The incidence of thyroid
disease is increasing dramatically worldwide, but it varies between countries.
Up to 20 million Americans were affected with some sort of thyroid disease in
2014, and this number is expected to grow 1. Hypothyroidism
is the most common type of thyroid disease whereas it is five to eight time
more in women than men 2. In the US, the
prevalence of biochemical and clinically evident hypothyroidism is about 4.6%
and 0.3% but it varies considerably by age group 3. Levothyroxine is
a synthetic thyroid hormone, used to treat hypothyroidism and prevention of
various types of goiters. It deactivates abnormal thyroid tissue growth or
function, and helps to maintain a clinical and biochemical euthyroid state in
thyroid gland 4, 5. In recent year,
concerns have been raised regarding the risk of levothyroxine medication for
various types of adverse effects. Also, thyroid disease appears to pose a
greater risk of breast 6, 7, pancreatic 8, and stomach
cancer 9.

Despite growing popularity
for the treatment of hypothyroidism, levothyroxine has further raised concerns
regarding cancer risk. Cornelli et al.10 reported that
levothyroxine is associated with increased risk of lung cancer; although
long-term use is associated with a reduction in risk of colorectal cancer 11. However, several
epidemiological studies were conducted which evaluated for an association
between levothyroxine use and cancer risk, but the results were inclusive. Additionally,
biological studies also showed an evidence that levothyroxine is linked to
overproduction of reactive oxygen species (ROS) which help to increase oxidative
stress in the body 12, 13. Also, oxidative
stress is considered as a main factor for various chronic conditions like
cancer and autoimmunity.

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Due to the possible biological
evidence and mixed results from epidemiological studies; We, therefore,
conducted a nationwide population-based case-control to investigate whether the
long-term use of levothyroxine is associated with an increased risk of cancer
when compared to non-levothyroxine users. To our knowledge, no study has
examined the relationship between levothyroxine use and risk of different
cancer in a large population.


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