bluuebunny/crossref_metadata_2025 huggingface dataset:
SAT-467 A Case of Pituitary Hyperplasia Secondary to Uncontrolled Primary Hypothyroidism
Authors: Alhumaidi Hebah , Rao Sarika , Kansal Dhruv
Published: May 2020

17 year old female presented for evaluation of galactorrhea of 3 months duration. Patient was diagnosed with papillary thyroid cancer and underwent total thyroidectomy in 2011. She was prescribed Synthroid 175 mcg but was not compliant with taking her medicine. In April 2019 she developed bilateral galactorrhea for which she was evaluated at an outside facility and was found to have a prolactin 143.7ng/mL (n 7.2-63) and TSH 996 mIU/L (n 0.5 -4.0). Pituitary MRI revealed pituitary macroadenoma measuring 1.5 x 1.4 x 1.2 cm with slight elevation of the optic chiasm and infundibulum. She was advised to restart Synthroid and was referred for the neurosurgery team at our facility for surgical resection of pituitary macroadenoma. Over the same period of time, she gained 25 lbs, developed headaches, excessive fatigue, constipation, hair loss, lower extremity swelling, and puffiness of her face. Her menstrual cycles were regular but this was only after she was placed on norelgestromin/ ethinyl estradiol transdermal patch. She denied visual changes. By the time she was seen at our clinic in June 2019, she was taking Synthroid daily for 1 month. TSH decreased to 1.0 mIU/L and prolactin improved to 68 ng/mL. IGF-1 was low at 98 ng/mL (n 149-509). ACTH, morning cortisol, and 24 hour urine free cortisol were within reference range. Visual field testing showed no visual defects. We advised patient to continue taking Synthroid and to follow up in 1 month. On the follow up visit in July 2019, TSH was 0.2 mIU/L, prolactin was 52 ng/mL and IGF-1 was 105 ng/mL. Pituitary MRI showed pituitary hyperplasia that has decreased compared to previous MRI, now measuring around 1 cm at the largest dimension without contact with the optic chiasm and the Infundibulum was at midline. Galactorrhea and headaches resolved and fatigue significantly improved.
MON-111 Plasma Insulin Measured with a Sensitive Immunoassay May Establish the Diagnosis of Congenital Hyperinsulinism Without Further Testing
Authors: Siersbæk Julie , Larsen Annette R , Nybo Mads , Christesen Henrik Boye Thybo
Published: May 2020

Background: The diagnosis of congenital hyperinsulinism (CHI) is often hampered by a plasma insulin (p-insulin) detection limit of 2-3 mU/L (14-21 pmol/L) by RIA methods.

Objective: To evaluate the diagnostic performance of a sensitive immunoassay for p-insulin and to find the optimal p-insulin cut-off for CHI versus other conditions with hypoglycaemia.

Design: Single centre retrospective cohort study.

Methods: Diagnostic tests with no medication, no i.v. glucose and under fasting conditions were performed in children with a clinical diagnosis of CHI. P-insulin concentrations determined at simultaneous p-glucose concentrations at least <3.2 mmol/L (57.5 mg/dL) were included in the analysis (n=61).

The diagnosis of CHI was either clinical (n=61) or by gold standard criteria: hypoketotic hypoglycaemia plus disease-causing genetic mutations and/or diffuse, focal or atypical pancreatic histopathology (n=57). Samples from 15 children with idiopathic ketotic hypoglycaemia (IKH, diagnosis by exclusion, p-ketones >1.5 mmol/L during hypoglycaemia) were used as controls.

P-insulin was measured by the high-sensitive assay (Cobas e411 immunoassay analyzer); lower detection limit 1.4 pmol/L (0.2 mU/L); normal range 18-173 pmol/L (2.57-24.7 mU/L). Concentrations <18 pmol/L were considered suppressed; ≥18 pmol/L un-suppressed.

Receiver operating characteristics (ROC) curves with determination of area under the curve (AUC) values were performed for the diagnostic performance of p-insulin in the diagnosis of CHI. Results: In the 61 samples from CHI patients, the median (range) p-insulin was un-suppressed in all diagnostic samples [90; 20-758 pmol/L (12.9; 2.9-109.1 mU/L)], while p-insulin was suppressed in all 15 samples from IKH patients [1.5; 1.5-9 pmol/L (0.21; 0.21-1.3 mU/L)]. The ROC AUC was 1.0 (95%CI. 1.0-1.0) for the diagnosis of CHI defined both by the clinic and by gold standard. The optimal p-insulin cut-off was 14.5 pmol/L (2.1 mU/L) or 12.5 pmol/L (1.8 mU/L), for CHI patients by use of a simultaneous p-glucose cut-off of <3.2 mmol/L (57.5 mg/dL; n=61), or 3.0 mmol/L (55 mg/dL; n=49), respectively.

Conclusions: The sensitive insulin assay performed excellent in diagnosing CHI with a ROC AUC of 1.0. The use of a p-insulin cut-off of 13 pmol/L (1.86 mU/L) during a diagnostic hypoketotic hypoglycaemia test may establish the diagnosis of CHI without further diagnostic testing.
SUN-284 Rare Case of Adipsic Diabetes Insipidus Post Astrocytoma Resection: Case Report
Authors: Alanazi Alanoud , Elamin Yasir , AlSaeed Zahra , Alabdrabalnabi Fatima
Published: May 2020

Background:

Adipsic diabetes insipidus (ADI) is a rare disorder triggered by injury to the hypothalamus impairing thirst osmoreceptors and the antidiuretic hormone syntheses leading to absence of thirst.

We are reporting a rare case of ADI Post astrocytoma resection who presented with a severe hypernatremia postoperatively.

Clinical Case:

A 16-year-old female known to have hypothalamic pilocystic astrocytoma post incomplete resection in 2014.

She presented in 2018 with one week history of sudden onset heachache, progressively worsen overtime, worst in the morning, there were no relieving factors. On examination she was conscious alert oriented GCS 15/15, Vital signs were normal, fundus exam within normal, pupil equal bilateral reactive to light, there was no focal neurological deficit. Systemic examination was unremarkable. Radiological imaging revealed interval size progression of previously seen suprasella region with extension into the floor of the third ventricle. Investigations: Renal profile & pituitary hormonal profile were normal. She underwent second stage resection.

Postoperatively, she developed asymptomatic hypernatremia with inability to sense thirst. On examination: Conscious, alert, BP:100/65, no postural drop, Pulse:95, Fluid balance negative 1L. Systemic examination was unremarkable. Laboratory investigations: Creat 0.77mg/dl (0.6–1), Na 173mEq/dl(136–145), K 3.3mEq/dl(3.5–5.1), Cl 134mEq/dl(98–107), Serum osmolality 363mOs/kg(285 -295), Urine osmolality 468mOs/kg(300 -1600), Urine Na 29mEq/L(20- 110) & Urine volume 1900. Diagnosis of ADI was made where she was treated with desmopressin. Her response was good with reduction in Na level of around 7- 9 mEq/L/Day. She was maintained on twice daily vasopressin, instructed to maintain her fluid intake 1–1.5 L/day and good urine output.

Conclusions:

Astrocytoma rarely linked with development of central diabetes insipidus and even fewer with adipsia. The absence of polydipsia and polyuria can be misleading. Long-term therapy should consider the benefits of vasopressin and fluid therapy against the risk of brain edema/herniation. Body weight and electrolytes monitoring essential & should be maintained a long with strict fluid intake.
SUN-048 Cardiometabolic Effects of Cross-Sex Hormone Therapy in Transgender Patients
Authors: Trebotic Lana Kosi , Deischinger Carola , Thomas Anita , Just-Kukurova Ivica , Trattnig Siegfried , Kaufmann Ulrike , Kautzky-Willer Alexandra
Published: May 2020

Background: Sex hormones are believed to play an important role in development and progression of cardiovascular disease. However, the gender gap in onset and mortality is not yet completely understood. Transsexuals undergoing hormone therapy are a promising collective for analysing the effects of sex hormones on cardiometabolic disease. Methods: Aim of this study is to identify gender specific cardiovascular changes attributed to high-dose cross-sex hormone therapy (HT) in male-to-female (MtF) and female to male (FtM) transgender patients by performing an oral glucose tolerance test (OGTT) and 3 Tesla magnet resonance spectroscopy for hepatic (HCL) and myocardial (MYCL) lipid content analysis. The control group (CON) is conducted by age, sex and BMI matched healthy individuals. Results: Until now we included 26 MtF,14 FtM patients and 12 age and BMI matched healthy controls. The mean age was comparable in all 3 groups (MtF 30.12±2.31, FtM 29.72±1,91, CON 30,23±1.22 as well as BMI (22.59±3.81, 21.62±2.53, 21.33±1.20 kg/m2, p=ns, respectively). The mean hormone therapy duration was similar in both groups (MtF 4.58±1.20 vs FtM 2.35±0,95, p=0,29). HOMA Index did not significantly differ between the groups (MtF 1,78±0,92 vs FtM 1,96±1.22 vs CON 1,8±1.01, p=0,3 vs 0,4 vs 0,3 respectively). HCL was significantly higher in MtF than FtM (1,50±0,41 % vs 0.54±0,33 %, p=0,022, respectively). We also found a significant correlation between ejection fraction (EF) and Testosterone levels (Spearmans Rho 0,80, p=0.002). Conclusio: These preliminary data could indicate a positive effect of Testosterone therapy on heart function. Contradictory to current data we found a higher HCL in MtF than FtM suggesting a not so protective estrogen effect when looking at the liver. Long-term studies are warranted to assess whether cross-sex HT results in different outcomes regarding cardiovascular disease.
MON-074 Ketotic Hypercalcemia; A Possible Side Effect of Managing Refractory Epilepsy with Ketogenic Diet
Authors: Dekelbab Bassem , Davydova Yafa , Levine Michael A
Published: May 2020

Background: Patients with epilepsy have multiple risk factors for low bone mass, including immobility, reduced muscle mass, and use of multiple anticonvulsant medications. The ketogenic diet (KD) has been used as an effective treatment of refractory epilepsy for decades, with multiple reports in medical literature describing adverse effects on bone and mineral metabolism including gradual loss of bone mineral density. There has been only one report of hypercalcemia in three children on the KD for refractory seizures. We now describe another case, highlighting the importance of considering the KD as a cause of hypercalcemia.. Case presentation: A 14-year-old girl with Rett syndrome, epilepsy, global developmental delay and gastrostomy tube dependency presented to the emergency room with marked dehydration. She had been on the KD for several years due to refractory epilepsy. Her parents had recently noticed thick oral secretions. The only change in her management plan was the recent change of her formula from Ketocal 3:1 to Ketocal 2.5:1. Lab studies showed hypercalcemia 15 mg/dL (ref 9.2-10.7) with ionized calcium of 7.99 mg/dL (ref, 4.8-5.2). She had normal serum calcium levels on multiple previous occasions, including 10.2 mg/dL 4 months prior to presentation. Other studies included increased BUN 37 mg/dL (ref, 7-21) and Creatinine 2.31 mg/dL (ref, 0.53-0.8). She had a low normal PTH 14 pg/ml (ref, 8-72), PTH-related peptide 0.6 pmol/l (ref, < 4.2), and 25-hydroxyvitamin D 66 ng/ml (30-100). 1,25-dihydroxyvitamin D level was low at 12.5 pg/ml (ref, 19.9-79.3), with increased urine calcium/creatinine ratio 1.00 mg/mg creat (Ref, 0.02-0.26). Beta Hydroxybutyrate was 3.45 mmol/l (ref, 0.02 - 0.27), without major change over the last year. Renal US was normal. She received IV hydration with improvement in serum calcium, BUN, and creatinine and was discharged on increased intake of free water and adjustment of KD to maintain Beta Hydroxybutyrate around 2 mmol/l. Her serum calcium currently ranges 10.5- 12 mg/dl, and will soon begin therapy with subcutaneous calcitonin. Conclusion: The KD has adverse effects on bone and mineral metabolism, and can lead to severe hypercalcemia and/or hypercalciuria as well as decreased bone density. Agents that decrease bone resorption are highly effective. Providers caring for children on this diet should be aware of such potential association. Reference: Hawkes CP, Levine MA. Ketotic hypercalcemia: a case series and description of a novel entity.J Clin Endocrinol Metab. 2014 May;99(5):1531-6.
MON-644 Prevalence of Non-Alcoholic Fatty Liver Disease and Liver Fibrosis in Patients with Type 2 Diabetes Mellitus
Authors: Fanous Nada , Bril Fernando , Leiva Eddison Godinez , Kalavalapalli Srilaxmi , Cusi Kenneth , Lomonaco Romina
Published: May 2020

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. The more severe form is non-alcoholic steatohepatitis (NASH) which can progress to liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). NASH is more common in patients with type 2 diabetes mellitus (T2DM). However, its true prevalence in unselected patients with T2DM in the United States remains unknown. In 2019, the American Diabetes Association recommended screening for NASH and liver fibrosis in all patients with T2DM with steatosis and/or elevated ALT. Screening focuses on liver fibrosis as associated with increased risk of cirrhosis and HCC. Still, a liver biopsy remains the gold standard to accurately assess the severity of liver disease. The aim of this study was to determine the prevalence of liver fibrosis in unselected patients with T2DM presenting to primary care or endocrinology clinics at a university hospital in the US. Secondary outcomes were to assess the prevalence of steatosis controlled attenuation parameter (CAP) and performance of vibration-controlled transient elastography (VCTE) as a non-invasive tool to identify patients with significant liver fibrosis. Patients with T2DM between ages of 21-79 and without a history of alcohol intake or other causes secondary causes of NAFLD were recruited for the study. Participants underwent screening for NAFLD at the time of their clinic visit by means of point-of-care CAP and VCTE. Initial evaluation also included obtaining patient demographics, routine chemistries, and fasting samples (on visit #2 if not fasting initially) for metabolic measurements and fibrosis biomarkers. Liver biopsies were offered to patients with a liver stiffness measurement (LSM) ≥8.0 kPa (i.e., highly likely to have moderate-to-severe fibrosis or ≥F2), or those with ≥7 kPa if AST ≥20 and had an APRI and/or FIB-4 score suggestive of being at high-risk of liver fibrosis (i.e., at least mild-to-moderate fibrosis or ≥F1). A total of 469 patients were recruited (age 59±12; 56% females; 60% non-Hispanic whites, 30% African Americans, 4% Asian; BMI 33±6 Kg/m2; A1c 7.5±1.7%; FPG 143±60 mg/dL; AST 22±11 U/L; ALT 24±17 U/L; triglycerides 156±151 mg/dL; LDL-C 88±37 mg/dL; HDL-C 47±13 mg/dL). The prevalence of NAFLD by CAP (≥280) was 67% with a mean CAP of 305±3. The prevalence of any fibrosis was 24% patients. Among those with fibrosis, 15% had moderate-to-severe fibrosis or ≥F2. In those that underwent a liver biopsy, 61% had moderate-to-severe fibrosis (F2-3). Our ongoing study demonstrates the high prevalence of liver steatosis and fibrosis in patients with T2DM. NASH is a common but under-recognized complication of T2DM that requires greater awareness among clinicians taking care of patients with diabetes. While the optimal screening strategy remains unclear, an approach based on plasma biomarkers and CAP/VCTE deserves further exploration moving forward.
SUN-017 Developmental Programming: Prenatal Testosterone Treatment Induced Metabolic Defects May Involve Premature Cellular Senescence
Authors: Puttabyatappa Muraly , Ciarelli Joseph Norman , Padmanabhan Vasantha
Published: May 2020

Prenatal exposure to excess testosterone (T) programs peripheral insulin resistance and dyslipidemia along with tissue-specific increases in ectopic lipid accumulation, oxidative stress and insulin resistance in liver and muscle of the early adult female sheep. Prenatal T increased inflammation and oxidative stress in the visceral (VAT) but not subcutaneous (SAT) adipose tissue, with no effect on insulin sensitivity in both depots. These systemic and tissue-specific metabolic changes are reminiscent of defects such as non-alcoholic fatty liver disease (NFLAD) common among aged individuals. Because it is known that gestational insults can program premature aging of reproductive organs and chronic cardiovascular abnormalities, we hypothesized that programming of premature cellular senescence is one of the ways through which gestational T induces premature aging of metabolic systems during early adulthood. To test this hypothesis, mitochondrial oxidative phosphorylation (OXPHOS) and telomere length, as measure of cellular senescence, were assessed in liver, muscle, VAT and SAT collected from control and prenatal T- (100mg T propionate twice a week from days 30-90 of gestation) -treated female sheep at 21 months of age. Genomic DNA was subjected to TeloTAGG Telomere Length Assay (Sigma-Aldrich, St Louis, MO) and whole tissue protein lysates analyzed by immunoblot using Total OXPHOS Human WB Antibody Cocktail (ab110411, Abcam, Cambridge, MA). Data were analyzed by Student’s t test and Cohen’s effect size analysis. Prenatal T-treatment induced 1) a trend (p = 0.09) towards a large magnitude increase in shorter telomere fragments (0.08 -3.6 KB) in the liver and 2) a non-significant large magnitude decrease in shorter telomere fragments in muscle and SAT without having any effect in the VAT. Prenatal T also induced a large magnitude increase in mitochondrial OXPHOS protein complexes II and IV in liver, without having an effect at the level of the muscle, VAT and SAT. These findings are suggestive that prenatal T-treatment induced hepatic defects may involve premature cellular senescence. The relevance of parallel increase in mitochondrial OXPHOS in the liver is unclear and remains to be explored. The defects observed in the muscle and SAT may occur independent of cellular senescence or alterations in mitochondrial function. The lack of change in telomere length and mitochondrial OXPHOS in spite of increased inflammation and oxidative stress in the VAT is suggestive of a potential protective function in play, consistent with maintenance of the insulin sensitivity in this tissue. This study, therefore, raises the possibility that metabolic defects programmed by gestational insults may involve premature aging of metabolic organs in a tissue-specific manner and have translational bearing in conditions associated with hyperandrogenic states.
SAT-670 The Perfect Storm for Diabetic Ketoacidosis
Authors: Abushamat Layla A , Bhalla Rajat , Reusch Jane E
Published: May 2020

Background

Diabetic Ketoacidosis (DKA) is a life-threatening endocrine emergency characterized by metabolic acidosis occurring in the setting of hyperglycemia due to relative insulin deficiency leading to lipolysis and production of serum ketones. Clinical circumstances can potentiate this process, such as acute infection or insulin discontinuation. Additionally, patients on SGLT2-inhibitors are at risk for euglycemic DKA. In people with type 2 diabetes, DKA is uncommon; however, a combination of precipitating factors in these patients can lead to a greater risk of DKA, particularly in the setting of SGLT2-inhibitor use.

Clinical Case

A 63 year old male with past medical history significant for uncontrolled type 2 diabetes (10 year duration, HgA1c=11.2%, on insulins detemir and aspart, metformin, and empagliflozin), coronary artery disease, and treatment refractory antibody-negative polymyositis (baseline CPK levels ~1000-2000, on a burst of prednisone for flare) presented with fever (101.2F), fatigue, myalgias, and nausea with poor oral intake and insulin cessation after recent IV zoledronic acid infusion for prevention of steroid-induced osteoporosis. He was found to be acidemic with bicarbonate=16, AG=18, Cr=1.6 (baseline 1.1), lactic acid=2.9, glucose=245, glucosuria/ketonuria, serum osmolality=295, and CPK=3613. No infectious etiology was found. Differential diagnosis of precipitating factors of DKA includes: steroid-induced hyperglycemia with lipolysis and insulin resistance; starvation ketosis from poor oral intake due to bisphosphonate-induced flu-like illness; metformin-associated lactic acidosis in setting of acute kidney injury; ketone production secondary to insulin cessation in setting of febrile illness; and SGLT2-inhibitor use with dehydration secondary to decompensated hyperglycemia. He was treated for DKA with insulin and volume resuscitation. He was discharged with discontinuation of empagliflozin.

Conclusion

In people with type 2 diabetes and multiple medical problems, a collusion of clinical factors leading to acidemia can occur simultaneously and lead to a drastically increased risk of DKA, especially in the setting of SGLT2-inhibitor use. Clinicians should have heightened awareness of minor predisposing factors that in combination can increase risk of DKA in a patient with type 2 diabetes.
MON-500 Cell Adhesion Molecules mRNA Expression in Thyroid Tumors
Authors: Teodoro Larissa , Peres Karina Colombera , Nascimento Matheus , Teixeira Elisangela Souza , Barreto Icleia Siqueira , Geraldo Murilo Vieira , Assumpção Ligia Vera Montalli , Tincani Alfio José , Maximo Valdemar , Bufalo Natassia Elena , Ward Laura Sterian
Published: May 2020

Thyroid cancer biology is extremely diverse. While some cases never progress clinically or do so indolently, others evolve aggressively and may even lead to death. Cell adhesion molecules are glycoproteins present in the cell membrane and play an important role in inflammatory and neoplastic diseases by recruiting immune cells to these sites. The aim of the present study was to investigate the role of mRNA expression of SELL, ICAM1 and ITGAL in thyroid tumors and their relationship with lymphocyte infiltration. We evaluated by RT-qPCR technique 191 thyroid nodules including 97 benign (79 females, 17 males; 49.8±12.5 years old) and 94 malignant (71 females, 23 males; 48.3±15.5years old) cases. Clinical and pathology data were obtained from 47 goiters; 50 follicular adenomas (FA); 74 papillary thyroid carcinomas (PTC), including: 29 classic papillary thyroid carcinomas (CPTC), 21 follicular variant of PTC (FVPTC), 12oxifilic variant of PTC (OVPTC), 12 tall cell papillary thyroid carcinomas (TCPTC); and 20 follicular thyroid carcinomas (FTC). All patients were managed according to a standard protocol based on current guidelines and followed-up for 78.7±54.2 months. SELL was more expressed in malignant (0.85±1.54 UA) than in benign (0.54±0.71 UA, p=0.0027) nodules. The same occurred with ICAM1 (0.99±1.41 vs. 0.46±0.85, p=0.0001), but not with ITGAL gene expression (1.04±1.63 vs. 0.76±1.21, p=0.2131). In addition, the expression of SELL was different when we compared PTC with FA (0.94±1.62 UA vs. 0.47±0.72 UA, p=0.0018) and FTC with FA (0.82±2.38 UA vs. 0.47±0.72 UA, p=0.0078). ICAM1 expression was lower in goiters (0.46±0.90 UA) when compared with PTC (0.93±1.22 UA, p=0.0030) and FTC (1.03±3.30 UA, p=0.0207). Higher expression of ICAM1 (1.16±3.04 UA vs. 0.52±0.96 UA, p=0.0064) and ITGAL (1.17±1.54 UA vs. 0.49±1.39 UA, p=0.0244) was observed in tumors with lymphocyte infiltrate. Also, ITGAL gene expression was higher in tumors that had distant metastasis at diagnosis (1.53±2.18 UA vs. 0.57±1.10 UA, p=0.0217). We were not able to demonstrate any association between any of the investigated molecules and patients’ outcome. In conclusion, our data suggest that cell adhesion molecules may play an important role in neoplastic thyroid cells proliferation. In addition, our findings show that gene expression of SELL and ICAM1 may assist in the histological characterization of follicular patterned thyroid nodules.
SUN-192 Spontaneous Adrenal Hemorrhage in a Patient with Antiphospholipid Syndrome on Rivaroxaban: A Potentially Fatal Complication
Authors: DiCenso Daniela Maria , Penaherrera Carlos A , Ayala Alejandro
Published: May 2020

Introduction: Primary Adrenal insufficiency is an uncommon complication of antiphospholipid syndrome, with an incidence of 0.4% [2]. It is often secondary to bilateral adrenal hemorrhage. We present a case of bilateral adrenal hemorrhage in a patient with APLS on anticoagulation with rivaroxaban. Case: 46-year-old m with a history of antiphospholipid syndrome, recently transitioned from warfarin to rivaroxaban for anticoagulation, who presented to the ED after a syncopal episode following a prior episode of abdominal pain with an unremarkable work-up. He subsequently developed severe fatigue, dizziness, headaches, nausea and 15 lbs weight loss. On presentation, the patient was hypotensive(72/45 mmHg) and tachycardic. Intravenous hydration was started with minimal response. Initial laboratory testing showed serum sodium of 121mmol/L, potassium of 5.5mmol/L and random cortisol of 0.8mcg/dL. The patient was admitted to the intensive care unit where he was started on vasopressors and hydrocortisone 50 mg IV every 8 hours. A non-contrast CT of the abdomen and pelvis showed thickening of the adrenal glands with decreased attenuation. MRI of the abdomen showed hyper-intensity of the adrenal glands bilaterally (T1 images), without post-contrast enhancement suggestive of bilateral adrenal hemorrhage. His electrolytes normalized, and he was successfully discharged home on hydrocortisone and fludrocortisone replacement with outpatient follow-up. Discussion: Atraumatic bilateral adrenal hemorrhage is rare, but remains one of the most common endocrine-related complications of antiphospholipid syndrome (APLS). The venous anatomical configuration of the adrenal gland increases risk of thrombotic hemorrhagic infarction[1]. Patients with APLS are commonly anticoagulated to prevent thrombosis. The ideal anticoagulation regimen remains controversial. Only three other cases of spontaneous bilateral adrenal hemorrhage on patients with APLS using new oral anticoagulants (NOACs) were reported. The use of NOACs seem to increase the already-elevated risk of adrenal hemorrhage seen in patients with APLS.

References:

1. Aldaajani, H. et al. Bilateral adrenal hemorrhage in antiphospholipid syndrome: Anticoagulation for the treatment of hemorrhage. Saudi Med J. 2018; 39(8): 829-833.

2. Cervera R, Piette JC, Font J, Khamashta MA, Shoenfeld Y, Camps MT, et al. Antiphospholipid syndrome: Clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients. Arthritis Rheum. 2002;46:1019-27.
SAT-030 The Barnsley Diabetes Hypogonadal Questionnaire (BDHQ) - Validation for the Clinical Use to Support the Diagnosis of Testosterone Deficiency in Men with Type 2 Diabetes (T2D)
Authors: Mumdzic Enis , Rao Preethi Mohan , Jones Thomas Hugh
Published: May 2020

The Aging Males’ Symptoms (AMS) scale is used to assess health-related quality of life (HRQOL) and erectile dysfunction (ED) in hypogonadal men. However, this questionnaire hasn’t been validated specifically for use in hypogonadal men with T2D. BDHQ was developed using data collected in the Barnsley Type 2 Diabetes Cohort Longitudinal Study based on AMS, The International Index of Erectile Function Questionnaire, and The Short Form (36) Health Questionnaire. Statistical analysis identified the 19 most sensitive and specific questions for identifying men with hypogonadism in a T2D population.

Objectives: To assess the significance of AMS and BDHQ in hypogonadal men with T2D.

Methods: The research data from a study involving men with T2D was used. All men were divided into 2 groups according to their baseline total testosterone (TT) status: group 1 (n = 82) - men with low TT (<10.4nmol/l; 300ng/dl), and group 2 (n = 64) - men with normal TT (≥10.4nmol/l; 300ng/dl). Data was also assessed using calculated freeT and bioavailableT. The statistical analysis was carried out using SPSS software and the data analysed using General Linear Model Univariate analysis of variance and Receiver Operating Characteristic (ROC) curve.

Results: Mean age for group 1 was 59.4 ± 10.1 years (range 25 - 77) and for group 2 was 61.5 ± 9.8 years (range 30 - 80). Mean TT for group 1 was 7.9 ± 1.8 nmol/l (range 1.3 - 10.3); for group 2TT was 14.9 ± 4.1 nmol/l (range 10.4 - 29.5). There was statistically significant difference in the scores in both questionnaires between the groups (AMS, p=0.012; BDHQ, p=0.035). Area under the curve (AUC) by ROC analysis showed no significant difference in sensitivity and specificity between the two questionnaires (AMS, AUC=0.623; BDHQ, AUC=0.606). To achieve sensitivity of 80%, it showed that the cut-off for positive test should be 40 out of 85 for AMS, and 44 out of 95 for BDHQ.

Conclusion: The BDHQ can be used to support a diagnosis of hypogonadism in the presence of persistent testosterone deficncy when TT is <10.4nmol/l. Whilst AMS is well-recognised tool for assessing HRQOL and ED in hypogonadal men in general population, the cut-off for positive test should be lower in diabetic population. In addition, this study showed that BDHQ is not inferior test to AMS in assessing HRQOL and ED in hypogonadal men with T2D.
SUN-352 The Effects of Acute Hyponatremia on Bone Remodeling Markers in Patients with Subarachnoid Hemorrhage
Authors: Garrahy Aoife , Galloway Iona , Hannon Anne Marie , Dineen Rose , Gan K J , Javadpour Mohsen , Tormey William T , Twomey Patrick J , McKenna Malachi J , Kilbane Mark , Sherlock Mark , Crowley Rachel K , Thompson Chris J
Published: May 2020

Animal data and cross-sectional human studies have established that chronic hyponatremia predisposes to osteoporosis; the effects of acute hyponatremia on bone remodeling are unknown. Serum markers of bone remodeling (total procollagen type 1 amino-terminal propeptide (P1NP), bone specific alkaline phosphatase (bone ALP), N-mid-osteocalcin (OCI) and C-terminal teleopeptides of type I collagen (CTX-1)) were assessed in a cohort of patients admitted with subarachnoid hemorrhage (SAH), who were prospectively studied over seven days. The ratio of P1NP:CTX-1 was calculated to report a bone formation index.

Twenty-two patients (13 women), median (IQR) age 53 (47, 62) years were recruited. Patients who developed post-SAH ACTH deficiency and those treated with glucocorticoids, or continuous enteral feeding were excluded. All patients were eunatremic on initial assessment. Eight patients developed acute hyponatremia, median nadir plasma sodium concentration (pNa) 131 (128, 132) mmol/L, and 14 remained eunatremic, nadir pNa 136 (133, 137) mmol/L. The groups were matched for age, 25-hydroxy Vitamin D, PTH, WFSS and Fischer scores. Serum cortisol concentration was greater in the hyponatremic group, 571 (504, 671) nmol/L, than the eunatremic group, 449 (400, 501) nmol/L, p=0.008. Bone remodeling markers and bone formation index (P1NP:CTX-1 ratio) were similar in the two groups at baseline.

There was a significant rise in CTX-1 in both hyponatremic patients, +0.15 (0.09, 0.37) μg/l, p = 0.009, and patients who remained eunatremic, +0.11 (-0.02, 0.23) μg/l, p = 0.04, with no significant difference between the groups. There was, however, a significant fall in P1NP:CTX-1 ratio in patients with acute hyponatremia, p = 0.02, but no significant change in eunatraemic patients, with significant between group difference, p = 0.02.

Changes in P1NP and OCI correlated positively with nadir pNa; r = 0.43, p = 0.04 and r = 0.61, p = 0.001 respectively. In addition, there was a positive correlation between change in P1NP:CTX-1 ratio and nadir pNa, r = 0.43, p = 0.04. There was no correlation between change in OCI or CTX-1 and nadir pNa. Serum cortisol was strongly negatively correlated with change in P1NP (r = -0.64, p = 0.001) but not with change in other bone remodeling markers.

Acute hyponatremia following SAH is associated with a fall in bone formation index; physiological hypercortisolemia may contribute to this. Further analysis with larger numbers will help us determine whether hyponatremia is an independent risk factor.
MON-305 Clinical Features in Patients with Hypercorticism
Authors: Negmatova Gulzoda Shuhratovna , Norshodieva Rukhangiz Utkurovna , Mirsaidova Umida Akmalovna
Published: May 2020

Cushing’s disease is a severe multimorbid pathology affecting mainly people of young working age. In most cases, the diagnosis of the disease is acute and the patient is observed for a long time by doctors of different specialties with complications of hypercorticism.

Purpose: To identify the most frequent clinical manifestations of hypercorticism at the time of diagnosis of Cushing’s disease, to analyze the relationship of clinical manifestations of hypercorticism with the main clinical and laboratory indicators.

Material and methods: 25 patients were examined, including 15 women and 10 men with Cushing’s disease, registered in Samarkand Endocrinology Clinic.

Results: Majority of patients (68%) were in age 25-40, the average age was 37. The median duration of the disease was 35,5 months. Matronism, the most characteristic manifestation of hypercortisolism was observed in 36% (9 patients). This is most often associated with hypercorticism symptoms were striae and acne, which were found in 56% (14 patients), osteoporosis 40% (10). The most frequent complaints were weight gain, fatigue, headache, menstrual disturbances. A number of symptoms had a positive correlation with cortisol levels.

Conclusion: Clinical manifestations of hypercorticolism are mainly nonspecific. Striae and acne were found in high frequency. Therefore these key features, namely a change in facial appearance, weight gain, elevation of BMI and the presence of genital virilisation should alert the clinician to the possibility of Cushing’s disease and initiate laboratory evaluation
MON-161 Body Weight Reduction Not Always Reduced Adrenal Gland Volume in Obese Patients
Authors: Chen Tao
Published: May 2020

Recent studies have shown that obesity is a major risk factor for idiopathic hyperaldosteronism (IHA). IHA patients have greater AGV than normal controls. However, it is unclear whether such changes are caused by obesity and whether losing weight could reverse the morphological and functional abnormalities of the adrenal gland. This study was to investigate the association of obesity with adrenal gland volume (AGV) and the effects of weight loss on AGV. This study recruited obese patients (N=25) who underwent sleeve gastrectomy and age- and sex-matched normal-weight (N=25) and overweight healthy volunteers (HV) (N=21). Thin-slice computed tomography was used to evaluate adrenal morphological changes. AGV was measured semiautomatically based on the digital imaging and communications in medicine (DICOM) image. The effects of weight loss on AGV were evaluated in patients for one year or more after sleeve gastrectomy. The results showed that left, right and total AGV were larger in obese patients than those in overweight and normal- weight HVs (6.77±0.36, 5.76±0.31, and 12.53±0.64 cm3 vs. 3.88±0.14, 3.09± 0.13 and 6.97± 0.24 cm3 vs. 3.38±0.23, 2.67±0.15 and 6.04±0.36 cm3). No statistically significant difference was identified between overweight and normal-weight HVs. Sleeve gastrectomy significantly reduced body weight (-27.1±2.5 kg), left AGV (-0.80±0.26 cm3), and right AGV (-0.88±0.20 cm2). However, the adrenal volume in five patients was not reduced, despite significant weight loss postsurgery. In brief, obesity leads to increased AGV, and in some cases, this effect seems to be irreversible. We speculate that obesity causes permanently adrenal morphological changes (increased volume or hyperplasia), and under certain circumstances, it results in excessive aldosterone secretion via altered adipokines (leptin, CTRP1, etc.).
MON-598 Vitamin B12 Deficiency Leads to Fatty Acid Metabolism Dysregulation and Increased Pro-Inflammatory Cytokine Production in Human Adipocytes and Maternal Subcutaneous and Omental Adipose Tissue
Authors: Samavat Jinous , Adaikalakoteswari Antonysunil , Boachie Joseph , McTernan Philip , Christian Mark , Saravanan Ponnusamy
Published: May 2020

Vitamin B12 (B12) is an essential micronutrient required for optimal hematopoietic, neurologic and other several metabolic reactions. Animal and clinical studies show that B12-deficiency is associated with maternal obesity, insulin resistance, and metabolic syndrome. Given the key metabolic role of adipose tissue, we investigated whether B12 deficiency may affect triglyceride synthesis and lipid metabolism leading to adipose tissue inflammation. The AbdSc pre-adipocyte cell line (Chub-S7) and human AbdSc primary pre-adipocytes were differentiated under different B12 concentrations (25pM,100pM,1nM,500nM). Human Om, Sc-AT and blood samples were collected from 106 pregnant women at delivery. SerumB12 and relevant metabolic risk factors were measured. Gene expression was performed by q-RTPCR, de novo triglyceride synthesis was quantified by radioactive tracing, ß-oxidation and palmitate-induced oxygen consumption rate was determined using seahorse-XF analyser. Adipocytes cultured in low-B12 conditions showed significantly increased expression (P<0.01) of triglyceride biosynthesis genes (ELOVL6,SCD,GPAT,LPIN1 and DGAT2), a significantly decreased expression (P<0.01) of ß-oxidation genes (FAT/CD36,CPT1-ß,ACADL,ECHS1 andACAA2) and an increased expression (P<0.01) of pro-inflammatory cytokines (IL-1, IL-6,IL-8,IL-18,TGF-β,TNF-α and MCP-1). These data were also confirmed in the AT of B12-deficient pregnant women. Additionally, real-time fatty acid flux synthesis and fatty-acid-oxidation induced by palmitate were significantly altered (P<0.05) in B12-deficient adipocytes. Our data highlights that B12-deficiency has profound effects on adipocyte dysfunction, opening new insights into the pathogenesis of maternal obesity and the relevance of micronutrient supplementation for pregnant mothers.
SAT-708 The Effect of Soybean Isoflavones in Developing Cerebellum
Authors: Ariyani Winda , Miyazaki Wataru , Amano Izuki , Koibuchi Noriyuki
Published: May 2020

Abstract ENDO 2020

The effect of soybean isoflavones in developing cerebellum

Thyroid hormone (TH) receptor (TR) and estrogen receptor (ER) play crucial roles in cerebellar development. TR and ER are involved in Purkinje cells dendrite growth, spines and synapse formation. They also regulate the functional maturation, intracellular metabolism, and migration of neuron and glial. Soybean isoflavones especially genistein, daidzein, and daidzein metabolite, S-equol were known to exert their action through TR, ER, and GPR30, that is a G-protein-coupled ER. However, the mechanisms of soybean isoflavone action on cerebellar development and function have not yet been extensively studied. We evaluated the effects of soybean isoflavone, such as genistein, daidzein, and S-equol, using mouse primary cerebellar culture, astrocyte-enriched culture, and C6 clonal cells. Soybean isoflavone augmented TH- or estradiol (E2)-mediated dendrite arborization of Purkinje cells. Such augmentation was suppressed by G15, a selective G-protein coupled ER (GPR30) antagonist, and ICI 182.780, an antagonist for ERs in both cultures. It also increased mRNA expression level of TH-responsive genes including Mbp, Bdnf, Rc3, Ntf3, Camk2b, and Hr. Moreover, genistein and daidazein also increased mRNA expression level of Syn1, Syp and Psd95 that are involved in synaptic plasticity.

On the other hand, in astrocytes, soybean isoflavone activated cell migration and F-actin rearrangements. Such effects were suppressed by G15, but not by ICI 182.780. Knockdown of GPR30 by RNAi also suppressed the cells migration. Protein expression levels of p-Akt (Ser473), p-Rac1/cdc42 (Ser71), RhoA, Rac1/2/3, and cdc42 also increased by soybean isoflavone. Co-exposure with Rhosin HCl, a selective RhoA inhibitor, reduced the cells migration and formation of stress fibers. These findings indicate that sobybean isoflavone may affect cerebellar development by acting to both neurons and astrocytes through several signaling pathways, including TR, ER, and GPR30.

Keywords:

EDC, ER, TR, GPR30, Neuron, Astrocyte
SUN-571 The Associations Between p,p’-DDE Levels and Serum Levels of Lipoproteins and Their Subclasses in an Elderly Population Determined by Lipidomics Analysis
Authors: Jugan Juliann Amela , Lind P Monica , Salihovic Samira , Stubleski Jordan , Kärrman Anna , Lind Lars , Merrill Michele La
Published: May 2020

Low biodegradability and high lipophilicity of p,p’-dichlorodiphenyldichloroethylene (DDE), a metabolite of the insecticide DDT, leads to transport with lipids and accumulation in adipose tissue. This persistence allows for DDE to effect adipose tissue and lipid metabolism. A few small human studies have shown an association between DDE and blood lipids, although with some inconsistent conclusions. The aim of this study was to investigate the association between DDE exposure and altered levels of circulating lipids in a large human cohort. To evaluate the associations between DDE and human lipid profiles, plasma was collected from a subset of elderly Swedes in the Prospective Investigation of the Vasculature of Uppsala Seniors (PIVUS) cohort who were free from lipid lowering medication (n = 571). DDE concentrations in plasma were measured using high-throughput solid phase extraction and gas chromatography-high resolution mass spectrometry. Lipidomic analysis of plasma was performed with nuclear magnetic resonance spectroscopy. Linear models of lipids and DDE were statistically adjusted for sex and body mass index. Detectable levels of DDE were found in the plasma samples of all subjects. With elevated DDE levels, the comprehensive lipoprotein profile showed an elevation in total concentration of all diameters of very low density lipoprotein (VLDL) (p<0.001), low density lipoprotein (LDL) (p<0.008), intermediate density lipoprotein (IDL) (p<0.02), and in small high density lipoprotein (HDL) (p<0.05). Triglycerides and DDE were associated to varying degrees in lipoproteins (IDL > VLDL > LDL > HDL) and within total serum (p<0.005). DDE levels were positively associated with cholesterol and cholesterol ester levels only in VLDL and LDL (p<0.05) and with apolipoprotein B (p<0.0009). The positive associations observed between each lipoprotein class and elevated DDE support previous data suggesting that DDE interacts with lipoproteins within plasma. We speculate that both physio-chemical and biological mechanisms may explain why DDE does not uniformly associate with lipids across lipoproteins.
SUN-176 A Case of Aldosterone-Producing Adenoma with Preoperative Use of a Novel Mineralocorticoid Receptor Antagonist Esaxerenone
Authors: Yamanami Hiroaki
Published: May 2020

Background: Esaxerenone is a novel mineralocorticoid receptor antagonist (MRA) with nonsteroidal structure and high selectivity to MR, which became clinically available in Japan in 2019.

Clinical Case: A 57-year-old woman showed a left adrenal incidentaloma (15mm) on MRI. Serological tests confirmed a diagnosis of primary aldosteronism: baseline plasma aldosterone concentration (PAC) was elevated (47.3 ng/dL, n < 15.9 ng/dL), and plasma renin activity (PRA) below sensitivity. PAC after saline infusion was 43.2 ng/dL. Overnight 1mg dexamethasone suppression test was negative. Her blood pressure had been well-controlled with amlodipine 5mg daily. Despite of large amount of potassium supplementation (96 mmol/day orally and 50 mmol/day intravenously), the level of serum potassium remained low (3.2 mmol/L). Adrenal venous sampling (AVS) was performed successfully, showing laterality index of 45.8 on left. Segmental AVS supported aldosterone hypersecretion from the tumor. After diagnosis, esaxerenone was introduced and the patient became normokalemic without potassium supplementation after a week. No adverse effect occurred in a period of two months before surgery. She underwent laparoscopic left total adrenalectomy. The tumor was positive for CYP11B2, consistent with aldosterone producing adenoma (APA). She became normotensive and normokalemic without any medications.

Conclusion: This case illustrates the preoperative effectiveness of esaxerenone on blood pressure and hypokalemia in patients with APA.

Key words: Esaxerenone; mineralocorticoid receptor antagonist; case report; adrenal venous sampling; primary aldosteronism; aldosterone producing adenoma
MON-477 Anti-Streptavidin Interference in Multiple Hormones Immunoassays: Case Report
Authors: Brito Luciana Pinto , Lenczuk Aline , Leopoldino Luciana , Lando Valeria Samuel , Mendonca Berenice Bilharinho , Lima-Valassi Helena
Published: May 2020

Automated immunoassays are the most commonly current methods used in clinicial laboratory to hormone tests, due short turnaround time and high specificity and sensibility. However immunoassays are not free from interferences. Several immunoassays use biotin-streptavidin interaction to anchor antigen-antibody complexes in solid phase and so are susceptible to biotine intake or anti-streptavidin antibody. In sample with these interferents, the results in competitive assays are falsely high and in non-competitive assays are falsely low. OBJECTIVE: To report a case of multiple hormones immunoassay interference by an anti-streptavidin antibody. MATERIAL AND METHODS: A 11-years-old boy with child obesity, and no other symptoms, had discordant laboratory results with markedly elevated free T4, total T4 and total T3 with normal TSH. Repeated measurements in the same sample and in a new collected sample confirmed the initial results and revealed low PTH and high TRAb without hypocalcemia or hyperthiroidism clinical pictures. All the parameters were measured on the automated Cobas e602, Roche plataform.The patient and your family denied biotin ingestion, so anti-streptavidin interference could explain the multiple interference.The serum was pre-incubated with streptavidin microparticles during an hour and centrifuged for 10min (3000 rpm) to removed the analytical interference. RESULTS: The results of post-incubation with microparticles were all in the normal range. Three control samples were not affected by the incubation. Since luminescence is inversely proportional to analyte concentration in competitive assays, low signals lead to falsely high levels (like in free T4, total T4, Total T3 and TRAb in our patient). The reverse occurs with immunometric assays, in which low signals result in falsely reduced values (like in PTH in our patient). CONCLUSION: In literature, streptavidin antibodies seem to be a rare occurrence. In samples with biotin or anti-streptavidin suspection, pre-incubation with streptavidin microparticles is a simple and effective procedure to remove this interference.