Flutamide, testolactone, and reduced hydrocortisone dose maintain normal growth velocity and bone maturation despite elevated androgen levels in children with congenital adrenal hyperplasia

Treatment outcome in congenital adrenal hyperplasia is often suboptimal due to hyperandrogenism, treatment-induced hypercortisolism, or both. We previ ously reported better control of linear growth, weight gain, and bone matur ation in a short term cross-over study of a new four-drug treatment regimen containing an antiandrogen (flutamide), an inhibitor of androgen to estrog en conversion (testolactone), reduced hydrocortisone dose, and fludrocortis one, compared to the effects of a control regimen of hydrocortisone and flu drocortisone. Twenty-eight children have completed 2 yr of follow-up in a s ubsequent long term randomized parallel study comparing these two treatment regimens. During 2 yr of therapy, compared to children receiving hydrocort isone, and fludrocortisone treatment, children receiving flutamide, testola ctone, reduced hydrocortisone dose (average of 8.7 +/- 0.6 mg/m(2).day), an d fludrocortisone had significantly (P less than or equal to 0.05) higher p lasma 17-hydroxyprogesterone, androstenedione, dehydroepiandrosterone, dehy droepiandrosterone sulfate, and testosterone levels. Despite elevated andro gen levels, children receiving the new treatment regimen had normal linear growth rate (at 2 yr, 0.1 +/- 0.5 so units), and bone maturation (at 2 yr, 0.7 +/- 0.3 yr bone age/yr chronological age). No significant adverse effec ts were observed after 2 yr. We conclude that the regimen of flutamide, tes tolactone, reduced hydrocortisone dose, and fludrocortisone provides effect ive control of congenital adrenal hyperplasia with reduced risk of glucocor ticoid excess. A long term study of this new regimen is ongoing.