title: Reference intervals for insulin-like growth factor-1 (igf-i) from birth to senescence: results from a multicenter study using a new automated chemiluminescence IGF-I immunoassay conforming to recent international recommendations.
abstract: BACKGROUND
  Measurement of IGF-I is a cornerstone in diagnosis and monitoring of GH-related diseases, but considerable discrepancies exist between analytical methods. A recent consensus conference defined criteria for validation of IGF-I assays and for establishment of normative data.
  
  
  OBJECTIVE
  Our objectives were development and validation of a novel automated IGF-I immunoassay (iSYS; Immunodiagnostic Systems) according to international guidelines and establishment of method-specific age- and sex-adjusted reference intervals and analysis of their robustness.
  
  
  METHODS
  We conducted a multicenter study with samples from 12 cohorts from the United States, Canada, and Europe including 15 014 subjects (6697 males and 8317 females, 0-94 years of age).
  
  
  METHODS
  We measured concentrations of IGF-I as determined by the IDS iSYS IGF-I assay.
  
  
  RESULTS
  A new IGF-I assay calibrated against the recommended standard (02/254) and insensitive to the 6 high-affinity IGF binding proteins was developed and rigorously validated. Age- and sex-adjusted reference intervals derived from a uniquely large cohort reflect the age-related pattern of IGF-I secretion: a decline immediately after birth followed by an increase until a pubertal peak (at 15 years of age). Later in life, values decrease continuously. The impact of gender is small, although across the lifespan, women have lower mean IGF-I concentrations. Geographical region, sampling setting (community or hospital based), and rigor of exclusion criteria in our large cohort did not affect the reference intervals.
  
  
  CONCLUSIONS
  Using large cohorts of well-characterized subjects from different centers allowed construction of robust reference ranges for a new automated IGF-I assay. The strict adherence to recent consensus criteria for IGF-I assays might facilitate clinical application of the results.
authors.affiliation: Endocrine Research Laboratories (M.Bid., M.Bie.), Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, 80336 Munich, Germany; Metabolic Center (N.F., H.W.), Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, 17475 Greifswald, Germany; Helmholtz Zentrum München-German Research Center for Environmental Health (GmbH) (R.T.E., A.D.), Institute of Epidemiology II, 85764 Neuherberg, Germany; Department of Endocrinology, Diabetes, and Nutrition (J.S., A.F.H.P., A.M.A.), Charité-University Medicine Berlin, 10117 Berlin, Germany; Experimental and Clinical Research Center (J.S.), Charité-University Medicine Berlin and Max-Delbrück Centre Berlin-Buch, 13125 Berlin, Germany; Center for Cardiovascular Research (J.S., A.M.A.), Charité-University Medicine Berlin, 10115 Berlin, Germany; Children's Clinic Randers (O.D.W.), DK-8900 Randers, Denmark; Göteborg Pediatric Growth Research Center (J.R.), The Sahlgrenska Academy at University of Gothenburg, 41685 Gothenburg, Sweden; Center for Pediatric Research (A.K.), Hospital for Children and Adolescents, Department of Women's and Child Health, University of Leipzig, 04103 Leipzig, Germany; Klinische Abteilung und Labor für Endokrinologie und Stoffwechsel (B.O.-P.), Universitätsklinik für Innere Medizin, Medizinische Universität Graz, 8036 Graz, Austria; Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe-Grosshadern (C.H.), Klinikum der Universität München, 81377 Munich, Germany; Medical Research Laboratory (J.F.), Department of Clinical Medicine, Faculty of Health, Aarhus University, DK-8000 Aarhus, Denmark; Department of Endocrinology and Internal Medicine (J.F.), Aarhus University Hospital, DK-8000 Aarhus, Denmark; and Department of Clinical Nutrition (A.F.H.P., A.M.A.), German Institute of Human Nutrition Potsdam-Rehbruecke, 14558 Nuthetal, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Bidlingmaier
authors.forename: Nele
authors.initials: N
authors.lastname: Friedrich
authors.forename: Rebecca T
authors.initials: RT
authors.lastname: Emeny
authors.forename: Joachim
authors.initials: J
authors.lastname: Spranger
authors.forename: Ole D
authors.initials: OD
authors.lastname: Wolthers
authors.forename: Josefine
authors.initials: J
authors.lastname: Roswall
authors.forename: Antje
authors.initials: A
authors.lastname: Körner
authors.forename: Barbara
authors.initials: B
authors.lastname: Obermayer-Pietsch
authors.forename: Christoph
authors.initials: C
authors.lastname: Hübener
authors.forename: Jovanna
authors.initials: J
authors.lastname: Dahlgren
authors.forename: Jan
authors.initials: J
authors.lastname: Frystyk
authors.forename: Andreas F H
authors.initials: AF
authors.lastname: Pfeiffer
authors.forename: Angela
authors.initials: A
authors.lastname: Doering
authors.forename: Maximilian
authors.initials: M
authors.lastname: Bielohuby
authors.forename: Henri
authors.initials: H
authors.lastname: Wallaschofski
authors.forename: Ayman M
authors.initials: AM
authors.lastname: Arafat
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D007223:Infant; D007231:Infant, Newborn; D007334:Insulin-Like Growth Factor I / Q000032:analysis* / Q000378:metabolism; D008163:Luminescent Measurements / Q000379:methods*; D008297:Male; D008875:Middle Aged; D012016:Reference Values
chemical_list: D007334:Insulin-Like Growth Factor I