title: 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.
authors.affiliation: Department of Diabetes and Endocrinology, GKT School of Medicine, St. Thomas' Hospital, London, UK.
authors.forename: Marie-Louise
authors.initials: ML
authors.lastname: Healy
authors.forename: Rolf
authors.initials: R
authors.lastname: Dall
authors.forename: James
authors.initials: J
authors.lastname: Gibney
authors.forename: Eryl
authors.initials: E
authors.lastname: Bassett
authors.forename: Christer
authors.initials: C
authors.lastname: Ehrnborg
authors.forename: Claire
authors.initials: C
authors.lastname: Pentecost
authors.forename: Thord
authors.initials: T
authors.lastname: Rosen
authors.forename: Antonio
authors.initials: A
authors.lastname: Cittadini
authors.forename: Robert C
authors.initials: RC
authors.lastname: Baxter
authors.forename: Peter H
authors.initials: PH
authors.lastname: Sönksen
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D049628:Body Size; D001842:Bone and Bones / Q000378:metabolism*; D005260:Female; D019382:Human Growth Hormone / Q000009:adverse effects* / Q000097:blood*; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D008297:Male; D013177:Sports; D019966:Substance-Related Disorders / Q000097:blood / Q000175:diagnosis*
chemical_list: D015415:Biomarkers; D018969:Insulin-Like Growth Factor Binding Proteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I