bluuebunny/crossref_metadata_2025 huggingface dataset:
6805 Impact of Feeding Types on Catch-Up Growth in Early Infancy Among Small-for-Gestational-Age Infants: A Nationwide Korean Study
Authors: Choi Jinjoo , Choe Yunsoo , Yang Seung
Published: October 2024

Disclosure: J. Choi: None. Y. Choe: None. S. Yang: None.

Purpose: The study aimed to compare growth patterns and catch-up growth (CUG) in small-for-gestational-age (SGA) infants up to age four, based on feeding type during the first 4-6 months, using nationwide data. Methods: A total of 42,295 children born SGA (21,917 boys, 52.%) who underwent the first (4-6 month), 2nd (9-12 month), 3rd (18-24 month) and 5th (42-48 month) National Health Screening Program for Infants and Children (NHSPIC) under the National Health Insurance Service from 2007 to 2014 were included. The study population was categorized into two groups based on the primary milk feeding type recorded in the self-reported questionnaire during the first round of NHSPIC: the ”Breastfed”group, and the "Formula-fed" group. Catch-up growth (CUG) was defined as a Height Standard Deviation Score (Ht SDS) of 3rd percentile or above at the 5th NHSPIC visits. We used propensity scores to 1:1 match breastfed and formula-fed group based on sex, birth weight, cesarean section, socioeconomic status, residance. Multivariate logistic regression analysis was performed to evaluate the effect of milk feeding type on CUG at 4 years of age. Results: 49.1% of infants (n = 20,774) were breastfed and 50.9% (n = 21,521) were formula-fed. The median birth weight was 2.7 kg (interquartile range: 2.5-2.9 kg), and 98.7% of the children (n = 41,752) achieved CUG by the 5th NHSPIC round. Following propensity score matching, both groups included 19,308 infants. At four years of age, the breastfed group showed a lower likelihood of achieving CUG compared to the formula-fed group (aOR 0.794, 95% CI 0.665-0.948). During the 1st NHSPIC round, the breastfed group had a significantly lower weight Z-score (mean: -0.05, range: -0.64 to 0.41) than the formula-fed group (mean: 0.14, range: -0.42 to 0.78, p < 0.001). This trend was more pronounced from the 1st to 2nd round, with greater decreases in both weight and height Z-scores for the breastfed group (weight difference: -0.36, range: -0.74 to 0.02; height difference: -0.21, range: -0.62 to 0.20) compared to the formula-fed group (weight difference: -0.17, range: -0.53 to 0.20; height difference: -0.13, range: -0.53 to 0.28, p < 0.001). However, from the 2nd round, the breastfed group demonstrated faster gains in both weight and height (p < 0.001). Conclusion : In a study of Korean SGA infants, those breastfed during the first 4-6 months post-birth had lower CUG rates at four years compared to formula-fed infants. The breastfed group exhibited less weight and height gain, especially between the 1st and 2nd NHSPIC rounds, aligning with the initial phase of solid food introduction. These findings may suggest the need for enhanced nutritional supplementation for breastfed SGA infants. Further research is necessary to explore other factors that may impact growth during this critical developmental period.

Presentation: 6/3/2024
6394 Prevalence of Diabetes Insipidus in Pediatric Patients Who Have Been Declared Dead by Neurologic Criteria
Authors: Larancuent Cesar Esteban , Merilan Valandrea , Leoncio Michael , Lozano Juan M , Totapally Balagangadhar R
Published: October 2024

Disclosure: C.E. Larancuent: None. V. Merilan: None. M. Leoncio: None. J.M. Lozano: None. B.R. Totapally: None.

Introduction: Death by neurological criteria (DNC) or brain death (BD), occurs in individuals who have sustained catastrophic brain injury and are in permanent coma with loss of all brainstem function, coupled with the inability to breathe in the setting of hypercarbia and acidosis. Diabetes insipidus (DI) occurs in many but not all patients with DNC. Several studies indicate varying prevalence rates of DI among pediatric patients with DNC. Objective: Our objective was to determine the prevalence of DI in children who have been declared DNC, and the frequency of DI in these children according to the mechanism of brain injury. Methods: A retrospective analysis of 57 pediatric inpatients 0-21 years subsequently declared BD at Nicklaus Children’s Hospital from January 2013 to June 2023. Data was gathered from the hospital's electronic medical records and the VPS database. The primary exposure is brain death, while the secondary exposure is the mechanism of brain injury. These injuries were categorized into anoxic, traumatic brain injury (TBI), and brain tumors/space-occupying lesions (malignancy). The prevalence of DI was assessed as the primary outcome, and it was compared between three etiologies for brain death using Pearson Chi-square. Due to the study's small sample size, the association between the cause of BD and DI was not adjusted by covariates, such as sex and age. This study was exempted by the IRB. Results: Of the 53 patients declared BD, 47 (88.7%, 95% CI 77.9% to 95.3%) were diagnosed with DI. The prevalence of DI did not change significantly according to the etiology of brain injury leading to BD (84.4%, 100.0%, and 92.3% for anoxic brain injury, TBI, and malignancy, respectively; p = 0.410). The characteristics of children according to the etiology of brain death are presented in Table 1. The characteristics of children according to the development of DI are presented in Table 2. ICU length of stay, the duration to brain death declaration, and eligibility for organ donation varied with the etiology of brain death (Table 1). Conclusions: The prevalence of DI is high in pediatric patients declared BD, and it is not significantly different based on the etiology of brain death. Given this high prevalence, diligent DI management is needed to improve organ donation outcomes.

Presentation: 6/2/2024
8137 Prevalence Of Overweight And Obesity In Dominican Children With Congenital Heart Disease
Authors: Rojas Rodríguez L D , Mateo Pérez M J , López Sención L C , San Martin V T , Grullón A
Published: October 2024

Disclosure: L.D. Rojas Rodríguez: None. M.J. Mateo Pérez: None. L.C. López Sención: None. V.T. San Martin: None. A. Grullón: None.

Background: Overweight and obesity can be detrimental to the health of children with congenital heart disease, potentially leading to or contributing to other chronic medical conditions such as hypertension. This, in turn, may increase the cardiovascular demands of these patients whose lives are already affected by a defective heart anatomy. Objective: To determine the prevalence of overweight and obesity in Dominican children with congenital heart disease. Methods: An observational cross-sectional study was conducted to determine the prevalence of overweight and obesity in children with congenital heart disease attending the Pediatric Cardiology Department at Children's Hospital (Santo Domingo, Dominican Republic), from July to December 2022. The study population was classified into categories of underweight, normal weight, overweight or obesity using the CDC Body Mass Index-for-age growth chart (2022), based on their age, weight, height, and sex. The parents of the patients were interviewed to gather information about their children’s medical history, as well as their diet type and level of physical activity. Diet type was assessed through a questionnaire about daily meals; diets in which processed foods and simple carbohydrates were predominant were categorized as unhealthy, while those with a predominance of proteins and complex carbohydrates were categorized as healthy. Physical activity levels were measured using the Assessment of Physical Activity Level Questionnaire (APALQ). Additionally, blood pressure values were categorized as normal or elevated/high based on the American Academy of Pediatrics Clinical Practice Guidelines for Screening and Management of High Blood Pressure in Children and Adolescents (2017). Results: A total of 84 patients with congenital heart disease were analyzed, with 11.9% (10/84) categorized as having overweight and 23.8% (20/84) categorized as having obesity. Among patients with overweight or obesity, unhealthy eating habits predominated in 66.7% (20/30), while a sedentary level of physical activity was reported in 56.7% (17/30). Additionally, among patients with overweight or obesity, 36.7% (11/30) had elevated/high blood pressure. Conclusion: About one-third of Dominican patients with congenital heart disease were found to have overweight or obesity. Additionally, about one-third of those with excess weight were found to have elevated/high blood pressure. These findings stress the need for urgent implementation of personalized interventions and educational programs focused on fostering healthier lifestyles. The ultimate goal is to reduce cardiovascular risks and improve the overall well-being of children living with congenital heart disease.

Presentation: 6/1/2024
8689 Salivary cortisol and cortisone levels in obese and non-obese Korean children
Authors: Jung M , Kim M , Choi Y , Yoo H W , Lee S , Yoo E G
Published: October 2024

Disclosure: M. Jung: None. M. Kim: None. Y. Choi: None. H. Yoo: None. S. Lee: None. E. Yoo: None.

Purpose: Measurement of salivary cortisol is non-invasive and the level correlates well with that of free cortisol, but data in children are insufficient. We measured salivary cortisol and cortisone levels in obese children and compared with those in non-obese healthy children. Methods: A Total of 84 (45 obese and 39 non-obese) children aged 6 to 12 years were recruited. Children with acute or chronic illness were excluded. Salivary samples were analyzed for cortisol and cortisone using liquid chromatography-tandem mass spectrometry. Serum cortisol levels were measured only in obese children. Results: There was no significant difference in salivary cortisol and cortisone levels between the non-obese and obese children. There was no gender difference in salivary cortisol and cortisone levels. Salivary cortisol correlated to serum cortisol levels in obese children (ρ = 0.428, P = 0.007). Salivary cortisone levels were related with salivary cortisol (ρ = 0.537, P <0.001), and inversely with sampling time range (ρ = -0.282, P= 0.009). There was no significant correlations between salivary cortisol or cortisone values and age or body mass index. Conclusions: There was no significant difference in salivary cortisol and cortisone levels between non-obese and obese children. Salivary cortisol correlated well with serum cortisol in obese children.

Presentation: 6/1/2024
8683 Composite Pheochromocytoma/Paraganglioma-Ganglioneuroma: Biochemical And Radiological Features
Authors: Agarwal Shubham , Dackiw Alan P B , Nwariaku Fiemu , Esteban Mosquera Jorge , Jia Liwei , Grace Roden Mary , Hamidi Oksana
Published: October 2024

Disclosure: S. Agarwal: None. A.P. Dackiw: None. F. Nwariaku: None. J.E. Mosquera: None. L. Jia: None. M.G. Roden: None. O. Hamidi: Advisory Board Member; Self; Corcept Therapeutics.

Introduction: Composite pheochromocytoma/paraganglioma with ganglioneuroma (PHEO-GN or PGL-GN) is a rare tumor consisting of chromaffin cells or ganglia tissue combined with a developmentally related neurogenic tumor. Composite tumors can be present in up to 10% of PHEO and are rare with just over 100 cases reported in published literature. We present a case series of patients with PHEO-GN and PGL-GN seen at our tertiary care center to examine their natural history, clinical, radiological, and biochemical characteristics. Methods: We conducted a retrospective longitudinal follow-up study of consecutive adult patients with histologically-proven PHEO-GN and PGL-GN seen between 2013 and 2023. We collected and summarized data on demographics, laboratory findings, radiological results, and clinical outcomes. Results: The cohort comprised 10 patients (60% women): 8 with PHEO-GN (1 diagnosed on autopsy), 1 with PGL-GN, and 1 with PHEO-ganglioneuroblastoma. The median age at diagnosis was 47 years (interquartile range [IQR], 35-60). Most (80%) tumors were discovered incidentally. The prevalence of a genetic syndrome was 40% and included multiple endocrine neoplasia (MEN) 2A, MEN 4, Neurofibromatosis 1, and hereditary PHEO-PGL syndrome due to succinate dehydrogenase type B gene mutation. Nine patients (90%) had biochemically functional tumors with adrenergic biochemical phenotype in 89% and noradrenergic in 11%. The tumor associated with MEN 4 also had dopamine secretion. The median elevation above the upper normal limit of plasma metanephrine was 7.4 (IQR, 1.6-12), 24-hour urine metanephrine was 7.12 (IQR, 3.7-8.8), plasma normetanephrine was 1.7 (IQR, 1.5-1.9), and 24-hour urine normetanephrine was 2.9 (IQR, 2.4-3.5). The median tumor size at the time of diagnosis was 4.2 cm (IQR, 3.3-5.2). The median pre-contrast HU on CT imaging was 37 HU (IQR, 20-40). The median time to surgical excision from the diagnosis was 2.7 months (IQR, 1.9-4.6). All patients that underwent surgery were alive without recurrence of disease at last follow-up visit with a median follow-up of 14.5 months (IQR, 0.5-18.4). Conclusions We present a series of 10 consecutive patients with composite PHEO-GN and PGL-GN. The prevalence of genetic syndrome (40%) was much higher than previously reported (up to 25% in prior reports). PHEO or PGL component of these tumors is commonly biochemically functional with metanephrine and normetanephrine elevation commonly seen. Metastatic or recurrent disease was not observed in our cohort, suggesting favorable outcomes after surgical resection.

Presentation: 6/2/2024
7780 Silver - Russell Syndrome and Free Insulin-like Growth Factor-1 Measurements
Authors: Oude Engberink R D , van den Bogert V , IJsselstijn L , van den Berg S A , van der Kaay D C
Published: October 2024

Disclosure: R.D. Oude Engberink: None. V. van den Bogert: None. L. IJsselstijn: None. S.A. van den Berg: None. D.C. van der Kaay: None.

Introduction: Silver - Russell syndrome (SRS) is a congenital condition characterized by prenatal and postnatal growth retardation. An underlying genetic cause is identified in approximately 60% of patients clinically diagnosed with SRS. The 2 main genetic alterations are loss of methylation of chromosome 11p15 (11p15 LOM) and maternal uniparental disomy of chromosome 7 (UPD(7)mat). Patients benefit from early and appropriate growth hormone (GH) treatment. However, GH treatment in SRS patients is associated with high levels (> 2 SDS) of immunoreactive Insulin-like Growth Factor-1 (IGF-1). As a result, clinicians often lower the GH dose, resulting in a suboptimal effect on growth, body composition and quality of life. There has been increased interest in measuring free IGF-1 in these conditions. Theoretically, the unbound fraction of IGF - i.e. the fraction that is readily dissociable from IGF binding proteins - is the biologically active fraction. Measurement of free IGF-1 might better reflect IGF-1 bioavailability and may be of benefit in optimizing GH treatment. Objective and methods: We explored levels of free IGF-I versus immunoreactive (total) IGF-1 in 22 SRS patients on GH treatment. Immunoreactive IGF-1 was measured on a routine immunochemistry analyzer (IDS-iSYS) and free IGF-1 was measured manually using a two-site antibody method (AnshLabs). Results: In this group of 22 SRS patients the mean immunoreactive IGF-1 was +1.96 +/- 0.48 SDS and the mean GH dose was 0.84 +/- 0.24 mg/m2/d. Subdividing into SDS categories, 45% of patients had an immunoreactive IGF-1 > 2 SDS. In this subset, 60% of patients had levels of free IGF-1 in the normal range (< 2 SDS). Further stratification into the underlying molecular defect showed that 11p15 LOM was associated with a more pronounced discrepancy between the level of immunoreactive IGF-1 (+2.64 SDS) and free IGF-1 (+0.25 SDS). Conclusion: In the majority of SRS patients on GH treatment, immunoreactive IGF-1 levels exceeded > 2 SDS, whereas free IGF-1 levels were within normal range. Measurement of free IGF-1 could provide clinicians with an additional tool to determine the dose of GH in SRS patients. Ongoing research will reveal the full potential of free IGF-1 measurements in disorders that affect the GH - IGF-1 axis.

Presentation: 6/3/2024
12405 A Severe Case Of Virilization Of Premenopausal Woman Secondary To A Rare Testosterone Producing Sertoli Cell Tumor
Authors: Waheed Sehrish , Vernetti Nicholas John , Nakhle Samer
Published: October 2024

Disclosure: S. Waheed: None. N.J. Vernetti: None. S. Nakhle: None.

Introduction: We present a case of a premenopausal woman with elevated testosterone who was diagnosed with an aggressive Sertoli cell tumor of the ovary. Case Description: A 49-year-old multiparous female presented to the clinic with hirsutism and markedly elevated testosterone levels. Her symptoms started a year before the presentation with diffuse alopecia, acne, and increased muscle mass. Last menstrual periods were 3 years, prior to the presentation.Denies any exposure to testosterone herself or indirectly through family. On physical exam, blood pressure 170/122 coarse features, oily skin, and muscular build. She had terminal hair loss and increased hair growth on face and arms. Laboratory data revealed testosterone levels of 9280 ng/dl (reference range premenopausal 18-55 ng/dl), free testosterone > 50 ng/dl (premenopausal0-4.2 ng/dl), LH <0.3 mIU/mL (2.4-12.6 mIU/mL), FSH <0.3 mIU/mL (3.6-12.5 mIU/mL), 17-OHP 2270 ng/dl (15-70 ng/dl), DHEA-S 71 ug/dl (<229 ug/dl), LDL 128 mg/dl, Creatinine 1.29 and hematocrit 56% (34-44.6%). CT abdomen/pelvis showed 10 cm ovarian mass. She underwent Total Abdominal Hysterectomy-Bilateral Salpingo Oophorectomy (TAH-BSO). After the surgery, her testosterone levels normalized and features of hyperandrogenism resolved. Pathology report revealed sex cord stromal tumor Not otherwise specified (NOS) with cellular atypia and possible aggressive behavior. Discussion: Androgen-producing tumors in women are rare neoplasms that can cause secondary virilizing characteristics. Of patients presenting with symptoms of hyperandrogenism, these tumors are found in ∼0.2% of cases. Androgen-producing tumors can arise from the ovary or the adrenal gland. Those arising from the ovary are rare, accounting for <5% of all ovarian tumors. Few cases of steroid cell tumors, not otherwise specified, have been reported in the literature.Testosterone elevation of more than 2 times upper normal limit increases the suspicion for cancer. In our patient, testosterone was 180 times above the normal range for women and 15 times above the normal range for men. With rapid virilization and significant elevation in testosterone, an androgen producing ovarian tumors should be considered.

Presentation: 6/2/2024
8303 Analysis of Over 2.2 Million Anti-Mullerian Hormone Patient Results Across Lifespan From Birth to Over 80 Years Using a Lab Developed Chemiluminescent Immunoassay
Authors: Cheng Cheng , Alfego David , Chun Kelly Y
Published: October 2024

Disclosure: C. Cheng: None. D. Alfego: None. K.Y. Chun: None.

Introduction: Anti-Mullerian hormone (AMH) is a glycoprotein produced by granulosa cells of the ovarian follicle in females and by Sertoli cells of the testes in males. AMH is best known to correlate with ovarian reserve in females. As such, AMH is among the most frequently ordered tests in reproductive age females. The clinical utility of AMH beyond ovarian reserve assessment, especially in males, pediatric and postmenopausal populations, is less commonly examined. As a national reference laboratory that serves approximately 50% of providers across the country, our large database provides an opportunity to examine the clinical utility of AMH testing in other areas of health besides fertility. Objective: To examine AMH test utilization across lifespan of males and females in the US. Methods: Retrospective AMH tests performed at Labcorp® endocrine specialty lab from year 2012 to 2023 of 2,229,845 female patients and 10,362 male patients have been analyzed. Patients with unspecified sex were excluded. Serum AMH levels from birth to 80 plus years for males vs females were compared. For clinical utility assessments, female results are separated into four age groups: pediatric (age 0-17), adult (age 18-39), perimenopausal (age 40-59), and postmenopausal (age >60), and males into pediatric (age 0-17), adult (age 18-59), and older adult (age >60). ICD-10 codes associated with testing order were reviewed for each subgroup based on age and sex Results: In postmenopausal females, AMH is most frequently ordered for evaluation of ovarian cancer, whereas menstrual disorders and PCOS make up the most frequent clinical entities associated with AMH orders in females <18 years. Fertility testing is the most common ICD-10 associated with AMH orders, particularly in reproductive age and perimenopausal females. The most common ICD-10s associated with AMH in pediatric males include delayed puberty, hypoplasia of penis, and childhood short stature. In the adult and older adult male groups, AMH is surprisingly found to also most commonly associate with fertility testing and hypogonadism, although the clinical significance of post pubertal AMH is less defined. Conclusion: AMH testing has most often been used for female fertility testing, but our data show that significant fraction (10-20%) of AMH testing is used to evaluate and manage other suspected endocrine disorders and malignancies including intersex conditions at birth, pubertal development disorder, polycystic ovarian syndrome, male gonadal disfunction at all ages and granulosa cell tumors. Analysis of our large database underscores a need for clinical study to better define AMH levels that are relevant for non-fertility-related conditions.

Presentation: 6/2/2024
8425 Cancer Risk in Transgender Veterans Undergoing Gender-Affirming Hormone Therapy in a Single Medical Center
Authors: Vanasco Alessandra , Chitnavis Annapurna , Vinales Karyne Lima , Correa Ricardo Rafael
Published: October 2024

Disclosure: A. Vanasco: None. A. Chitnavis: None. K.L. Vinales: None. R.R. Correa: None.

Background: The risk of cancer in the transgender patients while on Gender Affirming Therapy is still a source of safety concern among healthcare professionals. We aimed to assess the cancer incidence and potential risk factors in this population. Methods: An initial cohort of 428 charts within the Phoenix VA Healthcare System from January 1990 through October 2023 were identified using ICD codes consistent with a diagnosis of gender dysphoria. From this initial cohort, we completed a chart review of 94 patients who received GAHT through the endocrinology department. The collected information included type of cancer diagnosis, self-reported GAHT start date if not at the Phoenix VA, and risk factors for cancer (HPV, HIV, smoking history) along with recommended cancer screening, like latest mammogram, pap smear, and colonoscopy. Results: We identified 67 transgender women and 27 transgender men, 53.8± 16.0 and 43.8 years ± 12.6 years-old, with an average of 10 years of GAHT (10.1±7.4 years for estradiol therapy and 10.2±4.4 years for testosterone therapy, range 0.5-44 years of use). Cancer was diagnosed in 18 (27.7%) transgender women, including 8 skin, 3 lung, 2 prostate, 2 tongue, 1 thyroid, 1 musculoskeletal, 1 sinus, 1 bladder cancer. Among our transgender women, 37% were current and 33% were prior smokers. Two (3.0%) were HPV positive and both had cancer diagnoses, while two (3.0%) were HIV positive and neither had a cancer diagnosis. 19 (28.4%) underwent colonoscopies with benign results and 48 (71.6%) were untested. 21 (31.3%) underwent mammograms with benign findings, 1 (1.5%) had a mastectomy and reconstruction, and 45 (67.2%) were untested. Cancer was diagnosed in 3 (10.3%) transgender men, and included 2 skin, 1 breast, 1 cervical cancer. 4 (14.8%) were HPV positive, none of which had cancer. Forty percent of the transgender men were active smokers and an additional 30% were prior smokers. None were HIV positive. 8 (29.6%) underwent colonoscopy, 7 of which were benign and 1 pending results, and 19 (70.1%) were untested. Three (11.1%) underwent mammograms with benign findings, 16 (59.3%) had bilateral mastectomies, and 8 (29.6%) were untested. Eleven (40.7%) had pap smears with 10 benign findings and 1 ASCUS, 11 (40.7%) had hysterectomies, and 5 (18.5%) were untested. Conclusion: Our study sheds light on cancer incidence in transgender veterans undergoing GAHT. Incidence of cancer was higher in transgender women than transgender men, and the leading type of cancer for both groups was of the skin, not considered a GAHT risk. Significant numbers of both transgender men and women did not receive recommended health screenings, highlighting the need for improved education of screening importance.

Presentation: 6/2/2024
8551 Comparability of Free Testosterone Measurements
Authors: Zhou Hui , Sugahara Otoe , Danilenko Uliana , Vesper Hubert W
Published: October 2024

Disclosure: H. Zhou: None. O. Sugahara: None. U. Danilenko: None. H.W. Vesper: None.

Assessment of free testosterone (FT) has been recommended as a biomarker for diagnosis and management of hypogonadism and female hyperandrogenism. Reliable laboratory measurements are essential for properly diagnosing and treating these diseases. FT is currently measured using direct commercial immunoassays, assays using equilibrium dialysis (ED) or other separation techniques, or estimated by calculating free testosterone (cFT) using different formulas based on the levels of total testosterone and sex hormone binding globulin (SHBG). There are concerns about the accuracy and reliability of current methods that may negatively impact correct detection, treatment, and prevention in patient care. CDC’s Clinical Standardization Programs (CDC CSP) has developed an accurate, high throughput method using ED coupled with isotope dilution ultra-high-performance liquid chromatography tandem mass spectrometry (ED-UHPLC-MS/MS). The ED step uses an internationally recognized procedure and is performed in a custom designed dialyzer system that allows maintaining equal ratio of sample-to-buffer volume. The method uses certified pure primary reference material (National Measurement Institute-M914) as calibrator. The method has a limit of detection of 0.6 pg/mL, with an accuracy of ±5%, and precision less than 10% CV. The measurement range is 2 – 2000 pg/mL. The analytical performance of this method as well as other FT methods used in patient care was assessed using single-donor serum samples. The evaluated methods included two commercially available platforms utilizing Chemiluminescence Immunoassay or radioimmunoassay techniques, as well as six laboratory-developed assays using ED-LC-MS/MS. The results of the interlaboratory comparison study will help assessing the current level of agreement among FT assays, to identify potential factors causing differences among assays, and to assist with developing materials to improve the agreement among assays.

Presentation: 6/1/2024
5065 Cyproterone Acetate Versus Spironolactone In Transgender Women Commencing Estradiol: A Randomized Controlled Trial
Authors: Angus Lachlan M , Leemaqz Shalem , Kasielska-Trojan Anna , Mikołajczyk Maksym , Doery James , Zajac Jeffrey D , Cheung Ada S
Published: October 2024

Disclosure: L.M. Angus: Advisory Board Member; Self; Kirin Brewery. Speaker; Self; Kirin Brewery. S. Leemaqz: None. A. Kasielska-Trojan: None. M. Mikołajczyk: None. J. Doery: None. J.D. Zajac: None. A.S. Cheung: None.

Background: Transgender women commonly use cyproterone acetate or spironolactone as anti-androgens with estradiol to assist with feminization. However, the optimal anti-androgen is unclear. We aimed to assess the effect of these anti-androgens on breast development and hypothesized that cyproterone acetate would result in greater breast development than spironolactone due to greater androgen receptor antagonism and suppression of serum total testosterone. Design: Double-blind, randomised controlled trial Methods: Transgender women newly commencing estradiol were randomized to spironolactone 100mg daily or cyproterone acetate 12.5mg daily for six months. The primary outcome was measurement of breast development via breast chest distance with secondary outcomes of estimated breast volume using the BreastIdea Volume Estimator application and serum total testosterone using LCMS. Results: Fifty-five participants were included in per protocol analysis (cyproterone acetate group n=28, spironolactone group n=27). Baseline age, body mass index, breast indices, serum estradiol and serum total testosterone were comparable. At six months, the mean (standard deviation) breast chest distance was 9.2cm (3.0) in the cyproterone group versus 8.3cm (2.7) in the spironolactone group (p=0.27). The mean (SD) estimated breast volume was 190.25 mL (158.60) in the cyproterone acetate group and 157.84mL (112.03) in the spironolactone group (p=0.39) with significant inter-individual variation (range 20.27 - 787.77 mL). The mean (SD) serum total testosterone was 1.48 nmol/L (3.45) in the cyproterone acetate group and 4.29 nmol/L (5.44) in the spironolactone group (p=0.04). Serum estradiol levels were comparable. Use of cyproterone acetate was associated with mild hyperprolactinaemia and spironolactone with an increase in serum urea and creatinine. Conclusions: Choice of anti-androgen should be individualised based on clinician and patient preference, with consideration of associated side effects. Further research is needed to optimise breast development in transgender women.

Presentation: 6/3/2024
7850 Developmental ZNHIT3 expression in mice embryos in Mayer-Rokitansky-Küster-Hauser (MRKH) Syndrome related organs
Authors: Kira Dina , Eroglu Binnur , Hawkins Zoe , Chorich Lynn P , Brakta Soumia , Layman Lawrence C
Published: October 2024

Disclosure: D. Kira: None. B. Eroglu, MS, PhD: None. Z. Hawkins: None. L.P. Chorich: None. S. Brakta: None. L.C. Layman: None.

Introduction: MRKH is a severe form of the Mullerian duct (MD) anomaly where the upper 2/3 of the vagina and the uterus fail to develop. Individuals with MRKH still have normally functioning ovaries and normal chromosomes. MRKH may be isolated Mullerian aplasia (type 1) or associated with renal, skeletal, cardiac, and/or auditory dysfunction (type 2). The etiology of MRKH syndrome remains unknown for most probands, although a genetic contribution is likely. Most evidence suggests autosomal dominant inheritance with incomplete penetrance. WNT4 and HNF1B pathogenic variants have been identified in some MRKH individuals. Recently, our lab identified heterozygous (HTZ) ZNHIT3 loss of function variants in persons with MRKH, Both variants predict functional changes in the ZNHIT3 C-terminus and impair protein expression in vitro. Previously, other investigators found biallelic variants in the N-terminus of ZNHIT3 in individuals with PEHO syndrome, a severe autosomal recessive neurodevelopmental disorder characterized by extreme cerebellar atrophy. We are currently characterizing a novel Znhit3 knockout (KO) mouse model, in which homozygous KO mice exhibit embryonic lethality. We have demonstrated ZNHIT3 RNA expression in the human uterus, heart, kidney, and skeleton, but developmental expression of ZNHIT3 in wild type (WT) animals has not been studied. In the WT mouse embryo, the kidney forms between E8.0 and E11, while the MDs form through invagination of epithelium ∼E11.5 and extend along the Wolffian duct until reaching the cloaca at ∼E13.5. Hypothesis: We hypothesize that ZNHIT3 is involved in MD development and expressed in the urogenital system and MRKH-related organs during embryonic development of WT mice. Method: Timed mating of WT mice produced embryos for analysis. Embryos were dissected out at E11.5, 12.5 and 13.5, fixed in 4% PFA, embedded in paraffin, and sectioned sagittally at 5mm thickness. H&E staining was done to identify sections showing kidney, genital tubercle, skeleton and cerebellum. Immunohistochemistry was also done using a ZNHIT3 antirabbit antibody and DAPI as nuclear counter stain. Imaging was performed using the Keyence fluorescence microscope (BZ-X800) at 10x and 40x magnification. Results: At all 3 time points, ZNHIT3 protein expression was observed in the developing urogenital organs including kidneys and bipotential gonads, as well as in vertebral bones and cerebellum. Heart protein expression studies are ongoing. Conclusion: ZNHIT3 protein expression is seen as early as E11.5 and is present in MRKH-related organs, suggesting it may play a role in the development of urogenital and MRKH-related organs. These findings provide the basis to compare expression in the Znhit3 KO mouse, a mouse model for MRKH.

Presentation: 6/2/2024
7275 Diverse Reasons for Discontinuing Gender Affirming Hormone Therapy
Authors: Jain A , Irwig M S
Published: October 2024

Disclosure: A. Jain: None. M.S. Irwig: None.

Many Transgender and Gender Diverse (TGD) individuals take Gender Affirming Hormone Therapy (GAHT). A study that included 264 adults [67% assigned male at birth (AMAB)] in Georgia found that 2% (n=5) discontinued GAHT over a follow-up period of 64 months. Reasons identified were change in gender identity (n=2), financial barriers (n=2) and venous thrombosis (n=1). Discontinuation was temporary for 2 and permanent for 2. Here we describe the reasons why four TGD individuals discontinued GAHT. Case Descriptions: Patient 1, AMAB, came out as gay as a teenager. In his mid 30s he became unhappy which he attributed to a conflict between religion and his sexual orientation and failed relationships. He thought that changing his sex would solve his problems. He took injectable estrogen for 3-4 years. He subsequently underwent multiple gender-affirmation surgeries including facial feminization surgery, breast implants, an orchiectomy and vaginoplasty. Immediately following the breast implant surgery he had regrets and wanted them removed. He also regretted the vaginoplasty. He stopped estrogen following the bottom surgery. In his 40s he stated that he would like to detransition as he sees himself "as a fake" when looking in the mirror. Patient 2 was assigned female at birth. Puberty was associated with discomfort from having a large chest. In his late 20s he began injectable testosterone which he took for three years. He then decided to take a two year break as he was frustrated that he had not achieved the desired results and because he was still not able to pass as a man. He resumed testosterone two years ago and underwent top surgery. Patient 3, AMAB, knew from a young age that he was transgender. He took estrogen and an antiandrogen for > 5 years and underwent an orchiectomy and vaginoplasty. He was pleased with the results from the GAHT and surgeries. He presented as a woman for many years. A few years ago, however, he awoke one day with the thought that God wanted him to be a man. He decided to detransition and presented to the endocrinology clinic to start testosterone therapy. Patient 4, AMAB, began GAHT in her late 30s. She discontinued GAHT 4 years later due to lack of results (feminization, larger breasts, wider hips and a more curvy figure). She presented to the endocrinology clinic 2 years later, wanting to resume GAHT. Conclusion: In addition to the reasons identified by Gupta et al for discontinuation of GAHT, we also identified unrealistic expectations, not achieving the desired results and perceived conflict between religion and gender identity. Endocrinologists should be aware of the possibility of discontinuation of GAHT and know how to manage any potential complications such as hypogonadism that may arise. Reference: Gupta P et al. J Clin Endocrinol Metab. 2023.

Presentation: 6/2/2024
7472 Estrogen Monotherapy for Testosterone Suppression in Gender Diverse Patients
Authors: Zhou C , Jones Q , Kokosa S , Kelley C
Published: October 2024

Disclosure: C. Zhou: None. Q. Jones: None. S. Kokosa: None. C. Kelley: None.

Background: For gender diverse individuals assigned male at birth (AMAB), gender-affirming hormone therapy consists of estrogen in combination with anti-androgen medications. Exogenous estrogen use results in the development of feminine secondary sex characteristics while indirectly decreasing testosterone. Anti-androgens such as spironolactone, leuprolide, finasteride, or dutasteride work to further suppress testosterone with successful suppression levels <50ng/dL. However, use of these agents increases the risk of adverse side effects like hyperkalemia, polyuria, and orthostatic hypotension, thus is not suitable for everyone. Anecdotally, estrogen monotherapy has been sufficient in reducing testosterone levels to goal in some patients, however at this time there are no known studies which evaluate estrogen monotherapy and suppression of testosterone. The purpose of this study is to retrospectively review estrogen formulations and dosages in patients who have adequate testosterone suppression in the absence of anti-androgen medications. Methods: The study was a retrospective chart review of adult patients ages 18- 84.99 AMAB receiving gender-affirming estrogen between 9/2020 and 12/2023 seen within an endocrine clinic at a single academic institution. Patients younger than 18, those receiving anti-androgen medications, and those with history of orchiectomy were excluded from the study. Charts were reviewed for estrogen formulations and dosages and total serum testosterone levels. Retrospective chart review will continue with additional data expected in 2024. Results: Ten patients between the ages of 19-81 met the inclusion criteria. Of these, 7 patients identified as transfeminine and 3 identified as nonbinary. The 3 patients who identified as non-binary were not included in analysis as their treatment goals may not align with full feminization or testosterone suppression (total serum testosterone <50ng/dL). Testosterone suppression from estrogen monotherapy was achieved in 100% (n=7) of the transfeminine patients when serum estradiol was >100pg/mL. In those who achieved testosterone suppression, 5 used injectable formulations (estradiol valerate 4-6mg weekly) and 2 used transdermal patches (range of estradiol from 0.2mg twice weekly to 0.3mg three times weekly). Conclusions: Estrogen monotherapy may be effective in suppressing testosterone without the need for anti-androgen medications. So far, this was noted most commonly with use of injectable estrogen formulations. A limitation of the study is the small sample size, however ongoing data collection is anticipated. Additional research evaluating estrogen monotherapy and testosterone suppression is needed and has potentially significant implications for simplified treatment protocols for transfeminine patients.

Presentation: 6/2/2024
7745 Hirsutism in young girls, Beyond PCOS
Authors: Mishra Ipsita , Baliarsinha A K
Published: October 2024

Disclosure: I. Mishra: None. A. Baliarsinha: None.

Hirsutism is excessive terminal hair that appears in a male pattern in women.Though obesity,insulin resistance and PCOS are common cause of hirsutism in young girls,suspicion of other etiologies must be made on a background of overlapping features.We describe 3 cases of young females presenting with hirsutism with varied etiologies. Case 1.16 year 11months old female presented with oligomenorrhea -3years,excessive hair growth over face -2 years.On examination,BMI was 25.2 kg/m2,Grade 2 acanthosis,A3P5B5,modified FG- 16/36,clitoral length-1.3cm and clitoral index - 70 mm2.Biochemical evaluation revealed normal thyroid function tests,s.prolactin- 23.65 ng/ml,ONDST- 1.2 mcg/dl,LH - 1.49 IU/ml,FSH- 7.44IU/ml,serum testosterone- 70ng/dl,17OHP- 7.03 ng/ml,DHEAS- 553mcg/dl and post synacthen 17OHP- 36.89 ng/ml respectively. USG abdomen & pelvis was normal.HOMA-IR was 4.1. Diagnosis was LOCAH Case 2.19 year old female presented with hair growth in androgen dependent areas-5years, regular predictable menstrual cycles and was treated as a case of PCOS for 5 years with no changes in hair growth pattern.She was off therapy since 1 year prior presenting to us.On examination,BMI was 24 kg/m2,acanthosis absent,A3P5B5,modified FG- 18/36, clitoral length- 6 mm,clitoral index - 25mm2.Biochemical evaluation revealed normal thyroid function tests,s.prolactin- 22.9 ng/ml,ONDST- 0.508 mcg/dl,LH - 5.98 IU/ml,FSH- 5.29 IU/ml, serum testosterone- 23.4 ng/dl,17OHP- 1.01 ng/ml and DHEAS- 298 mcg/dl respectivelyUSG Abdomen & pelvis;RO - 5.7cc,LO - 5.6 cc with B/L PCOM.Review TVS was normal.In view of discordant results DHT and luteal phase serum progesterone were done which were 80.5 pg/ml and 2.1ng/ml respectively.HOMA IR was 1.9.Diagnosis was IDIOPATHIC HIRSUTISM. Case 3.12 year old female child presented with excessive hair growth over face,chest,back and abdomen- 1yr,hoarseness of voice - 1 yr,onset of breast enlargement apprx 8 to 9yrs with non-attainment of menarche.On examination BMI was 30 kg/m2,Grade 3 acanthosis, A3P5B3,modified FG- 15/36,clitoral length- 2.8 cm & clitoral index - 120 mm2. Biochemical evaluation revealed normal thyroid function tests,LH - 15.3 IU/ml,FSH- 6 IU/ml,s.prolactin- 11.2 ng/ml,ONDST- 0.38 mcg/dl,DHEAS- 161 mcg/dl,serum testosterone- 140 ng/dl,17OHP- 3.9 ng/ml and post synacthen 17OHP- 4.10 ng/ml respectively.USG abdomen-s/o PCOS with normal adrenals. In view of discordant results short DAST was done which was Testosterone(ng/dl)baseline-125;4hr-91.1, DHEAS (mcg/dl) baseline-180;4hr-188 cortisol (mcg/dl) baseline-7.04;4hr-0.95.HOMA-IR was 5.4. Diagnosis was PCOS(OVARIAN THECOSIS).Varied presentations of hyperandrogenic disorders occurs in young females.A need to revise the diagnosis must be made if no response is obtained with initial drug regimes.

Presentation: 6/3/2024
7838 Improvement of Cognition and Memory Scores in Transgender Individuals Within One Year of Initiating Gender-Affirming Hormone Therapy
Authors: Godar Cassandra M , De La Torre Sebastian C , Bonsu Osei , Shakir Mohamed K M , Hoang Thanh D
Published: October 2024

Disclosure: C.M. Godar: None. S.C. De La Torre: None. O. Bonsu: None. M.K. Shakir: None. T.D. Hoang: None.

Introduction: The use of gender-affirming hormone therapy (GAHT) in transgender individuals is known to provide many beneficial health effects to reduce gender dysphoria, reduce depressive symptoms, and increase overall quality of life. Cognitive function and memory ability are known to be influenced by sex hormone levels in studies of hormone replacement therapy in post-menopausal women, but studies of GAHT’s effects on cognition and memory in transgender patients have been scarcely reported. We discuss a study of cognitive testing in transgender individuals before and after 12 months of gender-affirming feminizing or masculinizing hormone therapy using a validated cognitive assessment tool. Methods: A prospective study of 32 transgender patients aged 18-45 years was approved by IRB at an academic medical center. The Wechsler Memory Scale 4th edition (WMS®-IV, Pearson) was administered to 19 transgender females and 13 transgender males prior to initiation of GAHT and again after one year of GAHT use. Mean scores were analyzed and reported for five categories of cognitive and memory function: auditory memory (AMI), visual memory (VMI), visual working memory (VWMI), immediate memory (IMI), and delayed memory (DMI). Mean scores for baseline and 12-month data were analyzed for total population and male and female subgroups. Results: Baseline mean WMS-IV values for the total study population were: AMI 105 points, VMI 78 points, VWMI 107 points, IMI 88 points, DMI 91 points. Mean values after 12 months of GAHT were: AMI 120 points, VMI 81 points, VWMI 110 points, IMI 99 points, DMI 102 points. Mean percent change from baseline to 12 months was as follows: AMI 13.4%, VMI 8.9%, VWMI 2.6%, IMI 12.8%, DMI 13%. Similar patterns were noted for both gender subgroups. Discussion: It is well-known that transgender individuals are subject to higher rates of depression, anxiety, and suicidality compared to the general population. Decreased cognitive function and memory are known effects of untreated depression. Our study demonstrated that treatment of gender dysphoria with GAHT provided a tangible cognitive and memory benefit. The long-term impact of GAHT on cognition and memory is not known and deserves additional study. Limitations of this study included the absence of a cis-gender control group and inability to stratify data based on age, which may provide additional significance.

Presentation: 6/2/2024
7955 Increased occurrence of psychiatric disorders and use of psychiatric-related medication in patients with congenital adrenal hyperplasia
Authors: Lind-Holst Marie , Hansen Dorte , Main Katharina Maria , Juul Anders , Andersen Marianne , Dunø Morten , Rasmussen Åse K , Jørgensen Niels , Gravholt Claus Hojbjerg , Berglund Agnethe
Published: October 2024

Disclosure: M. Lind-Holst: None. D. Hansen: None. K.M. Main: None. A. Juul: None. M. Andersen: None. M. Dunø: None. Å.K. Rasmussen: None. N. Jørgensen: None. C.H. Gravholt: None. A. Berglund: None.

Background: Clinical studies on psychiatric morbidity, quality of life and cognition in patients with congenital adrenal hyperplasia (CAH) imply impaired mental health. Epidemiological studies on psychiatric morbidity in CAH are, however, scarce. Methods: A registry study of hospital diagnoses and prescribed medication related to psychiatric disorders in a national cohort of patients (n=462) diagnosed with CAH from 1943 to 2018 compared to 100 randomly selected sex- and age-matched controls (n=44,527) from the general population. Psychiatric hospital diagnoses were available for in-patient contacts from 1968 and out-patient contacts from 1994. Medication data were available from 1995. Outcomes: CAH was associated with an increased risk of hospital contacts related to any psychiatric diagnosis (incidence rate ratio (IRR)=2.73, 95% CI 1.85-4.04), and this applied to both males (IRR=2.48, 95% CI 1.57-3.91) and females (IRR=3.20, 95% CI 1.58-6.50). Psychiatric disorders due to psychoactive substance use were more common among CAH males (IRR=3.55, 95% CI 1.58-7.96) and females (IRR=3.81, 95% CI 1.71-8.48). Males with CAH also had an increased risk of suicidal behaviour (IRR=10.66, 95% CI 3.74-30.42). By the age of 30 years, 23% of CAH females and 21% of CAH males had at least one diagnosis related to a psychiatric disorder while this was the case in 14% of female controls and 15% of male controls. Stratifying by sex and CAH phenotype there were important differences among groups. Prescription of medication related to psychiatric disorders was increased for CAH overall (HR=1.73, 95% CI 1.48-2.03) and males (HR=1.80, 95% CI 1.35-2.38) and females (HR=1.70, 95% CI1.36-2.38), separately. Age at the first prescription of any psychiatry-related medication was significantly earlier for patients than for controls (HR males=1.67, 95% CI 1.2-2.3; HR females=1.48, 95% CI 1.2-1.8). Thirty-five per cent (157/448) of CAH patients and 24% of controls had at least one prescription related to a psychiatric disorder within the study period. Interpretation: An increased risk of psychiatric morbidity, psychoactive substance use and use of medication related to poor mental health was seen in both males and females with CAH. The risk of suicidal behaviour was increased for patients with CAH, yet only significantly in CAH males. The study underlines the need for more attention and extension of psychological care and support for patients with CAH.

Presentation: 6/1/2024