156 GROWTH RETARDATION IN CHILDREN WITH CONGENITAL ADRENAL HYPERPLASIA (CAH) WITH PREDNISONE SUBSTITUTION IS NOT GROWTH HORMONE (GH) AND IGF 1 DEPENDENT

Abstract

Prednisone inhibits growth more potently than hydrocortisone. Supression of GH secretion has been discussed as one possible mechanism. In a retrospective study GH, IGF 1 and procollagen type III propeptide (P-III-NP and FAB), which correlates to growth velocity, were determined longitudinally in sera of 9 children with CAH (age: 6 to 11 ys) during an intermittent period of prednisone substitution (4mg/m2bid) for 6 to 24 months and a subsequent period of hydrocortisone substitution (20mg/m2/tid) for 24 months. Prednisone treatment led to a deceleration of mean growth velocity (0.5 to −4.7 SDS for bone age) without delay of scetetal maturation resulting in a mean decrease of final height prediction of 6 cm. While IGF 1 (4.7 ± 2.1 vs. 4.3 ± 1.2 U/ml, mean ± 1 SD) and GH (5.6 ± 6.1 vs. 4.0 ± 6.9 ng/ml) did not differ during both periods, P-III-NP (13.1 ± 3.5 vs. 28.6 ± 7.4 ng/ml) and FAB levels (63 ± 18 vs. 128 ± 29 ng/ml) were reduced (p<0.001) during prednisone substitution. During both regimens in 2 of these children the nocturnal GH secretion (above 2500 ng·min·ml−1), stimulated GH levels after insulin-induced hypoglycaemla (above 15 ng/ml) and after GRF administration (above 26 ng/ml) were normal. Our observation gives strong evidence that the impairment of growth by hydocortisone-equivalent doses of prednisone is not mediated by changes of GH and IGF1 secretion but rather by a peripheral inhibition of GH and IGF1 effects at the tissue level.