Is Methimazole Carcinogenic?
No, methimazole is not carcinogenic in humans based on current epidemiological evidence, despite animal studies showing thyroid tumors at high doses. 1, 2
Animal Studies vs. Human Evidence
The FDA label includes a black box warning based on animal toxicology studies where rats developed thyroid hyperplasia, adenoma, and carcinoma when given methimazole at doses 2-12 times the maximum human maintenance dose (calculated on surface area basis). 1 However, the clinical significance of these animal findings is explicitly stated as unclear in the FDA labeling itself. 1
Human Epidemiological Data
The most comprehensive systematic review examining this question (published 2022) evaluated all available human studies and found no evidence for a relevant role of methimazole or other antithyroid drugs on thyroid cancer risk. 2 This review included:
A large cohort study following patients treated for hyperthyroidism from 1946-2014 found zero deaths from thyroid cancer among patients treated exclusively with antithyroid drugs through the entire follow-up period. 2
The apparent increased thyroid cancer incidence in earlier reports (3.2/1000 in antithyroid drug-treated patients vs. 0.34-0.88/1000 in surgery/radioiodine groups) was explained by detection bias—patients on antithyroid drugs underwent subsequent thyroidectomy 30% of the time versus only 0.5-1.2% in other groups, creating more opportunities for cancer detection. 2
A nested case-control study initially suggested increased risk (OR 2.79 for ≥3 propylthiouracil prescriptions), but this was attributed to advanced diagnosis of underlying cancer, as evidenced by the much stronger association in no-lag analysis (OR 8.03), indicating reverse causation. 2
Two additional case-control studies found no association between antithyroid drug use and thyroid cancer. 2
Clinical Context
The FDA warning specifically states that "off-label and unnecessary use of spironolactone should be avoided" based on animal carcinogenicity data, yet subsequent large human studies with millions of patient-years found no cancer association. 3 This same pattern applies to methimazole—animal data suggesting risk, but human epidemiological data providing reassurance.
Practical Implications
- Continue methimazole therapy as clinically indicated for hyperthyroidism without concern for carcinogenic risk. 3, 1
- The standard 12-18 month treatment duration for Graves' disease is based on therapeutic efficacy, not cancer concerns. 4
- Monitoring during and after methimazole therapy should focus on thyroid function and known adverse effects (agranulocytosis, hepatotoxicity), not cancer surveillance. 4, 1