Long-term outcomes in patients with congenital adrenal hyperplasia treated with hydrocortisone modified-release hard capsules
File(s)
Published version
Author(s)
Arlt, Wiebke
de la Perriere, Aude Brac
Hirschberg, Angelica L
Merke, Deborah P
Newell-Price, John DC
Type
Journal 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.
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.
Date Issued
2025-07-01
Date Acceptance
2025-06-13
Citation
European Journal of Endocrinology (EJE), 2025, 193 (1), pp.76-84
ISSN
0804-4643
Publisher
Oxford University Press
Start Page
76
End Page
84
Journal / Book Title
European Journal of Endocrinology (EJE)
Volume
193
Issue
1
Copyright Statement
© The Author(s) 2025. Published by Oxford University Press on behalf of European Society of Endocrinology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/40576296
PII: 8165922
Subjects
21-hydroxylase deficiency
adrenogenital syndrome adrenal insufficiency
ADULTS
CHILDREN
Chronocort
COHORT
congenital adrenal hyperplasia
CRISES
Endocrinology & Metabolism
FREQUENCY
glucocorticoid
hydrocortisone
INSUFFICIENCY
Life Sciences & Biomedicine
Science & Technology
Publication Status
Published
Coverage Spatial
England
Date Publish Online
2025-06-17