The drugs, which include Keytruda (pembrolizumab) and Opdivo (nivolumab), have been used over the past several years to treat a growing number of cancer types and have had particular success in helping patients with melanoma and lung cancer. “They are changing the landscape of cancer therapy and have multiple [U.S.] Food and Drug Administration approvals for both solid and liquid cancers,” says Zoe Quandt, MD, the author of the new study and an endocrinologist with the of University of California in San Francisco. However, the longer the drugs have been in use, the more side effects have emerged in association with them.
Thyroid Problems More Common Than Expected
To gauge the rate of thyroid problems in patients being treated for cancer, Dr. Quandt and her colleagues looked at the health records of 1,146 patients who received checkpoint immunotherapy drugs for cancer at their institution from 2012 to 2018. The study showed that about 19 percent of patients developed thyroid dysfunction. Among these, 13.4 had hypothyroidism (a condition characterized by low thyroid hormone levels) and 9.5 had hyperthyroidism (production of excessive thyroid hormones). Some patients first experienced hyperthyroidism before converting to hypothyroidsm. In clinical trials involving these drugs, however, the rate of thyroid dysfunction was lower. Only 6.6 percent of patients developed hypothyroidism and 2.9 percent had hyperthyroidism. “We found a much higher percent of thyroid dysfunction than we were expecting,” Quandt says. “It appears to be much more common than was previously reported in clinical trials.” Thyroid problems that arise during checkpoint inhibitor therapy appear to be permanent, Quandt says. RELATED: Cancer News Update: Acupuncture Helps Cancer-Related Pain, Thyroid Cancer on the Decline, and More
A Growing Side Effect Profile
Checkpoint Inhibitors work by helping the immune system recognize and attack cancer cells. Part of their appeal is that they lack some of the more harsh side effects common to chemotherapy and radiation — toxic effects that can make patients miserable during cancer treatment. But as more immunotherapy drugs become available and are used in the real world, additional information is accumulating about their side effects. Side effect rates may be higher in the real world than in clinical trials, says Quandt, because some types of patients are restricted from entering clinical trials. “In the real world, we have fewer restrictions on who can get these drugs. We’re giving it to people with other [health] conditions,” she says. “As we give these drugs to a broader population, we are seeing more of these results.”
The Unique Sensitivity of the Thyroid Gland
It’s not clear why thyroid problems are appearing so commonly in patients taking checkpoint inhibitors, Quandt says. One possible explanation is that some people have mild undiagnosed thyroid dysfunction before being diagnosed with cancer. The immune checkpoint inhibitors, says Quandt, “could activate an underlying predisposition” to thyroid disease. It’s also possible that cancer patients are taking other medication that also interferes with normal thyroid function. For example, she said, renal cell carcinoma patients commonly take a kinase inhibitor that can also cause thyroid dysfunction. The study did not find a link between thyroid dysfunction and specific immune checkpoint inhibitors. However, thyroid dysfunction was more common in patients who received a combination of Opdivo and Yervoy (ipilimumab) compared with those who took either Keytruda, Opdivo, or Yervoy alone. The study is the first to show that thyroid problems may be more common in people with certain types of cancer. For example, thyroid dysfunction was found in 10 percent of patients with the brain tumor glioblastoma compared with 40 percent for people with renal cell cancer, a type of kidney cancer. More research is needed to examine why people with certain types of cancers may be more likely to experience thyroid problems on a checkpoint inhibitor, Quandt says. RELATED: How Psoriasis and Your Thyroid May Be Linked
Guarding the Thyroid Gland
It’s important for patients, oncologists, and endocrinologists to address any thyroid symptoms, Quandt says. Patients with cancer can experience weight loss, insomnia, and even atrial fibrillation from hyperthyroidsim, and fatigue and constipation from hypothyroidism. “An untreated patient can feel pretty awful,” she said. She recommends that oncologists conduct thyroid function tests before starting immunotherapy. “If the thyroid function is even a little abnormal prior to starting therapy, there is an increased risk of thyroid dysfunction developing, according to another study,” she says. Oncologists often treat thyroid problems that arise during cancer treatment, she said. “Many oncologists feel comfortable dealing with this on their own, and they usually do a good job of it as long as they are attentive to the labs [thyroid function tests results]. I think it is appropriate to refer to an endocrinologist for any extra support.”
