Objective: Compare the most frequently used weight-based GH dosing with an IGF-I level-based strategy in the treatment of children with severe GH deficiency. Additionally, analyse the influence of the GH receptor exon 3 polymorphism on IGF-I levels during GH therapy.
Design: Thirty children with GH deficiency on treatment with GH for 4.3+/-3.2 yr in a single University Hospital were divided in group W (weight-based GH dosing) and group I (IGF-I-based dosing). In group I, GH doses were changed by 8.3 microg/kg d to maintain IGF-I levels between 0 and +2 SDS, whereas in group W the dose was fixed at 30 microg/kg d in prepubertal and 50 microg/kg d in pubertal patients. Growth velocity was measured after 1 yr, IGF-I and IGFBP3 levels quarterly. GH receptor exon 3 was genotyped by PCR.
Results: Most patients in Group I reached target IGF-I levels after 6 months with a GH dose ranging between 25 and 66 microg/kg d (mean+/-SD, 38+/-8). Each change of 8.3 microg/kg d of GH dose, resulted in change of 1.17+/-0.6 SDS of IGF-I levels. Mean IGF-I levels were higher in Group I 0.8+/-0.5 SDS than in Group W -0.3+/-1.9 SDS (p<0.05), but growth velocities were similar, 6.8+/-2.6 cm/yr and 6.9+/-2.6 cm/yr (p=NS), respectively. Serum IGFBP3 levels were similar in both groups and were less useful to individualize GH therapy. Even treated with a similar mean GH dose, patients carrying at least one GH receptor d3-allele reached higher IGF-I levels (0.7+/-1.2 SDS) than those homozygous for the full-length allele (-0.3+/-1.2 SDS; p<0.05), however, growth velocities were not different.
Conclusions: By adjusting the GH dose, it was feasible to maintain IGF-I in the desired range (0-+2 SDS). Patients carrying at least one GH receptor d3-allele reached higher circulating IGF-I levels than those homozygous for the full-length allele. A multiple regression analysis failed to demonstrate an independent influence of IGF-I levels on GV during the 12 months of observation.