bluuebunny/crossref_metadata_2025 huggingface dataset:
MON-391 Implementation of an Osteoporosis Risk Assessment Instrument (ORAI) to Increase Referral Rates for DEXA Scanning in the Primary Care Setting
Authors: Saatciler Eda , Gillooly Diane , Toro Bernard , Lontai Peter
Published: May 2020

Abstract

Background/Purpose: Osteoporosis (OP)was first identified and named by healthcare professionals in the 18th century. Today, OP is still the source of fractures which impair mobility, leading to sub-acute stays at rehabilitation centers. A major obstacle is that primary care providers (PCPs) fail to identify warning signs of OP, and inform patients that Dual Energy X-Ray Absorptiometry (DEXA) scans that are one of the best procedures to assess bone health. This project addressed the issue of low rate of referrals for DEXA scans. Theoretical Framework: The Knowledge-to-Action (KTA) model was used to guide this study. Intervention: Implementation of osteoporosis risk assessment instrument. Methods (Design, Sample, Setting, Measures, Analysis): This includes pre-implementation phase, patients’ charts were reviewed; post-implementation phase, the number of people referred to have DEXA scans were analyzed; the evaluation phase, results compared to the previous data. The project focus exclusively on women and men ages 50 to 89 years in two primary care offices in New Jersey. Descriptive analyses concentrated on whether or not ORAI was the tool to increase DEXA scans. Results: The data analysis reflected that the baseline referral rates increased from 1.3 % to 42 % and patients who scored high on the risk assessment instrument have been referred more often than not. Moreover, patients who are at risk and younger than 65 years of age, risk assessment tools led to a positive referral for a DEXA scan. Those who are older than 65 years, risk assessment tools like ORAI should be given with fracture risk assessment tools. This is especially the case when dealing with men, a demographic group often overlooked in the fight against OP. Conclusions Implications: If this project is to be applied at other clinics, more and more patients would be referred, raising awareness of the medical benefits of early detection. Reasonably, covering a broader section of patients, earlier in their lives, will increase clinical income, bringing more patients to primary care offices.
SAT-584 Uc.336-As Inhibits White Adipocyte Differentiation and Promotes White to Brown Conversion
Authors: Li Yanbing , Guan Hongyu , Li Hai
Published: May 2020

Brown adipose tissue (BAT) has gained its popularity since it shows great potential in counteracting obesity and metabolic diseases development. Transcribed ultraconserved regions (T-UCRs), a novel class of long non-coding RNA (lncRNAs), have been implicated in regulating diverse biological processes, including the process of white fat browning. However, the functional and mechanistic details of T-UCRs in the browning process are poorly understood. Here, we identified that a T-UCR, uc.336-as, played an important role during the browning process. uc.336-as was significantly elevated during browning process induced by exendin-4 or β3-adrenergic agonist (CL316,243). Moreover, we found that uc.336-as promoted browning process and inhibited adipogenesis. Finally, we identified that uc.336-as promoted the expression of browning-related genes via influencing the p38 mitogen-activated protein kinase (p38 MAPK) signaling, an essential signal pathway in metabolism. Taken together, our data show that uc.336-as acts as a negative regulator in white adipocyte differentiation and promotes the browning process, suggesting a potential therapeutic role for uc.336-as in controlling obesity.
SUN-003 Very Restricted Carbohydrate (Ketogenic) Diet: A Rare Cause of a Recurrent Hypoglycemic-Euglycemic Diabetic Ketoacidosis in the Pregnancy
Authors: Yaron Marianna , Shalit Roy , Kreiser Doron , Cukierman-Yaffe Tali , Israel Eduardo , Yoeli Rakefet
Published: May 2020

Introduction: Although potential risk of DKA, ketogenic diet became popular among T1DM patients as proven to reduce the incidence of hypoglycemia, glycemic variability, and HbA1c (1).

Severe carbohydrate restriction had not been included among DKA precipitating factors in pregnancy since a minimum consumption of 175 g of carbohydrates a day is recommended for pregnant women by the IOM and ADA.

Proband: A 35-year-old pregnant woman (G2P1 at 29 weeks’ gestation) was admitted to the ICU because of a 12-hour history of severe nausea, 4 vomiting episodes (stomach contain), weakness, and metabolic acidosis accompanied by low normal BG values for pregnancy. She had a history of bulimia nervosa since 15 years of age that was well-controlled by severe carbohydrate restriction prior to pregnancy, and T1DM since 19 years of age. Her pre-pregnancy carbohydrate daily intake was ~ 20–30 g and BMI 24.1 kg/m2. Good glycemic control was established before conception and continued until delivery.

Upon admission, she was tachypneic and suffering from diffuse abdominal pain. Fetal monitoring and abdominal ultrasonography showed no significant changes, and the sonographic fetal weight was appropriate for gestational age.

The laboratory results revealed metabolic acidosis pH 7.23, bicarbonate 11.7 mmol/L, anion gap 22.5, and BG 78 mg/dL. Lactate and salicylate blood levels were normal. The blood β-hydroxybutyrate was highly positive and the patient was diagnosed with euglycemic DKA. She was managed with a continuous intravenous insulin infusion and fluid and electrolytes repletion.

The patient was discharged after three days of hospitalization only to return four days later because of the similar complaints with findings of blood β-hydroxybutyrate 7.7 mmol/L and BG levels of 61–65 mg/dL. Because of persistent ketonemia with low normal BG levels, patient was questioning about her dietary habits and revealed to maintain severe carbohydrate-restricted pre-conception eating manners. After repeated consultations by specialists for eating disorder, patient agreed to increase her carbohydrate intake to 120 gr per day.

Fetal brain MRI, fetal heart and brain ultrasound were performed to evaluate potential negative effects of ketones, and all were found normal. No major malformations were observed in the newborn, and a normal growth pattern was observed at 5 months of age.

Conclusion: This is the first report of a pregnant T1DM patient with long lasting bulimia nervosa excellently controlled by severe carbohydrate restriction prior pregnancy and occultly continued against medical advice through the pregnancy, causing repeatedly hypoglycemic-euglycemic DKA.

References: 1. Schmidt S, Christensen MB, Serifovski N, et al. Low versus high carbohydrate diet in type 1 diabetes: A 12-week randomized open-label crossover study. Diabetes Obes Metab 2019; 21:1680- 1688
SUN-260 Dual Role of Carboxypeptidase E in Prohormone Processing and a Novel Neurotrophic Factor Mediating Neuroprotection and Cognitive Functions in Hippocampal CA3 Neurons in Mice
Authors: Xiao Lan , Sharma Vinay , Toulabi Leila , Yang Xuyu , Lee Cheol , Abebe Daniel , Peltekian Areg , Arnaoutova Irina , Loh Yoke Peng
Published: May 2020

Stress causes release of glucocorticoids from the adrenals which then circulate to the brain. High concentrations glucocorticoid from chronic severe stress results in pathophysiology in the brain, including neuronal degeneration, cell death and cognitive dysfunction, leading to diseases such as Alzheimer Disease and Major Depressive Disorders. Neurotrophic/growth factors such as BDNF, NGF and NT3 have been linked to these pathological conditions. Carboxypeptidase E (CPE), a proneuropeptide/prohormone processing enzyme, also named neurotrophic factor-α1(NFα1) is highly expressed in the stress-vulnerable hippocampal CA3 neurons, and was shown to have neuroprotective activity from in vitro studies. Here we investigated if CPE-NFα1 functions in vivo, independent of its enzymatic activity, and the mechanism underlying its action. We generated knock-in mice expressing a non-enzymatic form of CPE, CPE-E342Q, but not wild-type CPE. The CPE-E342Q mice showed significantly decreased neuropeptide content and exhibited obesity, diabetes and infertility due to lack of prohormone processing activity, similar to CPE-KO mice. However, they showed no hippocampal CA3 degeneration, exhibited neurogenesis in the dentate gyrus, and displayed normal spatial learning and memory, similar to CPE wild-type mice, after weaning stress; unlike CPE-KO mice which showed hippocampal CA3 neuronal degeneration and cognitive deficits. Binding studies showed that radiolabeled CPE bound hippocampal cell membrane specifically, in a saturable manner. Binding of CPE and CPE-E342Q to hippocampal neurons activated Erk signaling and pre-treatment with either of these proteins protected neurons against H2O2- or glutamate-induced neurotoxcity by increasing BCL2 expression. In vitro and in vivo inhibitor studies demonstrated that this neuroprotective effect was independent of tyrosine kinase receptor signaling. Taken together, the data provide evidence that CPE-NFα1 is a unique neurotrophic factor which acts through a non-tyrosine kinase receptor to activate Erk-BCL2 signaling to protect hippocampal CA3 neurons against stress-induced neurodegeneration and maintaining normal cognitive functions in mice.
SAT-441 Transcriptome Analysis Under Differential Thyroid Hormone Treatment During Mouse Cerebellar Development
Authors: Yajima Hiroyuki , Sumiyasu Ishii , Miyazaki Wataru , Koibuchi Noriyuki
Published: May 2020

Background: Thyroid hormone (TH) plays essential roles in the development of the cerebellum by regulating transcription of target genes. TH binds to TH receptor (TR) located in the cell nucleus and stimulates transcription through TH response element (TRE). The expression of many genes is temporary and spatially regulated by TH during cerebellar development. However, the mode of transcription by TR may vary among target genes. In the liver, different duration of TH exposure resulted in distinct gene expression profiles. To examine the mechanisms of transcriptional regulation by TH in cerebellar development, gene expression profile induced by various TH exposure duration was studied. Methods: Anti-thyroid drug propylthiouracil (250 ppm in drinking water) was administered to C57BL/6J mice from the gestational day 14 to postnatal day (P) 7 to generate perinatal hypothyroid mice. To study the effect of continuous TH exposure, TH was subcutaneously administered to hypothyroid pups from P2 to P7 (6 days group). To study the effect of single TH administration, TH was injected on P7 and mice were sacrificed either 6 (6 hours group) or 24 hours (24 hours group) after injection. Cerebellar samples were collected to extract RNA and subject to microarray analysis. Microarray results were confirmed by RT-qPCR. Results: In microarray result, compared with mRNA levels of hypothyroid mice, 6 days group induced upregulation in 1007 genes and downregulation in 1009 genes, 6 hours group induced upregulation in 355 genes and downregulation in 977 genes, and 24 hours group induced upregulation in 365 genes and downregulation in 1121 genes. Only 7.6% of the genes were overlapped in three groups among positively regulated genes. In contrast, 57.2% of the genes were common in the negatively regulated genes. In RT-qPCR result, among genes known to harbor TRE, Hairless, Pcp2, and Nrgn, showed differential upregulation patterns. Hairless was upregulated in all groups, whereas Pcp2 was upregulated only in 5 days group and Nrgn was not upregulated in all groups. These results suggest that different mode of transcriptional regulation occurred in an exposure time-dependent manner of TH. Conclusion: We identified gene groups whose expression were modified by TH during cerebellar development. TH distinctively regulates transcription of target genes depending on the exposure schedule in mouse developing cerebellum.
SUN-244 Role of Activin, Follistatin, and Inhibin in the Regulation of KISS-1 Gene Expression in Hypothalamic Cell Models
Authors: Oride Aki , Kanasaki Haruhiko , Tumurgan Zolzaya , Tumurbaatar Tuvshintugs , Kyo Satoru
Published: May 2020

Kisspeptin (encoded by the Kiss-1 gene) in the arcuate nucleus (ARC) of the hypothalamus governs the hypothalamic-pituitary-gonadal (HPG) axis by regulating pulsatile release of gonadotropin-releasing hormone (GnRH). Meanwhile, kisspeptin in the anteroventral periventricular nucleus (AVPV) region has been implicated in estradiol (E2)-induced GnRH surges. Kiss-1-expressing cell model mHypoA-55 exhibits characteristics of Kiss-1 neurons in the ARC region. On the other hand, Kiss-1 expressing mHypoA-50 cells originate from the AVPV region. In the mHypoA-55 ARC cells, activin significantly increased Kiss-1 gene expression. Follistatin alone reduced Kiss-1 expression within these cells. Interestingly, activin-induced Kiss-1 gene expression was completely abolished by follistatin. Inhibin A, but not inhibin B reduced Kiss-1 expression. Activin-increased Kiss-1 expression was also abolished by inhibin A. Pretreatment of the cells with follistatin or inhibin A significantly inhibited kisspeptin- or GnRH-induced Kiss-1 gene expression in mHypoA-55 cells. In contrast, in the mHypoA-50 AVPV cell model, activin, follistatin, and inhibin A did not modulate Kiss-1 gene expression. The subunits that compose activin and inhibin, as well as follistatin were expressed in both mHypoA-55 and mHypoA-50 cells. Expression of inhibin βA and βB subunits and follistatin was much higher in mHypoA-55 ARC cells. Furthermore, we found that expression of the inhibin αsubunit and follistatin genes was modulated in the presence of E2 in mHypoA-55 ARC cells. The results of this study suggest that activin, follistatin, and inhibin A within the ARC region participate in the regulation of the HPG axis under the influence of E2.
MON-364 Severe Postoperative Encephalopathy in a Patient with Oncogenic Osteomalacia and Neurofibromatosis Type 1
Authors: Sarkar Sauradeep , Singh Amteshwar , Krug Esther Irina
Published: May 2020

Background: Acute hypophosphatemia superimposed on chronic phosphate depletion results in decline in intracellular ATP and 2,3-diphosphoglycerate levels, affecting virtually all organ systems. It can lead to metabolic encephalopathy, impaired myocardial and diaphragmatic contractility, skeletal and smooth muscle dysfunction, increase in erythrocyte rigidity leading to hemolysis, and increased risk for postoperative morbidity and mortality. Risk of symptomatic hypophosphatemia may be greater in patients with urinary phosphate wasting syndromes hospitalized for intercurrent illness. Tumor-induced (oncogenic) osteomalacia (TIO) is a rare paraneoplastic disorder associated with mesenchymal tumors caused by tumor production of fibroblast-derived growth factor-23 (FGF-23). FGF-23 impairs transport of phosphorus in renal tubules, inhibits renal 25(OH)-1-α-hydroxylase activity, causing decreased levels of calcitriol, leading to hyperphosphaturia, hypophosphatemia and osteomalacia. We present a case of a patient with underlying TIO who presented with acute hypophosphatemia following hip surgery.

Case: 50-year-old woman with Neurofibromatosis type-1(NF-1) complicated by TIO, presented after a fall resulting in left femur fracture requiring surgery. During her initial management in an outside hospital for 4 days and following transfer her home calcitriol and phosphorus replacement regimen was not administered leading to treatment interruption of 7 days. On postoperative day 1 she became hypotensive, tachycardic with non-specific ST-T changes and encephalopathic requiring ICU care. At the time of endocrinology consultation, she was non-verbal, not following simple commands, had severe hypophosphatemia, transaminitis, hyperbilirubinemia, elevated LDH, anemia and elevated troponin. She required aggressive phosphate and calcitriol replacement reaching 4 doses of 20mEq IV Na- Phos daily, Na-KPhos Q6H and Calcitriol IV 0.5mcg Q8H over the course of 72 hours. After 4 days in the ICU, once phosphorous levels normalized, she had dramatic improvement in mental status and gradual resolution of laboratory abnormalities.

Discussion: To our knowledge, this is the first report of a patient with TIO associated with NF-1 presenting with severe symptomatic hypophosphatemia causing metabolic encephalopathy and multiple organ dysfunction following surgery. It underscores the fact that abrupt interruption of calcitriol and phosphorus supplementation in such cases can cause acute hypophosphatemia carrying high morbidity. High phosphate replacement requirements are indicative of severity of phosphate depletion. This case illustrates importance of recognition of presence of urinary phosphate wasting syndrome in hospitalized patients in order to minimize risk of preventable complications and morbidity.
SAT-640 Glycemic Profile of Intravenous Glucocorticoid Induced Hyperglycemia Using Continuous Glucose Monitoring
Authors: Zhang Fan , Goldberg Zoe , Karam Jocelyne Georges
Published: May 2020

Background: Intravenous (IV) steroids are widely used in critically ill patients and with chemotherapy. It is well known that glucocorticoid-induced hyperglycemia (GCIH) occurs within 3 hours following oral administration of steroids with typical postprandial glycemic excursions lasting 24-36 hours. The recent increased availability of Continuous Glucose Monitoring (CGM) has allowed a detailed description of glycemic fluctuations in patients receiving steroids in different settings, however there is no reported observation of CGM findings following a single dose of IV Dexamethasone in a patient with diabetes. We present a case of glycemic pattern documented on CGM of a patient with type 2 diabetes, who had received 11 cycles of a single dose Dexamethasone-containing chemotherapy. Clinical Case: The patent is 70 years old female with history of type 2 DM of 19 years duration and metastatic pancreatic adenocarcinoma, diagnosed in November 2018, and treated with Fluorouracil and Dexamethasone 6mg IV on every other Wednesday since December 2018. Her diabetes was fairly controlled on Metformin, Repaglinide, Pioglitazone and Detemir insulin. Premeal Lispro was added while Metformin and Repaglinide were discontinued with the beginning of chemotherapy. She started using Freestyle Libre CGM in January 2019. During her visit in March 2019, the patient was taking Detemir Insulin 50 units in AM and 30 units at night, and Lispro 15 units before meals, in addition to correction insulin based on an Insulin Sensitivity Factor (ISF) of 1:25 for Blood Glucose (BG) above 200mg/dl. Unlike the reported postprandial hyperglycemic excursions associated with oral steroids, the patient’s CGM data showed a reproducible triphasic glycemic pattern following IV Dexamethasone, consisting of a steady state of hyperglycemia reached within 3 hours and lasting around 18-30 hours, followed by a transient BG improvement for 18-20 hours, and ending with another hyperglycemic plateau of 10-16 hours on day 3 post chemotherapy, with no association to meal intake. Given this recurrent pattern, the patient was advised to increase her bedtime Detemir insulin from 30 to 45 units and her correction ISF from 1:25 to 1:18 on days 1 and 2 after chemotherapy, with subsequent attenuation and shortening of GCIH. Conclusion: Our case report is the first one to describe CGM documented glycemic profile following a single dose of IV Dexamethasone in a patient with type 2 diabetes treated with insulin. The CGM data reveals a consistent steady GCIH, lasting around 48 hours, and reflecting the prolonged action of Dexamethasone. The transient BG improvement seen on day 2 is likely due to the Detemir dose self-increase and the carbohydrates intake decrease in response to day 1 hyperglycemia. A 48 hours modified insulin regimen based on higher dose of long acting and correction insulin improved Dexamethasone induced hyperglycemia.
SAT-453 Delayed TSH Elevation in Small for Gestational Age Infants: A Need for Second Screening?
Authors: Kang Seok-Jin , Lee Ga-Hyun
Published: May 2020

The incidence of CH with a delayed TSH elevation was higher in ELBW and VLBW infants compared with infants weighing ≥1500 grams. Second screening should be considered in preterm neonates, low birth weight (LBW) and very low-birth weight (VLBW) neonates, ill and preterm newborns admitted to NICU, specimen collection within the first 24 hours of life, and multiple births (particularly same-sex twins). Purpose of this study was to determine incidence of delayed TSH elevation with or without congenital hypothyroidism in SGA infants and to Investigate necessity for second screening. Retrospective analysis was performed. 66 SGA newborns with 34-40 weeks’ gestation born at Keimyung University Dongsan Medical Center from 2015 to 2018 were enrolled. Primary screening was performed 48 hours - 7 days after birth. Second screening including venous TSH and venous free T4 at postnatal 8-40 days. Exclusion criteria were infants with congenital hypothyroidism at primary screening (NBS), descendants of mothers with immune thyroid disease, congenital malformations, renal, hepatic, and metabolic diseases, history of steroid or dopamine usage. Initial NBS were collected onto pre-printed filter at the age of 2-7 days by heel prick. (normal TSH < 10 mIU/L). Second sample was obtained at the age of 8-49 days by venous sampling (normal TSH < 5 mIU/L). TSH and free T4 were measured on venous samples with Cobas 8000 e801 (electrochemiluminescence, Roche, Diagnostics, Basel, Switzerland) using standard methods.

Incidence of delayed TSH elevation was 27% (18/66). Of them number of transient hyperthyrotropinemia was 13. Mean TSH at initial elevation was 7.56 mIU/L and median age at initial TSH elevation was 18.6 days. Median age at resolution of TSH elevation was 41.5 days. Number of hypothyroidism undergoing l-thyroxine medication was 5. Mean TSH at initial elevation was 22.1 mIU/L. Median age at initial TSH elevation was 14 days. Mean peak TSH was 23.4 mIU/L.

The presence of delayed TSH elevation was not related to very low birth weight. SGA infants might be at a risk of delayed TSH elevation. Considering 2nd screening test within 1 month. Further study with more SGA infants are needed. Limitation of this study was relative small number of patients and iodine status was not considered
MON-377 Fracture Site in High-Energy Trauma Is Associated with Osteoporosis Risk
Authors: Chourpiliadis Charilaos Paulos , Bantouna Dimitra , Hourpiliadi Hara , Karvounis Evangelos , Jaume Juan Carlos , Paparodis Rodis
Published: May 2020

Background: In our recent studies, we noted that patients with history of high energy fractures commonly have underlying endocrine abnormalities and low bone mineral density (BMD). In this expanded patient population, we aimed to investigate whether the fracture site can better predict the risk of abnormal BMD.

Methods:We prospectively enrolled adult patients of both genders, with any history of high energy fracture. We measured serum PTH, vitamin-D and calcium and we performed BMD measurements with a DEXA scan. We split our subjects’ BMD, based on the lowest T- or Z-score in “Normal” (≥-0.9), “low bone mass” (LBM) (-1.0 to -2.4) and “Osteoporosis” (OST) (≤-2.5). We classified our patients according to fracture site, in vertebral, humeral, hip, tibial, malleolar-carpal, radial-ulnar and others, including rib fractures. Ratios were compared with χ 2 test, and continuous variables with one-way ANOVA.

Results: We enrolled 444 consecutive subjects with 543 fractures. n=315 (71.0%) subjects had low BMD: OST 25.9% and LBM 45.1%. Among subjects <50 years of age, 43.1% had LBM and 9.2% OST, while in those >50, 46.3% had LBM and 36.6% OST (p<0.0001). The cohort’s mean lowest T/Z score was -1.6±1.2. Subjects with >1 fracture had more frequently low T/Z score (p=0.015). History of vertebral fractures provided the lowest mean T/Z score overall (-2.4±1.1), in females (-2.5±0.9) and subjects >50 (-2.5±1.1). The same holds true for hip fractures in males (-1.9±1.2) and subjects <50 (-2.1±1.4). Subjects with vertebral fractures had the lowest Hip (-1.7±1.2) and Spine (-2.3±1.2) T/Z scores, while those with tibial fractures had the lowest Radius T/Z score (-1.8±1.3). History of vertebral fractures was associated with the highest rate of OST (65.9%) in our overall population, males (50%), females (67.5%), subjects >50 (70.0%), while subjects with history of tibial fractures had the highest rate of normal BMD (46.2%), in males (80%) and females (50.4%), and those <50 (75.0%). Vitamin-D deficiency was present in 81.4% of all subjects. PTH was significantly higher in patients with OST compared to LBM or normal BMD (p=0.0006).

Discussion: Patients with history of high energy fractures need to be screened with DEXA scan early, as they have high likelihood to suffer from osteoporosis.
MON-113 The Effect of Body Mass Index on the Peak Growth Hormone Level After Growth Hormone Stimulation Test in Children with Short Stature
Authors: Lee Nayeong , Cho Wonkyoung , Lee Yoonji , Kim Seulki , Lee Seonhwa , Choi Yujung , Ahn Moon Bae , Kim Shinhee , Cho Kyoungsoon , Jung Min-Ho , Suh Byung-kyu
Published: May 2020

Objective: The aim of this study is to evaluate the effect of body mass index (BMI) on peak growth hormone (GH) response after GH stimulation test in children with short stature.

Methods: Data was obtained from retrospective review of medical records who visited the pediatric endocrinology at St. Vincent hospital of catholic university for short stature from January 2010 to June 2019. We studied 115 children (aged 3-17 years old) whose height was less than 3percentile for one’s age and sex and who underwent GH stimulation test {GH deficiency (GHD) = 47, Idiopathic short stature (ISS) = 68)}. Peak GH response was stimulated by dopamine (n=111), clonidine (n=7), glucagon (n=19), insulin (n=56) and arginine (n=32). Birth weight, parental height, chronologic age, bone age, height SDS (standard deviation score), weight SDS, BMI SDS hemoglobin, fT4, T3 TSH, cortisol, ACTH, GH, IGF-1 SDS, IGF-BP3 SDS and peak stimulated GH were analyzed.

Results: In the characteristics of subject, weight SDS and BMI SDS in GHD group were increased than ISS group (p<0.000, p=0.000). Free T4 was decreased in GHD group than ISS group (p=0.012). In total group, BMI SDS was associated negatively with peak GH level stimulated by dopamine (r=-0.419, p<0.000), insulin (r=-0.271, p=0.044) and arginine (r=-0.368, p=0.038), but did not showed correlation with peak GH level stimulated by glucagon. In GHD group, BMI SDS showed negative correlation with peak GH level using dopamine (r=-0.356, p=0.015) and arginine (r=-0.509, p=0.022). In ISS group, BMI SDS was correlated negatively with peak GH using dopamine (r=-0.330, p=0.007). In multivariate regression analysis of GHD group, weight SDS and BMI SDS were the only two significant predictors of peak GH response in stimulation test stimulated by dopamine (ß=-0.576, p=0.015) and arginine (ß=-0.097, p=0.022). In ISS group, only mother’s height (ß=0.474, p=0.000) and TSH (ß=-2.251, p<0.000) were demonstrated statistically significant predictors of peak GH stimulated by dopamine in multivariate regression analysis. In case of using insulin as a stimulant in ISS group, there is nothing which has statistical significance as a predictor of peak GH response in multivariate regression analysis.

Conclusion: BMI was associated negatively with peak GH response after GH stimulation test in children with short stature, especially in GHD group.
MON-366 X Linked Hypophosphatemic Rachitism: Case Report in Adult Patient
Authors: Medina Adriana , Vargas Juan José , Romero Andres Florez , Coy Andres
Published: May 2020

BACKGROUND: X linked hypophosphatemia (XLH) is a rare genetic disorder, with an estimated prevalence of 1: 20,000 live births resulting from a mutation in the PHEX gene (phosphate regulatory endopeptidase), which causes increased levels of circulating fibroblast growth factor 23 (FGF23), reducing both renal reabsorption of phosphate and serum levels of 1,25-dihydroxyvitamin D3, causing chronic hypophosphatemia, rickets and osteomalacy. CLINICAL CASE: a 34 year old female with a height of 1.34 meters whose past medical history began at the age of three years old with a diagnosis of short stature, associated with genu varum and low serum phosphate levels. She received treatment with phosphate salts and calcitriol until eleven years old. During childhood, she underwent several surgical procedures to correct the genu varum. After stopping the treatment, she has presented four fractures in the lower extremities: bilateral femur, tibia and fibula that have required six surgical interventions (osteotomy, osteosynthesis and external fixation); the last surgery was performed in June of 2019; in addition, she has had multiple dental abscesses that required several oral surgeries. Current laboratory tests report: calcium 8.89 mg/dL (8.6-10), 24-hour urine calcium 72.17 mg (100-300) with urinary volume 1470 ml/24 h, serum creatinine 0.44 mg/dL (0.51-0.95), urine creatinine 43.72 mg/dL (29-226), serum phosphate 1.78 mg/dL (2.5-4.5), urine phosphate 17.75 mg/dL (40-136) PTH 86 pg/mL (15-65), alkaline phosphatase 134 ug/ dL (35-104), 25OH vitamin D 23 ng/mL (30-40). Tubular resorption of phosphate corrected for glomerular filtration rate (TmP/GFR:) 1.6 mg/dL (<2.8), Tubular Reabsorption of Phosphate (TRP) 89.96% (>80). Densitometry revealed a normal bone mineral density (BMD) in lumbar spine and hip. Radiographs of the lower limbs showed a difference of 19 mm of the right lower limb in anatomical length and 13 mm in functional length. A HLX genetic panel was performed, with a result of a definitely pathogenic Gene PHEX linked to chromosome X, with a pathological mutation 22 151 705 G> A p Trp456. The patient started treatment with calcitriol and dibasic phosphorus one month ago because of bone and muscle pain, stiffness, functional limitation, periodontal disease, recent hip fracture and indication of left hip replacement. She is candidate for burosumab (Anti-FGF23 Monoclonal Antibody) treatment.CONCLUSIONS: We present the case of adult patient with X-linked hypophosphatemia. Early treatment with phosphate is essential to avoid bone deformities. In adult patients, identifying pain, fractures or requirement of bone surgery, are indications for continuing treatment to improve quality of life, either with phosphate and calcitriol or with the new option, burosumab for pain control, improving functionality and stiffness.
SAT-440 Phthalates Expose and Thyroid Parameters in Euthyroid Patient with Type 2 Diabetes: Sex Specific Associations
Authors: Chen Yi , Chen Chi , Chen Jingsi , Zhang Wen , Wang Yuying , Wan Heng , Wang Ningjian , Chen Bo , Lu Yingli
Published: May 2020

Phthalates are ubiquitous in different environmental exposure media around the world. Recent years, issues on the relationships of phthalates and endocrine disorders raise attention. Evidence of thyroid disruption as a result of phthalates expose among euthyroid participants with diabetes is very limited. We aimed to evaluate the association between phthalate and thyroid function, and to explore whether thyroid autoimmunity mediated this association. Concurrent urine and blood samples were collected from 538 participant in METAL study. We measured urinary concentrations of ten phthalate metabolites (urinary creatinine adjusted), along with serum levels of thyroid-stimulating hormone (TSH), free thyroxin (FT4), free triiodothyronine (FT3), thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb). Euthyroidism was defined as TSH within normal range. After adjusting for age, sex (only with the entire sample), BMI and smoking status, linear regression analyses showed exactly opposite directional results among men and women. TSH levels were negatively associated with mono-2-ethyl-5-carboxypentylphthalate (MECPP), mono-2-ethyl-5-hydroxyhexylphthalate (MEHHP), mono-2-ethyl-5-oxohexylphthalate (MEOHP), mono-2-carboxymethyl-hexyl phthalate (MCMHP) and sum of di (2-ethylhexyl) phthalate metabolites (ΣDEHPm) in men, but positively associated with monoisobutylphthalate (MiBP) and mono-n-butylphthalate (MnBP) in women. Meanwhile, FT4 was positively associated with mono-2-ethylhexylphthalate percentage (%MEHP) in men, but negatively associated with MnBP, MEOHP and MCMHP in women. Further, in women, TPOAb was increasing along with the increased level of MEHP and %MEHP. In the mediation analysis, TPOAb demonstrated a mediating effect whereby MEHP or %MEHP had a positive effect on TSH and a negative effect on FT4 only in women (all P<0.05). We got a conclusion that among euthyroid participants with diabetes, urinary phthalate metabolites maybe associated with altered TSH, FT4 and TPOAb levels in different direction in men and women. Further, our present study maybe the first to suggest that TPOAb might be a potential mediator of the association between phthalate metabolites and thyroid function in women.
SUN-715 IIM May Influence Matured Oocytes’ DNA Methylation of PCOS Patients
Authors: Li Congru , Yu Yang
Published: May 2020

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of childbearing age and is the main cause of anovulatory infertility. To increase the number of oocytes obtained, controlled ovarian stimulation (COS) has become a routine choice for in vitro fertilization-embryo transfer (IVF-ET), which is one of the common assisted reproductive technologies for PCOS patients. However, for these patients, there is a high risk of ovarian hyperstimulation syndrome (OHSS). Obtaining in vitro maturation (IVM) of immature oocytes, and then in vitro fertilization and embryo transfer of mature oocytes provides a possible way for people to solve the above problems. Since the IVM technology will expose oocytes to in vitro conditions for a longer period of time, theoretically increasing the risk of the oocytes being affected by the culture environment, further research and explorations are needed for study in gene programming, epigenetics, etc. Therefore, to explore the impact of IVM operation on embryonic development is of great significance for further clarifying assisted reproductive safety and improving IVM operation conditions. Here we focused on DNA methylation reprogramming process which was essential for embryonic development. We tested the DNA methylation of sperm, IVM oocytes and IVM generated early stage embryos including pronucleus, 4cell, 8cell, morula, inner cell mass, trophoectoderm (TE) as well as six-week embryos by Nimble Gen Human DNA Methylation 3x729K CpG Island Plus RefSeq Promoter Array and compared the data with our published genome-wide DNA methylomes of human gametes and early embryos generated from in vivo maturation oocytes. We showed that IVM embryos show abnormal DNA methylation reprogramming pattern. By analyzing the abnormally reprogrammed promoters, we further found that IVM may affect the functions of demethylation related genes. Oocytes from IVM manipulation were tested with higher DNA methylation levels, and their abnormal methylated promoters mainly enriched in immune and metabolism pathways. Furthermore, we investigated the DNA methylation of TE, which was directly related with implantation process and revealed the abnormal methylated promoters were related with metabolism pathway too. Our data support that IVM may influence the DNA methylome of oocytes, which in turn affects the methylome of their embryos. However, due to the limited number of samples and the inability of the chip to cover all CpG sites, the results of this study require further research and validation.
MON-911 Debilitating Neuropsychiatry Symptoms in Pancreatic Insulinoma Co-Secreting Serotonin and IGF-1
Authors: Azman Siti Sanaa Wan , Rajoo Subashini , Rahmatullah Ijaz Hallaj , Rahim Anilah Abdul , Bidin Mohamed Badrulnizam Long
Published: May 2020

Background:

Insulinoma is the most common type of functioning pancreatic neuroendocrine tumor (NET). Polyhormonal secretions from the NET, giving rise to distinct clinical symptoms such as carcinoid symptoms are rare. Clinical Case: We report a 68-year-old woman who presented with four months history of recurrent diaphoresis, palpitations, tremors and chest tightness. These were associated with episodic paroxysms of flushing and diarrhoea. The physical examination was unremarkable. She was a well-nourished woman with BMI of 28 kg/m2. Initial laboratory tests ruled out any renal, liver abnormalities with normal cortisol and thyroid function test. Further evaluation confirms insulin mediated hypoglycaemia with low random blood sugar 2.5 mmol/l (4.4-7.8) and failure to suppress C-peptide, 1092 pmol/L (298-2350) and insulin levels, 12.7 mU/L (3-25). Urine 5-HIAA was markedly elevated 2430.37 µmol/day (3.66-42.89) with borderline elevation of serum chromogranin A level 122 ng/mL (27-94). IGF-1 was also raised at 416 ug/L (91-282). Two months later she presented with new onset of delirium, incoherence, agitation and restlessness independent of her hypoglycaemic events. These symptoms deteriorated and fluctuates throughout the day with period of normalcy in between. This has led to requirement of a full time caregiver for her. Cranial CT excluded any brain pathology. We are faced with a diagnostic challenge to localize the primary lesion as radiological imaging so far were normal. GALLIUM-68 PET CT showed physiological uptake in the uncinate process of the pancreas (SUVmax 14.4). Endoscopic ultrasound of the pancreas was normal. An intra-arterial calcium stimulation test with hepatic venous sampling (ASVS) confirms a lesion at the head of pancreas with two times increment of insulin from baseline at the gastroduodenal artery distribution. Despite elimination of hypoglycaemic events with Diazoxide 100mg twice daily, her neuropsychiatric symptoms persisted. We postulate that this might be from excessive peripheral production of serotonin by the pancreatic carcinoid tumour or a niacin deficiency state because of metabolic diversion of its precursor, tryptophan. Conclusion:

This case highlights the occurrence of debilitating neuropsychiatry manifestations in a likely neuroendocrine tumour arising from the head of pancreas secreting insulin, serotonin and IGF-1.
OR25-04 Over 14% of Inpatients with Euvolemic Hyponatremia Have Undiagnosed Adrenal Insufficiency
Authors: Kumar Amit , Ghosh Maria , Jacob Jubbin Jagan
Published: May 2020

Background- The commonest cause of euvolemic hyponatremia (EvHNa) is the syndrome of inappropriate antidiuretic hormone secretion (SIADH). The diagnosis of SIADH requires the exclusion of secondary adrenal insufficiency (AI) and untreated hypothyroidism. Studies have suggested about 4% of unselected patients presenting to the emergency room with EvHNa have undiagnosed SAI.1 Among patients admitted to specialized endocrine units this prevalence maybe as high as 20%.2Objective- To study the prevalence of undiagnosed AI among inpatients with EvHNa admitted to general medical wards. Methods- This was a prospective, single centre observational study conducted among inpatients with EvHNa. EvHNa was defined as patients with a serum sodium (Na) <135 mEq/L, with no clinical evidence of dehydration or fluid excess, and a urine spot Na >30mmol/L. In addition patients with recent vomiting, renal failure, recent diuretic use, uncontrolled hyperglycemia and patients with history of use of oral or parenteral steroids in the last 6 months were excluded. Adrenal functions were assessed by a modified porcine ACTH stimulation test which has been described recently by Nair et al. A cut off cortisol value of <18mg/dl after 60 minutes of ACTH injection was used to diagnose AI.3Results- One hundred and forty one (141) patients were included after informed consent and all underwent a modified ACTH stimulation test. They had a mean age of 58 years and 52.3% (n=74) were males. Modified ACTH stimulation testing suggested 20/141 (14.2%) had undiagnosed AI. The mean age among those with AI was 55.2 years. In only 25% (5/20) AI was suspected based on clinical presentation by the treating physician. Despite excluding patients with documented steroid use, the commonest cause of AI (9/20) was secondary AI due to exogenous steroid use including high potency inhaled steroids (5/9) and the use of undocumented steroids or steroid containing medicaments by alternative practitioners (4/9). Hypopituitarism was diagnosed as the cause of AI in 5 patients, which included unsuspected Sheehan’s syndrome in post menopausal women (3/5), non functioning pituitary adenoma (1/5) and lymphocytic hypophysitis (1/5). Despite primary AI not commonly presenting as EvHNa, 3/20 patients had primary AI and in the remaining 3 patients the aetiology of AI remained unclear. Conclusions- Undiagnosed AI is much more common in our country among inpatients presenting with EvHNa to medical units. This increase is primarily driven by inhaled and undocumented exogenous steroid use and undiagnosed Sheehan’s syndrome. An assessment of the hypothalamic-pituitary-adrenal axis is mandatory before making a diagnosis of SIADH. References -(1) Diederich et al. Eur J Endocrinol 2003; 148: 609-617. (2) Cuesta et al. Clin Endocrinol (Oxf) 2016; 85: 836-844. (3) Nair A et al. Eur J Endocrinol. 2019 Oct 1. pii: EJE-19-0558.R2.
MON-294 T2 MRI Signal Analysis of The Pituitary Gland Is Efficient in the Diagnosis of Acromegaly Due to GHRH Ectopic Secretion
Authors: Bonneville Jean Francois , Potorac Julia , Rohmer Vincent , Daly Adrian F , Beckers Albert M
Published: May 2020

Less than 1% of cases of acromegaly are secondary to ectopic secretion of Growth Hormone Releasing Hormone (GHRH), usually from a neuroendocrine tumor. Symptoms of ectopic acromegaly did not differ from classical acromegaly from pituitary origin. GH and IGF 1 values are in the same range. GHRH measurement only could make the correct diagnosis but is not routinely proposed in acromegaly. MRI of the pituitary gland is considered not very effective in ectopic acromegaly. In the literature (1), different patterns are described: pituitary enlargement (46%), adenoma (30%), empty sella (2%) or normal (20%). But T2MRI signal of the pituitary is never mentioned nor illustrated. Finally, in about 30 % of published cases, pituitary surgery, of course inefficient, was performed.

These data enhance the poor contribution of imaging studies in the published cases of ectopic acromegaly.

We have been able to obtain and read MRIs and particularly T2WI of 27 acromegalic patients- 20 female, 7 male- due to GHRH hypersecretion from a neuroendocrine tumor –principally bronchial carcinoid and pancreatic NET- which have been published or not. Remarquably, T2 sequences were available in only 27/61 cases we have collected. In all these 27 cases but two, the T2 signal was clearly hypointense if compared with the brain cortex, as it has been described in densely granulomated somatotropinomas (2). In one case with T2 hyperintensity, the pituitary mass presented the same imaging characters as multiple brain metastases from a bronchial carcinoïd. In one case, T2 signal was isointense. In 3 cases, tiny millimetric T2 hyperintense images were disseminated within pituitary hyperplasia. In several cases where pituitary MRI was considered as normal, correlation of the patient’age with pituitary size could make suspect an enlarged gland. In a case labeled empty sella, T2MRI signal of the pituitary remnant was hypointense. When coupling T2 and T1 gadolinium enhanced sequences, no pituitary adenoma was visualized and normal pituitary tissue was never identified along with pituitary hyperplasia.

In conclusion, T2 MRI hypointense signal of the pituitary gland is a better hallmark than pituitary hyperplasia for the diagnosis of acromegaly due to

GHRH ectopic secretion. Analysis of T2 MR signal in these cases is essential to avoid unnecessary interventions to the pituitary.

References

1 Ghazi A Endocrine 2013

2 Potorac J Endocr Relat Cancer 2015
SAT-451 Chronic Stress During Adolescence of Rats Shows Sex Dimorphism in the Thyroid Axis Response to Voluntary Exercise in Adulthood
Authors: Parra-Montes de Oca Marco Antonio , Gutiérrez-Mata Angélica , Charli Jean-Louis , Joseph-Bravo Patricia
Published: May 2020

Exposure to chronic stress during adolescence causes long-term effects on the response of Hypothalamus-Pituitary-Adrenal (HPA) axis, affecting behavior and energy homeostasis. Voluntary exercise activates the HP-Thyroid (HPT) axis allowing efficient fluxes of substrates to active target organs. Chronic stress in adult rats blunts HPT axis response to voluntary exercise in a sex-dependent manner (Front Endocrinol 10(418):1-13, 2019). As adolescents show sex-dependent responses to stress, we sought to evaluate the effect of chronic stress at this period in the response of HPT axis to voluntary exercise in adulthood. Wistar male and female rats were divided in an undisturbed group (Control, C) and one group exposed to chronic variable stress (CVS) where the rats were daily subjected to different stressors during postnatal day (PND) 30 to 60 for females and PND 30 to 70 for males. At adulthood (PND 74 for females and PND 84 for males) rats were exposed to running wheel following published protocol (Endocrinology 155:2020-2030, 2014). As females are more susceptible to stress during adolescence than males, additional independent experiments were performed with female rats kept in group or individual housing, since PND 30 (2 per cage or isolated (Iso)). At PND 64, Iso rats were housed in pairs and exposed to CVS every 3 days until PND 80; later, rats were exercised 26 days. Hormones were quantified by ELISA or RIA; mRNA expression was determined by RT-PCR. Voluntary exercise reduced fat mass in C groups, dependent on the amount of exercise performed; stressed rats exercised did not lose fat, indicating that adolescent stress avoids an appropriate energy distribution during exercise. The expression of Crh and Avp in hypothalamic paraventricular nucleus (PVN) decreased in stressed groups mainly in females, as reported. Exercise decreased corticosterone levels only in C rats, suggesting that CVS during adolescence modifies the HPA axis response to exercise. CVS inhibited Pomc expression induced by exercise and increased Npy expression in arcuate nucleus, decreased Trh expression in PVN for both sexes and in dorsomedial hypothalamus in males. Thyroid hormones were not altered in CVS males and Iso females; however, T3 and T4 levels were high in CVS females, so different stress exposures may modify the HPT axis state in females. The response to exercise of the target organs of thyroid hormones reveals with more accuracy the activity of HPT axis, exercise stimulated the expression of Adrb3 and Dio2 in brown adipose tissue of C females, and the expression of Dio2 and Pgc1a in skeletal muscle (gastrocnemius) of both sexes, changes attenuated by CVS. These results indicate that chronic stress during adolescence blunts the response of HPT axis to voluntary exercise, strongly in females than males.