TPO antibodies are immune proteins that mistakenly attack thyroid peroxidase, an enzyme your thyroid gland needs to produce hormones. Their presence in your blood signals that your immune system is targeting your own thyroid, and they’re the most common marker used to diagnose autoimmune thyroid disease. A result above 5.6 IU/mL is generally considered positive, though exact reference ranges vary by lab.
What Thyroid Peroxidase Does
Thyroid peroxidase (TPO) is an enzyme that sits on the surface of thyroid cells. Its job is to convert iodide from your bloodstream into active iodine atoms, then attach those atoms to a protein called thyroglobulin. This chemical reaction is the essential first step in making the two thyroid hormones your body depends on for metabolism, energy, and temperature regulation.
When your immune system produces antibodies against this enzyme, those antibodies trigger a destructive process that damages and gradually kills thyroid cells. Over time, this ongoing attack can reduce the gland’s ability to make hormones, leading to hypothyroidism. The damage doesn’t happen overnight. It can unfold over months or years, which is why some people test positive for TPO antibodies long before they notice any symptoms or show abnormal thyroid hormone levels.
Conditions Linked to TPO Antibodies
The condition most strongly associated with TPO antibodies is Hashimoto’s thyroiditis, the leading cause of hypothyroidism in developed countries. Most people diagnosed with Hashimoto’s have detectable TPO antibodies in their blood, making the test a key part of confirming the diagnosis. If your thyroid hormone levels are already low and a blood test reveals elevated TPO antibodies, Hashimoto’s is the likely explanation.
TPO antibodies also show up in Graves’ disease, the most common cause of hyperthyroidism. In one study of Graves’ disease patients, about 69% tested positive for TPO antibodies. Graves’ disease is primarily driven by a different antibody that stimulates the thyroid rather than destroying it, but the two types of antibodies frequently coexist.
A smaller number of people with positive TPO antibodies don’t have either condition. Mild elevations can occasionally appear in people with no thyroid disease at all, particularly older adults and women.
What Happens If You Test Positive
Testing positive doesn’t automatically mean you have or will develop thyroid disease. Research from a large population-based study in Tehran tracked people who were euthyroid (meaning their thyroid function was normal) but had positive TPO antibodies. After three years, about 65% remained euthyroid. Roughly 9% progressed to subclinical hypothyroidism, a mild, early form where TSH rises slightly but thyroid hormones stay in range. Only about 3% developed overt hypothyroidism or hyperthyroidism.
Among those who were still euthyroid at the three-year mark, the pattern continued: after six years total, 72% still had normal thyroid function, while 19% had developed subclinical hypothyroidism. The progression is real but gradual, and not everyone with positive antibodies ends up needing treatment. Regular monitoring, typically an annual thyroid function test, helps catch changes early.
Symptoms Even With Normal Thyroid Levels
One of the more frustrating aspects of TPO antibody positivity is that some people experience symptoms even when their thyroid hormone levels look perfectly normal on paper. Research estimates that roughly 5 to 10% of people with Hashimoto’s thyroiditis report persistent fatigue, weight gain, cold intolerance, constipation, or depression despite achieving normal TSH and free T4 levels with or without treatment.
Studies have found that individuals with positive TPO antibodies specifically report higher rates of fatigue, cognitive difficulty (sometimes called “brain fog”), irritability, and depressive mood compared to people without the antibodies, independent of thyroid hormone levels. The reasons aren’t fully understood, but the ongoing immune activity itself may contribute to how people feel, separate from whether the gland is producing enough hormone.
TPO Antibodies and Pregnancy
TPO antibody status carries particular importance for women who are pregnant or trying to conceive. Research comparing euthyroid women with and without TPO antibodies found that antibody-positive women had significantly higher rates of infertility, anemia, and preterm delivery. In one study, preterm birth occurred in 12.5% of the antibody-positive group versus 2.5% of controls.
Interestingly, the same study did not find a statistically significant difference in recurrent miscarriage rates between the two groups, and complications like preeclampsia and growth restriction were similar. The risks appear concentrated around fertility challenges and early delivery rather than a broad increase in every pregnancy complication. Because of these findings, many providers check TPO antibodies as part of a fertility workup or early prenatal screening, especially in women with a personal or family history of thyroid disease.
How Treatment Decisions Are Made
If your thyroid function is already clearly abnormal, with TSH above 10, guidelines from the American Thyroid Association and the American Association of Clinical Endocrinologists recommend thyroid hormone replacement. The role of TPO antibodies becomes more relevant in borderline cases.
For people with mildly elevated TSH (roughly 4.5 to 7.0) and no obvious symptoms, treatment isn’t automatic. But positive TPO antibodies tip the scale toward starting replacement therapy, because they signal that the thyroid is under immune attack and function is more likely to decline further. Other factors that influence the decision include whether you have symptoms of hypothyroidism, a goiter, cardiovascular risk factors, or plans for pregnancy.
If you’re euthyroid with positive antibodies, the typical approach is watchful waiting with periodic blood work rather than immediate treatment.
Selenium and Antibody Levels
Selenium supplementation is the most studied intervention for lowering TPO antibody levels without thyroid medication. In a clinical trial of euthyroid patients with autoimmune thyroiditis, 200 micrograms per day of selenium for three months produced a significant decrease in TPO antibody titers, with a median drop of about 106 IU/mL. The control group saw no meaningful change over the same period.
These results are promising, but a drop in antibody numbers on a lab report doesn’t necessarily translate to better thyroid function or fewer symptoms. Selenium is a trace mineral with a narrow safety window, and long-term supplementation above 400 micrograms per day can cause toxicity. If you’re considering it, the dose used in trials (200 micrograms) is well within safe limits for most adults, but it’s worth discussing with your provider, especially if you’re already getting selenium through diet or a multivitamin.