Effect of once-daily, modified-release hydrocortisone versus standard glucocorticoid therapy on metabolism and innate immunity in patients with adrenal insufficiency (DREAM): a single-blind, randomised controlled trial

Glucocorticoid replacement in Addison disease

“…In the present News & Views article, Muller and Quinkler discuss a recent study by Andrea M. Isidori and colleagues 6 . The study by Isidori et al reported that patients with adrenal insufficiency who were switched from thrice-daily hydrocortisone to once-daily MR-hydrocortisone had improved metabolic profiles and immune function compared with patients who continued on thrice-daily hydrocortisone.…”

Improving glucocorticoid replacement profiles in adrenal insufficiency

“…In addition to a significant corrected weight loss of 4 kg in the 'switch' group, the investigators reported significantly higher classical (CD14+CD16−) monocytes, with lower nonclassical (CD14−CD16+) monocytes and CD16+ mature natural killer cells in patients taking multiple‐daily cortisone acetate or hydrocortisone at baseline versus the healthy volunteers. Converting patients to once‐daily Plenadren was associated with improved numbers of the classical and nonclassical monocytes and the mature natural killer cells, with concordant decreases in the soluble CD16 immune marker (an indicator of natural killer cell immaturity) and reported rates of infection as measured by a questionnaire . These finding suggest that Plenadren may be less immunosuppressive than multiple daily dosing of glucocorticoids and that leucocytes may hold the key to assessing the adequacy of an individual's glucocorticoid replacement therapy.…”

“…Building on the early comparative findings that Plenadren may lower blood pressure, weight and improve HbA1c compared to multiple daily cortisone acetate or hydrocortisone, the DREAM study undertook a similar comparison . Although the primary outcome focussed on weight change, the DREAM study also looked at the effect of Plenadren on immune profiles.…”

“…In the DREAM study, a majority of the patients were on cortisone acetate, which depends on hepatic activation by 11β hydroxysteroid dehydrogenase (11βHSD1) to cortisol . It was assumed that 1mg of cortisone acetate was equivalent to 0.8 mg of hydrocortisone, but there is a large (21%‐95%) variability in bioavailability of cortisone acetate as well as tissue‐specific expression of 11βHSD1.…”

Predicting an adrenal crisis: can we do it?

“…There appear to be subtle defects in immune function and inflammatory parameters in patients on conventional replacement which may be lessened by slowrelease preparations [5], while others recommend prednisolone as an alternative glucocorticoid replacement [6]. Whatever the case, we are still some way from knowing how to provide the optimal replacement regimen, and how to avoid life-threatening adrenal crises.…”