bluuebunny/crossref_metadata_2025_split huggingface dataset:
MON-243 Atypical Presentation of Isolated Adrenocorticotropic Hormone Deficiency and Sheehan’s Syndrome
Authors: Lugo López Zahira Marie , Santana Nadyeschka Angelique Rivera , Diez Andrea del Toro , Garcia Michelle Marie Mangual , Sanchez Ernesto Sola , Gonzalez Bossolo Alex N 
Published: May 2020

Abstract
Introduction: Isolated adrenocorticotropic hormone (ACTH) deficiency is a rare pituitary hormone deficiency defined by secondary adrenal insufficiency and normal secretion of all other pituitary hormones. Patients present with fatigue, weakness, weight loss, anorexia, nausea, low cortisol levels and low ACTH levels. Isolated ACTH deficiency is more common in males and usually presents in the fifth decade of life. Main mechanisms involved in the pathogenesis are genetics and autoimmune causes, traumatic brain injury and infarction of the pituitary postpartum, known as Sheehan’s syndrome. Sheehan’s syndrome is characterized by postpartum hemorrhage, failure to lactate and menstrual irregularities and it can occur from immediate postpartum period to years after delivery. The most common hormone deficiencies are prolactin and growth hormone. Empty sella is the most common finding on brain MRI. We are reporting a case of a woman in her third decade with isolated ACTH deficiency due to Sheehan’s syndrome two years postpartum, able to lactate, with normal menses and normal brain MRI. Clinical Case: A 33-year-old woman G3P3A0 with hypothyroidism who was referred to Endocrinology clinics due to tiredness, fatigue and weakness. She reported postpartum hemorrhage requiring 4 PRBC transfusions and IV steroids after last pregnancy 5 years ago. Patient was able to lactate after pregnancy and continued in her usual state of health until 3 years ago when she referred loss of consciousness with traumatic head injury due to hypoglycemia. At Endocrinology office physical examination and vital signs were unremarkable, including no blood pressure or heart rate variations with positional changes. Despite hypothyroidism being adequately controlled, she continued with extreme fatigue and weakness affecting her quality of life, for which cortisol and ACTH levels were ordered. Laboratories showed normal electrolytes, negative autoantibodies, cortisol 0.20 μg/dL (5-25 μg/dL) and ACTH 22 pg/mL (10-60 pg/mL) suggesting partial isolated ACTH deficiency. ACTH stimulation test was done and noted with suboptimal response. Evaluation of other anterior pituitary hormones was normal. Brain MRI showed normal pituitary gland. She was started on hydrocortisone in AM and PM and symptoms resolved. Conclusion: Immediate recognition of isolated ACTH deficiency due to Sheehan’s syndrome is necessary due to the availability of effective treatment and morbidity and mortality associated with this serious condition. To our knowledge isolated ACTH deficiency due to Sheehan’s syndrome in which the patient was able to lactate and normal findings on brain MRI has not previously been reported.References: Shivaprasad C. Sheehan’s Syndrome: Newer advances. Indian J Endocrinol Metab. 2011 Sep; 15(3): S203-207. DOI:10.4103/2230-8210.84869.
SUN-580 PCSK9 and Lp(a): Association Between PCSK9 Level and Larger Apo(a) Isoform Size in African-Americans and Caucasians
Authors: Byambaa Enkhmaa , Kim Kyoungmi , Zhang Wei , Truax Kevin , Erdembileg Anuurad , Berglund Lars Folke 
Published: May 2020

Abstract
Introduction: An elevated level of lipoprotein(a) [Lp(a)] is an independent causal risk factor for cardiovascular disease. Non-genetic factors do not appreciably influence Lp(a) levels due to a strong genetic control. However, inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) has been shown to reduce Lp(a) levels. The association of PCSK9 with Lp(a) level and its major genetic determinant—apolipoprotein(a) [apo(a)] size—is not fully understood. In this study, we assessed the relationship between PCSK9, Lp(a) level, apo(a) size, age, and race/ethnicity.
Methods: Healthy Caucasian and African-American families were recruited from the general population (age range: 6–74 years, N=267). PCSK9 and Lp(a) levels were assayed enzymatically; apo(a) isoform and LPA allele sizes and isoform-specific Lp(a) levels were determined.
Results: In all participants, PCSK9 levels differed significantly by race/ethnicity, age, and sex. Thus, the mean PCSK9 levels were significantly higher in African-Americans vs. Caucasians (104 ± 29 vs. 95 ± 30 ng/mL, respectively, p=0.020), in adults vs. children (102 ± 29 vs. 92 ± 31 ng/mL, respectively, p=0.001) and in females vs. males (103 ± 30 vs. 94 ± 29 ng/mL, respectively, p=0.007). PCSK9 levels were not associated with total plasma Lp(a) levels neither in all participants nor in ethnicity-specific analyses. However, PCSK9 levels were significantly and positively associated with isoform-specific Lp(a) levels carried by the larger apo(a) size in all subjects (r=0.139, p=0.0361). In race/ethnicity analyses, a significant association was seen for African-Americans (r=0.268, p=0.0199), but not for Caucasians. In contrast, there were no significant associations of PCSK9 with isoform-specific Lp(a) levels for the smaller apo(a) sizes in all participants nor in ethnic-specific analyses. Of note, PCSK9 levels were significantly negatively associated with the larger apo(a) isoform sizes in all participants (r=-0.139, p=0.0366). Although significant in both groups, heritability of PCSK9 level was higher in Caucasians than in African-Americans (47% vs. 22%, respectively).
Conclusions: Among African-Americans, but not Caucasians, PCSK9 levels were associated with isoform-specific Lp(a) levels carried on larger, but not smaller, apo(a) sizes. The findings illustrate a diverging relationship of PCSK9 with isoform-specific Lp(a) levels.
SAT-607 The Vagus Nerve and the Hypothalamus Mediate Different Aspects of the Anorectic Effects of PYY3-36
Authors: Alonso Aldara Martin , Cork Simon C , Ma Yue , Arnold Myrtha , Herzog Herbert , Bloom Stephen R , Distaso Walter , Murphy Kevin Graeme , Salem Victoria 
Published: May 2020

Abstract
Background: Drugs that safely promote weight loss are required to treat the obesity crisis. The gut hormone peptide YY 3-36 (PYY3-36) is secreted post-prandially to suppress appetite via the Y2 receptor (Y2R). However, it is unclear whether PYY3-36 acts directly on the Y2R in the hypothalamic arcuate nucleus (ARC) or the afferent vagus nerve to inhibit food intake. Understanding the pathways by which PYY3-36 mediates its anorectic effects may facilitate the therapeutic targeting of this system.
Methods: Y2R knockdown in the ARC (ARC-Y2R-KD) was achieved by stereotactic injection of Cre-expressing adeno-associated virus (AAV-Cre) in Y2R-flox C57Bl/6 mice. Y2R KD in the vagus was achieved by bilateral microinjection of AAV-Cre into the nodose ganglia (NG), where the cell bodies of vagal afferents reside. An alternative germline model of sensory nerve Y2R knockdown was generated using Nav1.8-Cre mice crossed with the Y2R-flox strain (Nav1.8-Y2R-KD). Feeding behaviour over 10 days in metabolic cages and the effects of endogenously released (after oral gavage of a nutrient bolus) or exogenously-administered PYY3-36 were investigated.
Results: NG-Y2R-KD animals had 60% reduction in NG Y2R mRNA but remained responsive to cholecystokinin, a positive control of vagal functionality. This is the first example of receptor specific adult vagal deafferentation in mice. The Nav1.8-Y2R-KD model achieved 30% receptor KD. Feeding patterns in the ARC-Y2R-KD and NG-Y2R-KD groups were highly different from their controls, with smaller, faster meals in the KD groups. The anorectic effects (at the next meal) of endogenous PYY3-36 were attenuated in NG-Y2R-KD. Low dose exogenous PYY3-36 at 5 µg/kg significantly reduced 2h post injection food intake (FI) in the control groups (n=8; P=0.045) but this was abrogated in the NG-Y2R-KD group. This pattern was mirrored in the Nav1.8-Y2R-KD model: low dose PYY3-36 significantly reduced FI 1h post-IP compared to vehicle in controls (-0.19±0.05 g; P =0.036; n=8) but not in the Nav1.8-Y2R-KD (-0.004±0.111 g; n=3). Peripherally-administered PYY3-36 at a high dose (30 µg/kg) decreased FI in all groups, including ARC-Y2R-KD.
Summary: These results suggest that endogenous PYY3-36 modulates meal patterning. The vagus nerve mediates physiological PYY3-36 signalling but alternative pathways, not exclusively via the ARC, may be more important in mediating its pharmacological effects. This is relevant for the design of more effective weight loss agents.
SAT-046 Insulin-Like Growth Factor and Fibroblast Growth Factor 21 in Men with Klinefelter Syndrome
Authors: Chang Simon , Hjortebjerg Rikke , Bojesen Anders , Bjerre Mette , Gravholt Claus Hojbjerg 
Published: May 2020

Abstract
Background: Men with 47, XXY Klinefelter syndrome (KS) commonly present with obesity, metabolic disorders, and insulin insensitivity. The insulin-like growth factor (IGF) system has pleiotropic effects including regulation of glucose metabolism. Fibroblast growth factor 21 (FGF21) is associated with weight loss and favourable metabolic changes, but patients with obesity or type 2 diabetes might be resistant to this effect despite presenting with increased levels. Aim: To describe levels of components in the IGF system and FGF21 among men with KS, either treated or not treated with testosterone supplementation therapy (TT), in comparison with control males. Methods: A total of 66 men with KS were included, 33 without current TT and 33 with current TT. A control group of 70 healthy age-matched males were included. Serum levels of insulin-like growth factor 1 (IGF-1), insulin-like growth factor-binding protein 3 (IGFBP3), pregnancy-associated plasma protein A (PAPP-A), FGF21, and fibroblast activation protein (FAP) were compared between the three groups applying the Kruskal-Wallis test. Results: Levels of (IGF-1 µg/L) were not different between the groups (median (25-75 %), untreated KS 162 (140-201.5), treated KS 165 (128.5-215), controls 176.5 (150.8-214.5), p=0.5). Similarly, FGF21 levels (ng/L) were comparable between the groups (median (25-75 %), untreated KS 84.7 (53.3-217.6), treated KS 97.2 (56.4-224.8), controls 100.3 (66.0-191.0), p=0.9). Levels of IGFBP3, PAPP-A and FAP were also found to be comparable between the groups (p≥0.2). Conclusion: This was the first study investigating FGF21 in men with KS. Our results indicate that regulation of the IGF-1 system and levels of FGF21 are not altered in men with KS compared with age-matched controls, and that TT in men with KS does not affect these systems.
SUN-138 Functional Characterization of Tumor-Associated Germline TMEM127 Variants Reveals Novel Insights into Membrane Topology and Protein Trafficking
Authors: Flores Shahida , Zhang Xingyu , Cheng Ming , Dahia Patricia L 
Published: May 2020

Abstract
TMEM127, a tumor suppressor gene in hereditary pheochromocytomas and paragangliomas, encodes for a poorly characterized, ubiquitous, transmembrane (TM) protein with no substantial identity to any other protein and no identifiable functional domains other than putative TM domains. The function and regulation of TMEM127 remain poorly defined which limits prediction of pathogenicity of germline TMEM127 variants. Characterizing structure-function features of TMEM127 is relevant for understanding how dysfunction of this tumor suppressor can lead to inherited tumors. Moreover, a better understanding of TMEM127 functional domains and critical residues will increase our ability to identify pathogenic variants which will improve interpretation of genetic screening results and help guide clinical decisions for patients and their families. In this study, we investigated subcellular localization and steady-state levels of patient-derived, tumor-associated, germline TMEM127 variants (n=21; 16 missense and 5 truncating/frameshift/indel variants). We used confocal immunofluorescence and immunoblot analysis of GFP-TMEM127 constructs expressed in HEK293T cells. Wild-type (WT) TMEM127 localized predominantly to endo-lysosomal vesicles (punctate) with some plasma membrane localization. The localization of variant TMEM127 proteins displayed three distinct patterns: punctate (similar to WT), diffuse (cytoplasmic), and plasma membrane only. All diffuse proteins, and a few punctate proteins, decreased at a faster rate than the WT suggesting instability. Variants resulting in diffuse proteins occurred within TM domains and indicated that membrane binding ability was lost. This observation, supported by in silico analysis and selective permeability assays, led us to conclude that TMEM127 is a four-TM protein, not a three-TM protein, as previously predicted, with a novel TM domain in the N-terminus. One variant with predominantly plasma membrane localization indicated that membrane binding ability was maintained but internalization capability was lost. We identified an atypical, extended acidic dileucine motif in the C-terminal which is responsible for TMEM127 internalization and showed that it is mediated by clathrin. Our findings provide novel insights into structure-function features of TMEM127 which will allow for better understanding of its physiological role and improved prediction of pathogenic variants.
SUN-030 Tetraorchidism: A Rare Type of Polyorchidism
Authors: nagaraja soumya , Accacha Siham D , Angulo Moris Alejandro , George Sarita 
Published: May 2020

Abstract
Polyorchidism is defined as the presence of two or more testis. We report an interesting case of Tetraorchidism an extremely rare type of Polyorchidism in a 14-year-old boy with short stature due to Growth hormone deficiency. An extensive review of literature yielded only 200 case reports of Polyorchidism [1]. Most of these are case reports on triorchidism (3 testicles). There has been only 9 case reports of patients with (tetraorchidism) 4 testicles [2]. Most of them has been reported as incidental findings in adults.
This case is being reported due to its rarity. Here we elaborate on clinical presentation of Polyorchidism in children and their management plan. More specifically from Pediatric Endocrinology perspective, we discuss the influence of the Polyorchidism on the Tanner staging (by testicular volume), growth and pubertal development in boys.
Reference:
1. Amanda Myers, Bradley Morganstern and Ronnie Fine Urology, 2017-06-01, Volume 104, Pages 196-197,
2. Ibrahim H., Roberts M.J., and Hussey D.: Quadruple orchidopexy for torsion testis in an adolescent with polyorchidism: a case report. Urology 2016; 87: pp. 196-199.
SAT-241 Pituitary Stalk Interruption Syndrome Presenting as Neonatal Hypotonia
Authors: Bilbao Nordie Anne 
Published: May 2020

Abstract
Pituitary stalk interruption syndrome (PSIS) is a rare condition that include congenital anatomic abnormalities of the pituitary gland and hypopituitarism. There is a wide variety of clinical presentation, with the age at presentation encompassing from neonatal period to adulthood and including one or more pituitary hormone deficiencies. In recent literature there is increasing recognition of PSIS presenting in the neonatal period, mostly involving hypoglycemia. Our patient is a full-term male infant who presented in the newborn period with hypotonia and hypothermia. He also had hypoglycemia, which was initially thought to be associated to hyperinsulinism in the context of gestational diabetes. Micropenis was noted on physical exam. As part of the study for hypotonia, serial thyroid function tests were obtained revealing central hypothyroidism. A low dose ACTH stimulation test was performed which revealed adrenal insufficiency. The patient was started on cortisol and thyroid hormone replacement. Brain MRI showed an ectopic neurohypophysis located along the floor of the hypothalamus, a small anterior pituitary gland, and a partially absent infundibulum, findings consistent with pituitary stalk interruption syndrome. The patient received testosterone injections for micropenis and is being followed for development of other pituitary hormone deficiencies. PSIS is a rare congenital condition that is increasingly recognized in neonates manifesting with signs of hypopituitarism.
MON-330 Cancer Incidence in 1,296 Patients with Acromegaly Is Not Increased: A Nationwide Population-Based Study
Authors: Esposito Daniela , Ragnarsson Oskar , Johannsson Gudmundur , Olsson Daniel S 
Published: May 2020

Abstract
Background: Single- and multi-center studies have shown an increased incidence of malignancies in patients with acromegaly. These findings may be affected by selection bias. Our aim was therefore to investigate the incidence of malignancies in a nationwide unselected cohort of patients with acromegaly.
Methods: Adult patients diagnosed with acromegaly due to a pituitary tumor between 1987 and 2017 were identified in the Swedish National Patient Registry. All malignancies following the diagnosis of acromegaly were identified in the Swedish Cancer Registry that has a coverage of over 96%. Standardized incidence ratios (SIRs) for malignancies, with 95% confidence intervals (CI), were calculated by using the Swedish general population as a reference. Incidence of malignancies was also analyzed in sub-groups of patients treated with radiotherapy and in those having diabetes mellitus and hypopituitarism.
Results: A total of 1,296 patients with acromegaly were included (621 men, 675 women). The mean age (±SD) at diagnosis was 51.6±14.7 years. The mean follow-up was 12.7±8.3 years, with a total of 16,395 person years at risk. Pituitary surgery was performed in 842 (65%) patients and radiation therapy in 152 (12%) patients. The diagnosis of hypopituitarism and diabetes mellitus was recorded in 29% and 16% of patients, respectively. Overall, 186 malignancies were identified in patients with acromegaly as compared to 179 expected malignancies in the general population (SIR 1.04; 95% CI 0.90-1.20). Incidence of malignancies was similar in men and women [SIR 1.08 (95% CI 0.88-1.32) vs 1.00 (95% CI 0.80-1.23)]. Incidence of colorectal cancer (SIR 1.12; 95% CI 0.75-1.62) or malignancies of the respiratory system (SIR 1.22; 95% CI 0.76-1.84) was not increased. Incidence of kidney and ureter cancer (n=17) was, however, increased (SIR 3.81; 95% CI 2.22-6.11). In the entire study cohort, only three cases of thyroid cancer were recorded. SIR for malignancies in patients treated with radiotherapy (1.12; 95% CI 0.56-2.01) and in patients with hypopituitarism (SIR
0.91; 95% CI 0.68-1.18) or diabetes (SIR 1.08; 95% CI 0.78-1.45) did not differ from the general population.
Conclusions: This large nationwide population-based study showed that the overall incidence of malignancies in patients with acromegaly was not different from the general population. In particular, incidence of colorectal and thyroid cancer was not increased. Incidence of malignancies of the urinary tract was, however, increased.
MON-136 Reducing Unnecessary Inpatient Adrenocorticotropin Stimulation Tests
Authors: Ali Ridha , Lochnan Heather Anne , Shaw Julie , Tran Christopher S 
Published: May 2020

Abstract
Background:
Outpatient adrenocorticotropin (ACTH) stimulation tests can be challenging to interpret due to heterogeneously reported cut-offs. Inpatient stimulation tests present additional challenges due to the presence of acute illness and unreliable coordination of dynamic function testing on a busy inpatient service. This study aims to characterize the use of ACTH stimulation tests in hospitalized patients to determine necessity of testing.
Methods:
We conducted an inpatient audit of ACTH simulation tests done to rule out adrenal insufficiency between April 2018 to March 2019 at our institution. Normal post-ACTH response was defined as peak cortisol ≥500 nmol/L. Testing was considered inappropriate in patients with normal post-ACTH response who had a serum cortisol ≥250 nmol/L drawn during the same admission prior to stimulation testing. Cut-offs were based on previous analysis of 195 outpatient stimulation tests.
Results:
During the one-year study period there were 40 inpatients who had an ACTH stimulation test. Nineteen (48%) were considered unnecessary because patients either had a pre-ACTH serum cortisol ≥250 nmol/L and/or a 0-minute cortisol value just prior to the ACTH stimulation test ≥250 nmol/L. Except for a single instance where the patient was inappropriately on prednisone when basal cortisol was tested, all patients with any pre-ACTH cortisol ≥250 nmol/L had a normal post-ACTH response
Conclusion:
Institutions may avoid unnecessary inpatient ACTH stimulation tests by implementing protocols which ensure that basal cortisol levels are drawn and below locally determined cut-offs before proceeding to dynamic testing. To characterize further, a three-year analysis of inpatient ACTH stimulation tests is underway.
SAT-665 A Case of Hyperglycemia in Post Pancreas Transplant Patient-Is It Insulin Deficiency or Insulin Resistance
Authors: Polavarapu Preethi , Boerner Brian 
Published: May 2020

Abstract
Introduction
Pancreatic transplant (PTx) is a less commonly utilized option for patients with Type 1 Diabetes (DM1), usually with co-morbid end stage renal disease. Hyperglycemia in the post-PTx population can be multifactorial. We report a case of hyperglycemia with ketosis in a post-PTx patient due to insulin resistance and relative insulin deficiency.
Case Presentation
55-year-old male patient with DM1 who underwent simultaneous kidney-PTx. His immunosuppressant (IS) medications were tacrolimus, mycophenolate and prednisone. Tacrolimus levels were therapeutic and his transplant course was benign. He did not require insulin or other glucose-lowering medications post-PTx for 29 years. However, during evaluation for subacute illness with his PCP, he was found to have HbA1c of 12.6%, plasma glucose (PG) 776 mg/dl, and positive urine ketones. He was started on insulin degludec 24 units daily, which was quickly tapered to 8 units daily due to hypoglycemia. OGTT showed fasting PG of 93 mg/dl, 2-hour PG of 115 mg/dl, and stimulated C-peptide of 7.5 ng/ml. HbA1c improved to 7.4% after being on insulin for 1 month. Insulin degludec was tapered and discontinued within 2 months due to hypoglycemia despite low doses and robust PTx function. Home blood glucoses (BG) were controlled and HbA1c stable at 6% off insulin therapy. Eighteen months later, he was hospitalized for hyperglycemia with ketosis, without acidosis, during an upper respiratory infection. He was restarted on insulin (glargine, aspart). Once the acute stress resolved, his insulin dose needs reduced significantly, tapering down to insulin glargine 5 units daily. Along with daily home BG monitoring, HbA1c and C-peptide are performed every 3 months, with recent HbA1c 5.2% and C-peptide 3.0 ng/ml (simultaneous PG of 103 mg/dl).
Discussion
Causes of post-PTx hyperglycemia include graft failure due to acute or chronic rejection, insulin resistance, beta cell dysfunction due to IS medications, pancreatitis, or, rarely, recurrence of autoimmunity. Factors predicting hyperglycemia are pre-PTx insulin dose, BMI and acute rejection. New onset type 2 diabetes can occur due to insulin resistance from IS medications and genetic predisposition. Measurement of C-peptide after OGTT can help determine the cause. Insulin is the standard treatment even with detectable C-peptide, though oral glucose-lowering medications have been used in the setting of insulin resistance. In this patient, severe hyperglycemia occurred during stress. He had very low insulin dose requirements when the stress and hyperglycemia resolved and reasonable C-peptide values. This scenario was most consistent with hyperglycemia due to insulin resistance and subsequent relative insulin deficiency during stress, with continued PTx function. This illustrates the importance of detailed assessment and personalized treatment in patients with post-PTx hyperglycemia.