OR1,2 Targeted ablation of growth hormone receptors in the skeletal muscle improves metabolism and protects against diet-induced obesity in mice

Abstract

Clinical endocrinologists worldwide try to improve patients care through implementation of guidelines on diagnosis and treatment of GH related disorders, and cut-off levels mentioned in such guidelines are frequently used for interpretation of laboratory data. However, the variability between immunoassay results for GH measurements severely limits or makes impossible the applicability of international consensus guidelines in clinical practice. Reasons for the heterogeneity in GH assay results include the heterogeneity of the analyte itself – GH consists of several molecular isoforms. Furthermore, the interference from matrix components (mainly GH binding protein) has an influence on assay results. In addition, different reference preparations for calibration are available (a pituitary derived extract 80/505 and the recombinant preparations 88/624 and 98/574). Also the reporting of results in mass units or international units together with the application of variable conversion factors between both units led to confusion. On an international level, several groups proposed measures to improve the comparability of assay results. Some progress has been made, as the use of international units has been largely abandoned. However, there is still a problem with use of different calibrators, with a problematic situation for assays from specific manufacturers which are distributed with different calibrators in Europe and the US. In October 2010, the Growth Hormone Research Society (GRS) in collaboration with the International Federation for Clinical Chemistry and Laboratory Medicine (IFCC) as well as the International Society for IGF Research and the Pituitary Society organized an expert workshop to define criteria, strategies and ways to implement harmonization of GH and IGF-I assays. As first steps the use of a single, recombinant calibrator for all assays and reporting in mass units only has been agreed. In addition assays should specify their specificity, and ideally be specific for the 22kD GH isoform only. The combination of forces to reach a consensus was an important step forward. However, continuous efforts from the laboratory and the clinical side are required until the proposed measures to improve GH assay comparability are implemented and the universal adoption of decision limits can be recommended. Until then, the use of assay specific cut-offs for dynamic tests remains mandatory.