Thyroid Biomarkers: TPO Antibodies

Optimal Takeaways

The presence of thyroid peroxidase antibodies increases the risk of destruction and dysfunction of the thyroid gland leading to autoimmune thyroid diseases, including Hashimoto’s and Graves. Most individuals with these autoimmune disorders will have elevated TPO antibodies. However, some individuals may not be elevated, and levels may decrease once the condition is under control.

Elevated levels can be associated with autoimmune thyroid disease, thyroid cancer, lymphocytic thyroiditis, nodular goiter, rheumatoid arthritis, pernicious anemia, and breast cancer. Low levels of TPO antibodies suggest the absence of active autoimmune thyroid disease.

*Standard Range: 0.00 – 9.00 IU/mL (0.00 – 9.00 kIU/L)

The ODX Range: 0.00 – 6.80 IU/mL (0.00 - 6.80 kIU/L)

Low levels of TPO antibodies suggest the absence or remission of active autoimmune thyroiditis (Jeena 2013).

High levels of TPO antibodies are associated with hypothyroidism, Hashimoto’s thyroiditis, thyrotoxicosis, thyroid cancer, myxedema, rheumatoid arthritis, pernicious anemia (Pagana 2021), Graves’ disease, lymphocytic thyroiditis, nodular goiter (Jeena 2013), breast cancer (Ali 2013), post-partum thyroiditis, and insufficiency of selenium, and excess or insufficiency of iodine (Rayman 2019).

Overview

Thyroid peroxidase (TPO) antibodies, also known as anti-microsomal antibodies, are produced when cell fragments from the thyroid trigger a cytotoxic antibody response (Pagana 2021).

Thyroid peroxidase is the enzyme in the thyroid that facilitates the incorporation of iodine into thyroid hormones. Antibodies to TPO are present in most individuals with autoimmune thyroid disease, e.g., Hashimoto’s thyroiditis and Graves’ disease. Elevated TPO antibodies are also seen with nodular goiter and thyroid cancer. A retrospective cross-sectional study of 74 hospitalized patients being evaluated for thyroid disorders observed that two of the three hyperthyroid subjects had positive TPO antibodies with levels twice the upper limit of the standard range. TPO antibodies were increased in 60% of those diagnosed with hypothyroidism, with a mean TPO antibody level of 285 IU/mL. Researchers note that some hypothyroid patients had no antibodies, while some euthyroid subjects had elevated antibodies. The latter suggests a subclinical autoimmune process that may be associated with dysfunction in the future. Predisposing risk factors for autoimmunity should be evaluated, including genetic factors, aging, stress, infection, smoking, trauma, female gender, and nutrition status (Jeena 2013).

Micronutrients are vital to thyroid metabolism, including iodine, selenium, and iron, and insufficiency or excess can jeopardize thyroid homeostasis. TPO antibodies may increase with both excess and deficiency of iodine. Iron deficiency is common in autoimmune thyroiditis though it may be due to underlying conditions such as autoimmune gastritis or celiac disease, especially with ferritin below 70 ug/ L. Selenium is concentrated in the thyroid, and an insufficiency increases the risk of autoimmune thyroiditis. Sufficiency, on the other hand, reduces the risk of thyroid pathology and autoimmune thyroid disease. Higher selenium levels and supplementation, where appropriate, are associated with lower TPO antibodies in both Graves’ and Hashimoto’s autoimmune thyroiditis and with reduced symptoms in Graves’ (Rayman 2019).

The selenium content of food depends significantly on its availability in the soil on a regional basis. Selenium status should be assessed as part of a thyroid evaluation. Decreased vitamin D levels have been associated with increased TPO and thyroglobulin antibodies. However, researchers indicate that the association is unclear and that compromised vitamin D status may be due to the autoimmune process itself (Hu 2017).

Nutrient deficiencies are common in Hashimoto’s, including vitamins A, Bs, C, and D, copper, iron, iodine, magnesium, potassium, selenium, zinc, omega-3 fatty acids, fiber, and water. Modifying the diet in Hashimoto’s should ensure adequate intake of micronutrients and protein and may call for eliminating gluten if gluten intolerance is present. Celiac disease is up to 10 times higher in Hashimoto’s patients than in the general population, and in some cases, underlying celiac disease may cause nutrient deficiencies. In one study of 34 women newly diagnosed with Hashimoto’s and anti-tissue transglutaminase antibodies, a gluten-free diet significantly decreased TPO and thyroglobulin antibodies (Ihnatowicz 2020).

Thyroid dysfunction is prevalent and may contribute to increased morbidity from cardiovascular disease, neuropsychiatric disorders, hyperhomocysteinemia, hyperlipidemia, and osteoporosis. Subclinical and overt hypothyroidism and hyperthyroidism should be identified early to minimize their pathology. Detection of elevated thyroid antibodies can assist in clinical assessment (Legakis 2013).

Thyroid antibodies are detectable in Graves’ and Hashimoto’s several years before clinical diagnosis, and early evaluation may help identify those likely to develop the disease. A case-control study of 522 female active-duty personnel, comprising 87 Hashimoto’s cases, 87 Graves’ cases, and 348 controls, revealed that a significant number of those diagnosed with autoimmune thyroid disease had elevated TPO antibodies for several years prior to an official diagnosis. In those ultimately diagnosed with Hashimoto’s, 66% had elevated TPO antibodies for the entire 7-year assessment period prior to diagnosis, and 53% had elevated thyroglobulin antibodies during the same period. In those with Graves, 31% had elevated TPO antibodies in the 5-7 years prior to diagnosis (Hutfless 2011).

Accumulating research suggests an association between thyroid disorders and breast cancer though the extent of the association is still under investigation. In one study of 100 breast cancer patients and 75 controls, TPO antibodies were significantly higher than controls. At the same time, TSH, free T3, and free T4 were also more elevated in breast cancer patients but not significantly (Ali 2011).

*The ranges for TPO antibodies can differ between labs, though the basic background information for understanding their physiological importance remains the same. For example, the following ranges and different assessment methods are used by Labcorp:

Standard Range: 0.00 – 34.00 IU/mL (0.00 – 34.00 kIU/L)

The ODX Range: 0.00 – 34.00 IU/mL (0.00 – 34.00 kIU/L)

References

Ali, Athar, et al. "Relationship between the levels of serum thyroid hormones and the risk of breast cancer." J Biol Agr Healthc 2 (2011): 56-60

Hu, Shiqian, and Margaret P Rayman. “Multiple Nutritional Factors and the Risk of Hashimoto's Thyroiditis.” Thyroid: official journal of the American Thyroid Association vol. 27,5 (2017): 597-610. doi:10.1089/thy.2016.0635

Hutfless, Susan et al. “Significance of prediagnostic thyroid antibodies in women with autoimmune thyroid disease.” The Journal of clinical endocrinology and metabolism vol. 96,9 (2011): E1466-71. doi:10.1210/jc.2011-0228

Ihnatowicz, Paulina et al. “The importance of nutritional factors and dietary management of Hashimoto's thyroiditis.” Annals of agricultural and environmental medicine : AAEM vol. 27,2 (2020): 184-193. doi:10.26444/aaem/112331

Jeena, E. Jacob, M. Malathi, and K. Sudeep. "A hospital-based study of anti-TPO titer in patients with thyroid disease." Muller Journal of Medical Sciences and Research 4.2 (2013): 74.

Legakis, Ioannis et al. “Thyroid function and prevalence of anti-thyroperoxidase (TPO) and anti-thyroglobulin (Tg) antibodies in outpatients hospital setting in an area with sufficient iodine intake: influences of age and sex.” Acta medica Iranica vol. 51,1 (2013): 25-34.

Nishihara, Eijun et al. “Moderate Frequency of Anti-Thyroglobulin Antibodies in the Early Phase of Subacute Thyroiditis.” European thyroid journal vol. 8,5 (2019): 268-272. doi:10.1159/000501033

Pagana, Kathleen Deska, et al. Mosby's Diagnostic and Laboratory Test Reference. 15th ed., Mosby, 2021.

Rayman, Margaret P. “Multiple nutritional factors and thyroid disease, with particular reference to autoimmune thyroid disease.” The Proceedings of the Nutrition Society vol. 78,1 (2019): 34-44. doi:10.1017/S0029665118001192