Autoantibodies in Thyroiditis

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Autoimmune thyroid diseases are characterized by the presence of autoantibodies to multiple thyroid antigens [1] including thyroglobulin (TG), thyroid peroxidase (TPO), and the TSHR. As mentioned above, these proteins play essential roles in the production of thyroid hormone. With respect to specific diseases, Over 90% and ~80% of patients with GD have anti-TSHR and anti-TPO autoantibodies, respectively, while over 90% of patients with HT have anti-TPO and/or anti-TG autoantibodies. Unlike anti-TSHR antibodies, anti-TPO and anti-TG antibodies do not play a significant role in the pathogenesis of either HT or GD. However, they are helpful in the differential diagnosis and may serve as predictors of ensuing thyroiditis. The Whickam study, an extensive population-based study, showed that after a 20-year follow-up, the odds ratio (with 95% confidence) of developing thyroiditis in individuals with thyroid autoantibodies and elevated TSH but normal free T4 was 38 (22-65) for men and 173 (81-370) for women [2, 3]. In another study, which followed patients with subclinical hypothyroidism (TSH levels > 4 mU L-1) for over nine years, 59% of women with TPO autoantibodies became hypothyroid as compared to 23% of women without TPO autoantibodies [4]. Similarly, the presence of TPO and TG autoantibodies, along with abnormal TSH levels, is associated with a higher incidence of hypothyroidism in juveniles and children, but the evidence is less compelling for pregnant women [1].

A large proportion of women (~20-40%) have thyroid infiltration, and 1020% of these women are positive for anti-TPO autoantibodies [1, 5]; however, only approximately 3% of women show clinical disease. Together, TPO and TG antibodies are useful in confirming the diagnosis of Hashimoto's thyroiditis. Some contend that TG autoantibodies, which rarely occur on their own, may not be as useful [6], while others claim specific disease associations. For example, presence of TG antibodies, without TPO antibodies, often could be indicative of thyroid hypertrophy and small nodules. However, in patients with HT, it is more common to find both antibodies rather than the anti-Tg antibodies alone [7]. Since the presence of TG-specific antibodies could interfere with the measurement of TG, and the TG levels in the sera serve as very useful markers to detect recurrence of thyroid cancer, testing for anti-TG antibodies to ensure that they are not interfering with the TG assay will aid in the proper diagnosis of thyroid cancers. Therefore, measurement of anti-TPO and anti-TG antibodies could be of significant clinical value. In contrast, anti-TSHR antibodies not only serve as reliable markers for GD and primary myxedema (PM) but also play a very important role in the pathogenesis of these diseases.

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