved to 5.1%, metformin was stopped and he was maintained on Carvedilol 6.125 mg BID for HTN. He was diagnosed with osteoporosis with T score -4.0 at mean femoral neck, -2.9 for mean total hip with non-diagnostic spine. He had multi-level chronic compression fractures of the mid-thoracic spine. Conclusion: Delayed diagnosis of CS, as occurred in our patient, can result in detrimental consequences such as life threatening electrolyte abnormalities, cardiovascular events, fractures and premature death.1 Identifying CS can be challenging as clinical presentation is variable. 2,3 Early recognition, diagnosis and control of CS is crucial to decrease morbidity and mortality. Our patient demonstrated rapid resolution of DM, hypokalemia and lymphedema after surgery; however, prolonged exposure to endogenous cortisol resulted in compression fractures and osteoporosis requiring follow up treatment. References: 1. Ille I et al, The Multifarious Cushings. Acta Endocrinol.2019 15(2):261-269 2. Reimondo G et al, Lab differentiation of Cushings syndrome. Clin Chim Acta. 2008;388(1-2):5-14 3. Fan L et al, Association of hypokalemia with cortisol and ACTH levels in Cushings disease. Ann N Y Acad Sci. 2019