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Objective
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 cancer)).
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% 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.
Institute of Clinical Research, University of Southern Denmark, Odense, Denmark
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Background: Graves disease (GD) is an autoimmune condition characterized by the presence of antibodies against the thyrotropin receptor (TRAB), which stimulate the thyroid gland to produce excess thyroid hormone. Theoretically, TRAB could stimulate highly differentiated thyroid cancer tissue and/or metastases to produce thyroid hormone. Case: A 68-year-old male, with weight loss and palpitations, was diagnosed with thyrotoxicosis. A later MRI, due to persistent shoulder pain, revealed multiple bone metastases. A biopsy was diagnostic for follicular variant of papillary thyroid carcinoma, and total thyroidectomy was performed. One week after thyroidectomy the patient was admitted with severe hyperthyroidism. TRAB was >40 IU/mL (normal <0.7 IU/mL). High-dose antithyroid drug treatment was followed by high-dose radioactive iodine-131 (RAI) and local radiotherapy covering the right shoulder. Antithyroid drug treatment continued until after the fourth RAI dose. Hypothyroidism did not occur until following the fifth RAI treatment. Summary and Conclusions: We present a patient initially diagnosed with thyrotoxicosis and subsequently with metastatic follicular variant of papillary thyroid cancer. It is suggested that TRAB stimulated the highly differentiated extrathyroidal metastatic thyroid tissue to produce excessive amounts of thyroid hormone, delayed diagnosis, and potential aggravation of the course of thyroid cancer.