Radioiodine Therapy for Hyperthyroidism Presents No Longterm Cancer Risk

With Bryan Haugen, MD, FACP and Naomi Gronich, MD

First your doctor informs you that you have hyperthyroidism, then the treatment options are presented. Hearing the word radioactive is likely to be unsettling but fear not! Radioactive iodine therapy (or as it is more frequency referred to: radioiodine therapy) is commonly used to treat overactive thyroid, a condition also known as hyperthyroidism.

Overactive thyroid may be a sign of Graves disease or hyperthyroidism.Hyperthyroidism is an overactive thyroid that requires treatment to avoid serious complications; researchers evaluate whether radioiodine therapy warrants concern about cancer risk. Photo: sasirin pamai @ iStock.

Latest Study Looks to Address Concerns about Use of RAI for Hyperthyroidism

This treatment is given by mouth, usually as a small capsule. It works by killing off or destroying the thyroid cells so the thyroid gland does not continue to overproduce thyroid hormones.1

Radioactive iodine treatment has been used quite effectively for more than 60 years, and in the United States, more than 70% of adults who develop hyperthyroidism are treated with this approach.1

While it's safe and successful, controversy about the long-term safety is ongoing, especially concerns about whether treatment with radioactive iodine increases the risk of cancer.2  According to the American Thyroid Association, there has been no clear increase in any type of cancer, thyroid or other common cancers, with regard to exposure to RAI.1

Yet, a range of studies have produced mixed findings over the years. With the hope of settling this worrisome concern, a new study from Israel researchers provides some reassurance to patients faced with considering treatment with radioactive iodine to cure their hyperthyroidism.2

This research team followed more than 16,000 patients who were diagnosed with an overactive thyroid (hyperthyroidism, Graves’ disease), including more than 2,800 of them who were treated with radioactive iodine while the others getting other treatments (ie, drugs, surgery).

Some of the patients were diagnosed with obesity (21%) and had diabetes (13%), but those factors were not evaluated as risk factors for cancer in this study,2 says study co-author Naomi Gronich, MD, assistant professor of clinical pharmacology and internal medicine at Lady Davis Carmel Medical Center in Haifa, Israel.

As such, they can draw no conclusions about cancer risk related to these co-existing conditions or offer specific advice for those with obesity, diabetes, or heart disease, Dr. Gronich says.

More importantly, over the long period of monitoring patients after they were treated, ''we did not find any association between receiving radioiodine therapy for benign (noncancerous) hyperthyroidism, specifically there was no evidence of an increased risk for new cancer cases, overall," she says.

There was one possible exception—the study results did show an association between radioiodine therapy and greater risk for non-Hodgkin's lymphoma when the researchers looked at the analysis in the simplest way, known as univariate analysis.2 However, when other common variables that affect cancer risk (such as age) were considered, this relationship became so weak as to not make the threshold for any significant concerns from a statistical point of view.

Similarly, when looking at short-term data, a link was seen between RAI therapy and an increased risk of cancer, but that concern disappeared as patients were followed longer, extending to more than 7 years, on average, and as long as 15 years.2

Reasons other than Radioiodine Therapy Likely to Raise Cancer Risk 

The bottom line, Dr. Gronich told EndocrineWeb, is that over the long-term, ''treatment with radioiodine for hyperthyroidism is not associated with an increased risk for overall cancer. However, there might be an association with a slight increased risk for non-Hodgkin's lymphoma." She says more studies ''might be warranted to gain confirmation of the results." Meanwhile, doctors should discuss this possible slight increased risk of the NHL with their patients.

An expert not involved in the study sees the results as reassuring. For patients with hyperthyroidism getting the radioiodine treatment, the study suggests that the cancer risk is ''very low," says Bryan Haugen, MD, FACP, professor of medicine and pathology and head of the division of endocrinology, University of Colorado School of Medicine in Aurora.

Dr. Gronich shared some additional background on the treatment in responses to questions posed by EndocrineWeb. "Radioactive iodine is in widespread use for the treatment of benign hyperthyroidism resulting from Graves’ disease, toxic adenoma, multinodular goiter, and also for the treatment of thyroid cancer," he says.

She concedes that the research has produced mixed findings. In one study, the American Cooperative Thyrotoxicosis Therapy Follow-up Study, that was conducted many years ago, radioactive iodine therapy was not linked to the overall rate of cancer deaths or death from any specific cancer, after excluding patients undergoing surgery and anyone with a prior malignancy.3

Evidence Favorable to Use of Radioiodine Therapy for Graves’ Thyroid Disease

However, a recently published extended follow-up trial of 18,805 patients in the Cooperative Thyrotoxicosis Therapy Study, who underwent treatment for hyperthyroidism between 1946-1964, found a link between the radioiodine absorbed by each organ and the risk of death from cancer occurring in those organs.4

In response to these findings, experts from the Society for Endocrinology and the British Thyroid Association issued a statement urging caution in interpreting the results.5 They pointed out several limitations in the study design, such as the lack of a comparison or control group with hyperthyroidism. The experts also noted that factors such as smoking and obesity, which can affect cancer risk, were not addressed in the calculations, and these variables are known to increase the risk of developing cancer.

In the latest study, all patients received care at Clalit Health Services, which provides medical care to more than half of Israel's population. The patients were essentially all White, so it’s fair to say that Dr. that the findings might not apply to other populations, says Dr. Gronich.

Radioiodine Therapy and Cancer Risk: An Expert Evaluation of the Evidence in Hyperthyroidism

Overall, the new study is very reassuring, says Dr. Haugen who reviewed the study findings for EndocrineWeb. Unlike the study that looked at cancer deaths among those receiving RAI,4 the new study evaluated the risk of getting cancers based on type of treatment for hyperthyroidism,5 he points out. 

While the findings remain uncertain overall, one of the strengths of this Iatest study' is the clarity gained by having a control group, Dr. Haugen says, as this allowed for a direct comparison between patients who had the same diagnosis of hyperthyroidism but received different treatments. Many of the other studies used the general population as a control group, eliminating the ability to evaluate cancer rates across different treatments.

The study findings he says, ''makes me feel a bit better about talking to patients [about the option of radioactive iodine therapy]."

As for finding the link with the non-Hodgkin's lymphoma, Dr. Haugen says that any association here was not meaningful or worrisome as the link disappeared when other factors that known to contribute to increased risk of cancer (such as age) were considered. Because the link did not hold up in the second analysis, he says, ''it is more likely to be a statistical error."

Given the number of people affected and the clinician value to arriving at a clear answer, more studies will undoubtedly be done to settle any lingering questions, Dr. Haugen says. "This won't be the last word."

In addition, since the study included those known to have diabetes and to have obesity, the findings would seem to hold for these populations, too, he says. Higher thyroid hormone levels could stress the heart excessively in those with heart disease, he adds.

He agrees that the findings would probably hold up for most Caucasians but can't say based on the study if the same low risk of cancer holds for hyperthyroid patients in Western Europe, all of the U.S. or Asia.

What Are the Alternatives to Radioiodine Treatment for Hyperthyroidism?

Two other options exist to treat overactive thyroid (ie, Graves’ disease): antithyroid drugs—most notably methimazole, which block the ability of the thyroid gland to produce thyroid hormones,1  and surgery, in which all or most of the thyroid gland is removed.

Common side effects reported after taking methimazole includes skin reactions (eg, itching, hives, rash, jaundice),  nausea and heartburn, headache and dizziness, and joint discomfort.

In addition to the usual risks faced when having surgery, there is a significant downside to surgery in that patients become hypothyroid and need to take a thyroid hormone supplement for the rest of their lives, which in turn increases the risk of bone fracture and other issues. Thyroid supplementation is also necessary after radioiodine therapy.1

Neither Dr. Gronich or Dr. Haugen has any financial conflicts regarding this work.

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