Background: Children born small for gestational age (SGA) exhibit wide variations in the activity of growth hormone (GH)/insulinlike growth factorI (IGF-I) axis and this heterogeneity may result in supra physiological concentrations of IGF-I during GH treatment. The long-term effects of elevated IGF-I levels has been a matter of concern. We explored the variations in total IGF-I and bioactive IGF-I and the associations with growth and glucose metabolism in response to a fixed GH dose over 1 year in SGA children.
Methods: The North European Small for Gestational Age Study (NESGAS) is a multicenter study (n=101, 61 males) of GH therapy in prepubertal short SGA children. They received GH therapy at 67µg/kg/day for 1 year. IGF-I was measured by a commercial immunoassay and bioactive IGF-I was measured using the IGF-I kinase receptor activation assay (KIRA).
Results: Bioactive IGF-I at baseline was significantly lower among boys compared to girls (median (25-75 percentile) (-1.4SDS (-2.7 to -0.2)) and -0.2SDS (-1.40.4), respectively) (P=0.002). In contrast, no difference in bioactive IGF-I SDS according to gender was present after one year of GH treatment. No significant differences in total IGF-I were found between the genders before and after one year of high-dose GH treatment.
Bioactive IGF-I (SDS) was significantly correlated to height (SDS) at baseline and the association was stronger than the correlation between total IGF-I (SDS) and height (r:0.29, P=0.005 and r:0.17, P=0.10, respectively). After one year of high-dose GH treatment 68% (N=65) of the children in the entire cohort had increased levels of total IGF-I above + 2SD, whereas only 15% (N=15) had levels of bioactive IGF-I above the normal reference. Change in height (SDS) correlated significantly with baseline total IGF-I (SDS) (r:-0.25, P=0.02) but not with bioactive IGF-I (SDS) (r:-0.11, P=0.30). Bioactive IGF-I (SDS) correlated positively with total IGF-I (SDS) (r:0.35, P=0.001) and IGFBP-3 (SDS) (r:0.26, P=0.01) and correlated negatively with insulin sensitivity (HOMA-S) (r:-0.29, P=0.007) and IGFBP-1 (r:-0.18, P=0.08).
Conclusion: Bioactive IGF-I showed a stronger association with height compared to total IGF-I at start, but was not a good predictor of the one year response to high-dose GH treatment. Reassuringly, we found that only 15 % of the GH treated SGA children had supra-physiological levels of bioactive IGF-I after one year of high-dose treatment in contrast to elevated total IGF-I levels in 68% of the patients.
19 Sep 2019 - 21 Sep 2019