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

J Clin Endocrinol Metab. 2000 Mar;85(3):1114-20. doi: 10.1210/jcem.85.3.6462.

Abstract

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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • 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*
  • Bone Development / drug effects*
  • Bone Development / physiology*
  • Child
  • Child, Preschool
  • Female
  • Flutamide / administration & dosage
  • Flutamide / adverse effects
  • Flutamide / therapeutic use*
  • Follow-Up Studies
  • Growth / physiology*
  • Hormones / blood
  • Humans
  • Hydrocortisone / administration & dosage
  • Hydrocortisone / adverse effects
  • Hydrocortisone / therapeutic use*
  • Male
  • Testolactone / administration & dosage
  • Testolactone / adverse effects
  • Testolactone / therapeutic use*
  • Weight Gain / drug effects

Substances

  • Androgen Antagonists
  • Androgens
  • Anti-Inflammatory Agents
  • Antineoplastic Agents, Hormonal
  • Hormones
  • Testolactone
  • Flutamide
  • Hydrocortisone