Endocrine Abstracts

Since more than 40 years growth hormone (GH) measurement has been possible by immunoassay techniques. Although these methods have greatly augmented the diagnostic tools of endocrinologists following patients with GH-related disorders, their use has also brought about confusion and left uncertainties.

Cut-off levels for dynamic GH tests in the diagnosis of both GH deficiency and acromegaly have to be considered arbitrary, since different commercial hGH assay kits yield results discrepant by more than 200%. This heterogeneity in results has to be attributed to discrepancies in calibrators, but also to the epitope specificity of antibodies employed. hGH circulates in a variety of isoforms and antibodies vary in binding preference for these hGH isoforms. Ideally, an immunoassay should quantify the exact amount of GH molecules capable of activating the GH receptor homodimer. Use of the GH receptor ectodomain in combination with a selected monoclonal antibody (mab) targeting hGH’s site 2 of receptor interaction in the immunofunctional GH assay aims at this detection of bioactive hGH.

The different preferences of anti-hGH mabs for subsets of hGH isoforms was exploited in a strategy to distinguish recombinant hGH from hGH of pituitary origin, facilitating the detection of doping with rhGH in sports.

Medical treatment modalities of acromegaly have recently been augmented by the introduction of the GH-receptor antagonist pegvisomant, a mutated GH molecule. The measurement of endogenous hGH levels in the presence of more than 1000-fold concentrations of this drug was made possible by identification of anti-hGH mabs with epitope specificities for the very amino acid residues that are modified in pegvisomant.

Placental syncytiotrophoblasts transcribe and secrete a GH variant differing from pituitary hGH in 13 of the 191 amino acids. Studies using mabs specific only for placental GH indicate that it serves to induce a relative maternal state of insulin resistance thus securing a sufficient flux of nutrients to the feto-placental unit.