Guide to Thyroid Peroxidase Antibodies (TPO)
Summary
Thyroid peroxidase antibodies (TPO antibodies or TPOAb) are autoantibodies that target thyroid peroxidase, an enzyme essential for thyroid hormone production, and their presence may indicate autoimmune thyroid disease.
Why It Matters
Thyroid peroxidase is a crucial enzyme in your thyroid gland that helps produce thyroid hormones by facilitating the attachment of iodine to thyroglobulin. When your immune system mistakenly identifies this enzyme as foreign, it produces antibodies against it. These antibodies are called thyroid peroxidase antibodies or anti-TPO antibodies.
TPO antibodies are the hallmark of autoimmune thyroid disease. They’re present in approximately 90% of people with Hashimoto’s thyroiditis (the most common cause of hypothyroidism in the United States) and in about 75% of people with Graves’ disease (a common cause of hyperthyroidism). The presence of these antibodies indicates that your immune system is attacking your thyroid gland.
However, the presence of TPO antibodies doesn't necessarily mean you currently have thyroid dysfunction. Approximately 10%-15% of people without any thyroid disease have detectable TPO antibodies. But having these antibodies does increase your risk of developing thyroid problems in the future.
When TPO antibodies are present along with elevated thyroid stimulating hormone (TSH) or abnormal thyroid hormone levels, they help confirm that autoimmune disease is the cause of thyroid dysfunction. This distinction is important because it affects monitoring, treatment decisions, and assessment of risk for other autoimmune conditions.
TPO antibody testing is particularly valuable when TSH is elevated but symptoms are mild or unclear. The presence of antibodies confirms autoimmune thyroiditis and may help your provider decide whether to start treatment or monitor closely. High levels of TPO antibodies in euthyroid (normal thyroid function) individuals may predict future progression to hypothyroidism, with some studies suggesting a 2%-4% annual risk of developing overt hypothyroidism.
Associated Symptoms
TPO antibody levels themselves don't cause symptoms. Symptoms, when present, relate to the underlying thyroid dysfunction (hypothyroidism or hyperthyroidism) or thyroid inflammation.
Symptoms that may be associated with positive TPO antibodies in Hashimoto's thyroiditis (hypothyroidism):
- Fatigue: Persistent tiredness may result from decreased thyroid hormone reducing metabolism
- Weight gain: Unexplained increase despite no dietary changes may occur with slowed metabolism
- Cold intolerance: Feeling unusually cold may be related to reduced metabolic heat production
- Dry skin and brittle hair: Changes in texture and quality can result from decreased cellular activity
- Constipation: Slowed digestive processes may lead to less frequent bowel movements
- Muscle aches and weakness: Discomfort and reduced strength may develop
- Depression: Low mood may be related to thyroid hormone's effects on brain neurotransmitters
- Difficulty concentrating: Cognitive changes may occur with thyroid dysfunction
- Slowed heart rate: Decreased pulse may result from reduced thyroid hormone
- Menstrual irregularities: Heavier or more frequent periods may occur in women
- Thyroid enlargement (thyromegaly): Some people may notice neck fullness or discomfort
Symptoms that may be associated with positive TPO antibodies in Graves' disease (hyperthyroidism):
Note: In Graves' disease, thyrotropin receptor antibodies (TRAb) are the primary cause, but TPO antibodies are often also present.
- Rapid heartbeat: Tachycardia or palpitations may occur
- Unintentional weight loss: Despite normal or increased appetite
- Anxiety and nervousness: Heightened emotional responses
- Tremors: Fine shaking of the hands
- Heat intolerance and sweating: Excessive warmth sensation
- Eye changes: Bulging eyes (Graves' ophthalmopathy)
Important considerations:
- Many people with positive TPO antibodies have normal thyroid function and no symptoms
- TPO antibodies can be present years before thyroid dysfunction develops
- Symptoms vary widely in severity between individuals
- Some people with positive antibodies never develop thyroid dysfunction
Clinical Ranges
Lab Reference Ranges:
- Normal (Negative): <9 IU/mL (international units per milliliter)
- Elevated (Positive): ≥9 IU/mL
Note: Reference ranges may vary between laboratories. Some labs use <35 IU/mL as the cutoff.
Lifestyle Factors That Can Impact It
Once TPO antibodies develop, lifestyle factors may or may not impact antibody levels. However, certain factors may influence autoimmune activity or thyroid health:
Factors that may support overall thyroid and immune health:
- Adequate selenium intake: Selenium is important for thyroid function and may have modest effects on antibody levels in some studies
- Stress management: Chronic stress can affect immune system function
- Adequate sleep: Sleep supports immune regulation
- Avoiding smoking: Smoking is associated with increased risk of thyroid eye disease in Graves' disease
Factors that may negatively impact thyroid autoimmunity:
- Smoking: Associated with worse outcomes in thyroid eye disease
- Iodine excess: Very high iodine intake may trigger or worsen autoimmune thyroid disease in susceptible individuals
- Severe stress: May affect immune function
Important note: Lifestyle modifications may positively impact but not eliminate TPO antibodies once present. Treatment, however, should focus on managing thyroid function as well as symptomatology.
Other Factors That Can Impact It
Medical Conditions Associated with Positive TPO Antibodies
- Hashimoto's thyroiditis: The most common association; approximately 90% of people with Hashimoto's have elevated TPO antibodies
- Graves' disease: About 70%-75% of people with Graves' disease have elevated TPO antibodies
- Postpartum thyroiditis: Thyroid inflammation after pregnancy may be associated with TPO antibodies
- Subclinical hypothyroidism: Mildly elevated TSH with normal T4, often with positive antibodies
- Other autoimmune conditions: People with one autoimmune disease have increased risk for others, including type 1 diabetes, rheumatoid arthritis, celiac disease, and vitiligo
Genetic Factors
- Family history: Autoimmune thyroid disease tends to run in families; up to 50% of females and 30% of males with a first-degree relative who has Hashimoto's may have elevated TPO antibodies.
- Sex: Females are much more likely than males to develop thyroid autoimmunity (7-10 times higher prevalence)
Individual Factors
- Age: Prevalence of TPO antibodies increases with age
- Pregnancy: Can affect autoimmune thyroid disease; antibody levels may change during and after pregnancy
- Recent thyroid injury or inflammation: Can temporarily increase antibody levels
Environmental Factors
- Iodine intake: Both deficiency and excess can affect autoimmune thyroid disease risk
- Certain infections: Some viral infections may trigger autoimmune thyroid disease in genetically susceptible individuals
- Environmental toxins: Some chemicals may affect thyroid autoimmunity
Testing Accuracy and Stability
TPO antibody testing is generally reliable and highly sensitive for detecting thyroid autoimmunity.
Factors That Can Affect the Accuracy of Your Test
- Biotin supplements: Dietary supplements containing biotin may interfere with assays and skew results to be either falsely high or falsely low; for patients on recommended daily doses, samples should be drawn at least 8 hours after the last biotin dose; for mega-doses, consider waiting at least 72 hours
- Different assay methods: Various laboratories use different testing methods, which may give slightly different results
- Antibody titer variability: Levels can fluctuate somewhat over time, though presence/absence tends to be stable
- Gross hemolysis: Severely hemolyzed samples may be rejected
How It Relates to Other Markers
Other tests can provide insights about health status when viewed alongside TPO antibody results. These tests may include:
- TSH: Essential for determining if thyroid dysfunction is present; elevated TSH with positive TPO can suggest Hashimoto's thyroiditis
- Free T4 and Free T3: Assesses actual thyroid hormone levels to determine degree of dysfunction
- Thyroglobulin antibodies (TgAb): Another thyroid autoantibody often measured with TPO; if present alongside TPO, may indicate thyroid autoimmunity
- Thyrotropin receptor antibodies (TRAb) or thyroid stimulating immunoglobulin (TSI): Measured when Graves' disease is suspected; these stimulating antibodies are the primary cause of Graves' disease
- Thyroid ultrasound: May show characteristic changes of autoimmune thyroiditis including heterogeneous echotexture, hypoechogenicity, and altered blood flow
- Complete blood count: Some autoimmune conditions affect blood cells
- Other autoimmune markers: May be tested if other autoimmune diseases are suspected
What Results May Mean in the Context of Other Markers
- Positive TPO + Elevated TSH + Low or normal Free T4: May suggest Hashimoto's thyroiditis with hypothyroidism
- Positive TPO + Normal TSH + Normal Free T4: May indicate thyroid autoimmunity without current dysfunction; increased risk of future hypothyroidism
- Positive TPO + Low TSH + Elevated Free T4: Less common pattern; TPO can be present in Graves' disease
- Positive TPO + Positive TgAb: May indicate thyroid autoimmunity; both antibodies common in Hashimoto's
- Positive TPO + thyromegaly on examination: Supports diagnosis of Hashimoto's thyroiditis
Follow-up Considerations
If your TPO antibodies are positive, your provider may make some of the following recommendations. You should always speak to your doctor if you have medical questions or before making medical decisions.
When Re-Testing May be Appropriate
- TPO antibody levels: Monitoring thyroid autoantibodies along with thyroid function tests gives insights into a person's state of autoimmunity.
- TSH monitoring: If you have positive TPO with normal thyroid function, TSH should be checked every 6-12 months to watch for progression to hypothyroidism
- During pregnancy: If you have positive TPO, thyroid function should be monitored each trimester
- After the postpartum period: Thyroid function should be checked 3-6 months postpartum if antibodies were present during pregnancy
Additional Testing Your Doctor May Consider
- TgAb: Often tested alongside TPO to fully assess thyroid autoimmunity
- Thyroid ultrasound: May be performed to assess thyroid structure and identify nodules
- Additional autoimmune screening: Testing for celiac disease, type 1 diabetes, or other autoimmune conditions in some cases
- Vitamin D and selenium levels: Sometimes checked as these nutrients are important for immune and thyroid function
- Lipid panel: Hypothyroidism can affect cholesterol levels
- If pregnant: More frequent thyroid function monitoring throughout pregnancy
When Additional Care May Be Warranted
- Positive TPO with hypothyroidism: Treatment with thyroid hormone replacement may be recommended
- Positive TPO with subclinical hypothyroidism: Treatment may be considered, especially if antibody levels are high, TSH is >10, or symptoms are present
- Positive TPO in pregnancy: Close monitoring and treatment if TSH rises, as maternal hypothyroidism can affect fetal development
- Positive TPO with thyromegaly: May require closer monitoring or treatment
- Positive TPO with other autoimmune conditions: May need coordinated care for multiple conditions
- Rapid increase in TSH in someone with positive TPO: May indicate progression to overt hypothyroidism
Bibliography
References
- American Thyroid Association. “Hashimoto’s Thyroiditis.” Thyroid.org, updated 25 Aug. 2023.
- Faix JD. DeGroot’s Endocrinology. 8th ed. Elsevier; 2023.
- Caturegli P et al. Autoimmunity Reviews. 2014;13(4–5):391–397.
- Guber HA et al. Henry’s Clinical Diagnosis and Management by Laboratory Methods. 24th ed. Elsevier; 2022.
- Vargas-Uricoechea H et al. Antibodies. 2023;12(3):48.
- Pearce EN, Hollenberg AN. Goldman-Cecil Medicine. 27th ed. Elsevier; 2024.
- Franco JS et al. Autoimmunity: From Bench to Bedside. 2013.




