Randomised controlled trial of growth effect of hydrocortisone in congenital adrenal hyperplasia

The influence of 15 or 25 mg/m2 of daily oral hydrocortisone with fludrocortisone 0.1 mg/day on growth and laboratory findings was evaluated in a prospective randomised crossover trial over 12 months in 26 children with 21-hydroxylase deficiency. Nine non-salt losers had fludrocortisone stopped for a further six month period. Height velocity was significantly decreased during treatment with 25 mg/m2 as compared with 15 mg/m2. This was the most sensitive indicator of corticosteroid treatment excess. A dose dependent effect upon plasma concentrations of 17-hydroxyprogesterone, testosterone, and androstenedione was found but increased values were still detected in more than half of the determinations made during the 25 mg/m2 period. Height velocity and 17-hydroxyprogesterone concentrations were positively correlated. Growth hormone response to clonidine stimulation and insulin-like growth factor-1 concentrations were both within reference values and there was no difference between treatment periods. Withdrawal of fludrocortisone did not result in any difference for the non-salt losers. It was concluded that 25 mg/m2 of hydrocortisone depressed growth in children with congenital adrenal hyperplasia, and that full suppression, or even normalisation, of plasma concentrations of 17-hydroxyprogesterone and androgens should not be considered a treatment goal, but instead an indication of corticosteroid treatment excess.