Arlt Wiebke, Brac de la Perrière Aude, Hirschberg Angelica L, Merke Deborah P, Newell-Price John D C, Prete Alessandro, Rees D Aled, Reisch Nicole, Touraine Philippe A, Bendfeldt Hanna, Porter John, Coope Helen, Ross Richard J M
MRC Laboratory of Medical Sciences (MRC LMS), London W12 0HS, United Kingdom.
Imperial College London, Endocrinology, London SW7 2AZ, United Kingdom.
Eur J Endocrinol. 2025 Jun 30;193(1):76-84. doi: 10.1093/ejendo/lvaf130.
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).
This study aims to evaluate long-term safety, tolerability, and efficacy of MRHC.
This is an open-label follow-on study.
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.
Modified-release hard capsule treatment resulted in hydrocortisone dose reduction followed by a stable dose with improved biochemical control associated with fertility. Biochemical control could be reliably monitored by a single blood sample taken between 09:00 and 13:00 h. The incidence of adrenal crises was below that reported previously in patients with CAH.
氢化可的松缓释硬胶囊（MRHC，研发名称Chronocort）可替代生理性夜间皮质醇升高，并改善先天性肾上腺皮质增生症（CAH）的生化控制。
本研究旨在评估MRHC的长期安全性、耐受性和疗效。
这是一项开放标签的随访研究。
91例经典型CAH患者进入研究，平均年龄37岁，68%为女性，32%为男性，22例退出。中位治疗持续时间为4年（范围0.2 - 5.8年）。研究开始时氢化可的松中位剂量为30毫克/天，24周后降至20毫克/天，此后直至48个月保持稳定（P <.0001）。对于类固醇疾病标志物血清17-羟孕酮（17OHP）（P <.03）和雄烯二酮（A4）（P <.002），MRHC治疗后疾病控制得到改善。4年后，大多数患者的17OHP <正常上限（ULN）的4倍（71%），A4 < ULN（90%）。在09:00和13:00测量17OHP和A4得到类似结果。在整个研究期间未使用避孕药的37名年龄<50岁的女性中，5名怀孕（13.5%）。男性中，13.8%（4/29）伴侣怀孕。7例患者发生肾上腺危象，1例患者报告8次，发生率为每100患者年3.9次危象。
缓释硬胶囊治疗导致氢化可的松剂量降低，随后剂量稳定，生化控制改善且与生育相关。在09:00至13:00之间采集的单一血样可可靠地监测生化控制情况。肾上腺危象的发生率低于先前报道的CAH患者。
