Hypoalbuminemia associated with diffuse hypergammaglobulinemia in chronic diseases: lack of diagnostic specificity

Although elevated gamma globulin is known to produce hypoalbuminemia both experimentally and in disease, a low albumin concentration in chronic liver disease often is assumed to reflect impaired liver synthetic function. Albumin and gamma globulin measurements in a series of 200 patients with a variety of chronic diseases (including cirrhosis, connective tissue disease, chronic inflammation, and malignancy) associated with diffuse hypergammaglobulinemia were combined with similar measurements from a previous study (Am J Med 1959; 29:596-616). The mean serum albumin concentration correlated inversely with mean gamma globulin, irrespective of disease category. Double reciprocal plot analysis showed that the relationship fits a rectangular hyperbola (r = -0.915, P less than 0.001), with the mean albumin concentration approaching 2.31 g/dL at infinite gamma globulin. This suggests that serum albumin decreases to a similar extent in various chronic diseases and that hypoalbuminemia has no diagnostic implications, except to the extent that it reflects the severity of hypergammaglobulinemia.