THE IMPACT OF DOSAGE ON THE EFFECT OF GROWTH HORMONE THERAPY IN CHILDREN WITH IDIOPATHIC SHORT STATURE

Abstract

The growth response to growth hormone (GH) therapy in children with idiopathic short stature (ISS) is generally characterized by a rapid height velocity (HV) increment followed by a progressive decline. There are no data about the dose-response relationship in such children. We studied 24 children (19 M, 5 F) with ISS and a HV < P25, who, after two years of observation, underwent GH therapy over 3 years in three regimens: gr 1 and 2 received 3 and 4.5 IU/m2 b.s. 6 times per week, and gr 3 received 3 IU/m2 in the 1st year and 4.5 IU thereafter. The median HV SDS was -1.8 in the preinclusion year, and 0.3 in the pretreatment year (p<0.05). In the 1st year on GH the mean (SD) HV SDS rose from 0.4 (1.5) to 5.7 (2.4) on 3 IU/m2 (gr 1+3) and from 0.1 (0.7) to 7.1 (2.1) on 4.5 IU/m2. There was no statistical difference between the groups. In the 2nd and 3rd year the prepubertal children from all groups showed a similar decrease. Mean height SDS increased by 1.2 in all groups, compared to 0.3 in an untreated control group (n=40). Mean bone age (BA) in gr 1,2 and 3 increased by 3.4, 3.0 and 3.9 years (NS between groups). Predicted adult height SDS (Bayley Pinneau) increased by 1.6 (0.8) in group 2 (p=0.01), but not in groups 1 and 3 (p=0,31 and p=0.13). In conclusion: 1) short children selected on the basis of a low HV show a normal mean velocity in the next year; 2) the three dosage regimens lead to a similar initial growth acceleration followed by a similar decrease; 3) the higher dosage appears more effective in terms of predicted adult height, although attained final heights have to be awaited for definitive conclusions.