Mechanism and Significance of the Thymol Turbidity Test for Liver Disease.

An increase in the amounts of the globulin components of the serum has long been recognized in advanced states of liver disease (1, 2, 3), although the significance of the alteration has never been defined. It has been the basis of the Takata-Ara, Weltmann and the formol-gel reactions which have been used for many years in the diagnosis of liver disease. The nonspecific nature of these tests is now clear following the demonstration that positive reactions are found in any disease showing marked hyperglobulinemia (4, 5, 6). More recently, several new serum reactions, which appear to depend on small changes in the proteins of the serum, have been used for demonstrating liver disease. These include the cephalin flocculation, the colloidal gold and the thymol turbidity tests. The cephalin flocculation reaction has been studied in detail by Hanger and his coworkers (7, 8) and has been found to be a sensitive index of liver damage. The test may be positive in patients with liver disease who show normal serum protein values according to the usual methods of protein estimation and, conversely, the serum of patients with marked hyperglobulinemia may show negative cephalin flocculation reactions. The exact serum protein constituent that is altered in liver disease and is responsible for a positive cephalin flocculation test has not been clearly established; recent work by Hanger (8) appears to implicate albumin in addition to gamma globulin. The final solution to the problem is hampered by the complexity of the cephalin flocculation reaction, a fact which is also true of the colloidal gold reaction. The technique of the thymol turbidity test is much simpler, however, and probably consists of a direct precipitation of a protein appearing in liver disease by the addition of a thymol solution. It would seem, therefore, that a study of the mechanism of this reaction and the protein com-