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J Clin Endocrinol Metab. 2014 May;99(5):1675-86. doi: 10.1210/jc.2013-3060. Epub 2014 Jan 31.

Age- and sex-specific reference intervals across life span for insulin-like growth factor binding protein 3 (IGFBP-3) and the IGF-I to IGFBP-3 ratio measured by new automated chemiluminescence assays.

Author information

  • 1Metabolic Center (N.F., H.W.), Institute of Clinical Chemistry and Laboratory Medicine, and Department of Psychiatry and Psychotherapy (H.J.G.), University Medicine Greifswald, D-17475 Greifswald, Germany; Department of Psychiatry and Psychotherapy (H.J.G.), Helios Hospital Stralsund, D-18437 Stralsund, Germany; Children's Clinic Randers (O.D.W.), DK-8900 Randers, Denmark; Department of Endocrinology, Diabetes, and Nutrition (A.M.A., J.S., A.F.H.P.) and Center for Cardiovascular Research (A.M.A., J.S.), Charité-University Medicine Berlin, D-10117 Berlin, Germany; Department of Clinical Nutrition (A.M.A., A.F.H.P.), German Institute of Human Nutrition Potsdam-Rehbruecke, D-14558 Nuthetal, Germany; Helmholtz Zentrum Muenchen-German Research Center for Environmental Health (R.T.E., A.D.), Institute of Epidemiology II, D-85764 Neuherberg, Germany; Experimental and Clinical Research Center (J.S.), Charité-University Medicine Berlin and Max-Delbrück Centre Berlin-Buch, D-13125 Berlin, Germany; Göteborg Pediatric Growth Research Center (J.R., J.D.), The Sahlgrenska Academy at University of Gothenburg, SE-41685 Gothenburg, Sweden; Institut für Laboratoriumsmedizin (J.K.), Klinische Chemie, Molekulare Diagnostik, University of Leipzig, D-04103 Leipzig, Germany; Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe-Großhadern (C.H.), Klinikum der Universität München, D-81377 Munich, Germany; Endocrine Research Laboratories (M.B., M.B.), Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, D-80336 Munich, Germany; and Medical Research Laboratory (J.F.), Department of Clinical Medicine, Faculty of Health, Aarhus University, and Department of Endocrinology and Internal Medicine (J.F.), Aarhus University Hospital, DK-8000 C Aarhus, Denmark.

Abstract

CONTEXT:

Measurement of IGF-binding protein-3 (IGFBP-3) can aid the diagnosis of GH-related diseases. Furthermore, epidemiological studies suggest that IGFBP-3 and the molar IGF-I to IGFBP-3 ratio are associated with clinical end points like cancer or cardiovascular disease. However, their clinical use is limited by the lack of validated reference intervals.

OBJECTIVE:

The objective of the study was the establishment of age- and sex-specific reference intervals for IGFBP-3 and the molar IGF-I to IGFBP-3 ratio by newly developed automated immunoassays.

SETTING:

This was a multicenter study with samples from 11 cohorts from the United States, Canada, and Europe.

PARTICIPANTS:

A total of 14 970 healthy subjects covering all ages from birth to senescence participated in the study.

MAIN OUTCOME MEASURES:

Concentrations of IGFBP-3 and the IGF-I to IGFBP-3 ratio as determined by the IDS iSYS IGF-I and IGFBP-3 assays were measured.

RESULTS:

Both the concentration of IGFBP-3 and the IGF-I to IGFBP-3 ratio are mainly determined by age. IGFBP-3 concentrations increase until the age of 22 years, with a plateau being visible between 15 and 25 years. Determined by the high peripubertal peak in IGF-I, the peak in the IGF-I to IGFBP-3 ratio occurs already around the age of 15 years, with a slightly earlier and higher peak in females. Beyond the age of 60 years, IGFBP-3 concentrations remain higher in females, whereas IGF-I as well as the IGF-I to IGFBP-3 ratio remains significantly higher in males.

CONCLUSIONS:

We present an extensive set of assay-specific age- and sex-adjusted normative data for concentrations of IGFBP-3 and the molar IGF-I to IGFBP-3 ratio and demonstrate distinct sex specific differences across the life span.

PMID:
24483154
[PubMed - indexed for MEDLINE]
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