Sex Hormone-binding Globulin Research Articles

9208 Sex Hormones and Abdominal Muscle Area and Radiodensity in Men: A Multi-Ethnic Study of Atherosclerosis

Abstract Disclosure: A. Osmancevic: None. M. Allison: None. I. Miljkovic: None. C. Vella: None. P. Ouyang: None. P. Trimpou: None. B. Daka: None. Context: Information on the associations of testosterone, estradiol and sex hormone binding globulin (SHBG) levels with abdominal muscle volume and quality in men are unclear. Objective: To investigate the association between fasting serum sex hormones and CT-derived abdominal muscle area and radiodensity in adult men. Design: Cross sectional observational study using data from the Multi-Ethnic Study of Atherosclerosis. Participants: A community-based sample of 907 men aged 45-84 years; 878 men with complete data were included in the analysis. Main Outcome Measure(s): CT scans of the abdomen were interrogated for muscle characteristics. Multivariable linear regressions were used to test the associations. Results: After adjustment for age, race/ethnicity, visceral fat, CRP, lifestyle factors, comorbidities and medicine use, higher levels of both total testosterone and estradiol, but not SHBG, were associated with higher abdominal muscle area (B= 1.79, 95% CI 0.1 to 3.4, & B=1.79, 95% CI 0.4 to 3.2, respectively). After the same adjustment, levels of total testosterone showed a significant positive association (B= 0.3, 95% CI 0.0 to 0.6), while a significant inverse relationship was observed for SHBG with abdominal muscle radiodensity (B=-0.34, 95% CI -0.6 to -0.1). Conclusion: Our results indicate significant associations between sex hormones and abdominal muscle characteristics in men from several different race/ethnic groups. These findings reveal novel insights into the previously unrecognized role that SHBG may play in skeletal muscle adipose tissue distribution. Presentation: 6/2/2024

9240 Role Of Genetics In The Age-Related Testosterone Decline In Men: A UK Biobank Study

Abstract Disclosure: L. Ogoniak: None. S. Sandmann: None. J. Varghese: None. A.S. Busch: None. Background: Age-related decline in circulating serum testosterone concentrations is a well-established phenomenon in men. While the decline is partially linked to comorbidities such as obesity, type 2 diabetes (T2D), and cardiovascular disease (CVD), healthy ageing men present with rather stable levels. Recent genetic mapping studies demonstrated a large influence of common genetic variation on testosterone levels in men. However, increasing incidence rates of comorbidities in the ageing population are posing a challenge for the disentanglement of effects. Objective: Our study aims to investigate the genetic component of age-dependent testosterone decline in men. We hypothesize that the decline in testosterone levels in ageing men is primarily influenced by comorbidities, without significant alterations in the genetic architecture of testosterone levels. Material and Methods: We included 6,406 men with baseline and follow-up measurements of circulating serum concentrations of total testosterone (T), bioavailable testosterone (BAT) and sex hormone-binding globulin (SHBG) representing an independent sub-cohort of the UK Biobank study. We 1) assessed the association of baseline levels with the decline in sex steroids and 2) developed and verified polygenic risk score (PRS) models for T, BAT and SHBG based on 183,909 men from the UK Biobank (sub cohorts: 70% base, 15% target and 15% validation, follow-up cohort excluded for PRS development). Results: In the follow-up sub cohort, mean age (SD) at baseline was 58.2 yrs ( 7.5) and mean (SD) follow-up period was 4.3 (1.0) yrs. Mean (SD) BAT at baseline were 5.2 (1.32) nmol/L with a mean (SD) decline of 1.6 (24.4) % at follow-up. Baseline BAT, T and SHBG levels were significantly associated with the relative change of the respective biomarker at follow-up (-7.8, -2.9 and -0.4% per nmol/L, respectively, all p <0.001). After correcting for age at baseline, follow-up period and principal components 1-10, PGSTestosterone and PGSBAT were not associated with relative decline of the respective biomarker (both p = n.s.). Conclusion: Our study did not find evidence supporting a genetic component in the age-related decline of circulating serum T or BAT concentrations. Instead, in accordance to previous observational studies, our results suggest that rather non-genetic factors, e.g. increasing incidence rates of comorbidities, drive the age-related decline in sex steroid levels in men. Our study contributes to understanding the intricate relationship between genetic and non-genetic factors with age-related testosterone decline in men and offers valuable insights for potential interventions targeting age-related hormonal changes and associated health outcomes. Presentation: 6/2/2024

7078 Diagnostic Obstacles in Thyroid-Stimulating Hormone-Secreting Pituitary Adenoma (TSH-oma): A Case Report

Abstract Disclosure: V.A. Mendpara: None. P.P. Rao: None. M.D. Lundholm: None. Background: Thyroid-stimulating hormone-secreting pituitary adenoma (TSH-oma) is a rare cause of hyperthyroidism, forming 0.5-3% of all functioning pituitary tumors and <1% of hyperthyroid cases. Here, TSH secretion is autonomous and unresponsive to the normal negative feedback of thyroid hormones, leading to inappropriate TSH, T4 and T3 elevation. In the absence of clinical symptoms it can be difficult to distinguish between thyroid hormone resistance (THR) and lab errors. Clinical Case: A 44-year-old Swahili-speaking female with a history of type 2 diabetes was admitted for hypoglycemia requiring insulin adjustment. In her workup, thyroid function tests were obtained, revealing normal or low TSH (0.28 mIU/L) and high free T4 levels (2.7 ng/dL). At outpatient follow-up, repeat labs showed elevated TSH, T3 and FT4 (5.22 mIU/L, 377 ng/dL and 4.7 ng/dL, respectively). She reported weight loss, occasional palpitations, and chronic insomnia but denied other symptoms. Graves' antibodies (TSI, TSHR Ab) were negative. On exam, she had a 30-40 gm, smooth, non-tender thyroid without adenopathy, and a BMI of 23 kg/m2. The initial differential diagnosis included TFT lab error, THR or TSH-oma. A FT4 by equilibrium dialysis was high at 7.8 ng/dL (1.1-2.4 ng/dL). N-telopeptide (NTX) and sex hormone-binding globulin (SHBG) were elevated, consistent with a true hyperthyroid state. Genetic testing for THR posed time and cost barriers. Elevated alpha-subunit levels (87 ng/mL, normal ≤1.8 ng/mL) with normal levels of other pituitary hormones prompted a pituitary MRI, unveiling a 4.7 cm suprasellar bilobed pituitary mass abutting the optic chiasm and invading the cavernous and sphenoidal sinuses. She denied peripheral vision loss or headaches. Hyperthyroidism was managed with methimazole until surgical intervention for the TSH-oma. A transsphenoidal resection was performed with histopathological confirmation of a TSH-staining pituitary adenoma. She was started on levothyroxine for central hypothyroidism thereafter. Discussion: It is challenging to find the cause of abnormal TFTs when patients are asymptomatic and the differential includes THR, lab errors or TSH-oma. Inaccurate diagnosis can lead to delays in care or unnecessary thyroid ablation or pituitary surgery. Conversely, early identification and appropriate treatment of TSH-omas can prevent neurological and endocrinological complications, such as optic chiasm compression, visual disturbances, headache and hypopituitarism. Despite a lack of convincing symptoms of hyperthyroidism, we used confirmatory labs (NTX, SHBG) to rule in biochemical hyperthyroidism along with alpha-subunit testing and pituitary MRI to solidify the TSH-oma diagnosis, leading to surgical intervention. This case highlights the vital steps in the diagnosis of a TSH-oma, emphasizing the need for logical evaluation and differentiation of this rare condition. Presentation: 6/1/2024

8039 Role Of Genetics In The Age-Related Testosterone Decline In Men: A UK Biobank Study

Abstract Disclosure: L. Ogoniak: None. S. Sandmann: None. J. Varghese: None. A.S. Busch: None. Background: Age-related decline in circulating serum testosterone concentrations is a well-established phenomenon in men. While the decline is partially linked to comorbidities such as obesity, type 2 diabetes (T2D), and cardiovascular disease (CVD), healthy ageing men present with rather stable levels. Recent genetic mapping studies demonstrated a large influence of common genetic variation on testosterone levels in men. However, increasing incidence rates of comorbidities in the ageing population are posing a challenge for the disentanglement of effects. Objective: Our study aims to investigate the genetic component of age-dependent testosterone decline in men. We hypothesize that the decline in testosterone levels in ageing men is primarily influenced by comorbidities, without significant alterations in the genetic architecture of testosterone levels. Material and Methods: We included 6,406 men with baseline and follow-up measurements of circulating serum concentrations of total testosterone (T), bioavailable testosterone (BAT) and sex hormone-binding globulin (SHBG) representing an independent sub-cohort of the UK Biobank study. We 1) assessed the association of baseline levels with the decline in sex steroids and 2) developed and verified polygenic risk score (PRS) models for T, BAT and SHBG based on 183,909 men from the UK Biobank (sub cohorts: 70% base, 15% target and 15% validation, follow-up cohort excluded for PRS development). Results: In the follow-up sub cohort, mean age (SD) at baseline was 58.2 yrs ( 7.5) and mean (SD) follow-up period was 4.3 (1.0) yrs. Mean (SD) BAT at baseline were 5.2 (1.32) nmol/L with a mean (SD) decline of 1.6 (24.4) % at follow-up. Baseline BAT, T and SHBG levels were significantly associated with the relative change of the respective biomarker at follow-up (-7.8, -2.9 and -0.4% per nmol/L, respectively, all p <0.001). After correcting for age at baseline, follow-up period and principal components 1-10, PGSTestosterone and PGSBAT were not associated with relative decline of the respective biomarker (both p = n.s.). Conclusion: Our study did not find evidence supporting a genetic component in the age-related decline of circulating serum T or BAT concentrations. Instead, in accordance to previous observational studies, our results suggest that rather non-genetic factors, e.g. increasing incidence rates of comorbidities, drive the age-related decline in sex steroid levels in men. Our study contributes to understanding the intricate relationship between genetic and non-genetic factors with age-related testosterone decline in men and offers valuable insights for potential interventions targeting age-related hormonal changes and associated health outcomes. Presentation: 6/2/2024

9240 Role Of Genetics In The Age-Related Testosterone Decline In Men: A UK Biobank Study

Abstract Disclosure: L. Ogoniak: None. S. Sandmann: None. J. Varghese: None. A.S. Busch: None. Background: Age-related decline in circulating serum testosterone concentrations is a well-established phenomenon in men. While the decline is partially linked to comorbidities such as obesity, type 2 diabetes (T2D), and cardiovascular disease (CVD), healthy ageing men present with rather stable levels. Recent genetic mapping studies demonstrated a large influence of common genetic variation on testosterone levels in men. However, increasing incidence rates of comorbidities in the ageing population are posing a challenge for the disentanglement of effects. Objective: Our study aims to investigate the genetic component of age-dependent testosterone decline in men. We hypothesize that the decline in testosterone levels in ageing men is primarily influenced by comorbidities, without significant alterations in the genetic architecture of testosterone levels. Material and Methods: We included 6,406 men with baseline and follow-up measurements of circulating serum concentrations of total testosterone (T), bioavailable testosterone (BAT) and sex hormone-binding globulin (SHBG) representing an independent sub-cohort of the UK Biobank study. We 1) assessed the association of baseline levels with the decline in sex steroids and 2) developed and verified polygenic risk score (PRS) models for T, BAT and SHBG based on 183,909 men from the UK Biobank (sub cohorts: 70% base, 15% target and 15% validation, follow-up cohort excluded for PRS development). Results: In the follow-up sub cohort, mean age (SD) at baseline was 58.2 yrs ( 7.5) and mean (SD) follow-up period was 4.3 (1.0) yrs. Mean (SD) BAT at baseline were 5.2 (1.32) nmol/L with a mean (SD) decline of 1.6 (24.4) % at follow-up. Baseline BAT, T and SHBG levels were significantly associated with the relative change of the respective biomarker at follow-up (-7.8, -2.9 and -0.4% per nmol/L, respectively, all p <0.001). After correcting for age at baseline, follow-up period and principal components 1-10, PGSTestosterone and PGSBAT were not associated with relative decline of the respective biomarker (both p = n.s.). Conclusion: Our study did not find evidence supporting a genetic component in the age-related decline of circulating serum T or BAT concentrations. Instead, in accordance to previous observational studies, our results suggest that rather non-genetic factors, e.g. increasing incidence rates of comorbidities, drive the age-related decline in sex steroid levels in men. Our study contributes to understanding the intricate relationship between genetic and non-genetic factors with age-related testosterone decline in men and offers valuable insights for potential interventions targeting age-related hormonal changes and associated health outcomes. Presentation: 6/2/2024

8039 Role Of Genetics In The Age-Related Testosterone Decline In Men: A UK Biobank Study

Abstract Disclosure: L. Ogoniak: None. S. Sandmann: None. J. Varghese: None. A.S. Busch: None. Background: Age-related decline in circulating serum testosterone concentrations is a well-established phenomenon in men. While the decline is partially linked to comorbidities such as obesity, type 2 diabetes (T2D), and cardiovascular disease (CVD), healthy ageing men present with rather stable levels. Recent genetic mapping studies demonstrated a large influence of common genetic variation on testosterone levels in men. However, increasing incidence rates of comorbidities in the ageing population are posing a challenge for the disentanglement of effects. Objective: Our study aims to investigate the genetic component of age-dependent testosterone decline in men. We hypothesize that the decline in testosterone levels in ageing men is primarily influenced by comorbidities, without significant alterations in the genetic architecture of testosterone levels. Material and Methods: We included 6,406 men with baseline and follow-up measurements of circulating serum concentrations of total testosterone (T), bioavailable testosterone (BAT) and sex hormone-binding globulin (SHBG) representing an independent sub-cohort of the UK Biobank study. We 1) assessed the association of baseline levels with the decline in sex steroids and 2) developed and verified polygenic risk score (PRS) models for T, BAT and SHBG based on 183,909 men from the UK Biobank (sub cohorts: 70% base, 15% target and 15% validation, follow-up cohort excluded for PRS development). Results: In the follow-up sub cohort, mean age (SD) at baseline was 58.2 yrs ( 7.5) and mean (SD) follow-up period was 4.3 (1.0) yrs. Mean (SD) BAT at baseline were 5.2 (1.32) nmol/L with a mean (SD) decline of 1.6 (24.4) % at follow-up. Baseline BAT, T and SHBG levels were significantly associated with the relative change of the respective biomarker at follow-up (-7.8, -2.9 and -0.4% per nmol/L, respectively, all p <0.001). After correcting for age at baseline, follow-up period and principal components 1-10, PGSTestosterone and PGSBAT were not associated with relative decline of the respective biomarker (both p = n.s.). Conclusion: Our study did not find evidence supporting a genetic component in the age-related decline of circulating serum T or BAT concentrations. Instead, in accordance to previous observational studies, our results suggest that rather non-genetic factors, e.g. increasing incidence rates of comorbidities, drive the age-related decline in sex steroid levels in men. Our study contributes to understanding the intricate relationship between genetic and non-genetic factors with age-related testosterone decline in men and offers valuable insights for potential interventions targeting age-related hormonal changes and associated health outcomes. Presentation: 6/2/2024

9224 Evaluation of Safety and Efficacy of Administration of Estradiol by Subcutaneous Injection in Transgender Women

Abstract Disclosure: H. Perkins: None. H. Moreau: None. J. LaBudde: None. W. Craig: None. D.I. Spratt: None. Background: Off-label use of subcutaneous (SC) estradiol (E2) by transgender women for gender-affirming hormone therapy is becoming increasingly widespread, despite a lack of published data regarding its efficacy and safety. Methods: This retrospective cohort study used manual data extraction from electronic medical records for patients ages 18-79 years, currently or previously receiving oral (PO) 17-beta E2 or SC E2 valerate therapy at Maine Medical Center Reproductive Endocrinology and Infertility and Gender Clinics between 5/30/14-5/30/23, who completed E2 dose adjustments aimed at obtaining a serum E2 of 75-250 pg/mL. SC E2 was administered weekly and PO E2 daily. Serum testosterone (T), estrone (E1), and sex hormone binding globulin (SHBG) levels were recorded if drawn within 90 days of E2 measurement on an optimized dose. In a subset of patients receiving SC E2, serum E2 levels were drawn 1-2 days post- and pre-injection. All patient-reported local or systemic reactions were recorded. Data are expressed as median (full range) or mean ± standard deviation (full range). Results: 45 patients were included with no significant differences in demographics between PO (n=20) and SC (n=25) groups. Both groups achieved therapeutic E2 levels after dose adjustment without statistical difference in mean serum E2 (pg/mL) between SC and PO groups: 148.7 ± 41.0 (78-226) vs. 151.6 ± 31.7 (97-208); p=0.79 by t-test. In patients without orchiectomy, both SC and PO groups had T (ng/dL) suppressed to normal adult female range (10-55) in 11/12 SC patients and in 17/17 PO patients; median T was 14.0 (7.7-86) for SC vs. 20.6 (3.4-42) for PO; p=0.98 by Mann-Whitney U test. Median E2 dose (mg/week) in the SC group was 3.0 (1.4-6.0) and in the PO group was 42.0 (28-84). Median serum E1 (pg/mL) was lower in the SC group than the PO group: 73.5 (29-115), n=12 vs. 907 (596-1601), n=5, p<0.001 by Mann-Whitney U test. E1/E2 ratio was lower in the SC group than the PO group: 0.4 ± 0.1 vs. 8.0 ± 2.9; p<0.001 by t-test. There was no significant difference in median serum SHBG (nmol/L) between SC and PO groups: 71.7 (19.3-146.7), n=15 vs. 73.4 (51.0-187.4), n=14; p=0.20 by Mann-Whitney U test. Mean post- and pre-dose serum E2 levels in 5 patients were 138.0 ± 24.0 and 88.0 ± 57.6, respectively. There was one transient local reaction and no systemic allergic or inflammatory reactions in the SC group with no systemic reactions in the PO group. Conclusion: These results demonstrate that SC E2 at doses of 1.4-6 mg/week can be administered safely to achieve therapeutic serum E2 levels and suppress serum T levels to within the normal female range. Our preliminary data reveal lower serum E1 levels in the SC group than in the PO group suggesting reduced hepatic first-pass metabolism with SC administration; this pattern was not seen with serum SHBG levels. Post- and pre-dose serum E2 levels revealed only a mild decline in E2 levels between injections. 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

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

6961 Evaluation of Safety and Efficacy of Administration of Estradiol by Subcutaneous Injection in Transgender Women

Abstract Disclosure: H. Perkins: None. H. Moreau: None. J. LaBudde: None. W. Craig: None. D.I. Spratt: None. Background: Off-label use of subcutaneous (SC) estradiol (E2) by transgender women for gender-affirming hormone therapy is becoming increasingly widespread, despite a lack of published data regarding its efficacy and safety. Methods: This retrospective cohort study used manual data extraction from electronic medical records for patients ages 18-79 years, currently or previously receiving oral (PO) 17-beta E2 or SC E2 valerate therapy at Maine Medical Center Reproductive Endocrinology and Infertility and Gender Clinics between 5/30/14-5/30/23, who completed E2 dose adjustments aimed at obtaining a serum E2 of 75-250 pg/mL. SC E2 was administered weekly and PO E2 daily. Serum testosterone (T), estrone (E1), and sex hormone binding globulin (SHBG) levels were recorded if drawn within 90 days of E2 measurement on an optimized dose. In a subset of patients receiving SC E2, serum E2 levels were drawn 1-2 days post- and pre-injection. All patient-reported local or systemic reactions were recorded. Data are expressed as median (full range) or mean ± standard deviation (full range). Results: 45 patients were included with no significant differences in demographics between PO (n=20) and SC (n=25) groups. Both groups achieved therapeutic E2 levels after dose adjustment without statistical difference in mean serum E2 (pg/mL) between SC and PO groups: 148.7 ± 41.0 (78-226) vs. 151.6 ± 31.7 (97-208); p=0.79 by t-test. In patients without orchiectomy, both SC and PO groups had T (ng/dL) suppressed to normal adult female range (10-55) in 11/12 SC patients and in 17/17 PO patients; median T was 14.0 (7.7-86) for SC vs. 20.6 (3.4-42) for PO; p=0.98 by Mann-Whitney U test. Median E2 dose (mg/week) in the SC group was 3.0 (1.4-6.0) and in the PO group was 42.0 (28-84). Median serum E1 (pg/mL) was lower in the SC group than the PO group: 73.5 (29-115), n=12 vs. 907 (596-1601), n=5, p<0.001 by Mann-Whitney U test. E1/E2 ratio was lower in the SC group than the PO group: 0.4 ± 0.1 vs. 8.0 ± 2.9; p<0.001 by t-test. There was no significant difference in median serum SHBG (nmol/L) between SC and PO groups: 71.7 (19.3-146.7), n=15 vs. 73.4 (51.0-187.4), n=14; p=0.20 by Mann-Whitney U test. Mean post- and pre-dose serum E2 levels in 5 patients were 138.0 ± 24.0 and 88.0 ± 57.6, respectively. There was one transient local reaction and no systemic allergic or inflammatory reactions in the SC group with no systemic reactions in the PO group. Conclusion: These results demonstrate that SC E2 at doses of 1.4-6 mg/week can be administered safely to achieve therapeutic serum E2 levels and suppress serum T levels to within the normal female range. Our preliminary data reveal lower serum E1 levels in the SC group than in the PO group suggesting reduced hepatic first-pass metabolism with SC administration; this pattern was not seen with serum SHBG levels. Post- and pre-dose serum E2 levels revealed only a mild decline in E2 levels between injections. Presentation: 6/3/2024

9224 Evaluation of Safety and Efficacy of Administration of Estradiol by Subcutaneous Injection in Transgender Women

Abstract Disclosure: H. Perkins: None. H. Moreau: None. J. LaBudde: None. W. Craig: None. D.I. Spratt: None. Background: Off-label use of subcutaneous (SC) estradiol (E2) by transgender women for gender-affirming hormone therapy is becoming increasingly widespread, despite a lack of published data regarding its efficacy and safety. Methods: This retrospective cohort study used manual data extraction from electronic medical records for patients ages 18-79 years, currently or previously receiving oral (PO) 17-beta E2 or SC E2 valerate therapy at Maine Medical Center Reproductive Endocrinology and Infertility and Gender Clinics between 5/30/14-5/30/23, who completed E2 dose adjustments aimed at obtaining a serum E2 of 75-250 pg/mL. SC E2 was administered weekly and PO E2 daily. Serum testosterone (T), estrone (E1), and sex hormone binding globulin (SHBG) levels were recorded if drawn within 90 days of E2 measurement on an optimized dose. In a subset of patients receiving SC E2, serum E2 levels were drawn 1-2 days post- and pre-injection. All patient-reported local or systemic reactions were recorded. Data are expressed as median (full range) or mean ± standard deviation (full range). Results: 45 patients were included with no significant differences in demographics between PO (n=20) and SC (n=25) groups. Both groups achieved therapeutic E2 levels after dose adjustment without statistical difference in mean serum E2 (pg/mL) between SC and PO groups: 148.7 ± 41.0 (78-226) vs. 151.6 ± 31.7 (97-208); p=0.79 by t-test. In patients without orchiectomy, both SC and PO groups had T (ng/dL) suppressed to normal adult female range (10-55) in 11/12 SC patients and in 17/17 PO patients; median T was 14.0 (7.7-86) for SC vs. 20.6 (3.4-42) for PO; p=0.98 by Mann-Whitney U test. Median E2 dose (mg/week) in the SC group was 3.0 (1.4-6.0) and in the PO group was 42.0 (28-84). Median serum E1 (pg/mL) was lower in the SC group than the PO group: 73.5 (29-115), n=12 vs. 907 (596-1601), n=5, p<0.001 by Mann-Whitney U test. E1/E2 ratio was lower in the SC group than the PO group: 0.4 ± 0.1 vs. 8.0 ± 2.9; p<0.001 by t-test. There was no significant difference in median serum SHBG (nmol/L) between SC and PO groups: 71.7 (19.3-146.7), n=15 vs. 73.4 (51.0-187.4), n=14; p=0.20 by Mann-Whitney U test. Mean post- and pre-dose serum E2 levels in 5 patients were 138.0 ± 24.0 and 88.0 ± 57.6, respectively. There was one transient local reaction and no systemic allergic or inflammatory reactions in the SC group with no systemic reactions in the PO group. Conclusion: These results demonstrate that SC E2 at doses of 1.4-6 mg/week can be administered safely to achieve therapeutic serum E2 levels and suppress serum T levels to within the normal female range. Our preliminary data reveal lower serum E1 levels in the SC group than in the PO group suggesting reduced hepatic first-pass metabolism with SC administration; this pattern was not seen with serum SHBG levels. Post- and pre-dose serum E2 levels revealed only a mild decline in E2 levels between injections. Presentation: 6/3/2024

8551 Comparability of Free Testosterone Measurements

Abstract 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

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

6961 Evaluation of Safety and Efficacy of Administration of Estradiol by Subcutaneous Injection in Transgender Women

Abstract Disclosure: H. Perkins: None. H. Moreau: None. J. LaBudde: None. W. Craig: None. D.I. Spratt: None. Background: Off-label use of subcutaneous (SC) estradiol (E2) by transgender women for gender-affirming hormone therapy is becoming increasingly widespread, despite a lack of published data regarding its efficacy and safety. Methods: This retrospective cohort study used manual data extraction from electronic medical records for patients ages 18-79 years, currently or previously receiving oral (PO) 17-beta E2 or SC E2 valerate therapy at Maine Medical Center Reproductive Endocrinology and Infertility and Gender Clinics between 5/30/14-5/30/23, who completed E2 dose adjustments aimed at obtaining a serum E2 of 75-250 pg/mL. SC E2 was administered weekly and PO E2 daily. Serum testosterone (T), estrone (E1), and sex hormone binding globulin (SHBG) levels were recorded if drawn within 90 days of E2 measurement on an optimized dose. In a subset of patients receiving SC E2, serum E2 levels were drawn 1-2 days post- and pre-injection. All patient-reported local or systemic reactions were recorded. Data are expressed as median (full range) or mean ± standard deviation (full range). Results: 45 patients were included with no significant differences in demographics between PO (n=20) and SC (n=25) groups. Both groups achieved therapeutic E2 levels after dose adjustment without statistical difference in mean serum E2 (pg/mL) between SC and PO groups: 148.7 ± 41.0 (78-226) vs. 151.6 ± 31.7 (97-208); p=0.79 by t-test. In patients without orchiectomy, both SC and PO groups had T (ng/dL) suppressed to normal adult female range (10-55) in 11/12 SC patients and in 17/17 PO patients; median T was 14.0 (7.7-86) for SC vs. 20.6 (3.4-42) for PO; p=0.98 by Mann-Whitney U test. Median E2 dose (mg/week) in the SC group was 3.0 (1.4-6.0) and in the PO group was 42.0 (28-84). Median serum E1 (pg/mL) was lower in the SC group than the PO group: 73.5 (29-115), n=12 vs. 907 (596-1601), n=5, p<0.001 by Mann-Whitney U test. E1/E2 ratio was lower in the SC group than the PO group: 0.4 ± 0.1 vs. 8.0 ± 2.9; p<0.001 by t-test. There was no significant difference in median serum SHBG (nmol/L) between SC and PO groups: 71.7 (19.3-146.7), n=15 vs. 73.4 (51.0-187.4), n=14; p=0.20 by Mann-Whitney U test. Mean post- and pre-dose serum E2 levels in 5 patients were 138.0 ± 24.0 and 88.0 ± 57.6, respectively. There was one transient local reaction and no systemic allergic or inflammatory reactions in the SC group with no systemic reactions in the PO group. Conclusion: These results demonstrate that SC E2 at doses of 1.4-6 mg/week can be administered safely to achieve therapeutic serum E2 levels and suppress serum T levels to within the normal female range. Our preliminary data reveal lower serum E1 levels in the SC group than in the PO group suggesting reduced hepatic first-pass metabolism with SC administration; this pattern was not seen with serum SHBG levels. Post- and pre-dose serum E2 levels revealed only a mild decline in E2 levels between injections. Presentation: 6/3/2024

7494 Glycerol Phenylbutyrate Treatment of Two Patients with Monocarboxylate Transporter 8 Deficiency

Abstract Disclosure: A. Zung: None. N. Sonntag: None. U. Schweizer: None. E. Banne: None. D. Braun: None. Context: Monocarboxylate transporter 8 (MCT8) deficiency is a rare genetic disease that leads to severe global developmental delay. MCT8 facilitates thyroid hormone (TH) transport across the cell membrane, and the serum TH profile is characterized by high T3 and low T4 levels. Currently, the two thyromimetic agents 3,5-diiodothyropropionic acid (DITPA) and triiodothyroacetic acid (TRIAC) have been evaluated in the treatment of these patients, as they both partially restore intracellular TH action independent of MCT8. Recent studies have shown that the chemical chaperone sodium phenylbutyrate (NaPB) restored mutant MCT8 function and increased TH content in patient-derived induced pluripotent stem cells, making it a potential treatment for MCT8 deficiency. Objective: We aimed to assess the efficacy and safety of glycerol phenylbutyrate (GPB) in MCT8 deficiency. Methods: We treated two monozygotic twins aged 14.5 years with MCT8 deficiency due to P321L mutation with escalating doses of GPB over 13 months. We recorded TH, serum markers of peripheral hyperthyroidism, vital signs, anthropometric measurements and neurocognitive functions by several neurodevelopment validated tests. Resting metabolic rate (RMR) was measured by indirect calorimetry. Serum metabolites of GPB were monitored as a safety measure. In-vitro effects of NaPB were evaluated in MDCK1 cells stably expressing the MCT8P32[1]L mutation. Results: NaPB restored mutant MCT8 expression in MDCK1 cells and increased T3 transport into cells carrying the P321L mutation. GPB treatment yielded a dose-dependent decrease in FT3 and an increase in FT4 serum levels. The patients showed an elevation in cholesterol levels in parallel with GPB dose, but sex-hormone binding protein (SHBG), another marker of peripheral hyperthyroidism was not affected. The patients showed a significant weight gain simultaneously with a reduction in RMR. Only minor neuro-cognitive improvement was observed, mainly in hyperreflexia score, slight improvement in gross motor functions and a mild progression in cognitive functions. Serum metabolites of GPB did not exceed the toxic range but elevated liver transaminases restricted the dose intensification of GPB. Conclusions: In the first report of GPB treatment in MCT8 deficiency patients we found an improvement in TH profile and body-mass index (BMI). The reduction in T3 levels could contribute to the remarkable increase in BMI-SDS, since various aspects of peripheral hyperthyroidism in MCT8 deficiency, including poor weight gain, were attributed to elevated T3. The limited effects of GPB treatment on cognitive and motor functions can derive from the advanced age of the patients at the time of the intervention. Presentation: 6/2/2024

8162 A Unique Presentation of Ovarian Steroid Cell Tumor Causing Hyperandrogenism in a Postmenopausal Woman

Abstract Disclosure: A. Rehan: None. M. Pandey: None. I. Goyal: None. E. Punni: None. N. Shakir: None. Background:­­­ Steroid cell tumors of the ovary are a rare entity, constituting less than 0.1% of all ovarian tumors. These tumors can present with diverse endocrine and paraneoplastic effects, including androgen excess and polycythemia. Hyperandrogenism in females can lead to hirsutism, virilization, alopecia, menstrual irregularities, acne, and emotional changes, with complications including hyperlipidemia and insulin resistance. There are various causes of androgen excess in a female including polycystic ovary syndrome (PCOS), androgen-secreting tumors, Cushing’s syndrome, and congenital adrenal hyperplasia. In a postmenopausal woman displaying signs of androgen excess, one must consider androgen-secreting tumors, and even the rare ovarian steroid cell tumor as a possible cause. Clinical Case: A 62-year-old female with type 2 diabetes mellites, obstructive sleep apnea, anxiety and depression initially presented to her primary care provider with fatigue, light-headedness, and weight loss. Initial blood work done revealed a hemoglobin greater than 20 g/dL (NR 12-16) and hematocrit greater than 60% (NR 36-48), requiring several sessions of phlebotomy. Symptoms persisted and she was finally referred to a hematologist who noted physical exam findings of hirsutism and virilization, including temporal hair loss and excess facial/body hair growth. Other concerning signs included clitoromegaly, decrease in chest size, and deepening voice. Menopause had occurred at age 50, and the patient did not have any issues with fertility during her reproductive years. Biochemical evaluation revealed testosterone level of greater than 1500 ng/dL (NR 19-82) with normal sex hormone binding globulin level, DHEA-S 652 ug/dL (NR 29-220), appropriately suppressed FSH/ LH, and normal salivary cortisol levels. Tumor markers showed normal CEA, and alpha fetoprotein but elevated CA 125 to 80.5 U/ml (NR < 38.1). Pelvic ultrasound demonstrated a 12 cm heterogeneously echoic, vascular right adnexal mass concerning for ovarian malignancy. Pelvic MRI showed a 9.8 cm right sided cystic and solid adnexal mass. The patient underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy, peritoneal biopsies, and omentectomy. Pathology revealed a stage IA steroid cell tumor measuring 11.4 cm. After resection, the patient reported improvement in facial hair and fatigue. Labs showed normalization of hemoglobin, hematocrit, and testosterone levels. Conclusion: This rare case highlights the importance of considering steroid cell tumor as a cause of polycythemia with hyperandrogenism. Timely diagnosis and intervention play a critical role in preventing irreversible virilization, mitigating malignant risks, and, in certain instances, preserving fertility. Generally, the prognosis is favorable, and symptom and lab normalization is often achieved through surgical resection. Presentation: 6/2/2024

7467 Supplement Use Among Transgender Patients: Case Reports and Literature Review

Abstract Disclosure: H. Cunningham: None. Q. Jones: None. C. Kelley: None. The barriers to initiating gender affirming medical treatment are innumerable and increasing in the wake of wide-sweeping anti-trans legislation, leading many transgender individuals to utilize more accessible means of transitioning. We provide examples of patient-initiated supplement use at a gender medicine clinic in the Southeast. We describe a 60-year-old transgender woman who was unable to establish care due to lack of affirming providers in her region and insurance approval delays. She began taking Pueraria mirifica, along with saw palmetto and fenugreek, for feminization. Subsequently, her breast size increased from an A to B cup, and she noticed fat redistribution to her hips. When finally seen one year later, labs demonstrated suppressed luteinizing and follicle stimulating hormones and increased sex hormone binding globulin, with an associated decrease in estradiol and testosterone levels. Cessation of supplements resulted in lab normalization. Our second case describes masculinizing effects, including voice deepening, experienced by a transgender man using a supplement that contained "orchic extract.” Supplements used for gender affirmation can also have more adverse effects, including polycythemia in the setting of trenbolone, an illicit steroidogenic performance enhancing supplement used for masculinization by some patients assigned female at birth. Patients without access to gender affirming hormones through a medical provider, or who do not feel comfortable accessing health care, may be more likely to use supplements purchased online without a prescription. Considering this, we must create more safe spaces for gender affirming care and ask all transgender patients about supplement use. Providers should consider supplement use as a possible explanation for unexpected lab results. The literature on supplement use for gender-affirming effects is sparse; this presentation provides a summary of and contributes to the current literature on this topic. Presentation: 6/2/2024

Investigating the Genetic Association of 40 Biochemical Indicators with Parkinson's Disease.

The mechanisms of Parkinson's disease (PD) are not fully understood, which hinders the development of effective therapies. Research indicates that lower levels of biochemical indicators like bilirubin, vitamin D, and cholesterol may elevate the risk of PD. However, clinical studies on abnormal levels of biochemical indicators in PD patients' circulation are inconsistent, leading to ongoing debate about their association with PD. Here, we investigate the genetic correlation between 40 biochemical indicators and PD using a bidirectional two-sample Mendelian randomization (MR) approach to uncover potential causal relationships. Data from genome-wide association studies (GWAS) were utilized, with genetic variations from specific lineages serving as instrumental variables (IVs). The methodology followed the STROBE-MR checklist and adhered to the three principal assumptions of MR. Statistical analyses employed methods including inverse variance weighting (IVW), MR-Egger, weighted median, and weighted mode. Biochemical indicators including albumin, C-reactive protein (CRP), and sex hormone-binding globulin (SHBG) showed significant associations with PD risk. Elevated levels of albumin (OR = 1.246, 95% CI 1.006-1.542, P = 0.043) and SHBG (OR = 1.239, 95% CI 1.065-1.439, P = 0.005) were linked to higher PD risk. Conversely, increased CRP levels (OR = 0.663, 95% CI 0.517-0.851; P = 0.001) could potentially lower PD risk. The robustness of the results was confirmed through various MR analysis techniques, including assessments of directional pleiotropy and heterogeneity using MR-Egger intercept and MR-PRESSO methods. This study systematically reveals, for the first time at the genetic level, the relationship between 40 biochemical indicators and PD risk. Our research verifies the role of inflammation in PD and provides new genetic evidence, further advancing the understanding of PD pathogenesis. The study shows a positive correlation between albumin and SHBG with PD risk and a negative correlation between CRP and PD risk. This study identifies for the first time that SHBG may be involved in the onset of PD and potentially worsen disease progression.

A-078 Harmonization of Immunoassay Reference Intervals with LC-MS/MS for Total and Calculated Free Testosterone Measurement

Abstract Background Management of male hypogonadism relies on accurate serum testosterone testing and reference values. This study aimed to establish harmonized reference ranges for total and calculated free testosterone in adults using the Siemens Atellica immunoassay, validated against a reference method. Methods The Siemens Atellica IM total testosterone assay is a fully automated competitive chemiluminescent immunoassay. We conducted 25 de-identified serum samples. Inter-laboratory correlation studies for total testosterone were performed on in-house Siemens Atellica and liquid chromatography-tandem mass spectrometry (LC-MS/MS) at a reference laboratory. Free testosterone was calculated using the International Society for the Study of the Aging Male (ISSAM) Free Testosterone calculator, which can be accessed from the ISSAM website, http://www.issam.ch/freetesto.htm, using the assayed concentrations of testosterone and Sex Hormone Binding Globulin (SHBG) on the Siemens Atellica IM system. The Siemens Atellica IM SHBG assay is a sandwich monoclonal immunoassay. Calculated free testosterone was compared with LC-MS/MS. Deming and linear regression, and Bland-Altman plot were employed for data analysis. Reference intervals were adopted from the reference laboratory and verified using 20 male and 20 female healthy samples. Total testosterone: Male 240-950 ng/dL, Female 8-60 ng/dL; Free testosterone: Male 2.29-20.7 ng/dL, Female 0-1.08 ng/dL. Results Strong correlations were observed between Siemens Atellica and LC-MS/MS for total testosterone (R^2 = 0.9915, slope = 0.988, intercept = 35) and for calculated free testosterone (R^2 = 0.9645, slope = 0.988, intercept = -0.4). Adopted reference intervals were verified using local healthy samples. Conclusions Harmonized reference intervals for total and calculated free testosterone, validated on Siemens Atellica, offer consistent results comparable to LC-MS/MS. This study demonstrates the feasibility of establishing standardized reference ranges for testosterone assays across laboratories.