Growth hormone: isoforms, clinical aspects and assays interference

The measurement of circulating concentrations of growth hormone (GH) is an indispensable tool in the diagnosis of both GH deficiency and GH excess. GH is a heterogeneous protein composed of several molecular isoforms, but the physiological role of these different isoforms has not yet been fully understood. The 22KD GH (22 K-GH) is the main isoform in circulation, followed by 20KD GH (20 K-GH) and other rare isoforms. Studies have been performed to better understand the biological actions of the different isoforms as well as their importance in pathological conditions. Generally, the non-22 K- and 20 K-GH isoforms are secreted in parallel to 22 K-GH, and only very moderate changes in the ratio between isoforms have been described in some pituitary tumors or during exercise. Therefore, in a diagnostic approach, concentrations of 22 K-GH accurately reflect total GH secretion. On the other hand, the differential recognition of GH isoforms by different GH immunoassays used in clinical routine contributes to the known discrepancy in results from different GH assays. This makes the application of uniform decision limits problematic. Therefore, the worldwide efforts to standardize GH assays include the recommendation to use 22 K-GH specific GH assays calibrated against the pure 22 K-GH reference preparation 98/574. Adoption of this recommendation might lead to improvement in diagnosis and follow-up of pathological conditions, and facilitate the comparison of results from different laboratories.