Introduction: Adrenal insufficiency is a life-threatening disease. Conventional treatment requires multiple daily doses of immediate-release hydrocortisone or cortisone acetate causing non-physiological peaks and nadir of cortisol and it has been also associated with premature mortality, high frequency of infections, reduced quality of life, altered metabolic profile and reduced bone mineral density. A modified-release hydrocortisone (Plenadren®, Shire) by combining a rapid with an extended-release of the hormone can mimic the normal circadian rhythm of cortisol and may be administered as a single daily dose. Plenadren has been also associated with a reduction of body weight and blood pressure and improvement of the glyco-metabolic parameters.
Purpose: The study objectives are: (1) to compare the area underr the curve (AUC) of cortisol under conventional therapy and Plenadren and (2) to evaluate clinical (body weight, body composition, blood pressure), glyco-metabolic (HbA1c)) and bone (T score, BMD, serum bone alkaline phosphatase (BAP) and cross laps) parameters at 3, 6 and 12 months of treatment with Plenadren.
Materals and Methods: Thirteen patients (7 M/6 F; age 53±17 (m± S.D.)) with primary adrenal insufficiency in seven subjects and secondary in six cases were prospectively enrolled in the study.
Results: Daily cortisol profiles were more physiological on Plenadren and body exposure to cortisol, calculated as area under the curve, was not statistically significant between conventional therapy and Plenadren. Currently, the median follow-up is 9 months (range 324 months). In one obese and diabetic patient body weight decreased as well as fat mass while lean mass increased and HbA1c improved. In one patient with osteoporosis T score improved and accordingly cross laps decreased and BAP increased. All study parameters did not show significantly changes in the remaining patients.
Conclusions: Treatment with Plenadren provides a more physiological cortisol profile and in some patients shows a beneficial effect on glucose metabolism and bone and body composition without increasing adrenal crisis and/or infections.
20 - 23 May 2017
European Society of Endocrinology