TPO antibodies: what a high thyroid peroxidase antibody level means
Thyroid peroxidase antibodies (TPO Ab) · Thyroid antibodies (ordered with TSH and free T4) · reported in IU/mL (some reports use U/mL or kIU/L, which are equivalent)
Thyroid peroxidase antibodies (TPO antibodies, anti-TPO) are antibodies your immune system makes against thyroid peroxidase, the enzyme inside thyroid cells that attaches iodine to thyroglobulin to build thyroid hormone. They are the most sensitive blood marker of autoimmune thyroid disease: about 90 to 95 percent of people with Hashimoto's thyroiditis have them, as do 50 to 80 percent of people with Graves' disease. A negative result is reported below a cut-off that varies more than most tests, from under 9 IU/mL on some assays to under 35 IU/mL on others, so the number on your report only means something next to the reference range printed beside it.
A positive TPO antibody test does not mean your thyroid has failed. Around 10 to 13 percent of the general US population carries these antibodies, most of them women, and the majority have a normal TSH and no symptoms. What the antibodies tell you is that the immune system is reacting against the thyroid and that your risk of becoming hypothyroid over the coming years is higher than average: roughly 2 percent per year if the TSH is normal, and about 4 percent per year if the TSH is already mildly raised. Very high titers (over 500 or 1,000 IU/mL) are more strongly linked to progression than borderline ones.
The test is ordered when TSH is abnormal and the cause is unclear, when a goiter or thyroid nodules are found, before and during pregnancy in women with a history of thyroid problems or miscarriage, and in people with other autoimmune conditions such as type 1 diabetes, celiac disease or vitiligo. Once a result is positive it usually stays positive, and there is little value in re-measuring the antibodies themselves; what is followed afterwards is the TSH.
TPO Ab at a glance
- What it is: an antibody against thyroid peroxidase, an enzyme in thyroid cells; the main marker of Hashimoto's thyroiditis and autoimmune thyroid disease.
- Normal: below the lab's cut-off, usually under 9 IU/mL, 34–35 IU/mL or 60 IU/mL depending on the assay; always compare with the range on your own report.
- Positive with a normal TSH: autoimmune thyroiditis without hypothyroidism yet; risk of hypothyroidism about 2 percent per year, so TSH is rechecked every 6 to 12 months.
- Positive with a high TSH: Hashimoto's hypothyroidism (or subclinical hypothyroidism likely to progress); levothyroxine is usually started once TSH is over 10 mIU/L, and considered between 4.5 and 10.
- Positive in pregnancy: higher risk of miscarriage, preterm birth and postpartum thyroiditis; TSH is checked each trimester and treatment is considered at a lower TSH threshold.
- Next step: TSH and free T4 now and at intervals, thyroid ultrasound only if there is a goiter or nodule, and a check for linked conditions (B12 deficiency, celiac disease) if symptoms suggest them.
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What TPO Ab measures
Thyroid peroxidase sits on the inner surface of thyroid follicular cells and catalyses the two key steps of hormone production: oxidising iodide and attaching it to tyrosine residues on thyroglobulin, then coupling them to form T4 and T3. In autoimmune thyroiditis, T cells and B cells infiltrate the gland and B cells produce antibodies against this enzyme. The antibodies themselves are mostly a marker rather than the main cause of damage (T-cell attack and complement do most of the harm), but their level correlates with how much lymphocytic infiltration the gland contains.
The lab measures TPO antibodies with an immunoassay in international units per millilitre (IU/mL) standardised against a World Health Organization reference preparation. Despite the shared unit, assays from different manufacturers give different numbers and use different cut-offs, which is why the same person can be 'positive' at one lab and 'negative' at another. Older reports called the same antibodies antimicrosomal antibodies and reported them as titers such as 1:400.
TPO antibodies do not need fasting and have no daily rhythm. Levels can fall by 30 to 50 percent during pregnancy (immune suppression) and rebound after delivery, drift down on long-term levothyroxine, and rise transiently after a viral thyroiditis. They say nothing about current thyroid function; that comes from TSH and free T4 on the same draw.
Normal range for TPO Ab
Reference ranges vary between labs and by age, sex and pregnancy. Use the range printed on your own report.
| Group | Typical range (IU/mL (some reports use U/mL or kIU/L, which are equivalent)) | Notes |
|---|---|---|
| Negative (normal) | Below the assay cut-off: under 9 IU/mL, under 34–35 IU/mL or under 60 IU/mL depending on the lab | Labs differ widely; read your number against the printed range, not against someone else's result. |
| Borderline or weakly positive | Just above the cut-off to roughly 100 IU/mL | May be a true early signal or assay noise. Weakly positive results with a normal TSH are often simply rechecked with TSH in 6 to 12 months. |
| Clearly positive | About 100–500 IU/mL | Typical of Hashimoto's thyroiditis or Graves' disease. The level does not tell you how well the thyroid is working; TSH and free T4 do. |
| Strongly positive | Above 500–1,000 IU/mL (some assays report a maximum such as 'over 600' or 'over 1,300') | More lymphocytic infiltration of the gland and a higher rate of progression to hypothyroidism, but many people at this level still have a normal TSH for years. |
| General population | About 10–13 percent of US adults are positive; more women than men | Prevalence rises with age; in women over 60 it reaches 20 percent or more. |
| Pregnancy | Antibody levels fall by 30–50 percent across pregnancy | A negative test in late pregnancy can turn positive after delivery; a positive test in the first trimester identifies women at risk of postpartum thyroiditis. |
| Children and teenagers | Same cut-offs as adults | Positive TPO antibodies in a child are investigated the same way; Hashimoto's is the commonest cause of hypothyroidism after infancy. |
High (positive) TPO antibodies
A positive TPO antibody test means your immune system is reacting against your thyroid, which is the definition of autoimmune thyroid disease. Combined with a high TSH, it confirms Hashimoto's thyroiditis as the cause of hypothyroidism and ends the search for other explanations. Combined with a low TSH and symptoms of overactivity, it is consistent with Graves' disease, although the thyrotropin receptor antibody (TRAb or TSI) is the specific test for that. In both conditions the antibody level is used to make the diagnosis, not to guide treatment.
Positive TPO antibodies with a normal TSH, the result most people searching this page have, means autoimmune thyroiditis that has not (yet) reduced thyroid output. In the 20-year Whickham follow-up, women with antibodies and a normal TSH developed overt hypothyroidism at about 2 percent per year, compared with 4 percent per year when TSH was also raised. Put another way, most will not become hypothyroid in the next decade, but enough will that an annual TSH is worthwhile, and sooner if symptoms appear or you become pregnant.
The height of the number matters less than people expect. A TPO of 1,000 IU/mL and a TPO of 150 IU/mL are both simply positive; the higher value indicates more immune activity in the gland and a somewhat higher chance of progression, but it does not mean more severe disease or worse symptoms now. Levels fluctuate by 20 to 30 percent between draws, so a change from 400 to 300 is not a meaningful improvement and a rise from 300 to 400 is not a deterioration.
Common causes
Hashimoto's thyroiditis (chronic autoimmune thyroiditis)
The commonest cause of hypothyroidism in iodine-sufficient countries and the cause of 90 to 95 percent of positive results in people with a raised TSH. Lymphocytes infiltrate the gland, which may enlarge (goiter) early and shrink later.
Graves' disease
The commonest cause of hyperthyroidism; 50 to 80 percent of patients have TPO antibodies alongside the TSH receptor antibodies that actually drive the overactivity. Positive TPO in Graves' predicts a higher chance of later hypothyroidism after treatment.
Autoimmune thyroiditis without thyroid dysfunction
About one in ten adults carries TPO antibodies with a normal TSH. This is the most common reason for a positive test in someone who feels well, and it is a risk state rather than a disease.
Postpartum thyroiditis
Occurs in 5 to 10 percent of women in the year after delivery, and in 30 to 50 percent of women who were TPO-positive in early pregnancy. A brief overactive phase at 1 to 4 months is followed by an underactive phase; about one in five is left permanently hypothyroid.
Other autoimmune conditions
Type 1 diabetes, celiac disease, pernicious anemia, vitiligo, Addison's disease, rheumatoid arthritis, lupus and Sjögren's syndrome each raise the chance of TPO antibodies to 20 to 30 percent; the test is often ordered as part of screening in these groups.
Excess iodine
Iodine intake well above requirements (iodine or kelp supplements, amiodarone, iodinated contrast) increases the rate of thyroid autoimmunity. A population study in China found the incidence of autoimmune thyroiditis was higher in areas with excessive iodine intake than where intake was adequate.
Medications that trigger thyroid autoimmunity
Interferon-alpha, interleukin-2, immune checkpoint inhibitors (nivolumab, pembrolizumab, ipilimumab), alemtuzumab and lithium can induce or unmask thyroid autoimmunity, with TPO antibodies appearing during treatment.
Family history and genetics
Thyroid autoimmunity clusters in families; having a first-degree relative with Hashimoto's or Graves' roughly doubles to triples the chance of carrying antibodies. Turner and Down syndromes also carry a high rate.
Transient rise after subacute (viral) thyroiditis
Painful viral thyroiditis releases thyroid antigens and can cause low-level TPO antibodies for some months that then disappear; a persistently positive result afterwards suggests underlying autoimmune disease.
Symptoms that can go with it
- Often none: most people with positive TPO antibodies and a normal TSH feel entirely well
- If hypothyroidism has developed: tiredness, feeling cold, weight gain, constipation, dry skin, hair thinning, heavier periods, low mood, slowed thinking
- A painless, firm, symmetrical swelling at the front of the neck (goiter), sometimes with a sense of fullness or tightness
- If Graves' disease: weight loss, heat intolerance, palpitations, tremor, anxiety, eye grittiness or bulging
- In the months after childbirth: a short spell of anxiety and palpitations followed by fatigue and low mood (postpartum thyroiditis)
- Irregular or absent periods, difficulty conceiving, or recurrent early miscarriage
- Symptoms of linked conditions, such as numbness or tingling (B12 deficiency) or bloating and diarrhea (celiac disease)
Negative or low TPO antibodies
A negative TPO antibody test means no detectable autoimmune reaction against thyroid peroxidase, which makes autoimmune thyroiditis less likely as the explanation for an abnormal TSH, but not impossible. About 5 to 10 percent of people with Hashimoto's thyroiditis proven on ultrasound or biopsy are antibody-negative, and in these cases a thyroglobulin antibody test or an ultrasound showing the typical patchy, low-echo gland may clinch it.
There is no such thing as a TPO level that is 'too low'. A result reported as under 9, under 1 or simply 'negative' is the normal state and has no medical significance. If your TSH is high and antibodies are negative, the clinician looks for other causes of hypothyroidism: past thyroid surgery or radioiodine, neck radiotherapy, medications (amiodarone, lithium, checkpoint inhibitors), iodine deficiency or excess, congenital causes, or a pituitary problem.
Common causes
Normal, with no thyroid autoimmunity
The expected result in about 87 to 90 percent of adults. It does not need repeating unless a new thyroid problem develops.
Seronegative Hashimoto's thyroiditis
A minority of people with lymphocytic thyroiditis on ultrasound or biopsy have no detectable TPO antibodies; thyroglobulin antibodies are positive in some of them.
Non-autoimmune hypothyroidism
Thyroid surgery, radioiodine, external radiotherapy to the neck, amiodarone, lithium, iodine deficiency, infiltrative disease and central (pituitary) hypothyroidism all lower thyroid function without antibodies.
Antibodies that have faded on treatment or after pregnancy-related suppression
Titers can fall below the cut-off in the second half of pregnancy and in some people after years of levothyroxine, so a single negative result in someone with a past positive does not change the diagnosis.
Assay cut-off differences
A result of 20 IU/mL is negative on an assay with a cut-off of 34 but positive on one with a cut-off of 9. Check which range your lab uses before comparing with an earlier test elsewhere.
Symptoms that can go with it
- None; a negative result causes no symptoms
- If you have hypothyroid symptoms and a high TSH with negative antibodies, the symptoms still need treating; the negative antibody only changes the search for the cause
Read it alongside
- TSH — the test that says whether the thyroid is actually underactive; positive antibodies with a normal TSH is a risk state, with a TSH over 10 mIU/L it is hypothyroidism.
- Free T4 — low with a high TSH confirms overt hypothyroidism; normal with a mildly raised TSH is subclinical hypothyroidism.
- Thyroglobulin antibodies — the second thyroid autoantibody; positive in some antibody-negative Hashimoto's and essential in thyroid cancer follow-up.
- TSH receptor antibodies (TRAb or TSI) — the specific test for Graves' disease when TSH is low.
- Free T3 — helps characterise hyperthyroidism and is rarely needed in hypothyroidism.
- Vitamin B12 — pernicious anemia coexists with autoimmune thyroiditis in a few percent of patients and causes overlapping fatigue and numbness.
- tTG-IgA (celiac screen) — celiac disease is found in 2 to 5 percent of people with autoimmune thyroid disease and can impair levothyroxine absorption.
- Thyroid ultrasound — not a blood test, but the patchy low-echogenicity pattern of Hashimoto's can confirm the diagnosis when antibodies are borderline.
What usually happens next
- If TSH and free T4 are normal: no treatment; repeat TSH in 6 to 12 months and sooner if you develop symptoms, become pregnant or start a medication that affects the thyroid.
- If TSH is 4.5 to 10 mIU/L with normal free T4 (subclinical hypothyroidism): positive antibodies roughly double the rate of progression, which tips many clinicians toward a levothyroxine trial, particularly with symptoms, a goiter, pregnancy plans or a TSH drifting upward on repeat.
- If TSH is over 10 mIU/L or free T4 is low: levothyroxine replacement is standard regardless of antibody level; TSH is rechecked 6 to 8 weeks after each dose change.
- If you are pregnant or planning pregnancy: ask for TSH testing at confirmation of pregnancy and each trimester, and expect treatment to be considered if TSH rises above 2.5 to 4 mIU/L; mention any history of miscarriage.
- If TSH is low: ask about TSH receptor antibodies and whether a thyroid uptake scan is needed to tell Graves' disease from thyroiditis.
- Do not expect the antibody level to be re-measured routinely; it does not guide dosing and a lower or higher number does not change what is done.
Diet, lifestyle and natural levers with evidence
What can move TPO Ab once the cause is known. Nothing here replaces finding the cause.
Selenium
Moderate evidenceA meta-analysis of 16 randomised trials found that 200 mcg a day of selenium (usually selenomethionine) lowered TPO antibody levels at 3, 6 and 12 months in people with Hashimoto's taking levothyroxine, with reductions of around 20 to 50 percent of baseline in several trials, and at 3 months in those not on levothyroxine. Thyroid function, levothyroxine dose and symptoms were not clearly improved, and a Cochrane review judged the evidence insufficient for clinical benefit. It is most likely to help where selenium intake is low.
Keep total intake under 400 mcg a day; chronic excess causes hair and nail loss, nausea and nerve symptoms. One large trial linked 200 mcg a day to a higher rate of type 2 diabetes. Do not add selenium if you already eat Brazil nuts regularly without checking a level.
Vitamin D, if you are deficient
Preliminary evidenceLow vitamin D is consistently more common in people with Hashimoto's than in controls, and a meta-analysis of small randomised trials found that vitamin D supplementation (typically 1,000 to 4,000 IU a day, or weekly equivalents, for 3 to 6 months) lowered TPO antibody levels, with no clear effect on TSH. The trials were short, mostly in deficient people, and did not measure whether hypothyroidism was prevented. Correcting a level under 20 ng/mL is reasonable; megadoses are not.
Above 4,000 IU a day without monitoring risks high calcium; check a 25-hydroxyvitamin D level first.
Avoid excess iodine
Moderate evidenceIodine is needed to make thyroid hormone, but more than the thyroid needs increases thyroid autoimmunity and hypothyroidism: a five-year study of three Chinese regions found that areas with more-than-adequate or excessive iodine intake had higher rates of new autoimmune thyroiditis and subclinical hypothyroidism than an area with adequate intake. Adults need about 150 mcg a day (220 to 290 mcg in pregnancy and breastfeeding), which a normal diet with iodised salt supplies; kelp, bladderwrack and high-dose iodine drops supply far more.
Do not restrict iodine in pregnancy; a prenatal vitamin with 150 mcg is recommended. Mention amiodarone or recent contrast scans to your clinician.
Myo-inositol with selenium
Preliminary evidenceIn a 6-month randomised trial of 48 people with subclinical hypothyroidism and positive antibodies, 600 mg of myo-inositol plus 83 mcg of selenium lowered TSH by about 30 percent and reduced TPO and thyroglobulin antibody levels more than selenium alone. Later open-label studies reported similar antibody falls, but no large placebo-controlled trial has confirmed a clinical benefit.
Gluten-free diet, mainly if celiac disease is present
Preliminary evidenceCeliac disease is found in 2 to 5 percent of people with autoimmune thyroid disease, and in them a gluten-free diet improves absorption of levothyroxine and is treatment in its own right. In a 6-month pilot study of 34 women with Hashimoto's and no celiac disease, a gluten-free diet lowered TPO and thyroglobulin antibodies modestly compared with a normal diet, but it did not change TSH or free T4. The sensible step is to be screened for celiac disease rather than to remove gluten untested.
Going gluten-free before celiac testing makes the blood test and biopsy unreliable; test first.
When to see a clinician promptly
- Positive TPO antibodies with a TSH over 10 mIU/L, or a low free T4, which is overt hypothyroidism that needs treatment rather than observation.
- A positive result and you are pregnant, trying to conceive or have had a miscarriage: TSH needs checking at a lower treatment threshold and in each trimester.
- Severe hypothyroid features: marked slowing, confusion, a body temperature below normal, a slow pulse or extreme drowsiness, particularly in older adults in cold weather; myxedema coma is an emergency.
- A low TSH with a racing or irregular heartbeat, chest pain, fever, agitation or confusion: possible thyroid storm, needs emergency care.
- A rapidly enlarging, hard or painful thyroid, a single growing nodule, hoarseness, or difficulty swallowing or breathing.
- Hypothyroid symptoms that persist despite a normal TSH on treatment, or new symptoms such as numbness, bloating and diarrhea, or dizziness on standing, which may point to a linked condition (B12 deficiency, celiac disease, adrenal insufficiency).
Frequently asked questions
What is a normal TPO antibody level?
Normal is below the cut-off your lab prints next to the result, and that cut-off varies more than for most tests: under 9 IU/mL on some assays, under 34 or 35 on others, and under 60 on a few. A result below the cut-off is negative. Because the assays differ, a value of 25 IU/mL can be positive at one lab and negative at another, so compare with your own report, not with ranges quoted online.
Is a TPO of 100, 500 or 1,000 high?
All three are positive on every assay, and all three mean the same thing: autoimmune thyroid disease. A TPO of 1,000 IU/mL indicates more immune activity in the gland and a somewhat higher chance of progressing to hypothyroidism than 100, but it does not mean your thyroid is working worse right now; only TSH and free T4 tell you that. Values over 1,000 are common in Hashimoto's and are not an emergency.
What does it mean if my TPO antibodies are high but my TSH is normal?
It means you have autoimmune thyroiditis that has not reduced your thyroid output. About one in ten adults is in this position. Your risk of becoming hypothyroid is around 2 percent per year, roughly eight times that of someone without antibodies, so the usual plan is a TSH check every 6 to 12 months, no medication, and a lower threshold for testing if you develop symptoms or become pregnant. Treating with levothyroxine while TSH is normal has not been shown to help.
Does a high TPO mean I have Hashimoto's?
Positive TPO antibodies are the laboratory hallmark of Hashimoto's thyroiditis, and most clinicians use the term for anyone with positive antibodies, whether or not the thyroid has become underactive. Strictly, 'Hashimoto's hypothyroidism' needs a raised TSH as well. Positive TPO antibodies also occur in Graves' disease, after viral thyroiditis and in people with other autoimmune diseases, so the whole picture (TSH, free T4, symptoms, examination) decides the label.
Can TPO antibodies go down or go away?
They fluctuate and can drift down over years, especially on levothyroxine, during pregnancy and with selenium or vitamin D in some trials, but they rarely disappear altogether once established, and falling antibodies do not reliably mean the thyroid is recovering. Clinicians do not re-measure them routinely because the level does not change management. The number to follow is TSH.
Should I take levothyroxine if my TPO antibodies are high?
Not on the basis of the antibodies alone. Levothyroxine is started when TSH is over 10 mIU/L or free T4 is low, and considered when TSH is between 4.5 and 10, where positive antibodies, symptoms, a goiter or pregnancy plans tip the balance toward treating. In pregnancy the threshold is lower: guidelines advise treatment for TPO-positive women with a TSH above 4 mIU/L and suggest considering it above 2.5. A trial in antibody-positive women with normal TSH found levothyroxine did not increase live births.
What is the difference between TPO antibodies and thyroglobulin antibodies?
Both are thyroid autoantibodies, but against different targets. TPO antibodies attack the enzyme that makes thyroid hormone and are the more sensitive and specific marker of Hashimoto's. Thyroglobulin antibodies attack the storage protein, are positive in a smaller share of Hashimoto's patients, and have a second, separate use: they are measured alongside thyroglobulin in thyroid cancer follow-up because they interfere with that test. Labs usually run both when screening for autoimmune thyroid disease.
Can I get pregnant with high TPO antibodies?
Yes. Most women with positive antibodies and a normal TSH conceive and carry normally. The antibodies are associated with a higher rate of miscarriage and preterm birth, and with a 30 to 50 percent chance of postpartum thyroiditis, so the practical steps are a TSH check before conception and in each trimester, treatment if TSH rises above the pregnancy threshold, and a TSH at about 3 and 6 months after delivery. Taking levothyroxine when TSH is normal has not been shown to improve pregnancy outcomes.
References
- Thyroid antibodies. MedlinePlus, US National Library of Medicine (2023)View source
- Hashimoto's disease. Mayo Clinic (2024)View source
- Hashimoto thyroiditis. Merck Manual Professional Version (2024)View source
- Hollowell JG, Staehling NW, Flanders WD, et al.. Serum TSH, T4, and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). Journal of Clinical Endocrinology and Metabolism (2002)
- Vanderpump MP, Tunbridge WM, French JM, et al.. The incidence of thyroid disorders in the community: a twenty-year follow-up of the Whickham Survey. Clinical Endocrinology (1995)
- Jonklaas J, Bianco AC, Bauer AJ, et al.. Guidelines for the treatment of hypothyroidism: prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement. Thyroid (2014)
- Alexander EK, Pearce EN, Brent GA, et al.. 2017 Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and the postpartum. Thyroid (2017)
- Dhillon-Smith RK, Middleton LJ, Sunner KK, et al.. Levothyroxine in women with thyroid peroxidase antibodies before conception (TABLET trial). New England Journal of Medicine (2019)
- Wichman J, Winther KH, Bonnema SJ, Hegedüs L. Selenium supplementation for Hashimoto's thyroiditis: a systematic review and meta-analysis. Thyroid (2016)
- Teng W, Shan Z, Teng X, et al.. Effect of iodine intake on thyroid diseases in China. New England Journal of Medicine (2006)
- Nordio M, Pajalich R. Combined treatment with myo-inositol and selenium ensures euthyroidism in subclinical hypothyroidism patients with autoimmune thyroiditis. Journal of Thyroid Research (2013)
- Krysiak R, Szkróbka W, Okopień B. The effect of gluten-free diet on thyroid autoimmunity in drug-naïve women with Hashimoto's thyroiditis: a pilot study. Experimental and Clinical Endocrinology and Diabetes (2019)
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