title: Inaccuracy of insulin-like growth factor (IGF) binding protein (IGFBP)-3 assessment in the diagnosis of growth hormone (GH) deficiency from childhood to young adulthood: association to low GH dependency of IGF-II and presence of circulating IGFBP-3 18-kilodalton fragment.
abstract: BACKGROUND
  Poor sensitivity of IGF binding protein (IGFBP)-3 assessment in the work-up of GH deficiency (GHD) has been ascribed to the equal affinity of IGFBP-3 for IGF-I and IGF-II and to IGFBP-3 proteolysis.
  
  
  OBJECTIVE
  The objective of this study was to determine the IGF-II GH dependency and IGFBP-3 proteolysis in patients with GHD from childhood to young adulthood.
  
  
  METHODS
  This study was cross-sectional.
  
  
  METHODS
  This was a national multicenter study performed in university hospitals.
  
  
  METHODS
  One hundred thirty-one subjects (chronological age, 1.3-25 yr), 72 patients with GHD and 59 subjects with idiopathic short stature, were studied.
  
  
  METHODS
  IGF-I, IGF-II, and IGFBP-3 serum concentrations were measured by immunoradiometric assay. IGFBP-3 circulating forms were assessed by Western immunoblot (WIB) analysis.
  
  
  METHODS
  Main outcome measures were sensitivity and specificity of IGF-I, IGF-II, and IGFBP-3 measurements.
  
  
  RESULTS
  Sensitivity and specificity of IGFBP-3 measurement were 27 and 100%, respectively. IGFBP-3 sensitivity was 46% in young adulthood. Sensitivity and specificity of IGF-I were 69 and 81%, respectively. Sensitivity and specificity of IGF-II assessment were 23 and 97%, respectively. IGFBP-3 WIB revealed the presence of the intact form and the major 29-kDa fragment in both GHD and subjects with idiopathic short stature. In patients with GHD, WIB showed the presence of an additional smaller IGFBP-3 fragment migrating at approximately 18 kDa.
  
  
  CONCLUSIONS
  Our results suggest that in children and young adults with GHD, the low GH dependency of IGF-II together with IGFBP-3 proteolytic activity yielding the 18-kDa fragment concur to reduce the sensitivity of IGFBP-3 assessment, ultimately making it too inaccurate as a screening test in the work-up of GHD.
authors.affiliation: Rina Balducci Center of Pediatric Endocrinology, Department of Public Health and Cell Biology, Room E-178, Tor Vergata University, Via Montpellier 1, 00133 Rome, Italy. stefano.cianfarani@uniroma2.it
authors.forename: Stefano
authors.initials: S
authors.lastname: Cianfarani
authors.forename: Alice
authors.initials: A
authors.lastname: Liguori
authors.forename: Sergio
authors.initials: S
authors.lastname: Boemi
authors.forename: Mohamad
authors.initials: M
authors.lastname: Maghnie
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Iughetti
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Wasniewska
authors.forename: Maria E
authors.initials: ME
authors.lastname: Street
authors.forename: Stefano
authors.initials: S
authors.lastname: Zucchini
authors.forename: Gianluca
authors.initials: G
authors.lastname: Aimaretti
authors.forename: Daniela
authors.initials: D
authors.lastname: Germani
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D003430:Cross-Sectional Studies; D005260:Female; D019382:Human Growth Hormone / Q000172:deficiency*; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D007335:Insulin-Like Growth Factor II / Q000032:analysis*; D008297:Male; D010446:Peptide Fragments / Q000097:blood*
chemical_list: D018972:Insulin-Like Growth Factor Binding Protein 3; D010446:Peptide Fragments; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II