Cancer Risk Associated with Levothyroxine Therapy
Levothyroxine therapy itself does not cause cancer, but one large Swedish population study found a small increased relative risk of incident cancers (6-8% increased risk) in patients receiving levothyroxine treatment, though this association does not establish causation and may reflect underlying thyroid disease rather than the medication itself. 1
Evidence from Population Studies
The most relevant data comes from a 2020 Swedish cohort study that examined 253,193 patients receiving levothyroxine compared to over 8 million controls:
Men on levothyroxine showed an adjusted hazard ratio of 1.06 (95% CI 1.03-1.10) for overall cancer risk, representing approximately a 6% increased relative risk 1
Women on levothyroxine demonstrated an adjusted hazard ratio of 1.08 (95% CI 1.07-1.10) for overall cancer risk, representing approximately an 8% increased relative risk 1
For women specifically, increased risks were observed for cancers of the breast, endometrium, other female genitals, stomach, colon, liver, pancreas, urinary bladder, skin, leukemia, and unspecified primary tumors 1
For men, increased risks were found primarily for cancers of the thyroid gland and other endocrine glands 1
Critical Interpretation and Context
This association does not prove causation. Several important caveats must be considered:
The study authors themselves emphasized that levothyroxine should only be prescribed for approved indications and called for confirmation by other studies 1
Patients requiring levothyroxine often have underlying thyroid disease, which itself may be associated with altered cancer risk independent of the medication 1
The absolute risk increase is small—translating to approximately 6-8 additional cancer cases per 1,000 patients treated over several years 1
No major thyroid cancer guidelines (ESMO 2019, ESMO 2012, ESMO 2010) identify levothyroxine as a cancer risk factor, and these guidelines extensively discuss levothyroxine use for TSH suppression therapy without mentioning cancer risk as a concern 2
Known Risks of Levothyroxine Overtreatment
The established risks from levothyroxine relate to overtreatment causing iatrogenic hyperthyroidism, not cancer:
Cardiovascular complications: Increased risk of atrial fibrillation, coronary heart disease, and ischemic stroke, particularly with higher doses (≥170 μg/day showing HR 1.47 for CHD and 1.56 for ischemic stroke) 3
Bone health: Increased osteoporosis risk with cumulative doses >395 mg showing adjusted HR of 3.62 (95% CI 2.16-6.06) 4
TSH suppression complications: Approximately 25% of patients are inadvertently maintained on doses sufficient to fully suppress TSH, increasing risks for osteoporosis, fractures, and cardiac complications 5
Clinical Recommendations
When prescribing levothyroxine, focus on appropriate dosing rather than cancer risk:
For low-risk thyroid cancer patients free of disease, shift from suppressive to replacement therapy with TSH in the low-normal range (0.5-2 mIU/L) 2, 5
For primary hypothyroidism without cancer, target TSH within the normal reference range (0.5-4.5 mIU/L) 5
Monitor TSH every 6-8 weeks during dose titration and every 6-12 months once stable 5
Avoid chronic TSH suppression (<0.1 mIU/L) unless specifically indicated for high-risk thyroid cancer with structural incomplete response 2, 5
The priority should be preventing well-established complications of overtreatment (cardiovascular disease, osteoporosis, atrial fibrillation) rather than theoretical cancer risk, as these complications have stronger evidence and greater clinical impact on morbidity and mortality. 3, 4, 5