bluuebunny/crossref_metadata_2025_split huggingface dataset:
ODP276 THYROID CANCER CELLS ARE MORE RESISTANT THAN NORMAL CELLS TO BISPHENOL-A CYTOTOXIC EFFECT
Authors: Sterian Ward Laura , Rabi Larissa Teodoro , Nascimento Matheus , Teixeira Elisangela Souza , Dal’ Bó Cruz Izabela Fernanda 
Published: November 2022

Abstract
Bisphenol-A (BPA) is a well-known endocrine disruptor that produces important effects on thyroid metabolism, can interfere with TSH transcriptional activity, alter the transcription of T3-associated genes and, thus, modulate its activity in different cell lines. However, its direct effects on thyroid cells, especially on mutated thyroid cells, are still poorly understood. We tested 14 different concentrations of BPA, ranging from 0.4µg/mL to 400µg/mL, including LME (Specific Migration Limit =1μg/mL, recommended as acceptable by the Brazilian National Health Surveillance Agency-ANVISA) on two human thyroid cell lines: Nthy-ori 3-1 (from normal thyroid follicular cells) and TPC-1 (from papillary carcinoma). Cell viability analysis was made using the Trypan blue assay on cells exposed to BPA for 24h and 48h in technical and biological triplicate. We observed a non-monotone dose-response curve, characteristic of disruptors’ effect, on both cell lines, with greater cytotoxic effect with higher doses. In fact,100μg/mL already killed almost all Nthy-ori 3-1 cells (99% at 24h and 97% at 48h), whereasthe doses of 0.78µg/mL; 4µg/mL and 12.5µg/mL caused 50% kill. Optical microscopy revealed some irregular cells lost on the plate, and few debris with50μg/mL. Concentrations of 100 to 400µg/mL produced many dark small cells detached from the plate and clumps of dead cells. The SCI dose (1µg/mL - allowed in daily life), resulted in 79% of Nthy-ori 3-1 cell death after 24h of exposure. However, only 7% of the cell were dead after 48h of exposure to the SCI dose. This reduction in death rate after longer exposure to BPA was observed at all concentrations, suggesting a potent cellular recovery mechanism. The TPC-1 strain showed a different behavior, with a much more linear dose-dependent cytotoxic effect and much more resistance to the harmful effects of BPA at low doses. In fact, 0.4μg/mL to 3.125μg/mL produced less than 10% cell death, and microscopy confirmed the maintenance of the integrity of virtually all cells. On the contrary, BPA concentrations from 100 to 400µg/mL killed almost all TPC-1 cells at both 24h and 48h times. We conclude that this thyroid papillary carcinoma cell line is more resistant than the normal thyroid lineage to low BPA concentrations (from 0.4 to 50µg/mL) but this endocrine disruptor is highly cytotoxic at higher concentrations, causing more than 90% cell deaths on both normal and mutated thyroid cell lines.
Presentation: No date and time listed
ODP277 Urinary Concentrations of Polycyclic Aromatic Hydrocarbons and Childhood Obesity
Authors: Kim Shin-Hye , Park Mi Jung , Park Sung Kyun 
Published: November 2022

Abstract

Background
Polycyclic aromatic hydrocarbons (PAHs), primarily produced by incomplete combustion of organic materials, have been suggested as obesogens, but information on PAHs and obesity, especially in children, is limited. We examined the cross-sectional association between urinary concentrations of PAHs and obesity in the Korean pediatric population.

Methods
We analyzed the data of 2286 children and adolescents aged 3–17 years who participated in the Korean National Environmental Health Survey (KoNEHS) 2015–2017. Urinary concentrations of 2-naphthol, 2-hydroxyfluorene, 1-hydroxyphenanthrene, and 1-hydroxypyrene were assayed using gas chromatography-mass spectrometry. Covariate-adjusted standardization method was used for the urinary dilution adjustment. Overweight and obesity were defined as BMI-for-age ≥85th percentile and ≥95th percentile, respectively. Multiple linear and logistic regression models were performed to analyze the relationship of BMI z-score and overweight with urinary concentrations of PAHs after adjusting for age, sex, household income, parental education level, physical activity, fast-food consumption, and ETS exposure.

Results
Obese children showed significantly higher urinary 2-naphthol concentrations than normal-weighted children in the overall population [3.62 µg/L (95% confidence intervals (95% CI): 3.20, 4. 09) vs. 2.88 µg/L (95% CI: 2.62, 3.16)]. Similar findings were observed in the age groups 6-11 and 12-17 years. Significant increases in BMI z-scores for 10 times increase in urinary 2-naphthol concentrations were observed in the age groups 6-11 [0.31 z-score units, (95% CI: 0.13, 0.49), P = 0. 001] and 12-17 years [0.33 z-score units, (95% CI: 0. 05, 0.60), P=0. 02]. A significant but smaller association was observed between change in BMI z-score and 1-hydroxypyrene concentrations in the 6-11 year group [0.14 z-score units, (95% CI: 0. 02, 0.27), P=0. 03]. The multiple logistic regression models for overweight showed significant positive associations with the quartiles of 2-NAP in the overall population [OR (95% CI); 1.14 (0.83-1.55), 1.39 (1. 03, 1.88), 1.46 (1. 08, 1.99) in the 2nd, 3rd, and 4th quartile, respectively, compared with the 1st quartile; P-for-trend=0. 006]. Similar associations between 2-naphthol and overweight status were also observed in the 6-11 year and 12-17 year groups.

Conclusion
This result suggests a possible link between PAH exposure, particularly 2-naphthol, and obesity in the Korean pediatric population. Given the growing obesity rates among Asian children and adolescents, this finding warrants further studies on the impacts of long-term exposure of PAHs on childhood obesity and possible mechanisms for this association.
Presentation: No date and time listed
ODP278 A rare case of Ectopic ACTH secretion associated with Primary Gastric Choriocarcinoma
Authors: Abufaied Mohamad , Khan Adeel Ahmad , Saleh Ahmed Osman , Surchi Haval 
Published: November 2022

Abstract

Background
Ectopic ACTH production contributes to 10-15% of cases of Cushing's syndrome. Most cases are caused by neuroendocrine tumors of the lung, pancreas, or thymus. Other rare tumors causing ectopic ACTH secretion include esophageal tumor, gastric carcinoid tumor and squamous cell carcinoma of the larynx (1). We present a rare case of ectopic ACTH production causing Cushing syndrome due to primary gastric choriocarcinoma.

Case Presentation
A 27-year-old lady, not known to have any chronic illnesses, presented with two days history of epigastric pain. The patient also reported facial puffiness, leg swelling, generalized weakness and oligomenorrhea for the last four months. There was no history of easy bruisability or weight. She was not taking any medications. The patient did not smoke or use alcohol. Physical examination revealed conjunctival pallor, facial acne, wide striae on her thighs and hepatomegaly. The rest of the examination was normal. Lab tests showed microcytic anemia with hemoglobin of 7 gm/dl (12-15 gm/dl), hypokalemia (2.5 mmol/L; normal 3.5-5.3 mmol/L), AST 38 U/L (0-40 U/L) and ALT 45 U/L (0-41 U/L). β HCG was 1,506 mIU/mL (0 -5 mIU/ml). An abdominal ultrasound showed hepatomegaly with multiple echogenic solid mass lesions suspicious of metastatic origin. A CT abdomen showed a solid lesion in the fundal region of the stomach with multiple liver metastases and moderate ascites. An esophagogastroduodenoscopy showed fungating mass originating from the stomach fundus. Biopsy of the gastric mass revealed primary gastric adenocarcinoma, which was positive forCK 7, CK 19, beta hCG, CDX2 and CEA, consistent with the diagnosis of primary gastric choriocarcinoma. Due to widespread metastasis, the patient was started on palliative chemotherapy with dexamethasone 2 mg injection once daily along with capecitabine, cisplatin and pembrolizumab. In view of persistent hypokalemia and physical examination findings, a workup for Cushing's syndrome was performed. Early-morning serum cortisol was 1054 nmol/L (138–689 nmol/L), and plasma ACTH was 174 pg/ml (7.2-63.3 pg/ml) despite the patient being on intravenous 2 mg dexamethasone once daily for more than ten days. An MRI of the brain showed a normal pituitary gland. Based on these findings, the patient was diagnosed with Cushing's syndrome due to ectopic ACTH secretion. Unfortunately, her hospital course was complicated by massive upper gastrointestinal bleeding from the tumor, leading to her demise.

Conclusion
Gastric choriocarcinoma is a rare tumor associated with ectopic ACTH secretion leading to Cushing's syndrome. Reference: Imura H, Matsukura S, Yamamoto H, Hirata Y, Nakai Y. Studies on ectopic ACTH-producing tumors. II. Clinical and biochemical features of 30 cases. Cancer. 1975 May;35(5): 1430-7
Presentation: No date and time listed
PMON14 Estrogen Activity of Supplements Targeted for Post-Menopausal Women
Authors: O’Leary Emily , Davis Connor , Mancheski Molly , Ma Peng , Wiese Thomas 
Published: November 2022

Abstract
A wide variety of dietary supplements are available for the treatment of post-menopausal symptoms in women. Many women choose these supplements to avoid the potential unwanted side effects and long-term complications associated with traditional hormone therapy. In this study, we evaluated the in vitro estrogen activity of extracts from eleven supplements targeted for post-menopausal women to test the hypothesis that some of these supplements will induce estrogen activity in human breast cancer cell bioassays. Ethanol extracts (1 g: 1 mL) were prepared from the supplements: Amberen, Nature's Bounty Black Cohosh, Nature's Bounty St. John's Wort, Swanson Chasteberry Fruit, Nature's Way Red Clover, Promensil Real Health, Estroven, Relizen, Remifemin, and Equelle. Black cohosh, St. John's Wort, Chasteberry fruit, and red clover are standalone products that are not sold under a brand name. Promensil, Estroven, and Equelle contain isoflavones that have been reported to be estrogenic. Estroven and Remifemin contain black cohosh. Relizen contains a purified Swedish flower pollen extract and Amberen contains succinates, amino acids, minerals, and vitamin E. The estrogen activity of each extract was measured using both the T47D-kb-Luc estrogen responsive reporter gene and MCF-7 E3 proliferation estrogen bio-assays. The extracts from Nature's Way Red Clover, Promensil Real Health, and Equelle induced full estrogen agonist efficacy in the MCF-7 proliferation assay and more than full efficacy in the T47D-kb-Luc assay compared to estradiol. The agonist activity of these extracts in both bio-assays was inhibited by fulvestrant. Extracts from Nature's Bounty Black Cohosh, Nature's Bounty St. John's Wort, Swanson Chasteberry Fruit and Relizen induced less than full agonist estrogen activity only in the MCF-7 proliferation assay that was not, or not completely inhibited by fulvestrant. Thus, some supplements in this study likely target the estrogen receptor as agonists while others may be only weak estrogens that may also activate other proliferative pathways. While estrogen therapy is known to provide relief of some post-menopausal symptoms, estrogen use is associated with increased breast cancer risk. Consumers may benefit from information about the estrogen activity of supplements targeted for post-menopausal women. The results of this study may allow women to make more informed decisions about the use of these supplements. This study may be a prototype for evaluating the estrogen activity of dietary supplements for the purpose of informing consumers.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON17 Impaired cortisol regulation in Myotonic dystrophy
Authors: Mittal Ashima , Tipu Ali , Alkhaddo Jamil B , Jaiswal Gayatri 
Published: November 2022

Abstract

Introduction
- Myotonic dystrophy (MD) is the most common cause of adult-onset muscular dystrophy. It has impaired HPA axis regulation with exaggerated ACTH response to CRH mediated stimuli and abnormal cortisol metabolism. We present a case of myotonic dystrophy in a male with elevated cortisol levels. Case report - 54-year-old male with a past medical history of type 1 myotonic dystrophy (MD1) presented for evaluation of hypogonadism with complaints of feeling fatigued, progressive weakness of muscles. During the workup, he was noted to have elevated cortisol levels 30.2 mcg/dL (6-18.4) with elevated ACTH 220 pg/mL (10-48). Other notable lab results included low total testosterone levels of 231, 185 with elevated LH of 17.3 m IU/ml (2-9) and FSH 37.7 m IU/ml (1-12). Prolactin levels were minimally elevated to 21.4 ng/mL (4-15.2). On further inquiry, the patient did not have headaches or vision changes. The patient did not report weight gain, easy bruising, change in facial appearance. Physical exam was significant for bilateral gynecomastia and small testes. No cushingoid facies, abdominal stria, proximal myopathy was noted. Given elevated ACTH and cortisol levels, further laboratory data showed a lack of suppression of cortisol levels with 1 mg dexamethasone - cortisol 2.9 micro g/dL (&lt;1.8), elevated midnight salivary cortisol - 0.130, 0.102 ug/dl (0.010-0.090), and normal 24-hour urine cortisol levels -15 mcg/24 hours.

Discussion
– Even though Cushing's disease is one of the differential diagnoses for the above case, high cortisol levels have been reported in MD. Few mechanisms suggested causing this abnormality are increased ACTH responsiveness to CRH-mediated stimuli and abnormal cortisol metabolism. Patients with MD have high pro-inflammatory (IL-1 and TNF-a) markers, which mediate the increased ACTH responsiveness to CRH-mediated stimuli centrally by stimulating the HPA axis.1 In addition, IL-6 chronically stimulates steroidogenesis from the adrenal gland, whereas TNF-α inhibits ACTH-induced adrenal steroid synthesis and increases 11BHSD1 activity. Along with the impaired HP axis, abnormal metabolism of cortisol also contributes to elevated cortisol levels. Increased activity of 11 BHSD1 has been hypothesized to cause impaired clearance of cortisol.2 Impaired diurnal variation for cortisol is also seen in MD with elevated 24-hour cortisol levels. Elevated cortisol levels as in our case can be a diagnostic dilemma given impaired cortisol regulation as seen in MD.

References
Åsa Johansson et.al. Abnormal Cytokine and Adrenocortical Hormone Regulation in Myotonic Dystrophy, The Journal of Clinical Endocrinology & Metabolism, Volume 85, Issue 9, 1 September 2000, Pages 3169–76.Åsa Johansson et.al. Glucocorticoid Metabolism and Adrenocortical Reactivity to ACTH in Myotonic Dystrophy, The Journal of Clinical Endocrinology & Metabolism, Volume 86, Issue 9, 1 September 2001, Pages 4276–83
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
RF22 | PMON04 Sex- and Dose-Dependent Effects of In Utero Endocrine Disruptor Exposure on Offspring Behavior and Brain Monoamines
Authors: MohanKumar Sheba , Kaimal Amrita , Hooversmith Jessica , Al Mansi Maryam , Holmes Philip , MohanKumar Puliyur 
Published: November 2022

Abstract
Exposure to endocrine disruptors (EDs), including the well-known plasticizers bisphenol A (BPA) and di(2-Ethylhexyl) phthalate (DEHP), during the highly sensitive gestational period, can produce long-lasting behavioral changes in offspring. In this study, we hypothesized that gestational exposure to BPA and/or DEHP at various doses would alter stress-related behaviors and monoaminergic activity in a region-specific manner in exposed offspring. To test this, female Sprague-Dawley dams were orally administered saline (control group - 10 µL/kg BW), BPA (5 µg/kg body weight (BW)), DEHP (5 µg/kg BW or 7.5 mg/kg BW), a combination of BPA and low-dose (LD) DEHP (5 µg BPA + 5 µg DEHP/kg BW), or a combination of BPA and high-dose (HD) DEHP (5 µg BPA + 7.5 mg DEHP/kg BW) during days 6 through 21 of pregnancy. The male and female offspring of these dams underwent a battery of behavioral tests in adulthood. Brains collected from the offspring were microdissected to obtain the medial prefrontal cortex (mPFC), paraventricular hypothalamic nucleus (PVN), and hippocampus (HC), which were analyzed for monoamine and metabolite levels using High-Performance Liquid Chromatography (HPLC). While BPA and B+D (LD) female offspring demonstrated anxiolytic effects in the Open Field Test, DEHP (HD) male offspring showed feminized anxiety-like behavior in the Elevated Plus Maze. The offspring also displayed impaired fear responses in the Shock Probe Defensive Burying (SPDB) test. Males in most ED groups buried less than their control counterparts. Furthermore, low-dose ED treatments led to a robust preference for passive coping strategies in both male and female offspring. Within the brain, male offspring in the BPA, LD and HD DEHP, and B+D (HD) groups had diminished dopamine (DA) levels in the PVN, which corresponded with their reduced SPDB burying levels. Moreover, DEHP (LD) male offspring had elevated DA turnover in the mPFC, whereas B+D (LD) female offspring had enhanced norepinephrine levels in the HC, which may underlie their behavioral outcomes in the SDPB. The findings of this study have implications for sex differences in mood and anxiety disorders following prenatal exposures to BPA, DEHP, and their mixtures.
Presentation: Sunday, June 12, 2022 12:36 p.m. - 12:41 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
ODP279 A Case of Nephrogenic Diabetes Insipidus Diagnosed at an Advanced Age in a Female Patient with an AVPR2 Gene Mutation and Skewed×Inactivation
Authors: Nakata Kento , Kameda Hiraku , Kuwabara Saki , Yasui Ayano , Takahashi Yuka , Miya Aika , Nomoto Hiroshi , Cho Kyu Yong , Nakamura Akinobu , Miyoshi Hideaki , Okada Eri , Nozu Kandai , Atsumi Tatsuya 
Published: November 2022

Abstract

Background
Arginine vasopressin receptor 2 (AVPR2) gene mutationsare the most common cause of congenital nephrogenic diabetes insipidus (CNDI), and they are inherited in an X-linked recessive manner. Women are generally asymptomatic or mildly affected, but atypically severe cases have been reported. Skewed X inactivation, in which the X chromosome is unevenly active, is a cause of this atypical severe case.×chromosome inactivation is a developmental compensation mechanism that results in equal doses of X-linked genes between XX females and XY males and has been reported to be accentuated by aging.

Clinical Case
A 69-year-old woman had no family history of diabetes insipidus. Immediately after undergoing a craniotomy for subarachnoid hemorrhage in July, she showed marked polyuria of approximately 8000 mL/day and hypernatremia of 161 mEq/L. The use of desmopressin (15mcg/kg/day) did not improve herpolyuria. She was referred to our department in September for further investigation and treatment. Her urine osmolality remained hypotonic at approximately 60–80 mOsm/kg/H 2 O (50–1300 mOsm/kg/H 2 O) according to a water restriction test. Her urine osmolality increased slightly to 106 mOsm/kg/H 2 O in a desmopressin test. These results indicated that desmopressin was ineffective, and the patient was diagnosed with nephrogenic diabetes. Her urine output decreased to approximately 2500 mL/day with trichlormethiazide treatment. There was no significant anterior pituitary hypofunction. Genetic examination revealed a heterozygous mutation of the AVPR2 gene (c.656T&gt;G, p. Leu219Arg) in her X chromosome, and her X chromosome activity ratio was 79: 21 in a human androgen receptor assay, indicating skewed X inactivation.

Conclusion
We observed a case of CNDI in an elderly woman with no family history of the disease. In this case, a combination of the skewed X inactivation, presumably accentuated by aging, and the onset of subarachnoid hemorrhage, reduced her drinking water and led to the diagnosis of CNDI. References: (1)K. Kinoshita et al, J. Endocrinol. Invest. 27: 167-170, 2004. (2)Ding C et al, Am J Med Genet Part A. 2020; 182A: 1032–1040. (3)Y. Nomura et al, Journal of Clinical Endocrinology and Metabolism: 3434-3437, 1997.
Presentation: No date and time listed
PMON33 Non-Syndromic SRY Negative 46 XX Testicular Disorder of Sex Development (DSD); A rare cause of Infertility
Authors: Riaz Aiman , Barua Nabonita , Gordner Chelsea 
Published: November 2022

Abstract

Introduction
Male infertility can be categorized as endocrine and systemic disorders, primary testicular defects in spermatogenesis, sperm transport disorders and idiopathic male infertility. Chromosomal abnormalities are one of the primary testicular defects. The overall incidence of chromosome abnormalities in infertile men is estimated to be around 5.8%. XX male is a rare sex chromosomal disorder in infertile men. We present case of a young patient with infertility, azoospermia, hypergonadotropic hypogonadism and classical (46, XX) karyotype with negative FISH and SRY gene.
Case report: 28-Year-old gentleman was referred to adult endocrinology clinic as part of work up for infertility. Initial work up included 2 semen analyses which were consistent with azoospermia. Examination revealed height 180 cm, weight 77 kg, a body mass index 24 kg/m2, normal phenotypic male without gynecomastia and had normal male pattern hair distribution. Genital examination showed normal male phallus without hypospadias, a hypoplastic scrotum, bilateral firm testes, with no varicocele or hydrocele. Labs were suggestive of compensated primary hypogonadism (FSH 47.9 mIU/ml, LH 20.4 mIU/ml, total testosterone 397.9 ng/dl by LC/MS, free testosterone 15.76 ng/dl by equilibrium dialysis, Inhibin B &lt; 10 pg/ml, and anti-Mullerian hormone 0.390 ng/ml. Given normal testosterone levels, he was not started on testosterone replacement. Karyotype analysis revealed 46 XX and FISH was negative for SRY gene. CT imaging of abdomen and pelvis did not reveal any Mullerian structures, prostrate and seminal vesicles reported as normal. Patient met with a Urologist and was informed that testicular sperm extraction will not be a possibility for him. Patient had a detailed consultation with a geneticist for genetic and family counseling. Chromosome microarray analysis was obtained and was normal. Invitae Disorders of sex development (DSD) panel obtained for genetic sequencing of 53 genes including SOX-9, DHH, WNT4, WT1, was found to be non-diagnostic.

Conclusion and Discussion
SRY negative 46 XX male is a DSD and a rare genetic cause of male factor infertility, with a discrepancy between genotype and phenotypic sex. In the case presented, genetic work up for potential etiologies has been unrevealing. Further studies are needed to identify the genetic causes of the SRY negative 46 XX male phenotype. Physicians involved in care of these patients should orient with clinical management and prognosis. For Classical 46 XX Males seeking fertility, the current options include invitro-fertilization with donor sperm or adoption only. Testosterone replacement should be considered to correct hypogonadism for physical and sexual well-being. Genetic consultation should be sought in all these cases.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.