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

Pediatric Endocrinology (A.G., Z.H.) and Sleep Laboratory (S.S., G.P.), Rambam Medical Center, Haifa 31096, Israel; Pediatric Endocrine Unit (A.G., I.K.), Clalit Health Maintenance Organization, Haifa 35013, Israel; Ha’Emek Medical Center (Y.T.-R.), Afula 18101, Israel; and the Faculty of Medicine, Technion–Israel Institute of Technology (Y.T.-R., G.P., Z.H.), Haifa 32000, Israel

Address all correspondence and requests for reprints to: Ze’ev Hochberg, M.D., Ph.D., Meyer Children’s Hospital, Rambam Medical Center, Haifa 31096, Israel. E-mail: z_hochberg{at}rambam.health.gov.il.

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.