title: Hypothyroidism: a possible risk factor for liver cancer in patients with no known underlying cause of liver disease.
abstract: OBJECTIVE
  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.
authors.affiliation: Miles and Shirley Fiterman Center for Digestive Diseases, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
authors.forename: Arvind
authors.initials: A
authors.lastname: Reddy
authors.forename: Chiranjeev
authors.initials: C
authors.lastname: Dash
authors.forename: Apinya
authors.initials: A
authors.lastname: Leerapun
authors.forename: Teresa A
authors.initials: TA
authors.lastname: Mettler
authors.forename: Linda M
authors.initials: LM
authors.lastname: Stadheim
authors.forename: Konstantinos N
authors.initials: KN
authors.lastname: Lazaridis
authors.forename: Rosebud O
authors.initials: RO
authors.lastname: Roberts
authors.forename: Lewis R
authors.initials: LR
authors.lastname: Roberts
mesh_terms: D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000150:complications*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007037:Hypothyroidism / Q000150:complications*; D008113:Liver Neoplasms / Q000150:complications*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D012042:Registries; D012307:Risk Factors