Background: The diagnosis of severe primary IGF-I deficiency (IGFD) in children with normal growth hormone (GH) peak in stimulation tests (stimGH) should be confirmed by IGF-I increase <15.0 ng/ml during generation test (IGF-GT), however the significance of IGF-GT has been questioned by some researchers.
Objective and hypotheses: Evaluation of the significance of IGF-GT in children with normal stim GH and IGFD, with respect to efficacy of growth-promoting therapies.
Method: Analysis comprised 110 children with height SDS (hSDS) <−2.0, stimGH >10.0 ng/ml and IGF-I SDS <−1.0, subjected to IGF-GT with daily GH dose 0.033 μg/kg, during 7 days.
Results: In 24 children with hSDS <−3.0 and IGF-I SDS <−2.5, the increase of IGF-I ranged from 25 to 357 ng/ml (none of them fulfilled the criteria of severe primary IGFD). The patient with IGF-I increase 25 ng/ml was treated with mecasermin up to final height (FH) with hSDS increase from −3.69 to −1.67. Other 10 of these 24 ones were treated with GH up to FH, with hSDS increase from −3.60±0.41 to −1.26±0.60. In other three patients with hSDS <−3.0 and IGF-I SDS <−1.5, increasing in IGF-GT by 2339 ng/ml, currently treated with mecasermin, height velocity (HV) increased significantly. In 60 children with hSDS <−2.0 and IGF-I SDS <−1.0 increasing in IGF-GT by 51514 ng/ml, subjected to GH therapy, HV during 1st year of treatment increased from 3.7±0.9 to 8.7±2.6 cm/year; 55 out of them completed GH therapy with hSDS increase from −3.01±0.67 to −1.37±0.87.
Conclusion: The diagnosis of primary IGFD should be confirmed by IGF-GT, as some children with severe IGFD benefit during GH therapy despite normal stimGH that speaks for non-primary IGFD and against GH insensitivity. It seems reasonable to increase cut-off level of IGF-I SDS and of IGF-I response in IGF-GT for qualifying children to mecasermin therapy.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology