title: IGF-1 Levels, Complex Formation, and IGF Bioactivity in Growth Hormone-Treated Children With Prader-Willi Syndrome.
abstract: BACKGROUND
  Children with Prader-Willi syndrome (PWS) attain high-serum immunoreactive IGF-1 levels during a standard-dose GH treatment, which leads to concern, but lowering the dose deteriorates their body composition.
  
  
  OBJECTIVE
  The objective of the study was to evaluate serum IGF-1, IGF binding protein (IGFBP)-3, and acid-labile subunit (ALS) levels, complex formation, and IGF bioactivity in GH-treated PWS children.
  
  
  METHODS
  This was a cross-sectional study.
  
  
  METHODS
  The setting of the study was a Dutch PWS cohort.
  
  
  METHODS
  Forty GH-treated PWS children compared with 41 age- and sex-matched healthy controls participated in the study.
  
  
  METHODS
  Interventions included GH treatment (1.0 mg/m(2) · d = ∼0.035 mg/kg · d).
  
  
  METHODS
  Serum IGF-1, IGFBP-3, and ALS levels, complex formation, and IGF bioactivity by IGF-1 receptor kinase activation assay were measured.
  
  
  RESULTS
  Serum IGF-1, IGFBP-3, and ALS levels and IGF-1 to IGFBP-3 ratio were significantly higher in GH-treated PWS children than in healthy controls. The 150-kDa ternary complex formation was, however, also significantly higher than in controls, indicating that most of serum IGF-1 is sequestered in the ternary 150-kDa complex with ALS and IGFBP-3. Young GH-treated PWS children [median (interquartile range) aged 5.2 (4.3-7.2) y] exhibited higher serum IGF bioactivity than controls, but no difference was observed in IGF bioactivity between older GH-treated PWS children, aged 14.9 (13.8-16.2) years, and controls. The proportion of IGF bioactivity of total serum IGF-1 was, however, lower in GH-treated PWS children than in controls. Serum immunoreactive IGF-1 levels did not correlate with IGF bioactivity in GH-treated children with PWS, in contrast to a strong positive correlation in healthy controls.
  
  
  CONCLUSIONS
  In GH-treated PWS children, most serum IGF-1 is sequestered in the 150-kDa complex. Higher IGF bioactivity was found only in young GH-treated PWS children and not in the older ones. IGF bioactivity during GH showed a wide variation, and there was a disrupted correlation with immunoreactive IGF-1 levels, which makes immunoreactive IGF-1 levels an inappropriate indicator for GH dosing in PWS children.
authors.affiliation: Dutch Growth Research Foundation (N.E.B., A.C.S.H.-K.), 3016 AH Rotterdam, The Netherlands; Department of Pediatrics (N.E.B., J.S.R., A.C.S.H.-K.), Subdivision of Endocrinology, Erasmus Medical Center/Sophia Children's Hospital, 3000 DR Rotterdam, The Netherlands; and Department of Clinical Chemistry and Haematology (J.v.D., G.H.D.), Laboratory of Endocrinology and Department of Medical Genetics, Section of Metabolic Diseases, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands.
authors.forename: N E
authors.initials: NE
authors.lastname: Bakker
authors.affiliation: Dutch Growth Research Foundation (N.E.B., A.C.S.H.-K.), 3016 AH Rotterdam, The Netherlands; Department of Pediatrics (N.E.B., J.S.R., A.C.S.H.-K.), Subdivision of Endocrinology, Erasmus Medical Center/Sophia Children's Hospital, 3000 DR Rotterdam, The Netherlands; and Department of Clinical Chemistry and Haematology (J.v.D., G.H.D.), Laboratory of Endocrinology and Department of Medical Genetics, Section of Metabolic Diseases, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: van Doorn
authors.affiliation: Dutch Growth Research Foundation (N.E.B., A.C.S.H.-K.), 3016 AH Rotterdam, The Netherlands; Department of Pediatrics (N.E.B., J.S.R., A.C.S.H.-K.), Subdivision of Endocrinology, Erasmus Medical Center/Sophia Children's Hospital, 3000 DR Rotterdam, The Netherlands; and Department of Clinical Chemistry and Haematology (J.v.D., G.H.D.), Laboratory of Endocrinology and Department of Medical Genetics, Section of Metabolic Diseases, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands.
authors.forename: J S
authors.initials: JS
authors.lastname: Renes
authors.affiliation: Dutch Growth Research Foundation (N.E.B., A.C.S.H.-K.), 3016 AH Rotterdam, The Netherlands; Department of Pediatrics (N.E.B., J.S.R., A.C.S.H.-K.), Subdivision of Endocrinology, Erasmus Medical Center/Sophia Children's Hospital, 3000 DR Rotterdam, The Netherlands; and Department of Clinical Chemistry and Haematology (J.v.D., G.H.D.), Laboratory of Endocrinology and Department of Medical Genetics, Section of Metabolic Diseases, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands.
authors.forename: G H
authors.initials: GH
authors.lastname: Donker
authors.affiliation: Dutch Growth Research Foundation (N.E.B., A.C.S.H.-K.), 3016 AH Rotterdam, The Netherlands; Department of Pediatrics (N.E.B., J.S.R., A.C.S.H.-K.), Subdivision of Endocrinology, Erasmus Medical Center/Sophia Children's Hospital, 3000 DR Rotterdam, The Netherlands; and Department of Clinical Chemistry and Haematology (J.v.D., G.H.D.), Laboratory of Endocrinology and Department of Medical Genetics, Section of Metabolic Diseases, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands.
authors.forename: A C S
authors.initials: AC
authors.lastname: Hokken-Koelega
mesh_terms: D000293:Adolescent; D002352:Carrier Proteins / Q000378:metabolism; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D005260:Female; D006023:Glycoproteins / Q000378:metabolism; D019382:Human Growth Hormone / Q000627:therapeutic use*; D006801:Humans; D007223:Infant; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D046912:Multiprotein Complexes / Q000378:metabolism; D009426:Netherlands; D011218:Prader-Willi Syndrome / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D006023:Glycoproteins; D046912:Multiprotein Complexes; C075944:insulin-like growth factor binding protein, acid labile subunit; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I