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Summaries for the Public from recent articles in Clinical Thyroidology
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GRAVES’ DISEASE
How can immune checkpoint inhibitor therapy for cancer affect thyroid function in patients with history of Graves’ disease?
BACKGROUND
Immune checkpoint inhibitors (ICIs) are a class of drugs that are very effective and increasingly used in certain cancer treatment, such as melanoma, lung cancer, kidney cancer, lymphoma, or bladder cancer. These medications work by enhancing a person’s own immunity against cancer cells by blocking “off switches” on immune cells and using the patient’s immune system to destroy the cancer. Development of these drugs has greatly improved cancer treatment. However, ICIs have also been associated with allowing the immune system to attack endocrine glands. The thyroid is the most common target, with thyroid hormones abnormalities occurring in up to 20% of patients receiving treatment.
The most common types of thyroid problems from ICIs are hypothyroidism (low thyroid hormone levels) and thyrotoxicosis (high thyroid hormone levels) from destructive thyroiditis (inflammation of thyroid gland leading to release of thyroid hormone). Development of hyperthyroidism (overproduction of thyroid hormone from the thyroid gland) from ICIs is rare. Risk factors for developing hypothyroidism due to Graves’ disease after ICI treatment are unclear.
The current study was conducted to evaluate potential relationship between history of Graves’ disease and development of thyroid problem among patients treated with ICIs.
THE FULL ARTICLE TITLE
Suzuki K, et al. Increased risk of hyperthyroidism induced by immune checkpoint inhibitors in patients with existing or prior Graves’ disease: a nested prospective cohort study with propensity score matching. Front Endocrinol (Lausanne) 2025;16:1701500; doi: 10.3389/ fendo.2025.1701500. PMID: 41404503
SUMMARY OF THE STUDY
A group of 19 patients with preexisting Graves’ disease receiving ICI treatment between 2015 and 2024 in Japan were included in GD-ICI group. Patients in the GD-ICI group were compared with 95 patients without history of Graves’ disease and receiving ICI treatment (Control 1 group) and 269 patients with Graves’ disease but not receiving ICI treatment (Control 2 group). Patients in the Control 1 group had same age, sex, baseline thyroid antibody status, and the type of ICI treatment received as the patients in the GD-ICI group.
Patients in Control 2 group had similar history of Graves’ disease as patients in GD-ICI group. Thyroid hormone levels and thyrotropin receptor antibody (TRAb, thyroid receptor antibody that is elevated in Graves’ disease) levels were monitored during ICI treatment in GD-ICI and Control 1 group. Information on Control 2 group was obtained from medical records.
Among the 19 GD-ICI patients, 13 patients had Graves’ disease in remission (not taking anti-thyroid drugs) and 6 patients were taking low-dose anti-thyroid drugs. Overall, the number of patients with development of thyroid problems was similar between GD-ICI group and Control 1 group (26.3% vs 29.5%). However, TRAbpositivity was more frequent in GD-ICI group than Control 1 group (15.8% vs 0%). On the other hand, rates of destructive thyroiditis and hypothyroidism were not significantly different between GD-ICI and Control 1 groups. In GD-ICI group, only 40% of thyrotoxicosis was due to destructive thyroiditis, while 100% of thyrotoxicosis in Control 1 group were due to destructive thyroiditis. When assessing potential impact of ICI treatment on development of hyperthyroidism, patients in GD-ICI group had significantly higher rate of hyperthyroidism than Control 2 group (15.8% vs 3.7%).
WHAT ARE THE IMPLICATIONS OF THIS STUDY?
The authors of this study concluded that patients with current or prior Graves’ disease have an increased risk of developing hyperthyroidism after treatment with ICIs. These data suggests that these patients may need to be carefully monitored and evaluated to determine the cause of elevated thyroid hormone levels during ICI treatment. Graves’ disease may require anti-thyroid drugs while destructive thyroiditis is generally treated only for symptoms such as palpitations. Destructive thyroiditis also resolves on its own in several months. Therefore, establishing the correct cause of thyrotoxicosis is important to provide appropriate treatment. The current National Comprehensive Cancer Network guidelines recommend monitoring thyroid function tests every 4-6 weeks while patient is receiving ICI treatment. If thyrotoxicosis develops, the guidelines recommend treating palpitations and consider evaluation for Graves’ disease if thyrotoxicosis persists for another 4-6 weeks. This would be a reasonable approach with referral to endocrinologists for management of hyperthyroidism if thyrotoxicosis persists on repeat testing. Particular attention can be paid to patients with preexisting autoimmune thyroid disease, as they are at a higher risk of exacerbation of their underlying autoimmunity while receiving ICI treatment.
— Sun Y. Lee, MD
ATA RESOURCES
Hyperthyroidism (Overactive): https://www.thyroid.org/hyperthyroidism/
Graves’ Disease: https://www.thyroid.org/graves-disease/
Thyroiditis: https://www.thyroid.org/thyroiditis/
ABBREVIATIONS & DEFINITIONS
Autoimmune thyroid disease: a group of disorders that are caused by antibodies that get confused and attack the thyroid. These antibodies can either turn on the thyroid (Graves’ disease, hyperthyroidism) or turn it off (Hashimoto’s thyroiditis, hypothyroidism).
Hypothyroidism: a condition where the thyroid gland is underactive and doesn’t produce enough thyroid hormone. Treatment requires taking thyroid hormone pills.
Hyperthyroidism: a condition where the thyroid gland is overactive and produces too much thyroid hormone. Hyperthyroidism may be treated with antithyroid meds (Methimazole, Propylthiouracil), radioactive iodine or surgery.
Thyroiditis: inflammation of the thyroid, most commonly cause by antibodies that attack the thyroid as seen in Hashimoto’s thyroiditis and post-partum thyroiditis. It can also result from an infection in the thyroid.
Graves’ disease: the most common cause of hyperthyroidism in the United States. It is caused by antibodies that attack the thyroid and turn it on.
Antibodies: proteins that are produced by the body’s immune cells that attack and destroy bacteria and viruses that cause infections. Occasionally the antibodies get confused and attack the body’s own tissues, causing autoimmune disease.
TRAb: antibodies often present in the serum of patients with Graves disease that are directed against the TSH receptor, often causing stimulation of this receptor with resulting hyperthyroidism.
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