Differential hormone-binding characteristics of thyroxine-binding globulin in hepatocellular carcinoma and cirrhosis

To determine whether previous observations suggesting reduced ability of thyroxine-binding globulin (TBG) to bind exogenous thyroid hormones in hepatocellular carcinoma (HCC) might form the basis of a useful clinical test, we have investigated a larger series involving 49 patients and 10 healthy subjects. The binding ratio (mol hormone bound/mol TBG at a given hormone concentration) for both T4 and T3 was significantly reduced when compared to both cirrhotic and normal subjects. No overlap in T4 binding occurred between HCC patients and the control groups. Serial measurements on serum samples obtained from five cirrhotic patients who ultimately developed HCC revealed significant reductions in binding for both hormones up to 60 months prior to the clinical diagnosis of HCC. A reduced ability to bind thyroid hormones appears to be a specific feature of serum TBG from HCC patients and is one of the earliest alterations seen among cirrhotic subjects who ultimately develop the disease.