#3-94E. Rethinking Adrenal Replacement: Once-Daily Prednisolone vs. Thrice-Daily Hydrocortisone (JAMA Netw Open, 2026)

What is the optimal glucocorticoid replacement strategy for patients with adrenal insufficiency? In this episode, we review a double-blind, crossover randomized clinical trial comparing the conventional thrice-daily standard-dose hydrocortisone regimen against once-daily low-dose prednisolone (2-5 mg) in 46 adult patients with hypoadrenalism over four-month treatment periods. The trial's most crucial finding indicates that once-daily prednisolone significantly slowed bone turnover and improved cardiometabolic markers—including reductions in body weight, waist circumference, and HbA1c—without negatively impacting patients' subjective well-being. However, when critically appraising this study, physicians should note that it primarily evaluated surrogate biochemical markers over a relatively short timeframe, highlighting the need for future longitudinal trials to assess clinical outcomes like fractures or major adverse cardiac events. For the listening physician, this research is highly relevant as it suggests that a simpler, once-daily prednisolone prescription could offer a safer, metabolically advantageous, and convenient alternative to traditional multi-dose hydrocortisone, potentially transforming daily clinical practice in managing adrenal insufficiency.

Citation: Sirazum Choudhury, Karim Meeran, et al. Prednisolone Once Daily vs Hydrocortisone Thrice Daily in Hypoadrenalism: A Randomized Clinical Trial. JAMA Network Open. 2026. DOI: 10.1001/jamanetworkopen.2026.2982

Disclaimer: This audio summary is based on personal interpretation and does not guarantee the exact content of the original paper. Please refer to the original article for details.