Thyroid Peroxidase Antibodies and Pregnancy

Abstract

In this issue of Endocrine Practice (pages 244 to 248), Ortega-Gonzalez and colleagues report on the frequency of thyroid peroxidase antibodies (formerly known as thyroid microsomal antibodies) in pregnant women born in Mexico who were healthy, who had type 2 diabetes, or who had gestational diabetes. Thyroid peroxidase (TPO), an important enzyme in thyroid hormonogenesis, catalyzes the iodination of tyrosine residues of thyroglobulin (Tg) to form monoiodotyrosine and diiodotyrosine ( 1. Davies T.F. Pathogenesis of Hashimoto’s thyroiditis (chronic autoimmune thyroiditis). in: Up to Date. 7(3). 1999 Google Scholar ). It also couples iodotyrosyl residues to form triiodothyronine and thyroxine (T4). TPO is a 107-kd glycoprotein (933 amino acids) located on the luminal surface of the microvilli of thyroid epithelial cells, and its gene has been cloned ( 2. Magnusson R.P. Chazenbalk G.D. Gestautas J. et al. Molecular cloning of the complementary deoxyribonucleic acid for human thyroid peroxidase. Mol Endocrinol. 1987; 1: 856-861 Crossref PubMed Scopus (111) Google Scholar ). When the TPO is used as antigen in mice experiments, it induces autoimmune thyroiditis; this outcome provides evidence for its potential role in the pathogenesis of Hashimoto’s thyroiditis in humans ( 3. Kotani T. Umeki K. Hirai K. Ohtaki S. Experimental murine thyroiditis induced by porcine thyroid peroxidase and its transfer by the antigen-specific T cell line. Clin Exp Immunol. 1990; 80: 11-18 Crossref PubMed Scopus (56) Google Scholar ). Almost all patients with Hashimoto’s thyroiditis have high serum concentrations of antibodies to Tg and TPO, and lymphocytes from thyroid tissue of patients with Hashimoto’s thyroiditis secrete thyroid antibodies spontaneously in vitro. The antibodies are usually IgG1 or IgG3, which are able to fix complement and pass through the placenta. The autoimmune response to TPO is polyclonal, and these antibodies can lyse thyroid cells in vitro and inhibit TPO enzyme activity ( 1. Davies T.F. Pathogenesis of Hashimoto’s thyroiditis (chronic autoimmune thyroiditis). in: Up to Date. 7(3). 1999 Google Scholar ). These antibodies are also found at lower concentrations in patients with other thyroid diseases and in some persons, especially older women and relatives of patients with autoimmune thyroiditis, with no clinical or biochemical evidence of thyroid disease. TPO antibodies are more prevalent in patients with type 1 diabetes mellitus, another autoimmune disease. Kasim and Bessman ( 4. Kasim S. Bessman A. Thyroid autoimmunity in type 2 (non-insulin-dependent) diabetic patients of Caucasoid, black, and Mexican origin. Diabetologia. 1984; 27: 59-61 Crossref PubMed Scopus (5) Google Scholar ), however, did not find that the presence of thyroid microsomal antibodies was more common in persons with type 2 diabetes when compared with sex-and race-matched control subjects. These investigators noted that thyroid microsomal antibodies had a significantly higher frequency in Mexican women than in African American women. The current study confirms the finding that TPO antibodies are not more frequent in patients with type 2 diabetes—that is, TPO antibodies were detected in the serum of women without diabetes as frequently as in those with type 2 diabetes or gestational diabetes. Of interest, this study also found a high frequency of TPO antibodies in these pregnant Mexican women. Of the 150 pregnant women studied, 40 to 50%—whether healthy or with type 2 diabetes or gestational diabetes—had a slightly positive or strongly positive test result for TPO antibodies. This prevalence is much higher than that reported previously in pregnant patients (about 14%) ( 1. Davies T.F. Pathogenesis of Hashimoto’s thyroiditis (chronic autoimmune thyroiditis). in: Up to Date. 7(3). 1999 Google Scholar ). The question that arises is whether the presence of these antibodies has any clinical significance.