Clinical Endocrinology (1997) 47, 43–50 Serum IGF-I and IGF binding proteins 2 and 3 as potential markers of doping with human GH Andrew T. Kicman, John P. Miell*, J. Derrick Teale², Jake Powrie‡, Peter J Wood§, Paul Laidler, Peter J. Milligan¶ and David A. Cowan Drug Control Centre, King’s College London, London, *Department of Medicine, King’s College School of Medicine, London, ² Clinical Laboratory, Royal Surrey County Hospital, Guildford, ‡Department of Medicine, United Medical and Dental Schools of Guy’s and St Thomas’s Hospitals, London, §Regional Endocrine Unit, Southampton General Hospital, Southampton and ¶Computing Centre, King’s College London, London, UK (Received 4 September 1996; returned for revision 15 October 1996; finally revised 20 November 1996; accepted 31 January 1997) Summary OBJECTIVE IGF-I and IGF binding protein (IGFBP)-3 levels in man are positively regulated by GH status; in contrast, evidence suggests an inverse relationship between GH status and IGFBP-2. We investigated the effects of somatropin administration on the serum concentrations of these analytes, together with serum and urinary concentrations of GH, to evaluate their potential as markers in the development of a test for detecting doping with GH in sports competitors. DESIGN Somatropin was administered subcuta- neously at a dose of 0 . 15 U/kg bodyweight/day at 1000 h for 3 days to eight healthy men (20–32 years old). MEASUREMENTS Serum concentrations of GH, IGF-I, IGFBP-2 and -3 were determined in blood samples collected at 1600 h on the days prior to (day ¹1), during (days 0, 1 and 2), and following administration (days 3 and 7). Urine was collected continuously from days ¹2 to 3 and then on day 7. RESULTS Serum and urinary concentrations of GH were only raised on the days of administration whereas, following cessation of somatropin, the increases in the serum concentrations of IGF-I and IGFBP-3 were sustained for at least 1 day (30 h). Serum IGFBP-2 decreased during the period of administration and was still suppressed on day 3. The concentration ratios of IGFBP-3 to IGFBP-2 and IGF-I to IGFBP-2 increased markedly with admin- istration and both ratios were still significantly aug- mented compared with basal values 30 h after the last administration. CONCLUSION With acute administration of soma- tropin to healthy men the serum concentration of IGFBP-2 decreases and the ratios of serum IGF-I/ IGFBP-2 and IGFBP-3/IGFBP-2 increase. These ratios should be considered in the development of a test for detecting somatropin administration in sport. Anecdotal evidence suggests that some competitors are using synthetic human GH (somatropin) as a non-steroidal anabolic agent which evades effective measures for the detection of administration of anabolic-androgenic steroid hormones (Duchaine, 1989). In addition, some athletes and bodybuilders believe that somatropin is more potent than anabolic steroids or that somatropin could be used in conjunction with steroids to increase muscular size and strength. These factors, together with a wider availability of somatropin due to the success of recombinant DNA techniques, are likely to solicit its misuse in sport. Di Pasquale states in Beyond Anabolic Steroids (1990) that the doses of somatropin used by athletes have varied from 4 units three times per week, to 10 units per day for many weeks. Aware of the potential problem, the International Olympic Committee’s (IOC) Medical Commission included ‘GH’ as a listed compound in the new doping class of ‘peptide hormones and analogues’ (Kicman & Cowan, 1992). Nonetheless, there is as yet no IOC-approved method for detection of somatropin administration. Only untimed urine samples are currently available from athletes as blood collection was considered to be too invasive to the individual. However, with the growing awareness that somatropin and erythropoietin are being misused in sport, the collection of blood is being considered as an additional option that could facilitate the introduction of tests for detection of doping with these hormones. The prognosis for a dope test relying on a single measure- ment of somatropin in biological fluids is poor for several reasons. Current immunoprocedures cannot differentiate soma- tropin from endogenous GH due to the structural homology. An attempt was made to distinguish exogenous GH from pituitary GH by measuring the isotopic ratio of 13 C/ 12 C. Two of three commercial preparations did not show enough difference from pituitary-derived GH to be suitable for further developmental 43  1997 Blackwell Science Ltd Correspondence: Dr A. Kicman, Drug Control Centre, King’s College London, Manresa Road, London SW3 6LX, UK. Fax: 0171 351 2591.