Risk and prognosis of HCC in patients with thyroid disease: A nationwide cohort study

Background: Thyroid hormone levels are associated with HCC in animal studies. We examined HCC risk and prognosis in patients with thyroid disease. Methods: We included all Danish citizens with a hospital diagnosis for thyroid disease after January 1, 1980, and/or a filled prescription for thyroid medication after 1995. They were 1:10 age-matched, sex-matched, and calendar year–matched with population comparators without thyroid disease diagnoses. All were followed through 2021 for HCC diagnosis and death. Results: We included 529,330 patients, followed for up to 42.0 years. Among those with hyperthyroid disease, a current low TSH was associated with lower HCC incidence (adjusted HR: 0.66, 95% CI: 0.29–1.47). Nontoxic goitre was associated with lower mortality after HCC diagnosis (adjusted HR: 0.77, 95% CI: 0.59–1.00), corresponding to an estimated 6 months’ increased survival. Those with hypothyroid disease and a high current TSH had a higher HCC incidence (adjusted HR: 2.07, 95% CI: 1.03–4.18). Conclusions: Overall, in this large population-based study, a suppressed TSH level was associated with either lower HCC incidence or longer survival, while an elevated TSH level was associated with higher HCC incidence. Interpreted by TSH level, this suggests that an excess of thyroid hormones protects against HCC and that a deficit in thyroid hormones increases the HCC risk. The therapeutical implications are uncertain.