Increased serum reverse triiodothyronine levels at diagnosis of hepatocellular carcinoma in patients with compensated HCV-related liver cirrhosis.

Abstract

The aim of this study was to investigate changes in thyroid hormone metabolism in relation to the development of hepatocellular carcinoma (HCC) in patients with HCV-related liver cirrhosis. The study group (Group A) comprised 31 patients (25 M, 6 F; median age 62.1 years, range 54.0-81.5 years) affected by HCV-related liver cirrhosis with superimposed HCC. Acute and chronic systemic disease, other than cirrhosis, inducing 'euthyroid sick syndrome' was excluded in all patients. Serum TSH, FT4, FT3, rT3, and thyroxine-binding globulin (TBG) levels were retrospectively evaluated in frozen aliquots drawn at the time of tumour diagnosis and every 6 months for 3-7 years before HCC diagnosis. The control group (Group B) comprised 29 patients affected by HCV-related liver cirrhosis without HCC, matched for sex, age and grade of liver dysfunction. At the time of HCC diagnosis, all patients in Group A were euthyroid with serum TSH, FT4, FT3 and TBG values not significantly different from those of cirrhotic patients of Group B. However, at diagnosis Group A patients had serum rT3 values that were significantly higher than those in Group B (35.0 ng/dl, range 12.0-162.0 vs. 19.0 ng/dl, range 10.0-51.0; Group A vs. Group B; P < 0.001). Serum rT3 values above the normal range were found in 12 patients in Group A (38.7%) but in only one of the patients from Group B (3.4%) (chi2 10.2; P = 0.001). The serum rT3 levels were not significantly correlated to the Child grade of liver cirrhosis (rho 0.1; P = 0.5). The intrasubject analysis demonstrated that a significant increase in serum rT3 levels occurred at the time of HCC diagnosis but serum FT4, FT3 and TSH values did not change significantly. A receiver operating curve (ROC) demonstrated that a 6-monthly increase in serum rT3 levels of at least +22.5% identified patients with HCC with a diagnostic accuracy of 81.7%. Our study has demonstrated that development of hepatocellular carcinoma is accompanied by a significant increase in serum rT3 levels in patients with low-grade HCV-related liver cirrhosis who had no other illness causing the 'euthyroid sick syndrome'.