Toward the Development of a Test for Growth Hormone (GH) Abuse: A Study of Extreme Physiological Ranges of GH-Dependent Markers in 813 Elite Athletes in the Postcompetition Setting

Abstract

There is a need to develop a test to detect GH abuse by elite athletes. Measured levels of GH in blood or urine, however, provide little information on the GH-IGF-I axis. Previous studies have identified a series of indirect markers of GH action that are markedly altered by the administration of GH, but to a lesser degree by acute exercise. This study was undertaken to determine the physiological range of these GH-dependent variables in elite athletes after a competitive event to determine whether such values differ from resting values in normal and athletic subjects and to establish whether any adjustments to this range are required on the basis of age, gender, demographic characteristics, or the nature of the exercise performed. Serum samples were collected from 813 elite athletes (537 males and 276 females; age range, 17-64 yr) from 15 sporting disciplines within 2 h of completion of a major competitive event. IGF-I, IGF-binding protein 2 (IGFBP-2), IGFBP-3, acid-labile subunit, and the bone and soft tissue markers, osteocalcin, carboxyl-terminal propeptide of type I procollagen, carboxyl-terminal cross-linked telopeptide of type I collagen, and procollagen type III were measured. Sporting category, gender, age, height, weight, body mass index (BMI), and racial group of the athlete were documented, and results were compared both to normative data and to values obtained from elite athletes under resting conditions. Forty-one percent of IGF-I values in male athletes and 41% of values in female athletes were above the upper limits of 99% reference ranges derived from resting values in a normal population. Postcompetition levels of all variables except carboxyl-terminal propeptide of type I procollagen and carboxyl-terminal cross-linked telopeptide of type I collagen differed from resting values. There was a consistent age-dependent fall in measured levels of all variables (P < 0.0001) with the exception of IGFBP-2, which increased with age (P < 0.0001). BMI, but not height, exerted a small, but significant, influence on several variables. After adjustment for age, there were no significant differences in the levels of any of the measured variables between sporting categories. IGFBP-2 and IGFBP-3 were lower in 35 black athletes compared with those in 35 white athletes matched for age, gender, height, BMI, and sporting category. We have demonstrated that there are predictable age-dependent levels of GH-dependent markers in elite athletes that are consistent even at the extremes of physical exertion and that these are independent of sporting category. Normative data applicable to white athletes are provided. This provides important groundwork for the development of a test for GH abuse, although these values may be specific for the reagents and assays used.

GH response to GHRH plus arginine is impaired in lipoatrophic women with human immunodeficiency virus compared with controls

“…However, as HIV-infected patients are mainly lipoatrophic, in this study they represent a different patient population from females of approximately the same age in previous studies (7) and caution is therefore needed in drawing conclusions when comparing different studies due to the GH assay variability (13,14) and other factors, such as ethnicity (29), which could lead to different results. Since GHRHCArg only tests pituitary reserve, this methodological approach does not allow us to obtain information about hypothalamic functioning in the current study.…”

The use of growth hormone (GH)‐dependent markers in the detection of GH abuse in sport: Physiological intra‐individual variation of IGF‐I, type 3 pro‐collagen (P‐III‐P) and the GH‐2000 detection score

“…The intra-assay CV was 10AE1%, 6AE3% and 5AE7% at serum concentrations of 61AE5, 340AE8 and 776AE9 ng/ml respectively as previously described. 9 Serum P-III-P concentration was determined by a two-stage sandwich IRMA (CIS Biointernational, Oris Industries, Gif-sur-Yvette, France) with intra-assay CVs of 5AE7%, 9AE1%, and 6AE7% at serum concentrations of 0AE95, 0AE62 and 1AE18 U/ml respectively. Sample pretreatment was not needed.…”

“…As expected, many of the GH-2000 scores in Figs 2 and 3 were below 0 (shown in further detail in Table 2). This is because the GH-2000 detection formulae were calibrated against elite athletes 9 and amateur athletes have lower scores. 21 In the GH-2004 longitudinal study, maximal exercise led to a small but significant increase in IGF-I concentrations (mean difference 20AE9 ng/ml, P < 0AE0001).…”

“…8 Although IGF-I and P-III-P are more stable than GH, there is a wide inter-individual variability which is partly dependent on age, gender, body weight, habitual physical activity, diet and androgen or oestrogen use. 2,[9][10][11] This variation could mean that those with lower baseline marker concentrations are harder to catch. This issue has also been relevant for the detection of testosterone abuse.…”

A proteomic approach combining MS and bioinformatic analysis for the detection and identification of biomarkers of administration of exogenous human growth hormone in humans

“…The second technique is based on monitoring a number of downstream GH biomarkers, with IGF-I and procollagen III N-terminal peptide, being the most important candidates [8,[13][14][15]. One major problem with these approaches is that they are all dependent on the availability of stable and reliable immunoassays, and changes in the performance of the commercial assay kit might result in the need to re-establish the reference intervals [16]. In recent years, there has been increasing interest in the use of MS for biological applications such as the identification of biomarkers of disease, disease progression or response to therapy, and monitoring biomarker levels in serum and plasma [17][18][19].…”