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Clinical Trial
. 2025 Jun 30;193(1):76-84.
doi: 10.1093/ejendo/lvaf130.

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

Wiebke Arlt  1   2 , Aude Brac de la Perrière  3 , Angelica L Hirschberg  4   5 , Deborah P Merke  6 , John D C Newell-Price  7 , Alessandro Prete  8   9 , D Aled Rees  10 , Nicole Reisch  11 , Philippe A Touraine  12 , Hanna Bendfeldt  13 , John Porter  13 , Helen Coope  13 , Richard J M Ross  7
Affiliations
Free article
Clinical Trial

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

Wiebke Arlt et al. Eur J Endocrinol. .
Free article

Abstract

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 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.

Keywords: 21-hydroxylase deficiency; Chronocort; adrenogenital syndrome adrenal insufficiency; congenital adrenal hyperplasia; glucocorticoid; hydrocortisone.

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Conflict of interest statement

Conflict of interest: The authors have the following conflicts of interest to declare in relation to this work: W.A., A.B.d.l.P., A.L.H., D.P.M, J.D.C.N.-P., A.P., D.A.R., and N.R. were study investigators. D.P.M has received research funds from Diurnal Ltd. (now Neurocrine UK Ltd.) through an NIH Cooperative Research and Development Agreement. R.J.M.R. and J.P. are consultants to, H.B. a contractor to, and H.C. an employee of Neurocrine UK Ltd. N.R. is on the editorial board of EJE. She was not involved in the review or editorial process for this paper, on which she is listed as an author.

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