The following is a summary of “Tissue Glucocorticoid Metabolism in Adrenal Insufficiency: A Prospective Study of Dual-release Hydrocortisone Therapy,” published in the December 2023 issue of Endocrinology by Dineen, et al.

Patients with adrenal insufficiency (AI) require lifelong glucocorticoid (GC) replacement therapy. Cortisol availability within tissues is regulated by the isozymes of 11β-hydroxysteroid dehydrogenase (11β-HSD). For a study, researchers sought to hypothesize that corticosteroid metabolism is altered in AI patients due to the nonphysiological pattern of immediate-release hydrocortisone (IR-HC) replacement therapy. A once-daily dual-release hydrocortisone (DR-HC) preparation (Plenadren®) offers a more physiological cortisol profile and may impact corticosteroid metabolism in vivo.

The prospective crossover study assessed the impact of 12 weeks of DR-HC on systemic GC metabolism, cortisol activation in the liver, and subcutaneous adipose tissue in 51 patients with AI (primary and secondary) compared to IR-HC treatment and age- and BMI-matched controls.

Patients with AI receiving IR-HC showed higher 24-hour urinary cortisol excretion than healthy controls (72.1 µg/24 hours [IQR 43.6-124.2] vs 51.9 µg/24 hours [35.5-72.3], P = .02), with lower global activity of 11β-HSD2 and higher 5-alpha reductase activity. Following the switch from IR-HC to DR-HC therapy, there was a significant reduction in urinary cortisol and total GC metabolite excretion, which was most significant in the evening. There was an increase in 11β-HSD2 activity. The hepatic 11β-HSD1 activity was not significantly altered after switching to DR-HC, but there was a significant reduction in the expression and activity of 11β-HSD1 in subcutaneous adipose tissue.

Using comprehensive in vivo techniques, they demonstrated abnormalities in corticosteroid metabolism in patients with primary and secondary AI receiving IR-HC. The dysregulation of pre-receptor glucocorticoid metabolism results in enhanced glucocorticoid activation in adipose tissue, ameliorated by treatment with DR-HC.

Source: academic.oup.com/jcem/article/108/12/3178/7204092