Methodological Causes of Discrepancies in Radioimmunoassay for Digoxin in Human Serum

In our series of 73 patients, definite indications of toxici-ty were always associated with a serum digoxin con-centration of 2.0 ng/mI or higher, while in the possibly intoxicated and nonintoxicated patients only 24 % and 10%, respectively, had a concentration this high. The nonintoxicated patients included significantly more with subnormal serum albumin Concentrations. In vitro addi-tion of radiolabeled digoxin and antibody showed that sera from many patients with hypoalbuminemia will en-hance the binding of the label, which could result in a di-goxin radioimmunoassay value as much as threefold low. These results were unrelated to other serum con-stituents, including the associated hyperglobulinemia, or to methodologic problems in the immunoassay. The proportion of digoxin bound to serum proteins was not significantly different between the normal (38 % ± 3%) and hypoalbuminemic (31 % ± 3%) individuals, and so this could not explain the difference in the assay results. We conclude that patients whose serum albumin con-centrations are low may show erroneously low radioim-munoassay values for serum digoxin, and that this may explain why some patients receiving high doses of di-goxin are found to have unexpectedly low apparent concentrations of digoxin in their serum. Additional Keyphrase: hypoalbuminemia Radioimmunoassay for serum digoxin (1-4) has rapidly gained acceptance among clinicians as a po-tentially valuable procedure in identifying the di-goxin-intoxicated patient. Use of this assay has mdi