Thyroid Hormones and Mortality Risk in Euthyroid Individuals: The Kangbuk Samsung Health Study

Context: Hyperthyroidism and hypothyroidism, both overt and subclinical, are associated with all-cause and cardiovascular mortality. The association between thyroid hormones and mortality in euthyroid individuals, however, is unclear. Objective: To examine the prospective association between thyroid hormones levels within normal ranges and mortality endpoints. Setting and Design: A prospective cohort study of 212 456 middle-aged South Korean men and women who had normal thyroid hormone levels and no history of thyroid disease at baseline from January 1, 2002 to December 31, 2009. Free T-4 (FT4), free T-3 (FT3), and TSH levels were measured by RIA. Vital status and cause of death ascertainment were based on linkage to the National Death Index death certificate records. Results: After a median follow-up of 4.3 years, 730 participants died (335 deaths from cancer and 112 cardiovascular-related deaths). FT4 was inversely associated with all-cause mortality (HR = 0.77, 95% confidence interval 0.63-0.95, comparing the highest vs lowest quartile of FT4; P for linear trend = .01), and FT3 was inversely associated cancer mortality (HR = 0.62,95% confidence interval 0.45-0.85; P for linear trend = .001). TSH was not associated with mortality endpoints. Conclusions: In a large cohort of euthyroid men and women, FT4 and FT3 levels within the normal range were inversely associated with the risk of all-cause mortality and cancer mortality, particularly liver cancer mortality.