Thyroid peroxidase (TPO) is a key enzyme in the synthesis of thyroid hormone. TPO is involved in thyroid hormone synthesis (organification and coupling reactions). TPO is a major antigen corresponding to thyroid-microsomal autoantibodies. Anti-TPO auto antibodies are very important to diagnose autoimmune thyroid diseases and also in estimating its clinical course. Autoimmune thyroid disease is detected mostly by measuring circulating antibodies to thyroglobulin which is uncommon measurement of antibodies to TPO that gives reliable information about autoimmune thyroid disease. Eighty percent of Grave’s disease patients have high levels of antiTPO antibodies. About 4% of subclinical hypothyroid patients with positive TPO antibodies develop clinical hypothyroidism. There is always a controversy on the relationship between breast cancer and thyroid disorders. As these tissues, i.e., breast and thyroid, originate embryologically from the same type of cells, hypothyroid/hyperthyroid females are more prone to develop benign or malignant breast tumors. The studies on breast cancer patients indicate increased thyroid disorders in breast cancer patients, most commonly Hashimoto’s thyroiditis accounts to increased thyroid disorders in these patients. This is independent of hormonal receptor status of the patient. These findings suggest the usefulness of screening for thyroid disease in any patient with breast cancer. Keywords: Anti-thyroid peroxidase, breast cancer, thyroid
Thyroid peroxidase (TPO) is a key enzyme in the synthesis of thyroid hormone. TPO is involved in thyroid hormone synthesis (organification and coupling reactions). After iodide enters the thyroid, it is trapped and transported to the apical region of thyroid follicular cells. The oxidation of iodide to iodine is catalyzed by the enzyme TPO. This reaction requires H 2 O 2 and NADPH and NADPH is from Hexose MonoPhosphate (HMP) shunt pathway. The coupling of iodine atom to protein thyroglobulin is also catalyzed by TPO. [1]
TPO is a major antigen corresponding to thyroid-microsomal autoantibodies. AntiTPO autoantibodies are very important to diagnose autoimmune thyroid diseases and also in estimating its clinical course. [2] Human TPO was found to bind to both IgG and IgM from patients with autoimmune thyroid diseases. The binding of IgG to microsomes is inhibited by TPO. [3] Hashimoto’s thyroiditis and Grave’s disease are commonly seen autoimmune thyroid diseases. There are two specific regions of antiTPO antibodies binding, and there are differences in the autoantibody response to TPO in Hashimoto’s and Grave’s diseases. [4] Systemic lupus erythrematosus (SLE) is an autoimmune disease which also secretes antibodies to TPO, these antibodies are of IgG type. These IgG antibodies do not inhibit TPO activity in contrast to IgG secreted from patients of thyroid disorders. [5] Autoimmune thyroid disease is detected mostly by measuring circulating antibodies to thyroglobulin which is uncommon measurement of antibodies to TPO that gives reliable information about autoimmune thyroid disease. Eighty percent of Grave’s disease patients have high levels of anti-TPO antibodies. About 4% of subclinical hypothyroid patients with positive TPO antibodies develop clinical hypothyroidism. TPO antibodies fix complement, and a complex of membrane and complement are formed, these complexes are present in autoimmune thyroid disease patients. Placental passage of these antibodies has no effect on fetal thyroid, which indicates that T-cell damage is required to initiate autoimmune damage to thyroid. [1] The complex interaction between genetic and environmental factors may lead to autoimmune thyroid diseases. The genes identified are HLA-DR gene locus, non-MHC genes such as CTLA-4, CD40, PTPN 22, thyroglobulin, and TSH receptor gene. The environmental factors include low iodine content, infections, smoking, various medications, and also due to stress. [6] It is reported by several authors that stress influences the immune system and thus there is a relation between stress and worsening of autoimmune thyroid disorders. [7]
There is always a controversy on the relationship between breast cancer and thyroid disorders. As these tissues, i.e., breast and thyroid, originate embryologically from the same type of cells, hypothyroid/hyperthyroid females are more prone to develop benign or malignant breast tumors. There is an increased prevalence of hyperthyroidism in postmenopausal women. A study conducted on postmenopausal breast cancer patients showed an increased thyroid hormone/estradiol ratio, which suggests a tumor growth promoting effect caused by this misbalance. [8] Sodium/iodide symporter (NIS) gene is expressed approximately one-third of human breast cancer tissue. Its expression is independent of the hormonal receptor status of the patient (TSH-R gene, ER/PR). [9] The studies on breast cancer patients indicate increased thyroid disorders in breast cancer patients, most commonly Hashimoto’s thyroiditis accounts to increased thyroid disorders in these patients. This is independent of hormonal receptor status of the patient. These findings suggest the usefulness of screening for thyroid disease in any patient with breast cancer. [10] In a study conducted on females with breast-related problems, we found that 3.2% (n = 31) are having thyroid disorders (goiter, hypothyroidism) and a raise in anti-TPO levels is found in females with the advancement in their age. [11] Thus, in conclusion serum antiTPO levels are raised in thyroid disorders especially autoimmune thyroid diseases and all the patients with breast cancer should be screened for thyroid disorders before therapy. This helps us to know the relationship between breast cancer and thyroid disorders.
Source of Support: None, Conflict of Interest: None
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