Determining the normal range for IGF-I, IGFBP-3, and ALS: new reference data based on current internal standards

Wien Med Wochenschr. 2014 Sep;164(17-18):343-52. doi: 10.1007/s10354-014-0299-4. Epub 2014 Sep 4.


Background: The measurement of insulin-like growth factors (IGF-I) and insulin-like growth factor-binding protein (IGFBP-3) often serves as first-line testing in children with growth disorders. The role of acid-labile subunit (ALS) as a screening parameter for homozygous or heterozygous mutations of the ALS gene still has to be determined.

Methods: IGF-I, IGFBP-3, and ALS were measured in 252 samples from children and adolescents. Reference curves were fitted using generalized additive model for location, scale and shape (GAMLSS) models and SD-Scores were calculated. Bootstrap analysis was used to quantify the uncertainty of the estimated percentiles. Bland-Altman plots were used to investigate the discrepancy between our newly estimated standard deviation scores (SDS) and SDS calculated on the basis of previous reference data.

Results: We present reference data for enzyme-linked immunosorbent assay (ELISA) measurements based on recommended internal standard for IGF-I, IGFBP-3, and ALS suitable for calculation of SD-scores. The Bland-Altman plot shows a rough agreement between the previous SDS calculation and our new one only for SDS around 1; for SDS at -2, an average difference of 0.83 SD was noticed.

Conclusion: Our IGF-I reference values for the interval of interest in diagnosing growth hormone deficiency (GHD) (prepubertal age) are solid as proved by bootstrap analysis. The difference in calculated SD scores by using data provided previously highlights the importance of using labor and method specific reference data.

MeSH terms

  • Adolescent
  • Austria
  • Carrier Proteins / blood*
  • Child
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Glycoproteins / blood*
  • Growth Disorders / blood*
  • Growth Disorders / diagnosis*
  • Humans
  • Insulin-Like Growth Factor Binding Protein 2 / blood*
  • Insulin-Like Growth Factor I / metabolism*
  • Male
  • Mass Screening
  • Reference Standards


  • Carrier Proteins
  • Glycoproteins
  • Insulin-Like Growth Factor Binding Protein 2
  • insulin-like growth factor binding protein, acid labile subunit
  • Insulin-Like Growth Factor I