bluuebunny/crossref_metadata_2025 huggingface dataset:
SUN-221 Subclinical Alpha-1 Antitrypsin Deficiency Is Associated with Increased Free Cortisol Fraction in Plasma and Altered Glucocorticoid Delivery to Tissues
Authors: Boyle Luke David , Nixon Mark , Underhill Caroline M , Hill Lesley A , Homer Natalie Z M , Andrew Ruth , Hammond Geoffrey L , Lewis John G , Stimson Roland H , Walker Brian Robert
Published: May 2020

Background

Corticosteroid Binding Globulin (CBG) binds >85% of plasma cortisol and controls the circulating free cortisol pool. Proteolytic cleavage by neutrophil elastase is proposed to reduce CBG binding affinity and increase free cortisol availability to inflamed tissues. The CORtisol NETwork (CORNET) consortium found that genetic variation at a locus spanning SERPINA1 (encoding alpha-1 antitrypsin, A1AT, the endogenous inhibitor of neutrophil elastase) and SERPINA6 (CBG) contributes to morning total plasma cortisol variation. We hypothesised that A1AT deficiency increases CBG cleavage and hence free plasma cortisol, resulting in increased tissue cortisol delivery in adipose and in HPA axis negative feedback. We tested this in recall-by-genotype studies of people who are heterozygous for inactivating mutations in SERPINA1.

Methods

16 healthy carriers of one of the two most common A1AT-deficiency single nucleotide polymorphisms (rs17580 & rs28929474) and 16 age-, gender- and BMI-matched controls were recruited from the Generation Scotland Biobank. Participants underwent combined receptor antagonist stimulation of the HPA axis (‘CRASH’) testing using RU486 400mg and spironolactone 200mg, or placebo in a double blind randomised crossover design. Plasma free cortisol was measured by isotopic dilution and ultrafiltration, total cortisol by LC-MS/MS, total CBG by ELISA, CBG binding capacity by radioligand displacement assay, and ACTH by immunoassay. Serum A1AT was measured by ELISA. Tissue cortisol (LC-MS/MS) and expression of glucocorticoid dependent transcripts (qPCR) were measured in subcutaneous adipose samples collected by needle biopsy.

Results

Serum A1AT was confirmed lower in those with heterozygous mutations vs wild type controls (411.3 +/- 27.44 vs 565.1 +/- 23.38 mg/dL, p=0.0002). No measurable differences in total CBG or CBG binding capacity were observed. However, plasma free cortisol fraction was higher in those carrying A1AT mutations (16.13 +/- 0.2 vs 13.88 +/- 0.04 %, p<0.0001). Adipose cortisol concentrations were not significantly different but expression of glucocorticoid responsive genes e.g. PER1 was 54% higher (p=0.014) in A1AT-deficient subjects. Plasma cortisol was elevated during CRASH testing in both groups, with the increment versus placebo tending to be lower in A1AT-deficient subjects (82.5 +/- 6.7 vs 126.7 +/- 6.8 nM).

Conclusion

Alpha-1 antitrypsin mutation heterozygosity, common in the general population, is associated with higher free cortisol fraction, consistent with enhanced cleavage of CBG. This is associated with evidence of enhanced delivery of glucocorticoid to adipose tissues but reduced HPA negative feedback, suggesting tissue-specific control of cortisol delivery by CBG.
SAT-719 Prenatal Exposure to Bisphenol A, S and F Increases Blood Pressure in Female Rats
Authors: Al Mansi Maryam H , Chuang YenJun , MohanKumar Puliyur S , MohanKumar Sheba M J
Published: May 2020

Cardiovascular diseases are the leading causes of mortality among men and women. With the new blood pressure guidelines from the American Heart Association, almost half of the United States population has hypertension (45.6%). The reasons for this high prevalence of hypertension in our population could be several, but the effect of emerging contaminants are overlooked and understudied. Bisphenol-A (BPA) is a widely used plasticizing agent that contaminates the environment. Most humans are exposed to BPA on a daily basis and urine levels of this endocrine disrupting chemical (EDC) are positively correlated with hypertension. The FDA banned the use of BPA in baby bottles in 2012, however, it is still being used in food containers and plastics. Currently, several BPA analogs such as bisphenol-S (BPS) and bisphenol-F (BPF) are used to replace BPA in the plastic industry. But their physiological effects are not clear. In order to study the effects of these EDCs on the development of hypertension, we exposed pregnant Sprague Dawley (SD) rats to saline, 5 µg/Kg BW of BPA, BPS or 1µg/kg BW of BPF. The offspring were allowed to reach adulthood before implantation with a radiotelemeter (Data Sciences International; HD-S10) in the femoral artery for undisturbed monitoring of systolic, diastolic and mean arterial blood pressure and heart rate. Recordings were measured once a week for 11 weeks over 24 hours to establish day and night readings. Night-time systolic BP was significantly elevated in BPA, BPF and BPS exposed rats compared to control. During the day, systolic BP was significantly higher in the BPA group compared to control. Diastolic BP was elevated in the BPS and BPF groups. Heart rate was elevated the most in the BPS group. These results indicate that prenatal exposure to low levels of BPA analogs has a profound effect on hypertension.
SUN-512 Graves’ Disease Induced Renal Tubular Acidosis
Authors: Aljaberi Asma Khaled , Shamsi Shamma Al
Published: May 2020

Thyroid gland can affect kidney function in different ways. Thyroxine as a master hormone of metabolism and growth works in many cellular levels include the renal tubules.

We present a 34-year-old Emirati gentleman who presented with multiple episodes of hypokalemic periodic paralysis. Blood test revealed thyrotoxic state, with highly positive serology for thyroid peroxidase, anti-thyroglobulin and thyrotropin receptor antibodies. Thyroid uptake scan confirmed homogenous diffuse uptake consistent with toxic diffuse goitre [Graves’ disease]. In view of recent fracture, bone profile and DXA scan were done. Investigations revealed vitamin D deficiency and below expected for age bone mass density.

The patient was started on symptomatic treatment with propranolol, IV and oral potassium along with IVF hydration. Routine blood work during admission showed a persistent normal anion Gap metabolic acidosis, serum bicarb 15 mmol/l. 24 hours urine electrolytes revealed normal potassium, sodium, high magnesium, low calcium and PH levels. Biochemical lab results suggested type 1 renal tubular acidosis. As the patient had hypokalaemia, high urine magnesium and low urine calcium and limbs weakness, Gitleman Syndrome was considered in the differential diagnosis. Whole Exome Sequencing (CentoXome GOLD®) was sent which came back negative. The following gene panels were studied: Renal tubular acidosis panel: ATP6V0A4, ATP6V1B1, CA2, EHHADH, HNF4A, SLC34A1, SLC4A1, SLC4A4. Bartter Syndrome panel: ATP6V1B1, BSND, CA2, CASR, CLCNKA, CLCNKB, CLDN16, CLDN19, FXYD2, HSD11B2,KCNJ1, KCNJ10, KLHL3, NR3C2, SCNN1A, SCNN1B, SCNN1G, SLC12A1, SLC12A2, SLC12A3, SLC4A1, SLC4A4, WNK1. Gene related to Gitelman syndrome: SLC12A3

Renal tubular acidosis was treated with KCL 600mg PO TID, Na bicarb 1200mg PO BID and spironolactone 25 mg PO OD. The patient received radioactive iodine (RAI) as the ultimate treatment for Graves’ disease. He developed hypothyroidism post RAI ablation and commenced on levothyroxine. Improvement of the metabolic acidosis was noticed in line with improvement of thyroid function. Na bicarb and spironolactone tablets were stopped eventually as the patient was euthyroid clinically and biochemically.

Overt hyperthyroidism is associated with accelerated bone remodelling, leading to hypercalciuria, which can predispose to nephrocalcinosis and renal tubular damage, and therefore causes type 1 renal tubular acidosis. Once the patient becomes euthyroid, bone remodelling and urine calcium return to normal levels and that would correct the renal acidosis.

This case report serves to highlight the effect of Graves’ disease on renal tubules which may result in type 1 renal tubular acidosis. This effect could be reversible with normalization of thyroid function.
MON-133 Hyponatremia in Hospital Care
Authors: Durkan Maeve Catherine , O’ Murchu Oisin
Published: May 2020

Hyponatremia (serum sodium <136 mmol/L) is associated with significant morbidity and mortality. International guidelines suggest a clear algorithm for investigation, inclusive of measurements of paired urine sodium and osmolality, TFTs and a morning cortisol. The aim of this study was to prospectively investigate the assessment, management and clinical outcomes associated with hyponataemia in hospital admissions. Methods:This prospective study was conducted from Sept 9, 2018-Oct 3,2018. All admissions through the MAU were included excepting surgery & oncology and admissions in the prior 3 months. Follow-up data was collected in the six months post admission. Information on all hyponatremic admissions was through combined review of patient charts and hospital laboratory database. Results: 418 patients in total were admitted, of whom 75 (18%, 35 male, 40 female) had measurable hyponatremia. Mean age was 74 (SD=14). 63 patients (84%) had mild hyponatremia (130-135mmol/L), 9 (12%) had moderate hyponatremia (125-129mmol/L) and 3 (4%) had severe (<125 mmol/L) hyponatraemia on admission. 4 (5%) patients only had measurements of paired serum and urine osmolality & sodium, 19 (25%) had TFTs measured, and 1 (1%) had an early morning cortisol. Only 9 (12%) were assessed by a consultant endocrinologist. 47 (63%) were taking a culprit medication (known to cause hyponatremia) on admission, and 15 patients/47 (32%) had the presumed causal medication discontinued. This resulted in an average rise in serum sodium of 4.7mmol/L by discharge. Mean length of hospital stay was 7 days for mild, 9 days for moderate and 16 days for severe hyponatremia cases, and 2 patients died in-hospital. Of the 73 surviving patients, 23 (31%) did not have a sodium remeasured at discharge and 27 (37%) were discharged with persistent hyponatraemia. 20 patients (27%) were re-admitted in the following 6 months. Over the same time period, 12/73 (16%) of hyponatraemic patient admissions died, compared to 13 /332 (4%) of normo-natraemic admissions,which was statistically significant χ²(1, N = 405) = 16.2, p < 0.01. Conclusions:Hyponatraemia was a highly prevalent condition on admission accounting for 18% of all admissions, which was under investigated and underestimated. Endocrine evaluation was underutilised. Hyponatraemia was associated with a longer length of stay, and a four-fold excess in mortality in the six months post-discharge. These findings emphasise the need for formal assessment and treatment along a dedicated protocol for all patients and we have proposed a ‘hospital alert’ system be installed for automatic consultation.
SAT-460 Myxedema Coma Mimicking Cardiogenic Shock Treated with Levothyroxine
Authors: Chaker Bayan , Chaker Mahmoud , Alim Hussam , El-Zein Louna S
Published: May 2020

Myxedema coma is a medical emergency with a mortality rate of 30–50%. It is a commonly missed diagnosis and can lead to multiple cardiovascular complications which are reversible with levothyroxine treatment. IV levothyroxine should be initiated based on clinical suspicion without waiting for laboratory results.

We report a case of a 71-year-old female with a history of CABG 10 years ago, who presented to the emergency department with a syncopal episode. The patient denied aura, vomiting, jerky movements, rolling eye movements, bowel/bladder incontinence, and palpitations. She reported having exertional chest pain for a couple of months. Her home medications included metoprolol succinate 50 mg daily, hydralazine 50 mg twice daily, Imdur 30 mg daily, and levothyroxine 300 mcg daily which the patient reported taking rarely. On admission, the temperature was 36°C, HR 43, BP 75/49 which dropped to 60/40, RR 9, and SpO2 of 93% on 2LPM. Physical exam showed euvolemia with brisk reflexes and delayed relaxation. Blood work revealed Na of 133 mM/L (L), Cr 6.4 mg/dL (H) from a baseline of 2.4 mg/dL, and a troponin of 0.26 ng/mL (H). EKG showed first degree AV block with new T-wave flattening not seen on previous EKGs. A fluid challenge for hypotension elicited no response and the patient was started on a dopamine drip for cardiogenic shock, a heparin drip for ACS, and was transferred to the CCU. BP improved to 140s/70s with a HR remained in the 50s. On the 2nd day of admission, blood work revealed a TSH of >150 (H), free T4 of 0.6, total T3 of 34 (L) and a random cortisol of 15.5 microgram/dL. On the 3rd day of admission, the patient was given 200 mcg of IV levothyroxine. At that time, the patient was on a dopamine drip with a BP of 144/94 with a HR of 64. Twelve hours later, the patient’s BP went up to 197/105 with a heart rate of 65 prompting discontinuation of the dopamine drip and administration of hydralazine and amlodipine. On the morning of the fourth day of admission, BP went up to 236/116 with a HR of 75 and the patient was started on a nicardipine drip. Blood work 3 days after starting levothyroxine revealed a TSH of >150, free T4 of 0.9, and a total T3 of 70. The patient was discharged on levothyroxine 150 mcg daily, amlodipine 10 mg, hydralazine 50 mg q6hrs, and Imdur 30 mg daily.

The patient’s myxedema score was 75 on admission. However, thyroid function tests were not checked with initial labs despite the presence of avert clinical features. As a result, the patient was started on a dopamine drip which could have been avoided. This underlines the importance of early recognition and management of myxedema coma. Having a low total T3 with a low normal FT4 could be explained by recent intake of high dose levothyroxine at home after a significant period of non-compliance. Fortunately, levothyroxine administration to this patient has reversed cardiovascular abnormalities including bradycardia and hypotension within hours when it was given promptly.
MON-356 Atypical Femur Fracture with Denosumab
Authors: Mirza Faryal S , Nallu Ravali
Published: May 2020

Background: Osteoporosis (OP) is a systemic disease that is associated with increased risk for fractures. Anti-resorptive medications (ARM) are an effective modality for treatment and prevention of fractures in OP. Long-term use of ARM like bisphosphonates (BP) is associated with increased risk of atypical femoral fractures (AFF). Denosumab (DM) is monoclonal antibody that targets receptor activator of nuclear factor KB ligand (RANKL). A few cases of AFF with DM have been reported in patients who have previously been on long term BP therapy. We present a case where the patient had only received two zoledronic acid (ZA) infusions, last one three years prior to being initiated on DM and experienced AFF.

Case: 73-year-old postmenopausal woman presented to the emergency room with sudden onset pain in the right thigh. Patient was standing and reaching into her closet when she felt a snap in right thigh followed by inability to move the right leg or bear weight on it. X-ray of the right femur showed a displaced femoral shaft fracture with a short transverse fracture line and a spike, without comminution.

History was significant for OP for which she received raloxifene for a couple of years followed by ZA in 2013 and 2015 by her primary care. Fracture history was significant for a wrist fracture in 2015, and T12 and L1 fractures in 2017 from coughing while on Medrol dospak for an acute episode of bronchitis. In 2017, bone density showed L1-L4 T score of -2.0, the left total hip T score was -1.8 and left femoral neck T score was -2.5 consistent with OP. Work up for secondary causes of OP was unremarkable. Due to recent T12 and L1 compression fractures, she was recommended DM. She received DM in June 2018 as she was undergoing a dental implant followed by December 2018 and June 2019 and presented with the right femoral fracture in November 2019.

Past history was significant for idiopathic pulmonary fibrosis which had been relatively stable without need for long-term steroid therapy. History was negative for diabetes or kidney disease. Menarche was at age 14, menopause at 52 and she did not take any hormone replacement therapy.

She underwent surgical fixation with intramedullary rod. Due to concern about ARM associated sub-trochanteric fracture in the right femur, left femur was imaged. She had cortical beaking in the distal third of the left femur, and underwent prophylactic medullary nailing of the left femur as well.

Conclusion: AFF are an uncommon complication of ARM used for OP. Not many cases of AFF have been reported with the use of DM and most of the reported cases are associated with prolonged BP therapy. Our case is unusual in that AFF occurred in the absence of prolonged BP therapy and raises concern that a couple of ZA infusions in the past can also increase the risk of AFF. Clinicians need to have a high index of suspicion and may consider doing femur x-rays in patients who have previously been on BP prior to starting DM.
MON-346 Secondary Hyperparathyroidism and Other Complications in a Post-Roux-En-Y Patient: A Case Report
Authors: Chan Jessica Michelle , Havins Bradley S
Published: May 2020

Roux-en-y Gastric Bypass is a very common surgical procedure in managing morbid obesity. Approximately 303,890 roux-en-y surgeries were performed in the United States in between the years of 2012 to 2017, and the number is steadily increasing as more Americans are diagnosed with obesity.i

This featured case report describes a 52-year-old female presenting with complications seven years following Roux-en-y gastric bypass. Four years post-operatively, she presented to the ER with a pelvis fracture. It was incidentally found that she had osteoporosis with a t-score of -2.9. It was also found that her bone mineral density (BMD) for women for her age was low with a z-score of -3.5 and her 10-year probability of getting fractures was high with a Fracture Risk Assessment Tool (FRAX) score of 6.2%. Seven years following Roux-en-y gastric bypass, she presented to our primary care office with Vitamin B12 deficiency and secondary hyperparathyroidism due to Vitamin D deficiency. We attempted to correct the deficiencies with high dose of Vitamin D, Vitamin B12, and calcium citrate. Eight months later, the B12 levels was normalized, but the secondary hyperparathyroidism and Vitamin D deficiency were not corrected. This case illustrates the complications that can occur following a Roux-en-y Gastric Bypass, importance of supplement compliance, and proper follow-up with Roux-en-y patients.

Endnotes

i American Society for Metabolic and Bariatric Surgery. (2018). Estimate of Bariatric Surgery Numbers, 2011-2017 | American Society for Metabolic and Bariatric Surgery. [online] Available at: https://asmbs.org/resources/estimate-of-bariatric-surgery-numbers [Accessed 31 Oct. 2019].
SUN-261 Deletion of Hepatic Kisspeptin Results in Abnormal Glucose Metabolism in Female Mice
Authors: Aloqaily Bahaa , Kwon Hyokjoon , Negron Ariel L , Wondisford Fredric E , Radovick Sally
Published: May 2020

Kisspeptin is a hypothalamic protein critical for neuroendocrine control of pubertal development and fertility and is modulated by nutritional signals. Kisspeptin has been localized to specific neurons located in the arcuate and anteroventral periventricular (AVPV) nuclei of the hypothalamus and is secreted to control GnRH mediated pubertal maturation and reproduction. Kisspeptin has also been localized to peripheral tissues including the liver, fat, gonads, intestine and placenta, although its role in these tissues is unclear. The objective of current study is to define the role of hepatic kisspeptin as a metabolic sensor. A floxed Kiss1 mouse has been developed, and ablation of liver-specific Kiss1 was achieved in two to three month old Kiss1f/f male and female mice given a single tail vein injection of thyroid hormone-binding globulin (TBG) promoter-driven Cre recombinase adeno-associated virus (AAV-CRE). A control group of Kiss1f/f male and female mice received an injection of AAV-GFP, expressing green fluorescent protein. Two weeks after injection, a glucose tolerance test (GTT) was performed followed by an insulin tolerance test. To determine whether changes had occurred in the reproductive axis, estrous cyclicity was assessed by daily vaginal smears and estrous cycle phases determined by vaginal cytology. Mice were euthanized four weeks post-injection and tissues were collected for RNA extraction and gene expression analysis via qRT-PCR. As expected, qRT-PCR data showed absence of Kiss1 expression in the liver of AAV-CRE mice compared to AAV-GFP mice with no changes in kisspeptin gene expression were noted in the ovary, testes, spleen, pancreas, arcuate or AVPV. Estrous cyclicity was also not affected by viral ablation of hepatic Kiss1. Elevated fasting glucose and glucose intolerance in the GTT were found in AAV-CRE compared to AAV-GFP females (P < 0.05). No differences in AAV-CRE and AAV-GFP male mice were found, indicating the importance of Kiss1 in glucose homeostasis in females. The insulin tolerance test was not statistically different between groups or treatments. Further research is required to elucidate the mechanism by which hepatic kisspeptin alters glucose metabolism in mice in a sexually-dimorphic fashion.
SAT-627 Racial and Ethnic Differences in Metabolic Disease in Obese Adolescents with Polycystic Ovary Syndrome
Authors: Andrisse Stanley , Reyes Yesenia Garcia , Pyle Laura , Nadeau Kristen , Kelsey Megan Moriarty , Cree-Green Melanie
Published: May 2020

Background: Polycystic ovary syndrome (PCOS) affects up to 15% of women and is associated with a multitude of metabolic complications including insulin resistance, type 2 diabetes, cardiovascular disease, and hepatic steatosis. In the general population, metabolic disease rates vary by race and ethnicity. The interaction of race and ethnicity with PCOS-related metabolic disease in adolescent youth has not been extensively examined. Methods: Secondary analysis of data from overweight and obese (>90 BMI%ile) adolescent (12-21 years) female participants with PCOS enrolled across 4 protocols. Measurements included fasting hormone and metabolic measures, a 2-hour oral glucose tolerance test and MRI for hepatic fat. Groups were compared by ANOVA, with and without correction for BMI or chi-square tests for proportions. Results: Participants included 39 white (NHW 15.7±0.2 years; 97.7±0.2 BMI%ile), 50 Hispanic (15.2±0.3 years; 97.9±0.3 BMI%ile) and 12 black (NHB 16.0±0.6 years; 98.6±0.4 BMI%ile) adolescents. BMI%ile was different between groups (p=0.04), but age of menarche, free testosterone and hirsutism severity were not. Hepatic markers of insulin resistance were worse in Hispanic youth, including lower sex hormone binding globulin and TG/HDL ratio (p<0.001), although HOMA-IR was worst in NHB (p=0.009) and Hispanic (p=0.036) compared to NHW youth. There were no significant differences in insulin concentrations—either fasting or during the OGTT—although fasting C-peptide was higher in Hispanic (p=0.008) compared to NHW youth. Fasting and 2-hour glucose concentrations were not different between groups. HbA1c was highest in NHB (5.7±0.4%, p<0.001 vs. NHW, p=0.026 vs. Hispanic), then Hispanic (5.5±0.3, p<0.001 vs. NHW), then NHW (5.2±0.3) youth. Fasting triglycerides differed between groups (p=0.029), being highest in Hispanic youth (129 [105,167] mg/dL). The frequency of hepatic steatosis (NHW 42%, Hispanic 62% NHB 25%, p=0.032) and the metabolic syndrome components HDL <40 mg/dL (NHW 61%, Hispanic 82% NHB 50%, p<0.001) and HbA1c 5.7-6.4% (NHW 5%, Hispanic 36% NHB 50%, p<0.001) were different between the groups. Conclusions: Adolescents with PCOS appear to show similar racial and ethnic variation to the general population in terms of metabolic disease components.
SAT-173 SAMD9 (Sterile Alpha Motif Domain-Containing 9) Expression in Adrenocortical Tumors
Authors: Bueno Ana C , Santos Carlos H , More Candy CB , Stecchini Monica F , Ramalho Leandra NZ , Ramalho Fernando S , Moreira Ayrton C , Brandalise Silvia R , Yunes Andres , Castro Margaret De , Antonini Sonir RR
Published: May 2020

Introduction: SAMD9 variants are associated with colon, breast and lung tumors. SAMD9 mutations result in adrenal hypoplasia, suggesting its importance in adrenal development. We investigated the contribution of abnormal expression of SAMD9 and its homologous, SAMD9L, to the pathogenesis of pediatric adrenocortical tumors (pACT) Objective: To evaluate the involvement of SAMD9 and SAMD9L in normal human adrenal cortex development and adrenocortical tumorigenesis, as well as to evaluate their association with tumor presentation and patient outcome. Methods: pACT samples (n= 72), normal pediatric adrenal cortices (n= 11), and normal fetal and post-natal adrenals (20 weeks of gestation to 10 years of age; n= 51) were enrolled. Protein expression of SAMD9 (immunohistochemistry) and SAMD9/SAMD9L mRNA levels were evaluated (qPCR). The associations between SAMD9/SAMD9L expression in pACT with tumor presentation (P53 p.R337H genotype and metastasis occurrence) and patient outcome (Overall (OS) and Disease-Free Survival) were analyzed. In silico, publicly available data from pediatric patients with ACT available in the Gene Expression Omnibus were used to evaluate the aforementioned associations with SAMD9 (GSE76021) and SAMD9L (GSE76019) mRNA levels. In vitro, SAMD9 subcellular localization pattern was investigated in the ACT cell line NCI-H295R (immunofluorescence). Results: Nuclear and cytoplasmic SAMD9 expression was observed throughout all different phases of adrenal development evaluated. However, in pACT samples, 26% presented nuclear and 86% cytoplasmic immunostaining. In line, NCI-H295R cells presented mostly cytoplasmic SAMD9 immunostaining under basal conditions. No differential expression was observed between SAMD9 or SAMD9L mRNA levels in pACT and in normal pediatric adrenals. Moreover, no association between SAMD9 immunostaining, SAMD9 or SAMD9L mRNA levels, tumor presentation and patient outcome were observed in our cohort, nor in the in silico evaluation. Conclusion: SAMD9 is nuclear and cytoplasmic expressed during adrenal cortex adrenal development and its loss of function is associated with adrenal hypoplasia. On the other hand, SAMD9 is mostly cytoplasmic expressed in pACT and immortalized NCI-H295R cells. No differential expression of SAMD9 nor its counterpart SAMD9L mRNA were associated with tumor presentation and pediatric patient outcome.
SUN-263 In Vitro Modeling of Brain-Bone Communication: Factors Secreted from Immortalized Female Kisspeptin Neurons Modulate Gene Expression in Osteoblasts
Authors: James Teagan , Weinman Marcus , Chappell Patrick Everett
Published: May 2020

While the sex steroid hormone estrogen (E2) is essential for maximum reproductive fitness, circulating E2 is also involved in maintaining skeletal homeostasis in females. E2 in male and female animals has been shown to stimulate cancellous bone formation via activation of estrogen receptor alpha (ERα), and it was widely thought that this effect was mediated directly at the level of bone. A recent study, however, demonstrated a large increase in bone density in female mice in which ERα was deleted from specific neuroendocrine neurons in the arcuate nucleus of the hypothalamus, specifically those expressing kiss1, a population required for fertility and pubertal progression. Bone from transgenic Kiss1-cre X ERα floxed females showed higher osteoblast functioning, accompanied by increases in the expression of sp7 and runx2, positing the existence of a direct neural-bone regulatory axis that is altered by circulating E2 at the level of the brain (Herber et al., Nat Commun 2019).

Our laboratory recently published a study demonstrating that GnRH and Kisspeptin, typically thought to act primarily within the neuroendocrine reproductive axis, are synthesized and secreted in an autocrine fashion by canine osteosarcoma cells in vitro, and that these neuropeptides can stimulate tumor cell proliferation (BMC Cancer 2019). Separately, our lab has also recently generated two immortalized Kiss1-expressing and –secreting cell lines, KTaR-1 (representative of female arcuate Kiss-1 neurons) and KTaV-3 cells (representative of female AVPV Kiss-1 neurons) (Endocrinology 2017). In the current study, we have combined these two in vitro models to explore if factors secreted by female ARC-derived KTaR-1 cells may affect multiple parameters of osteoblast function, including sp7 and runx2 expression (evaluated by qPCR), and ability to form bone matrix (evaluated by Alizarin Red assay). Preliminary results suggest that exposure canine osteosarcoma (COS) cells to conditioned media from KTaR-1 cells leads to increases in sp7 expression in an E2-dependent manner, such that 24h E2-deprivation of these neurons stimulates secretion of osteogenic factors. Additionally, media from both KTaR-1 and KTaV-3 cells stimulated Ca2+ production from cultured osteoblasts, as evaluated by Alizarin Red. We are continuing to explore these in vitro interactions using COS cells, as well as normal osteoblasts (cNOB) and immortalized cNOBs, and are evaluating media and exosomal proteomics to further characterize putative factors. While further study is required, these initial results suggest that our immortalized neuronal KP cell models may provide useful molecular tools to explore the regulation of this newly-proposed neural-bone axis.
MON-002 The Effect of GNRHR Autoantibody on Reproduction Function and Insulin Signaling Intermediates in a New Animal Model of Polycystic Ovary Syndrome
Authors: Li Hongliang , Guo Yankai , Zhang Gege , Deng Jielin , Fischer Hayley , Craig LaTasha B , Yu Xichun , Kem David C
Published: May 2020

Background: Polycystic ovary syndrome (PCOS), a metabolic and reproductive associated disease, defined as hyperandrogenism with reproductive dysfunction including menstrual disorder, anovulation, infertility, polycystic ovary and so on. We previously showed reported a high percentage of activating autoantibodies (AAb) directed toward the second extracellular loop (ECL2) of gonadotropin-releasing hormone receptor (GnRHR) in PCOS patients, and further demonstrated elevated GnRHR-autoantibody (GnRHR-AAb) could induced insulin resistance in energy storage and peripheral tissue in immunized animals. In the present study, we have now induced specific GnRHR-ECL2 AAb in rats and explored the underlying mechanisms of their resultant reproductive dysfunction. Methods: Sixteen SD rats were randomly divided into 2 groups: a GnRHR group (n=8) and a control group (n=8). Rats in the GnRHR group were immunized with GnRHR ECL2 peptide while the controls were not. Epitope mapping of GnRHR-ECL2-directed AAb was performed using octapeptide multipin solid-phase peptides. Rat estrus cycle was measured through pudendum appearance and vaginal smears. Ovarian and pituitary tissues were collected to observe ovarian morphological changes, to examine the expressions of proteins and genes of insulin signaling pathway by Quantitative real-time PCR respectively. The concentration of inflammatory cytokines in the ovary was detected by Bio-plex Pro™ magnetic bead-based assays on the Bio-plex®. Results: The GnRHR-AAb titers and activity in the GnRHR group were significantly higher than the control group, and the GnRHR-AAb from the immunized rats reacted predominantly with the peptide sequence FSQCVTHC of the GnRHR-ECL2. Numbers of LH pulses and concentration of testosterone in GnRHR group were significantly higher than control group. The GnRHR group exhibited lower frequency of in the appearance of proestrus and estrous phases while the control group represented had a higher frequency in the appearance of metestrus and diestrus stages on estrus cyclicity. The GnRHR-immunized group showed demonstrated increased atretic follicles, decreased corpora lutea, loosely packed granulosa cells, and thecal cell hyperplasia in ovarian tissue compared with controls group. There was GnRHR group represented increased expressions of IRS-1, PI3K and GLUT-1 in ovarian and pituitary tissues compared with control group. However, no obvious changes of inflammatory cytokines are observed in ovarian tissues between two groups. Conclusion: Chronic elevated GnRHR-AAb exerts induced reproductive dysfunction through increased ovarian LH secretion and androgen production, thus likely leading to compensatory hyperinsulinemia which ultimately enhanced insulin signaling in reproductive tissues to exert more and androgen production to, which may provide a novel etiological mechanism for PCOS.
SAT-207 Adrenocortical Carcinoma in Untreated Congenital Adrenal Hyperplasia
Authors: David Julia , Yagudayev Lev , Galagan Robert
Published: May 2020

Background:

Congenital adrenal hyperplasia (CAH) is a group of rare inherited autosomal recessive disorders characterized by a deficiency of various enzymes participating in steroid hormone synthesis. It occurs in 1 in 5000 to 1 in 15000 births. The most common (90-95%) cause of CAH is the absence of the enzyme 21-hydroxylase. We are presenting a case of a 34 year old male with untreated congenital adrenal hyperplasia due 21-hydroxylase deficiency and metastatic adrenocortical carcinoma.

Case:

A 34 year old male with a history of classic congenital adrenal hyperplasia (CAH) untreated since childhood presented with symptoms of right abdominal pain, anorexia and weight loss. His family history was significant for one brother diagnosed with CAH, father with liver and pancreatic cancer and another brother with colon cancer. After 2 weeks of treatment with NSAIDs for the pain, his abdominal pain worsened and patient also reported dyspnea with minimal exertion and dry cough. The patient was admitted to TUMC and his evaluation revealed a large right adrenal mass (17x11cm) with multiple liver and lung lesions suggestive of metastatic cancer. The adrenal mass was needle biopsied and pathology results were diagnostic of adrenal cortical carcinoma.

His baseline morning cortisol level was 22.45 mcg/dL, ACTH 13.2 (n=7.2-63.3), androstenedione 291 ng/dL (n=27-152), 17-hydroxy progesterone 10,850 ng/dL (n=27-199), testosterone 140 mg/dL, renin 1.295 ng/ml/h (n=0.167-5.38), aldosterone unable to assay due to interference and LDH 2011 U/L (n=87-241). He failed an overnight 1mg dexamethasone suppression test with cortisol of 20.17 in the morning. During hospitalization, his clinical condition gradually deteriorated with hypotension, altered mental status, acute respiratory failure and acute liver failure with an AST 2787 units/L (n <39), ALT 399 (n=30-65) and ALP 1013 units/L (n=40-120). Oncology decided that the patient was a poor candidate for antineoplastic treatment therefore he was offered hospice care and eventually expired.

Discussion:

There have been reports of benign and malignant adrenal tumors in patients with CAH. It has been surmised that ACTH is the driver of adrenal tumor transformation in these patients. Our patient with adrenocortical carcinoma presented at a late stage with widespread metastases resulting in death. His elevated cortisol level occurred in association with low normal ACTH and the failed 1mg overnight dexamethasone suppression test are consistent with tumor production of cortisone. Considering that he had untreated CAH since childhood, we assume elevated ACTH levels were present until tumor transformation occurred.
MON-238 A Diagnostic “Headache” in a Pregnant Woman with Diabetes Insipidus: Blame the Placenta or the Pituitary?
Authors: Aziz Khalid , Pokhrel Ashna , Ramirez Beatriz E , Sultana Sanjeda , Houston Caroline
Published: May 2020

Background

Diabetes insipidus (DI) occurs in 1/30,000 pregnancies and can be difficult to recognize due to normal peripartum physiology. The most common etiology is excess production of placental vasopressinase, which degrades maternal anti-diuretic hormone. Although rare, hypothalamic and pituitary disorders must also be considered in pregnant patients presenting with DI. We present the case of a pregnant woman presenting with diabetes insipidus and pituitary apoplexy.

Clinical case

We were called to see a 33 year old female with polyuria and polydipsia on post-partum day #2. She had presented to the ED at 29.4 weeks of her 5th pregnancy (G5P4) with an unrelenting headache, nausea, and vomiting for 12 hours. She was tachycardic, hypertensive, and had no focal neurologic deficits. Fetal evaluation was reassuring. Admission labs included serum sodium of 147 mEq/L (n 136-145), serum potassium 2.8 mEq/L (n 3.4-4.4), and urine specific gravity of 1.003 (n 1.005-1.030). Glycemic parameters, renal function, and hepatic function were normal. She remained tachycardic despite vigorous IV fluid administration. Overnight into hospital day #3 she began to have uterine contractions with fetal decelerations, and betamethasone was given. It was noted that she had produced 8L of urine over the preceding 24 hours. Serum sodium was 159 mEq/L with urine osmolality of 78 mOsmol/kg (n 300-900). A presumptive diagnosis of gestational DI was made and 2 mcg of subcutaneous DDAVP was given. Shortly thereafter she delivered a healthy infant. Maternal blood loss was minimal. Over the next 12 hours her urine became concentrated and her serum sodium decreased, but by the next morning she re-developed dilute polyuria.

At the time of our evaluation, her headache had resolved and she had no focal neurologic deficits. She had no apparent signs of glucocorticoid or thyroxine deficiency but had not begun to lactate. Biochemical evaluation included early morning cortisol of 4.6 ug/dL (n 3.5-18.3), TSH 0.46 uIU/mL (n 0.35-4.94), free T4 0.76 ng/dL (n 0.70-1.48), and prolactin 26.6 ng/mL (n 5.2-26.5). Pituitary MRI showed a mildly enlarged gland with central T1 hyperintensity, consistent with apoplexy. A regimen of hydrocortisone and DDAVP was initiated.

Conclusion

Pituitary apoplexy is uncommon during pregnancy but is potentially life-threatening for the mother and fetus if it goes unrecognized. The significant physiologic growth of the pituitary during pregnancy may increase the risk of apoplexy. A severe headache is the most common symptom and may be accompanied by signs of pituitary dysfunction. Although diabetes insipidus is more often caused by placental physiology, pituitary apoplexy must also be considered in a pregnant woman who has concurrent neurologic symptoms.
SAT-366 Hypercalcemia Due to Castleman’s Disease
Authors: Khan Sarah Adil , Shah Neel L
Published: May 2020

Castleman’s disease is a group of poorly understood lymphoproliferative disorders in which pro-inflammatory cytokines are hyper-produced, causing a constellation of symptoms. This patient was diagnosed with a rare subtype of idiopathic multicentric Castleman’s called TAFRO, which is a subclass characterized by thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis (R), and organomegaly (O). This is a case of hypercalcemia likely secondary to Castleman’s disease. To our knowledge, only two such cases have been reported, and none with this rare subtype of the disease. The mechanism of hypercalcemia in Castleman’s disease is thought due to lymph node macrophages expressing vitamin D activating enzyme 25-hydroxyvitaminD 1-alpha-hydroxylase, and possibly due to increased bone-turnover from osteoclasts production by IL-6. The treatment is managing the primary cause of the disorder: high doses of systemic steroids, immunosuppressants and IL6-inhibitors. We present a case of a 53 year old Hispanic female with a PMH of type 2 diabetes mellitus. She had hypercalcemia with a corrected calcium 12 mg/dl and a normal PTH 16.2pg/ml, with low levels of 1,25-OH vitamin D 8.3pg/ml, and 25-OH vitamin D 16.6ng/ml. PTHrP was undetectable. Phosphorous was normal at 3.3 mg/dl. Given that the iPTH was low normal, and with low 25-OH and 1,25-OH vitamin D levels, primary hyperparathyroidism was thought unlikely. SPEP showed a chronic disease pattern. TSH was also noted to be normal. Quantiferon tuberculin test, HHV6, HHV8 and HIV were negative. IgG, IgA, IgM levels were normal. She also had elevated alkaline phosphatase at 108 U/L. No other bone markers were checked. After steroid therapy, her corrected calcium came down to 10.1. Her Castleman’s disease was diagnosed via histopathology of lymph node biopsy showing follicular hyperplasia with atretic germinal centers, penetrating blood vessels, expanded mantle zones, hypervascular interfollicular regions and intense interfollicular plasmacytosis consistent with Castleman’s disease. Initial CT Chest with contrast showed diffuse lymphadenopathy in the retropectoal, axillary, prevascular, pretracheal, paratracheal, and retroperitoneal regions. She had anasarca with ascites, requiring paracentesis with ascites fluid that was negative for malignancy. She was also diagnosed with acute thrombotic microangiopathy via kidney biopsy for workup of thrombocytopenia and acute renal injury. She was initially treated with PLEX and dexamethasone 40mg, then switched to methylprednisolone, was also tried on riuxamab and cylclosporine. She failed therapy with an IL-6 inhibitor, Siltuximab, due to pulmonary edema requiring hospitalization. Currently, she is on a drug holiday and will resume lower doses of cyclosporine. Clinicians should consider an underlying lymphoproliferative disorder in the differential for a patient with hypercalcemia.
SUN-684 The Dance of Diabetes
Authors: Thakkar Aditi , Jalil Fatima , Taxel Pamela
Published: May 2020

Nonketotic hyperglycemic chorea-ballism (NKHCB) is a rare movement disorder typically associated with uncontrolled type 2 diabetes. It is often the result of a focal lesion of the contralateral basal ganglia. Here we present a case of a patient who presented with hyperglycemic chorea as the initial manifestation of their diabetes. A 73 year old caucasian female with no known past medical history was brought to the emergency room with involuntary movements of the left face, arm and leg. These movements were sudden in onset and not suppressible. Her vitals were stable on arrival and exam was benign apart from choreiform movements of the left arm, left leg and left perioral muscles. Her labs were significant for a random blood glucose level of 418 mg/dl and HbA1c of 12%. As part of her workup she underwent a CT head which showed an asymmetric hyperdensity involving the right putamen. She underwent additional workup of chorea to exclude infection, vitamin deficiencies, heavy metal poisoning, electrolyte imbalances, liver dysfunction, all of which returned negative. She eventually underwent an MRI of the brain which showed symmetric, mildly bright T1 signal within both putamen suggestive of mild bilateral calcium deposition bilaterally. The patient was further evaluated by neurology who felt that her overall clinical presentation and imaging findings were consistent with a diagnosis of NKHCB. She was placed on an insulin regimen with significant improvement in blood glucose levels. Her symptoms resolved within two weeks as noted on outpatient follow up. NKHCB is a rare condition that manifests in the setting of uncontrolled nonketotic diabetes mellitus. The exact underlying pathophysiology of changes seen on imaging of patients with NKHCB is not fully understood. The diagnosis is based on typical clinical and radiological features including the presence of ballistic or choreiform movements in the setting of marked hyperglycemia and the absence of ketoacidosis. This case is unusual as her chorea was the presenting symptom of her diabetes which was previously undiagnosed. The characteristic radiological feature is a high signal intensity basal ganglia lesion on the T1-weighted brain MRI. The mainstay of treatment includes normalization of the blood glucose, although in some cases antipsychotic use has been described. In most cases, complete resolution of symptoms has been reported within 10 months. Given the excellent prognosis with management of blood glucose, non ketotic hyperglycemia is an important differential to consider in a patient presenting with chorea-hemiballismus.
SUN-678 Telediabetes Improves A1C and Patient Satisfaction: A Pilot Study in a VA Institution
Authors: Behari Gauri , Vinales Karyne Lima , Correa Ricardo Rafael , Reaven Peter , Harman Sherman Mitchell
Published: May 2020

Introduction: Rural Americans experience significant health disparities and have poorer health outcomes compared to their urban counterparts. Access to health care services in rural areas remains an ongoing challenge. Telehealth services can efficiently and effectively improve access to healthcare for people living in rural and remote areas. However, it is unclear if telemedicine services would be effective in the veteran population. Therefore, we have initiated a pilot studyto verify the effectiveness and satisfaction of diabetes care delivered through telehealth (Telediabetes) in a Phoenix VA community-based outpatient clinic (CBOC).

Methods: The Southeast CBOC is a remote VA clinic in Phoenix with the largest volume of patients with diabetes. Inclusion criteria were patients with type 2 diabetes that have been seen at least one time in the endocrinology clinic at the Phoenix VA and were willing toparticipate in telemedicine. Of the 36 patients that qualified for the study, 20 (55%) were scheduled, 11 (31%) were unreached, and only 5 (14 %) declined. Interventions included optimizing use of newer diabetes medications such as GLP-1 agonists and SGLT2 inhibitors andefforts to improve adherence to treatment regimens. Methods to improve adherence included offering home self-monitoring of blood glucose, increased frequency of visits, including home video conferencing and recommending referrals to nutrition and clinical pharmacists for amultidisciplinary approach. Patient satisfaction was assessed through a validated 5-question survey using a Likert scale 1-5 immediately after each visit. The primary outcomes were change in A1c and patient satisfaction.

Results: 95% (17/18) of the participants were males, the mean age was 62.5±.14.0 years-old, and the mean BMI was 34.4±6.8 kg/m2. Median follow-up time was 189 days (range: 89-417). During follow-up, A1c decreased by 0.8% (baseline: 9.5±2.2 vs. post-visit: 8.7±2.0%, p=0.017).Overall, all patients were fully satisfied (Likert score of 5) with the telediabetes visits and 94% of the patients would choose telehealth over face-to-face appointments. Up to now 37% of patients have had at least a second visit with telediabetes.

Conclusion: Telediabetes is an effective alternative to face-to-face visits for rural veterans, as demonstrated in other communities. The high patient satisfaction and decrease in A1c in this study showed that the program can be expanded to increase access to diabetes care in remoteareas.
SAT-714 Cadmium, an Endocrine Disruptor of the Reproductive Axis in Mice
Authors: Fiordelisio Tatiana , Santiago Yorgui , Romero Itayetzi
Published: May 2020

Endocrine disruptors, are chemicals that can alter organism endocrine system. Within these, the heavy metal cadmium is one of the most toxic industrial and environmental metals. Neuroendocrine system act in precise amounts and moments in time, disturbances caused by endocrine disruptors are suspected to be implicated in the recent declining fertility. The effect of cadmium, intraperitoneally injected, on the intracellular calcium activity of gonadotropes was evaluated in an ex vivo preparation of the entire pituitary gland of male BalbC mice by calcium imagenology techniques. In preliminary results, an increase in baseline intracellular calcium activity was observed, as well as an increase in the number of gonadotropes that respond to a GnRH and express gonadotropins. In addition, a change in the pattern of response to GnRH was observed, the biphasic type response being predominant, and an oscillatory depolarization of greater intensity and duration in response to KCl, which is not affected by nifedipine. The results allow us to infer that cadmium affects the function of pituitary gonadotropes and thus probably fertility.