Hydrocortisone Dosing during Puberty in Patients with Classical Congenital Adrenal Hyperplasia: An Evidence-Based Recommendation

Context: Patients with congenital adrenal hyperplasia (CAH) are at risk for early pubertal development and diminished pubertal growth. Liberal treatment with glucocorticoids will prevent early puberty but may inhibit growth outright. Objective: The aim of the study was to determine an optimal range for hydrocortisone dosing during puberty in children with classical CAH who were exclusively treated with hydrocortisone. Methods: The effects of glucocorticoid treatment for classical CAH were retrospectively analyzed in 92 patients (57 females). Growth pattern, final height (FH), and mean daily hydrocortisone dose were recorded. Results: Pubertal growth was significantly reduced in all patients: salt-wasting (SW) females, 13.8 +/- 7.4 cm; simple virilizing (SV) females, 13.1 +/- 6.2 cm; vs. reference, 20.3 +/- 6.8 cm (P < 0.05); and SW males, 17.7 +/- 6.7 cm; SV males, 16.2 +/- 5.7 cm; vs. reference, 28.2 +/- 8.2 cm (P < 0.05). Decreased pubertal growth resulted in FH at the lower limit of genetic potential (corrected FH in SW females, -0.6 +/- 0.9; SV females, -0.3 +/- 0.9; SW males, -0.8 +/- 0.8; and SV males, -1.0 +/- 1.0). During puberty, mean daily hydrocortisone dose was 17.2 +/- 3.4 mg/m(2) in females (SW, 17.0 +/- 3.3; SV, 17.4 +/- 3.5) and 17.9 +/- 2.5 mg/m(2) in males (SW, 17.4 +/- 2.0; SV, 18.7 +/- 3.1). In a logistic regression model, a significant correlation between hydrocortisone dose and FH was found (P < 0.01), and the positive predictive value for short stature rose from below 30% to above 60% when hydrocortisone dose exceeded 17 mg/m(2). Conclusion: With conventional hydrocortisone treatment, pubertal growth is significantly reduced in both sexes, resulting in a FH at the lower limit of genetic potential. These deleterious effects on pubertal growth can be reduced if hydrocortisone does not exceed 17 mg/m(2). (J Clin Endocrinol Metab 94: 3882-3888, 2009)