Thyroid Changes During Immunotherapy

This page is for people getting immunotherapy drugs called checkpoint inhibitors. It explains how these drugs can affect the thyroid, what the blood tests mean, and when to call.

NCI explains that checkpoint inhibitors block the signals that switch off T cells, so the T cells can attack cancer. The immune system can also act on healthy tissue. NCI lists an overactive or underactive thyroid among the side effects of checkpoint inhibitors. The thyroid is a small gland at the front of the neck.

The FDA label for pembrolizumab gives numbers for about 2,800 people who got it alone. Hypothyroidism (underactive thyroid) occurred in 8% of them. Hyperthyroidism (overactive thyroid) occurred in 3.4%. Thyroiditis occurred in 0.6%. Rates were higher in some groups. For example, hypothyroidism occurred in 16% of patients with head and neck cancer.

The FDA labels say hypothyroidism can follow hyperthyroidism. So the thyroid may be overactive first and underactive later.

The FDA labels say thyroiditis can occur with or without a hormone gland disorder. An overactive thyroid may show up first.

MedlinePlus lists these symptoms of an overactive thyroid: a pounding or racing heartbeat, hand tremor, sweating, heat intolerance, sleep problems, anxiety, and weight loss.

The labels say your team treats an overactive thyroid as clinically indicated. MedlinePlus says beta-blockers can ease a fast heartbeat, tremor, sweating, and anxiety until the overactive thyroid is controlled. The nivolumab label shows that some people with hyperthyroidism received antithyroid medicine, and some received corticosteroids. Your team decides what you need.

MedlinePlus lists these early symptoms of an underactive thyroid: constipation, feeling cold, fatigue, joint or muscle pain, pale or dry skin, sadness, thin or brittle hair, weakness, and weight gain. They are easy to blame on cancer treatment in general. Blood tests check thyroid hormone (free T4) and TSH, a hormone that signals the thyroid.

The pembrolizumab label says most people with hypothyroidism needed long-term thyroid hormone replacement.

Treatment is a daily levothyroxine tablet. It is a synthetic form of thyroid hormone. It replaces the hormone your thyroid is not making.

The FDA label says to take it once a day on an empty stomach, one-half to one hour before breakfast. It also says to keep it at least 4 hours apart from iron and calcium supplements and antacids. Fiber, walnuts, soy flour, and grapefruit juice can also lower absorption.

The label says the dose depends on factors such as age, body weight, and heart health. People with heart disease, and older adults, start on a lower dose. The label says to check TSH 6 to 8 weeks after any dose change. Do not change your dose yourself.

For most people, the tablet continues after immunotherapy ends. Ask who takes over prescribing and monitoring at that point.

The FDA labels say thyroid function should be checked before treatment starts and periodically during treatment. The labels also say to watch closely for symptoms of immune-related reactions. Ask how often your team will check. Ask to be told your results either way. Then you can connect how you feel to the numbers.

The FDA labels say your team may pause or permanently stop immunotherapy depending on how severe the thyroid problem is. In the pembrolizumab label, hypothyroidism led to permanent stopping in fewer than 0.1% of patients and a pause in 0.5%. Everyone whose treatment was paused for hypothyroidism restarted after symptoms improved. Your team decides what is right for you.

• Call 911 or go to the nearest emergency department for chest pain, a fast or irregular heartbeat, severe breathlessness, confusion, fainting, dizziness, a very low body temperature, or being hard to wake. MedlinePlus lists a change in alertness, dizziness, and a rapid, irregular heartbeat as reasons to call 911 for an overactive thyroid. Tell whoever sees you that you are on immunotherapy. Do not drive yourself.
• Call your care team right away, day or night, for a fever, chills, a new rash, diarrhea, belly pain, a new cough, or trouble breathing. NCI lists fever, chills, rash, diarrhea, and trouble breathing among immunotherapy side effects. ACS says to tell your team about anything new or unusual. Report new side effects right away. Also call right away for vomiting you cannot keep down, severe weakness, or dizziness on standing that keeps getting worse. If you are also on chemotherapy, call right away for a temperature of 100.4°F (38°C) or higher. Call for a sore throat, mouth sores, or burning when you pass urine. Call for any other sign of infection too. A normal temperature is not a reason to wait.
• Call your care team right away for palpitations, a swollen or tender neck, a headache that does not go away, or unusual thirst. MedlinePlus says to contact your provider for symptoms of an overactive thyroid.
• Call your care team the same day for new heat or cold intolerance, a marked weight change, or deepening tiredness. MedlinePlus lists these among thyroid symptoms.

• NCI: Immune Checkpoint Inhibitors
• NCI: Immunotherapy Side Effects
• FDA label (DailyMed): Keytruda (pembrolizumab)
• FDA label (DailyMed): Opdivo (nivolumab)
• FDA label (DailyMed): Synthroid (levothyroxine)
• MedlinePlus: Hypothyroidism
• MedlinePlus: Hyperthyroidism
• American Cancer Society: Immune Checkpoint Inhibitors and Their Side Effects