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Modified-release hydrocortisone in congenital adrenal hyperplasia

Merke, Deborah P., Mallappa, Ashwini, Arlt, Wiebke, Brac de la Perriere, Aude, Hirschberg, Angelica Lindén, Juul, Anders, Newell-Price, John, Perry, Colin G., Prete, Alessandro, Rees, D. Aled ORCID:, Reisch, Nicole, Stikkelbroeck, Nike, Tourraine, Phillippe, Maltby, Kerry, Treasure, F Peter, Porter, John and Ross, Richard J. 2021. Modified-release hydrocortisone in congenital adrenal hyperplasia. Journal of Clinical Endocrinology and Metabolism 106 (5) , e2063-e2077. 10.1210/clinem/dgab051

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Background Standard glucocorticoid therapy in congenital adrenal hyperplasia regularly fails to control androgen excess, causing glucocorticoid over-exposure and poor health outcomes. We investigated whether modified-release hydrocortisone (MR-HC), which mimics physiologic cortisol secretion, could improve disease control. Methods 6-month randomized phase III study, MR-HC versus standard glucocorticoid, followed by single-arm MR-HC extension study. Primary outcomes were change in 24-hour standard deviation score (SDS) of androgen precursor 17-hydroxyprogesterone (17OHP) for phase III, and efficacy, safety and tolerability of MR-HC for the extension study. Results The phase III study recruited 122 adult CAH patients. While the study failed its primary outcome at 6 months, there was evidence of better biochemical control on MR-HC, with lower 17OHP SDS at 4 (P=0.007) and 12 (P=0.019) weeks, and between 07:00h to 15:00h (P=0.044) at 6 months. The percentage of patients with controlled 09:00h serum 17OHP (<1200 ng/dl) was 52% at baseline, at 6 months 91% for MR-HC and 71% for standard therapy (P=0.002), and 80% for MR-HC at 18 months extension. The median daily hydrocortisone dose was 25mg at baseline, at 6 months 31mg for standard therapy and 30mg for MR-HC, and after 18 months 20mg MR-HC. Three adrenal crises occurred in phase III, none on MR-HC and 4 in extension study. MR-HC resulted in patient-reported benefit including menses restoration in eight patients (one on standard therapy), and 3 patient and 4 partner pregnancies (none on standard therapy). Conclusion MR-HC improved biochemical disease control in adults with reduction in steroid dose over time and patient-reported benefit.

Item Type: Article
Date Type: Publication
Status: Published
Schools: MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Neuroscience and Mental Health Research Institute (NMHRI)
Additional Information: This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (
Publisher: Oxford University Press
ISSN: 0021-972X
Date of First Compliant Deposit: 10 February 2021
Date of Acceptance: 22 January 2021
Last Modified: 05 May 2023 16:49

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