SERUM GROWTH-HORMONE (GH) BINDING-PROTEIN, IGF-I AND IGFBP-3 IN PATIENTS WITH BETA-THALASSEMIA MAJOR AND THE EFFECT OF GH TREATMENT

OBJECTIVE Levels of IGFI have been shown to be low in transfusion-depe ndent thalassaemia and there is preliminary evidence to suggest that t his may be reversed by GH treatment, In this further study we have eva luated serum growth hormone (GH) binding protein (GHBP), IGF-I and IGF BP-3 in patients with beta-thalassaemia major and the effects of GH tr eatment on these various parameters, PATIENTS Fifty-six transfusion de pendent patients with beta-thalassaemia major without GH deficiency be tween 2 and 20 years of age were studied, Thirteen non-GH deficient pa tients with heights of -1.5 SD or more were treated with GH at a dose of 0.14 IU/kg/day subcutaneously for 1 year. MEASUREMENTS Serum GHBP, IGF-I and IGFBP-3 were measured in all the patients, In the 13 patient s treated with GH, these serum parameters were measured before and aft er 3, 6 and 12 months of treatment, RESULTS The mean serum GHBP concen trations were normal in both prepubertal and pubertal children but the serum IGF-I and IGFBP-3 concentrations were low throughout childhood and adolescence, There was a significant correlation between serum IGF -I and IGFBP-3 concentrations (r=0.79; P=0.0001) but there was no corr elation between the height SDS of the patients with serum GHBP, IGF-I or IGFBP-3 levels, GH treatment in the 13 patients resulted in signifi cant growth acceleration associated with a significant rise in the ser um IGF-I and IGFBP-3 and a significant fall in serum GHBP concentratio ns, CONCLUSIONS The low serum concentrations of IGFI and IGFBP-3 in th e presence of normal GH reserve and serum GHBP concentrations in patie nts with beta-thalassaemia suggest a state of partial GH insensitivity at the post-receptor level. This partial GH insensitivity state can b e overcome by supraphysiological doses of exogenous GH, The lack of co rrelation of IGF-I, IGFBP-3 and GHBP with height SDS of the patients i mply that the growth failure commonly observed in patients with P-thal assaemia major may not be specifically related to dysregulation of the GH-IGF-I axis. GH therapy resulted in significant increase in serum I GF-I and IGFBP-3 but a significant fall in GHBP.