bluuebunny/crossref_metadata_2025_split huggingface dataset:
SAT-333 Autoimmune Polyglandular Syndrome Type 1 in a Patient with Bipolar Disorder
Authors: Rajwani Aakash , Eckman Ari 
Published: May 2020

Abstract
Autoimmune Polyglandular Syndrome Type 1 (APS-1) is clinically defined as the presence of at least two components of the classic triad of hypoparathyroidism, adrenal insufficiency and mucocutaneous candidiasis. It is commonly seen amongst Finns, Sardinians and Iranian Jews and is a very rare condition, with a challenging set of management.
50-year old female with a known past medical history of Bipolar disorder, Primary Adrenal Insufficiency, Hypothyroidism, Alopecia was transferred from an acute psychiatric facility for medical clearance. Patient was noted to have findings initially suggestive of Subarachnoid Hemorrhage on a CT scan of the Head which was later deemed to be likely dystrophic calcification. During her stay on the medical floors, patient was found to be unresponsive and hypotensive, after a bout of agitation. She had to be urgently intubated and started on stress doses of steroids (Hydrocortisone 100 mg every 8 hours) and was upgraded to the Intensive Care Unit (ICU). Patient was eventually successfully weaned off the ventilator and steroid doses were slowly tapered. During her hospital course she was noted to have gradually decreasing Calcium levels, down to a corrected Calcium level of 7.6. Further workup for the hypocalcemia revealed a Vitamin D Level of 12, and Parathyroid Hormone (PTH) level of 0. Patient was subsequently started on adequate Calcium and Vitamin D supplementation for the same. After a few days when the family was located and contacted through social work support, and a more thorough history was obtained, it was found that one out of the patient’s three sisters had a similar constellation of deficiencies. Patient had previously been diagnosed with a polyendocrine syndrome, however she was irregular with her medication compliance and follow-up outpatient with her endocrinologist due to her persistent psychiatric issues and poor social support.
APS-1 is an autosomal recessive disorder caused by mutation in AIRE, the autoimmune regulator gene which is hypothesized to be playing an important role in the generation of regulatory T cells. Although the complete pathogenesis is unclear, mutation in generation of these regulatory cells leads to autoantibody formation. Hypoparathyroidism or Chronic persistent Mucocutaneous Candidiasis is usually the first manifestation seen during adolescence and adrenal insufficiency usually manifests later. A variation of other autoimmune syndromes can be observed, with Hypothyroidism, Type-1 Diabetes Mellitus and Primary Hypogonadism being a few of them. Treatment primarily involves replenishment of the hormones of the underperforming gland. Management of a complex syndrome like APS-1 in a patient with psychiatric disabilities can be challenging and needs a multi-disciplinary approach involving the endocrinologist, the primary care physician and the psychiatrist.
SUN-417 Long Working Hours Are Associated with Hypothyroidism: A Cross-Sectional Study with Population-Representative Data
Authors: Lee Young Ki , Lee Dong-eun , Hwangbo Yul , Lee You Jin , Lee Eun Kyung 
Published: May 2020

Abstract
Background: Studies have highlighted the adverse effects of long working hours on workers’ health; however, the association of long working hours with thyroid function has not been studied. This study aimed to assess long working hours as a risk factor for thyroid dysfunction.
Methods: This cross-sectional study was based on data obtained from the Korea National Health and Nutrition Examination Survey conducted from 2013 to 2015. A total of 2,160 adults who worked 36–83 hours per week were included. Thyroid function was defined based on the population thyroid-stimulating hormone reference ranges, after excluding individuals with positive results for thyroid peroxidase antibody. The association between working hours and thyroid function was confirmed via multinomial logistic regression.
Results: Hypothyroidism was more prevalent among those with longer working hours (3·5% vs. 1·4% for 53–83 and 36–42 working hours per week, respectively). Individuals who worked longer hours had an increased odds for hypothyroidism (odds ratio 1·46, 95% confidence interval 1·12−1·90, per 10 hour increase in working hours per week), after adjustment for age, sex, body mass index, urine iodine concentration, smoking status, shift work, and socioeconomic characteristics such as occupation, income level, and educational attainment. The association between working hours and hypothyroidism was consistent in various subgroups stratified by sex or socioeconomic characteristics.
Conclusions: To our knowledge, this study is the first to show that long working hours are associated with hypothyroidism. Our findings suggest that appropriate monitoring and treatment of hypothyroidism are necessary among individuals who work long hours.
SAT-499 Myxedema Coma Presenting as Large Pericardial Effusion with Cardiac Tamponade
Authors: Ramos Freyja Diana A , Cheng Matilde Melanie N , Tugna Sheryl N 
Published: May 2020

Abstract
Background
Myxedema coma is a life-threatening decompensated form of hypothyroidism. Current treatment recommendation is intravenous levothyroxine. However, in areas where parenteral form of levothyroxine is unavailable, levothyroxine tablet is the only option.
Clinical Case
A 48-year old male known to have chronic glomerulonephritis and hypertension, came in due to lacerated scalp wound sustained after falling asleep. Pertinent laboratory exams showed mild anemia, hemoglobin 10.6 g/dL (reference range 13–17) and hyponatremia 128mmol/L (reference range 136–145). His estimated creatinine clearance was 60mL/min. Cranial CT scan showed no signs of acute hemorrhage or fracture. There was scalp swelling and laceration with subgaleal hematoma over the frontal region. Electrocardiogram showed low voltage complexes. Chest radiograph showed an enlarged cardiac silhouette suggesting pericardial effusion. Transthoracic echocardiography was requested revealing a massive pericardial effusion with tamponade physiology. Patient underwent emergency pericardial window with pericardiostomy tube placement, debridement and suturing of scalp laceration under general anesthesia. He was able to tolerate the procedure well but noted to have decreased sensorium post-operatively. ABG revealed respiratory acidosis with pH 6.9 and incalculable pCO2. He was subsequently intubated. Further laboratory investigations showed undetected FT4 0.0ng/dL (reference range 0.58–1.64) and elevated TSH 23.87µIU/mL (reference range 0.38–5.33). Anti-TPO was elevated 333 µIU/ml (reference range 0–35). He was started on hydrocortisone followed by levothyroxine 200 µg tablet through NGT daily. His condition improved after few days and was weaned off from mechanical ventilator. Repeat echocardiogram showed resolution of previously noted massive pericardial effusion with preserved systolic and diastolic functions. He was eventually discharged after a month on levothyroxine. Follow-up after 1 month, patient was clinically stable with normal thyrotropin level at 0.67µIU/mL.
Conclusion
Myxedema coma is a life threatening form of hypothyroidism and may be difficult to recognize initially especially in patients with pre-existing kidney disease due to overlap in clinical findings. Treatment with levothyroxine administered enterally is possible especially if the intravenous form is unavailable.
OR14-05 Hepatocyte Peroxisome Proliferator-Activated Receptor Gamma (PPARG) Offsets the Anti-Steatogenic Effects of Thiazolidinediones in Obese Male Mice
Authors: Muratalla Jose T , Lee Samuel M , Remon-Ruiz Pablo , Norris Gregory H , Cordoba-Chacon Jose 
Published: May 2020

Abstract
Pparg is a nuclear receptor that regulates glucose and lipid metabolism. Thiazolidinediones (TZD) are PPARG agonists that may reduce hepatic steatosis through their effects in adipose tissue. However, some studies suggest that expression and activation of hepatocyte Pparg promotes steatosis. In this study, we have assessed the relevance of hepatocyte Pparg, and its TZD-mediated activation in the development and/or reduction of steatosis, with adult-onset hepatocyte-specific Pparg knockout (PpargΔHep) mice. We reported that a single iv injection of AAV8-TBG-Cre in Pparg-floxed mice, knocked out hepatocyte Pparg expression (PpargΔHep mice), and that prevented diet-induced steatosis. In this study, a group of 5 wk-old Pparg-floxed mice were fed a low fat (LF) or a high fat (HF) diet for 7 weeks before generating control and PpargΔHep mice. Then, half of the HF-fed mice in each group were switched to a HF diet supplemented with the TZD Rosiglitazone maleate, for 5 weeks. HF diet induced mild obesity (36.8 +/- 1.4 g of body weight [BW]), while TZD slightly increased BW (41.3 +/- 1.3 g) and insulin sensitivity. Liver weight was not altered in HF-fed mice with or without TZD, and we did not observe any effect induced by PpargΔHep. Due to the mild phenotype observed in this cohort, we generated a 2nd cohort adjusting for age and length of diet. Briefly, 10 wk-old Pparg-floxed mice were fed a LF or HF diet for 16 weeks before generating control and PpargΔHep mice. Then, half of the HF-fed mice in each group were switched to a HF diet supplemented with Rosiglitazone maleate for 7 weeks. In this group of mice, HF diet induced obesity (50.1 +/- 1.05 g BW), and increased liver weight independent of hepatic Pparg expression. TZD treatment exacerbated obesity (62.4 +/- 1.2g BW) and adiposity, but increased insulin sensitivity as compared to mice fed a HF diet without TZD. Interestingly, PpargΔHep mice fed a HF diet with TZD showed enlarged subcutaneous white and brown adipose tissue weight, and a dramatic reduction in liver weight and steatosis as compared to obese control mice treated with TZD. The expression of hepatic Cd36, Cidea, Cidec, and Fabp4 was increased by TZD in a Pparg-dependent manner in HF-fed mice. Altogether, this data suggest that hepatocyte Pparg expression may offset the antisteatogenic actions of TZD in mice with severe obesity. In obese and insulin resistant individuals, TZD-mediated activation of hepatocyte Pparg may exacerbate steatosis.
OR09-04 Common Genetic Variants Associated with SERPINA6 Expression in Liver Influence Cortisol-Responsive Transcriptional Networks in Human Adipose Tissue
Authors: Bankier Sean A , Crawford Andrew A , Wang Lingfei , Sukhavasi Katyayani , Ermel Raili , Andrew Ruth , Ruusalepp Arno , Timpson Nicolas J , Smith George Davey , Bjorkegren Johan L M , Walker Brian R , Michoel Tom 
Published: May 2020

Abstract
A genome wide meta-analysis by the CORtisol NETwork (CORNET) consortium(1) has identified genetic variants spanning the SERPINA6/SERPINA1 locus on chromosome 14, associated with morning plasma cortisol and predictive of cardiovascular disease (Crawford et al, Unpublished). SERPINA6 encodes Corticosteroid Binding Globulin (CBG), responsible for binding most cortisol in blood and putatively mediating delivery of cortisol to target tissues. We hypothesised that genetic variants in SERPINA6 influence CBG expression in liver and cortisol delivery to extra-hepatic tissues, influencing cortisol-regulated gene expression.
The Stockholm Tartu Atherosclerosis Reverse Networks Engineering Task study (STARNET)(2) provides RNA sequencing data in 9 vascular and metabolic tissues from 600 genotyped individuals (mean age 65.8, 70.3% male) undergoing coronary artery bypass grafting. We used STARNET to identify SNPs associated with plasma cortisol at genome wide significance in CORNET as cis-eQTLs for SERPINA6 in liver and as trans-eQTLs for the expression of genes across STARNET tissues. Causal inference methodologies(3) were then employed for the network reconstruction of these trans-genes and their downstream targets.
We identified 21 SNPs that both were associated with cortisol at genome wide significance in CORNET (p ≤ 5x10-8) and were cis-eQTLs for SERPINA6 expression in liver (q ≤ 0.05). Moreover, these SNPs were trans-eQTLs for sets of genes in liver, subcutaneous and visceral abdominal adipose tissue, with over-representation of known glucocorticoid-regulated genes in adipose. The highest confidence gene network identified was specific to subcutaneous adipose, with the interferon regulatory trans-gene, IRF2, controlling a putative glucocorticoid-regulated network. Targets in this network include LDB2 and LIPA, both associated with coronary artery disease.
We conclude that variants in the SERPINA6/SERPINA1 locus mediate their effect on plasma cortisol through variation in SERPINA6 expression in liver, and in turn affect gene expression in extra-hepatic tissues through modulating cortisol delivery. This supports a dynamic role for CBG in modulating cortisol delivery to tissues. The cortisol-responsive gene networks identified here represent candidate pathways to mediate cardiovascular risk attributable to elevated cortisol.
(1) Bolton, et al. (2014) PLOS Genet. 10:e1004474., (2) Franzén et al. (2016). Science 353:827., (3) Wang and Michoel. (2017). PLOS Comput. Biol. 13:e1005703.
MON-029 Polycystic Ovary Syndrome (PCOS) in Adolescent Girls:Toward a Simple On-Treatment Predictor of Post-Treatment Ovulation Rate
Authors: Ibanez Lourdes , Díaz Marta , Cereijo Ruben , Bassols Judit , Lopez-Bermejo Abel , Villarroya Francesc , de Zegher Francis 
Published: May 2020

Abstract
There is no approved treatment for adolescent girls with PCOS. The vast majority of these patients are guided into a trajectory that starts with oral contraceptive (OC) treatment, leads into oligo-anovulatory subfertility, then into the use of assisted reproductive techniques, and ultimately into pregnancies with a double-to-triple risk for complications (such as gestational diabetes, preeclampsia and preterm birth) potentially with lifelong sequelae in the offspring.
Evidence is converging into the insight that adolescent PCOS is frequently driven by hepato-visceral fat excess (“central obesity”) ensuing from a mismatch between (rather restrictive) prenatal and (rather abundant) postnatal nutrition, on a background of genetic susceptibility (Trends Endocrinol Metab 2018;29:815). This insight has prompted the exploration of an alternative PCOS treatment that aims at reducing the central-fat excess (without causing weight loss in non-obese girls) in order to normalize the entire phenotype, including ovulation rate.
So far, this alternative approach has been tested in two randomized controlled pilot studies that were performed in non-obese girls with PCOS and with no need for contraception (total N=62; age 16 yr; BMI 24 Kg/m2; treatment for 1 year; ovulation assessment during the post-treatment year). In these studies, the effects of an OC were compared to those of SPIOMET, which is a low-dose combination of spironolactone (= a mixed anti-androgen and -mineralocorticoid, also activating brown adipose tissue; Diab Ob Metab 2019;21:509), pioglitazone and metformin (= two insulin sensitizers acting through different mechanisms).
Pooled results of the pilot studies confirm the first report (J Adolesc Health 2017;61:446) that SPIOMET has more normalizing effects than OC; there were approximately 3-fold more ovulations post-SPIOMET than post-OC; normovulation occurred only post-SPIOMET; anovulation was &gt;10-fold more frequent post-OC.
Pooled results also disclosed two new features of adolescent PCOS: low concentrations of circulating CXCL14 (= a brown adipokine, signaling activity in brown adipose tissue; Cell Metab 2018;28:750) and miR-451a (= an inhibitor of THRSP-mediated hepatic lipogenesis; Mol Cell Endocrinol 2018;474:260), both of which remain abnormally low on OC, but normalize on SPIOMET treatment. The on-treatment Z-scores of fasting insulin and miR-451a explained together approximately 50% of the variation in post-treatment ovulation rates. This simple duo, if validated in larger and more diverse PCOS populations, may become a first on-treatment predictor of post-treatment ovulation rate.
MON-042 The Effect of Exercise Training on Reproductive and Cardiometabolic Outcomes in Women with Polycystic Ovary Syndrome: A Pilot Randomized Controlled Trial
Authors: Benham Jamie L , Booth Jane E , Doucette Steve , Friedenreich Christine M , Rabi Doreen M , Sigal Ronald J 
Published: May 2020

Abstract
Exercise may improve cardiometabolic, reproductive and psychological outcomes in women with Polycystic Ovary Syndrome (PCOS). Clinical Practice Guidelines recommend exercise to treat PCOS, but the most effective exercise prescription is unclear. The aim of this randomized controlled trial was to evaluate the effects of six months of thrice weekly high-intensity interval training (HIIT) and continuous aerobic exercise training (CAET) programs compared with no exercise in previously-inactive women aged 18–40 years with PCOS. The primary outcome was change in ovulation rate. Ovulation was assessed with daily at home ovulation prediction kits, and confirmed with serum progesterone levels. Fisher’s exact test was used to compare groups. Secondary outcomes included change in BMI, waist circumference, blood pressure, A1C, fasting glucose, fasting insulin, and lipids and were analyzed using repeated measures mixed models. 47 women were randomly assigned to no exercise control (n=17), HIIT (n=16), or CAET (n=14). 22/33 (66.7%) women ovulated during the intervention period: no exercise: 8/12 (66.7%), HIIT: 8/11 (72.7%), and CAET: 6/10 (60%); NS between groups. BMI decreased significantly in the CAET group compared with control (-1 kg/m2, p=0.01) and compared with HIIT (-0.9 kg/m2, p=0.04). Mean waist circumference decreased significantly in all groups with no significant difference between groups. There were no significant within- or between- group changes for body weight. No within- or between group differences were identified for mean blood pressure, A1C, fasting glucose, fasting insulin, or triglycerides. Mean LDL-C was significantly different between the HIIT and CAET groups (-0.33 mmol/L, p=0.03), as LDL-C decreased in the HIIT group but not in the CAET group. HDL-C increased in the HIIT group compared with the no exercise group (0.18 mmol/L, p=0.04), with no significant difference between the CAET and no exercise groups (p=0.47). In conclusion, CAET and HIIT interventions in women with PCOS did not affect ovulation rates. CAET and HIIT both were effective at improving anthropometrics and some cardiometabolic health markers in women with PCOS. Further studies are needed to determine optimal exercise prescriptions for reproductive, anthropometric and cardiometabolic outcomes in women with PCOS.
SAT-299 Chronic Treatment Of Juvenile Hypothalamic Pomc-deficient Mice With RM-493 Prevents The Development Of Obesity
Authors: Thompson Zoe , Shah Bhavik P , Low Malcolm J 
Published: May 2020

Abstract
Arc-Pomc knockout mice have a disruption of the two neural enhancers for the Pomc (proopiomelanocortin) gene, resulting in selective loss of Pomc gene expression in the arcuate nucleus of the hypothalamus. This gene targeting strategy leaves pituitary Pomc expression unaffected. These mice are hyperphagic starting at weaning, and develop progressive obesity, infertility and insulin resistance over their lifetime. RM-493 (setmelanotide) is a melanocortin-4 receptor agonist that has shown promise in treating humans with Pomc null mutations. In this preclinical study, we investigated the effects of chronic RM-493 treatment using subcutaneously implanted osmotic minipumps in two groups of male mice: Arc-Pomc knockout mice, fed regular chow throughout the study period, and their wildtype counterparts, fed a 45% high-fat diet. Each of these groups of mice was randomized into three treatment cohorts at weaning: one that was given RM-493 throughout the entire study period (4–24 weeks of age, “RM-493” group), one that was given RM-493 only for the first 4 weeks of the study (4–8 weeks of age, “switch” group) and then switched to vehicle, and one cohort that received vehicle for the entire study (“vehicle” group). We serially measured body weight, food intake, body composition, glucose tolerance, insulin tolerance, and several measures of metabolism using the Comprehensive Lab Animal Monitoring System, including oxygen consumption, energy expenditure, ambulatory activity and lipid and glucose oxidation.
Among other results, at the end of the study (24 weeks of age), Arc-Pomc knockout mice in the RM-493 group weighed significantly less than either the switch or vehicle groups (p&lt;0.05). Arc-Pomc knockout mice on RM-493 also had higher energy expenditure when compared to the switch and vehicle groups (p&lt;0.05). In addition, RM-493 improved the glucose-insulin index for Arc-Pomc knockout mice (p&lt;0.05). According to our preliminary results, wildtype mice on high-fat diet, treated chronically with RM-493, did not differ in any of these measurements from their switch and vehicle groups.
We conclude that the obesity syndrome caused by a loss of hypothalamic Pomc expression was completely blocked by RM-493 treatment started before the onset of obesity, with no apparent desensitization to the drug’s action over 20 weeks. However, the beneficial effects of a single month’s treatment were steadily reversed within one month after switching to vehicle treatment. In contrast to the dramatic effects of RM-493 in the genetic obesity syndrome, at this time, there does not appear to be any phenotypic changes in wild-type mice with RM-493 administration on the development of obesity or secondary metabolic disruptions in response to high-fat diet consumption.