Free dissociable insulin-like growth factor I (IGF-I), total IGF-I and their binding proteins in girls with Turner syndrome during long-term growth hormone treatment

Objective To investigate the effect of GH treatment on free IGF-I levels in girls with Turner syndrome (TS) and to verify relationships between free IGF-I levels and total IGF-I, IGFBP-1, 2 and 3. Additionally, to analyse whether free IGF-I, total IGF-I, IGFBP-3 or its ratio were related to IGF-I bioactivity outcome parameters. Design Sixty-five girls with TS were randomly assigned to three different GH-dosage groups (1.3, 2.0 and 2.7 mg/m(2)/day). Mean duration of GH therapy was mean (SD) 8.7(2.0) years. Free IGF-I, total IGF-I and IGFBP-1, -2, -3 were determined at baseline, first, second, third and fifth year of GH therapy, before the start of oestrogen therapy, during the final year of GH treatment, 6 months after GH and 4.8(2.0) years after GH discontinuation. Main outcome During GH treatment, mean free IGF-I levels stayed < +2 standard deviation score (SDS), whereas mean total IGF-I and IGF-I/IGFBP-3 ratio were > +2 SDS. There were no differences in free IGF-I levels between the three GH groups, whereas total IGF-I and ratio levels were significantly higher in the highest GH group. The following variables contributed significantly to predicting the square root of free IGF-I levels: age, GH dose, oestrogen dose, IGFBP-1, IGFBP-3, body mass index and total IGF-I or IGF-I/IGFBP-3 ratio. However, the explaining variance did not exceed 55%. Several IGF-I bioactivity outcome parameters positively correlated with total IGF-I and IGF-I/IGFBP-3 ratio, whereas free IGF-I did not. Conclusions During long-term GH therapy in girls with TS, mean free IGF-I levels stayed within the normal range, whereas mean total IGF-I and IGF-I/IGFBP-3 ratio exceeded the upper normal range. Although total IGF-I and the IGF-I/IGFBP-3 ratio did not accurately represent free IGF-I levels, they seemed to better represent the IGF-I bioactivity than the measured free IGF-I.