Prednisolone vs Hydrocortisone for Hypoadrenalism—An Uneven Battle

The study by Meeran et al 1 is a double-blind randomized clinical trial in which once-daily low-dose prednisolone (3-5 mg) is compared with hydrocortisone given thrice daily, both titrated according to individual patients' needs.Of the patients (aged 18-70 years) included in the study, 16 patients had primary adrenal insufficiency and 31 had secondary adrenal insufficiency.Patients were randomized to 4 months of once-daily prednisolone in the morning or hydrocortisone 3 times a day then vice versa for another 4 months.Patients with type 1 and type 2 diabetes were excluded from the study.One of the main findings of the study was that the cardiometabolic outcomes in patients receiving low-dose prednisolone were improved after switching from hydrocortisone, with glycated hemoglobin decreasing by -0.7 mmol/mol with prednisolone, even though fasting glucose, insulin, and Homeostatic Model Assessment for Insulin Resistance score did not vary significantly between the treatment arms.The authors stated that bone formation and resorption markers, including osteocalcin, procollagen type 1 N-terminal propeptide, and urinary N-terminal telopeptide, were significantly lower with prednisolone compared with hydrocortisone.The most frequent regimens in the hydrocortisone arm were 10 mg plus 5 mg plus 5 mg (22 patients) and 10 mg plus 5 mg plus 2.5 mg (10 patients).The most frequently used doses in the prednisolone arm were 3 mg (19 patients) and 4 mg (22 patients).No adrenal crisis occurred in any group throughout the study period, so both regimens were considered safe.If patients were receiving fludrocortisone, they were taking a stable dose. 1 No corticosteroid replacement doses, regimens, and corticosteroid equivalent doses come from randomized clinical trials (RCTs).The search for the most physiologic preparation, mimicking the