Endocrine Abstracts

JOINT1339

Background: New hydrocortisone formulations with modified release are increasingly used in treating patients with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD). The goal is better androgen control while reducing overall glucocorticoid exposure through more physiological hydrocortisone release and replacement. However, the effects of switching from conventional glucocorticoid therapy to modified-release hydrocortisone (MR-HC) on steroid metabolism remain uninvestigated

Methods: The steroid metabolome in 24-h urine samples was analyzed in 22 patients with classic CAH due to 21OHD (10 women, 12 men). Before the switch, 10 patients received conventional hydrocortisone, 9 prednisolone, and 3 combination therapy. The switch to MR-HC was performed using equivalent dose conversion (prednisolone conversion factor = 5). Urine samples were collected before and six months after the switch and analyzed using gas chromatography-mass spectrometry (GC-MS).

Results: Based on serum androstenedione and 17-OHP levels, three patients were classified as not well controlled at baseline. After switching, one patient transitioned from well-controlled to not well-controlled, and another showed the opposite trend. Median hydrocortisone-equivalent dosages were 25 mg (IQR 24.375–35.625) before and 27.5 mg (IQR 20–35) after the switch to MR-HC (P = 0.109). The switch led to a trend toward increased major cortisol metabolites (5α-THF + THF + THE, P = 0.093) and overall urinary cortisol metabolites (5α-THF + THF + THE + a-C + b-C + a-Cl + b-Cl; P = 0.059) in those previously on HC. No absolute change in 17-OHP metabolites (Po-5β3α, Po-5α3α, PT, 11-OH-P) or significant change in overall 11-oxygenated androgens was observed. In women, 11-deoxygenated androgens showed a declining trend (P = 0.071), leading to a significant increase in the 11-oxygenated (11OH-An + 11O-An + 11OH-Et) to 11-deoxygenated androgen ratio (An + Et + A5-3β, 17α + A5-3β, 17β + DHEA + 16α-OH-DHEA + A5T-16α) from 0.64 (IQR 0.24–2.10) to 2.75 (IQR 1.67–5.75, P = 0.007), indicating increased adrenal suppression. In men, no significant change in 11-oxygenated or deoxygenated androgens was found. However, individually, significant PT reductions (6790 vs. 2982 µg/d) were seen in 14/22 patients, 11OH-An reductions (828 vs. 426 µg/d) in 12/22, and An reductions (823 vs. 433 µg/d) in 12/22.

Conclusion: While overall glucocorticoid exposure remained comparable, trends toward increased urinary cortisol metabolites suggest a shift in cortisol metabolism, possibly reflecting optimised cortisol availability resulting in increased adrenal androgen suppression. Individual patients of both sexes may therefore benefit from a switch to modified-release hydrocortisone.