bluuebunny/crossref_metadata_2025_split huggingface dataset:
SAT368 Severe Hyperandrogenism in a Young Woman with Elevated BMI: A Case Study of The Role of Weight Loss in The Management of PCOS
Authors: Ortega Susel Rodriguez , Bass Ilana R 
Published: October 2023

Abstract
Disclosure: S. Rodriguez Ortega: None. I.R. Bass: None.
Background: Increased adiposity enhances the phenotypic expression and severity of hyperandrogenism in women with Polycystic Ovarian Syndrome (PCOS). Weight loss has been associated with improved endocrine features in women with PCOS and elevated Body Mass Index (BMI). Bariatric surgery can be an effective means of significant weight loss and restoration of the hypothalamic pituitary axis. Case Presentation: A 21-year-old Hispanic nulligravid woman presented with history of oligomenorrhea, weight gain and hirsutism. Her symptoms started after menarche at 15 years old with irregular periods, hair growth on her face and neck, and rapid weight gain. She was evaluated by an endocrinologist and was found to have an elevated total testosterone level by LC/MS on several different occasions: 309ng/dl, 259ng/dl and 229 ng/dl, as well as elevated androstenedione 346 ng/dl (41-262ng/dl). She was treated with metformin and oral contraceptive pill for two years and then referred for second opinion. On our physical exam, she had a BMI of 44.60 kg/ m2, a deep voice, Ferriman Gallwey score of 12 and acanthosis nigricans. OCPs were held for three months for accurate testing and work up revealed total testosterone 164.7 ng/dl (10.0-55.0 ng/dl), sex hormone binding globulin 25.4 nmol/L (24.6-112.0 nmol/L), bioavailable testosterone 84.3ng/dL (51.4%), DHEAs 375 µg/dl (110-431.7 µg/dl), and androstenedione 264 ng/dl (41-262 ng/dl). Other causes of hyperandrogenism such as hyperprolactinemia, hypothyroidism and congenital adrenal hyperplasia were ruled out. MRI pituitary from outside facility was reviewed and was normal. MRI abdomen and pelvis with/without contrast was performed, which demonstrated normal adrenal glands and an 8.1 cm midline pelvic cyst, containing a 0.7 cm enhancing solid nodule. She was referred for surgery for concern for possible virilizing tumor. The cyst was surgically removed and intra-operative ovarian exploration and cytopathology from pelvic washing were negative. She was referred for bariatric surgery and underwent a sleeve gastrectomy. After 6 weeks, she lost 30lbs, BMI improved to 37.1 kg/ m2 and her menses resumed. Repeat labs showed improvement in her androgens: total testosterone 64.8ng/dl, SHBG 104nmol/L, androstenedione 127ng/dl. After 8 months, she lost 110lbs and has dramatic improvement in her hirsutism and clearance of her acanthosis nigricans. Conclusion: Sustained lifestyle changes and weight loss are a mainstay in the treatment of patients with PCOS and obesity. Bariatric surgery results in durable weight loss and restores the normal physiological balance of sex hormones and improves signs and symptoms of hyperandrogenism.
Presentation Date: Saturday, June 17, 2023
SAT369 Rare Cause of Hyperandrogenism and Elevated 17 OH Progesterone Levels - Ovarian Steroid Cell Tumor (NOS)
Authors: Shafi Amtul , Surrey Garnet Meier 
Published: October 2023

Abstract
Disclosure: A. Shafi: None. G. Meier Surrey: None.
Background:There are several causes of hyperandrogenism. We report a rare cause of hyperandrogenism and elevated 17 OH progesterone levels due to ovarian steroid cell tumor
Clinical Case: A 21 yr old female presented to our clinic for evaluation of secondary amenorrhea and hirsutism for 2 years. She also endorsed deepening of voice and possible clitoromegaly. On physical exam she had hirsutism, acne with mild clitoromegaly. Labs were pertinent for normal TSH, Ft4, prolactin, DHEAS, am cortisol 14.85 ug/dl, ACTH 16 pg/ml (6-50), IGF-1 303 ng/ml (830-456), but elevated total and free testosterone 394.5 ng/dl (10-75), 70.5 pg/ml (0.2-5) respectively, elevated 17 OH progesterone 842 ng/dl (23-431 ng/dl depending on the menstrual phase). Due to testosterone &gt;3x ULN, and significant symptoms of hirsutism/hyperandrogenism there was a concern for androgen producing tumor and therefore CT abdomen and Pelvis was obtained which showed “heterogeneously enhancing right adnexal mass measuring 6 x 5.1 x 5.4 cm causing leftward displacement of the uterus and left ovary. Right ovary was not identified and is likely inseparable from the right adnexal mass”. She underwent a laparoscopic Right salpingo oophorectomy with pelvic washings, peritoneal biopsies and omental biopsy. Pathology of ovary showed a steroid cell tumor, NOS. Pt seen 2 months post surgery pt reported that her menstrual cycles had become regular, however she continued to have acne and hirsutism for which she was referred to Dermatology. Post surgery 17 OH progesterone levels had normalized. Conclusion:Steroid cell tumors of the ovary are extremely rare, accounting for only 0.1% of all ovarian tumors. The clinical presentation may take many forms, including abdominal pain, distention, irregular menstrual cycles, and hirsutism. Labs can show elevated 17 OH progesterone levels. Therefore among other etiologies clinicians should also consider Ovarian Steroid cell tumor (NOS) as a possible cause for hypernadorgenism and elevated 17 OH progesterone levels
Presentation Date: Saturday, June 17, 2023
SAT376 Luteinizing Hormone Secretion in Hyperandrogenic Girls Taking Spironolactone or Metformin
Authors: Burt Solorzano Christine Michele , Gilrain Melissa , Kim Su Hee , McCartney Christopher Rolland 
Published: October 2023

Abstract
Disclosure: C.M. Burt Solorzano: None. M. Gilrain: None. S.H. Kim: None. C.R. McCartney: None.
Peri-pubertal hyperandrogenism (HA) typically relates to excess adrenal and/or ovarian androgen production in response to adrenocorticotropin (ACTH) and/or luteinizing hormone (LH), respectively. Spironolactone and metformin are commonly used medications to treat adolescent androgen excess. We examined how end-organ responsiveness and LH pulse patterns are affected by these medications in adolescents with HA. We studied free testosterone (T) levels (including baseline and peaks after ACTH and recombinant human chorionic gonadotropin [r-hCG] stimulation), oral glucose tolerance testing (OGTT), and 12-hr overnight LH secretion (sampled q 10 min) in post-menarcheal girls with HA before and after 3-months of either spironolactone (100 mg BID) or metformin (500 mg BID). Free T was calculated using total T (LC-MS/MS) and sex hormone binding globulin (SHBG).To date, 3 girls (aged 12-18) have been studied using spironolactone and 4 girls (aged 14-17) using metformin. (1 girl was studied twice, once with each medication.) After spironolactone treatment, free T changed by -19% (-58 to +37) (median [range]) unstimulated, by -53% (-62 to -15) after ACTH, and by -54% (-66 to +12) after r-hCG. Peak insulin level during OGTT changed by +28% (+16 to +98). Overnight LH pulse frequency changed by -64% (-89 to -10) and LH mean by -74% (-89 to -17). Two subjects in the spironolactone group demonstrated luteal LH patterns despite serum progesterone concentrations &lt; 0.7 ng/mL. In the metformin group, free T changed by +35% (-32 to +125) unstimulated, by 36% (-54 to +66) after ACTH, and by 21% (-41 to +105) after r-hCG. Peak insulin level during OGTT changed by -47% (-74 to +102). LH pulse frequency changed by +10% (-29 to +22) and LH mean by +1% (-2 to +74). To summarize findings to date, mean LH and LH pulse frequency decreased in all three subjects taking spironolactone, including marked reductions in two subjects who demonstrated luteal LH patterns. While free T levels decreased in some of these girls, this seems unlikely to account for such marked changes in LH secretion. And despite similar decreases in T and also decreases in peak insulin in some girls taking metformin, LH pulse frequency did not change markedly. LH pulse patterns in two girls taking spironolactone suggest a progesterone-like effect on LH pulsatility. Spironolactone can cause irregular uterine bleeding, and canrenone (the major metabolite of spironolactone) binds to uterine progesterone receptors competitively (Fernandez MD, Br J Clin Pharm 1983). However, to our knowledge, this is the first report of LH pulse changes in HA girls using spironolactone. Further studies are needed to confirm this finding.
Presentation Date: Saturday, June 17, 2023
SAT382 Lean Mass and Associated Factors in Women with PCOS with Different Phenotypes
Authors: Fighera Tayane Muniz , dos Santos Betania Rodrigues , Spritzer Poli Mara 
Published: October 2023

Abstract
Disclosure: T.M. Fighera: None. B.R. Santos: None. P.M. Spritzer: None.
Introduction: Obesity, insulin resistance and hyperandrogenism are common findings in women with PCOS. These abnormalities have been associated with muscle mass changes reported in previous studies, with conflicting results comparing women with PCOS versus non-PCOS controls. The aim of the present study was to evaluate clinical and laboratory variables related to lean body mass according to PCOS phenotype. METHODS: In this case-control study, we analyzed 133 women of reproductive age, recruited through public advertisement at the outpatient clinic of a University Hospital. Inclusion criteria were body mass index (BMI) ranging from 18.5 to 39.9 kg/m², age between 17 and 35 years and no intake of drugs known to interfere with hormone levels for at least 3 months before the study. Women with diabetes, thyroid dysfunction, liver or renal disease were excluded. PCOS was defined according to the Rotterdam Consensus. The study protocol was approved by the local Ethics Committee, and written informed consent was obtained from all participants. Blood pressure, BMI, body composition by dual-energy X-ray absorptiometry (DXA), and laboratory measurements for metabolic and hormonal variables were performed in all subjects. Creatinine values were used as an indirect marker of lean mass. RESULTS: Median age was 28 years (23-31), and the median BMI was 27.9kg/m² (24.1-33.7), with higher BMI in women with the AB phenotype of PCOS (n=59) compared to ovulatory (C phenotype) PCOS (n=23) and controls (n=51) (p=0.005). Women with the AB phenotype of PCOS presented higher Ferriman-Gallway score (p&lt;0.001), systolic (p=0.001) and diastolic blood pressure (p=0.002), insulin levels (p=0.006), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) (p=0.008), metabolic syndrome prevalence (p&lt;0.001), testosterone (p=0.008), free androgen index (FAI) (p&lt;0.001), fat mass index (FMI) (0.015), and android-to-gynoid (AG) fat ratio (p=0.036) compared to controls. Appendicular lean mass index (ALMI) was higher in the AB phenotype than controls [7.01 (6.33-8.02) vs 6.69 (5.94-7.09), p= 0.024] and the C phenotype [6.60 (6.16-7.22), p=0.022]. A positive correlation was observed between ALMI and creatinine, even after adjustment to BMI, in women with AB phenotype (rho=0.319, p=0.023), but not with ovulatory PCOS (rho=0.293, p=0.238) or controls (rho=0.277, p=0.097). In a multivariate linear regression model, creatinine, HOMA-IR, and FMI were positively associated with ALMI, explaining 38.4% of the variation in lean mass. CONCLUSIONS: The present results suggest that the higher lean mass observed in women with the AB phenotype of PCOS is associated with hyperinsulinemia and higher fat mass. Sources of research support: INCT/CNPq and FAPERGS
Presentation Date: Saturday, June 17, 2023
SAT384 Is This A Case of Androgen-Secreting Endometrial Cancer in A Postmenopausal Woman?
Authors: Taqi Vian , Rimal Priya , Gilden Janice L 
Published: October 2023

Abstract
Disclosure: V. Taqi: None. P. rimal: None. J.L. Gilden: None.
Background: Hirsutism (HIR) is a common disorder of women of reproductive age, often due to polycystic ovary syndrome (PCOS). During post menopause (PM), there is usually diminishment of androgenizing hormone levels and symptoms associated with PCOS. However, rapidly progressive HIR and symptoms of virilization in PM women should always raise the question of androgen-secreting tumors, whether of ovarian or adrenal origin. Other rare causes include ovarian hyperthecosis and Leydig cell hyperplasia. We present a rare case of hyperandrogenism with endometrial carcinoma, associated with increasing hirsutism and normal ovarian imaging and pathology. Clinical case: A 56-year-old woman G3P3 PM for 2 yrs, with Type 2 Diabetes, obesity, HTN, hypercholesterolemia, IBS, Factor S Leiden, menarche at age 12-13 yrs, and PCOS s/p laser HIR removal, and previous regular menses, was referred to endocrine clinic for increasing HIR with diffuse hair loss for 6 months and suprapubic/abdominal discomfort. She also had prior corneal melanoma treated with radiation and cardiac ablation for arrhythmia. Her paternal grandmother had uterine cancer. Physical Exam: VS BP=121/78; HR=66; BMI=31 Kg/m²: (Ferriman-Gallwey score 16/36) with HIR on face, abdomen, chest and back, but no other virilization or cushingoid signs. Initial labs: elevated total and free testosterone (59 ng/dl, n&lt;45), (9.3 pg/ml, n&lt;6.4) respectively, unconjugated DHEA (55 ng/dL, n 77-85) low DHEA-S (29 mcg/dl, n 35- 430 mcg/dl) 17-OHP (50 ng/dL, repeat 44 (n≤ 45) with normal prolactin (5.4 ng/mL, n 0.7-31.6) ACTH (7 pg/mL, n 0-47), salivary cortisol &lt;0.03 mcg/dL, FSH (50.3 mIU/mL ;n=5.9-72.8), LH (29.7 mIU/ml, n 1.1-52.4), estradiol (21.71 pg/mL (n &lt;11-32.2). CT abdomen-hepatic steatosis, normal adrenals. US- heterogenous mass uterine fundus 1.1 x 1.0 x 1.0 cm with subendometrial calcifications, subcm follicles in ovaries. MRI-hypoechoic 0.7X0.8X0.7 cm uterine lesion, normal ovaries; Endometrial biopsy-disordered proliferative endometrium. Hysteroscopy with biopsy confirmed grade I endometrial adenocarcinoma. A total laparoscopic abdominal hysterectomy with bilateral oophorectomy (TAH/BSO) was performed. Pathology-endometrial carcinoma, endometroid type F1GO stage 1A with positive estrogen and progesterone receptors, normal ovaries. By 3 months postop, the HIR significantly decreased with normalized total and free testosterone levels (14 ng/dl), (1.8 pg/ml). Conclusion: This is a rare case of hyperandrogenism associated with endometrial cancer in a postmenopausal woman causing hirsutism with the resolution of symptoms and normalization of androgen levels following TAH/BSO. Clinicians should be aware to thoroughly evaluate postmenopausal women who develop sudden increasing signs of androgenization, particularly if it is of recent onset, and consider other rare diagnoses.
Presentation Date: Saturday, June 17, 2023
THU570 Isoform Specific Gene Regulation By Progesterone Receptors Drives Expansion Of Breast Cancer Stem Cell Expansion In 3D Cell Culture Models
Authors: Gillis Noelle E , Ha Truong Thu , Lange Carol A 
Published: October 2023

Abstract
Disclosure: N.E. Gillis: None. T.H. Truong: None. C.A. Lange: None.
Exposure to progesterone is a risk factor for breast cancer, and numerous PGR polymorphisms are linked to breast, endometrial, and ovarian cancer. Two progesterone receptor (PR) isoforms are expressed from PGR in breast tissues: full-length PR-B and truncated PR-A. In normal breast epithelia, PR isoforms are equally expressed and mostly function as A:B heterodimers. An imbalance of this ratio, and thus a predominance of homodimers, is frequent in ER+ breast cancer. Luminal A-type estrogen receptor positive (ER+) tumors often exhibit an elevated PR-A:PR-B ratio that predicts resistance to tamoxifen. It has recently been shown that PRs promote endocrine resistance and drive expansion of breast cancer stem-like cell (CSC) populations. However, the isoform-specific molecular mechanisms of PR action in ER+ breast cancers remain undefined. The goal of our current work is to map the progesterone-driven gene expression in CSC cells through transcriptomic profiling of T47D cells grown in spheroid-culture conditions that express exclusively PR-A or PR-B. This transcriptomic data has been integrated with phenotypic studies of T47D and MCF7 cells that express a single isoform of PR. Our data shows PR-A is a regulator of the cell cycle and of senescence, while PR-B mediates cell metabolism and intracellular signaling. We further integrated our cell line data with transcriptomes from patient tumors that have been classified based on their PR-A:PR-B ratio and their response to treatment with anti-progestins. Our results are a first step towards re-defining the role of PRs in gene regulation within the CSC population.
Presentation Date: Thursday, June 15, 2023
THU571 Mechanisms Of Estrogen-induced Skeletal Muscle Fibrosis In An Inguinal Hernia Humanized Aromatase Mouse Model
Authors: Potluri Tanvi , Zhao Hong , Yin Ping , Stulberg Jonah J , Lieber Richard L , Bulun Serdar E 
Published: October 2023

Abstract
Disclosure: T. Potluri: None. H. Zhao: None. P. Yin: None. J.J. Stulberg: None. R.L. Lieber: None. S.E. Bulun: None.
Mechanisms of Estrogen-Induced Skeletal Muscle Fibrosis in an Inguinal Hernia Humanized Aromatase Mouse Model Abdominal skeletal muscle weakening via fibrosis and atrophy leads to inguinal herniation. Despite the high prevalence and morbidity of inguinal herniation, the mechanisms and etiology are largely unknown. We developed a transgenic mouse model with the human aromatase gene (Aromhum), where all male mice develop spontaneous scrotal hernias at puberty. The lower abdominal muscles (LAM) in these mice can synthesize estradiol (E2), which activates the stromal fibroblasts, leading to fibrosis and herniation. Remarkably, the administration of Estrogen Receptor Alpha (ERα) antagonist Fulvestrant to the herniated mice reverses fibrosis and herniation. We use this novel model to uncover mechanisms of E2-induced skeletal muscle fibrosis and its subsequent reversal. Hernia-Associated Fibroblasts (HAFs) were isolated from LAM tissues and cultured under estrogen-replete (10nM E2) and deplete (10nM E2 + 100nM Fulvestrant) conditions. The cells were analyzed using ERα ChIP-seq, ATAC-seq, and RNA-seq to observe genetic, epigenetic, and transcriptomic changes (n = 10-15 mice/group in 3 technical replicates).Via RNA-seq, we identified 853 differentially expressed genes between E2 and E2+Fulvestrant treated fibroblasts. These genes were associated with the extracellular matrix, WNT signaling, TGFβ, and focal adhesions were enriched in our study. We further identified 657 E2-upregulated annotated genes common between ATAC-seq and ChIP-seq. Overall, 58 genes were identified across all three datasets, including known E2-responsive genes such as Pgr, as well as extracellular modulators such as Adamts3, Adamts6, Pcdh7, Ltbp1, Fbln5, and Fbln7. Furthermore, E2-ERα activation also directly induced the expression of other transcription regulators, such as Pbx1, Id2, Hlf, Zfp521, and Zfp618. Together, we identified the core E2-modulated genes in HAFs that lead to skeletal muscle fibrosis and reversal. To validate these findings, we performed RNAscope on human inguinal hernia tissues. We detected PBX1, PIEZO2, NRP2, LTBP1, NCAM1, and ADAMTS6 expression in the herniated fibrotic regions of the samples. In contrast, there is no expression of these genes in corresponding healthy muscle fibers.Using this Aromhum mouse model, we characterized, for the first time, characterize E2 mechanisms in skeletal muscle fibrosis and herniation. In addition, we provide an insight into the specific disease-causing fibroblast populations and markers that can form the source for future therapeutics to treat hernias and other fibrotic disorders.
Presentation Date: Thursday, June 15, 2023
FRI164 The Glucocorticoid Receptor is Required for Efficient Aldosterone-induced Transcription by the Mineralocorticoid Receptor
Authors: Johnson Thomas A , Fettweis Gregory , Wagh Kaustubh , Almeida-Prieto Brian , Hager Gordon L , Alvarez de la Rosa Diego 
Published: October 2023

Abstract
Disclosure: T.A. Johnson: None. G. Fettweis: None. K. Wagh: None. B. Almeida-Prieto: None. G.L. Hager: None. D. Alvarez de la Rosa: None.
The glucocorticoid and mineralocorticoid receptors (GR and MR, respectively) have distinct, yet overlapping physiological and pathophysiological functions. There is evidence in the literature that the two receptors interact both functionally and physically, but the global role of this interdependence is poorly understood (1,2). Here, we analyze the impact of GR co-expression on MR genome-wide chromatin binding and transcriptional responses to aldosterone and glucocorticoids. Our data show that GR co-expression alters MR genome-wide binding in locus- and ligand-specific ways. MR binding to consensus hormone response elements is affected by GR. Additionally, gene responses by MR in the absence of GR are weak and show poor correlation with chromatin binding. In contrast, co-expression of GR greatly potentiates genome-wide MR-mediated transcription, particularly in response to aldosterone. These aldosterone-mediated transcriptional responses do not occur with GR alone. Finally, single molecule tracking of MR in live cells indicates that the presence of GR contributes to productive chromatin binding events. Together, our data indicate that co-expression of GR enables optimal aldosterone-mediated MR transcriptional activity, even in the absence of glucocorticoids.
REFERENCES: (1) Mayumi Nishi et al., J Neuroscience. 2004 May 26; 24(21):4918 - 4927. (2) Liu et al., PNAS. Dec 1995; 92: 12480-12484.
Presentation Date: Friday, June 16, 2023
OR11-06 Biological Activity Of Lumisterol Hydroxymetabolites And Their Mechanism Of Action
Authors: Slominski Andrzej T , Kim Tae-Kang , Podgorska Ewa , Janjetovic Zorica , Stefan Joanna , Ravichandran Senthilkumar , Slominski Radomir M , Song Yuwei , Song Yuhua , Szpotan Justyna , Mobley Alisa A , Raman Chander , Tang Edith K Y , Jetten Anton M , Holick Michael F , Tuckey Robert C 
Published: October 2023

Abstract
Disclosure: A. Slominski: None. T. Kim: None. E. Podgorska: None. Z. Janjetovic: None. J. Stefan: None. S. Ravichandran: None. R.M. Slominski: None. Y. Song: None. Y. Song: None. J. Szpotan: None. A. Mobley: None. C. Raman: None. E. Tang: None. A.M. Jetten: None. M.F. Holick: None. R. Tuckey: None.
While the role of vitamin D3 in body homeostasis is well established, the functions of its photoderivative, lumisterol (L3), are gradually being appreciated. Previously, we reported that L3 can be metabolized by CYP11A1 and CYP27A1 to mono- and dihydroxy-L3. Furthermore, we have shown that 7DHC reductase (DHCR7) does not act on L3 and its metabolites [(OH)nL3]. In the current study, we show the presence of CYP27A1-derived 25(OH)L3, (25R)27(OH)L3 and (25S)27(OH)L3 in human epidermis and serum, and the capability by human keratinocytes to generate them from L3 substrate. Furthermore, these metabolites inhibited keratinocyte proliferation and stimulated cell differentiation. They, together with CYP11A1-derived (OH)nL3 acted as ligands on the human aryl hydrocarbon (AhR), liver X (LXR α and β), and peroxisome proliferator-activated (PPARγ) receptors as demonstrated by functional assays, molecular modeling, and activation of the CYP1A1 and CYP1B1, which are downstream of the AhR. These findings indicate that these hydroxyderivatives can regulate physiological functions by acting on AhR, LXRs and PPARγ receptors and activate respective downstream signaling pathways. Thus, L3 produced in the skin by UVB, can act as a pro-hormone that is metabolized into biologically active metabolites by CYP11A1 and CYP27A1 that can not only regulate skin functions but also other biological functions after their entry into the systemic circulation. These findings open, previously unanticipated, exciting new areas of research on the physiological role of (OH)nL3, and L3 through action on AhR, LXRs and PPARγ receptors.
Presentation: Friday, June 16, 2023