Within-subject variability and analytic imprecision of insulinlike growth factor axis and collagen markers: implications for clinical diagnosis and doping tests

Clin Chem. 2008 Aug;54(8):1268-76. doi: 10.1373/clinchem.2008.105726. Epub 2008 Jun 20.

Abstract

Background: The utility of insulinlike growth factor (IGF) axis and collagen markers for a growth hormone (GH) doping test in sport depends on their stability and reproducibility. We sought to determine short-term within-subject variability of these markers in a large cohort of healthy individuals.

Methods: We measured IGF-I, IGF binding protein 3 (IGFBP-3), acid labile subunit (ALS), and the collagen markers N-terminal propeptide of type I procollagen (PINP), C-terminal telopeptide of type I collagen (ICTP), and N-terminal propeptide of type III procollagen (PIIINP) in serum samples obtained on multiple occasions (median 3 per participant) over a 2- to 3-week period from 1103 elite athletes (699 men, 404 women) ages 22.2 (5.2) years [mean (SD)]. We estimated between-subject and within-subject variances by mixed-effects ANOVA.

Results: Within-subject variance accounted for 32% to 36% and 4% to 13% of the total variance in IGF markers and collagen markers, respectively. The within-subject CV ranged from 11% to 21% for the IGF axis markers and from 13% to 15% for the collagen markers. The index of individuality for the IGF axis markers was 0.66-0.76, and for the collagen markers, 0.26-0.45. For each marker, individuals with initial extreme measured values tended to regress toward the population mean in subsequent repeated measurements. We developed a Bayesian model to estimate the long-term probable value for each marker.

Conclusions: These results indicate that in healthy individuals the within-subject variability was greater for IGF-I than for the collagen markers, and that where a single measurement is available, it is possible to estimate the long-term probable value of each of the markers by applying the Bayesian approach. Such an application can increase the reliability and decrease the cost of detecting GH doping.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Analysis of Variance
  • Biomarkers / blood
  • Clinical Laboratory Techniques* / methods
  • Clinical Laboratory Techniques* / standards
  • Cohort Studies
  • Collagen / analysis*
  • Collagen / blood
  • Doping in Sports / prevention & control*
  • Female
  • Growth Hormone / blood*
  • Humans
  • Insulin-Like Growth Factor Binding Protein 3 / blood
  • Insulin-Like Growth Factor I / analysis*
  • Male
  • Sensitivity and Specificity
  • Sports / standards*
  • Substance Abuse Detection* / methods
  • Substance Abuse Detection* / standards

Substances

  • Biomarkers
  • Insulin-Like Growth Factor Binding Protein 3
  • Insulin-Like Growth Factor I
  • Growth Hormone
  • Collagen