bluuebunny/crossref_metadata_2025_split huggingface dataset:
MON-035 Does Androgen Exposure Result in Germline Transmission of PCOS-Like Phenotypes and Can It Be Reversed?
Authors: Lu Haojiang , Manti Maria , Risal Sanjiv , Lindgren Eva , Benrick Anna , Deng Qiaolin , Stener-Victorin Elisabet 
Published: May 2020

Abstract
Daughters of women with polycystic ovary syndrome (PCOS) are more likely to be diagnosed with PCOS, including reproductive and metabolic dysfunctions. Our recent research has demonstrated that dihydrotestosterone (DHT) exposure during late pregnancy results in transgenerational transmission of PCOS susceptibility to female offspring. But it remains unclear whether the transmission of the PCOS-like phenotypes is induced by in utero environment or via germ cell reprogramming, and whether treatment by exercise or androgen receptor blocker, flutamide, can prevent disease transmission. To model PCOS condition, donor mice were implanted with a continuous releasing DHT or vehicle pellet at 4 weeks of age. A subset of DHT exposed F0 donors had either free access to running wheels or were implanted with a slow-releasing flutamide pellet. Mice were exposed with or without treatment for either 6 weeks before IVF or 10 weeks prior to phenotypic testing. Here we present the phenotype of the F0 donors and the result of IVF to generate first (F1) and second (F2) generation offspring. Donors weigh more already after 2 weeks of DHT exposure and had more fat mass with larger adipocyte size, impaired glucose tolerance, and heavier kidney after 10 weeks of androgenization, which was reversed by both flutamide and exercise intervention. Moreover, DHT exposure increased circulating androgens and donors were completely acyclic. Simultaneous treatment with flutamide reversed the elevated androstenedione, testosterone, and restored estrus cyclicity, indicating that androgen receptor blocker can reverse hyperandrogenemia and reproductive dysfunction, whereas exercise failed to improve these phenotypes. After 6 weeks of exposure or treatment, donor oocytes were superovulated for IVF. Fewer oocytes per donor were found in androgenized + flutamide lineage, but no significant difference was observed in oocyte to two-cell embryo conversion rate after fertilization among all groups. Although the number of live offspring at weaning was similar among all groups, a trend of more F1 male than female offspring was found in both androgenized and androgenized + exercise lineage. Similar results were obtained in the F1 females when generating F2 offspring by IVF, which androgenized + flutamide lineage showed fewer oocytes per donor upon superovulation and more F2 male than female offspring was obtained in androgenized lineage at weaning. We here show that the androgenized donors develop clear PCOS-like phenotypes and give rise to more male than female F1 and F2 offspring. While blocking androgen receptor reverses both metabolic and reproductive disturbance in the donor, it also shows a negative impact on the donor and F1 female oocyte maturation process, although number of offspring via IVF is not affected. Excercise, however, only reverses the metabolic phenotypes in the F0 donor mice with no impact on IVF outcome.
MON-158 Rates of Illnesses in Patients with Congenital Adrenal Hyperplasia
Authors: Mallappa Ashwini , Sinaii Ninet , El-Maouche Diala , Veeraraghavan Padmasree , Joyal Elizabeth , Hargreaves Courtney J , Merke Deborah P 
Published: May 2020

Abstract
Background: Classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is the most common cause of primary adrenal insufficiency during childhood and patients are at risk for life-threatening adrenal crisis. In a recent study from our group, we reported gastrointestinal and upper respiratory tract infections as the two most common precipitating events for adrenal crises and hospitalizations across all ages. We also reported 11 incidents of life-threatening hypoglycemic events in children, sometimes accompanied by seizures.
Objective: To evaluate the annual rates of illnesses in patients with CAH.
Methods: We retrospectively reviewed longitudinally collected data over 23 years from 156 CAH patients enrolled in our CAH natural history study (www.clinicaltrials.gov #NCT00250159). Incidence of illnesses and occurrence of stress-dose days were computed per person-years. Incidence rate ratio (IRR) with 95% confidence intervals (CI) were calculated for comparisons.
Results: A total of 2298 visits (1909 for children and 389 for adults) were available for evaluation among the 156 patients (21-OHD: 97.4%). A total of 1870 illness events (1664 in children) were observed in 143 patients (121 children) and 2710 stress-dose days (2460 in children) were observed in 141 patients (120 children) during the study period. The incidence rate of illnesses was higher in children than adults (1.5 vs. 0.5 illnesses/person-years, IRR = 3.1, 95% CI 2.7 - 3.6; P&lt;.0001) with incidence highest in young patients: 2.5 illnesses/person-years in &lt;3 year olds. Similarly, the stress-dose days were higher in children than adults (2.2 vs. 0.6 days/person-years, IRR = 3.8, 95% CI 3.3 - 4.3; P&lt;.0001).
Conclusions: Patients with CAH do not appear to have higher rates of infectious illnesses than expected, but remain at risk for life-threatening adrenal crises. As expected, illness rates are higher during childhood than adulthood. Prevention of adrenal crisis is crucial and is best accomplished through repeated age-specific education of patients and caregivers.
Acknowledgement: This research was supported by the Intramural Research Program at the National Institutes of Health (NIH), Bethesda, Maryland.
OR04-01 MRAP2 Regulates Energy Homeostasis by Promoting Primary Cilia Localization of MC4R
Authors: Bernard Adelaide A , Naharros Irene Ojeda , Guglielmetti Florence Bourgain , Yue Xinyu , Vaisse Christian 
Published: May 2020

Abstract
Genetic studies in humans and mice have demonstrated that the Melanocortin 4 Receptor (MC4R) is essential for adequate regulation of food intake and body weight. MC4R is expressed in a small population of hypothalamic neurons and very little is known about its molecular and cellular dynamics in vivo. We have recently demonstrated that MC4R localizes to and functions at the primary cilia of select hypothalamic neurons to control energy homeostasis. The primary cilium is a solitary hair-like organelle that serves as an antenna sensing extracellular environment. Defective primary cilia lead to a series of conditions known as ciliopathies, that can manifest through a variety of clinical features, including hyperphagia and obesity.
Here we establish that the ciliary localization and the body weight regulating activity of MC4R is dependent on a single-pass transmembrane accessory protein: the Melanocortin Receptor Associated Protein 2 (MRAP2). Specifically, we show that deleting MRAP2 specifically from MC4R neurons (MC4RMRAP2-/-) leads to early onset obesity and hyperphagia. In vitro, co-expression of MRAP2 in ciliated IMCD3 cells increases MC4R localization to the primary cilium. We further demonstrate that MRAP2 and MC4R colocalize specifically at the primary cilium in vivo, and that MC4R fails to localize to the primary cilium when MRAP2 is deleted.
These findings highlight the role of the primary cilium in the control of energy homeostasis, and the importance of accessory proteins for the localization of GPCRs to the primary cilium where they exert their function, in this case being critical for the regulation of energy homeostasis.
MON-345 Hypercalcemia After Placement of Antibiotic-Loaded Calcium Sulfate Beads
Authors: Lane Kyrstin , Kim Sarah , Grock Shira , Freeby Matthew 
Published: May 2020

Abstract
Calcium sulfate beads are used to fill bone voids in bone loss and nonunion, as well as in the management of bone and joint infections.1 Specifically, Stimulan® is an absorbed form of antibiotic-loaded calcium sulfate beads which delivers high local antibiotic concentrations for treatment of infection, but has also been associated with hypercalcemia in 5.4% of cases.1 Despite the significant morbidity associated with hypercalcemia, there is little published literature describing this important complication.
In our institution, five patients hospitalized between March 2019 and September 2019 with normal baseline calcium levels developed hypercalcemia as a complication of Stimulan® placement. Typically, 10 to 60 cc of Stimulan® were inserted in each surgery, with the exception of 120cc in one surgery. Three patients required a second surgery with antibiotic bead placement, and hypercalcemia occurred with both initial and subsequent surgeries. The onset of hypercalcemia varied from post-operative day one to four. The peak corrected calcium was 10.7-16.1 mg/dL which corresponded to ionized calcium of 1.57 to &gt;2.20 mmol/L (normal 1.09-1.29 mmol/L). The patient with the highest bead volume had the highest calcium. Calcium peaked on post-operative days three to five. Patients were treated with intravenous fluids, furosemide, calcitonin and anti-resorptives including denosumab and zoledronic acid. Four patients required hemodialysis. Three patients required dialysis for symptomatic hypercalcemia and in one patient the indication was multifactorial. Calcium typically normalized by post-operative day 14 to 21, but hypercalcemia duration was unknown in two patients (one died; one had hypercalcemia on hospital discharge).
As illustrated in our cases, patients who develop hypercalcemia after their initial antibiotic bead placement may be at risk for recurrent hypercalcemia if additional surgeries use antibiotic beads. Higher bead volume may be associated with more significant hypercalcemia.1 Although previous cases have reported milder hypercalcemia, our cases demonstrate that hypercalcemia can be more severe and prolonged, necessitating dialysis in addition to traditional therapies. 1-3
References:
1.Kallala R, Harris WE, Ibrahim M, Dipane M, McPherson E. Use of Stimulan absorbable calcium sulphate beads in revision lower limb arthroplasty: Safety profile and complication rates. Bone Joint Res. 2018 Nov 3;7(10):570-579.
2.Kallala R, Haddad FS. Hypercalcaemia following the use of antibiotic-eluting absorbable calcium sulphate beads in revision arthroplasty for infection. Bone Joint J. 2015 Sep;97-B(9):1237-41.
3.Carlson Jr. CR, Markulis E, Thompson E, Havill J. A novel case of hypercalcemia following the use of calcium sulfate beads. Nephrol Open J. 2015; 1(1): 17-19.
MON-058 Precocious Puberty and Hypothyroidism in a Pediatric Case
Authors: Sea Jessica L , Head Michael J , Chiu Harvey Kenn 
Published: May 2020

Abstract
Background: Hypothyroidism with secondary sellar/suprasellar mass is rarely associated with precocious puberty. Here we describe a rare case of pediatric hyperprolactinemia and precocious puberty secondary to hypothyroidism, marked TSH elevation, and pituitary hyperplasia.
Clinical Case: A 9-year-old female, with onset of thelarche and menses occurring at age 7 and 8 respectively, presented with primary hypothyroidism (Free T4 &lt;0.11; n=4.9-11.4mcg/mL), elevated TSH (1620.0mU/mL; n=0.3-4.7mU/mL), hyperprolactinemia (108.6ng/mL; n=3.0-23.1ng/mL), and elevated serum estradiol (37.6pg/mL; n=10pg/mL). The patient had coarse scaly skin, diminished energy, and poor growth lasting 1 year. There were no associated gastrointestinal issues, temperature intolerance, nor visual impairments noted during this time.
Magnetic resonance imaging revealed a large mass (1.48cm) with suprasellar extension and a mass effect on the optic chiasm. The patient was then started on Levothyroxine and Cabergoline, to reduce serum prolactin levels. However, upon follow-up two months later, the patient had hypoprolactinemia (2.0ng/mL; n=3.0-23.1ng/mL). The patient was referred to neurosurgery for resection of the sellar mass. Endocrinology was also consulted, at which point Cabergoline was discontinued and Levothyroxine was gradually increased.
Follow up 4 months later showed prolactin levels had normalized to 11.4ng/mL (3.0-23.1ng/mL). Serum LH and FSH were within normal ranges (1.2mIU/mL and 4.2mIU/mL, respectively). TSH, though still elevated (47.35mU/mL; n=0.3-4.7mU/mL), was significantly reduced compared to the prior measurement (1620mU/mL). Serum levels of Free T4 increased to 1.06mcg/mL (n=4.9-11.4mcg/mL). Levothyroxine was titrated up and a repeated pituitary MRI demonstrated a significant decrease in the size of the mass with resolution of the suprasellar extension and mass effect on the optic chiasm. Further, the patient’s menses ceased and thelarche resolved upon correction of T4 and regression of the pituitary mass.
Conclusions: While rare, primary hypothyroidism and TSH-driven pituitary hyperplasia can result in a large mass effect with suprasellar extension, causing secondary hyperprolactinemia by a mass effect and central precocious puberty. This case highlights the benefits for evaluating underlying hypothyroidism as a cause for hyperprolactinemia and sellar/suprasellar mass.
SUN-040 Hormone Replacement Therapy in Transgender Unmasks Testicular Tumor
Authors: Tran Kelvin , Elshimy Ghada , Correa Ricardo Rafael , Harman Sherman Mitchell 
Published: May 2020

Abstract
Introduction In transwomen, hormonal replacement therapy typically usually consists of anti-androgen and/or estrogens. Per Endocrine Society 2017 guidelines, patients should be evaluated every 3 months in the first year for appropriate signs of feminization and adverse reactions. This includes measuring serum testosterone every 3 months initially and the testosterone level should be &lt; 50 ng/dL. We describe a case of a transwoman patient diagnosed with testicular seminoma during surveillance of hormonal replacement therapy (HRT). Case presentation A 31-year-old male-to-female transgender presents to the endocrine clinic for HRT. She previously had seen another provider for HRT and was started on estradiol valerate 5 mg weekly and leuprolide 3.75 mg every month. After 5 months of therapy, she reported that her testosterone level remained elevated, so spironolactone 100 mg BID was subsequently added. Despite adherence, she was dismayed at how little physical changes she achieved after 1.5 years of HRT. She denies taking exogenous substances or OTC mediation containing androgens. Her examination reveals a male habitus and musculature with male voice, male diamond pubic hair pattern, adult penis size and scrotum measuring 20 cc’s bilaterally. Initial labs revealed total testosterone 131 ng/dl, free testosterone 30.8 ng/dl, bioavailable testosterone 64.6 ng/dl, SHBG 12 nmol/L, LH &lt; 0.07 IU/L, FSH &lt; 0.1 IU/L, and estradiol 146 pg/ml. Due to non-suppressed testosterone level despite undetectable gonadotropins, adrenal androgen labs were obtained which was normal. However, her HCG-beta tumor marker was elevated, 12 IU/L (0-3). This prompted a scrotal ultrasound which revealed 3.2 cm right testis mass. Follow-up PET/CT revealed increased activity localized to the right testis without findings of metastasis. Patient underwent right orchiectomy with pathology revealing seminoma stage 1A pT1bMx. At 2 months postop, her total testosterone is now 8 ng/dl, and she reports that her breast tissue has increased and skin softened. Conclusion Hyperandrogenism can be easily diagnosed in females given more obvious clinical features; however, except for precocious puberty, there are typically no obvious features of exogenous testosterone production in males. Thus, typically no workup is undertaken in males to look for underlying cause, including testicular cancer. While presence of scrotal mass is the most common initial presentation, patients can be asymptomatic until tumor burden is high and there is metastasis. Transwomen should be monitored by obtaining estradiol and testosterone levels following the Endocrine Society guidelines. If patient is on GnRH agonist, her testosterone level should be almost completely suppressed (T &lt;50). A testosterone level &gt; 50 ng/dL while on GnRH therapy should warrant workup for exogenous sources, including testicular cancer and adrenal abnormalities.
SUN-132 KLF5 Is a Poor Prognostic Marker and Therapeutic Target for Middle Eastern Papillary Thyroid Carcinoma
Authors: Al-Kuraya Khawla S , Siraj Abdul K , Poyil Pratheeshkumar , Padmaja Divya , Parvathareddy Sandeep Kumar , Al-Dayel Fouad 
Published: May 2020

Abstract
Thyroid cancer is the second most common malignancy among females in Saudi Arabia, with Papillary thyroid carcinoma (PTC) accounting for 80-90%. The Kruppel-like factor 5 (Klf5) is a transcription factor that play a critical role in cell transformation, proliferation and oncogenesis. Immunohistochemical analysis of KLF5 was performed in 1219 PTC cases. KLF5 over-expression was noted in 65.1% (793/1219) of PTCs, and was significantly associated with tall-cell variant (p &lt;0.0001), extrathyroidal extension (p = 0.0003), lymph node metastasis (p &lt; 0.0001) and stage IV tumors (p &lt; 0.0001). Significant association was also noted with HIF-1α over-expression (p = 0.0492). Interestingly, KLF5 over-expressing tumors showed poor disease-free survival (p = 0.0066). Functional studies in PTC cell lines showed that KLF5 co-immunoprecipitated with HIF-1α. Knockdown of KLF5 decreased the expression of HIF-1α while KLF5 was not affected by HIF-1α inhibition, suggesting that KLF5 is a functional upstream of HIF-1α. Down-regulation of KLF5 using specific inhibitor, ML264 or siRNA inhibited cell invasion and migration. In addition, treatment of PTC cell lines with ML264 resulted in inhibition of proliferation and induction of apoptosis in a dose-dependent manner. Furthermore, silencing of KLF5 significantly decreased the self-renewal ability of spheroids generated from PTC cells. Our findings confer that KLF5 may be a potential therapeutic target for the treatment of papillary thyroid cancer.
SUN-001 Identification of Dehydroepiandrosterone-s (DHEA-s) Elevation Due to Performance Enhancing Supplements
Authors: Shin Terry , Plunkett Mary T , Hoang Thanh Duc , Mai Vinh Q , Shakir Mohamed K M 
Published: May 2020

Abstract
Background: Recreational athletes and individuals in certain occupations may utilize supplements with the goal of enhancing their physical performance and strength. These individuals may be reluctant to provide their supplement use history due to the stigma associated with performance enhancing drugs. We report a case of supplement use causing elevated dehydroepiandrosterone sulfate (DHEA-S) levels in a young woman presenting with alopecia. Clinical Case: A 29-year-old Caucasian woman presented for evaluation of progressive alopecia spanning 7 years. She was initially managed by dermatology with topical ketoconazole and clobetasol creams followed by intra-lesional triamcinolone injections. Despite treatment, she had minimal improvement. She reported menarche at age 15 with normal regular monthly menstrual cycles and normal breast development. She has no significant medical history. Physical exam was unremarkable other than localized alopecia and athletic build. She denied any medication use. Routine laboratory screening showed a DHEA-S of 624 ug/dL (ref. 35-430) with repeat DHEA-S at 602.2 ug/dL. Complete blood count, metabolic panel, thyroid function test, total/free testosterone, estradiol, 17-hydroxprogesterone, urinary 17-ketosteroids, prolactin, and iron panel were all within normal limits. Anabolic abuse screen was negative. Adrenal imaging was normal. After discussion on elevated DHEA-S results, patient revealed that she was taking a supplement that contained enobosarm (Ostarine). She was instructed to discontinue the supplement and repeat her labs but she was lost to follow up. Discussion: Developed in 1997, enobosarm is a selective androgen receptor modulator (SARMs) that is increasingly used as a performance-enhancing drug. SARMs have tissue specific androgenic receptor effect and patients on SARMs can present with a completely normal hypothalamic-pituitary gonadal axis without biochemical evidence of hyperandrogenism; which was the case in our patient. Conventional anabolic drug abuse screens do not detect SARMs. There have been multiple studies that have evaluated different performance enhancing supplements and nearly 25% of tested products contained compounds that were not correctly labeled. It is therefore uncertain what may have raised this patient’s DHEA-S levels, but the authors theorize the supplement may have contained exogenous DHEA rather than a direct effect of enobosarm. Unfortunately, there is paucity of data or literature on the effect of SARMs on androgen hormone synthesis and DHEA-S levels. A PubMed search for SARMs and DHEA-S levels led to zero returns. It is important for clinicians to recognize and identify the possibility of SARM or supplement use in order to guide diagnostic and management decisions. Further investigation is needed to understand the impact of SARMs on laboratory data and its long term effects.
SAT-171 Adrenocortical Carcinoma in Thailand: A 10-Year Retrospective Review in a Single Tertiary Center
Authors: Gomutput Patrawon , Parksook Wasita Warachit , Sunthornyothin Sarat 
Published: May 2020

Abstract
Background: Adrenocortical carcinoma (ACC) is a rare and fatal endocrine malignancy. This retrospective review aims to investigate treatment outcomes and clinical characteristics of 18 patients diagnosed with ACC at King Chulalongkorn Memorial Hospital from 2009 to 2018. Methods: We reviewed medical records regarding the presenting symptoms, hormonal investigations, imaging results, staging, modalities of treatment and outcomes. Results: Of the 18 patients, 14 patients were female (77%). The median age at diagnosis was 47.5 years [interquartile range (IQR) 39.5-58.2]. Mass effects and/or hormonal hypersecretion were the most common presentation, documented in 7 (38%) and 6 (33%) patients respectively. Autonomous adrenal hormone excess was found in 10 patients (56%). Cushing’s syndrome and elevated dehydroepiandrosterone sulphate (DHEAS) were documented in 9 (50%) and 7 patients (41%) respectively. Mineralocorticoid excess was found in 1 patient (6%). At initial staging, 9 patients (50%) were in advance or metastatic stage. Surgery was performed in 17 patients (94%) and 13 patients (76%) were in remission. However, recurrence was observed in 6 patients (33%), with the median disease-free interval of 13.5 months (IQR 12.0-25.0 months). In patients with stage 2 disease, open surgery resulted in longer disease-free interval despite larger tumor size, compared with laparoscopic surgery. Final outcomes revealed that 8 patients (44%) had remission, 2 patients (11%) had persistent disease and 6 patients (33%) died. Combination therapy (adrenalectomy, radiation, medications and local control such as metastatectomy, radiofrequency ablation and transarterial chemoembolization) was documented in 11 patients (61%). All patients with remission received complete tumor resection and presented at early stages of cancer, with the majority of them having non-functioning tumors. The median follow-up time was 34 months (IQR 9-73). Conclusions: ACC is a rare and fatal disease with high mortality rates. Diagnosis is time-sensitive and requires multimodality approach.