Summary
TPO Antibodies are immune proteins that mistakenly target thyroid peroxidase — the enzyme responsible for thyroid hormone synthesis. Elevated TPO Ab is the hallmark of Hashimoto's thyroiditis, the leading cause of hypothyroidism in the UK, and is also raised in the majority of Graves' disease cases.
Measuring TPO Ab explains why the thyroid is malfunctioning. A person with elevated TSH and high TPO Ab has a confirmed autoimmune cause for their hypothyroidism, changing both prognosis and management. Even when thyroid function appears normal, significantly elevated TPO Ab predicts a higher lifetime risk of progressing to overt hypothyroidism.
TPO antibodies are tested alongside TSH and Free T4 to diagnose autoimmune thyroid disease, identify patients who need closer monitoring, and investigate unexplained symptoms in those with a family history of thyroid conditions.
What It Is
Thyroid peroxidase (TPO) is an enzyme on the surface of thyroid follicular cells. It catalyses two critical reactions in thyroid hormone synthesis: the oxidation of iodide, and the coupling of iodotyrosines to form T3 and T4.
In autoimmune thyroid conditions, the immune system generates antibodies that target and attack this enzyme. These antibodies can be detected in the bloodstream years or even decades before clinical dysfunction develops, reflecting an ongoing immune assault on thyroid tissue.
TPO Ab is elevated in approximately 95% of Hashimoto’s thyroiditis cases and 70–80% of Graves’ disease cases, making it the most sensitive single autoimmune marker for thyroid disease.
Functions
Autoimmune disease marker
Confirms immune activation against the thyroid gland — the root cause in the majority of thyroid disorders.
Disease progression predictor
Elevated TPO Ab predicts likelihood of developing hypothyroidism. High titres are associated with faster progression.
Treatment decision guide
Identifying autoimmune aetiology helps determine whether to monitor or treat subclinical hypothyroidism.
Fertility and pregnancy risk marker
Elevated TPO Ab is associated with increased miscarriage risk and postpartum thyroiditis — relevant in reproductive health assessment.
Reference Ranges
Serum TPO Antibodies
Measured in IU/mL| Status | Range (IU/mL) | What it means |
|---|---|---|
| Negative | < 34 | No significant autoimmune activity — thyroid unlikely to be under immune attack. |
| Borderline | 34–100 | Low-level antibodies present — monitor annually with full thyroid function. |
| Elevated | > 100 | Significant autoimmune activity — consistent with Hashimoto's or Graves' disease. Warrants clinical assessment. |
TPO Ab ranges vary between assay manufacturers. Very high titres (>1000 IU/mL) are associated with more aggressive thyroid destruction. A single negative result does not completely rule out autoimmune thyroid disease.
Symptoms of Imbalance
Most symptoms from elevated TPO Ab are those caused by the thyroid dysfunction it produces.
- No specific symptoms from negative TPO Ab — absence of thyroid autoimmunity is normal and expected
- Fatigue disproportionate to apparent thyroid function results
- Fluctuating thyroid symptoms — cycles of hypo- and hyperthyroid phases
- Neck discomfort or visible goitre
- Recurrent miscarriage or fertility difficulties
- Low mood, anxiety, and brain fog
- Joint pain and muscle aches
- Postpartum thyroid symptoms after childbirth
Causes of Imbalance
- No pathological cause — a negative result is the expected normal finding
- A small number of autoimmune thyroid disease cases are genuinely seronegative
- Hashimoto's thyroiditis
- Graves' disease
- Other autoimmune conditions (type 1 diabetes, coeliac disease, rheumatoid arthritis)
- Family history of autoimmune thyroid disease
- Postpartum thyroiditis
- Excessive iodine intake
- Certain medications (interferon, amiodarone, lithium)
FAQs
Elevated TPO Ab with normal TSH is called euthyroid autoimmune thyroiditis. Most guidelines do not recommend starting levothyroxine at this stage. Annual TSH monitoring is advised because around 5% of people progress to overt hypothyroidism each year. Some clinicians also recommend selenium 200 mcg/day and an anti-inflammatory diet to reduce immune activity.
Yes. Selenium supplementation (200 mcg/day) has been shown in clinical trials to reduce TPO Ab titres in Hashimoto’s patients. Levothyroxine treatment can also modestly reduce antibody levels over time. A gluten-free diet may lower levels in those with concurrent coeliac disease or non-coeliac gluten sensitivity.
Yes, significantly. Women with elevated TPO Ab have higher rates of miscarriage, preterm delivery, and postpartum thyroiditis even when TSH is normal. Current guidelines recommend TSH monitoring throughout pregnancy in TPO Ab-positive women, with levothyroxine started if TSH rises above 2.5 mIU/L in the first trimester.
Both are thyroid autoimmune antibodies. TPO Ab targets the enzyme that makes thyroid hormones and is more sensitive for Hashimoto’s and Graves’. TG Ab targets the protein that stores thyroid hormones. Testing both together gives the highest diagnostic sensitivity — a small but important group are TG Ab positive but TPO Ab negative.
Yes, approximately 5–10% of people with confirmed Hashimoto’s are seronegative for both antibodies. If clinical suspicion is high, thyroid ultrasound can show the characteristic heterogeneous appearance of Hashimoto’s even when antibodies are negative.
References
- Caturegli P, et al. Autoimmune thyroid diseases. Am J Pathol. 2020;190(2):1–28. View source
- Negro R, et al. Levothyroxine in TPO Ab-positive women undergoing assisted reproduction. J Thyroid Res. 2011;2011:521895. View source
- Toulis KA, et al. Selenium supplementation in Hashimoto's thyroiditis: a meta-analysis. Thyroid. 2010;20(10):1163–1173. View source