Does Levothyroxine Really Increase Thyroid Cancer Risk?

Dismaying Suggestion From Flawed Study

scanning of a thyroid
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People who don’t produce enough thyroid hormone—and are thus hypothyroid—benefit from levothyroxine, or synthetic thyroid hormone. Thyroid hormone is essential for proper metabolism. For the most part, the administration of thyroid hormone yields few adverse effects, and overdose is rare. Some more common negative side effects include palpitations, increased heart rate, flushing, sweating, and nervousness.

However, new research links the regular use of levothyroxine (Synthroid) with thyroid cancer. Although interesting, this small study is by no means definitive and needs further investigation.

Research

In a July 2017 article published in the Journal of Clinical Pharmacology, Hung and co-authors examined the association between levothyroxine and thyroid cancer using population-based analysis. Drawing from data representing 1 million Taiwanese people, Hung and colleagues identified 1285 adults who received a first-time diagnosis of thyroid cancer between January 1, 2001, and December 31, 2013.

These adults with thyroid cancer were then matched with 3855 adults without thyroid cancer (i.e., the control group) who were similar in age, sex, and physician visits. In total, there were 5140 adults. Among these 5140 adults, the researchers identified 70 adults who were diagnosed with hypothyroidism by an endocrinologist but had no history of thyroid surgery.

Results were adjusted with respect to monthly income, geographical location, urbanization, tobacco use, and various diseases. Statistically, these 70 people with hypothyroidism differed in one major way: thyroid cancer diagnosis.

Hung and colleagues identified 37 adults with hypothyroidism who later went on to develop thyroid cancer.

They also identified 33 adults with hypothyroidism who didn’t develop thyroid cancer. The researchers then compared these two groups with respect to many factors, including regular use of levothyroxine.

The researchers found that the adults with thyroid cancer were more likely to also be diagnosed with hypertension, diabetes, osteoporosis, and hyperlipidemia.

Most notably, Hung and colleagues found that adults with hypothyroidism who regularly took levothyroxine were more likely to develop thyroid cancer. Irregular levothyroxine use, however, was not associated with thyroid cancer.

Thyroid Hormone and Cancer

Thyroid hormone is necessary for normal growth, development, and metabolism. Because cancer refers to uncontrolled cellular division, it’s been hypothesized that thyroid hormone could somehow “catalyze” cancer. In humans, few studies and limited research supports the hypothesis that thyroid hormone contributes to cancer.

Notably, in a 2009 study titled “Thyroid Function and Cancer Risk: A Prospective Population Study,” Hellevik and co-authors did find a link between higher levels of thyroid hormone and certain types of cancer. They followed 29,691 Norwegians for 9 years. At the beginning of the observation period, none of these people had been diagnosed with thyroid disease.

The researchers found that people who had low thyrotropin levels at the beginning of the study, which is suggestive of hyperthyroidism, were at greater risk for later developing lung and prostate cancer. (There was no association between hyperthyroidism and colon cancer or breast cancer.)

Furthermore, Hellevik and colleagues found that hypothyroidism isn’t linked to cancer risk.

Conversely, other research suggests that people who develop hypothyroidism after being diagnosed with head and neck cancer live longer. Furthermore, people with breast cancer who have autoimmune thyroid disease—and thus hypothyroidism—may live longer, too.

In other words, certain research hints at the possibility that lower thyroid levels may somehow be protective against the effects of cancer. In animal studies, levothyroxine has been shown to stimulate tumor growth and spread. Moreover, hypothyroidism slows down tumor growth, limits tumor spread, and improves survival.

Mechanism

The pituitary gland releases a hormone called thyroid-stimulating hormone (TSH). Administration of thyroid hormone in the form of levothyroxine suppresses TSH levels by negative feedback. Without TSH, the thyroid loses purpose and shrinks. For this reason, thyroid hormone is used as suppressive treatment for thyroid nodules and goiters.

Intuitively, a shrinking thyroid should be less likely to become cancerous. However, with levothyroxine administration, it’s hypothesized that higher dosages of thyroid hormone may somehow overcome this suppressive effect and turn cancerous.

Although the mechanism is unclear, levothyroxine may either mediate or moderate tumor formation. In other words, levothyroxine may play a direct or indirect role in tumor formation. According to Hung and co-authors:

To date, there seem to be no studies reporting the possible mechanisms of thyroxin-related carcinogenesis. Nevertheless, the phenomenon might be explained in 2 possible ways. First, the thyroxin might act as an enhancing agent in the normal carcinogenesis pathways …. Second, thyroxin on its own might stimulate the growth of thyroid cancer cells.

What Does This Mean?

Taken alone, this research finding that regular levothyroxine use is tied to later thyroid cancer means little. These results are based on an isolated research study that was relatively small. Furthermore, there may be issues with the research design.

First, few people who take levothyroxine for hypothyroidism go on to develop thyroid cancer or other types of cancer. Specifically, Hung and colleagues found that only 2.88 percent of subjects with hypothyroidism went on to develop thyroid cancer. Furthermore, only 0.86 percent of subjects without hypothyroidism went on to develop thyroid cancer.

Second, this study is merely the first to show an association between regular levothyroxine use and thyroid cancer. Keep in mind that an association is different from a cause. The researchers didn’t prove that levothyroxine causes thyroid cancer.

According to Hung and co-authors:

[A]lthough the findings suggest an association between thyroid cancer and regular thyroxin use, additional studies are needed to further evaluate and validate these findings …. Although the true role of thyroxin in thyroid cancer development remains to be investigated, physicians might consider this association when treating patients with subclinical hypothyroidism.

The authors readily acknowledge that their findings are associations that need to be fleshed out on the basis of further research. This study is small and we need larger sample sizes to really flesh out any association.

Interestingly, the authors make one tentative recommendation that clinicians might keep this association in mind when prescribing levothyroxine patients with subclinical hypothyroidism, or mild thyroid failure. This recommendation is probably premature.

Third, the basic premise of the research may be flawed. Specifically, the researchers don't distinguish between different causes of hypothyroidism. Mild hypothyroidism, which may require more infrequent use of levothyroxine, is different from more severe hypothyroidism, which may require regular use of levothyroxine, and this intrinsic difference may account for increased rates of cancer seen among regular thyroxine users. Essentially, the researchers are apples and oranges.

Fourth, the researchers used insurance data to define regular and irregular thyroid use, which is a questionable approach.

A Word From Verywell

If left untreated, hypothyroidism can be uncomfortable and distressing. People with hypothyroidism experience fatigue, constipation, depression, dry skin, weight gain, and more. Levothyroxine is an effective treatment for hypothyroidism and can improve quality of life. Lots of people take levothyroxine every day without any problems.

If your physician has prescribed you regular levothyroxine for treatment of hypothyroidism, you shouldn’t be too concerned with this medication causing cancer. For the vast majority of people, the benefit of levothyroxine far outweighs any potential adverse effects, including possible cancer. Furthermore, this study linking regular levothyroxine use and thyroid cancer is small and may have issues with design. Ultimately, the link that the researchers propose really needs much more investigation before any definitive claims can be made.

You shouldn't change your medication regimen for fear of thyroid cancer based on this single small, likely flawed study. If you're regularly taking levothyroxine under your physician's supervision, please follow through with this treatment plan. Any changes in your treatment plan must be discussed with your physician.

If you’re concerned about the link between levothyroxine and thyroid cancer—or anything else, for that matter—please discuss this with your endocrinologist or primary care physician. By asking questions, you not only assuage your own concerns but also learn more about your condition. Insight is an important part of successful treatment.

Sources

Cantrell F. Chapter 150. Thyroid Hormone. In: Olson KR. eds. Poisoning & Drug Overdose, 6e New York, NY: McGraw-Hill; 2012.

Hellevik, AI, et al. Thyroid Function and Cancer Risk: A Prospective Population Study. Cancer Epidemiology, Biomarkers & Prevention. 2009;18:570-574.

Hung, SH, Chung, SD, Lin, HC. Thyroxin Use Is Associated With Increased Risk of Thyroid Cancer in Patients With Hypothyroidism. The Journal of Clinical Pharmacology. July 19, 2017. (e-pub ahead of print)

Stoll, SJ, et al. Thyroid Hormone Replacement After Thyroid Lobectomy. Surgery. 2009;146:554-560.

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