Published in

Oxford University Press (OUP), Journal of Clinical Endocrinology and Metabolism, 2021

DOI: 10.1210/clinem/dgab051

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Modified-release Hydrocortisone in Congenital Adrenal Hyperplasia

This paper was not found in any repository, but could be made available legally by the author.
This paper was not found in any repository, but could be made available legally by the author.

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Abstract

Abstract 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.