Endocrine Abstracts

Recombinant human growth hormone (rhGH) is abused as a performance enhancing drug, but our knowledge about this is mainly based on rumours, confessions of former athletes and on actions of the police. For many years, the detection of rhGH application by biochemical methods was thought to be impossible. Physiological and biochemical properties of hGH made the development of a test method difficult. rhGH is identical in amino acid sequence and chemical properties to the main, 22 kD isoform of endogenous GH. Half life in circulation is extremely short, and concentrations are highly variable between and within individuals due to pulsatile secretion and influence of factors like stress, sleep and nutrition. Thus, quantification of GH alone is not a reliable measure to decide about the origin of the GH molecules in a sample. To develop a test, two independent approaches are investigated: One is based on the analysis of changes in GH dependent parameters in blood. Application of rhGH induces an increase in IGF-I, IGFBPs and markers of bone and cartilage turnover which exceeds normal fluctuation and is more pronounced than that seen after physiological elevation of circulation GH. A combination of markers allows identification of athletes treated with rhGH, provided the appropriate reference ranges for each hormone are available. The second approach is based on analysis of the GH isoform composition of a sample. A wide spectrum of homo- and heterodimers of different GH isoforms is secreted by the pituitary, whereas rhGH is monomeric 22 kDa GH only. After application of rhGH the 22 kDa isoform becomes predominant, and this can be demonstrated by specific immunoassays. Such assays have been validated in large studies and tested during the Athens and Torino Olympic games. Their routine use in anti doping laboratories now is established to allow regular out of competition testing.