Hyperthyroidism and the Risk of Non-Thyroid Cancer: A Danish Register-Based Long-Term Follow-Up Study

Objectives: Cancer is the second most common cause of death worldwide. It is currently debated whether thyroid dysfunction is a modifiable cancer risk factor. Our aim was to evaluate the risk of cancer in patients with hyperthyroidism.

Methods: This is a register-based nationwide cohort study of individuals with a diagnosis of hyperthyroidism. Each hyperthyroid case was matched with four reference individuals according to age and sex. Using Fine and Gray competing risk regression models, we studied the association of hyperthyroidism and subsequent all-cause cancer diagnoses, adjusted for preexisting morbidity. Sub-analyses were stratified for cause of hyperthyroidism (Graves’ disease and toxic nodular goiter, age when diagnosed with hyperthyroidism, sex, and cancer localization (lung-, prostate-, breast-, and colorectal).

Results: The cohort consisted of 95,469 patients with hyperthyroidism (followed for a median of 10.9 years (range: 5.2-17.2)), and 364,494 reference individuals (followed for a median of 11.2 years (range: 5.4-17.4)). Hyperthyroidism was associated with increased all-cause cancer risk (sub-distribution hazard ratio (SHR): 1.12; 95% confidence interval (CI): 1.10-1.14), as well as an increased risk of breast- (SHR: 1.07; 95% CI: 1.02-1.13), lung- (SHR: 1.20; 95% CI: 1.16-1.26), and prostate cancer (SHR: 1.10; 95% CI: 1.02-1.19), but not colorectal cancer (SHR: 1.04; 95% CI: 0.99-1.09). Sub-analyses stratified for age when diagnosed with hyperthyroidism and cause of hyperthyroidism yielded similar results.

Conclusion: In this register-based study, patients with hyperthyroidism had an increased risk of cancer, in particular lung, prostate, and breast cancer. Whether a causal link exists remains to be proven.