Endocrine Abstracts

Background: Hypogonadism is frequent in men with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD). It has recently been demonstrated that testicular adrenal rest tumors (TART) are a source of 11-oxygenated androgens that might impair testicular function, in addition to their local compressive effects. Data on long-term course of testicular function in men with 21OHD and the role of potential influential factors such as presence of TART and 11-oxygenated androgen formation is sparse.

Methods: Retrospective single-center study in 30 men with classic 21OHD (n=11 with TART, n=16 without TART, n=3 unknown). Median age at baseline was 31.0 years (IQR 26-38). The median observation period was 12 years (IQR 8-13). Levels of testosterone (T), 17-hydroxyprogesterone (17-OHP), androstenedione (A4) and 11-oxygenated androgens were measured simultaneously by LC-MS/MS.

Results: On average, 43.2% (No TART) and 54.6% (TART) of all T measurements in each individual patient were below the reference range (n.s.) with gonadotropin levels being inappropriately normal or suppressed in most patients. In multivariate mixed model analysis, including age, BMI, type of glucocorticoid (GC), GC-equivalence dosage and phenotype, T levels were comparable between men with and without TART. 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) and increased in those with TART (Baseline 9.48 ± 1.68 vs. last visit 14.9 ± 2.3 nmol/l (P=0.006). At baseline, the A4/T-ratio 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, indicating a decrease in the A4/T-ratio in men with TART (P=0.04). This resulted in 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 nmol/l) 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.