The present long term management of children with congenital adrenal hyperplasia (CAH) is non-physiological and suboptimal requiring administration of hydrocortisone (cortisol) or cortisone acetate three times per day and Florinef daily. The amount of cortisol administered must be carefully monitored and regulated depending on the child's size, growth rate, and bone age. Over suppression of the adrenal gland leads to growth failure , delay in bone age, and a Cushingoid appearance while under suppression leads to the over production of abnormal adrenal androgens which lead to accelerated growth , advancement of the bone age, premature fusion of the epiphysises and ultimately in virilization and very short stature. The purpose of this study is to determine if the physiologic replacement of cortisol by subcutaneous administration of cortisol will provide a new therapeutic modality for the treatment of CAH. Specifically, we want to determine if it will 1) reduce the amount of steroid required to achieve normal physiologic plasma concentrations of cortisol, 2)normalize the plasma concentrations of ACTH, and 3) normalize the circulating concentrations of abnormal hormones generated by the adrenal glands. This will be accomplished in three parts by: A. Refining the technique of administration and dosing of cortisol by a subcutaneous route utilizing a portable infusion pump in normal adult volunteers who are parents of children with CAH. B. Determining the pulsatile nature of ACTH, cortisol, delta-4- androstenedione, and 17-hydroxyprogesterone secretion in normal prepubertal children (who are siblings of children with CAH) and prepubertal children with CAH on present accepted therapeutic regimens. C. Determining whether subcutaneous boli of cortisol can mimic the pulsatile nature of cortisol secretion seen in normal children in the children with CAH. D. Determine whether subcutaneous boli of cortisol delivered in physiologic amounts can suppress the abnormal plasma concentrations of 17-hydroxyprogesterone, (4-androstenedione and ACTH in children with CAH.
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