bluuebunny/crossref_metadata_2025_split huggingface dataset:
SUN-724 Associations of GPR174 and ITM2A Genes on X Chromosome with Early Onset Autoimmune Thyroid Disease in Korean
Authors: Lee Nayeong , Cho Wonkyoung , Shin Hyeri , Lee Yoonji , Kim Seulki , Lee Seonhwa , choi yujung , Ahn Moon Bae , Baek Incheol , Kim Shin-Hee , Cho Kyoungsoon , Jung Min-Ho , Kim Taigyu , Suh Byung-Kyu 
Published: May 2020

Abstract
Background: Autoimmune thyroid diseases (AITDs) are female predominant and the biology of sexual dimorphism is not clearly understood. Recently, GPR174 and ITM2A on X chromosome have been newly suggested as autoimmune thyroid disease susceptible loci.
Methods: Fourteen single nucleotide polymorphisms in immune related genes on X chromosome were analyzed in 108 Korean children (girls =90, boys =18) with AITD [Hashimoto disease (HD) = 40, Graves′ disease (GD) = 68, thyroid-associated ophthalmopathy (TAO) = 37, and non-TAO =60] with gender ratio matched normal control 106 controls (female = 43, male = 63).
Results: In AITD, the frequencies of GPR174 rs3810711 T allele (OR=6.0, cP =0.000), GRP174 rs3827440 T allele (OR=6.0, cP =0.000), ITM2A-GPR174 rs5912838 A allele (OR=2.7, cP =0.001) were increased and of GPR174 rs3810711 CC genotype (OR=0.2, cP =0.000), GRP174 rs3827440 CC genotype (OR=0.2, cP =0.000), ITM2A-GPR174 rs5912838 CC genotype (OR=0.4, cP =0.000)were lower than controls. In GD, the frequencies of GPR174 rs3810711 T allele (OR=8.4, cP =0.000), GRP174 rs3827440 T allele (OR=8.4, cP =0.000), ITM2A-GPR174 rs5912838 A allele (OR=3.3, cP =0.000) were increased and GPR174 rs3810711 CC genotype (OR=0.1, cP =0.000), C allele (OR=0.5, cP =0.044), GRP174 rs3827440 CC genotype (OR=0.2, cP =0.000), C allele (OR=0.5, cP =0.044), ITM2A-GPR174 rs5912838 CC genotype (OR=0.4, cP =0.000) were lower than controls. In HD, the frequencies of GPR174 rs3810711 T allele (OR=3.9, cP =0.003), GRP174 rs3827440 T allele(OR=3.9, cP =0.003) were increased and GPR174 rs3810711 CC genotype (OR=0.3, cP =0.004), rs3827440 CC genotype (OR=3.9, cP =0.003) were lower than controls. In thyroid-associated ophthalmopathy, the frequencies of GPR174 rs3810711 T allele (OR=7.9, cP =0.000), GRP174 rs3827440 T allele (OR=7.9, cP =0.000), ITM2A-GPR174 rs5912838 A allele (OR=3.1, cP =0.001) were increased and of GPR174 rs3810711 CC genotype (OR=0.1, cP =0.000), GRP174 rs3827440 CC genotype (OR=0.1, cP =0.000), ITM2A-GPR174 rs5912838 CC genotype (OR=0.3, cP =0.014)were lower than controls.
Conclusions. Our results suggest that polymorphisms of GPR174 and ITM2A genes on X chromosome might contribute to the pathogenesis of AITD.
SAT-196 The Use of 11C-metomidate PET-CT to Detect Unilateral Primary Hyperaldosteronism
Authors: Harjanto Sumitro , Maung Aye Chan , Puar Troy , Gardner Daphne 
Published: May 2020

Abstract
Background
Identifying causative adrenal lesions presents a significant diagnostic burden for physicians and radiologists. We describe the use of radiolabelled metomidate to lateralise primary hyperaldosteronism.
Case presentation
A 52-year old Chinese man with a 5-year history of hypertension was referred for hypokalemia [K 2.7 mmol/L (3.6 - 5.0)]. He had been on Telmisartan 80 mg and Amlodipine 10 mg daily and blood pressure at home ranged 110-120 / 70-80 mmHg. There was no history of poor oral intake, persistent diarrhea or vomiting, and he was not on any other prescription or alternative medications. There was no significant family history of hypertension or sudden cardiac death. Clinic blood pressure was 140/84 mmHg. There were no features suggestive of Cushing’s syndrome.
Repeat biochemical tests confirmed hypokalemia (K 3.1 mmol/L), and associated raised bicarbonate 37.3 mmol/L [19 - 29]. Magnesium and creatinine were normal. Aldosterone-renin Ratio was elevated at 8.1 (serum Aldosterone 611 pmol/L [97.3 - 834.0], active renin 2.7 pg/ml [1.8 – 59.4]). Post-saline infusion, non-suppressible serum aldosterone levels of 1137 pmol/L was demonstrated, consistent with autonomous aldosterone production.
A computed tomography of the adrenal revealed a 2.3 cm x 1.9 cm nodule on the left adrenal gland consistent with lipid rich adenoma.
Adrenal vein sampling (AVS) under continuous synacthen infusion was performed. Adrenal to peripheral cortisol ratio was ≥10 for either adrenal veins, confirming cannulation of the adrenal veins. Aldosterone-cortisol ratios showed lateralization to the left adrenal gland (lateralization ratio of 10.35). There was contralateral suppression of the right adrenal gland with ratio of 0.41.
11C-Metomidate PET-CT scan demonstrated a maximum standardised uptake value (SUVmax) of 26.8 over the left adrenal nodule, while the SUVmax of the right adrenal gland was 16.2. Ratio of the left to right adrenal gland SUVmax was 1.65 (above the threshold of 1.25); and was concordant with AVS. This confirmed that the patient had a left functional adrenal adenoma responsible for hyperaldosteronism.
Our patient underwent a left adrenalectomy, and histology was consistent with adrenal cortical adenoma. Prior to surgery he required 72 mmol/l of potassium supplementation daily to maintain K levels of 3.3 – 4.0 mmol/L. Two weeks post-operatively, he was normokalemic (K 4.9 mmol/L) without potassium supplementation. Serum aldosterone normalized to 159.3 pmol/L (active renin 9.3 pg/ml). Blood pressure is well controlled on amlodipine 5mg daily.
Conclusion
Targeted molecular imaging such as 11C-Metomidate PET-CT could aid localisation of functional adrenal disease to guide definitive surgical management. In the future, this could obviate the need for invasive and technically complex procedures like AVS.
SUN-516 Unplanned Pregnancy Post Thyroid RAI Ablation
Authors: Bhalodkar Arpita , Busta Agustin 
Published: May 2020

Abstract
A patient’s pregnancy and fetus are at an increased risk for complications secondary to history of recent RAI ablation and maternal secondary hypothyroidism.
A 31 year old female with a recent history of miscarriage presented with abnormal thyroid function tests and was history of low dose levothyroxine use. She complained of a 3 month history of extreme fatigue, palpitations and 18 pound weight loss at the time of presentation. Her thyroid stimulating immunoglobulin was 9.21 IU/L (0-0.55), free thyroxine 6.2ng/dL (0.9-1.8), free triiodothyronine 20.04 pg/mL (1.8-4.6) with a suppressed TSH 0.01 uIU/ml (0.27 - 4.2). She was started on methimazole. Her 24 hour radioactive iodine uptake was 60% and she subsequently underwent radioactive iodine-131 ablation in capsule form. She failed the ablation after 7 months and remained on methimazole during that duration. Her second radioactive iodine uptake was 58% and she underwent a second RAI ablation. Her TSH was 50 uIU/ml and her free thyroxine was 0.1 ng/dl. She was started on levothyroxine for replacement. Patient unexpectedly became pregnant approximately six weeks after her radioactive iodine treatment.
Studies have shown that with the exception of miscarriages, there is no evidence that exposure to radioiodine affects the outcome of subsequent pregnancies and offspring. Although the number of children born of mothers exposed to radioiodine is relatively small, the present data indicates that there is no reason for patients exposed to radioiodine to avoid pregnancy. The only adverse effect observed in the study series is an increased incidence of miscarriages in women exposed to therapeutic radioiodine during the year which preceded conception. The fetus would be at risk due to maternal hypothyroidism.
Discussion: Radioactive iodine exposure does not appear to be associated with an increased risk of miscarriage or abnormal subsequent pregnancies.
Conclusion: Pregnancies achieved after exposure to radioactive iodine treatment do not appear to be at increased risk for negative outcomes. Nevertheless, it is recommended that pregnancy be avoided for 1 year following radioactive iodine therapy to allow reproductive function to normalize.
SAT-130 The Intermediate Prolactin Receptor Is a Breast Cancer Oncogene
Authors: Grible Jacqueline M , Zot Patricija , Harrell J Chuck , Idowu Michael , Clevenger Charles V 
Published: May 2020

Abstract
Epidemiological, cellular, and genetic analyses indicate the hormone prolactin (PRL) and its cognate receptor in humans (hPRLr) are significantly involved in breast cancer pathogenesis. Recent evidence demonstrated that a truncated mouse PRLr (mPRLrT) is oncogenic when expressed with canonical long mPRLr (mPRLrL). mPRLrT shares significant sequence homology with a naturally-occurring and widely-expressed hPRLr isoform, the intermediate hPRLr (hPRLrI). As determined by tissue microarray (TMA), hPRLrI is expressed in &gt;85% of breast cancer, with expression increasing as a function of both tumor grade and Ki67 status. To confirm the oncogenic potential of hPRLrI, isoform-specific hPRLrI knock-down (KD) was performed in breast cancer cell line MCF7. hPRLrI KD resulted in a significant decrease in proliferation, migration, and anchorage-independent growth. Given the homology between mPRLrT and hPRLrI, we hypothesized hPRLrI may similarly induce transformation, when expressed alongside wild-type long hPRLr (hPRLrL). hPRLrL/I co-expression in the immortalized but not transformed human breast cell line MCF10A resulted in a significant increase in proliferation, migration, and anchorage-independent growth. These results were not observed following overexpression of either isoform alone, demonstrating that hPRLrL/I co-expression is necessary to induce transformation of normal mammary epithelia. To test our hypothesis in vivo, we established MCF10A xenografts using female NSG mice. Following intraductal injection, we observed rapid tumor growth in the hPRLrL/I cohort, significantly over that of expressing either isoform alone. To determine mechanisms of transformation, we examined both differential protein stability and altered signaling events. In analyzing receptor degradation, a cycloheximide assay revealed hPRLrL stability is increased when heterodimerized with hPRLrI. hPRLrL turnover is impaired in breast cancer, indicating this phenomenon may be involved in the observed hPRLrI-mediated transformation. Regarding differential signaling, we examined the Jak2/Stat5a pathway. Jak2 is a promiscuous kinase whose oncogenic actions are well-characterized, while Stat5a is a transcription factor whose activities are critical in attenuating the oncogenicity of Jak2. Following PRL stimulation, it was observed that hPRLrL/I co-expression induced approximately two-fold greater Jak2-Y1007/1008 phosphorylation (pJak2) compared to that induced by hPRLrL expression alone. Further, it was observed that hPRLrL/I co-expression induced ten-fold less Stat5a-Y694 phosphorylation (pY-Stat5a) than hPRLrL expression alone. These data indicate unchecked pJak2 activity may also be a contributing mechanism in the observed transformation. Overall, these results demonstrate that hPRLrI, alongside hPRLrL, is sufficient for transformation of normal breast tissue.
SUN-722 Liver Leptin Receptor Gene Network Moderates the Effects of Early Life Adversity on Anxiety and Depression Problems in Children and Adolescents
Authors: Sobreira de Lima Randriely Merscher , Barth Barbara , Arcego Danusa Mar , Filho Euclides José de Mendonça , Patel Sachin , Wang Zihan , Pokhvisneva Irina , Sassi Roberto Britto , Hall Geoffrey B C , Bittencourt Ana Paula Santana de Vasconcellos , Meaney Michael Joseph , Dalmaz Carla , Silveira Patricia Pelufo 
Published: May 2020

Abstract
Leptin is a hormone involved in the regulation of food intake, with receptors largely expressed centrally and peripherally, in structures like the hypothalamus and the liver. Beyond its well-known actions as an energy-balance regulator, leptin is linked to psychiatric disorders. Considering that the association between genetic and early environmental factors contributes to psychopathology, disruptions of leptin signaling could be a key mechanism in this interaction. To investigate this possibility, we created an expression-based polygenic risk score (ePRS) reflecting variations in the function of the LepR gene network in the liver and hypothalamus, and investigated its interaction with postnatal adversity on Child Behavior Checklist in 4 years old children (main cohort: MAVAN, N=137) and 17 years old teenagers (Replication Cohort: ALSPAC, N=2630). There is an interaction effect between adversity exposure and liver-based LepR-ePRS, increasing depressive and anxiety problems on the MAVAN cohort (β=78.16, p=0.02, β=83.77, p=0.01). In ALSPAC, the results were replicated, showing an interaction between adversity exposure and liver-based LepR-ePRS, increasing the depression score and somatic symptoms (β=24.65, p=0.005; β=33.51, p=0.009). No significant interactions were found using the hypothalamus-based LepR-ePRS (p&gt;0.05), suggesting specificity for the liver LepR gene network to predict these behavioral outcomes. A parallel-independent component analysis showed relationships between the SNPs from the liver ePRS-LepR and gray matter density in cortical areas involved in emotion regulation (middle frontal gyrus, inferior parietal lobule and anterior cingulate). Finally, the relationship between gene and MRI components in this analysis is moderated by the history of early life adversity exposure. Enrichment analysis of the liver LepR co-expression network shows that these genes are related to biological processes including regulation of glucose transport, cholesterol metabolism and cellular glucose homeostasis, which indicates possible underlying mechanisms linking peripheral metabolism-related gene expression and the development of emotional symptoms. Our data supports the hypothesis that exposure to early adversity affects emotional behavior, and the liver LepR gene network is an important moderator of these effects. Further studies on development of emotional symptoms should consider metabolic markers to understand these complex phenotypes.
SUN-625 The Impact of Age on Outcomes of Hyperosmolar Hyperglycemia Among Adult Patients with Diabetes. from the National Inpatient Sample
Authors: Ahmed Fatima , Abugroun Ashraf , Elhassan Manar , Seyoum Berhane 
Published: May 2020

Abstract
Objective: There is paucity of literature on the impact of age on outcomes hyperosmolar hyperglycemic state (HHS) among adult patients with diabetes. The aim of the study was to evaluate the effect of age on the outcome of patients admitted for the management of HHS. Methodology: The National Inpatient Sample (NIS) was queried for all patients who were admitted with a diagnosis of HHS during the years 2005-2014. The primary outcomes of the study were all-cause mortality, acute myocardial infarction (MI), and acute stroke. The secondary outcomes were acute kidney injury (AKI), rhabdomyolysis, acute respiratory failure (ARF), need for mechanical ventilation (MV) length of stay (LOS), and total cost of stay. Results: Overall, 188,725 patients were admitted for HHS. Mean age was 55.9, standard error of the mean (SEM): 0.1. Majority were of middle age. Females were (43.9%), Caucasians were 37.4% while African Americans were 35.2%. Total mortality was 1.1%, MI was 1.3% and stroke was 1.1%. Most common secondary outcome was AKI seen in 31.3% followed by ARF seen in 2.9% of total. The mean cost was 7887 $ (SEM: 84.6) and mean LOS was 4.1 days (SEM: 0.03). Young age was defined as age ≤ 35 years, middle age was &gt; 35 and ≤ 65 years, old age was &gt; 65 years. Mortality was 0.3 %, 0.6%, 2.5% in young, middle and older aged groups respectively. Similarly, higher age correlated with increased risk for MI, stroke and all secondary outcomes. On multivariable analysis, age was an independent predictor for all adverse outcomes. Compared to young patients, middle and older age groups had higher odds for mortality with adjusted odds ratio (aOR) 2.23 [95%CI:1.10-4.52], p=0.03 and aOR 7.35 [95%CI: 3.27-16.53], p&lt;0.001 respectively, higher risk for stroke with aOR 9.32 [95%CI: 2.92-29.7], p&lt;0.001 and aOR 17.46 [95%CI:5.23-58.3], p&lt;0.001 and higher risk for MI aOR 5.18 [95%CI:2.15-12.51], p&lt;0.00 and aOR 5.80 [95%CI:2.27-14.80], p&lt;0.00 for middle and older age groups respectively. In addition, compared to the younge age group, the risk for rhabdomyolysis, AKI, ARF, MV, total cost and LOS was significantly higher among middle and older age groups respectively. Conclusion: Age is an important determinant for adverse outcomes among patients with hyperosmolar hyperglycemic sate.
SAT-147 Endogenous Expression of TCF21 by CRISPR/dCas9 System Results in Different Biological Responses in Adrenocortical Carcinoma and Hepatocarcinoma
Authors: Kremer Jean Lucas , Passaia Barbara dos santos , Lotfi Claudimara Ferini Pacicco 
Published: May 2020

Abstract
Transcription factor 21 (TCF21/POD-1/Epicardin) inhibits the expression of SF-1 (NR5A1) by binding to the promoter E-box site in adrenocortical carcinoma (ACC). In contrast, TCF21 promotes increased expression of LRH-1 in hepatocarcinoma cell line, HepG2 cells, by binding to the Small Heterodimer Partner (SHP/NR0B2) promoter region, an LRH-1 negative regulator. Epigenetic alteration induced TCF21 loss of function and has been associated with increased of cellular migration and invasion. In ACC, TCF21 promoter is hypermethylated and less expressed. Our aim was to evaluate the effect of TCF21 by expressing or silencing TCF21 in adrenocortical pediatric adenoma, ACA-T7 cells, in ACC cell lines SW-13 and H295R cell line, and in HepG2 cell line. Were used CRISPR/dCas9/TCF21 and pCMVMycPOD1 or siRNATCF21 to express and silence TCF21, respectively. Increased expression of TCF21 in H295RpCMVMycPOD1 and SW-13CRISPR/dCas9/TCF21 cells resulted in significantly decreased cell migration and invasion (53.2±36.1%/70.8±26.5% and 82.6±4.2%/100%, respectively). In ACA-T7/siRNATCF21 cells, the inhibition of TCF21 resulted in significant increase migration and invasion capacity (45.0±12.7%/33.1±17.4%) compared with ACA-T7 cells. Higher TCF21 expression in HepG2CRISPR/dCas9/TCF21 increased invasion [147.08±16.54% (p&lt;0.0001)]. Analysis of metalloproteinase genes expression showed that TCF21 significantly (p&lt;0.01) increased MMP8 expression in SW-13CRISPR/dCas9/TCF21 and H295R/pCMVMycPod-1 whereas decreased MMP9 and MMP2 (p&lt; 0.0001). The opposite effect was observed in ACA-T7/siRNATCF21. Moreover, in HepG2CRISPR/dCas9/TCF21 cells was observed an increase of MMP2 and MMP9 expression (p&lt;0.001). These results suggest that TCF21 regulate epithelial mesenchymal transition and vice versa (EMT/MET) in tumors depending on cellular context. Supported by Fapesp and Capes.
SAT-210 When Acne, Hirsutism and Menstrual Irregularities Are More Than PCOS
Authors: Rios Paola , Zuniga Gabriela , Manzano Alex 
Published: May 2020

Abstract
Background: Polycystic ovarian syndrome (PCOS) mimics non-classic congenital hyperplasia (NCCAH), presenting with hyperandrogenic symptoms. NCCAH is usually diagnosed later in life, where 21-hydroxylase (21OHD) is the most common deficiency. There are more than 300 mutations in 21OHD, being V281L one of the described mutations.
Clinical Case: 23 y/o female patient G0P0 comes to the office complaining of irregular periods, frontal hair loss, weight gain, acne and hirsutism. She has had noticed these changes since menarche; however, her acne was getting worse. Was seen 2 months prior to presentation by her gynecologist who order a free Testosterone that was elevated (6.4 pg/mL, n&lt;4.2 pg/mL), with normal TSH (1.1 uIU/mL, n,0.45-4.5). She was not taking any medication. Her mother has history of 2 spontaneous abortions and her sister has acne and hirsutism as well. On physical exam BMI was 26, it was noticed comedones and papules on her face, back and shoulders. Ferriman-Gallwey scale was &gt;8. At the initial visit due to the clinical scenario, it was thought that she had hyperandrogenic syndrome, probably secondary to PCOS. Serum blood test were ordered and showed an elevated total testosterone (71 ng/dL, n,8-48ng/dL), free testosterone (8.4 pg/mL, n&lt;4.2 pg/mL), 17- OH pregnenolone performed by liquid chromatography-tendem mass spectrometry (LC-MS/MS) was (429 ng/dL, n, 35-290 ng/dL luteal phase) and androstenedione LC-MS/MS (1941 ng/dL, n, 41-262 ng/dL) which confirmed NCCAH diagnosis due to 21OHD. She had no desire to become pregnant at the time of evaluation; however, was concern about fertility and genetics. Was started on OCPs and genetic testing was positive for V281L mutation in the CYP21A2 gene, being homozygous for this mutation. Three months after, her acne and frontal hair loss were better, and a trial of spironolactone 50 mg daily, was prescribed. For her sister and mother was suggested to consult endocrinology, due to possible same disease.
Conclusion: this case highlights the importance of recognizing NCCAH as a cause of hyperandrogenism. Molecular genetic analysis should be offered with genetic counseling to patients, since they can carry a severe allele which can affect their progeny. Clinicians should be aware of the importance of family history when diagnosing NCCAH on their patients; for detection, treatment and genetic counseling of NCCAH on family members as well, as found in this case.
MON-013 Effect of Poor Circumstance in Utero on Adiponectin Gene Expressions Through Epigenetic Changes in Offspring
Authors: Masuyama Hisashi , Mitsui Takashi , Eto Eriko , Hayata Kei 
Published: May 2020

Abstract
The links between obesity and metabolic syndrome in parents and their offspring and the role of genes and a shared environment are not completely understood. Adipocytokines play important roles in glucose and lipid metabolism. We have already developed the model mice for transgenerational effect of obesity and metabolic syndrome and demonstrated that exposure to a high fat diet in utero might cause a metabolic syndrome-like phenomenon through epigenetic modifications of adipocytokine, adiponectin and leptin gene expressions in offspring of the model mice. In this study, we examined whether poor circumstance in utero affected the adiponectin gene expression and epigenetic changes of this gene using samples from umbilical cord in patients with hypertensive disorder of pregnancy (HDP) and fetal growth restriction (FGR) or gestational diabetes mellitus (GDM) and heavy for date fetus (HFD) compared with normal pregnant women without HDP, GDM and abnormal fetal growth. We observed that the poor circumstance under HDP with HGR or GDM with HFD caused significantly lower adiponectin gene expression and higher methylation level of histone H3 at lysine 9 of the promoter of adiponectin gene compared with normal control. Thus, poor circumstance in utero affected adiponectin gene expressions through epigenetic modifications, which might result in the increased risk for metabolic syndrome of offspring.