Glucocorticoid replacement therapy is essential to life in adrenal insufficiency (AI). Individuals with the condition have a life expectancy that is reduced by up to 12 years because of cardiometabolic adverse effects possibly due to mild over-replacement.

Hydrocortisone is the most common treatment given thrice daily and usually prescribed in a one-size-fits-all manner. Prednisolone is an alternative medication. Only recently has it been used at very low doses of 2-5 mg once daily, with doses tailored to individuals. There is a vacuum of evidence comparing its safety and efficacy to hydrocortisone, leading to hesitance in its uptake.

The Objective Markers and New Indicators in Adrenal Insufficiency Disease (OMNI-AID) study is a cross-sectional observational study that recruited healthy volunteers, AI patients receiving low-dose prednisolone, patients taking standard hydrocortisone and patients receiving high-dose glucocorticoids. Individuals attended a study visit, where anthropometric and subjective health data, blood and urine samples were collected. These were used to assess bone health, cardiovascular risk, glycaemic handling, immunity and subjective health, between the groups. The principal aim was to compare prednisolone and hydrocortisone therapy in the treatment of AI.

The results demonstrate no significant difference between cohorts of patients receiving hydrocortisone and prednisolone in any of the parameters measured. The cohort receiving hydrocortisone did have elevated markers of cardiovascular risk indicated by a higher high-sensitivity CRP and triglycerides than healthy volunteers. They were noted to have higher insulin levels and indices of insulin secretion, suggesting a hyperinsulinaemic normoglycaemic state. All glucocorticoid group patients showed elevated neutrophils compared to the healthy volunteers suggesting relative glucocorticoid over-exposure.

Taken together, this study presents data indicating minor differences between hydrocortisone and prednisolone replacement detectable only by comparison to healthy volunteers, with no overt difference between the two. This suggests that either medication can be safely used for the management of AI.