Radioreceptor and Radioimmunoassay Quantitation of Human Growth Hormone in Acromegalic Serum: Overestimation by Immunoassay and Systematic Differences Between Antisera1
Circulating hGH in patients with acromegaly was measured by a radioreceptor assay (RRA) and the results compared to those obtained by radioimmunoassay (RIA) with two different antisera. With both antisera, RIA measurement exceeded RRA quantitation of hGH, the differences being neither analytic nor related to the sampling or handling of any subgroup of test sera. RIA hGH levels measured with one antiserum, raised in this laboratory, exceeded RRA levels by 42 ± 7% (p < 0.001), and with the second antiserum, distributed by the National Pituitary Agency, the difference was almost twice as great (80 ± 13%, p < 0.001). Comparison of the hGH levels measured by the two antisera also showed a significant difference (22 ± 6%, p < 0.005); individual samples differed by as much as 100%. Two peaks of hGH immunoreactivity were found when serum from acromegalic patients was filtered on Sephadex G-100. The minor peak, of larger molecular weight, was not detected by RRA. However, most of the difference between the two assays was accounted for by differences within the major peak corresponding to monomeric hGH, the RRA detecting less than the RIA. These important systematic differences between anti-hGH antisera may, if not recognized, influence both the diagnosis of acromegaly and the assessment of response to treatment. Our observations further suggest that hGH molecules of reduced or absent biological activity circulate in acromegalic patients, thus helping to account for some of the discrepancies between immunochemically measured hGH levels and clinical severity of disease.