ESPE Abstracts

Background: Hormone replacement in congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) aims at mimicking the physiologic secretion patterns of cortisol and aldosterone. However, available glucocorticoid preparations do not allow to achieve an adequate cortisol peak during the early morning hours, a milder peak during the evening, and low cortisol serum levels at night. As a consequence, intermittent ACTH hypersecretion may induce the development of testicular adrenal rest tumours (TART), and recurring phases of adrenal androgen excess may suppress central hypothalamic-pituitary-gonadal axis activity, which both may impair spermatogenesis and thus male fertility.

Patients and Methods: Twenty males with salt-waisting (SW) or simple virilising (SV) CAH (confirmed by biallelic CYP21A2 mutations) consented to switching ongoing standard treatment to the recently licensed modified-release hydrocortisone formulation Efmody®. In n = 17 semen samples (analysed according to WHO standards) and hormonal parameters (measured by LC-MSMS) were evaluated at baseline and over a period of 12 months of MR-HC treatment. Three men discontinued MR-HC due to suspected adverse effects, including joint pain, increased appetite and deteriorated mood.

Results: The median age of men included in the evaluation was 28 years (20-47). The median Efmody® dose required for optimal cortisol replacement was 16 mg/m² (10-22.7), corresponding to 30 mg/day (25-50), with one third of the daily dose taken at 7:00 a.m. and two thirds taken at 11.00 p.m. The dose of fludrocortisone was not changed. 17-OHP serum concentrations significantly decreased from a median of 9.1 nmol/l (1.3-374) to a median of 3.4 (0.95-69.6); P = 0.013, and androstenedione decreased from 2.0 nmol/l (0.76-33.8) to 1.3 (0.16-10.81); P = 0.113; n.s. Median sperm concentrations rose from 6.3 mill/ml (0-53.6) to 12.7 mill/ml (0-74.8); P = 0.1; n.s.; while total sperm counts significantly increased from a median of 20.8 (0-111.7) to 44.3 (0-111.7); P = 0.026. Serum LH rose from a median of 3.6 U/l (0.4-11.4) to 4.7 U/l (0.7-11.5), in concert with median serum testosterone concentrations, which increased from 14.5 (7.2-24.8) to 19.8 nmol/l (8.1-48.7), while median INSL3 concentrations did not change: 2.34 ng/ml (0.22-16,1) vs. 2.32 (0.15-19.8). Median BMI decreased slightly, but significantly, from 27,2 (22,6-51,6) to 27,0 (22,7-46,9) kg/m2.

Conclusion: The modified release hydrocortisone preparation Efmody® seems to be a valid alternative to conventional glucocorticoid replacement in men with CAH, with potential beneficial effects on hypothalamic-pituitary-adrenal and -gonadal axis hormone concentrations, semen quality and body weight.