bluuebunny/crossref_metadata_2025_split huggingface dataset:
OR22-05 Rare Biallelic Variants in Obesity-Related Genes in the Madrid Pediatric Obesity Cohort
Authors: Martos-Moreno Gabriel Á , Moeller Ida Hatoum , Martín-Rivada Álvaro , Pérez-Jurado Luis A , Argente Jesús 
Published: May 2020

Abstract
BACKGROUND: Obesity is a heterogenous disease resulting from environmental and genetic factors and is characterized by disordered energy balance, regulated in part by the hypothalamic melanocortin-4 receptor (MC4R), including neuronal ciliary assembly and trafficking pathways.1 Rare loss-of-function variants in genes encoding components of this pathway are associated with severe obesity and hyperphagia, with or without additional features.2 However, such rare genetic disorders may be underestimated due to a lack of genetic screening in individuals with severe obesity.3 Our objective was to identify and characterize rare genetic variants in a Spanish population from Madrid with childhood obesity. Methods: This analysis was conducted from a prospectively-collected cohort of children with obesity, generally with a BMI&gt;+3DS. Participants were sequenced for 35 obesity-related genes, including 23 genes related to Bardet-Biedl (BBS) and Alström syndromes, plus an additional 12 genes associated with non-syndromic, monogenic causes of obesity, to identify individuals with rare (&lt;1% frequency in gnomAD) potentially biallelic (homozygous and compound heterozygous) non-synonymous variants in protein-coding regions. Results: Of the 1019 Spanish patients with obesity, 493 (48.4%) were female and the mean age and BMI were 10.41 ± 3.38 years and 4.38 ± 1.76 SDS (79.8% above +3 SDS), respectively. We identified 26 rare potentially biallelic variants in 25 unique individuals, including 2 individuals with homozygous variants in POMC, 3 individuals with two variants in SRC1, one individual with two variants in ADCY3, and one individual with a homozygous mutation in LEP. In addition, we identified 18 individuals with biallelic mutations in one of 23 BBS or ALMS1 genes, including two individuals with known pathogenic variants and clinically confirmed BBS. Conclusions: Rare and potentially biallelic sequence variants were identified in 25 individuals with childhood obesity. These results support the use of genetic testing for individuals with severe obesity who may be candidates for specific clinical interventions or additional targeted therapies.
SAT-052 A Novel Oral Testosterone Therapy (TLANDO) Safely Restores Testosterone to Eugonadal Levels with Fixed Dose Treatment
Authors: DelConte Anthony , Patel Mahesh V , Papangkorn Kongnara , Chidambaram Nachiappan , Bruno Benjamin J , Kim Kilyoung , Frank Joel , Khera Mohit , Miner Martin , Kaminetsky Jed , Vignozzi Linda , Goldstein Irwin 
Published: May 2020

Abstract
Most testosterone (T) replacement therapy (TRT) products have relied on dose titration to achieve eugonadal levels. However, dose titration in clinical practice can be time-consuming, expensive, and subject to errors. TLANDO (LPCN 1021) is a novel oral testosterone undecanoate (TU) product absorbed via the intestinal lymphatic pathway. A previous clinical study (NCT02081300) suggested that titration with TLANDO has little to no impact to improve PK profiles. The objective of this study was to assess whether fixed dose of TLANDO can restore testosterone to eugonadal levels. A 24 day, open-label, single-arm, multicenter study with TLANDO in hypogonadal men (NCT03242590) was conducted. Subjects (N=95) received 225 mg testosterone undecanoate orally twice a day (i.e., 30 minutes after morning and evening meals) for 24 days. On Day 24, blood samples were collected over a 24 hour period. The primary endpoint was the percentage of TLANDO-treated subjects who achieved a 24-hour average serum T concentration within the eugonadal range of 300 to 1080 ng/dL after 24 days of treatment. Mean peak serum T concentration was calculated based on daily TLANDO administration at Day 24. Key safety endpoints included incidence of adverse events (AEs), physical examination results, clinical laboratory test results, and changes in HCT, lipids, and PSA. Treatment compliance was calculated as a percentage of the amount of study drug used divided by the amount of study drug expected to be used. 94 subjects completed the study with mean age of 56.0 years, mean BMI 32.8 kg/m2, and baseline T level 202 ± 75 ng/dL. 80% of subjects achieved a 24-hour average serum T concentration within the normal range at Day 24. The lower and upper bounds of the 95% confidence interval was 72% and 88% respectively. Following daily administration of TLANDO at Day 24, the mean peak serum T concentration was 1178 ± 484 ng/dL. The incidence of treatment emergent adverse events (TEAEs) was 21%. The most frequently reported TEAEs were blood prolactin increase (6.3%), weight increase (2.1%), headache (2.1%), and musculoskeletal pain (2.1%). No deaths were reported during the study. Increase in hematocrit (0.9%) and PSA (0.2 μg/L) was observed. Decrease in lipids was observed (-6.9 mg/dL for HDL, -1.5 mg/dL for LDL, -8.9 mg/dL for triglycerides, and -10.6 mg/dL for total cholesterol). Overall mean treatment compliance was 99.7 ± 4.9%. In conclusion, a twice-daily, fixed-dose of TLANDO (450 mg TU total daily dose) successfully achieved target serum T level and achieved a safety profile consistent with that of other approved TRT products.
SUN-924 Functioning Abdominal Paraganglioma Presenting as Acute ST-Elevation Myocardial Infarction
Authors: Kongkit Jaruwan , Leelaprute Meythee , Houngngam Natnicha , Snabboon Thiti 
Published: May 2020

Abstract
Background:
Functioning paraganglioma is a rare catecholamine-producing tumor that arises in the sympathetic nervous system. It usually presents with sustained or paroxysmal hypertension accompanied by episodes of its classic triad of headache, palpitation, and diaphoresis. However, a wide range of signs and symptoms may be present. We report an unusual manifestation as acute myocardial infarction, which accidentally diagnosed by the trigger response from metoclopramide injection.
Case presentation
A 66-year-old woman with medical history of well-control hypertension, dyslipidemia and type 2 diabetes mellitus for 8 years presented with typical angina pain for 1 hour. She denied history of chest pain or triad symptoms of pheochromocytoma/paraganglioma (PCC/PGL). Her physical examination was unremarkable except severe hypertension, 206/89 mmHg, and occasional sinus tachycardia. Acute inferior wall myocardial infarction was proposed by an electrocardiogram study, acute ST elevation in lead II, III and aVF, and highly elevated cardiac enzymes. Echocardiogram and coronary angiography showed preserved left ventricle function (LV ejection fraction 70%) without regional wall motion abnormality. No evidence of coronary artery disease was found. During the catheterization, the cardiologist raised the possibility of the presence of PCC/PGL from her fluctuating blood pressure, 73/42 to 206/113 mmHg, after 10-mg metoclopramide injection to control her vomiting. Computer tomography of the abdomen showed a lobulated heterogeneous enhancing left para-aortic mass with internal necrosis, 6.1x4.9x4.1 cm in size, abutting left anterolateral aortic wall and encasing celiac trunk, superior mesenteric artery, and left renal arterial wall. Her hormonal study showed 24-hour urine fractionated metanephrine/normetanephrine levels of 2,924 nmol (&lt;1,777 nmol)/4,328 nmoL(&lt; 3,279 nmol), respectively, and plasma free metanephrine/normetanephrine levels of 93.66 pg/mL (0-96.6 pg/mL)/233.61 pg/mL (0-163.05 pg/mL). She underwent surgical tumor removal with uneventful outcome and the pathology confirmed the diagnosis of functioning PGL. During 2-years follow-up, the patient remained asymptomatic and her hormonal and functioning imaging study showed no recurrence. The genetic testing for PCC/PGL panel was negative.
Conclusion:
We present an unusual manifestation of PCC/PGL as acute coronary syndrome. The clinician should remind this tumor as the differential diagnosis, especially in a patient with negative coronary angiogram.
SAT-404 Neonatal Hypocalcemic Seizures in Offspring of a Mother with Familial Hypocalciuric Hypercalcemia Type 1 (FHH1)
Authors: Hannan Fadil M , Dharmaraj Poonam , Gorvin Caroline M , Soni Astha , Nelhans Nick D , Olesen Mie Kronborg , Boon Hannah , Cranston Treena , Thakker Rajesh V 
Published: May 2020

Abstract
Background: Familial hypocalciuric hypercalcemia type 1 (FHH1) is caused by loss-of-function mutations of the calcium-sensing receptor (CaSR), and considered to be a benign condition associated with mild-to-moderate hypercalcemia (1). However, the children of parents with FHH1 can develop a variety of disorders of calcium homeostasis in infancy.
Objective: To further characterise the range of calcitropic phenotypes in the children of a mother with FHH1.
Methods: We assessed a three generation FHH kindred by clinical, biochemical and mutational analysis following informed consent.
Results: The kindred comprised a hypercalcemic male, his daughter who had hypercalcemia and hypocalciuria, and her four children, of whom two had asymptomatic hypercalcemia, one was normocalcemic, and one suffered from transient hypocalcemic seizures during infancy. The hypocalcemic infant had a serum calcium of 1.57 mmol/L (normal, 2.0-2.8) and PTH of 2.2 pmol/L (normal, 1.0-9.3) as a consequence of maternal hypercalcemia, and required treatment with I-V calcium gluconate infusions. Mutational analysis identified a novel heterozygous p.Ser448Pro CaSR variant in the hypercalcemic family members, but not in the children with hypocalcemia or normocalcemia. Three-dimensional modelling using a reported crystal structure of the dimeric CaSR showed the mutated Ser448 residue to be located in the CaSR extracellular domain, and predicted the p.Ser448Pro variant to disrupt a hydrogen bond interaction across the extracellular CaSR dimer interface. The variant Pro448 CaSR, when expressed in HEK293 cells, was shown to significantly impair CaSR-mediated intracellular calcium mobilisation and mitogen-activated protein kinase (MAPK) responses following stimulation with extracellular calcium, thereby demonstrating it to represent a loss-of-function mutation.
Conclusion: These studies have identified a novel loss-of-function CaSR mutation which caused asymptomatic hypercalcemia in a mother and her children who had inherited the mutation. However, one child who did not inherit the mutation developed transient neonatal hypocalcemic seizures as a consequence of maternal hypercalcemia. These findings highlight the importance of assessing serum calcium and undertaking CaSR mutational analysis in the newborn offspring of a mother with FHH1.
Reference: (1) Hannan FM, Kallay E, Chang W, Brandi ML, Thakker RV. The calcium-sensing receptor in physiology and in calcitropic and noncalcitropic diseases. Nat Rev Endocrinol. 2018; 15(1): 33-51.
SAT-735 Effects of Androgen Receptor Activation on Angiogenesis
Authors: Huo Yen-Nien 
Published: May 2020

Abstract
The effect of androgen on angiogenesis has been documented. However, its molecular mechanisms underlying has not been well illustrated. Here, we conducted both in vitro migration assay and proliferation assay to investigate whether androgen receptor activation have any impacts on the angiogenesis. Treatment with an androgen receptor (AR) agonist, metribolone (R1881) at a range of concentrations (0.05-5 nM) or dihydrotestosterone (DHT) at a range of concentrations (0.5-2 nM) caused concentration-dependent inhibition of proliferation and migration in human umbilical venous endothelial cells (HUVEC). Blockade of the AR activity by pre-treatment with HF (5 nM), an AR antagonist, or knockdown of AR expression using the lenti-virus shRNA technique abolished the R1881-induced proliferation and migration inhibition in HUVEC, suggesting that AR receptor activation can inhibit endothelial cell proliferation and migration. To further delineate the signaling pathway involved in the AR activation-induced proliferation inhibition, our data indicate that R1881 inhibited proliferation in vascular endothelial cells through activating the AR/cSrc/AKT/p38/ERK/NFκB signaling pathway, which in turn up-regulated the expression of p53, p21 and p27 protein, and finally reduced endothelial cell proliferation. To investigate signaling pathway involved in the AR activation-induced migration inhibition, our data showed that R1881 can reduce the membrane translocation of RhoA and Rac-1, suggesting that inhibition of the RhoA and Rac-1 activity might be involved in the R1881-inhibited endothelial cell migration. Over-expression of RhoA prevented the R1881-inhibited endothelial cell migration and this effect was abolished by pre-treatment with Y27623, a ROCK inhibitor, confirming that inhibiting RhoA activity participated in the R1881-inhibited endothelial cell migration. Using the zebrafish and Matrigel angiogenesis models, we also demonstrated that R1881 inhibited angiogenesis through the AR-mediated pathway in vivo.
SUN-390 Computed Tomography Derived Skeletal Muscle Radiodensity Is Better Predictor of Muscle Power Than Skeletal Muscle Area in Community-Dwelling Older Adults
Authors: Choi Heewon , Hong Namki , Park Narae , Kim Chang Oh , Kim Hyeon Chang , Choi Jin Young , Youm Yoosik , Rhee Yumie 
Published: May 2020

Abstract
Computed tomography (CT) derived skeletal muscle area (SMA) and muscle radiodensity (SMD) reflect distinctive quantitative, qualitative characteristics of skeletal muscle. Peak jump power reflects the ability to exert force within a limited time, which has greater relationship with mobility and risk of falls. CT-based SMA and SMD may have potential as useful surrogates for muscle function. However, the association of CT-based muscle parameters, especially SMD, with peak jump power has not been investigated yet. Community-dwelling older adults enrolled in the Korean Urban Rural Elderly study from 2016 to 2018 underwent abdominal CT scans and countermovement two-legged jumping test on ground reaction force platform. SMA and SMD were measured at CT images at L3 vertebral level. Mean age of 1523 patients was 74.7 years and 65.1% was female. For peak jump force, L3SMA was stronger contributing factor than SMD (standardized beta of SMA vs. SMD = 0.16 vs. 0.08 for men; 0.12 vs. 0.05 for women; p &lt; 0.05 for all). However, SMD was a better indicator of peak jump power compared to SMA in both sexes (standardized beta of SMD vs. SMA = 0.21 vs. 0.17 for men; 0.15 vs. 0.13 for women; p &lt; 0.05 for all). These associations remained robust even after adjustment for age, height, weight, triglyceride, HDL cholesterol, high sensitivity C-reactive protein, and insulin resistance. One standard deviation decrease of SMD was associated with 8% elevated odds of low jump power relative to weight after adjustment for potential confounders (adjusted OR = 1.08, p &lt; 0.001), whereas the association between SMA and low jump power was attenuated. SMD improved discrimination for individuals with low jump power when added to SMA and conventional risk factors (Area under the receiver-operating characteristics curve 0.732 to 0.750, p=0.006). SMD was an independent predictor of jump power with additive discriminatory value to SMA and conventional risk factors. Our findings suggest the potential complimentary role of SMD as muscle quality indicator beyond muscle mass as a surrogate for muscle function.
MON-915 Acute Abdominal Pain and the Pheochromocytoma
Authors: Weiner Yotam , Jameel Omar 
Published: May 2020

Abstract
Background:
Pheochromocytomas are neuroendocrine tumors that release large amounts of metanephrines and catecholamines, resulting in a wide array of symptoms including hypertension, diaphoresis, and headaches. If left unrecognized they can lead to serious morbidity including ischemic or hemorrhagic CVA, encephalopathy, MI, Aortic Dissection, and renal injury.
Clinical Case:
A 62-year-old male began having difficulties with his blood pressure over the past year. He was first hospitalized for an acute ischemic CVA with hypertensive urgency. His blood pressure was generally controlled throughout the admission but he continued to have intermittent elevations. After transferring to an inpatient rehabilitation unit he had an episode of acute nausea, severe lower abdominal pain, and emesis following dinner. He was tachycardic and hypertensive up to 190/115. Acute abdominal imaging revealed constipation but no obstruction. His symptoms resolved, returning a few hours later with another episode of acute nausea, vomiting, and severe lower abdominal pain, with blood pressure 210/126 and tachycardia. IV Metoprolol, Hydralazine and pain medications did not significantly improve his blood pressure, he was subsequently started on a Nitroglycerin drip. Abdominal workup was unremarkable, he was stabilized and discharged back to rehabilitation on increased oral medications. He continued to have blood pressure spikes up to 200/124 with nausea, vomiting, and severe abdominal pain until a Clonidine patch was started, after which his blood pressure was better controlled. He was discharged home with continued outpatient therapies.
A few weeks later he returned to the ER with nausea and severe abdominal pain, blood pressure at home was 254/185. On exam he was diaphoretic, tachycardic, and tachypneic. A CTA scan was obtained without signs of dissection. A Nitro drip with IV push Hydralazine were not effective at controlling his blood pressure, and so Lisinopril, Amlodipine, and a Clonidine patch were added. Over the next few days he had progressively fewer hypertensive elevations and his symptoms were only present during hypertensive episodes. An extensive workup for secondary hypertension was started. 24-hour plasma and urine Metanephrines were within normal limits. Urine Normetanephrine was elevated to 1266 ug/24h (Ref 88-444). Urine Norepinephrine was elevated to 124 ug/24h (Ref 15-80), Urine Dopamine was elevated to 578 ug/24h (Ref 65-400), and total Catecholamines were elevated to 133 ug/24h (Ref 15-100).
Conclusion:
This case illustrates the variance in presentations for Pheochromocytoma and the importance of maintaining a high index of suspicion for secondary causes in patients with intractable hypertension. While commonly reported symptoms include nausea and hypertension, the presentation of acute abdominal pain as the primary complaint is also an important feature of this disease.
SUN-007 Elevated Levothyroxine Requirements Post-Partum as Initial Presentation of Placenta Accreta
Authors: Bao Ginny W , Weinberg Melissa E , Kwan Christina 
Published: May 2020

Abstract
Introduction: It is well known that estrogen plays an important role in thyroid regulation. We report an unusual case of post-partum placenta accreta causing pathologic estrogen secretion leading to increased levothyroxine (LT4) requirements and inability to lactate.
Case: A 36-year-old woman with history of Hashimoto’s hypothyroidism presented post-partum day 11 after a normal vaginal delivery with inability to produce breast milk and mildly elevated TSH levels. Prior to her pregnancy, she required an equivalent dose of 142 mcg of LT4 supplementation daily, which increased appropriately to 171 mcg during pregnancy. After delivery, LT4 was decreased to 150mcg in anticipation of normalization of levothyroxine requirements to pre-pregnancy level. However, she had difficulty lactating and was found to have elevated prolactin, estradiol, and TSH levels. The following day, she presented to her obstetrician for persistent vaginal bleeding and was found to have placenta accreta requiring dilation and curettage (D&C). Her LT4 requirements eventually dropped to 125 mcg with decreasing beta-HCG and estrogen levels after successful D&C treatment. She was also then able to produce sufficient breast milk for lactation.
Discussion: This case highlights the effect of estrogen on LT4 requirements during physiologic pregnancy and postpartum with placenta accreta. It is expected that hypothyroid patients have approximately 25-50% increased thyroid replacement requirements during pregnancy, which normalizes soon after delivery.1 Estrogen increases thyroxine-binding globulin and lowers circulating free thyroxine2,, which causes higher thyroid replacement requirements. Estrogen is also known to inhibit lactation. Our patient demonstrates that this holds true even in a pathologically high estrogen state from placenta accreta. Our case uniquely demonstrates a temporal association between estrogen levels and LT4 requirements in the post-partum hypothyroid patient. Patients with inappropriately high TSH levels after delivery should prompt investigation into pathologic causes of elevated estrogen-states, as levothyroxine requirements are expected to normalize immediately post-partum.
References:
1. Bungard TJ, Hurlburt M. Management of hypothyroidism during pregnancy. CMAJ. 2007;176(8):1077-8.
2. Alexander EK, Marqusee E, Lawrence J, Jarolim P, Fischer GA, Larsen PR. Timing and magnitude of increases in levothyroxine requirements during pregnancy in women with hypothyroidism. N Engl J Med. 2004 Jul 15;351(3):241-9.
SAT-245 A Rare Case of Clival Primary Diffuse Large B-Cell Lymphoma Presenting with Panhypopituitarism and Unmasked Diabetes Insipidus
Authors: Sonnabend Hajerah , Go Muriel Tania L , Iyengar Ravi M 
Published: May 2020

Abstract
Background: Central adrenal insufficiency (AI) is known to conceal diabetes insipidus (DI) by impairing free water clearance from the renal system and inhibiting polyuria, which is later unmasked by the initiation of glucocorticoids. The instances of masked DI in the literature are confined to case reports - the actual incidence is unclear. There have been no documented cases of masked DI secondary to a clival tumor, which remains a rare cause of hypopituitarism. Here we discuss a case of primary diffuse large B-cell lymphoma (DLBCL) of the clivus presenting with panhypopituitarism and the development of DI upon glucocorticoid initiation.
Clinical Case: A 60-year-old man with DLBCL initially presented to an outside institution with headache, diplopia, and right eye ptosis. Brain MRI showed enhancement of the clivus without obvious pituitary gland involvement. He underwent biopsy with partial resection of the tumor and pathology confirmed DLBCL. His course was complicated by persistent fevers. Extensive work-up was unrevealing and he was transferred to our institution for further management. On admission, infectious work-up was positive for C. Difficile. He later developed septic shock requiring vasopressors and broad-spectrum antibiotics. Despite prolonged antibiotics, he remained hypotensive. Due to proximity of the clivus and sella, there was concern for pituitary involvement. A random cortisol was 9.1 [3.7-19.4 ug/dL], subsequent 250ug cosyntropin stimulation test yielded 13.1 and 14.9 at 30- and 60-minutes, respectively. Given inadequate stimulation and persistent hypotension in this critically ill patient, he was then started on stress dose hydrocortisone (HC) with prompt resolution of hypotension. Further work-up of the pituitary axes was consistent with anterior hypopituitarism: ACTH 5 [6-50 pg/mL], TSH 0.336 [0.350-4.940 uIU/mL], free T4 0.5 [0.7-1.5 ng/dL], FSH 0.3/LH 0.1 [1-10 mIU/mL], IGF-1 &lt;16 [41-279 ng/mL], prolactin &lt;1 [3-16 ng/mL]. On day two of HC stress dosing, he developed hypernatremia and polyuria. Urine studies were consistent with DI and desmopressin was started with subsequent improvement.
Conclusion:This is the first documented case of DLBCL of the clivus leading to panhypopituitarism. For tumors in close proximity to the pituitary, there should be a low threshold for pituitary axes evaluation. In addition, masked DI from central AI remains rare and requires close attention by the Endocrinologist following initiation of glucocorticoids.