Thyroid peroxidase antibodies (TPO antibodies)
TPO antibodies mark autoimmune thyroid disease. Cutoffs depend on the assay: five assays run on the same men gave upper limits from 6.4 to 28.7 IU/mL. Positive results went with more later hypothyroidism, miscarriage and preterm birth. In two large trials, levothyroxine for antibody-positive women with normal thyroid function did not change live births or miscarriage.
- Status
- A blood test ordered by a clinician and also sold direct to consumers by some US laboratories. FDA classifies thyroid autoantibody immunological test systems as class II devices [1]. The cutoff for a positive result depends on the assay, and the US National Library of Medicine describes a normal result only as a negative test [2][3].
- Measures
- Antibodies in blood against thyroid peroxidase, an enzyme of the thyroid gland. A related test measures antibodies against thyroglobulin [1][4].
- Also called
- TPO antibodies, TPOAb, TPO Ab, anti-TPO, thyroid peroxidase antibodies, thyroperoxidase antibodies, antithyroid peroxidase antibodies, antimicrosomal antibodies, thyroid microsomal antibodies, thyroid antibodies, thyroid autoantibodies, thyroglobulin antibodies, TgAb, anti-Tg, antithyroglobulin antibodies
- Tested for
- Hashimoto thyroiditis, autoimmune thyroid disease, cause of an underactive thyroid, risk of future hypothyroidism, miscarriage risk, pregnancy planning
Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on
Linked in research3
- StrongLinked to more miscarriage and preterm birth in women with normal thyroid function, with preterm birth in 6.6% of antibody-positive women against 4.9%.
- ModerateLinked to later hypothyroidism: over 20 years, women with thyroid antibodies alone had 8 times the odds, and 38 times with a raised TSH as well.
- LimitedLimited evidence: a guideline review reports postpartum thyroiditis in 33 to 50% of women who were thyroid antibody positive in the first trimester.
Reported risks0
No risks sourced yet.
Reference ranges
Each range is the one its source published, in IU/mL. Where sources differ, each is shown.
Busselton Health Study, Australia, 2010, assay reference limit
Adults tested with the Immulite immunoassay · [5]
| Range | What the source calls it |
|---|---|
| 35 or below IU/mL | "reference range" |
| above 35 IU/mL | No name given |
The upper limit of the reference range for the Immulite platform used in this cohort, printed as 35 kIU/L, which is the same number as IU/mL. It applies to that assay only. In one comparison of five automated assays, a newer Immulite model among them, upper limits set in the same group of men ran from 6.4 to 28.7 IU/mL [2]. The same cohort used an upper limit of 55 kIU/L for thyroglobulin antibodies, a separate test with its own scale [5].
Busselton Health Study, Australia, 2010, cutoff that predicted hypothyroidism
Adults tested with the Immulite immunoassay · [5]
| Range | What the source calls it |
|---|---|
| 29 or below IU/mL | No name given |
| above 29 IU/mL | No name given |
The level that served as the cutoff for predicting hypothyroidism 13 years later in 1,184 adults, found by receiver operating characteristic analysis and printed as above 29 kIU/L. It sits below the 35 kIU/L reference limit of the same assay. The matching figure for thyroglobulin antibodies was above 22 kIU/L [5]. A pooled analysis of 11,212 pregnant women likewise reported that the cutoffs in current use may be too high, because antibody levels below the manufacturers' cutoffs already went with more premature delivery [6].
What has been shown to move it
Shown to lower it1
Hashimoto's thyroiditis
Mixed results: thyroid antibodies fell in people with Hashimoto's in both reviews, while reviews disagree on whether TSH changed.
The numbers and sources
- Effect
- Thyroid peroxidase antibodies fell in both reviews. In people on levothyroxine, the weighted mean difference after 3 months was -271 (95% CI -366 to -175) [5]. Across 29 cohorts, the SMD was -0.96 (95% CI -1.36 to -0.56) [6]. On TSH, sources disagree. In people not on thyroid hormone, a 2017 review found no change in TSH, quality of life or ultrasound findings [7]. A 2024 review found TSH lower (SMD -0.21, 95% CI -0.43 to -0.02, 869 people) [6].
- Population
- Adults with chronic autoimmune thyroiditis, 16 trials [5], 9 trials [7] and 35 studies [6].
- Sources
- [5], [6], [7]
- Caveats
- Antibody levels are a lab marker. The 2016 review rated evidence quality low [5], and the 2024 review moderate, with I² of 90% for antibodies [6].
How it compares with the reference method
Did not match the reference method1
Differences between assays
One study found upper reference limits for TPO antibodies from 6.4 to 28.7 IU/mL across five automated assays run on the same men.
The numbers and sources
- Compared with
- Four other automated immunoassays run on the same blood samples
- Effect
- Using the reference group that the National Academy of Clinical Biochemistry guideline specifies, the upper reference limits in men and women were 28.7 and 29.0 IU/mL on Immulite 2000 XPi, 24.6 and 25.4 on Maglumi 2000 Plus, 6.4 and 6.9 on Kryptor Compact Plus, 8.3 and 10.0 on Phadia 250 and 14.2 and 17.9 on Liaison XL. These were lower than the limits stated by the manufacturers, except for Liaison XL in women, by 11.3% to 66.8%. The five methods did not compare well with each other, although all were standardized against the same international reference preparation [2].
- Population
- 120 men and 120 women under 30 with TSH of 0.5 to 2.0 mIU/L, a normal thyroid ultrasound and no thyroid or other autoimmune disease [2].
- Sources
- [2]
- Caveats
- One Italian study of 240 people. The authors attribute the differences to the TPO antigen preparations the assays use [2]. A result is read against the cutoff of the assay that produced it.
What studies tie it to
Linked in research3
Later hypothyroidism
Linked to later hypothyroidism: over 20 years, women with thyroid antibodies alone had 8 times the odds, and 38 times with a raised TSH as well.
The numbers and sources
- Effect
- In a 20-year British follow-up, positive thyroid antibodies alone carried odds ratios for developing hypothyroidism of 8 in women (95% CI 5 to 15) and 25 in men (10 to 63). With a raised TSH as well, the odds ratios were 38 (22 to 65) and 173 (81 to 370) [7]. In an Australian cohort, hypothyroidism 13 years later was present in 12.0% of antibody-positive women whose baseline TSH was 2.5 mU/L or less, 55.2% at 2.5 to 4.0 mU/L and 85.7% above 4.0 mU/L [5]. In a 5-year Chinese survey, 14.44% of people positive for TPO or thyroglobulin antibodies developed thyroid dysfunction, against 3.31% of those without antibodies [8]. Among 82 women with subclinical hypothyroidism, overt hypothyroidism developed in 58.5% of those with microsomal antibodies and 23.2% of those without [9]. A US guideline puts progression from subclinical to overt hypothyroidism at 4.3% a year with TPO antibodies and 2.6% a year without [4].
- Population
- 2,779 adults in the Whickham Survey [7]. 1,184 adults in the Busselton Health Surveys [5]. 3,018 people in three Chinese regions with different iodine intakes [8]. 82 women followed a mean 9.2 years [9].
- Sources
- [7], [5], [8], [9], [4]
- Caveats
- Observational. The studies used different antibody assays and cutoffs, and earlier ones measured antibodies by semiquantitative methods, not automated immunoassay [5]. The US guideline also reports that about 75% of people with chronic autoimmune thyroiditis have raised antibody levels, many with normal thyroid function at the time [4].
Miscarriage and preterm birth
Linked to more miscarriage and preterm birth in women with normal thyroid function, with preterm birth in 6.6% of antibody-positive women against 4.9%.
The numbers and sources
- Effect
- A meta-analysis of women with normal thyroid function found an odds ratio for miscarriage with thyroid autoantibodies of 3.90 in 19 cohort studies (95% CI 2.48 to 6.12) and 1.80 in 12 case-control studies (1.25 to 2.60). The odds ratio for preterm birth was 2.07 (1.17 to 3.68) [10]. In pooled individual data on 47,045 pregnant women, preterm birth occurred in 6.6% of TPO antibody-positive women and 4.9% of antibody-negative women (odds ratio 1.33, 95% CI 1.15 to 1.56) [11]. A pooled analysis of 11,212 pregnant women found the association with premature delivery rose with the antibody concentration [6].
- Population
- 31 studies with 12,126 women for miscarriage and 5 studies with 12,566 women for preterm birth [10]. 47,045 pregnant women in 19 cohorts, of whom 7.5% were TPO antibody positive [11]. 11,212 pregnant women in Dutch birth cohorts [6].
- Sources
- [10], [11], [6]
- Caveats
- Observational. Each study applied its own assay and cutoff, so a positive result does not mean the same level across studies.
Thyroid inflammation after childbirth
Limited evidence: a guideline review reports postpartum thyroiditis in 33 to 50% of women who were thyroid antibody positive in the first trimester.
The numbers and sources
- Effect
- The American Thyroid Association reports that women who are thyroid antibody positive in the first trimester have a 33 to 50% risk of postpartum thyroiditis, and that women with the highest antibody levels have the highest risk. It reports that 10 to 20% of cases result in permanent hypothyroidism [15].
- Population
- A guideline summary of earlier studies, whose sizes it does not give [15].
- Sources
- [15]
- Caveats
- Secondhand figures from guideline text, not a primary study.
Mixed results1
Live birth and miscarriage in trials of levothyroxine for antibody-positive women
Mixed results: two large trials of levothyroxine in antibody-positive women with normal thyroid function found no change in live births or miscarriage, after small earlier trials reported fewer miscarriages.
The numbers and sources
- Effect
- In a placebo-controlled trial of 952 women with TPO antibodies, normal thyroid function and a history of miscarriage or infertility, the live-birth rate was 37.4% with levothyroxine 50 micrograms a day and 37.9% with placebo (relative risk 0.97, 95% CI 0.83 to 1.14), with no significant differences in pregnancy loss or preterm birth [12]. In an open-label trial of 600 antibody-positive women having in vitro fertilization, miscarriage rates were 10.3% with levothyroxine and 10.6% without, and live-birth rates 31.7% and 32.3% [13]. Earlier, a pooled estimate from two small randomized studies gave a relative risk of miscarriage of 0.48 (0.25 to 0.92) [10]. In one earlier study, 115 antibody-positive pregnant women were divided into a levothyroxine group and an untreated group, with miscarriage in 3.5% and 13.8% [14].
- Population
- 952 women at 49 UK hospitals, drawn from 19,585 tested [12]. 600 women at one hospital in China [13]. 115 antibody-positive pregnant women in Italy [14].
- Sources
- [12], [13], [10], [14]
- Caveats
- These trials treated women who had the antibodies and did not set out to lower the antibody level. The largest trial started treatment before conception and the Chinese trial was open label [12][13].
Checked, no link found1
Thyroid disease when only thyroglobulin antibodies are positive
One large US survey found thyroglobulin antibodies without TPO antibodies were not significantly associated with thyroid disease, while TPO antibodies were.
The numbers and sources
- Effect
- In the NHANES III survey, thyroglobulin antibodies were positive in 10.4% and TPO antibodies in 11.3% of people who reported no thyroid disease. TPO antibodies were significantly associated with hypothyroidism or hyperthyroidism and thyroglobulin antibodies were not. Thyroglobulin antibodies alone, in the absence of TPO antibodies, were not significantly associated with thyroid disease [16].
- Population
- 17,353 people aged 12 and older representing the US population from 1988 to 1994, of whom 16,533 reported no thyroid disease [16].
- Sources
- [16]
- Caveats
- One cross-sectional survey, using the assays of its time. Positive antibodies were more common in women, rose with age and were less common in Black participants (4.5%) than in white participants (12.3%) [16].
Sources
- US Food and Drug Administration. 21 CFR 866.5870, Thyroid autoantibody immunological test system. Electronic Code of Federal Regulations. https://www.ecfr.gov/current/title-21/section-866.5870
- D'Aurizio F, Metus P, Polizzi Anselmo A, et al. Establishment of the upper reference limit for thyroid peroxidase autoantibodies according to the guidelines proposed by the National Academy of Clinical Biochemistry: comparison of five different automated methods. Autoimmunity Highlights. 2015. https://doi.org/10.1007/s13317-015-0070-x
- US National Library of Medicine. Thyroid peroxidase antibody. MedlinePlus Medical Encyclopedia. Reviewed January 25, 2026. https://medlineplus.gov/ency/article/003556.htm
- Garber JR, Cobin RH, Gharib H, et al. Clinical Practice Guidelines for Hypothyroidism in Adults: Cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Endocrine Practice. 2012. https://doi.org/10.4158/ep12280.gl
- Walsh JP, Bremner AP, Feddema P, et al. Thyrotropin and Thyroid Antibodies as Predictors of Hypothyroidism: A 13-Year, Longitudinal Study of a Community-Based Cohort Using Current Immunoassay Techniques. The Journal of Clinical Endocrinology and Metabolism. 2010. https://doi.org/10.1210/jc.2009-1977
- Korevaar TIM, Pop VJ, Chaker L, et al. Dose Dependency and a Functional Cutoff for TPO-Antibody Positivity During Pregnancy. The Journal of Clinical Endocrinology and Metabolism. 2018. https://doi.org/10.1210/jc.2017-01560
- 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. https://doi.org/10.1111/j.1365-2265.1995.tb01894.x
- Li Y, Teng D, Shan Z, et al. Antithyroperoxidase and Antithyroglobulin Antibodies in a Five-Year Follow-Up Survey of Populations with Different Iodine Intakes. The Journal of Clinical Endocrinology and Metabolism. 2008. https://doi.org/10.1210/jc.2007-2368
- Huber G, Staub JJ, Meier C, et al. Prospective Study of the Spontaneous Course of Subclinical Hypothyroidism: Prognostic Value of Thyrotropin, Thyroid Reserve, and Thyroid Antibodies. The Journal of Clinical Endocrinology and Metabolism. 2002. https://doi.org/10.1210/jcem.87.7.8678
- Thangaratinam S, Tan A, Knox E, et al. Association between thyroid autoantibodies and miscarriage and preterm birth: meta-analysis of evidence. BMJ. 2011. https://doi.org/10.1136/bmj.d2616
- Consortium on Thyroid and Pregnancy Study Group on Preterm Birth, Korevaar TIM, Derakhshan A, et al. Association of Thyroid Function Test Abnormalities and Thyroid Autoimmunity With Preterm Birth: A Systematic Review and Meta-analysis. JAMA. 2019. https://doi.org/10.1001/jama.2019.10931
- Dhillon-Smith RK, Middleton LJ, Sunner KK, et al. Levothyroxine in Women with Thyroid Peroxidase Antibodies before Conception. New England Journal of Medicine. 2019. https://doi.org/10.1056/nejmoa1812537
- Wang H, Gao H, Chi H, et al. Effect of Levothyroxine on Miscarriage Among Women With Normal Thyroid Function and Thyroid Autoimmunity Undergoing In Vitro Fertilization and Embryo Transfer: A Randomized Clinical Trial. JAMA. 2017. https://doi.org/10.1001/jama.2017.18249
- Negro R, Formoso G, Mangieri T, et al. Levothyroxine Treatment in Euthyroid Pregnant Women with Autoimmune Thyroid Disease: Effects on Obstetrical Complications. The Journal of Clinical Endocrinology and Metabolism. 2006. https://doi.org/10.1210/jc.2005-1603
- 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. https://doi.org/10.1089/thy.2016.0457
- 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). The Journal of Clinical Endocrinology and Metabolism. 2002. https://doi.org/10.1210/jcem.87.2.8182