Should all patients with adrenal insufficiency or a subgroup of patients with prediabetes be treated with dual‐release hydrocortisone?

Abstract

Guarnotta et al 1 compare the effects of dual-release (DR) hydrocortisone 36 months' treatment in 13 patients with primary adrenal insufficiency and 36 with secondary adrenal insufficiency, compared to conventional glucocorticoid treatment. A retrospective evaluation was conducted on the effects of 36 months of DR hydrocortisone therapy on visceral adiposity, insulin secretion and insulin sensitivity.Forty-nine patients with adrenal insufficiency were recruited. They had been on stable conventional glucocorticoid treatment before entering the study and underwent clinical and metabolic evaluation at baseline (during conventional glucocorticoid treatment) and at 12, 24 and 36 months after switching to DR hydrocortisone. DR hydrocortisone is a formulation that consists of an extendedrelease core surrounded by an immediate release coating. DR hydrocortisone absorption is rapid (17-20 minutes for the 20 mg tablet in the fasting state) and can induce an adequate increase in morning cortisol levels with a peak concentration time similar to the one observed with conventional hydrocortisone. However, it produces a more gradual decline in cortisol concentrations than conventional hydrocortisone. DR hydrocortisone was developed to obtain a more physiological circadian cortisol exposure time after a once-daily administration. 2 Although a lot of work has been done to optimise glucocorticoid treatment with more physiological formulations of hydrocortisone in the last two decades, there has been no consistent evidence that more physiological replacement of corticosteroid therapy is superior to the conventional once, twice or thrice daily dosages of shortacting corticosteroids. However, previous studies did not carefully measure insulin sensitivity and secretion during DR hydrocortisone.Guarnotta et al report that long-term DR hydrocortisone is associated with an improvement in insulin secretion and sensitivity in patients with impaired fasting glucose and/or impaired glucose tolerance. The investigators also report an improvement of other parameters (body mass index, waist circumference, glycated haemoglobin and high-density-lipoprotein-cholesterol) in the entire cohort (including those patients without prediabetes).As reported by the Authors, the retrospective design is the main limitation to the study as a cross-over study design would have been preferable for the assessment and verification of the effects of DR hydrocortisone. The small sample size is another principal limitation.The cohort of patients studied by Guarnotta et al is too heterogeneous to draw a definitive conclusion on the role of DR hydrocortisone therapy on glucose homeostasis and insulin sensitivity, but these findings justify for future study on the topic. Future studies should contain adequate numbers of patients with primary and secondary hypoadrenalism.It is well known that exogenous glucocorticoids affect glucose metabolism, and induce peripheral insulin resistance by impairing insulin signalling. This will lead to decreased glucose disposal and incre...