A randomized crossover trial suggests that once-daily low-dose prednisolone may offer modest cardiometabolic advantages compared with conventional thrice-daily hydrocortisone in patients with adrenal insufficiency.
In the double-blind study, researchers compared once-daily prednisolone (2 to 5 mg) with thrice-daily hydrocortisone over two 120-day treatment periods in 46 patients with primary or secondary adrenal insufficiency. The trial evaluated differences in bone turnover markers and cardiometabolic outcomes between the two replacement strategies.
Bone turnover was statistically significantly slower during the prednisolone treatment period. Compared with hydrocortisone, prednisolone was associated with lower levels of several bone markers, including carboxylated osteocalcin, undercarboxylated osteocalcin, urinary N-terminal telopeptide, and procollagen type 1 N-terminal propeptide.
Prednisolone therapy was also associated with modest improvements in several cardiometabolic measures. Patients experienced greater reductions in body weight, body mass index, waist circumference, and glycated hemoglobin compared with hydrocortisone during the treatment period.
There were no differences in subjective health outcomes between treatments, including quality-of-life measures.
Overall safety outcomes did not differ between the treatments. Across the study, 133 adverse events were recorded in 37 patients, with the most common events including viral illnesses and lethargy. No adrenal crises occurred during the trial.
In an accompanying invited commentary, Mira Emilova Boyanova, MD, noted that “a high proportion of patients undergoing conventional corticosteroid replacement therapy are still overtreated or following inappropriate replacement regimens,” increasing the risk of osteoporosis and cardiometabolic complications while physicians prioritize prevention of adrenal crisis.
Boyanova also cautioned that the clinical significance of some findings remains uncertain. Although the study reported lower bone turnover markers with prednisolone, she wrote that the magnitude of change was small compared with reductions typically seen with antiresorptive therapies.
Hydrocortisone remains the preferred replacement therapy in most clinical guidelines, typically administered in divided doses totaling 15 to 25 mg daily, with prednisolone considered an alternative option in some patients.
The researchers emphasized that the findings were based on surrogate markers and that longer-term studies are needed to determine whether these differences translate into meaningful clinical outcomes, such as fracture risk or cardiovascular events.
The researchers reported no competing interests.
Source: JAMA Network Open
