Intra-individual variation of GH-dependent markers in athletes: comparison of population based and individual thresholds for detection of GH abuse in sports.

The GH-2000 discriminant functions, using insulin-like growth factor I (IGF-I) and the N-terminal propeptide of type III procollagen (PIIINP), enabled the detection of growth hormone (GH) doping despite the broad inter-individual normal range of both peptides. The sensitivity of the discriminant function-based methodology may perhaps be further increased in future by applying individual athlete profiles. The purpose of the present study was to evaluate the intra-individual variability of IGF-I, PIIINP and the GH-2000 scores in athletes. For this purpose a total of eight blood samples were taken from each of fifty male and female elite athletes over a period of up to 18 months. The IGF-I and PIIINP levels, we found, lay predominantly within the reference range for elite athletes. The intra-individual variability for IGF-I ranged between 6 and 26%, while that for PIIINP ranged between 6 and 33%. The intra-individual variations of both parameters were higher in female than in male subjects and were found to be mostly moderate. We found that the intra-individual variations of the GH-2000 test scores, expressed as CV, ranged from 4 to 36% and were in most of the subjects markedly smaller than the inter-individual variation. Individual cut-offs for the GH-2000 scores would be lower than population based ones in most of the cases.

Validation of the growth hormone (GH)-dependent marker method of detecting GH abuse in sport through the use of independent data sets.

CONTEXT: The detection of exogenously administered growth hormone (GH) poses a formidable challenge but a detection method based on the measurement of two GH-dependent markers, IGF-I and type 3 pro-collagen (P-III-P) has been proposed. The measurement of multiple markers in conjunction with discriminant functions can improve the sensitivity and specificity of detection compared with single marker analysis. OBJECTIVE: To provide further validation of the GH-dependent marker approach. DESIGN: Analysis of discriminant function scores for GH detection on independent datasets. SETTING: Two independent (GH-2000 and Kreischa) double blind, placebo controlled, hGH administration studies. SUBJECTS: Healthy active male volunteers. INTERVENTION: GH-2000 proposed a discriminant function involving IGF-I and P-III- P while the Kreischa function involved IGF-I, P-III-P and IGFBP-3. After adjustment for assay differences the formulae were applied to the other dataset. OUTCOME MEASURES: Ability to detect GH use in independent datasets using a predefined specificity of approximately 1 in 10000. RESULTS: The GH-2000 formula was able to detect 90% of those receiving GH in the Kreischa study at one or more time points during the study period. This sensitivity was similar to that obtained on the original GH-2000 dataset. The Kreischa formula correctly identified 41% of individuals receiving GH in the GH-2000 study. CONCLUSIONS: The study provides further validation that the test proposed by GH-2000 based on IGF-I and P-III-P concentrations can be used to detect subjects receiving exogenous GH.

Pharmacokinetics and pharmacodynamics of GH: dependence on route and dosage of administration.

OBJECTIVE: Pharmacokinetic and pharmacodynamic data after recombinant human GH (rhGH) administration in adults are scarce, but necessary to optimize replacement therapy and to detect doping. We examined pharmacokinetics, pharmacodynamics, and 20 kDa GH after injection of rhGH at different doses and routes of administration. DESIGN: Open-label crossover study with single boluses of rhGH. METHODS: Healthy trained subjects (10 males, 10 females) received bolus injections of rhGH on three occasions: 0.033 mg/kg s.c., 0.083 mg/kg s.c., and 0.033 mg/kg i.m. Concentrations of 22 and 20 kDa GH, IGF-I, and IGF-binding proteins (IGFBP)-3 were measured repeatedly before and up to 36 h after injection. RESULTS: Serum GH maximal concentration (Cmax) and area under the time-concentration curve (AUC) were higher after i.m. than s.c. administration of 0.033 mg/kg (Cmax 35.5 and 12.0 microg/l; AUC 196.2 and 123.8). Cmax and AUC were higher in males than in females (P < 0.01) and pharmacodynamic changes were more pronounced. IGFBP-3 concentrations showed no dose dependency. In response to rhGH administration, 20 kDa GH decreased in females and remained suppressed for 14-18 h (low dose) and 30 h (high dose). In males, 20 kDa GH was undetectable at baseline and throughout the study. CONCLUSIONS: After rhGH administration, pharmacokinetic parameters are mainly influenced by route of administration, whereas pharmacodynamic variables and 20 kDa GH concentrations are determined mainly by gender. These differences need to be considered for therapeutic use and for detection of rhGH doping.