Insulin sensitivity and body composition in children with classical and nonclassical congenital adrenal hyperplasia

Reduced insulin sensitivity and increased fat mass have been reported in children and adults with congenital adrenal hyperplasia (CAH). To understand the potential mechanisms underlying these differences, we assessed insulin sensitivity and body composition in children with classical or nonclassical (late-presenting) CAH compared with normal controls.

Thirty-seven children with CAH (26 classical and 11 nonclassical) median (range) age 9.4 year (0.5-15.8) were compared with 41 healthy control children age 11.0 year (3.2-17.1). All children had an overnight fasting blood sample and body composition assessed by DEXA. Pubertal children (14 CAH and 19 controls) also had an oral glucose tolerance test. Classical and nonclassical CAH groups were each compared with controls, adjusting for age, gender and pubertal status. Results Classical CAH children had more fat mass than controls (P = 0.03), while nonclassical CAH children had more lean mass (P = 0.006) and higher systolic blood pressure (P = 0.003) than control children. Among pubertal children, nonclassical CAH children had higher mean insulin (0-120 min; P = 0.04), stimulated insulin (0-30 min; P = 0.02), 120 min insulin (P = 0.004) and 120 min glucose levels (P = 0.03) than controls, but no difference in disposition index.

Greater body fat in classical (early-presenting) CAH children could reflect the effects of lifetime glucocorticoid therapy. In contrast, the greater lean mass and parameters of insulin resistance in nonclassical (late-presenting) CAH children likely indicate the adverse metabolic effects of prolonged postnatal androgen excess.