Age related IGF-I changes and IGF-I generation in thalassemia major

We measured serum concentrations of insulin like growth factor-I (IGF-I) in 20 thalassemic males with short stature (height SDS <-2) and/or slow growth velocity (GV <-1 SD) throughout their childhood and adolescence, compared these data with normal reference data validated in our lab, and evaluated their growth hormone secretion in response to clonidine and glucagon stimulation. We also performed IGF-I generation test on 26 patients with beta thalassemia major (BTM) before and after blood transfusion to evaluate the effect of increased hemoglobin (Hb) on IGF-I and its response to GH. We obtained the following results. 1) No statistical difference in age, HSDS, target height SDS or bone age was observed between BTM patients with growth hormone deficiency (GHD) compared to those with normal GH secretion (GHS). 2) The age-related levels in serum total IGF-I in thalassemic males were significantly decreased from early childhood to 18 years of age compared to normal subjects. Thalassemic males with GHD did not show any significant peak of IGF-I levels until 18 years of age, whereas thalassemic males with normal GH response to provocation (GHS) achieved a significant peak level of IGF-I that was attenuated and late compared to normal males. The basal serum IGF-I concentrations at different ages did not differ between the GHD and GHS groups until the age of 12 years. After 12 years of age, IGF-I levels were significantly higher in thalassemic children with GHS. A significant increase in the circulating basal IGF-I concentrations from 53 +/-35 ug/l to 82.6 +/- 39 ug/L was achieved with increasing Hb concentration after blood transfusion. The serum total IGF-I levels increased significantly with the administration of human growth hormone (hGH) for 4 days, both before and after blood transfusion. The peak IGF-I response to GH injections did not differ before compared to after blood transfusion. The percent increment of IGF-I levels generated after GH injections was higher in thalassemic children with GHD as compared to those with GHS both before and after blood transfusion. In conclusion, our results showed that agerelated serum IGF-I concentrations were significantly lower in short thalassemic patients, with and without GHD, during childhood and adolescence, compared to normal standards. Correction of anemia significantly increased serum concentration of IGF-I but does not affect the increase of IGF-I in response to GH stimulation.