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

Journal article
Authors Nele Friedrich
Ole D Wolthers
Ayman M Arafat
Rebecca T Emeny
Joachim Spranger
Josefine Roswall
Jürgen Kratzsch
Hans J Grabe
Christoph Hübener
Andreas F H Pfeiffer
Angela Doering
Maximilian Bielohuby
Jovanna Dahlgren
Jan Frystyk
Henri Wallaschofski
Martin Bidlingmaier
Published in The Journal of clinical endocrinology and metabolism
Volume 99
Issue 5
Pages jc20133060
ISSN 1945-7197
Publication year 2014
Published at Institute of Clinical Sciences, Department of Pediatrics
Pages jc20133060
Language en
Subject categories Pediatrics


Context: Measurement of IGFBP-3 can aid the diagnosis of growth hormone related diseases. Furthermore, epidemiological studies suggest that IGFBP-3 and the molar IGF-I/IGFBP-3 ratio are associated with clinical endpoints like cancer or cardiovascular disease. However, their clinical use is limited by the lack of validated reference intervals. Objectives: Establishment of age- and sex-specific reference intervals for IGFBP-3 and the molar IGF-I/IGFBP-3 ratio by newly developed automated immunoassays. Setting: Multicentre study with samples from 11 cohorts from the USA, Canada and Europe Participants: 14,970 subjects healthy subjects covering all ages from birth to senescence. Main outcome measures: Concentrations of IGFBP-3 and the IGF-I/IGFBP-3 ratio as determined by the IDS iSYS IGF-I and IGFBP-3 assays. Results: Both the concentration of IGFBP-3 and the IGF-I/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/IGFBP-3 ratio occurs already around the age of 15, with a slightly earlier and higher peak in females. Beyond the age of 60, IGFBP-3 concentrations remain higher in females, whereas IGF-I as well as the IGF-I/IGFBP-3 ratio remain 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/IGFBP-3 ratio and demonstrate distinct sex specific differences across lifespan.

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