Alternate Day Prednisone Therapy in Congenital Adrenal Hyperplasia: Adrenal Androgen Suppression and Normal Growth

Abstract

Daily glucocorticoid therapy of children with congenital adrenal hyperplasia (CAH) frequently results in a suboptimal mature height. In contrast, pharmacological doses of prednisone given on alternate days generally allow normal growth in children with autoimmune, hematological, and renal disorders. Moreover, alternate day prednisone therapy suppresses adrenal androgen secretion on both the day on and the day off therapy in patients with systemic lupus erythematosus. We hypothesized that alternate day prednisone therapy might be efficacious in the treatment of CAH. To evaluate this hypothesis, we studied an 11-yr-old girl with salt-losing 21-hydroxylase deficiency and severe asthma treated with alternate day prednisone therapy (20 mg every other day) for over 3 yr. During this period her linear growth was along the 65th percentile, and her bone age paralleled her chronological age. Pubertal development was normal, and she had no signs of androgen or glucocorticoid excess. In keeping with her clinical picture, basal (24-h samples drawn every 60 min) and ovine CRH-stimulated plasma adrenal androgen (dehydroepiandrosterone sulfate and delta 4-androstenedione) concentrations and 24-h urinary 17-ketosteroid excretion were low on both the day on and the day off prednisone. However, her plasma ACTH and 17-hydroxyprogesterone levels were markedly elevated on both days. The adrenal androgen suppression, therefore, appeared independent of the level of ACTH, suggesting different regulation of the zona fasciculata and the zona reticularis. GH secretion, assessed by measurement of plasma GH every 20 min for 48 h, was normal on both the on and off days of prednisone therapy. Therefore, in this girl pharmacological doses of prednisone given on alternate days caused sustained adrenal androgen suppression and allowed normal growth and pubertal development, despite persistently elevated plasma ACTH and 17-hydroxyprogesterone levels.