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

• Published in: The journal of clinical endocrinology and metabolism 2000-03, Vol.85 (3), p.1114-1120
• Main Authors: MERKE, D. P, KEIL, M. F, JONES, J. V, FIELDS, J, HILL, S, CUTLER, G. B
• Format: Article
• Language: English
• Subjects: Adrenal Hyperplasia, Congenital - complications; Adrenal Hyperplasia, Congenital - drug therapy; Adrenal Hyperplasia, Congenital - pathology; Androgen Antagonists - administration & dosage; Androgen Antagonists - adverse effects; Androgen Antagonists - therapeutic use; Androgens - blood; Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - adverse effects; Anti-Inflammatory Agents - therapeutic use; Antineoplastic Agents, Hormonal - administration & dosage; Antineoplastic Agents, Hormonal - adverse effects; Antineoplastic Agents, Hormonal - therapeutic use; Biological and medical sciences; Bone Development - drug effects; Bone Development - physiology; Child; Child, Preschool; Female; fludrocortisone; Flutamide - administration & dosage; Flutamide - adverse effects; Flutamide - therapeutic use; Follow-Up Studies; Growth - physiology; Hormones - blood; Hormones. Endocrine system; Humans; Hydrocortisone - administration & dosage; Hydrocortisone - adverse effects; Hydrocortisone - therapeutic use; Male; Medical sciences; Pharmacology. Drug treatments; testolactone; Testolactone - administration & dosage; Testolactone - adverse effects; Testolactone - therapeutic use; Weight Gain - drug effects
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.85.3.1114

Treatment outcome in congenital adrenal hyperplasia is often sub-optimal due to hyperandrogenism, treatment-induced hypercortisolism, or both. We previously reported better control of linear growth, weight gain, and bone maturation in a short term cross-over study of a new four-drug treatment regimen containing an antiandrogen (flutamide), an inhibitor of androgen to estrogen conversion (testolactone), reduced hydrocortisone dose, and fludrocortisone, compared to the effects of a control regimen of hydrocortisone and fludrocortisone. Twenty-eight children have completed 2 yr of follow-up in a subsequent long term randomized parallel study comparing these two treatment regimens. During 2 yr of therapy, compared to children receiving hydrocortisone, and fludrocortisone treatment, children receiving flutamide, testolactone, reduced hydrocortisone dose (average of 8.7 +/- 0.6 mg/m2 x day), and fludrocortisone had significantly (P < or = 0.05) higher plasma 17-hydroxyprogesterone, androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and testosterone levels. Despite elevated androgen levels, children receiving the new treatment regimen had normal linear growth rate (at 2 yr, 0.1 +/- 0.5 SD units), and bone maturation (at 2 yr, 0.7 +/- 0.3 yr bone age/yr chronological age). No significant adverse effects were observed after 2 yr. We conclude that the regimen of flutamide, testolactone, reduced hydrocortisone dose, and fludrocortisone provides effective control of congenital adrenal hyperplasia with reduced risk of glucocorticoid excess. A long term study of this new regimen is ongoing.