title: 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.
abstract: 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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
authors.affiliation: Department of Pediatrics, Division of Endocrinology, Erasmus MC, Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Ellen M N
authors.initials: EM
authors.lastname: Bannink
authors.forename: Jaap
authors.initials: J
authors.lastname: van Doorn
authors.forename: Theo
authors.initials: T
authors.lastname: Stijnen
authors.forename: Stenvert L S
authors.initials: SL
authors.lastname: Drop
authors.forename: Sabine M P F
authors.initials: SM
authors.lastname: de Muinck Keizer-Schrama
mesh_terms: D000704:Analysis of Variance; D019540:Area Under Curve; D002648:Child; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004958:Estradiol / Q000627:therapeutic use; D015914:Estrogen Replacement Therapy; D005260:Female; D005951:Glucose Tolerance Test; D006130:Growth Disorders / Q000188:drug therapy* / Q000209:etiology; D019382:Human Growth Hormone / Q000627:therapeutic use*; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D013997:Time Factors; D014424:Turner Syndrome / Q000097:blood* / Q000188:drug therapy*
chemical_list: D018970:Insulin-Like Growth Factor Binding Protein 1; D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D019382:Human Growth Hormone; D004958:Estradiol; D007334:Insulin-Like Growth Factor I