Thyroid Peroxidase Antibodies (TPOAb): Understanding Your Blood Test Series

1. Overview: What this test reveals and why it is important

Thyroid peroxidase (TPO) is a key enzyme located in the thyroid follicular cells. It catalyses the iodination of tyrosine residues on thyroglobulin and the coupling of iodotyrosines to form thyroid hormones (T3 and T4). TPO antibodies (TPOAb) are autoantibodies directed against this enzyme, primarily of the IgG class.

The presence of TPOAb indicates autoimmune thyroid disease (AITD) , the most common organ‑specific autoimmune disorder. TPOAb is the most sensitive test for detecting autoimmune thyroiditis:

· Hashimoto’s thyroiditis (chronic lymphocytic thyroiditis) – >90% of patients are TPOAb‑positive.

· Atrophic thyroiditis – a variant of Hashimoto’s with thyroid atrophy.

· Postpartum thyroiditis – 80% of affected women have TPOAb.

· Graves’ disease – 60–80% of patients have TPOAb (indicating concurrent autoimmune thyroiditis).

TPOAb is complement‑fixing and can directly injure thyroid follicular cells, contributing to hypothyroidism. However, the antibody titre does not correlate perfectly with disease severity; some individuals have high titres with normal thyroid function, while others have low titres with overt hypothyroidism.

Clinical utility:

· Diagnosis of autoimmune thyroid disease – a positive TPOAb confirms an autoimmune aetiology for hypothyroidism or hyperthyroidism.

· Prediction of future hypothyroidism – in euthyroid individuals with positive TPOAb, the risk of developing hypothyroidism is increased (approximately 2–4% per year).

· Risk stratification in pregnancy – TPOAb positivity in euthyroid pregnant women is associated with increased risk of miscarriage, preterm delivery, and postpartum thyroiditis. Some guidelines recommend levothyroxine in TPOAb‑positive euthyroid pregnant women with TSH >2.5 mIU/L.

· Monitoring – TPOAb titres are not used to monitor treatment response but may decline slowly over years with levothyroxine therapy or selenium supplementation.

Important principle: A positive TPOAb does not mandate treatment unless thyroid dysfunction (elevated TSH, low free T4) is present. The antibody itself is not the target; the thyroid hormone imbalance is.

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2. What does it measure

a. Units of measurement

· International units per millilitre (IU/mL) or kilo‑international units per litre (kIU/L) – quantitative.

· Titre – semi‑quantitative (e.g., 1:100, 1:400, 1:1600) – less common in modern laboratories.

· Positive / negative – qualitative or based on cut‑off.

b. Normal Range and Interpretation

(Reference ranges vary by laboratory, assay method, and population; the following are general guidelines.)

Negative / normal:

· Typically < 5–9 IU/mL or < 35 IU/mL depending on the assay.

· Undetectable is ideal.

Positive:

· Low‑positive: 10–50 IU/mL (assay‑dependent).

· Moderate‑positive: 50–200 IU/mL.

· High‑positive: >200 IU/mL.

Interpretation notes:

· Higher titres are more specific for Hashimoto’s thyroiditis but do not reliably predict the rate of progression to hypothyroidism.

· TPOAb can be positive in healthy individuals (10–15% of euthyroid adults, especially women and the elderly) without progression to thyroid dysfunction.

· Isolated TPOAb positivity with normal TSH and free T4 – no treatment; monitor thyroid function annually.

· TPOAb and TgAb (thyroglobulin antibodies) often coexist; measuring both increases diagnostic sensitivity.

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3. Other factors connected to this

a. Direct correlation (factors that directly influence TPOAb positivity)

Genetic factors:

· Strong familial aggregation – first‑degree relatives of patients with AITD have increased prevalence of TPOAb.

· HLA‑DR3, HLA‑DR5, CTLA‑4, PTPN22, and thyroglobulin gene polymorphisms are associated with susceptibility.

Sex and hormones:

· Female predominance (5–10:1) – oestrogen may enhance autoimmune responses.

· Peak incidence occurs between 30–60 years.

Iodine intake:

· Excess iodine can precipitate or exacerbate autoimmune thyroiditis in susceptible individuals (iodine induces oxidative stress and exposes TPO antigen).

· Iodine deficiency may reduce TPOAb positivity rates.

Infections:

· Viral infections (EBV, hepatitis C, HIV) – molecular mimicry or bystander activation.

· Yersinia enterocolitica – proposed but controversial.

Medications:

· Interferon‑alpha, interleukin‑2, alemtuzumab, lithium, amiodarone – can induce TPOAb positivity and thyroid dysfunction.

· Immune checkpoint inhibitors (anti‑PD‑1, anti‑CTLA‑4) – high rates of thyroiditis and TPOAb seroconversion.

Other autoimmune diseases:

· Type 1 diabetes, pernicious anaemia, Addison’s disease, vitiligo, coeliac disease, rheumatoid arthritis, Sjögren syndrome, SLE – increased prevalence of TPOAb.

Pregnancy:

· TPOAb often declines during pregnancy (immune tolerance) and rebounds postpartum (immune reconstitution) – accounts for postpartum thyroiditis.

Smoking:

· Paradoxical effect: Smoking is protective against Hashimoto’s (reduces TPOAb) but increases risk of Graves’ disease.

Radiation:

· External radiation to the neck (e.g., for lymphoma) can trigger autoimmune thyroiditis.

b. Indirect correlation (factors that influence TPOAb interpretation or cause false results)

· Assay variability: Different immunoassays (ELISA, RIA, chemiluminescence) have different cut‑offs and sensitivities. Use same laboratory for serial testing.

· Biochemical interference: High levels of biotin (>5 mg/day) in supplements can cause falsely low TPOAb results in streptavidin‑based immunoassays. Discontinue biotin at least 48 hours before testing.

· Haemolysis, lipaemia, or high rheumatoid factor may interfere with some assays.

· Age: TPOAb prevalence increases with age, especially in women.

· Ethnicity: Higher prevalence in Caucasian populations; lower in some Asian and African populations.

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4. Disorders related to abnormal values

a. When TPOAb is positive (clinically significant)

Autoimmune thyroid diseases:

· Hashimoto’s thyroiditis: Most common cause of hypothyroidism in iodine‑sufficient regions. Diffuse goitre (early), later atrophic. Positive TPOAb in >90%. May have concurrent TgAb. Gradual thyroid failure.

· Atrophic thyroiditis: Variant without goitre; often higher antibody titres.

· Postpartum thyroiditis: Typically occurs 2–6 months postpartum. TPOAb positivity predicts risk. May present with transient thyrotoxicosis followed by hypothyroidism; permanent hypothyroidism in 20–30%.

· Painless (silent) thyroiditis: Similar to postpartum but not related to pregnancy.

· Graves’ disease: TPOAb positive in 60–80%; indicates coexistent autoimmune thyroiditis. Higher risk of hypothyroidism after radioactive iodine or surgery.

Other conditions with elevated TPOAb (not always associated with thyroid dysfunction):

· Euthyroid autoimmune thyroiditis: Positive TPOAb with normal TSH and free T4. Increased risk of progression to overt hypothyroidism (2–4% per year).

· Other autoimmune diseases: As above.

· Chronic hepatitis C, interferon‑treated patients.

· Healthy elderly: Up to 20% may have low‑positive TPOAb without disease.

b. When TPOAb is negative

· Negative TPOAb does not exclude autoimmune thyroid disease – 10% of Hashimoto’s and 20–40% of Graves’ are TPOAb‑negative (seronegative).

· Non‑autoimmune hypothyroidism: Post‑surgical, post‑radioiodine, post‑radiation, congenital, infiltrative (amyloidosis, haemochromatosis).

· Non‑autoimmune hyperthyroidism: Toxic adenoma, toxic multinodular goitre, subacute (de Quervain’s) thyroiditis.

· Normal healthy individuals.

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5. Best way to address aberrant levels

Important principle: TPOAb positivity is not treated. Thyroid dysfunction, if present, is treated. The goal is to normalise TSH, not to lower antibody titres. However, certain interventions (selenium, levothyroxine) have been shown to reduce TPOAb levels over time, which may reflect reduced autoimmune activity.

a. Quick ways or using Medications

For hypothyroidism (elevated TSH):

· Levothyroxine (LT4):

· First‑line therapy for hypothyroidism of any cause.

· Synthetic T4; identical to endogenous hormone. No animal products.

· Dose: 1.6 mcg/kg/day (adults); start low in elderly or those with cardiac disease.

· Goal: Normalise TSH (usually 0.5–2.5 mIU/L; individualised).

· Levothyroxine therapy is associated with a gradual decline in TPOAb titres over 6–24 months, likely due to reduced antigen presentation and immune activation.

· Liothyronine (LT3) or combination therapy:

· Not routinely recommended; reserved for selected patients with persistent symptoms despite normal TSH on LT4.

· No evidence of superior antibody reduction.

For hyperthyroidism in Graves’ disease (TPOAb often positive):

· Antithyroid drugs: methimazole (preferred), propylthiouracil (second‑line, especially first trimester).

· Radioactive iodine or thyroidectomy for definitive treatment.

· TPOAb may persist or decline after treatment; not used to monitor.

For euthyroid TPOAb‑positive individuals:

· No medication indicated unless TSH rises above threshold (guidelines vary; consider treatment if TSH >10 mIU/L or >2.5–4.0 mIU/L with symptoms or pregnancy).

· Selenium supplementation (see below) may reduce TPOAb and improve quality of life.

For pregnancy:

· TPOAb‑positive euthyroid women with TSH >2.5 mIU/L: Levothyroxine is recommended to reduce miscarriage and preterm delivery risk.

· TPOAb‑positive with normal TSH (<2.5): Controversial; some guidelines recommend LT4, others do not. Discuss with obstetric medicine specialist.

Do not self‑prescribe levothyroxine – requires medical supervision with regular TSH monitoring.

b. Using Supplements or Holistic medicine

Supplements with evidence for reducing TPOAb and supporting thyroid health:

· Selenium:

· Strongest evidence for reducing TPOAb titres and improving thyroid ultrasound morphology.

· Mechanism: Incorporation into selenoproteins (glutathione peroxidases, thioredoxin reductases) reduces oxidative stress in the thyroid.

· Preferred form: Selenomethionine (plant‑derived, organic, better absorbed and retained than sodium selenite).

· Dose: 80–200 mcg/day (typically 200 mcg).

· Duration: Effects on TPOAb detectable at 3–6 months; maximal at 6–12 months.

· Caution: Do not exceed 400 mcg/day (risk of selenosis). Selenium is not a substitute for levothyroxine when hypothyroidism is present.

· Vitamin D:

· Deficiency is highly prevalent in AITD and correlates with higher TPOAb titres and disease severity.

· Supplementation may reduce TPOAb and TgAb, especially in deficient individuals.

· Preferred: D3 (cholecalciferol) from lichen.

· Dose: 600–2000 IU/day for maintenance; higher doses (2000–4000 IU/day) for deficiency correction, under guidance.

· Myo‑inositol:

· Second messenger in TSH signalling; improves TSH response and may reduce TPOAb in Hashimoto’s with subclinical hypothyroidism.

· Often combined with selenium.

· Dose: 600–1200 mg/day.

· Preferred source: Plant‑derived (corn, rice bran); fermentation‑derived available.

· Magnesium:

· Cofactor for thyroid hormone synthesis; deficiency may impair thyroid function.

· Some studies show reduced TPOAb with magnesium supplementation.

· Preferred forms: magnesium glycinate, citrate, malate. Avoid oxide (poor absorption).

· Zinc:

· Essential for thyroid hormone synthesis and immune regulation.

· Deficiency common in AITD; supplementation may improve T3 levels and reduce TPOAb.

· Preferred form: zinc picolinate or zinc citrate.

· Dose: 15–30 mg elemental zinc/day; monitor copper with long‑term use.

· Curcumin (turmeric):

· Anti‑inflammatory; inhibits NF‑κB and may reduce autoimmune activity.

· Limited evidence in AITD; small studies show reduction in TPOAb.

· Use phytosomal, liposomal, or with piperine for bioavailability.

· Avoid products with added synthetic folic acid or cyanocobalamin.

· Omega‑3 fatty acids (EPA/DHA):

· Anti‑inflammatory; may reduce autoimmune activity.

· Preferred source: Algae oil – sustainable, plant‑based, direct EPA/DHA, no marine contaminants.

· Avoid conventional fish oil (overfishing, ocean pollution, ethical concerns).

· Dose: 1–3 g/day EPA/DHA.

· Probiotics / prebiotics:

· Modulate gut microbiota; emerging evidence suggests benefit in AITD (reduced TPOAb, improved TSH).

· Preferred sources: fermented plant foods (kimchi, sauerkraut, kombucha, miso, tempeh); standardised probiotic supplements with documented strains (e.g., Lactobacillus reuteri, Bifidobacterium longum).

· Vitamin B12 and folate:

· Autoimmune gastritis (pernicious anaemia) is associated with AITD; deficiency exacerbates fatigue and neurological symptoms.

· Use methylcobalamin and methylfolate – active forms, avoid synthetic folic acid and cyanocobalamin.

· Dose: methylcobalamin 1000–2000 mcg/day, methylfolate 400–1000 mcg/day if deficient.

· L‑carnitine:

· May ameliorate symptoms of hyperthyroidism but has no role in Hashimoto’s; not recommended for TPOAb reduction.

Supplements to AVOID:

· Excessive iodine – can exacerbate autoimmune thyroiditis. Avoid kelp, seaweed supplements, and high‑dose iodine preparations (unless specifically prescribed for iodine deficiency, which is rare in iodine‑sufficient regions).

· Synthetic folic acid – avoid; use methylfolate.

· Cyanocobalamin – avoid; use methylcobalamin.

· High‑dose biotin – interferes with thyroid function tests; avoid or discontinue 48 hours before testing.

· Unregulated herbal blends – hepatotoxicity risk; no proven benefit.

General caution: Many supplements are not standardised and may interact with levothyroxine (e.g., calcium, iron, magnesium should be taken at least 4 hours apart from LT4). Always discuss supplements with your endocrinologist or primary care provider.

c. Using Diet and Foods (following a plant‑forward, ecologically sustainable approach)

Diet is a cornerstone of reducing systemic inflammation and supporting thyroid health. A well‑designed, nutrient‑dense, anti‑inflammatory plant‑based diet can complement medical therapy, reduce autoimmune activity, and improve overall well‑being.

Core dietary principles – what to emphasise:

· Anti‑inflammatory dietary pattern:

· Mediterranean‑style plant‑forward diet – abundant vegetables, fruits, legumes, whole grains, nuts, seeds, olive oil.

· High in polyphenols, fibre, unsaturated fats, and antioxidants.

· Low in refined carbohydrates, added sugars, and saturated fats.

· Consistently associated with lower inflammatory markers and reduced autoimmune disease activity.

· Adequate protein intake:

· Essential for tissue repair, immune function, and thyroid hormone transport.

· Plant‑based protein sources (hierarchy adhered):

· Primary: legumes (lentils, chickpeas, beans, soy products – tofu, tempeh, edamame).

· Fungi / algae: mycoprotein (Quorn), spirulina, chlorella.

· Biotechnology: precision‑fermented dairy proteins (animal‑free whey, casein) – acceptable emerging options.

· Dairy / eggs: permitted but not emphasised; low‑fat fermented dairy (yoghurt, kefir) if tolerated (many with AITD have coexistent lactose intolerance).

· Meat, poultry, fish: deliberately omitted. Effective plant‑based alternatives exist to meet all nutritional requirements. There is no need for animal products to support thyroid health.

· Selenium‑rich plant foods:

· Brazil nuts – 1–2 nuts per day provide ~100–200 mcg selenium. Avoid excess ( >4 nuts/day risk of selenosis).

· Sunflower seeds, chia seeds, flaxseeds, mushrooms, whole grains, legumes – variable content.

· Zinc‑rich plant foods:

· Pumpkin seeds, hemp seeds, chickpeas, lentils, cashews, quinoa.

· Soaking and sprouting legumes and seeds reduces phytate and enhances zinc absorption.

· Iron‑rich plant foods:

· Lentils, chickpeas, tofu, pumpkin seeds, quinoa, fortified cereals, dark leafy greens (cooked).

· Iron deficiency impairs thyroid hormone synthesis.

· Enhance absorption with vitamin C; avoid tea/coffee with meals.

· Vitamin D:

· Sunlight exposure primary; fortified plant milks; supplement from lichen if needed.

· Vitamin B12:

· No reliable plant‑based whole food source. Must be supplemented – methylcobalamin from fermentation, non‑animal, ecologically responsible.

· Folate:

· Avoid folic acid‑fortified foods. Choose unfortified grains and products.

· Natural folate sources: dark leafy greens, legumes, asparagus, beets, avocado, citrus fruits.

· Iodine:

· Do not supplement unless confirmed deficiency (rare). Adequate intake from iodised salt (¼–½ tsp/day), sea vegetables in moderation (nori, wakame – limit to avoid excess). In AITD, avoid excessive iodine (kelp supplements, high‑dose iodine).

· Antioxidant‑rich foods:

· Berries, green tea, dark chocolate (≥70% cocoa), extra virgin olive oil, turmeric, ginger, cruciferous vegetables, onions, garlic, apples, citrus.

What to avoid or severely limit:

· Ultra‑processed foods, refined carbohydrates, added sugars – promote inflammation, insulin resistance, and dysbiosis.

· Excess iodine – avoid kelp supplements, seaweed tablets, high‑dose iodine drops.

· Goitrogenic foods (cooking neutralises): Raw cruciferous vegetables (cabbage, kale, broccoli, cauliflower) contain goitrin and thiocyanates that can interfere with iodine uptake when consumed in massive raw quantities. Cooking inactivates goitrogens. Moderate consumption of cooked cruciferous vegetables is safe and encouraged.

· Soy isoflavones: Theoretical concern that high doses of soy may interfere with thyroid hormone absorption in those with iodine deficiency or on stable levothyroxine. Soy foods (tofu, tempeh, edamame) are safe in moderation, but maintain consistent timing with levothyroxine (take thyroid medication on empty stomach, 60 minutes before or 4 hours after soy products).

· Gluten: Only restrict if coexistent coeliac disease (more common in AITD) or documented non‑coeliac gluten sensitivity. Empirical gluten‑free diet in all AITD is not evidence‑based.

· Alcohol: May interfere with thyroid function and medication metabolism; limit or avoid.

· Smoking: Increases risk of Graves’ and worsens ophthalmopathy; cessation essential.

Specific dietary considerations in AITD:

· Gluten‑free diet trial: Some studies suggest that a gluten‑free diet may reduce TPOAb in patients with coexistent coeliac disease or gluten sensitivity. In seronegative AITD without coeliac disease, evidence is weak. If trialled, do so under dietitian supervision for a defined period (3–6 months), with careful monitoring of TPOAb and clinical symptoms. Avoid unnecessary restrictive diets.

· Nightshades, dairy, eggs: No consistent evidence for elimination unless individual intolerance.

Lifestyle factors with proven benefit in AITD:

· Stress reduction: Chronic stress elevates cortisol, which suppresses thyroid function and may exacerbate autoimmunity. Mindfulness, meditation, yoga, adequate sleep (7–9 hours).

· Regular moderate aerobic and resistance exercise: Reduces fatigue, improves mood, supports metabolic health. No evidence of harm.

· Weight management: Hypothyroidism causes weight gain; obesity exacerbates autoimmunity. Maintain healthy weight with balanced diet and exercise.

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6. How soon can one expect improvement and the ideal time frame to retest

TPOAb titres change slowly. They are not used to monitor treatment response, but serial testing may be performed in research or specific clinical situations.

For levothyroxine therapy in hypothyroidism:

· TSH normalises in 4–8 weeks after achieving appropriate LT4 dose.

· TPOAb declines gradually over 6–24 months; reduction of 20–50% is common.

· TPOAb rarely becomes negative once positive, especially if titres were high.

For selenium supplementation:

· TPOAb reduction detectable at 3–6 months; maximal effect at 6–12 months.

· Reduction of 20–50% reported; effect persists with continued supplementation.

For vitamin D supplementation:

· TPOAb reduction observed after 6–12 months in deficient individuals.

For pregnancy:

· TPOAb declines during pregnancy and rebounds postpartum. Testing in pregnancy should be interpreted with gestation‑specific reference ranges (if available).

Retesting interval summary:

· Euthyroid, TPOAb‑positive, normal TSH: Repeat TSH annually. Do not routinely repeat TPOAb. If repeated, no more often than every 1–2 years.

· On levothyroxine with stable TSH: TPOAb retesting is not indicated. If performed for patient reassurance, interval ≥1 year.

· Selenium or vitamin D supplementation: TPOAb may be retested at 6–12 months to assess response; if no change, continued supplementation unlikely to alter titre.

· Pregnancy: TPOAb status usually known preconception; retesting during pregnancy not routinely required.

· Research settings: As per protocol.

Do not retest TPOAb more often than every 6 months – meaningful change does not occur faster.

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Conclusion

Thyroid peroxidase antibodies are the serological fingerprints of autoimmune thyroid disease. Their presence confirms what the gland itself may already be whispering: that the immune system has turned its attention to the thyroid, and that vigilance – and often intervention – is required.

Yet a positive TPOAb is not a disease; it is a predisposition. It does not mandate treatment, only surveillance. The decision to initiate levothyroxine rests on TSH, not antibody titre. The decision to recommend selenium rests on the patient's desire to modulate autoimmune activity and the clinician's judgment.

The antibody itself is not the enemy; it is the smoke, not the fire. The fire is the lymphocytic infiltration, the cytokine release, the gradual erosion of follicular architecture. Levothyroxine extinguishes the clinical flames; selenium may dampen the embers.

A plant‑based, ecologically responsible diet – rich in legumes, whole grains, nuts, seeds, and algae‑derived omega‑3s – provides the anti‑inflammatory nutritional foundation that supports patients with AITD. It supplies selenium from Brazil nuts, zinc from pumpkin seeds, and fibre for gut health. It avoids the hidden synthetic folic acid that pervades fortified animal products and the excessive iodine that may exacerbate thyroiditis. There is no requirement for meat; its displacement by plants is itself a therapeutic and ecological act.

TPOAb is a number. The patient is a story of fatigue, weight change, temperature dysregulation, and resilience. Listen to the patient, not the titre – but when the titre is high, listen carefully.

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Note on dietary recommendations on this site:

For the sake of our environment we adhere to the following dietary preference hierarchy:

1. Plant‑based

2. Fungi / algae / fermented

3. Biotechnology / lab‑grown / cultures

4. Dairy / eggs

5. Meat / fish / poultry (only if no effective alternative exists)

Special notes on thyroid health:

· Selenium: Choose selenomethionine, preferably from plant‑ or fermentation‑based sources. Brazil nuts are an excellent whole‑food source, but limit to 1–2 nuts per day.

· Iodine: Do not supplement unless deficiency is confirmed. Avoid kelp and seaweed supplements.

· Folic acid: Synthetic folic acid should be avoided; use methylfolate if folate supplementation is required.

· Vitamin D: Choose D3 from lichen.

· Omega‑3: Choose algae oil over fish oil.

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