Advantages of IRMA over RIA in the measurement of ACTH

A technically simple and rapid two-site immunoradiometric assay (IRMA) for human ACTH, based on monoclonal antibodies (MAbs), was compared with a clinically validated ACTH radioimmunoassay (RIA). Both methods measure ACTH 1-39 in unextracted plasma and cross-react <0.5% with ACTH fragments. ACTH levels were assessed in 103 patient samples: for concentrations in the range 5.3-1000 ng/L, results by the two methods were significantly correlated (r = 0.82, n = 86, P <0.001). The IRMA was more sensitive and had a wider working range than the RIA (detection limits 5.3 ng/L (IRMA) vs 11 ng/L (RIA); CV <10% between 19 and 1000 ng/L (IRMA) and CV <15% between 30 and 400 ng/L (RIA)). In two patients for whom discrepant results were obtained, measurement of ACTH by bioassay and ACTH precursors by direct IRMA demonstrated the greater accuracy of the ACTH IRMA result. The improved performance of the IRMA combined with its many practical advantages compared to RIA, make it ideal for use in detailed clinical and physiological studies which have previously been hampered by the poor reliability of ACTH measurement.