Control of Childhood Congenital Adrenal Hyperplasia and Sleep Activity and Quality with Morning or Evening Glucocorticoid Therapy

Context: Traditionally, hydrocortisone (HC) replacement therapy in congenital adrenal hyperplasia (CAH) is given by three daily doses, albeit not necessarily of equal quantity. Although a higher dose in the morning better imitates the physiological diurnal variation, a late-night higher dose was suggested to better suppress early morning hypothalamic-pituitary-adrenal axis peak activity. Yet, increased night cortisol has been claimed to be associated with sleep disturbances and insomnia. Objective: Our objective was to evaluate evening vs. morning high-HC dose with respect to disease control, sleep pattern, and daytime activity in children with CAH. Design: An open-label, cross-over, randomized trial of 15 children with classical CAH was performed. Patients were randomized to receive 50% of the daily HC in the morning or evening for 2 wk; the other two doses included 25% of the daily dose each. Outcome Measures: Disease control was assessed by 0800-h 17-hydroxyprogesterone, testosterone, androstenedione, and dehydroepiandrosterone sulfate on the last day of each treatment schedule. Sleep and daytime activity were assessed by a 7-d actigraph. Results: Basal morning androstenedione, 17-hydroxyprogesterone, dehydroepiandrosterone sulfate, and testosterone levels during the high-morning and high-evening HC treatment schedules were comparable. There were no significant differences in sleep or daytime activity. Conclusions: With respect to disease control, sleep quality and daytime activity were not affected by treatment schedules. We recommend the high-morning dose schedule in replacement therapy of children with CAH. (J Clin Endocrinol Metab 93: 4707-4710, 2008)