Basal and stimulated levels of growth hormone, insulin-like growth factor-I (IGF-I), IGF-I binding and IGF-binding proteins in beta-thalassemia major.

A significant percentage of children with β-thalassemia major shows retardation in longitudinal growth as they progress towards puberty due to skeletal dysplasia, endocrine gland hypofunction or trace element deficiencies. The aim of this study was to evaluate GH/IGF-I secretion and action in prepubertal patients with 13-thalassemia major. Eight prepubertal patients with short stature (group A) and seven prepubertal patients with normal stature (group B) were studied. Basal and stimulated (after administration of the hexapeptide Hexarelin) GH levels were measured with IRMA (Nichols); IGF-I and IGFBP-3 levels were measured with RIA (Nichols). IGF-I binding proteins (IGFBPs) were analyzed qualitatively with Western ligand blot. IGF-I binding to B-lymphocytes of the patients was also measured with competitive binding studies using human recombinant IGF-I and 1 2 5 I-IGF-I (Amersham). Basal GH levels did not differ statistically between the groups. Peak GH levels after Hexarelin stimulation test were higher in group A (A: 27.9 ′ 15.6 ng/ml vs B: 9.1 ′ 4.7 ng/ml) (Wilcoxon test, p <0.05). IGF-I levels in the two groups were low-normal and comparable (A: 168.0 ′ 81.6 ng/ml vs B: 126.6 ′ 25.5 ng/ml). IGFBP-3 levels were low in both groups (A: 1.21 ′ 0.27 μg/ml vs B: 1.08 ′ 0.20 μg/ml). Western ligand blot did not reveal any discernible difference in IGFBPs. However, IGF-I binding on B-lymphocytes was at least 20% lower in group A compared to group B (t-test, p <0.01). IGF-I binding inversely correlated with peak GH levels (r = -0.54, p <0.05). Patients in group A were older and chronological age correlated with IGF-I levels (r = 0.53, p <0.05) whereas it inversely correlated with IGF-I binding (r = -0.63, p <0.05). Moreover, patients in group A had higher ferritin levels. No correlation was found between ferritin levels, desferrioxamine dose/compliance or liver enzyme levels and the parameters of the GH axis studied. However, desferrioxamine dose*years correlated with IGFBP-3 (r = 0.56, p <0.05) and correlated inversely with IGF-I binding (r = -0.74, p <0.01). In conclusion, we have shown adequate GH secretion, higher secretive capacity after the administration of Hexarelin and lower IGF-I binding in prepubertal β-thalassemic patients with short stature. Whatever the cause, reduced IGF-I action has to be considered when treating β-thalassemic patients with short stature.