Background & Aims: Up to 25% of hepatocellular carcinomas (HCCs) seen in U.S. centers are of unknown etiology. Animal studies suggest that hypothyroidism can directly cause liver cell damage and might be a risk factor for HCC. We conducted a case-control study to evaluate the relationship between hypothyroidism and HCC. Methods: Cases (n = 54) were HCC patients seen at Mayo Clinic Rochester in whom no underlying etiology for chronic liver disease could be determined. Two groups of controls were selected, HCC patients with HCV (n = 57) and HCC patients with alcoholic liver disease (n = 49). Hypothyroidism was defined as thyroid-stimulating hormone level >5.0, history of hypothyroidism before HCC diagnosis, or a history of being on thyroid replacement at the time of HCC diagnosis. We used multivariate logistic regression to model the relationship between hypothyroidism and HCC etiology. Results: Of the 160 patients, 18 (11%) had a history of hypothyroidism. Twelve (22%) of those with no known etiology for HCC, 2 (4%) of those with HCV, and 4 (8%) of those with alcoholic liver disease had hypothyroidism. Patients with HCC of unknown etiology were significantly more likely to have a history of hypothyroidism as compared with HCC patients with HCV (adjusted odds ratio, 12.7; 95% confidence interval, 1.4-117.1) and as compared with all controls (adjusted odds ratio, 6.8; 95% confidence interval, 1.1-42.1). Conclusions: Hypothyroidism is more prevalent in HCC patients with an unknown etiology. It should be further investigated as a potential risk factor in liver carcinogenesis.
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