A PRELIMINARY-STUDY OF FLUTAMIDE, TESTOLACTONE, AND REDUCED HYDROCORTISONE DOSE IN THE TREATMENT OF CONGENITAL ADRENAL-HYPERPLASIA

Treatment outcome in congenital adrenal hyperplasia is often suboptima l due to hyperandrogenism, treatment-induced hypercortisolism, or both . As a new approach, we hypothesized that the effects of androgen coul d be blocked by an antiandrogen (flutamide) and an inhibitor of androg en to estrogen conversion (testolactone), thus allowing the hydrocorti sone dose to be reduced. We conducted a short term pilot study in 12 c hildren with congenital adrenal hyperplasia in a randomized cross-over open design to determine whether flutamide, testolactone, reduced hyd rocortisone dose, and fludrocortisone are more effective than hydrocor tisone and fludrcortisone treatment in normalizing linear growth, weig ht gain, and bone maturation. Each regimen was administered for 6 mont hs, with a 3-month washout period, consisting of hydrocortisone and fl udrocortisone treatment, between regimens. Compared to hydrocortisone and fludrocortisone treatment, the regimen of flutamide, testolactone, reduced hydrocortisone dose (from 12.9 to 7.9 mg/m(2) . day), and flu drocortisone produced an increase in plasma 17-hydroxyprogesterone lev els (P < 0.05) and a decline in urinary cortisol (P < 0.01), Linear gr owth rate (-0.9 +/- 0.5 vs. 1.4 +/- 0.6 SD U; P = 0.003), weight veloc ity (-0.80 +/- 0.4 vs. 0.6 +/- 0.4 SD U; P = 0.01), and bone maturatio n (0.6 +/- 0.6 vs. 1.4 +/- 0.9 yr bone age/yr chronological age; P = 0 .02). Although no important adverse effects were observed, the known p otential for flutamide-induced hepatotoxicity made frequent monitoring essential. We conclude that the regimen of flutamide, testolactone, r educed hydrocortisone dose, and fludrocortisone improves the short ter m control of growth and bone maturation in children with congenital ad renal hyperplasia. Long term studies are required to determine whether this approach can improve these children's growth and development.