bluuebunny/crossref_metadata_2025_split huggingface dataset:
6626 Fertility considerations in Klinefelter Syndrome complicated by hypogonadotrophic hypogonadism
Authors: Govinna Mauli , Sarlos Stella , Allan Carolyn A , Giri Rinky 
Published: October 2024

Abstract
Disclosure: M. Govinna: None. S. Sarlos: None. C.A. Allan: None. R. Giri: None.
Background: Klinefelter syndrome (KS) remains underdiagnosed with less than 50% of men ever diagnosed and &gt;90% of diagnoses only occurring when fertility is sought. MicroTESE (microscopic testicular sperm extraction) is now successful in 47-69% [1]. Optimal timing of the procedure is uncertain. Case: A 14-year-old male student with a history of renal stones (normal genitourinary tract anatomy) and anxiety presented with a six-day history of new onset headaches and transient visual blurring. MRI scan showed a 2.1cm pituitary lesion with local mass effect and minimal compression of the optic chiasm. Pre-operative pituitary panel: FSH 29.8 IU/L (1.2 - 5.2 IU/L); LH 8.8 IU/L (2.0 - 8.0 IU/L); testosterone 10.9 nmol/L (0.7 - 17.6 nmol/L). Remainder of anterior pituitary function was normal; no AVP deficiency. On examination, Tanner stage P4 G4, testicular volumes 5-6ml (right) and 6-8ml (left) (expected range 15-20ml). Height 175cm (75th centile) and weight 60.1kg (63rd centile). Transsphenoidal resection (TSS) of the pituitary lesion was performed. Intraoperative appearances were suggestive of craniopharyngioma adherent to the pituitary stalk, with stalk transection to achieve complete resection. Post-operatively AVP-deficiency, hypocortisolism and secondary hypothyroidism required replacement therapy. Histopathology was subsequently consistent with Rathke’s cleft cyst. Karyotype testing confirmed 47 XXY genotype (Klinefelter syndrome). Post-TSS FSH and LH levels were 0.7IU/L (1.2 - 5.2 IU/L) and 0.3 IU/L (2.0 - 8.0 IU/L); with testosterone &lt;0.1 nmol/L (0.7 - 17.6 nmol/L), consistent with hypogonadotrophic hypogonadism superimposed on a background of primary hypogonadism. Testosterone replacement therapy was commenced following discussion regarding potential future fertility options. Discussion: This diagnosis of KS highlights the importance of thorough assessment of pubertal development and testicular examination. Small testes with hypergonadotrophic hypogonadism in the context of pituitary pathology should trigger further assessment. Fertility preservation procedures in prepubertal and adolescent boys with KS remain controversial [2]. This patient represents a unique scenario whereby he is LH and FSH deficient post TSS. Whilst prior treatment with hCG does not increase sperm retrieval in non-mosaic KS [3] there may be a role for gonadotrophin therapy prior to undertaking microTESE in our patient. To date, there are no reported cases. References: 1. Sá R et al. Genes 2023, 14, 647. 2. Pook CJ et al. Front Reprod Health. 2021 Aug 3;3:629179.3. Guo F et al. Fertil Steril. 2020 Nov;114(5):997-1005.
Presentation: 6/1/2024
8417 Knowledge Of PCOS and Its Complications In A Population Of Hispanic Women
Authors: Rivera-Rodriguez Y G , Diaz Rios B , Casas Loyola C M , Marin Rodriguez B , Alicea Reyes P A , Romaguera J , Gonzalez-Rodriguez L A 
Published: October 2024

Abstract
Disclosure: Y.G. Rivera-Rodriguez: None. B. Diaz Rios: None. C.M. Casas Loyola: None. B. Marin Rodriguez: None. P.A. Alicea Reyes: None. J. Romaguera: None. L.A. Gonzalez-Rodriguez: Research Investigator; Self; Eli Lilly & Company.
Purpose: Polycystic Ovary Syndrome (PCOS) is a common endocrine disorder affecting women across their lifespan, with metabolic complications that are often overlooked. Studies have revealed an inadequate understanding of PCOS, its complications, and management. There is also limited information about this condition in Hispanic women. The purpose of this study is to assess the knowledge about PCOS and its complications among a sample of Hispanic women living in Puerto Rico. Methods: This is a descriptive cross-sectional study of Hispanic women aged 21-45 years recruited from the General Endocrinology and Gynecology Clinics at the UPR-RCM Clinics. A self-administered questionnaire assessing their knowledge about PCOS, and its complications was given. Patients were classified according to PCOS diagnosis. Results were compared between the groups. Results: A total of 47 women were included in this study. Approximately 45% of participants had a diagnosis of PCOS. Most participants agreed that PCOS involves a set of symptoms associated with hormonal imbalances (94%) and irregular menses (91%). Only 40% of participants considered PCOS a chronic condition without a cure and only 34% acknowledge weight loss as one of the treatments of this condition. Two-thirds of participants didn’t know that PCOS can be diagnosed with blood tests. When assessing their knowledge about complications related to PCOS, we found that only 36% associated PCOS with an increased risk of cardiovascular disease, 56% with obesity and 62% with abnormal blood glucose levels. When comparing the knowledge about their condition in patients with a diagnosis of PCOS, we found increased knowledge about signs and symptoms such as hirsutism, hair loss and weight gain when compared to controls. However, when assessing their knowledge about complications related to PCOS, neither group recognized PCOS as a chronic condition, or associated PCOS with cardiovascular, metabolic complications and/or increased risk of cancer. Conclusion: Our study suggests that there is a lack of general knowledge about PCOS and its long-term complications among a sample of Hispanic women in reproductive years. Most importantly, our data showed that even patients with a diagnosis of PCOS do not understand their condition or comprehend the associated complications. Our study emphasizes the need to develop educational tools and strategies to improve the general population knowledge about this condition and raise awareness about preventable complications and the importance of early treatment.
Presentation: 6/3/2024
8125 Long-term Effects of Gender Affirming Hormone Therapy (GAHT) on Lipid Profile
Authors: Le Guillaume , Pinkson Sheila , Trejo Jonathan , Tripathy Devjit 
Published: October 2024

Abstract
Disclosure: G. Le: None. S. Pinkson: None. J. Trejo: None. D. Tripathy: None.
Long-term Effects of Gender Affirming Hormone Therapy (GAHT) on Lipid Profile There is differential effect of long-term Estrogen and Testosterone therapy on lipid profile. While oral estradiol therapy in post-menopausal women has been associated with increased serum triglyceride and HDL, testosterone therapy in hypogonadal men decreases total cholesterol, LDL and HDL cholesterol. However, the long-term effects of Estrogen and Testosterone on lipid profile in transgender patients are not clear. We conducted a retrospective study to analyze the long-term effects of GAHT in transgender men and women followed in Endocrinology Clinic at Veterans Affairs Hospital. 36 transgender men (age 38 ± 2 years, on IM Testosterone cypionate) and 54 transgender women (age 46 ± 2 years, 36 on E2 tablet, 12 on patch, 6 on IM) were followed for 46 ± 5 months and 61 ± 5 months, respectively. Total cholesterol, triglyceride, HDL, LDL cholesterol, systolic and diastolic blood pressures, and BMI were compared before and after initiation of therapy. As expected, following GAHT, total testosterone was higher (546 ± 48 vs. 35 ± 9 ng/dL, P&lt;0.001) in transgender men; in transgender women, serum E2 was higher (110 ± 9 vs. 26 ± 2 pg/dL, P&lt;0.001) and total testosterone was suppressed (444 ± 29 ng/dL vs. 66 ± 13 ng/dL). In transgender men, after a follow-up period of approximately 4 years, there were no significant changes in lipid profile (total cholesterol 178 ± 8 vs. 175 ± 8 mg/dL, triglyceride 121 ± 4 vs 134 ± 12 mg/dL, HDL 47 ± 2 vs. 44 ± 2 mg/dL, LDL 107 ± 7 vs. 106 ± 8 mg/dL, all p=NS). Similarly in transgender women, no difference in lipid profile (total cholesterol 170 ± 5 vs. 175 ± 4 mg/dL, triglyceride 118 ± 7 vs 140 ± 9 mg/dL, HDL 49 ± 2 vs. 53 ± 3 mg/dL, LDL 99 ± 4 vs. 97 ± 4 mg/dL, all p=NS) was observed after 5 years of GAHT. There were no differences in lipid profile regardless of E2 tablet, patch or IM therapy. In transgender men, there was an increase in diastolic blood pressure (72 ± 3 vs. 76 ± 2 mmHg, P&lt;0.05) while in transgender women there was decrease in systolic blood pressure (124 ± 2 vs. 118 ± 2 mmHg, p&lt;0.005), and slight increase in BMI (28 ± 0.9 vs. 30 ± 1 kg.m2, P&lt;0.005). In conclusion, long-term testosterone therapy in transgender men and estrogen therapy in transgender women was not associated with worsening lipid profile. Estrogen therapy was associated with lower BP in transgender women and testosterone therapy led to higher BP in transgender men.
Presentation: 6/2/2024
7407 Normosmic Idiopathic Hypogonadotropic Hypogonadism in Women: A Case Report and Comprehensive Review
Authors: Bustamante E G , Sulehri M , Patoli I , Karunakaran A 
Published: October 2024

Abstract
Disclosure: E.G. Bustamante: None. M. Sulehri: None. I. Patoli: None. A. Karunakaran: None.
Normosmic Idiopathic Hypogonadotropic Hypogonadism (nIHH) in Women: A Case Report and Literature ReviewIntroduction: IHH is a rare genetic disorder affecting gonadotropic-releasing hormone (GnRH) production and/or action, resulting in diminished sex steroid levels. Characterized by the absence of spontaneous pubertal development. In women, it manifests with normal adrenarche but absent thelarche and menarche. Our case highlight a late diagnosis of IHH in a 34-year-old woman with primary amenorrhea. Case report: A 34 year old lady with a history of primary amenorrhea sought evaluation. At age 16, she underwent assessment for short stature and primary amenorrhea, denying anosmia, headache, visual disturbances. Evaluation revealed bone age concordant with chronological age and normal MRI Brain. Pelvic ultrasound (US) showed small premenarchal uterus and ovaries. She initiated oral contraceptive pills (OCP) and experienced regular menses. Seeking fertility assistance at age 24, a normal Hysterosalpingogram was followed by successful delivery of twins after ovarian stimulation. Post-delivery menses did not resume and OCP was not restarted. Family history revealed a sister with irregular periods requiring OCP.Subsequently workup at age 30 showed Estradiol 22 pg/ml, FSH/LH 4.1/2.3 mUI/mL; normal PRL, TFT, DHEAS, 17OHP. Repeat Pelvic US showed normal uterus, endometrial stripe normal at 0.24 cm and non-visualized ovaries. PCOS testing negative for hyperandrogenism. Progesterone challenge resulted in no withdrawal bleeding. Brain MRI demonstrated a 2.2 x 1.3 mm hypoenhancing ovoid mass in the pars Intermedia of the pituitary gland suggestive of pituitary microadenoma. Pituitary axis hormonal testing was normal. Karyotype revealed 46 XX (normal female). Genetic evaluation identified a pathogenic variant (p.R35C) in GNRH1 gene. Her final diagnosis: nIHH. Discussion HH is diagnosed in 5% of all women with primary amenorrhea and is divided into 2 major categories: Kallmann syndrome and nIHH. The majority of known causes of HH can be attributed to mutations in KAL1, FGFR1, or GNRHR. The p.R35C variant has been associated with autosomal dominant nIHH. Diagnosis involves clinical suspicious, low LH/FSH and sex steroid levels, normal hypothalamic–pituitary imaging, and exclusion of differentials.Treatment goal for female focus on regular breast and uterine development, as well as the capability to conceive. Use of hormonal replacement therapy and/or gonadotropins or pulsatile GnRH for ovarian stimulation are essential. ConclusionWhile IHH predominantly affects men, limited literature explores its manifestation in women and its impact on fertility. The identification of a GNRH1-related nIHH variant highlights the role of genetic testing in specific HH diagnoses. Failure to diagnose in adolescence may compromise women overall well-being
Presentation: 6/1/2024
12540 Epigenetic Subtyping Of Adrenocortical Carcinoma In Archival Material And Implications For Disease Evolution
Authors: Mohan D , Lerario A M , Almeida M Q , Mendonca B B , Latronico A , Fragoso M C , Hammer G D 
Published: October 2024

Abstract
Disclosure: D. Mohan: None. A.M. Lerario: None. M.Q. Almeida: None. B.B. Mendonca: None. A. Latronico: None. M.C. Fragoso: None. G.D. Hammer: None.
Adrenocortical carcinoma (ACC) is a rare cancer of the adrenal cortex, to date cured only by surgery. Pangenomic studies demonstrate that ACC is comprised of three molecular subtypes with distinct clinical outcomes. CIMP-high ACC, the most aggressive molecular subtype, is defined by abnormal epigenetic patterning including inappropriate DNA methylation. CIMP-high status of the primary tumor accounts for 30% of all ACC, but 70% of metastatic relapses. It remains unclear if ACC transitions molecular subtypes, e.g. acquires CIMP-high status, during metastatic dissemination. We and others have demonstrated that G0S2 methylation is a sensitive and specific single-locus biomarker capturing CIMP-high ACC. However, our prior studies utilized frozen tissues, often only available at specialized centers. Here, we measured G0S2 methylation in an expanded cohort of n=73 formalin-fixed paraffin-embedded (FFPE) primary, recurrent, and metastatic ACC samples. We show that G0S2 methylation status is stable in archival FFPE material, concordant with measurement in frozen specimen (Pearson r=0.94, n=28). We identify that, within individual patients, the G0S2 methylation status of the primary is often preserved in the metastasis or recurrence. These data suggest that ACC subtype switching is not required for metastatic evolution. In cases of advanced ACC with accessible lesions amenable to biopsy, epigenetic subtypes can be diagnosed prior to oncologic resection, enabling subtype-specific therapeutic interventions in the neoadjuvant setting.
Presentation: 6/1/2024
12485 Evaluating B7-H3-CAR T Cell Therapy In Preclinical Models Of Pediatric Adrenocortical Tumors
Authors: Modolo Pinto Emilia , Epperly Rebecca , Santiago Teresa , Sheppard Heather , Clay Michael , Morton Christopher , Nguyen Phuong , Zhou Yinmei , Woolard Mary A , O’Reilly Carla , Justice Julie , Akers Walter , Johnson Melissa , Cheng Cheng , Zambetti Gerard , Davidoff Andrew M , Ribeiro Raul , DeRenzo Christopher 
Published: October 2024

Abstract
Disclosure: E.M. Pinto: None. R. Epperly: None. T. Santiago: None. H. Sheppard: None. M. Clay: None. C. Morton: None. P. Nguyen: None. Y. Zhou: None. M.A. Woolard: None. C. O'Reilly: None. J. Justice: None. W. Akers: None. M. Johnson: None. C. Cheng: None. G. Zambetti: None. A.M. Davidoff: None. R. Ribeiro: None. C. DeRenzo: None.
Over the past decade, significant progress has been achieved in understanding the underlying molecular mechanisms driving adrenocortical tumorigenesis, with the identification of several genetic and molecular drivers of this disease. However, a lack of preclinical models has hindered the discovery of new therapeutic treatment modalities, particularly in the pediatric population. In this study we describe the development of three patient-derived xenograft models for pediatric adrenocortical tumors (SJ-ACC3, SJ-ACC4, and SJACT030812_X1), which recapitulate the molecular features and heterogeneity of these rare tumors. All three models were derived from aggressive tumors, harboring TP53 and ATRX variants. We evaluated the efficacy of various chemotherapeutic agents in two models. SJ-ACC3 tumors exhibited sensitivity to cisplatin and topotecan, while SJ-ACC4 demonstrated limited response to all evaluated drugs including cisplatin, doxorubicin, and etoposide. Consistent with adult adrenocortical tumors, we found that most primary pediatric adrenocortical tumors express the tumor associated antigen B7-H3 (CD276), regardless of their molecular subtype. Notably, B7-H3 was highly expressed in two of our models, SJ-ACC4 and SJACT030812_X1, with limited expression in SJ-ACC3. Critically, we demonstrated that B7-H3 CAR T cells exhibited significant antitumor activity in both B7-H3-positive models, clearing tumors in most mice. These findings suggested that CAR T cells therapy targeting B7-H3 might be a promising therapeutic strategy for pediatric patients with high-risk adrenocortical tumors.
Presentation: 6/3/2024
7131 The Morbidity Pattern in Females with 45,X/46,XY Mosaicism
Authors: Stochholm K , Gravholt C H , Berglund A 
Published: October 2024

Abstract
Disclosure: K. Stochholm: None. C.H. Gravholt: None. A. Berglund: None.
Background: Turner syndrome (TS) includes females with 45,X/46,XY mosaicism, a rare variant with a prevalence of 2.1 per 100,000 newborn females. Specific knowledge about their associated health outcomes is limited. Aim: To investigate the morbidity pattern in a national cohort of females with 45,X/46,XY. Methods: Data were retrieved for all females diagnosed with 45,X/46,XY from 1960 to 2018 (n=46) and for 4,377 age-matched females from the general population. Morbidity were investigated using Cox regression analysis on registry data regarding hospital diagnoses, redeemed medication, and surgery codes. Results: 45,X/46,XY was associated an increased overall risk of a hospital diagnosis (Hazard ratio (HR): 1.6, confidence interval (CI): 1.2-2.1). The risk of undergoing surgery was significantly increased before the age of 40 years (HR: 1.6, CI: 1.0-2.5), but not in total (HR: 1.2, CI: 0.8-1.7). The HR of redeeming medication was similar to comparators, HR: 1.2, CI: 0.86-1.66. Dividing hospital diagnoses into 18 chapters according to the International Classification of Diseases, 45,X/46,XY had a significantly increased risk of diagnoses due to endocrine disorders (HR=3.6, CI: 2.3-5.8), disorders of the ear (HR=7.1, CI: 4.5-11.3), disorders of the circulation (HR=2.8, CI: 1.7-4.9), and due to congenital malformations (HR=25.1, CI: 17.5-35.8). Among specific diagnoses with a significantly increased risk were gonadal dysfunction, valve diseases, hypertensive diseases, diseases of arteries and aneurisms. Surgery due to disorders of the heart and greater vessels were significantly increased in total (HR=9.3 CI: 2.2-40.4), as were surgery on the aortic valve (HR=36.9, CI: 3.3-409.2), and on female genitalia (HR=2.1, CI: 1.3-3.4), whereas obstetric surgery was significantly decreased (HR 0.2, CI: 0.0-0.7). In females with 45,X/45,XY, there were no registrations related to gonadoblastoma as neither ovarian surgery nor registrations on cancer of the ovary were present. The HR of redeeming a prescription was significantly decreased in the categories of dermatologicals (HR=0.6, CI: 0.4-0.9), musculoskeletal (HR=0.6, CI: 0.4-0.9), antiparasitics (HR=0.5, CI: 0.2-0.8), and in respiratory system (HR=0.6 CI: 0.4-0.9), and significantly increased in systemic hormones (HR=2.2, CI: 1.4-3.7) and in sex hormones (HR=2.9, CI: 2.0-4.1). Conclusion: 45,X/46,XY in females is associated with an increased morbidity with a skewed pattern, as indicated by an overall increased risk of hospital diagnoses, but a unaffected usage of prescribed medication. Surgical procedures were affected with a pattern as in others with Turner syndrome, with a surprisingly absent registration of procedures linked to gonadoblastoma. This study is most likely curtailed by the limited number of females diagnosed with 45,X/46,XY, however the imperative for systematic follow-up is underlined.
Presentation: 6/1/2024
7975 TLR4 Signaling Modulates Reproductive and Metabolic Outcomes in a Mouse Model of Polycystic Ovary Syndrome
Authors: Wiggins Kiara Dominique , Del Mundo Zena , Ayala Angulo Julio A , Lopez Miranda , Garcia Christopher , Nguyen Christy , De La Torre Jamie-Jean , Saba Angelina , Trinh Davina , Nicholas Dequina 
Published: October 2024

Abstract
Disclosure: K.D. Wiggins: None. Z. Del Mundo: None. J.A. Ayala Angulo: None. M. Lopez: None. C. Garcia: None. C. Nguyen: None. J. De La Torre: None. A. Saba: None. D. Trinh: None. D. Nicholas: None.
Polycystic Ovarian Syndrome (PCOS), characterized by disruptions in both reproductive and metabolic functions, is associated with abnormal immune system activity and chronic inflammation. Although the precise mechanistic drivers of chronic inflammation in PCOS are not fully elucidated, elevated serum levels of lipopolysaccharide (LPS) have been observed. We propose that Toll-like receptor 4 (TLR4) signaling, influenced by dysregulated LPS levels, is a central driver of chronic inflammation affecting both reproductive and metabolic pathways. To investigate this hypothesis, we subcutaneously implanted a nonsteroidal aromatase inhibitor, Letrozole (LET), in pubertal TLR4 knockout mice (TLR4KO) and C57BL/6J (wild type) mice. Our five-week LET treatment revealed that TLR4KO mice successfully entered all phases of the estrous cycle, with normalized Luteinizing Hormone (LH) and increased Follicle Stimulating Hormone (FSH) levels. These findings highlight TLR4's role in shaping cycling patterns and regulating fundamental hormonal pathways vital for reproductive health. Despite the genetic manipulation of the inflammatory pathway leading to a reduction in overall body weight gain, it had no discernible impact on the overall body composition of fat and lean mass. Additionally, our study found that dysregulation of blood glucose levels over time was independent of reduced body weight. TLR4KO mice demonstrated inefficient glucose clearance compared to wild-type mice, hinting at potential increases in insulin resistance, imbalances in adipose tissue inflammation, or possible alterations in the gut microbiota. Our study underscores the significance of disrupting the pro-inflammatory TLR4 pathway in shaping the reproductive and metabolic phenotypes in Letrozole-induced PCOS. The investigation into TLR4 becomes pivotal for comprehending the role of chronic inflammation in PCOS development or progression, offering valuable insights into potential therapeutic targets.
Presentation: 6/2/2024