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.