title: Free/dissociable insulin-like growth factor (IGF)-I, not total IGF-I, correlates with growth response during growth hormone treatment in children born small for gestational age.
abstract: BACKGROUND
  IGF-I plays an important role in pre- and postnatal growth. Its serum levels are regulated by metabolic and genetic factors. Mean total IGF-I in short, small for gestational age (SGA) children is reduced, but within the normal range. Free/dissociable IGF-I is the bioactive form of IGF-I.
  
  
  OBJECTIVE
  The aim of the study was to investigate changes in free IGF-I during GH treatment in short SGA children and to evaluate whether free IGF-I levels contribute to predicting first-year growth response and/or adult height. DESIGN, SETTING, AND INTERVENTION: We conducted a randomized, double-blind GH dose-response study with a GH dose of either 1 mg/m(2).d (group A) or 2 mg/m(2).d (group B). Free IGF-I, total IGF-I, and IGF binding protein (IGFBP)-3 were determined at baseline, after 1 and 5 yr, at stop, and 6 months after GH discontinuation.
  
  
  METHODS
  We studied 73 (46 male) short SGA children (36 group A) with a baseline mean age of 7.7 (2.2) yr and a mean GH duration of 8.2 (2.1) yr.
  
  
  METHODS
  Untreated SGA children had a mean free IGF-I sd score (SDS) of -0.2 (1.2), not related to total IGF-I. During GH therapy, free IGF-I significantly increased to 1.6 (0.7) SDS, as did total IGF-I and IGFBP-3 [2.0 (0.8) and 1.3 (0.9), respectively]. Multiple regression analysis showed that baseline free IGF-I and IGFBP-3 were negatively correlated with adult height SDS, whereas baseline bone age delay, target height SDS, baseline height SDS, and GH dose were positively correlated. Free IGF-I was also negatively correlated with first-year growth response.
  
  
  CONCLUSIONS
  Circulating baseline free IGF-I and IGFBP-3 were better predictors for adult height in GH-treated SGA children than total IGF-I, or total IGF-I to IGFBP-3 ratio. This suggests a possible role for free IGF-I measurement in predicting the effect of GH therapy in short SGA children.
authors.affiliation: Erasmus MC-Sophia Children's Hospital, Department of Pediatrics, Dr. Molewaterplein 60, 3015 GJ 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: Paul G H
authors.initials: PG
authors.lastname: Mulder
authors.forename: Anita C S
authors.initials: AC
authors.lastname: Hokken-Koelega
mesh_terms: D000328:Adult; D000375:Aging / Q000502:physiology; D001827:Body Height / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D005260:Female; D006128:Growth / Q000187:drug effects*; D013006:Growth Hormone / Q000627:therapeutic use*; D019382:Human Growth Hormone / Q000097:blood*; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age / Q000097:blood*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D011237:Predictive Value of Tests
chemical_list: D018972:Insulin-Like Growth Factor Binding Protein 3; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone