Martin Bidlingmaier1, Nele Friedrich, Rebecca T Emeny, Joachim Spranger, Ole D Wolthers, Josefine Roswall, Antje Körner, Barbara Obermayer-Pietsch, Christoph Hübener, Jovanna Dahlgren, Jan Frystyk, Andreas F H Pfeiffer, Angela Doering, Maximilian Bielohuby, Henri Wallaschofski, Ayman M Arafat. 1. 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.
Abstract
CONTEXT: 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. OBJECTIVES: 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. SETTING AND PARTICIPANTS: 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). MAIN OUTCOME MEASURES: 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.
CONTEXT: 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. OBJECTIVES: 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. SETTING AND PARTICIPANTS: 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). MAIN OUTCOME MEASURES: 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.
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