Abstract
Autoimmune diseases have a high prevalence in the population, and autoimmune thyroid disease (AITD) is one of the most common representatives. Thyroid autoantibodies are not only frequently detected in patients with AITD but also in subjects without manifest thyroid dysfunction. The high prevalence raises questions regarding a potential role in extra-thyroidal diseases. This review summarizes the etiology and mechanism of AITD and addresses prevalence of antibodies against thyroid peroxidase, thyroid-stimulating hormone receptor (TSHR), and anti-thyroglobulin and their action outside the thyroid. The main issues limiting the reliability of the conclusions drawn here include problems with different specificities and sensitivities of the antibody detection assays employed, as well as potential confounding effects of altered thyroid hormone levels, and lack of prospective studies. In addition to the well-known effects of TSHR antibodies on fibroblasts in Graves’ disease (GD), studies speculate on a role of anti-thyroid antibodies in cancer. All antibodies may have a tumor-promoting role in breast cancer carcinogenesis despite anti-thyroid peroxidase antibodies having a positive prognostic effect in patients with overt disease. Cross-reactivity with lactoperoxidase leading to induction of chronic inflammation might promote breast cancer, while anti-thyroid antibodies in manifest breast cancer might be an indication for a more active immune system. A better general health condition in older women with anti-thyroid peroxidase antibodies might support this hypothesis. The different actions of the anti-thyroid antibodies correspond to differences in cellular location of the antigens, titers of the circulating antibodies, duration of antibody exposure, and immunological mechanisms in GD and Hashimoto’s thyroiditis.
Highlights
Autoimmune diseases (AD) represent a spectrum of disorders caused by inflammation of organs due to production of antibodies against self-structures and cytotoxic action of T cells
Prevalence of breast, colon, kidney, uterine, and ovarian cancer was increased in autoimmune thyroid disease (AITD) patients with high titer anti-thyroid-stimulating hormone receptor (TSHR) antibodies, but numbers were too low for statistical analysis
The authors identified a protective effect of anti-thyroid peroxidase (TPO) and anti-Tg antibodies for breast cancer in this study and a previous study on the association of benign thyroid diseases and cancer [149]
Summary
Autoimmune diseases (AD) represent a spectrum of disorders caused by inflammation of organs due to production of antibodies against self-structures and cytotoxic action of T cells. High thyroid hormone levels were linked to breast cancer incidence, suggesting that the antibodies themselves were not important in the pro-cancer action. Prevalence of breast, colon, kidney, uterine, and ovarian cancer was increased in AITD patients with high titer anti-TSHR antibodies, but numbers were too low for statistical analysis.
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