SAT282 Hypogonadism In Men With Congenital Adrenal Hyperplasia. A Retrospective Longitudinal Analysis With A Special Focus On Testicular Adrenal Rest Tumors And 11-oxygenated Androgens
Authors: Auer Matthias K , Lottspeich Christian , Bidlingmaier Martin , Nowotny Hanna Franziska , Tschaidse Lea , Auchus Richard Joseph , Reisch Nicole 
Published: October 2023

Disclosure: M.K. Auer: None. C. Lottspeich: None. M. Bidlingmaier: None. H.F. Nowotny: None. L. Tschaidse: None. R.J. Auchus: None. N. Reisch: None.

Background: Hypogonadism is a common issue in men with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD). While this is mostly resulting from extra-gonadal steroid production, testicular function may also be impaired due to the presence of testicular adrenal rest tumors (TART). In addition to their local compressive effects, it has recently been demonstrated that TART are a source of 11-oxygenated androgens that might impair testicular function. Little is known about the long-term course of testicular function in men with 21OHD in general and the role of potential influential factors such as presence of TART and 11-oxygenated androgen formation in particular. Methods: Retrospective single-center study in 30 men with classic 21OHD (N = 11 with TART, N = 16 without TART, N = 3 unknown TART status). Median age at baseline was 31.0 years (IQR 26-38). Median observation period was 12 years (IQR 8-13). The median number of outpatient visits and blood samplings per patient during this time was 8.5 (IQR 6-10). Testosterone (T), 17-hydroxyprogesterone (17-OHP), androstenedione (A4) and 11-oxygenated androgens were measured simultaneously from stored serum samples by LC-MS/MS. Results: On average, 43.2% (No TART) and 54.6% (TART) of all T measurements in each patient were below the reference range (n.s.). In most patients, gonadotropin levels were normal or suppressed. In univariate as well as multivariate mixed model analysis, including age, BMI, type of glucocorticoid (GC), GC-equivalence dosage and phenotype (salt wasting vs simply virilizing), T levels were comparable between men with and without TART. While T levels remained stable during the observation period in men without TART (Baseline 11.37 ± 1.52 nmol/l, last visit 12.1 ± 2.1 nmol/l) they increased in those with TART (Baseline 9.48 ± 1.68 vs. last visit 14.9 ± 2.3 nmol/l (Time*Group F1,7.247 = 7.558; p = 0.006). At baseline, the A4/T-ratio as a marker of adrenal T production was significantly higher in men with TART (1.39 ± 1.63) than in those without (0.27 ± 1.63), and there was a Time*Group interaction, again indicating a decrease in the A4/T-ratio in men with TART (F1,47.843 = 2.008; p = 0.04). This resulted in only a trend for the A/T-ratio being higher in men with TART (0.5 ± 1.6 vs 0.3 ± 1.5; p = 0.057) across the whole observation period. 11-ketotestosterone levels were higher in men with TART (1.8 ± 0.006 pg/ml) than in men without TART (0.68 ± 0.006 nmol/l) but remained unchanged over time in both groups. Conclusion: A normal serum T does not exclude hypogonadotropic hypogonadism in men with 21OHD, which is a common problem that appears to remain stable in the long run. The presence of TART does not have a negative effect on T-levels. In contrast, the detection of TART should prompt further assessment, including A4, gonadotropins, and 11-ketotestosterone, followed by treatment optimization to improve gonadal T production.

Presentation: Saturday, June 17, 2023