Establishment of IGF-1 and IGFBP-3 continuous reference percentiles from data of healthy children using three kinds of immunoassay systems

Background and aims: Appropriate continuous reference intervals (RIs) for serum insulin-like growth factor 1 (IGF-1) and insulin-like growth factor-binding protein 3 (IGFBP-3) are important for diagnosing growth hormone deficiency or excess.

Material and methods: We retrospectively reviewed serum IGF-1 and IGFBP-3 levels in Korean children aged 0-17 years who were diagnosed as healthy during a short stature workup in the outpatient clinics of three hospitals. IGF-1 and IGFBP-3 levels were measured using various immunoassays, including Liaison XL for IGF-1, an immunoradiometric assay (IRMA) for IGFBP-3 (n = 5522), and Immulite 2000 (n = 3036) and cobas e801 (n = 314). We established RIs from the 2.5th to 97.5th percentile RI curves using the lambda-mu-sigma (LMS) method for each sex group.

Results: Pediatric serum continuous IGF-1 and IGFBP-3 reference percentiles by LMS method were found to be immunoassay method-dependent, but aligned relatively well with the manufacturers' RIs. IGFBP-3 levels displayed notable discrepancies among the different immunoassay methods.

Conclusion: Age- and sex-specific pediatric LMS based continuous reference intervals are method dependent and they should be calculated for dynamic parameters that show variations throughout childhood.