Do Thyroid Medications Increase The Risk of Lung Cancer?

Many of my readers were worried about taking thyroid medications in 2013 after an Italian study began circling the internet. This study found increased rates of lung cancer in people who took T4 containing thyroid medications, but not increased rates of breast, colorectal and gastric cancer.

Researchers decided to conduct this study because thyroid medications can increase oxidative stress in the body through the overproduction of reactive oxygen species by mitochondria (keep in mind that hypothyroidism itself is associated with an increase of oxidative stress as well, but a different type).

We know that oxidative stress can lead to chronic inflammation, which in turn has been connected to most chronic conditions, including cancer, diabetes, and heart disease (among others).

Previous studies have shown that some cancer cells have thyroid hormone receptors on them and that taking T4 can promote the growth of lung cancer cells. Rat studies have found that while deiodination of T4 (the breakdown of T4 to produce T3 and later get eliminated from the tissue) can happen in lung tissues, it doesn’t happen as readily in the lungs as it does in other parts of the body. Thus T4 supplementation can potentially lead to excess levels of T4 within the lungs due to poor breakdown.

Researchers compared the sales data of levothyroxine from pharmacies in 18 different Italian regions to the rates of various cancers in women within the same regions and found that the regions that had a higher intake of levothyroxine, also had higher rates of lung cancer as well. Thus, they found a correlation between the intake of levothyroxine and lung cancer.

During my PharmD studies (Doctor of Pharmacy Degree), I had extensive training in evaluating medical journals and studies. I had an entire semester long course on just this topic and am the proud owner of a few textbooks that I was required to read on the subject! A big part of obtaining my degree was dependent on my grades for “journal clubs” during my clinical rotations where my critique of medical journal studies was analyzed and ripped apart by a group of my peers. This is because you can determine how trustworthy a study is based on the study design, methods, and statistical analysis used by the researchers. The better the methods and study design, the less likely chance the results were just a fluke or coincidence. Since graduating from pharmacy school, I’ve probably read tens of thousands of research articles over the last decade of being a clinical pharmacist. My point is, I know a thing or two about how to evaluate studies, and I was not super impressed with the lung cancer and levothyroxine study.

My critique of this particular study is as follows:

1. Correlation does not equal causation. Studies have also correlated the incidence of rape to eating ice cream. Of course, common sense will tell us that this does not mean that ice cream leads to rape. Rather more people eat ice cream in the summer, when people are more likely to leave their homes, and thus attacked, compared to the winter. (-)
2. Poor study design- this study looked at rates of lung cancer in people who purchased thyroid medications through data mining, looking at prescription data and cancer data in the same region, NOT in the same people! (-)
3. We don’t have sufficient studies looking at Hashimoto’s/hypothyroidism, which also causes oxidative stress, on its impact on lung cancer. After all, some of the same factors that cause Hashimoto’s can contribute to asthma, would it be a stretch to say they could contribute to another type of lung condition? (-)
4. The researchers didn’t properly account for smoking status, a known risk factor for lung cancer. People weren’t asked individually, and the information was not retrieved from their medical records. The researchers used data from the Italian Statistical Institute instead to estimate smokers within each region. While no studies have been done on Hashimoto’s patients self-medicating with cigarettes, I can say that I have seen this to be the case. It makes sense that a person who was helped by smoking would likely continue to smoke. This has been documented in people with mental illness and schizophrenia- smoking can provide temporary relief of their symptoms, and so thus more people with mental illness are likely to be smokers. As smoking is much more culturally acceptable in Europe compared to the United States, I would not be surprised if many of the patients with Hashimoto’s who developed lung cancer actually did because they smoked. (-)
5. If all cancers are associated with oxidative stress, then why would we only see a rise in lung cancer, but not others? (-)
6. A brand new study (March 2016- hot off the presses) has reported that taking levothyroxine actually reduces the overall oxidative stress in Hashimoto’s.

My Interpretations and Recommendations

This study hasn’t definitively proven that thyroid medications increase the risk of lung cancer. In my opinion, the benefit of taking thyroid medications still outweighs the risk of lung cancer for most people. That said, it’s always best to take precautions.

1. Following the root cause approach though removing lifestyle factors and infections that can contribute to the oxidative stress burden in the body will reduce the overall risk of chronic diseases, including cancer and autoimmunity.
2. The study found that the prevalence of cancers in Southern Italy, where the Mediterranean diet, associated with a lower risk of inflammation is more common, was much lower than the rest of Italy. Eating a real-food anti-inflammatory diet is always a great idea!
3. Quitting smoking, we know that smoking is the BIGGEST risk factor for lung cancer. If you smoke cigarettes, the single best thing you can do to reduce your risk is to quit.
4. Taking antioxidants like Selenium, Glutathione, and N-Acetylcysteine will help reduce the oxidative stress in the thyroid gland and the rest of the body, further reducing inflammation and our risks.
5. Taking T4/T3 containing medications (when tolerated) may reduce the risk of lung cancer. The study focused specifically on T4 containing medications which need to be converted to T3 in the body to be utilized most efficiently. T4 to T3 conversion occurs in many tissues in the body, including lung tissues. The authors hypothesized that the lung cancer resulted from the T4 excess. Their hypothesis was that T4/T3 combination medications would have a reduced risk of lung cancer.

References

1. Cornelli U, Belcaro G, Recchia M, Finco A. Levothyroxine and lung cancer in females: the importance of oxidative stress. Reprod Biol Endocrinol. 2013;11(1):75. doi:10.1186/1477-7827-11-75.
2. Reuter S, Gupta S, Chaturvedi M, Aggarwal B. Oxidative stress, inflammation, and cancer: How are they linked?. Free Radical Biology and Medicine. 2010;49(11):1603-1616. doi:10.1016/j.freeradbiomed.2010.09.006.
3. Ates I, Altay M, Yilmaz F et al. The Impact of Levothyroxine Sodium Treatment on Oxidative Stress in Hashimoto’s Thyroiditis. Eur J Endocrinol. 2016: EJE-15-1061. doi:10.1530/eje-15-1061.