Testosterone Research Articles

8462 Synergistic Outcomes Of hCG And GLP1-RA Combination Therapy: Improved Body Composition And Carbohydrate Metabolism

Abstract Disclosure: F. Comite: None. K. O'Malley: None. Objective: Precision medicine prevents and reverses diseases of aging by way of systematic analysis of body composition and extensive blood biomarkers. Andropause, the age-related reduction of free testosterone (FT) in males, elicits symptoms primarily of muscle loss, decreased libido, and diminished energy. Exogenous testosterone therapy (TTx) subsequently increases lean body mass (LBM) and improves both libido and energy levels in affected males. More recently, stimulation of endogenous testosterone from the testes, human Chorionic Gonadotropin (hCG) has emerged as a compelling physiologic alternative to TTx. Common comorbidities to andropause are DMII and/or obesity. Recent literature surrounds the use of GLP-1 receptor agonists to improve insulin sensitivity in these disorders of carbohydrate metabolism. A primary benefit secondary to GLP-1 use is reduction of fat mass; however, concerns of this monotherapy surround loss of muscle.[1] Remarkably, when treated adjunctly with GLP-1s, hCG therapy significantly mitigates muscle loss while maintaining optimal carbohydrate biomarkers. The efficacy and benefits of hormonal optimization through hCG therapy simultaneous to GLP-1 intervention were investigated. Methods: In this retrospective analysis, a cohort of 20 males ≥30 years of age were reviewed at baseline timepoints and 18 months post treatment-initiation. Participants underwent biweekly hCG and weekly GLP-1 subcutaneous injections. Exclusion criteria restricted use of alternative GLP-1/GIP combination medication. Paired T-Tests were used to determine a relationship between LBM, FT, percent body fat (PBF), fasting glucose (FG), fasting insulin (FI), and HbA1c at each timepoint. Results: Body composition analysis as shown via bioelectrical impedance proved baseline PBF (mean=24.60) significantly reduced post-treatment (p<0.05, mean=18.08) for all participants. In addition, relevant carbohydrate metabolic biomarkers FG, FI, and HbA1c provided significant reductions (p<0.05). Initial FT (mean=67.76) and LBM (mean=150.36) increased significantly at follow-up (p<0.05) with values of 167.55 and 154.91, respectively. Discussion: Using metrics of precision medicine, our interpretation reveals a promising combination therapy for males experiencing andropause. The novel use of hCG to optimize FT levels enhances muscle, while simultaneously, fat loss and reversal of harmful carbohydrate metabolic markers resultant from GLP-1 therapy are achieved. Muscle loss due to overall weight loss is thus ameliorated. Our findings merit further investigation of the magnitude of downstream improvements, particularly in energy and libido.

7874 Management Of “Hyperandrogenism” Confounded By Dermatology Biotin Prescriptions

Abstract Disclosure: S.S. Sundar: None. S. Shankar: None. M.S. Vaishnav: None. L. Lekkala: None. S. Sathyanarayana: None. C. Siddlingappa: None. K. M: None. T.-. Kamala: None. R.B. V: None. V. Nath: None. M.D. Chitra: None. P. Ravikumar: None. Introduction: Immunoassay interferences include: Cross-reactions, heterophile antibodies, biotin and anti-analyte antibodies, with positive or negative bias, leading to difficulties in clinical decision-making (confounding diagnosis, unnecessary investigations or inappropriate treatments). The interfering substance may be exogenous (e.g., drug or substance absorbed by patient) or endogenous (e.g., antibodies produced by patient). Clinical Case 2023 Dec 1 Dermatology management for hyperandrogenism 28-year-old female evaluated for acne 3 years (increased 4 months), hair fall 6 months and hirsutism 3 years (threading) Total Testosterone 443 ng/dL (10-55) CLIA Free Testosterone 8.9 pg/mL (0.1-6.4) ELISA DHEAS 209 µg/dL (35-430) CLIA S Cortisol 8 am 6.9 µg/dL (2.6-10.5) CLIA LH 4.2 mIU/mL (1.9-12.5); FSH 5.3 mIU/mL (3.0-8.0) T3 133 ng/dL (80-200); T4 8.5 ug/dL (4.8-12.7), TSH 3.78 µIU/mL (0.5-5.3) HbA1c 5.0%; Glucose fasting 81 mg/dL; Insulin fasting 39.4 mU/L (3-25); HOMA-IR 5.2; HOMA%B 380; HOMA%S 19.2; T3 133 ng/dL (80-200) 2023 Dec 14 Endocrinology for “scaringly” very high testosterone levels Menstrual history: Menarche 11 years; Cycles regular. Unmarried Family history: Diabetes++; Hirsutism+; Infertility- Physical exam: Height 159 cm; Weight 55 kg; BMI 21.8 kg/m2; Ferriman Gallwey score 11; Pulse 75; BP 79/62; Thyroid: Grade 0. In view of total testosterone levels in “neoplastic androgen excess” range, further endocrinology evaluations (multiple labs and assays) were carried out. However, discordance between the mild clinical versus severe biochemical hyperandrogenism was noted. Review of the dermatology prescription indicated that patient had consumed only one 10 mg tablet of biotin 36 hours before the earlier blood draw obtained by dermatologist. Total Testosterone 22.3 and 33.8 ng/dL (6-82) ECLIA; 19.7 (15-70) LCMS Free Testosterone 0.69 pg/mL (< 2.85) (ELISA) DHEAS 101 µg/dL (45-380) LCMS Androstenedione 104 ng/dL (75-205) LCMS 17OH Progesterone 0.89 ng/mL (0.16-2.05) EIA; 0.40 (0.35-2.9) LCMS S Cortisol 5.92 ug/dl (6-18) ECLIA; 5.45 (5-23) LCMS FSH 2.74; LH 6.07; Prolactin 20.1 ng/mL (4.7-23.3) T3 114 ng/dL; T4 7.2 µg/dL; TSH 1.29 Diagnosis Falsely elevated total testosterone (and free testosterone) levels due to biotin immunoassay interference. Clinical Lessons: Very limited studies exist confirming the exact clinical indications for biotin (eg: improvement of hair quality or quantity, or nail growth). FDA warning highlights biotin’s interference (false elevations or reductions) with immunoassays relying on biotin-streptavidin technology. Physicians must ask patients about supplement usage, and discontinue biotin for 8 hours for patients taking 10 mg/day, 3 days for 100-300 mg/day, 7 days for children taking 2 and 15 mg/kg/daily, and inform laboratory if diagnostic test was performed while taking biotin. Presentation: 6/2/2024

5116 Postmenopausal Hyperandrogenism due to Rare Ovarian Tumor

Abstract Disclosure: M. Salim: None. S. Dasaraju: None. Y. Lee: None. S. Afzal: None. B.K. Erickson: None. M.A. Khalifa: None. L.A. Burmeister: None. Background: Hyperandrogenism in postmenopausal women may arise from either ovarian or adrenal source and can pose challenging diagnostic dilemma. Clinical Case: A 66-year-old multigravida, post-menopausal woman presented with a 3-month history of worsening alopecia. Her past medical history included diabetes mellitus type 2 and breast cancer. Menarche was at age 12. There was no history of infertility. Menopause was in her 40’s. She had been shaving her upper lip and chin hair every 3 days for the past 10 years. Scalp hair loss had accelerated in the last 3 months, with loss of the bangs. Physical exam was significant for body mass index 34, deep voice, and clitoromegaly. Laboratory tests showed testosterone 160 ng/dL, (8-60 ng/dL), free testosterone 3.37 ng/dL (0.06-0.38 ng/dL), androstenedione 2.196 ng/mL (0.13-0.82 ng/mL), sex hormone binding globulin (SHBG) 31 nmol/L (30-135 nmol/L), dehydroepiandrosterone-sulfate (DHEAS) 86 ug/dL (13-130 ug/dL), 17-hydroxy progesterone 96 ng/dL (<51 ng/dL), inhibin A 1.1 pg/mL (<6.9 pg/mL), inhibin B <10 pg/mL (<16 pg/mL), adrenocorticotropic hormone 38 pg/mL (<47 pg/mL), and cortisol 12.2 ug/dL (4-22 ug/dL). Response to 1 mg overnight dexamethasone suppression test demonstrated persistently elevated testosterone (160 ng/dL), and incomplete suppression of androstenedione (0.827 ng/mL) and cortisol (2.4 ug/dL). Computerized tomography (CT) scan showed a left adrenal nodule (12 mm, 5 Hounsfield units, stable compared to imaging 2 years prior) and unremarkable appearance of the ovaries. Pelvic ultrasound did not show ovarian tumor on the right and left ovary was not seen. Adrenal and ovarian vein sampling suggested the ovaries as the source of the testosterone. Given the ovarian vein sampling results, a multidisciplinary discussion between endocrinology and gynecologic oncology concluded that bilateral salpingo-oophorectomy (BSO) was the next best step for diagnosis and management. Laparoscopic BSO was performed. Intraoperatively, the ovaries appeared grossly normal with the exception of dilated ovarian veins. Histopathology showed bilateral Leydig cell tumors (left: 1.5 cm; right: 2.0 cm) and a 0.7 cm left ovarian Brenner tumor. At 1-year postoperative follow-up, alopecia had resolved. Laboratory evaluation showed normalization of the testosterone (23 ng/dL), free testosterone (0.47 ng/dL). Androstenedione (1.023 ng/mL) was lower than before surgery but higher than reference range. Conclusion: The presented rare case of postmenopausal virilization is even more unique due to the synchronous presence of 2 rare ovarian tumors, both capable of causing hyperandrogenism, including bilateral ovarian Leydig cell tumor, Brenner tumor and adrenal incidentaloma. Despite normal appearing ovaries on imaging studies, BSO was ultimately necessary for diagnosis and management. Presentation: 6/3/2024

5116 Postmenopausal Hyperandrogenism due to Rare Ovarian Tumor

Abstract Disclosure: M. Salim: None. S. Dasaraju: None. Y. Lee: None. S. Afzal: None. B.K. Erickson: None. M.A. Khalifa: None. L.A. Burmeister: None. Background: Hyperandrogenism in postmenopausal women may arise from either ovarian or adrenal source and can pose challenging diagnostic dilemma. Clinical Case: A 66-year-old multigravida, post-menopausal woman presented with a 3-month history of worsening alopecia. Her past medical history included diabetes mellitus type 2 and breast cancer. Menarche was at age 12. There was no history of infertility. Menopause was in her 40’s. She had been shaving her upper lip and chin hair every 3 days for the past 10 years. Scalp hair loss had accelerated in the last 3 months, with loss of the bangs. Physical exam was significant for body mass index 34, deep voice, and clitoromegaly. Laboratory tests showed testosterone 160 ng/dL, (8-60 ng/dL), free testosterone 3.37 ng/dL (0.06-0.38 ng/dL), androstenedione 2.196 ng/mL (0.13-0.82 ng/mL), sex hormone binding globulin (SHBG) 31 nmol/L (30-135 nmol/L), dehydroepiandrosterone-sulfate (DHEAS) 86 ug/dL (13-130 ug/dL), 17-hydroxy progesterone 96 ng/dL (<51 ng/dL), inhibin A 1.1 pg/mL (<6.9 pg/mL), inhibin B <10 pg/mL (<16 pg/mL), adrenocorticotropic hormone 38 pg/mL (<47 pg/mL), and cortisol 12.2 ug/dL (4-22 ug/dL). Response to 1 mg overnight dexamethasone suppression test demonstrated persistently elevated testosterone (160 ng/dL), and incomplete suppression of androstenedione (0.827 ng/mL) and cortisol (2.4 ug/dL). Computerized tomography (CT) scan showed a left adrenal nodule (12 mm, 5 Hounsfield units, stable compared to imaging 2 years prior) and unremarkable appearance of the ovaries. Pelvic ultrasound did not show ovarian tumor on the right and left ovary was not seen. Adrenal and ovarian vein sampling suggested the ovaries as the source of the testosterone. Given the ovarian vein sampling results, a multidisciplinary discussion between endocrinology and gynecologic oncology concluded that bilateral salpingo-oophorectomy (BSO) was the next best step for diagnosis and management. Laparoscopic BSO was performed. Intraoperatively, the ovaries appeared grossly normal with the exception of dilated ovarian veins. Histopathology showed bilateral Leydig cell tumors (left: 1.5 cm; right: 2.0 cm) and a 0.7 cm left ovarian Brenner tumor. At 1-year postoperative follow-up, alopecia had resolved. Laboratory evaluation showed normalization of the testosterone (23 ng/dL), free testosterone (0.47 ng/dL). Androstenedione (1.023 ng/mL) was lower than before surgery but higher than reference range. Conclusion: The presented rare case of postmenopausal virilization is even more unique due to the synchronous presence of 2 rare ovarian tumors, both capable of causing hyperandrogenism, including bilateral ovarian Leydig cell tumor, Brenner tumor and adrenal incidentaloma. Despite normal appearing ovaries on imaging studies, BSO was ultimately necessary for diagnosis and management. Presentation: 6/3/2024

9243 Postmenopausal Hyperandrogenism due to Rare Ovarian Tumor

Abstract Disclosure: M. Salim: None. S. Dasaraju: None. Y. Lee: None. S. Afzal: None. B.K. Erickson: None. M.A. Khalifa: None. L.A. Burmeister: None. Background: Hyperandrogenism in postmenopausal women may arise from either ovarian or adrenal source and can pose challenging diagnostic dilemma. Clinical Case: A 66-year-old multigravida, post-menopausal woman presented with a 3-month history of worsening alopecia. Her past medical history included diabetes mellitus type 2 and breast cancer. Menarche was at age 12. There was no history of infertility. Menopause was in her 40’s. She had been shaving her upper lip and chin hair every 3 days for the past 10 years. Scalp hair loss had accelerated in the last 3 months, with loss of the bangs. Physical exam was significant for body mass index 34, deep voice, and clitoromegaly. Laboratory tests showed testosterone 160 ng/dL, (8-60 ng/dL), free testosterone 3.37 ng/dL (0.06-0.38 ng/dL), androstenedione 2.196 ng/mL (0.13-0.82 ng/mL), sex hormone binding globulin (SHBG) 31 nmol/L (30-135 nmol/L), dehydroepiandrosterone-sulfate (DHEAS) 86 ug/dL (13-130 ug/dL), 17-hydroxy progesterone 96 ng/dL (<51 ng/dL), inhibin A 1.1 pg/mL (<6.9 pg/mL), inhibin B <10 pg/mL (<16 pg/mL), adrenocorticotropic hormone 38 pg/mL (<47 pg/mL), and cortisol 12.2 ug/dL (4-22 ug/dL). Response to 1 mg overnight dexamethasone suppression test demonstrated persistently elevated testosterone (160 ng/dL), and incomplete suppression of androstenedione (0.827 ng/mL) and cortisol (2.4 ug/dL). Computerized tomography (CT) scan showed a left adrenal nodule (12 mm, 5 Hounsfield units, stable compared to imaging 2 years prior) and unremarkable appearance of the ovaries. Pelvic ultrasound did not show ovarian tumor on the right and left ovary was not seen. Adrenal and ovarian vein sampling suggested the ovaries as the source of the testosterone. Given the ovarian vein sampling results, a multidisciplinary discussion between endocrinology and gynecologic oncology concluded that bilateral salpingo-oophorectomy (BSO) was the next best step for diagnosis and management. Laparoscopic BSO was performed. Intraoperatively, the ovaries appeared grossly normal with the exception of dilated ovarian veins. Histopathology showed bilateral Leydig cell tumors (left: 1.5 cm; right: 2.0 cm) and a 0.7 cm left ovarian Brenner tumor. At 1-year postoperative follow-up, alopecia had resolved. Laboratory evaluation showed normalization of the testosterone (23 ng/dL), free testosterone (0.47 ng/dL). Androstenedione (1.023 ng/mL) was lower than before surgery but higher than reference range. Conclusion: The presented rare case of postmenopausal virilization is even more unique due to the synchronous presence of 2 rare ovarian tumors, both capable of causing hyperandrogenism, including bilateral ovarian Leydig cell tumor, Brenner tumor and adrenal incidentaloma. Despite normal appearing ovaries on imaging studies, BSO was ultimately necessary for diagnosis and management. Presentation: 6/3/2024

8125 Long-term Effects of Gender Affirming Hormone Therapy (GAHT) on Lipid Profile

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<0.001) in transgender men; in transgender women, serum E2 was higher (110 ± 9 vs. 26 ± 2 pg/dL, P<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<0.05) while in transgender women there was decrease in systolic blood pressure (124 ± 2 vs. 118 ± 2 mmHg, p<0.005), and slight increase in BMI (28 ± 0.9 vs. 30 ± 1 kg.m2, P<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

8125 Long-term Effects of Gender Affirming Hormone Therapy (GAHT) on Lipid Profile

Abstract Disclosure: G. Le: None. S. Pinkson: None. J. Trejo: None. D. Tripathy: None. 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<0.001) in transgender men; in transgender women, serum E2 was higher (110 ± 9 vs. 26 ± 2 pg/dL, P<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<0.05) while in transgender women there was decrease in systolic blood pressure (124 ± 2 vs. 118 ± 2 mmHg, p<0.005), and slight increase in BMI (28 ± 0.9 vs. 30 ± 1 kg.m2, P<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

7394 Testicular Function in Young Adults with Growth Hormone (GH) Deficiency Previously Treated with GH: Comparison with Normal Controls

Abstract Disclosure: R. Cannarella: None. A. Crafa: None. S. Sapienza: None. M.M. Caruso: None. A.E. Calogero: None. Background: We have previously reported that treatment with recombinant human growth hormone (rhGH) can influence testicular growth and puberty onset in children with GH deficiency (GHD), and suggested GH as a determinant of testicular growth in childhood (doi: 10.3389/fendo.2021.619895). Limited evidence is available on testicular function in post-pubertal GHD patients. Objective: This prospective controlled study was undertaken to evaluate testicular function in young GHD adults previously undergone to GH treatment. Patients and Methods: Post-pubertal patients with non-syndromic GHD (>18 years), in whom GH therapy was discontinued after reaching the therapeutic goal, were required to have a complete evaluation of testicular function. Those who agreed were enrolled in our study. Age-matched healthy men older than 18 years served as controls. Exclusion criteria were: the presence of varicocele, urogenital infections, cryptorchidism, hypospadias, hypogonadism, testicular trauma or torsion, and other congenital or acquired disorders capable of interfering with testicular function. The study outcomes were: serum gonadotropins and total testosterone (TT), conventional sperm parameters, and testicular volume (TV) measured by ultrasound examination. Between-group analysis was performed using the Student’s t-test for independent samples or the Mann-Whitney test, for normally or non-normally distributed variables, respectively. Data were reported as mean±standard deviation for non-skewed data and median (interquartile range) for skewed data. Results: 26 patients with GHD and 25 age-matched controls (18.8±3.3 years vs. 20.1±3.6 years; p=0.18) were enrolled. Patients and controls did not differ for serum luteinizing hormone [2.6 (1.5-4.9) IU/L vs. 3.5 (2.8-4.8) IU/L); p=0.2], follicle-stimulating hormone [3.4 (2.2-4.3) IU/L vs. 3.1 (2.3-4.3) IU/L); p=1.0], and TT [5.7 (4.7-6.8) ng/dL vs. 6.0 (5.1-7.4) ng/dL); p=0.4] levels. At semen analysis, GHD patients had lower semen volume (2.1±1.4 mL vs. 3.5±1.5 mL; p=0.002), total sperm count [135.0 miL/ejaculate (54.3-229.0) vs. 231.3 miL/ejaculate (124.8-285.0); p=0.03], progressive motility [25.5% (15.0-34.0%) vs. 32.0% (30.0-36.5); p=0.02], and total motility [56.0% (49.0-62.0) vs. 66.5% (62.5-70.0); p=0.0001] compared to controls. No difference was found in sperm concentration [73.0 miL/mL (45.0-92.0) vs. 68.0 miL/mL (39.0-90.0); p=1.0] and normal morphology [8.5% (7.0-12.0) % vs. 10.0% (7.5-14.0); p=0.3]. Importantly, GHD patients had lower right (13.3±3.4 mL vs. 16.9±4.1 mL; p=0.001) and left (12.5±3.4 mL vs. 16.3±3.8 mL; p=0.0005) TV. Conclusion: This study provides the first evidence of lower TV and slightly worse semen parameters in patients with GHD compared to healthy controls. Serum GH levels during growth may be important for achieving normal testicular volume and spermatogenesis in adulthood. Presentation: 6/2/2024

9277 Testicular Function in Young Adults with Growth Hormone (GH) Deficiency Previously Treated with GH: Comparison with Normal Controls

Abstract Disclosure: R. Cannarella: None. A. Crafa: None. S. Sapienza: None. M.M. Caruso: None. A.E. Calogero: None. Background: We have previously reported that treatment with recombinant human growth hormone (rhGH) can influence testicular growth and puberty onset in children with GH deficiency (GHD), and suggested GH as a determinant of testicular growth in childhood (doi: 10.3389/fendo.2021.619895). Limited evidence is available on testicular function in post-pubertal GHD patients. Objective: This prospective controlled study was undertaken to evaluate testicular function in young GHD adults previously undergone to GH treatment. Patients and Methods: Post-pubertal patients with non-syndromic GHD (>18 years), in whom GH therapy was discontinued after reaching the therapeutic goal, were required to have a complete evaluation of testicular function. Those who agreed were enrolled in our study. Age-matched healthy men older than 18 years served as controls. Exclusion criteria were: the presence of varicocele, urogenital infections, cryptorchidism, hypospadias, hypogonadism, testicular trauma or torsion, and other congenital or acquired disorders capable of interfering with testicular function. The study outcomes were: serum gonadotropins and total testosterone (TT), conventional sperm parameters, and testicular volume (TV) measured by ultrasound examination. Between-group analysis was performed using the Student’s t-test for independent samples or the Mann-Whitney test, for normally or non-normally distributed variables, respectively. Data were reported as mean±standard deviation for non-skewed data and median (interquartile range) for skewed data. Results: 26 patients with GHD and 25 age-matched controls (18.8±3.3 years vs. 20.1±3.6 years; p=0.18) were enrolled. Patients and controls did not differ for serum luteinizing hormone [2.6 (1.5-4.9) IU/L vs. 3.5 (2.8-4.8) IU/L); p=0.2], follicle-stimulating hormone [3.4 (2.2-4.3) IU/L vs. 3.1 (2.3-4.3) IU/L); p=1.0], and TT [5.7 (4.7-6.8) ng/dL vs. 6.0 (5.1-7.4) ng/dL); p=0.4] levels. At semen analysis, GHD patients had lower semen volume (2.1±1.4 mL vs. 3.5±1.5 mL; p=0.002), total sperm count [135.0 miL/ejaculate (54.3-229.0) vs. 231.3 miL/ejaculate (124.8-285.0); p=0.03], progressive motility [25.5% (15.0-34.0%) vs. 32.0% (30.0-36.5); p=0.02], and total motility [56.0% (49.0-62.0) vs. 66.5% (62.5-70.0); p=0.0001] compared to controls. No difference was found in sperm concentration [73.0 miL/mL (45.0-92.0) vs. 68.0 miL/mL (39.0-90.0); p=1.0] and normal morphology [8.5% (7.0-12.0) % vs. 10.0% (7.5-14.0); p=0.3]. Importantly, GHD patients had lower right (13.3±3.4 mL vs. 16.9±4.1 mL; p=0.001) and left (12.5±3.4 mL vs. 16.3±3.8 mL; p=0.0005) TV. Conclusion: This study provides the first evidence of lower TV and slightly worse semen parameters in patients with GHD compared to healthy controls. Serum GH levels during growth may be important for achieving normal testicular volume and spermatogenesis in adulthood. Presentation: 6/2/2024

7472 Estrogen Monotherapy for Testosterone Suppression in Gender Diverse Patients

Abstract 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

7472 Estrogen Monotherapy for Testosterone Suppression in Gender Diverse Patients

Abstract 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

8319 Pituitary Apoplexy Leads to the Spontaneous Resolution of Hypercortisolism Secondary to Cushing Disease: A Clinical Case

Abstract Disclosure: N. Sweis: None. J. Sanchez Perez: None. M. Fariduddin: None. R.M. Sargis: None. D.J. Toft: None. S. Reutrakul: None. Background: Pituitary apoplexy is a potentially fatal condition involving the infarction or hemorrhage of the pituitary gland. Rarely, it can occur in the setting of an ACTH-secreting pituitary adenoma. Clinical Case: A 27-year-old female with a past medical history of obesity, spontaneous miscarriages, and amenorrhea presented to the ER with an acute onset frontal headache of throbbing quality, associated with nausea and vomiting. The headache began two days prior, rapidly intensified, and did not improve with oral acetaminophen. CT of the head revealed an enlarged pituitary gland, while neurovascular imaging showed no abnormalities. Her neurologic examination was normal. She denied visual changes, photophobia, neck rigidity, fevers, chills, or recent infections. Furthermore, she endorsed a weight gain of about 40 pounds over the past year despite no change in dietary habits. This was accompanied by amenorrhea, hair thinning, itchy comedonal acne, hirsutism, and a loss of libido. Her physical examination was remarkable for the presence of cushingoid features including violaceous abdominal striae, facial acne, moon facies, a dorsal fat pad, and acanthosis nigricans around the neck and axillae. Pituitary MRI with and without contrast showed an enlarged sellar and suprasellar macroadenoma measuring approximately 2.1x1.4x1.2 cm abutting the optic chiasm. The visualized lesion contained hemorrhagic products, suggesting pituitary apoplexy. Biochemical testing on admission included a low morning plasma cortisol of 6.5 ug/dL (ref. range: 6.7-22.6 ug/dL), a 24-hour urine free cortisol of 12.0 (<=45.0 ug/24 hour), and an elevated ACTH of 145.0 pg/mL (7.2 - 63.3 pg/mL). A1c was 5.8% (<5.7%). Serum levels of prolactin, IGF1, GH, LH, FSH, TSH, Free T4, estradiol, total and bioavailable testosterone were within normal limits. She was evaluated with an ACTH stimulation test, which showed a morning cortisol level of 1.2 ug/dL at baseline, lower from prior. Cortisol levels were adequately increased at 19.6 ug/dL and 22.6 ug/dL, 30 and 60 minutes after the administration of Cosyntropin 250 mcg, respectively (>=18 ug/dL after 30-60 mins). The level of ACTH at the time was also decreased to 76.6 pg/mL. The patient was therefore started on steroid replacement therapy with hydrocortisone and later underwent transsphenoidal resection of the pituitary mass without complications. Histopathological examination of the resected mass showed pituitary adenoma cells with diffuse weak to moderate ACTH staining, most consistent with a sparsely granulated corticotroph pituitary adenoma. Conclusion: We report an interesting case of Cushing disease that spontaneously resolved after pituitary apoplexy. Our case underlines the importance of close monitoring of such patients who may rapidly undergo a period of adrenal insufficiency after hypercortisolism. Presentation: 6/3/2024

8283 Diabetes Mellitus in Patients with Hemochromatosis- A Diagnostic and Therapeutic Challenge

Abstract Disclosure: U. Rafat: None. M. Siddiqui: None. J.L. Gilden: Other; Self; Novartis Pharmaceuticals. A. Moid: Other; Self; Novartis Pharmaceuticals. Background: Primary Hemochromatosis is a genetic condition most commonly due to two sets of mutations in the Human homeostatic iron regular Protein (HFE) gene. HFE modulates the expression of hepcidin, which regulates intestinal iron absorption, plasma iron concentration and distribution of iron in tissues. Hemochromatosis patients are at high risk for developing diabetes mellitus (DM) due to iron overload in the pancreas with damage to Beta cells and impaired insulin secretory capacity. Hemochromatosis is often called Bronze Diabetes due to brown discoloration of the skin from accumulation of iron, and is characterized by hepatic fibrosis, fatigue, arthralgias, cirrhosis, DM, arthropathy, pigmentation and cardiomyopathy. Case: We present a Caucasian male with homozygous hereditary hemochromatosis, diagnosed by liver biopsy at age 40 due to transaminitis and Ferritin level of 1500 ng/mL and Genetic testing- 2 copies of HFE gene pathogenic variant (C282Y). He was later diagnosed with DM age 51, started on Metformin and referred to Endocrine clinic with abdominal bloating, and polyarticular arthralgias. Physical exam=Vital Signs normal (WT. 231lbs, BMI 34), with splenomegaly, but normal musculoskeletal exam and skin without bronze discoloration. Both parents had T2DM. Lab- Hb a1c 8.7% (0.0-5.6), Iron saturation 71% (10-50), Ferritin 66.3 ng/mL (26-388), C-Peptide 3.30 ng/ml (0.81-3.85), with glucose level of 119 mg/dL, and negative IA-2 <5.4 U/mL, negative Islet cell antibody, GAD 65 <5 IU/mL (nl <5), Insulin Autoantibody <0.4 U/mL (nl <0.4), and Zinc Transporter 8 antibodies <10 U/mL (nl <15). Liver tests- AST 39 U/L(10-37), ALT 77 U/L (10-65), ALP 89 U/L (45-117), total bilirubin 1.1 mg/dL(0.2-1.2). Hormonal evaluation included TSH 1.2 uIU/mL (0.55-4.78), ACTH 19 pg/mL (0-47), AM Cortisol 16.28 ug/d (5.30-22.50) IGF1 158 ng/mL (50-317) FSH 9.6 mIU/mL(l.40-18.10), LH 5.09 mIU/mL (1.50-9.30), Prolactin 7.40 ng/mL(2.10-17.70), total testosterone 374 ng/dL(250-1100), free testosterone 66.2 pg/mL (35.0-155.0). Echocardiogram-left ventricular hypertrophy and thick right ventricular wall with concerns for iron overload. Hba1c improved to 6.6% on Metformin. Fructosamine 351umol/L (151-300). In the absence of advanced cardiac, hepatic and other organ involvement, and presence of elevated C-peptide and high BMI, this patient is being managed as T2DM, with low threshold to initiate insulin therapy considering possibility of concomitant Bronze DM. Conclusion: It is important to determine type of DM, so appropriate management options can be devised. While insulin is recommended for management in Bronze Diabetes, insulin sensitizers, such as metformin and/or GLP 1 agonists can be used in type 2 DM. One must also consider therapy based upon the risk of cancer and acute pancreatitis in the setting of pancreatic iron overload, when considering antihyperglycemic therapies. Presentation: 6/2/2024

5175 A Rare Case of Type B Insulin Resistance Syndrome

Abstract Disclosure: S. Fatima: None. A. Champion: None. S. Ward: None. Q. Aziz: None. K.E. Izuora: None. Introduction: Severe insulin resistance may be defined as a severely diminished response to insulin’s biological effects and is characterized by substantial hyperinsulinemia and impaired glucose response to endogenous and exogenous insulin. We hereby present a rare case of Type B Insulin Resistance Syndrome (TBIRS). Case:40-years old female with history of systemic lupus erythematosus (SLE), diabetes mellitus was admitted with multiple rheumatologic complaints, including arthralgias, oral ulcers, skin rash, and hair loss secondary to SLE flare. Endocrinology was consulted for diabetes management. Her HbA1c had increased from 7.3% to 11.6% in 3 months despite taking Glargine 45 units daily, Lispro 15 units pre-meals and metformin. She noticed 80 lbs weight loss for past 6 months. Her BMI was 26 and exam showed acanthosis of neck, armpits, groin, hair loss on scalp, multiple genital ulcers, and facial rash. She was noted to have refractory hyperglycemia despite high insulin doses. By 14th day of hospitalization, she was on 287 units of insulin (3.4units/kg) daily. We suspected TBIRS in the setting of SLE. Metformin and pioglitazone were started. Further testing showed insulin level 152mIU/ml (2.6-14.9mIU/ml), C-peptide 1.7 ng/ml (1.1-4.4 ng/ml), islet-cell antibody negative, GAD-65 antibody <5 u/ml, insulin antibody 6.5 uU/ml, IGF-1 14 (79-259 ng/ml), adiponectin 13.3 (2.4-17.9 ug/ml), testosterone 7 (8-60 ng/dl), free testosterone <0.2 (0-4.2 pg/ml), total cholesterol 200 mg/dl (<200 mg/dl), triglycerides 85 mg/dl (<150 mg/dl), LDL 154 mg/dl (<100 mg/dl), HDL 29 mg/dl (>60 mg/dl). She was transferred to National Institute of Health for further care. She was confirmed to have TBIRS by insulin receptor antibody testing, started on regular insulin U500 initially, and then switched to IV insulin drip requiring up to 1700 units of insulin per hour. She received methylprednisolone, cyclophosphamide (2 doses), rituximab (2 doses), hydroxychloroquine and IV immunoglobulin. Her stay was complicated by hemophagocytic lymphohistiocytosis. She was discharged on U-500 Regular insulin, 1000 units with breakfast and 500 units with lunch, Prednisone 60 mg daily and Hydroxychloroquine. Two months later she was found unresponsive at home secondary to hypoglycemic seizures. She required dextrose drip and was discharged on Glargine 16 units and Lispro 6 units with meals. Conclusion: TBIRS is caused by a highly specific polyclonal autoantibody against the cell surface insulin receptor that decreases the cellular insulin response and causes refractory hyperglycemia. About 100 cases have been reported in literature. 60% of the cases are associated with SLE. The goal of therapy is to reverse the hypercatabolic state with high doses of insulin and to eliminate the autoantibodies with immunosuppressive therapy. The most common cause of mortality is hypoglycemia. Presentation: 6/3/2024

8138 Pituitary Stalk Interruption Syndrome (PSIS) in a patient with Isolated Hypogonadotropic Hypogonadism

Abstract Disclosure: A. Thomson: None. R. Osman: None. Pituitary Stalk Interruption Syndrome in a Patient with Isolated Hypogonadotropic Hypogonadism Pituitary Stalk Interruption syndrome (PSIS) is a rare cause of hypopituitarism, characterized by a radiologic constellation of thin or interrupted pituitary stalk, hypoplasia, or aplasia of the anterior lobe and with the presence of an ectopic posterior pituitary (EPP). It is most commonly associated with isolated growth hormone deficiency (IGHD) and is often diagnosed in childhood. We present one case of a patient with isolated hypogonadotropic hypogonadism in adulthood, subsequently found to have an PSIS on MRI. A 45 year old male patient presented to our clinic with hypogonadism. He gradually started developing decreasing libido, fatigue, and loss of erections. He had normal puberty and childhood growth, and has fathered one child. He denied history of anosmia or visual symptoms. Subsequent hormonal testing showed: morning Total Testosterone: 145 ng/dl (normal 264-916 ng/dl), Free testosterone 1.5 pg/ml (normal 6.8-21.5 pg/ml), LH 1.1 mIU/ml (normal 1.7-8.6 mIU/ml) and FSH of 3.6 mIU/ml (normal 1.5-12.4 mIU/ml). Prolactin was minimally elevated at 21 ng/ml (normal 4.0 - 15.2 ng/ml). Thyroid, IGF-1, cortisol, and ferritin levels were within normal limits. Repeat levels showed similar findings. He denied ever taking any form of exogenous testosterone. His pituitary MRI revealed a small volume of anterior pituitary tissue, measuring 0.2cm x 0.7cm x 0.7cm, without discrete pituitary adenoma, a hypoplastic midline stalk measuring 1.3 mm in AP diameter (nl 2-3 mm), with a T1 hyperintense nodularity measuring 0.6cm x 0.4cm along the posterior aspect of the sella turcica consistent with EPP. No additional structural abnormality or any mass lesions were identified. He was subsequently started on replacement testosterone therapy and his symptoms resolved. PSIS usually presents in childhood with IGHD. Patients may have other pituitary hormone deficiencies and congenital central nervous system defects, although panhypopituitarism is rare. There have been reports in children with delayed puberty and isolated hypogonadotropic hypogonadism who have been found to have PSIS. Only one othercase of an adult female patient exhibiting hypogonadotropic hypogonadism as the only manifestation of PSIS has been documented in the literature. Our case highlights the potential for an adult male to present later in life with hypogonadotropic hypogonadism as a manifestation of PSIS. The marginally elevated prolactin level may be due to lack of inhibition of hypothalamic dopamine on lactotroph cells within the pituitary caused by the EPP, although it is doubtful that this has clinical significance. This is a rare presentation of PSIS, clinicians should be mindful ofthis radiological constellation and the potential for isolated hypogonadotropic hypogonadism presenting unusually in the adulthood. Presentation: 6/3/2024

6983 Pembrolizimab Induced Hypophysitis: Uncommon Side Effect Leading To Late Diagnosis

Abstract Disclosure: T. Chaudhary: None. O. Syed: None. A. Shridar: None. R. Kaur: None. O. Chaudhary: None. M.S. Zubair: None. Background: Pembrolizumab, an immune checkpoint inhibitor, has shown efficacy inducing remission in various malignancies. Associated immune-related adverse effects (irAEs) have been recorded but cases of concomitant hypophysitis and thyroiditis are rare. Clinical case: The patient is a 41-year-old male with a past medical history significant for metastatic melanoma of the left calf, status post sentinel lymph node biopsy and left inguinal lymph node dissection, treated with pembrolizumab for one year. He initially presented with a severe headache that was preceded by two months of fatigue and impaired concentration. CT and MRI head were both unremarkable while lab work was significant for cortisol 0.2 ug/dL and adrenocorticotropic hormone (ACTH) 1.1 pmol/L. A full hormone panel was ordered which showed normal insulin-like growth factor-1 (IGF-1), luteinizing hormone (LH), and follicle-stimulating hormone (FSH). Free testosterone was at the lower end of normal. Prolactin was elevated at 27.3 ng/mL. The thyroid function tests showed primary hypothyroidism with elevated thyroid stimulating hormone (TSH) at 109 uIU/mL, low T4 at 1.5 ug/dL, and low free T4 at 0.4 ng/dL. There were no signs or symptoms of posterior pituitary dysfunction. The patient was diagnosed with hypophysitis and started on hydrocortisone 20 mg once daily along with levothyroxine 175 mcg once daily. DEXA scan showed normal bone mineral density. Subsequently, the patient presented to our care and reported symptom improvement after taking the prescribed medication however he continued to develop fatigue by the end of the day. Therefore, hydrocortisone prescription was switched to 15 mg in the morning and 10 mg at noon. A repeat thyroid function panel, sex hormone binding globulin, and LH were ordered, to be followed up at the patient's next visit. The patient was also advised to wear a medical alert bracelet at all times moving forward. Conclusion: Due to non-specific symptoms at onset, hypophysitis can be undiagnosed or misdiagnosed therefore it is important to have a high clinical suspicion with patients on PD-1 inhibitors presenting with such symptoms. It is also imperative to order a full set of hormones as this patient had concomitant primary hypothyroidism. Presentation: 6/1/2024

6963 A Rare Case Presentation of Untreated Congenital Adrenal Hyperplasia with Bilateral Giant Myelolipoma

Abstract Disclosure: F. Omran: None. S. Bromley: None. M. Ilahi: None. M. Zena: None. W. Al-Refaie: None. J. Delto: None. A. Singh,: None. Background: Adrenal myelolipoma is a rare benign neoplasm predominantly composed of mature adipose tissue and intermixed myeloid tissue, often associated with conditions like Congenital Adrenal Hyperplasia. The etiology of this neoplasm is not definitively known although there are numerous hypotheses, including research suggesting that excess ACTH could be responsible for the pathogenesis. Clinical Case: A 40-year-old female with a history of congenital adrenal hyperplasia noncompliant with treatment. She presented with cholelithiasis (s/p laparoscopic cholecystectomy), abdominal imaging revealed incidental finding of a large right retroperitoneal mass. She was noted to have generalized excessive hirsutism in male distribution, small breasts, enlarged clitoris, male body habitus, and amenorrhea after stopping steroids years prior. Laboratory workup showed the following hormonal abnormalities: elevated ACTH (1080 pg/ml), elevated testosterone (243 ng/dl) and free testosterone (31.3 pg/ml), elevated androstenedione (23.431 ng/ml), and low LH (<0.02 miu/ml), low FSH (<0.02 miu/ml). CT abdomen showed right lobulated retroperitoneal mass of 4x14.3x20cm with internal fat and soft tissue components, left lobulated retroperitoneal mass of 13.7x4.7x7.5cm with soft tissue and fat components. CT guided-biopsy showed pathology consistent with adrenal myelolipoma: fatty areas with interspersed hematopoietic tissue components, peripheral rim of normal adrenal cortical tissue. Given the large size of the mass and compressive effects on surrounding organs, patient underwent exploratory laparotomy with resection of right retroperitoneal mass, nephrectomy, and adrenalectomy. Discharged on hydrocortisone and fludrocortisone, instructed to follow up by endocrinologist, always wear medical alert bracelet, and provided with hydrocortisone emergency kit. Conclusion: This case serves as a classic presentation of a rare disease state. Adrenal myelolipomas, a rare benign adrenal neoplasm, have been found in several disorders associated with chronic ACTH hypersecretion including congenital adrenal hyperplasia. Most CAH patients with myelolipomas have untreated or poorly treated CAH. Adrenal myelolipomas that are asymptomatic and <5cm in size are usually monitored if one is certain there is no occult malignancy. If these tumors are symptomatic or >7cm, patients should undergo surgical excision. These patients should be followed by endocrinology. Importantly, further guidelines should be further developed for management. Presentation: 6/3/2024

8267 A Case of Pineal Gland Cyst and Adrenal Adenoma- Is this a New Syndrome?

Abstract Disclosure: M. Siddiqui: None. U. Rafat: None. S. Shaik: None. J.L. Gilden: None. Background: The Pineal Gland receives information through a complex multi-neuronal pathway and is responsible for the secretion of melatonin, a hormone regulated by circadian rhythm and suppressed by light stimuli. Melatonin is involved in biological rhythms and regulates immunomodulation, temperature homeostasis and maturation of hypothalamic-pituitary and gonadal axis, and can also modulate thyroid, prolactin, growth hormone, cortisol, and ACTH activity. Other effects include downregulation of thyroid activity. In addition, studies have shown that pineal body extracts can cause a minor increase in the zona glomerulosa and fasciculata of the adrenal gland. Case: A 54-year-old male with recurrent nephrolithiasis, obstructive sleep apnea and chronic rhinosinusitis, first presented to Endocrinology Clinic in 2018 for evaluation of an incidental adrenal adenoma (CT abdomen -2.8 cm, less than 10 Hounsfield units, left sided lipid rich adrenal adenoma). He had new onset erectile dysfunction, decreased libido, and fatigue. Initial lab work including LH, FSH, TSH, midnight salivary cortisol, ACTH, plasma cortisol AM, free and total testosterone, aldosterone, plasma and urine metanephrines/normetanephrines were all normal. MRI brain-1 cm thin-walled pineal cyst with internal characteristics compatible with proteinaceous benign pineal cyst. He was then lost to follow-up for 5 yrs due to the COVID pandemic. He had tried taking “testosterone protein builders”, but his symptoms remained. In addition, he now has twice weekly dull occipital headaches, relieved by ibuprofen. Lab tests-elevation in 1of 2 MN salivary cortisol samples at 0.58 mcg/dL (nl≤0.09), ACTH 12pg/mL(0-47), IGF1 261 ng/mL(50-317), and low total testosterone 222 ng/dl (250-1100) Free testosterone 36 pg/mL(35-155), borderline low TSH 0.386 µIU/ml(0.55-4.78), Free T3 and Free T4 were normal, thyroid antibodies-negative . Rest of the hormone evaluation was otherwise normal, LH 4.90 mIU/mL(1.5-9.3), FSH 11.10 mIU/mL (1.4-18.1), Prolactin 6.8 ng/mL(2.1-17.7). Thyroid Ultrasound-homogeneous echogenicity of the thyroid gland without discrete thyroid nodules. Repeat MRI brain- benign pineal cyst which was stable with no midline shift or mass effect. Repeat CT adrenal gland-lipid rich adrenal adenoma slightly reduced in size from 2.8 to 2.4 cm. Lab tests returned to normal one month later. Conclusion: Although it is unclear whether there is an exact association between this patient’s pineal cyst and adrenal adenoma, there have been intermittent hormonal abnormalities and symptoms consistent with hypogonadism and/or adrenal, also possibly related to the pineal abnormality. Although more research needs to be conducted explaining the relationship between the pineal and pituitary, and the adrenal gland, this clinical case suggests that there may be a relationship between these two abnormalities and symptoms. Presentation: 6/2/2024

7452 A Diagnostically Challenging Case of Hyperandrogenism in Postmenopausal Woman

Abstract Disclosure: M.S. Hossain: None. S. Hossain: None. B. Gautam: None. H. liao: None. S.C. Kumar: None. D.S. Rosenthal: None. Background: The diagnosis of new-onset severe hyperandrogenism in postmenopausal women is rarely encountered, posing a unique challenge for clinicians. Ovarian hyperthecosis and androgen-secreting tumors are the usual suspects in post menopause. In our case ovarian hyperthecosis is the primary consideration but elevated 17-OH Progesterone (17-OHP) introduces the potential co-existence of Non classical congenial adrenal hyperplasia (NCCAH) or rare instances of Sertoli-Leydig Cell Tumor (SLCT). Case Presentation: A 70 years old female, with no past medical history, referred to the Endocrinology clinic for significantly elevated testosterone level. She reported excessive hair growth in various areas of her body since 2022, which required shaving almost every day. She also reported male pattern hair loss and weight loss of 15 lbs over the last three months. She denied headache, vision changes, deepening of voice, history of fertility problems and use of exogenous testosterone. Her vital sign were normal. On examination, she had clitoromegaly, terminal hair growth on her upper lip and chin, breast atrophy, male pattern baldness, but no cushingoid or acromegaly features. Blood tests showed significantly elevated total testosterone: 1422 ng/dl (2-45); free testosterone: 147.9 pg/ml (0.2-3.7) and Estradiol: 64 pg/ml (Postmenopausal <31) with low LH: 7.6 mIU/ml (Postmenopausal 10.0-54.7) and FSH: 22.2 mIU/mL (Postmenopausal 23-116). Her serum ACTH, DHEA Sulfate, 11-deoxycortisol, 17 OH pregnenolone, TSH, Free T4, prolactin, IGF-1 were normal while her 17-OHP: 396 ng/dl (<45 ng/dl) was significantly elevated. An ACTH stimulation test showed 17-OHP level of 734 ng/dl at 30 minutes and 901 ng/dl at 1 hour. Pelvic ultrasonography: right ovary of 2.3 x 1.6 x 1.9 cm and the left ovary of 3.1 x 1.8 x 3.0 cm. MRI showed normal adrenal glands but a prominent left ovary. Patient was referred to the Obstetrics department to undergo bilateral oophorectomy for the definitive diagnosis and treatment. Discussion: The current ACTH stimulation test for non-classical congenital adrenal hyperplasia is validated for premenopausal women but lacks standardization in post-menopausal state. In our case, distinguishing the source of elevated 17-OHP between adrenal (NCCAH) and ovarian (SLCT) was difficult. Unexpected asymmetry in ovarian size observed in our case further complicates the scenario, contrasting with the typical symmetrical enlargement seen in ovarian hyperthecosis. Pending surgical pathology will further guide the management. This case highlights the complexity of diagnosing hyperandrogenism in postmenopausal women, emphasizing the significance of thoroughly exploring differential diagnoses and meticulously analyzing laboratory results. Presentation: 6/2/2024

7789 PCOS and probiotics - a randomized controlled trial with a comparison to metformin

Abstract Disclosure: B.M. Obermayer-Pietsch: None. B. Valentin: None. B. Luegger: None. R. Regina: None. C.W. Haudum: None. V. Tandl: None. Polycystic ovary syndrome (PCOS) has a complex association not only with gonadal hormones, but also with insulin resistance and the gut – showing a decreased alpha diversity of the microbiome in PCOS women. Based on our previous investigations, we conducted a randomized controlled trial (RCT) using probiotics (OMNi-BiOTiC®, Institut Allergosan) and placebo daily, compared to a metformin group over 6 months. In this RCT, we included 112 women with PCOS, defined by Rotterdam criteria. Clinical and biochemical characterisation covered medical history with cycle abnormalities, Ferriman–Gallwey (FG) Score and anthropometric data. Hormonal profiles included gonadal hormones with a focus on androgens and AMH. Oral glucose tolerance tests (oGTT) with parallel insulin/c-peptide determinations and stool sampling for microbiome determination at every visit were done. Study participants were randomized 2:1 for probiotics/placebo or metformin (Glucophage®, Merck) and further 1:1 between probiotics and placebo for 6 months followed by a voluntary 6 months period on probiotics only. NGS for microbiome profiles was carried out. 93 PCOS women completed the study, 19 drop-outs for various reasons including 6 pregnancies were recorded (5 in the probiotic/placebo group, 1 in the metformin group). Participants were 27±5 years old, obesity with a BMI >30 was found in 35% of them. Initial cycle duration ranged from 22 to 200 days, 18% had amenorrhoea. Hirsutism was present with a mean FG score of 12,7±7,71. Mean levels (±standard deviation, reference range, no units depicted) for total testosterone were 0,38±0,15 (0,14-0,77), SHBG 54,1±29,0 (19–117), free testosterone 3,2±3,1 (0,45-2,19) and AMH 8,9±4,8 (0,17-7,37). Initial oGTTs showed insulin resistance prevalent in 43%, with an overall reduction to 36% at visit 2. Weight loss over 6 months was documented in 37%, cycle abnormalities decreased overall to 14%. Group comparisons and microbiome characterisation are ongoing. No serious adverse reactions related to the study medication were recorded. All intervention products were well tolerated in our PCOS study cohort. Based on the intended cycle normalisation, 6 pregnancies were recorded. Metabolic changes were seen both in the probiotic/placebo and in the metformin groups, with fewer changes in the placebo group despite nutritional counselling. Microbiome changes were recorded in both intervention groups. Presentation: 6/3/2024