Treatment and disease effects on short-term growth and adult height in children and adolescents with 21-hydroxylase deficiency.
BACKGROUND
In clinical practice, height velocity and rate of bone maturation during each follow-up interval are among the parameters used to modify glucocorticoid treatment in children with 21-hydroxylase deficiency. There is controversy on the relative importance of treatment and disease variables for short-term growth and final height.


METHODS
Short- and long-term growth data of 87 patients (n = 35 salt-wasting form; n = 52 simple virilizing form) were analysed retrospectively by stepwise multiple regression.


RESULTS
Height SDS for chronological age (HtSDSCA) was elevated prior to treatment in boys (m = 3.22, p < 0.0001) and decreased when compared to HtSDSCA > or = 4 years after the start of treatment in both boys (m = -0.64, p < 0.0001) and girls (m = -1.24, p < 0.0023). When the simultaneous effects of hydrocortisone dose, salt-wasting status, degree of hormonal control, and patient sex on short-term growth between follow-up visits were analysed, only a minor effect of hydrocortisone dose (partial coefficient of determination [Pr2] = 0.04, p < 0.011) and salt-wasting status (Pr2 = 0.03, p < 0.024) in the prepubertal group, and a small effect of the treatment quality rating in the pubertal group (Pr2 = 0.07, p < 0.0042) on height velocity SDS for chronological age (HVSDSCA) were noted. Height velocity SDS for bone age (HVSDSBA) was influenced to a similar degree by treatment quality (Pr2 = 0.098, p < 0.0017) in the prepubertal, and by hydrocortisone dose (Pr2 = 0.063, p < 0.021) in the pubertal group. Mean daily hydrocortisone doses used in normally growing patients ranged between 17.9 and 21.8 mg/m2/d if analysed separately for sex and salt-wasting status. 34 patients had reached final height which with the exception of one boy was below the population mean and ranged from 82.3% to 100.1% of target height in the total group. 41.2% of the patients had adult short stature (HtSDS < -2). Treatment with synthetic glucocorticoids for more than 1 year started before the age of 1.5 years was associated with the most severely compromised final height SDS (m = -3.73, p < 0.029).


CONCLUSIONS
The proportion of the short-term height velocity SDS that can be explained by the tested treatment and disease variables is low (< or = 9.8%). Conclusions drawn from observed changes in height velocity during single short follow-up intervals on treatment modalities must therefore be viewed with caution. In the long run, however, use of daily hydrocortisone doses > 25 mg/m2/day and of synthetic glucocorticoids started early in the course of the disease does not only lead to a transient deceleration of height velocity in growing children with 21-hydroxylase deficiency, but carries a definite risk for decreased final height.
Hauffa
B P
BP
Dept. of Pediatric Endocrinology, University Children's Hospital, University of Essen, F. R. Germany.
Winter
A
A
Stolecke
H
H
D000293:Adolescent; D000312:Adrenal Hyperplasia, Congenital / Q000188:drug therapy* / Q000201:enzymology; D000328:Adult; D000365:Age Determination by Skeleton; D001827:Body Height / Q000187:drug effects*; D002648:Child; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D008297:Male; D011627:Puberty / Q000187:drug effects; D012189:Retrospective Studies; D014882:Water-Electrolyte Balance / Q000187:drug effects
D005938:Glucocorticoids; D006854:Hydrocortisone