Abnormal and Euthyroid Ranges of Thyroid Hormones in Serum and Liver Cancer Mortality: A Cohort Study

Abstract

Background: This study aimed to evaluate the relationship of serum thyrotropin (TSH) and thyroid hormone concentration with liver cancer mortality. Methods: A cohort of 517,996 Korean adults, who did not have liver cancer at baseline and attended a health screening including free thyroxine (FT4) and TSH, were followed for up to 16 years. High and low TSH and FT4 were defined as those above the upper bound of reference interval and those below the lower bound of reference interval of their corresponding reference intervals, respectively. Mortality information was ascertained through National Death Records. The adjusted HR (aHR) with 95% confidence interval (CI) were estimated using a Cox proportional hazard model. Results: During a median follow-up of 8.1 years, 376 deaths from liver cancer were identified. Subjects with low FT4 levels were associated with an elevated risk of liver cancer mortality with a corresponding multivariable aHR 2.25 (95% CI: 1.62-3.12) compared with those with normal FT4 levels. Within the euthyroid range, there was also a dose-dependent inverse relationship between FT4 level and liver cancer mortality (P < 0.001). Levels of TSH and free T3 had no significant association with liver cancer mortality. Conclusions: The risk of liver cancer mortality increased as FT4 level decreased, both within the normal and abnormal ranges of thyroid function. Impact: Thyroid function within the abnormal and normal ranges might affect liver cancer mortality. Further study is warranted to elucidate the role of thyroid hormone in development of liver cancer including the underlying biological mechanism.