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 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.
Merke
D P
DP
Warren Grant Magnuson Clinical Center, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda Maryland 20892-1862, USA. merked@mail.nih.gov
Keil
M F
MF
Jones
J V
JV
Fields
J
J
Hill
S
S
Cutler
G B
GB
D000312:Adrenal Hyperplasia, Congenital / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D000726:Androgen Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000728:Androgens / Q000097:blood; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001846:Bone Development / Q000187:drug effects* / Q000502:physiology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005485:Flutamide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006128:Growth / Q000502:physiology*; D006728:Hormones / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D013738:Testolactone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015430:Weight Gain / Q000187:drug effects
D000726:Androgen Antagonists; D000728:Androgens; D000893:Anti-Inflammatory Agents; D018931:Antineoplastic Agents, Hormonal; D006728:Hormones; D013738:Testolactone; D005485:Flutamide; D006854:Hydrocortisone