Abstract
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.
Highlights
In the present study we have measured the serum thyroid hormones together with their binding proteins in a large series of patients with HCC and various control groups including uncomplicated cirrhosis and other primary tumours with or without hepatic metastases
Comparison of T4 levels in HCC patients showed no significant difference between those with and without cirrhosis
TBG levels were significantly higher in HCC patients than in those with uncomplicated cirrhosis (28±+11 g ml- compared to 20.4+7.6upgmlP, P
Summary
The 59 patients with HCC (46 males, 13 females) were aged 17-74 years. In each case the diagnosis was established histologically or by the combination of an elevated serum alphafoetoprotein (AFP) (>500ngml-1) and characteristic arteriographic appearances. The stored serial sera (which had been frozen once and not previously thawed before the assay) came from patients included in a prospective study of the development of HCC in cirrhosis (Zaman et al, 1985) These comprised 25 patients with histologically confirmed cirrhosis, none of whom at the time of the first available samples had any clinical or scanning evidence of HCC, or an elevated serum AFP level. In each individual case at least 2 and up to 4 serum samples were available over a follow-up period of between 1 and 6 years Of these 25 patients, 10 developed HCC. The aetiology of the underlying cirrhosis (diagnosed between 13 and 72 (mean 45)) months previously was alcoholic 6, chronic active hepatitis 3 and primary biliary cirrhosis 6 None of these patients was included in the first part of the study. Correlations between TBG and T4 and T3 were assessed using logarithmic transformation of the TBG values on account of the skewed distribution of TBG values in the normal population (Gershengorn et al, 1976; Kalk et al, 1982)
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