Long-term outcomes in patients with congenital adrenal hyperplasia treated with hydrocortisone modified-release hard capsules

作者：Wiebke Arlt, Aude Brac de la Perrière, Angelica Lindén Hirschberg, Deborah P. Merke, John D C Newell-Price, Alessandro Prete, Aled Rees, Nicole Reisch, Philippe A. Touraine, Hanna Bendfeldt, John M. Porter, Helen Coope, Richard John M Ross · 发表于：European Journal of Endocrinology · 年份：2025 · DOI：10.1093/ejendo/lvaf130 · 被引用次数：13 · 研究领域：Sexual Differentiation and Disorders、Adrenal Hormones and Disorders、Hormonal and reproductive studies

BACKGROUND: Hydrocortisone modified-release hard capsules (MRHC, development name Chronocort) replace the physiological overnight cortisol rise and improve the biochemical control of congenital adrenal hyperplasia (CAH). AIM: This study aims to evaluate long-term safety, tolerability, and efficacy of MRHC. METHODS: This is an open-label follow-on study. RESULTS: Ninety-one patients with classic CAH, mean age 37 years, 68% female, 32% male, entered the study and 22 discontinued. Median treatment duration was 4 years (range 0.2-5.8). Median hydrocortisone dose at study entry was 30 mg/day and reduced to 20 mg/day after 24 weeks and stayed stable thereafter until 48 months (P < .0001). Disease control improved on MRHC for the steroid disease markers serum 17-hydroxyprogesterone (17OHP) (P < .03) and androstenedione (A4) (P < .002). After 4 years, the majority of patients had a 17OHP < 4-fold upper limit of normal (ULN) (71%) and an A4 <ULN (90%). Measurement of 17OHP and A4 at 09:00 h and 13:00 h gave similar results. Of the 37 women < 50 years of age who were not on contraceptives over the whole study period, 5 became pregnant (13.5%). Of the men, 13.8% (4/29) had a partner pregnancy. Seven patients had an adrenal crisis with 1 patient reporting 8 of these giving an incidence of 3.9 crises per 100 patient years. CONCLUSIONS: Modified-release hard capsule treatment resulted in hydrocortisone dose reduction followed by a stable dose with improved biochemical control associated wi...