bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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 &lt;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 &lt;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

Abstract
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

Abstract
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 &lt;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 (&gt;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

Abstract
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 &lt;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 (&gt;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 (&lt;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

Abstract
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 &gt;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

Abstract
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&lt;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&lt;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

Abstract
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 &gt;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

Abstract
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.