Cross-reactivity of monomeric and dimeric biosynthetic human growth hormone in commercial immunoassays

Commercial kits give different measurements for concentrations of growth hormone (GH, somatotropin) in serum. Most notably, a two-site monoclonal-antibody-based immunoradiometric assay (IRMA) from Hybritech routinely yields lower values than do conventional RIAs in which polyclonal antibodies are used. We used purified dimeric biosynthetic human GH as a model compound to investigate the specificity of five commercial immunoassays for size variants of GH. In all five assays, biosynthetic monomeric GH was significantly more potent than pituitary-derived standard GH supplied with the kits. Dimeric GH was significantly less potent than monomer in four of the five assays, and cross-reactivities varied more than fivefold, from 15% to 84%. Using three commercial kits selected for their specificity for dimeric GH, we measured GH in serum samples from 18 normal adults. The mean GH concentrations in serum--0.7 (Hybritech, IRMA), 1.8 (Diagnostic Products, RIA), and 3.1 (Cambridge, RIA) micrograms/L--differed significantly, but in the same rank order as that obtained in the experiments on dimer cross-reactivity.