Journal
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
Volume 99, Issue 5, Pages 1675-1686Publisher
ENDOCRINE SOC
DOI: 10.1210/jc.2013-3060
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Funding
- German Federal Ministry of Education and Research [FKZ 01ET1003D]
- Clinical Institute, Health, Aarhus University
- Johannes M. Klein og Hustrus Mindelegat
- Forskningsfonden Laegekredsforeningen for Aarhus Amt
- Kong Christian den Tiendes Fond
- Overlaege Johan Boserup og Lise Boserups Legat
- Koventualinde Emilie De Lancy's Fond
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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.
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