bluuebunny/crossref_metadata_2025_split huggingface dataset:
FRI451 Effect Of Estrogen Replacement On Various Metabolic Parameters In Turner’s Syndrome
Authors: Mishra Ipsita , Jena Sweekruti , Baliarsinha Anoj Kumar 
Published: October 2023

Abstract
Disclosure: I. Mishra: None. S. Jena: None. A.K. Baliarsinha: None.
Turner’s Syndrome is a rare genetic disorder caused by complete or partial X chromosome monosomy in a phenotypic female, and is associated with increased morbidity and mortality for cardiovascular diseases, impaired glucose tolerance, liver dysfunction and dyslipidemia. Estrogen therapy was initially focused on pubertal induction and preservation of bone health. Recent longitudinal studies have shown the beneficial effect of estrogen therapy on various metabolic parameters, liver dysfunction and insulin resistance in these patients.To study the effect of estrogen therapy on various metabolic parameters, a cohort of 24 adolescent girls with Turner’s Syndrome planned for hormonal replacement therapy were recruited. Baseline data of detailed history, clinical examination, biochemical evaluation including glycemic status, lipid profile, liver function test and fibroscan were collected. At 6 month follow-up of estrogen replacement, repeat biochemical evaluation and fibroscan were done.The data obtained was entered into Microsoft Excel Worksheet and analysed using Statistical Package for Social Sciences (SPSS, IBM Corp. Released 2020. IBM SPSS Statistics for Windows, Version 27.0. Armonk, NY: IBM Corp.). The normal distribution of data was confirmed with Shapiro-Wilk's test and appropriate parametric tests were employed. Mean and standard deviation were computed for all continuous variables. At baseline visit and 6 month follow up, statistically
significant improvement, was found in fasting plasma glucose, post-prandial plasma glucose, fasting insulin, HOMA-IR, VLDL and total bilirubin with estrogen therapy. Maximum reduction (p &lt;0.001) was seen in LDL, AST, ALT and fibroscan values .No improvement was seen in triglyceride, HDL, direct bilirubin and ALP levels. Estrogen has been shown to improve insulin sensitivity and suppress gluconeogenesis by transcription factor Foxo1(1). Hepatoprotective role of estrogen has been explained by anti-inflammatory effects and protection from oxidative stress, mainly mediated via β estrogen receptor(2). Beneficial effects of estrogen on lipid profile have been verified in several studies. We conclude that the benefits of estrogen therapy in Turner’s Syndrome are much beyond the limit of puberty induction and bone health and pleiotropic actions of estrogen still need to be elucidated with further studies.
Reference: (1) Yan et al; Estrogen Improves Insulin Sensitivity and Suppresses Gluconeogenesis via the Transcription Factor Foxo1. Diabetes 1 February 2019; 68 (2): 291–304. (2) Koulouri O et al. Liver dysfunction in Turner's syndrome: prevalence, natural history and effect of exogenous oestrogen. ClinEndocrinol (Oxf). 2008 Aug;69(2):306-10.
Presentation: Friday, June 16, 2023
FRI168 LH-hCG Receptor Is Expressed In All Three Zones Of Normal Adrenal Glands But Not In Aldosterone-Producing Micronodules
Authors: Reda Sarah Alicia , Kirschenbaum Alexander , Yao Shen , Milgram Lucas , Rege Juilee , Levine Alice C 
Published: October 2023

Abstract
Disclosure: S.A. Reda: None. A. Kirschenbaum: None. S. Yao: None. L. Milgram: None. J. Rege: None. A.C. Levine: None.
Embryologically, the adrenals and gonads develop from the urogenital ridge with differential migration and differentiation. Post-natally, pituitary adrenocorticotropic hormone (ACTH) stimulates adrenal cortical cell growth and steroidogenesis, whereas pituitary luteinizing hormone (LH) regulates gonadal cell growth and steroidogenesis. However, there are multiple reports of gonadal tumorigenesis driven by high ACTH (in congenital adrenal hyperplasia) and adrenal cortical tumorigenesis driven by high LH/human chorionic gonadotropin (hCG) levels (adrenal tumors in pregnant and postmenopausal females). We studied the immunohistochemical expression of LH/hCG receptor (LH/hCG-R) in normal adrenal glands from 12 kidney donors (four male and eight female, two of which were &lt;50 years of age and six were &gt;50 years of age). Some of these specimens also contained aldosterone producing micronodules (APMs). Staining was performed for Synaptophysin, aldosterone synthase (CYP11B2), LH/hCG-R, WNT/β-Catenin, and DLK-1. In normal adrenal tissue, we first used synaptophysin stain to identify the nerves in the adrenal cortex as well as the adrenal medulla (M). CYP11B2 staining demonstrated immunoreactivity in a linear pattern throughout the Zona Glomerulosa (ZG) in five of the 12 samples. Faint expression of LH/hCG-R was detected in all twelve samples throughout the three layers of the adrenal cortex: the ZG, Zona Fasciculata (ZF) and Zona Reticularis (ZR). However, there were occasional cells in both the ZR and ZF that stained intensely for LH/hCG-R expression. LH/hCG-R immunoreactivity was also noted in the progenitor-rich subcapsular (SC) region. WNT β-Catenin, a transcription factor involved in the proliferation of adrenal cortical cells, stained most heavily in the SC/ZG region, possibly representing adrenal cortical progenitor cells. DLK-1, an adrenal cortical progenitor cell marker, was also expressed in the subcapsular zone. In adrenal tissues containing APMs, CYP11B2 immunostaining revealed areas of CYP11B2 positive cells that dip into the ZF, with no preserved linear staining for CYP11B2 in the ZG. LH/hCG-R stained most densely in the SC and ZG regions, with little to no immunoreactivity in the APMs. WNT β-Catenin likewise stained the SC and ZG regions with no expression in the APMs. Our findings suggests that LH/hCG-R is expressed sporadically in normal adrenal cortical tissue, but densely at times in all three zones of the adrenal cortex and the subcapsular area where the putative adult progenitor cells reside. The LH/hCG-R does not appear to be expressed throughout the entirety of APMs.
Presentation: Friday, June 16, 2023
SAT357 Rising Incidence, Health Resource Utilization and Costs of Polycystic Ovary Syndrome in the United Kingdom
Authors: Berni Tom , Morgan Chris , Rees Aled 
Published: October 2023

Abstract
Disclosure: T. Berni: None. C. Morgan: None. A. Rees: None.
Background: Polycystic Ovary Syndrome (PCOS) is a common disorder but trends in incidence and impact on health resource utilization are not known. Objectives: 1. To describe secular trends in prevalence and incidence of PCOS in the UK. 2. To establish healthcare resource use and associated primary and secondary care costs. Methods: Data were extracted from the Clinical Practice Research Datalink Aurum database and linked Hospital Episode Statistics (HES) database (2004-2021). Patients (≥18 yrs) of acceptable research quality and eligible for linkage to HES were included. A diagnosis of PCOS was established from medcode or ICD-10 codes. Point prevalence was assessed at the midpoint of each year from 2004-2020. Incident cases (2004-2021) were defined as a first diagnosis (index date) at least 90 days after practice registration. Costs from index date were compared for incident cases (n=132,925) and controls matched (1:1) by age, BMI category and primary care practice. Primary care contacts were assigned an average cost as listed in the Unit Costs of Health and Social Care 2019. Prescription items were assigned a net ingredient cost from the Prescription Cost Analysis for England 2019. Inpatient admissions and outpatient consultations were processed into Healthcare Resource Groups and costed to the National Tariff. Results: The incidence of diagnosed PCOS increased from 1.22 per 1000 person years in 2004 to 1.77 in 2012 and 2.20 in 2019. Point prevalence increased from 0.9% in 2004 to 2.1% in 2012 and 3.4% in 2020. Mean contacts per person year (ppy) for patients with PCOS versus controls were 0.43 vs 0.25 for inpatients (p&lt;0.001), 3.29 vs 1.83 for outpatients (p&lt;0.001) and 6.46 vs 4.71 (p&lt;0.001) for primary care. Mean healthcare costs (ppy) were £748 vs £438 (p&lt;0.001) for inpatients, £383 vs £216 (p&lt;0.001) for outpatients, £156 vs £111 for primary care and £114 vs £87 (p&lt;0.001) for primary care prescriptions. Total health care contacts ppy were 10.81 vs 6.21 (p&lt;0.001) and total associated costs were £1400 vs £852 (p&lt;0.001). Conclusion: The prevalence and incidence of diagnosed PCOS has risen significantly in the United Kingdom over the last two decades. This may be partly due to increased ascertainment and recording on computerised systems. Health resource utilization and costs were almost doubled in women with PCOS compared to controls.
Presentation Date: Saturday, June 17, 2023
SAT367 A Rare Case of Ovarian Cellular Fibroma Producing Testosterone
Authors: Rai Harpreet Kaur , Dandona Paresh 
Published: October 2023

Abstract
Disclosure: H.K. Rai: None. P. Dandona: None.
Background: Ovarian fibromas are hormonally inactive, benign sex cord-stromal tumors. However, the occurrence of ovarian fibromas in a woman presenting with post-menopausal bleeding, hirsutism, and elevated testosterone levels raises suspicion of such tumors being functionally active.Case: 62-year-old menopausal woman presented for evaluation of worsening facial hair for the past year. She reported vaginal spotting for the past two months and was following up with a gynecologist. She denied acne, male pattern baldness, or any other virilizing features. She was also recently diagnosed with polycythemia; hematological workup was remarkable for elevated testosterone. Her blood work was significant for elevated testosterone levels and hemoglobin, results as follows: total testosterone: 160ng/dl (2-45 ng/dL), free testosterone: 25.4pg/ml (0.1-6.4 pg/ml), sex hormone binding globulin (SHBG): 26 nmol/L (14-73 nmol/L), estradiol: &lt;15 pg/ml (post-menopausal range: &lt;/=31 pg/ml), FSH: 17.3mIU/ml (23.0-116.3mIU/ml), LH: 19.1mIU/L (10.0-54.7 mIU/mL), prolactin: 5.7 ng/mL (2.0-20.0 ng/mL), DHEAS: 78 mcg/dL (12-133 mcg/dL), 8 AM cortisol: 17 mcg/dL (10-20 mcg/dL), ACTH: 11pg/ml (6-50pg/ml), Hb: 16.6g/dl (11.7-15.5 g/dL) and hematocrit: 49.8% (35.0-45.0%). Ultrasound pelvis showed heterogeneous thickened endometrium, small left-sided intramural leiomyoma of the uterus and ovaries were not well identified. MRI pelvis with and without contrast showed a 2.4 cm left uterine fibroid. A simple cyst was noted in the right ovary and two para-ovarian cysts were noted on the left ovary. The overall appearance of both ovaries was similar to a CT scan done a year earlier. She underwent a total hysterectomy with bilateral salpingo-oophorectomy. Surgical pathology was remarkable for cellular fibroma of both ovaries. After surgery, the patient's facial hair significantly improved, and she was noted to have normal testosterone levels (total testosterone: 23, free testosterone: 2.6, SHBG: 50). Her hemoglobin normalized as well, reaching a value of 13 g/dL. Conclusion: Our patient presented with post-menopausal bleeding, hirsutism, polycythemia, and increased testosterone levels. After she underwent total hysterectomy with bilateral salpingo-oopherectomy, her symptoms resolved. Testosterone and hemoglobulin levels returned to normal. Surprisingly, ovarian cellular fibroma on both sides was identified by surgical pathology. Ovarian cellular fibromas are rarely linked to endocrine activity, but with this case, we want to emphasize that its hormonal activity needs further exploration in the future.
Presentation Date: Saturday, June 17, 2023
SAT372 Obstructive Sleep Apnea (OSA) Risk Among Patients With Polycystic Ovary Syndrome (PCOS)
Authors: Christ Jacob P , Shinkai Kanade , Corley Jamie , Pasch Lauri , Cedars Marcelle Ivonne , Huddleston Heather 
Published: October 2023

Abstract
Disclosure: J.P. Christ: None. K. Shinkai: None. J. Corley: None. L. Pasch: None. M.I. Cedars: None. H. Huddleston: None.
Background: Risk of OSA is increased up to seven-fold among patients with PCOS independent of body mass index (BMI). The cause of this increased risk is poorly understood. Likely a bi-directional relationship exists whereby OSA may worsen insulin resistance and hyperandrogenism which in turn may alter airway physiology. Improved understanding of the link between OSA risk and reproductive and metabolic features of PCOS could reveal new strategies to improve a variety of health outcomes for this population. Objective: To assess associations between OSA risk and reproductive and metabolic features among patients with PCOS. Methods: A cross-sectional analysis of patients that underwent a standardized evaluation for PCOS at a single tertiary center from 2017 to 2022 was completed. Patients were eligible for inclusion if they were aged 18-44, met modified Rotterdam criteria for PCOS and had completed a Berlin Questionnaire (BQ) for OSA risk assessment. The BQ contains 10 questions in 3 categories and a high-risk response was recorded if 2 out of 3 categories were positive. All patients underwent standardized anthropometric, ultrasound, endocrine, and metabolic phenotyping. PCOS features were compared between those with and without a high risk BQ. Results: Of the 572 patients screened, 309 patients with PCOS met inclusion criteria. Of these, 104 (33.7%) patients had a high risk BQ. Compared to those without a high risk BQ, those with high-risk BQ had significantly higher waist to hip ratio (WHR) (mean ± standard deviation, 0.9±0.1 vs 0.8±0.1), LDL (113±31.1 vs 103.3±26.5 mg/dL), triglycerides (132±75 vs 89±55 mg/dL), fasting insulin (22±21.2 vs 13.9±16.9 mIU/mL), 2-hour insulin (125±141.2 vs 68.4±108.9 mIU/mL), fasting glucose (100±39 vs 88±20 mg/dL), 2-hour glucose (125.7±56.4 vs 101.7±40 mg/dL), hemoglobin A1c (5.7±1.1 vs 5.2±0.6%), C-reactive protein (6.2±5.7 vs 2.8±3.8 mg/L), ALT (37±50 vs 27±27 U/L), free testosterone (6.5±3.9 vs 5.1±3.5 pg/mL), and lower HDL (49.7±12.4 vs 61.1±16.5 mg/dL) and sex hormone binding globulin (SHBG) (32.3±20.2 vs 53.7±37 nmol/L); p&lt;0.05 for all comparisons. In multivariable regression, controlling for WHR and age, C-reactive protein (β=0.095, p=0.005), SHBG (β=-0.014, p=0.037), HDL (β=-0.025, p=0.032) and Hemoglobin A1c (β=0.421, p=0.073) were found to independently predict presence of high risk BQ. Conclusions: High risk for OSA is a frequent finding among patients with PCOS. Risk for sleep apnea appears to be associated with markers of dysglycemia, dyslipidemia, inflammation, and hyperandrogenism independent of adiposity. Future research is needed to determine if treatment of OSA has metabolic and/or reproductive benefits.
Presentation Date: Saturday, June 17, 2023
FRI173 Investigation Of Cut Off Values For Identifying Cortisol Excess In Adrenal Venous Blood Sampling
Authors: Watanabe Kazuki , Nakai Kazuki , Tsuru Tani Yuya , Hirose Rei , Saito Jun , Nishikawa Tetsuo 
Published: October 2023

Abstract
Disclosure: K. Watanabe: None. K. Nakai: None. Y. Tsurutani: None. R. Hirose: None. J. Saito: None. T. Nishikawa: None.
Objective: Primary aldosteronism (PA) is sometimes accompanied by subclinical Cushing’s syndrome (SCS). However, there is no defined cutoff value for excess cortisol (Cort) in adrenal venous blood sampling (AVS). Meanwhile, some reports have shown AVS usefulness in overt Cushing’s syndrome. This study analyzed AVS parameters to determine the cutoff value of excess Cort in AVS. Methods: The Cort-producing adenoma (CPA) group included patients with adrenal tumors who had a Cort level of ≥ 5 mg/dL after a 1 mg dexamethasone suppression test (DST) and underwent segmental AVS (sAVS) at our hospital from 2009-2020 (n = 75). Patients who underwent AVS on only one side had an adrenocorticotropic hormone (ACTH) level of &gt; 10 pg/mL after 1 mg DST, a midnight Cort level of &lt; 5.0 mg/dL, bilateral cortisol-producing tumors, and/or adrenal cancer, were excluded (n = 26). The control group with normal Cort secretion included patients with Cort level of &lt; 1.8 mg/dL after 1 mg DST who underwent sAVS and whose resected adrenal tumor was negative or weakly positive in 11β-hydroxylase cytochrome P450 staining (n = 45). We compared the various sAVS values between the CPA and control groups. Results: Forty-nine patients in the CPA and 45 in the control groups were analyzed. Compared with the control, the CPA group had a significantly higher maximum Cort level in the tributary veins flowing from the tumor (1220 [860.1-1584.4] vs. 928 [695.5-1350.0], p = 0.016). Meanwhile, Cort levels in the central vein on the tumor side were not significantly different between the two groups (895 [614.7-1312.7] vs. 820 [590.5-1065.0], p = 0.202). The CPA group had a significantly lower minimum Cort level in all tributary veins (117 [73.1-241.5] vs 559 [386.0-794.0], p &lt; 0.001), and Cort level in the central vein on the non-tumor side (176 [93.9-394.0] vs 766 [499.5-1090.0], p &lt; 0.001). The ratio of each value showed that the maximum Cort level in tributary veins flowing from the tumor/minimum Cort level in all tributary veins (9.59 [3.75-21.23] vs 1.65 [1.45-2.06], p &lt; 0.001) and Cort level in the central vein on the tumor side/Cort level in the central vein on the non-tumor side (4.44 [1.95-11.35] vs 1.04 [0.73-1.34], p &lt; 0.001) were significantly higher in the CPA group. The former had the largest area under the curve for the receiver operating characteristic curve in various indices (AUC = 0.948, 81.6% sensitivity and 97.8% specificity when 3.28 was set as the cut-off value). Conclusion: Novel cutoff values were proposed to identify excess cortisol in AVS.
Presentation: Friday, June 16, 2023
SAT379 Potassium Levels in Women with PCOS Using Spironolactone for Long-term
Authors: Oliveira Thais Areias , Marchesan Lucas Bandeira , Spritzer Poli Mara 
Published: October 2023

Abstract
Disclosure: T.A. Oliveira: None. L.B. Marchesan: None. P.M. Spritzer: None.
Introduction. Polycystic Ovary Syndrome (PCOS) is the most common endocrine disorder among women of reproductive age. Spironolactone (SPL) has been used off-label to manage hyperandrogenic manifestations in women with PCOS but the incidence of hyperkalemia in these population is scarce. Materials and Methods. In this retrospective study, we assessed data collected from electronic medical records of women with PCOS that received spironolactone, in addition to other drugs, to manage hyperandrogenic manifestations. Women with PCOS, defined by the Rotterdam criteria, without heart or kidney disease, who were treated with SPL for a minimum of 12 months and had records of serial potassium concentrations, were included for the analyses. Mild hyperkalemia was defined as potassium concentration between 5.1 to 5.5mEq/L, moderate 5.6 to 6,0mEq/L or severe ≥ 6,0mEq/L. Results. Data from 78 women with PCOS with potassium dosages totaling 98 measurements, were analyzed. Mean age was 29.1 ± 9.6 years, BMI 32.2 ± 8.1 kg/m², 9 had Diabetes (9.2%) and 22 (22.4%) pre-diabetes. SPL was used in association with combined oral contraceptives (COCP) in 55 participants (56.1%), progestin only pill (POP) in 21 (21.4%), metformin (MTF) in 35 (35.7%) and ACEi/angiotensin receptor blockers (ARBs) in 15 (15.3%). The median SPL dose was 100mg (50 to 150mg). Ten(12,8%) women had hyperkalemia, 4 of them more than once during follow-up, all classified as mild. The most common minor adverse effects included menstrual irregular bleeding in 8 (8.2%) in 5 using POP irregularly and 3 using COCP, followed by dizziness in 6 (6.1%) and postural hypotension in 3 (3.1%). Only in two cases (2.1%) SPL was discontinued due to poor tolerance, one due to breast pain and the other due to cramps. Conclusion: The present study suggests that women with PCOS, without kidney or heart diseasee, using SPL associated with hormone contraception for managing clinical hyperandrogenism, have a low incidence of hyperkalemia, no life-threatening episodes, well-tolerated minor adverse effects and a low rate of drug discontinuation. Sources of research support: INCT/CNPq and FAPERGS.
Presentation Date: Saturday, June 17, 2023
SAT434 Estradiol Controls GnRH-II Gene Expression In The Hypothalamus And Pituitary Gland Of Female Rhesus Macaques (Macaca Mulatta)
Authors: Lomniczi Alejandro , Luisa Appleman Maria , Urbanski Henryk F 
Published: October 2023

Abstract
Disclosure: A. Lomniczi: None. M. Appleman: None. H.F. Urbanski: None.
It has been known for many years that rhesus macaques express two forms of gonadotropin-releasing hormone (GnRH-I and GnRH-II) in the medial basal hypothalamus (MBH), and that both forms are capable of stimulating the release of luteinizing hormone (LH) in vivo. However, while much has been published about the role of GnRH-I in reproduction, very little is known about the function of GnRH-II. To shed light on this issue, we studied the expression pattern of these two genes in different parts of the monkey hypothalamus, median eminence and pituitary gland. Quantitative PCR (qPCR) analysis revealed that while GnRH-I is preferentially expressed in the Arcuate Nucleus (ARC), Median Eminence (ME), Supraoptic Nucleus (SON) and Suprachiasmatic Nucleus (SCN); GnRH-II was highly expressed in the SON, ARC-ME and Paraventricular Nucleus (PVN), confirming our previously published in situ hybridization studies. Strikingly, GnRH-II mRNA was also detected in the pituitary gland, a site where GnRH-I was not found. We have previously demonstrated that maximum hypothalamic GnRH-II expression occurs around the time of the preovulatory LH surge, when estrogen (E2) levels are maximal, but no significant changes in GnRH-I mRNA levels occur. Here using an ovariectomized (OVX) macaque model subjected to E2 replacement paradigm, designed to mimic the plasma E2 levels observed during the preovulatory estradiol peak, we performed RNAseq and qPCR from the PVN and pituitary gland to identify genes differentially regulated by E2. While GnRH-I mRNA was not affected by E2 treatment in any of the tissues studied, pituitary GnRH-II expression highly correlated with estrogen levels (r&gt;0.8; p&lt;0.01), with over a hundred-fold increase in mRNA expression. Taken together, these data suggest that pituitary GnRH-II (but not GnRH-I) gene expression is induced by a positive feedback action of estradiol. This novel finding raises the possibility that GnRH-II plays a major role in triggering the preovulatory LH surge in primates, not only at the ARC-ME but also at the pituitary level.
Presentation Date: Saturday, June 17, 2023