Problems with GH and IGF1 assays: progress?
Measuring circulating concentrations of GH and insulin-like growth factor (IGF1) is crucial to biochemically establish the diagnosis of GH-related disorders such as acromegaly and GH deficiency. Many commercial or in-house immunoassays are in use. Controlled studies and regular external quality assessment schemes document considerable disparities in GH and IGF1 concentrations reported when different assays are used. Among the reasons for the differences are the molecular heterogeneity of the analytes and standard preparations, epitope specificity of the antibodies used but also differences in the techniques used to reduce interference from binding proteins. Obviously, poor comparability of assay results between laboratories impedes wider application of evidence based guidelines for diagnosis and treatment. Therefore, endocrinologists and clinical chemists started an international collaborative to discuss steps to improve the situation. Recently, the GH Research Society (GRS) in collaboration with the International Federation for Clinical Chemistry and Laboratory Medicine (IFCC), the International Society for IGF Research and the Pituitary Society organized an expert workshop to define strategies towards harmonization of GH and IGF1 assays. One recommendation from this meeting is the adoption of one defined international standard for GH- and one for IGF1-assays. For GH assays, the isoform specificity of the antibodies must be known, but ideally assays should specifically recognize the 22 kDa isoform only. Assay specific normative data for dynamic tests were considered mandatory until better harmonization is achieved. For IGF1 assays, appropriate measures to exclude the interference from IGF binding proteins (IGFBPs) and the quality of the normative data were indentified as key issue for assay quality. In addition to assay specific recommendations, the participants encouraged the improvement of internal quality control procedures and the development of external quality control programs on an international level to improve assay comparability and patient care.