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

• Published in: Clinical endocrinology (Oxford) 2006-09, Vol.65 (3), p.310-319
• Main Authors: Bannink, Ellen M. N., Van Doorn, Jaap, Stijnen, Theo, Drop, Stenvert L. S., De Muinck Keizer-Schrama, Sabine M. P. F.
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Area Under Curve; Biological and medical sciences; Child; Dose-Response Relationship, Drug; Drug Administration Schedule; Endocrinopathies; Estradiol - therapeutic use; Estrogen Replacement Therapy; Female; Fundamental and applied biological sciences. Psychology; Glucose Tolerance Test; Growth Disorders - drug therapy; Growth Disorders - etiology; Human Growth Hormone - therapeutic use; Humans; Insulin-Like Growth Factor Binding Protein 1 - blood; Insulin-Like Growth Factor Binding Protein 2 - blood; Insulin-Like Growth Factor Binding Protein 3 - blood; Insulin-Like Growth Factor Binding Proteins - blood; Insulin-Like Growth Factor I - analysis; Medical sciences; Time Factors; Turner Syndrome - blood; Turner Syndrome - drug therapy; Vertebrates: endocrinology
• ISSN: 0300-0664; 1365-2265
• DOI: 10.1111/j.1365-2265.2006.02594.x

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/m2/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.