Original Investigation

Prednisolone Once Daily vs Hydrocortisone Thrice Daily in Hypoadrenalism

JAMA Network Open 10.1001/jamanetworkopen.2026.2982

March 24, 2026 at 11:00 AM EDT

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Are there differences in bone turnover between once-daily low-dose prednisolone and multiple-daily standard-dose regimens of hydrocortisone on cardiometabolic outcomes in patients with adrenal insufficiency?In this randomized clinical trial of 46 adults with adrenal insufficiency, bone turnover was slowed with prednisolone treatment, which was also associated with reductions in body weight, waist circumference, and glycated hemoglobin. Bone formation and resorption markers were elevated with hydrocortisone treatment, despite no detectable differences in subjective health outcomes.These results suggest that once-daily low-dose prednisolone is a safe alternative to standard regimens of hydrocortisone for treatment of adrenal insufficiency, which may have better cardiovascular outcomes.

Corresponding Author: Karim Meeran, MD, Division of Diabetes, Endocrinology, and Metabolism, Commonwealth Building, Sixth Floor, Hammersmith Hospital, Imperial College London, Du Cane Road, London W12 0NN, UK (k.meeran@imperial.ac.uk).

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