Reference Intervals for Insulin-like Growth Factor-1 (IGF-I) From Birth to Senescence: Results From a Multicenter Study Using a New Automated Chemiluminescence IGF-I Immunoassay Conforming to Recent International Recommendations

• Published in: The journal of clinical endocrinology and metabolism 2014-05, Vol.99 (5), p.1712-1721
• Main Authors: Bidlingmaier, Martin, Friedrich, Nele, Emeny, Rebecca T, Spranger, Joachim, Wolthers, Ole D, Roswall, Josefine, Körner, Antje, Obermayer-Pietsch, Barbara, Hübener, Christoph, Dahlgren, Jovanna, Frystyk, Jan, Pfeiffer, Andreas F. H, Doering, Angela, Bielohuby, Maximilian, Wallaschofski, Henri, Arafat, Ayman M
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Aging - blood; Automation; Chemiluminescence; Child; Child, Preschool; Female; Growth hormones; Humans; Immunoassay; Immunoassay - methods; Infant; Infant, Newborn; Insulin-like growth factor I; Insulin-Like Growth Factor I - analysis; Insulin-Like Growth Factor I - metabolism; Insulin-like growth factors; Life span; Luminescent Measurements - methods; Male; Middle Aged; Reference Values; Senescence
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2013-3059

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.