Growth inhibition by glucocorticoid treatment in salt wasting 21-hydroxylase deficiency: in early infancy and (pre)puberty.
In patients with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, adult height is below target height. This may result from growth inhibition by glucocorticoid treatment. Previous studies suggest that glucocorticoids have a dose-dependent negative effect on growth in CAH patients and that this effect is age dependent. This study analyzed the correlation between glucocorticoid dose and growth in these patients. A retrospective study was carried out on growth data from 48 patients with classic salt-wasting 21-hydroxylase deficiency who all had been diagnosed in the first year of life and treated from the moment of diagnosis with glucocorticoids and mineralocorticoids. Analysis of the effect of prescribed glucocorticoid dose on growth was performed in age intervals, by analysis of covariance (ANCOVA). The dependent variables height for age z-score (HAZ), weight for age z-score (WAZ) (both corrected for secular trend), and weight for height z-score (WHZ), at 10 selected ages (1, 2, 4, 6, 8, 10, 12, 14, 16, and 18 yr) were explained by 1) mean daily glucocorticoid dose per body surface in the preceding age interval; 2) HAZ, WAZ, or WHZ value at the beginning of the age interval; 3) HAZ, WAZ, or WHZ value 1 yr before the beginning of the considered age interval; and 4) midparental height (only for HAZ). ANCOVA showed that the daily glucocorticoid dose had significant negative effects on HAZ between the ages of 6 and 12 months and between the age of 8-10 and 12-14 yr (and a trend toward significance between 10-12 yr). The negative glucocorticoid effect on HAZ in the age interval of 12-14 yr was as large as in the interval between 6 and 12 months of age. Weight and weight for height were not significantly influenced by glucocorticoid dose in any of the age intervals. We conclude that in CAH patients in the first year of life and between the ages of 8 and 14 yr, there is a dose-dependent negative effect of glucocorticoids on linear growth. Therefore, the daily glucocorticoid dose in these periods should be sufficient to avoid androgen excess, but as low as possible to allow optimal linear growth and adult height.
Stikkelbroeck
Nike M M L
NM
Departments of Pediatric Endocrinology, University Medical Center Nijmegen, 6500 HB Nijmegen, The Netherlands.
Van't Hof-Grootenboer
Bep A E
BA
Hermus
Ad R M M
AR
Otten
Barto J
BJ
Van't Hof
Martin A
MA
D000293:Adolescent; D000312:Adrenal Hyperplasia, Congenital / Q000150:complications* / Q000188:drug therapy; D000375:Aging / Q000502:physiology; D000704:Analysis of Variance; D001827:Body Height / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D005260:Female; D005938:Glucocorticoids / Q000009:adverse effects* / Q000627:therapeutic use; D006130:Growth Disorders / Q000139:chemically induced*; D006801:Humans; D007223:Infant; D008137:Longitudinal Studies; D008297:Male; D012189:Retrospective Studies; D013255:Steroid 21-Hydroxylase / Q000378:metabolism*
D005938:Glucocorticoids; D013255:Steroid 21-Hydroxylase