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

作者：Friedrich Nele; Wolthers Ole D; Arafat Ayman M; Emeny Rebecca T; Spranger Joachim; Roswall Josefine; Kratzsch Juergen; Grabe Hans J; Huebener Christoph; Pfeiffer Andreas F H; Doering Angela; Bielohuby Maximilian; Dahlgren Jovanna; Frystyk Jan; Wallaschofski Henri; Bidlingmaier Martin^*

来源：Journal of Clinical Endocrinology & Metabolism, 2014, 99(5): 1675-1686.

DOI：10.1210/jc.2013-3060

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.

• 出版日期2014-5