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November 1, 2021

What Does Elevated Anti-TPO Mean if Other Thyroid Markers are Normal?

Thyroid peroxidase (TPO) is the enzyme that attaches iodine to the amino acid tyrosine to form thyroxine (T4 thyroid hormone). Autoantibodies against TPO attack the thyroid gland itself, initially causing the release of T4 followed by a compensating decrease in TSH.

Anti-TPO antibodies should be investigated even if other thyroid biomarkers are normal or even optimal. Elevated antibodies could be an early sign of developing autoimmune thyroid disease.

Researchers suggest anti-TPO should be added to TSH and thyroid hormone measurement or used as a standalone marker for detecting early stages of autoimmune thyroiditis. Anti-TPO is considered a more sensitive autoimmune marker than anti-thyroglobulin antibodies which are more sensitive for detecting differentiated thyroid cancer. However, both antibodies may be detected up to 7 years prior to a diagnosis of autoimmune thyroid disease so early assessment is prudent.[i]

Chronic autoimmune thyroiditis, known as Hashimoto thyroiditis or chronic lymphocytic thyroiditis, is the primary cause of hypothyroidism in developed countries. It is characterized by the destruction of thyroid tissue by the body’s own immune system.

Though biochemical evidence may not be present early in the disease, the hallmark blood chemistry profile once Hashimoto’s has progressed is an elevated TSH, decreased free and total thyroid hormones, and in most cases elevated anti-TPO. Antithyroglobulin and TSH receptor-blocking antibodies may be present as well.[ii]

A 2-year evaluation of thyroid biomarkers in 4,581 euthyroid subjects revealed that 73% of those who developed hypothyroidism were positive for anti-TPO an average of 252 days prior to the disruption of thyroid hormone levels.[iii]

Thyroid function is heavily dependent on nutritional status and can be impaired by the insufficiency of key micronutrients. These include vitamins A, D, B2, B12, and folate, calcium, chromium, copper, iodine, iron, selenium, zinc, tyrosine, phenylalanine, asparagine, carnitine, and serine. Specific observations include significantly lower serum T4 with riboflavin (B2) deficiency; significantly increased levels of TSH, anti-TPO, and anti-Tg with folate deficiency; and significantly elevated anti-TPO with carnitine deficiency. Circulating thyroid hormones may be decreased due to the lack of amino acids required for carrier protein synthesis.[iv]

Vitamin D deficiency is associated with an increased incidence of autoimmune disorders. In newly diagnosed Hashimoto’s and Graves’ disease patients, vitamin D levels were deficient at 17.05 ng/mL (42.6 nmol/L) and 14.9 ng/mL (37.2 nmol/L) respectively, well below optimal levels. Low serum vitamin D was significantly associated with elevated anti-TPO in these groups.[v]

Supplementation with 200 ug/day of sodium selenite decreased anti-TPO antibodies in a prospective study of women with autoimmune thyroiditis and mild selenium deficiency. Antibody levels completely normalized in nine women receiving supplementation.[vi] Supplementation with selenium should be done with caution and may not be indicated in selenium-sufficient individuals.

Elevated anti-TPO is also independently associated with elevated homocysteine in both Hashimoto’s and Graves’ disease.[vii] Micronutrient insufficiency associated with homocysteine metabolism should be addressed including vitamins B6, B12, and folate.

Here you can see that assessing anti-TPO as well as micronutrient status can enhance evaluation of thyroid function and risk of dysfunction and, ideally, delay or prevent the onset of disease.


[i] Siriwardhane, Thushani et al. “Significance of Anti-TPO as an Early Predictive Marker in Thyroid Disease.” Autoimmune diseases vol. 2019 1684074. 28 Jul. 2019, doi:10.1155/2019/1684074

[ii] Mincer, Dana L. and Ishwarlal Jialal. “Hashimoto Thyroiditis.” StatPearls, StatPearls Publishing, 28 September 2021.

[iii] Siriwardhane, Thushani et al. “Significance of Anti-TPO as an Early Predictive Marker in Thyroid Disease.” Autoimmune diseases vol. 2019 1684074. 28 Jul. 2019, doi:10.1155/2019/1684074

[iv] Krishnamurthy, Hari Krishnan, et al. "Effect of Micronutrients on Thyroid Parameters." Journal of Thyroid Research 2021 (2021)

[v] Unal, Asli Dogruk et al. “Vitamin D deficiency is related to thyroid antibodies in autoimmune thyroiditis.” Central-European journal of immunology vol. 39,4 (2014): 493-7. doi:10.5114/ceji.2014.47735

[vi] Gärtner, Roland et al. “Selenium supplementation in patients with autoimmune thyroiditis decreases thyroid peroxidase antibodies concentrations.” The Journal of clinical endocrinology and metabolism vol. 87,4 (2002): 1687-91. doi:10.1210/jcem.87.4.8421

[vii] Li, Fang et al. “Thyroid Peroxidase Antibody is Associated with Plasma Homocysteine Levels in Patients with Graves' Disease.” Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association vol. 128,1 (2020): 8-14. doi:10.1055/a-0643-4692

Tag(s): Biomarkers

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