A major breakthrough in treating non-thyroid cancer has been the development of a class of cancer drugs known as immunotherapy. These drugs activate a patient’s own immune system to attack and destroy cancer cells. One of the more effective cancer immunotherapy drugs belong to a class known as immune checkpoint inhibitors (ICI). Since these ICI drugs activate the patient’s immune system, it is not surprising that other autoimmune diseases may develop or flare during the treatment with ICI. The thyroid is one of the most common glands affected and ICI drugs can cause both hyperthyroidism and hypothyroidism.
Autoimmune thyroid disease, where antibodies get confused and attack the thyroid, is the most common cause of hyperthyroidism and hypothyroidism. Serum thyroid peroxidase antibodies (TPOAbs) and thyroglobulin antibodies (TgAbs) are positive in up to 90% of patients with autoimmune thyroid disease. The role of these antibodies in the pathogenesis of ICI-related thyroid disease remains poorly understood. The goal of this study was to characterize the association of TPOAb and TgAb with the development of ICI-related thyroid disease and to examine the role antibodies may play as to predict the development of ICI-related thyroid disease.
THE FULL ARTICLE TITLE
Muir CA et al 2022 Association of antithyroid antibodies in checkpoint inhibitor-associated thyroid immune-related adverse events. J Clin Endocrinol Metab 107(5):e1843– e1849. PMID: 35104870.
SUMMARY OF THE STUDY
The authors performed a study of adults with melanoma undergoing ICI treatment to characterize the association of antithyroid antibodies with the development of thyroid ICI-related thyroid disease. Serum samples, collected prior to the first dose of ICI and at the onset of any ICI-related thyroid disease (or 30–60 days after first dose of ICI in patients who remained with normal thyroid function), were retrieved to measure TPOAbs and TgAbs.
Additional demographic, treatment, and cancer outcome information was obtained from a central database. The study measured the change in serum TPOAb and TgAb levels from baseline and during ICI treatment and whether increases in antibodies were associated with the development of ICI-related thyroid disease. Change from baseline was defined as new antibody positivity or a >50% increase in level for patients with baseline antibody-positive status. The average age was 65 years; 60% were male, reflecting the male predominance in melanoma diagnoses. The average follow-up time was 13.8 months.
Of 122 patients with paired samples, only 31 (25%) remained with normal thyroid function. For the other 75% of patients, the first thyroid function abnormality was mild hyperthyroidism in 47 (39%), overt hyperthyroidism in 37 (30%), and overt hypothyroidism in 7 (6%). A positive baseline TPOAb level was present in 19 patients (16%), with TgAbs present in 28 patients (23%); 16 patients (13%) were positive for both antibodies. Positive TPOAb/TgAb levels at baseline were 97% and 100%, respectively, specific for the eventual development of a ICI-related thyroid disease. In patients with positive baseline TPOAb and TgAb levels, the average antibody titer was statistically significantly higher in patients who developed overt ICI-related thyroid disease (thyrotoxicosis or hypothyroidism). Although those who were negative for thyroid antibodies at baseline were at lower individual risk of thyroid dysfunction, this group comprised most of the people who developed overt thyroid dysfunction in the study.
Only overt thyrotoxicosis was associated with a statistically significant rise in thyroid autoantibody titer as compared with baseline. In patients with overt hyperthyroidism, TgAb positivity (but not TPOAb positivity) was associated with progression to permanent hypothyroidism.
WHAT ARE THE IMPLICATIONS OF THIS STUDY?
This study shows that almost all patients with positive TPOAb or TgAb titers at baseline developed a thyroid ICI-related thyroid disease, although the majority of patients who developed overt hyperthyroidism or hypothyroidism were antibody-negative at baseline. A higher level of antithyroid antibody at baseline may predict the development of overt versus mild disease. Overt hyperthyroidism was associated with a significant increase in TPOAb and TgAb titers and the development of new thyroid antibodies. Both Oncologists as well as Endocrinologists need to be aware of these findings since the use of ICI drugs are increasing all the time.
—Alan P. Farwell, MD
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.
Subclinical Hypothyroidism: a mild form of hypothyroidism where the only abnormal hormone level is an increased TSH. There is controversy as to whether this should be treated or not.
Overt Hypothyroidism: clear hypothyroidism an increased TSH and a decreased T4 level. All patients with overt hypothyroidism are usually treated with 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.
Subclinical Hyperthyroidism: a mild form of hyperthyroidism where the only abnormal hormone level is a decreased TSH.
Overt Hyperthyroidism: clear hyperthyroidism a decreased TSH and an increased T4 level. All patients with overt hyperthyroidism are usually treated with antithyroid meds.
TPO antibodies: these are antibodies that attack the thyroid instead of bacteria and viruses, they are a marker for autoimmune thyroid disease, which is the main underlying cause for hypothyroidism and hyperthyroidism in the United States.
Thyroglobulin antibodies: these are antibodies that attack the thyroid instead of bacteria and viruses, they are a marker for autoimmune thyroid disease, which is the main underlying cause for hypothyroidism and hyperthyroidism in the United States.