Hydrocortisone dosing during puberty in patients with classical congenital adrenal hyperplasia: an evidence-based recommendation.
BACKGROUND
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).


CONCLUSIONS
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).
Bonfig
Walter
W
University Children's Hospital, Division of Endocrinology, Ludwig Maximilians University, D-80337 Munich, Germany. walter.bonfig@med.uni-muenchen.de
Pozza
Susanne Bechtold Dalla
SB
Schmidt
Heinrich
H
Pagel
Philipp
P
Knorr
Dietrich
D
Schwarz
Hans Peter
HP
D000293:Adolescent; D000312:Adrenal Hyperplasia, Congenital / Q000188:drug therapy* / Q000503:physiopathology; D001827:Body Height / Q000187:drug effects*; D002648:Child; D004334:Drug Administration Schedule; D019317:Evidence-Based Medicine; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage* / Q000009:adverse effects*; D016015:Logistic Models; D008297:Male; D011627:Puberty / Q000187:drug effects*; D011629:Puberty, Precocious / Q000503:physiopathology / Q000517:prevention & control*; D012372:ROC Curve; D012189:Retrospective Studies
D006854:Hydrocortisone