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Pre-existing thyroid autoimmunity is associated with increased thyroid cancer risk

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Autoimmune disease is a major cause of thyroid problems in the US. This is a group of disorders that are caused by antibodies that get confused and attack the thyroid (thyroid autoimmunity). These antibodies can either turn on the thyroid (Graves’ disease, hyperthyroidism) or turn it off (Hashimoto’s thyroiditis, hypothyroidism). Thyroid autoimmunity has been proposed to be a risk factor for the development of thyroid cancer by causing chronic inflammation in the thyroid gland. Chronic inflammation is known to come before the development of cancer in many other body tissues. Hashimoto’s thyroiditis, the most common autoimmune thyroid disease in the United States, can be diagnosed through measurement of thyroid autoantibodies in the blood, the appearance of the gland on ultrasound or after examining the gland after surgery. Previous studies have suggested an association between autoimmune thyroid disease and thyroid cancer. The aim of this study is to determine whether there is an association of thyroid cancer with autoimmune thyroid disease by evaluating for the presence of thyroid autoantibodies in thyroid cancer patients with or without diagnosed autoimmune thyroid disease.

McLeod DSA et al 2022. Pre-existing thyroid autoimmunity and risk of papillary thyroid cancer: A nested casecontrol study of US active-duty personnel. J Clin Oncol. Epub 2022 Apr 13. PMID: 35417260.

This study included U.S. active-duty military personnel diagnosed with thyroid cancer from 1996 to 2014. The study data was obtained from combining 3 groups of data related to the US military: a comprehensive dataset including demographic information and medical diagnoses, the central military cancer registry, and a serum bank that collects samples from military personnel approximately every two years. A total of 451 cases with serum available both 3-5 years and 7-10 years before the date of thyroid cancer diagnosis were randomly selected. The cases were age- and sex-matched to randomly selected controls. Serum thyroid peroxidase antibodies (anti-TPO), thyroglobulin antibodies (antiTg-Ab), and nicotine, a biomarker for exposure to tobacco were measured.

The majority of patients (61%) were male, with an average age of 36 years. Overall, 80% of patients had classical papillary thyroid cancer (PTC), while the rest had the follicular variant of PTC. Patients with pre-existing high anti-TPO antibody levels measured in banked sera collected 7 to 10 years prior to the thyroid cancer diagnosis had nearly double the odds of developing thyroid cancer. This association was 2.5 increased in females as compared to 1.6 times increased in males. In addition, the thyroid cancer risk increased as the serum anti-TPO antibody levels increased. Smoking did not affect the association between thyroid autoimmunity and thyroid cancer in this population.

Additional analysis showed that a pre-existing diagnosis of autoimmune thyroid disease accounted for 35% of the increased likelihood of these patients to be diagnosed with thyroid cancer. However, these patients had more favorable cancer features (e.g., smaller cancer size and less often spread into the neck lymph nodes), indicating a less aggressive cancer and/or diagnosis at earlier stages in thyroid cancer patients with known thyroid autoimmunity because of increased screening in this group.

This study showed that long-standing autoimmune thyroid disease (up to 10 years prior to thyroid cancer diagnosis) is associated with papillary thyroid cancer. Patients with higher thyroid autoantibody titers had a higher risk of developing papillary thyroid cancer. Patients with known thyroid autoimmune disease were diagnosed with thyroid cancer at earlier stages, because of close monitoring of these patients.

— Alina Gavrila, MD, MMSC


Antibodies: proteins produced by the body’s immune cells that attack and destroy potentially harmful foreign substances, bacteria/viruses that cause infections as well as abnormal body cells. Occasionally the antibodies get confused and attack the body’s own tissues, causing autoimmune disease.

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).

Thyroid antibodies (thyroid peroxidase/TPO and thyroglobulin/Tg 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.

Hashimoto’s thyroiditis: the most common cause of hypothyroidism in the United States. It is caused by antibodies that attack the thyroid and destroy it.

Papillary thyroid cancer (PTC): the most common type of thyroid cancer. There are 4 variants of papillary thyroid cancer: classic, follicular, tall-cell and noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP).

Lymph node: bean-shaped organ that plays a role in removing what the body considers harmful, such as infections and cancer cells.