Within-Subject Variability and Analytic Imprecision of Insulinlike Growth Factor Axis and Collagen Markers: Implications for Clinical Diagnosis and Doping Tests

• Published in: Clinical chemistry (Baltimore, Md.) Md.), 2008-08, Vol.54 (8), p.1268-1276
• Main Authors: Nguyen, Tuan V, Nelson, Anne E, Howe, Christopher J, Seibel, Markus J, Baxter, Robert C, Handelsman, David J, Kazlauskas, Ray, Ho, Ken K
• Format: Article
• Language: English
• Subjects: Adult; Analysis of Variance; Analytical, structural and metabolic biochemistry; Athletes; Biological and medical sciences; Biomarkers - blood; Clinical Laboratory Techniques - methods; Clinical Laboratory Techniques - standards; Cohort Studies; Collagen - analysis; Collagen - blood; Data analysis; Doping in Sports - prevention & control; Female; Fundamental and applied biological sciences. Psychology; Growth disorders; Growth Hormone - blood; Growth hormones; Humans; Insulin; Insulin-Like Growth Factor Binding Protein 3 - blood; Insulin-Like Growth Factor I - analysis; Investigative techniques, diagnostic techniques (general aspects); Male; Medical diagnosis; Medical sciences; Metabolic disorders; Minority & ethnic groups; Sensitivity and Specificity; Sports - standards; Substance Abuse Detection - methods; Substance Abuse Detection - standards; Variance analysis
• ISSN: 0009-9147; 1530-8561
• DOI: 10.1373/clinchem.2008.105726

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. 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. 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. 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.