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Serum thyroxine was significantly higher in 59 patients with hepatocellular carcinoma than in normal subjects, patients with uncomplicated cirrhosis (48), or other primary tumours with or without hepatic metastases (50). Elevated thyroxine levels appeared attributable to high levels of thyroxine binding globulin which showed a positive linear correlation with serum thyroxine in all groups studied. Despite this hyperthyroxinaemia all patients appeared clinically euthyroid and, consistent with this, T3 was elevated in only one patient and the free thyroxine index was normal in all. Amongst a group of 25 cirrhotic patients who were followed-up for between 12 and 72 months, there was a striking dissociation between the TBG values of those destined to develop HCC and those who did not. In the former group TBG rose steadily with time whereas in the latter group levels remained stable, or, more often, fell. The rises in TBG occurred prior to any clinical signs of tumour development and may be one of the earliest serological changes to occur during carcinogenesis in the cirrhotic liver.

Hyperthyroxinaemia in hepatocellular carcinoma: Relation to thyroid binding globulin in the clinical and preclinical stages of the disease