According to the American Thyroid Association, over 12% of the U.S. population will develop a thyroid disorder at some point in their lives. Autoimmune thyroid disease (AITD) is the most common organ-specific autoimmune disease, affecting up to 5% of the population.
Thyroid peroxidase (TPO) antibodies are one marker of thyroid autoimmunity and a predictor of clinical thyroid dysfunction. According to the National Health and Nutrition Examination Survey (NHANES III), 11.3% of the U.S. population has positive TPO antibodies. These antibodies hold the potential to change thyroid function and affect physical and mental health.
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What Are Thyroid Peroxidase Antibodies?
TPO is an enzyme in the thyroid gland involved in thyroid hormone production. These hormones—thyroxine (T4) and triiodothyronine (T3)—regulate critical body functions, including metabolism, energy use, and temperature control.
TPO has three roles in thyroid hormone production:
- TPO converts iodide into iodine.
- TPO helps attach iodine to thyroglobulin's (TG) tyrosine residues. TG is a thyroid hormone-precursor protein produced by thyroid cells.
- TPO helps link the iodinated tyrosines together to make T4 and T3.
TPO antibodies are a specific type of protein made by the immune system that targets and attacks TPO. When these antibodies bind to TPO, they can impair the thyroid's ability to produce hormones properly, which may lead to hypothyroidism (underactive thyroid) or other thyroid-related disease.
Role in the Immune System
Autoimmunity occurs when the body's immune system mistakenly targets its own healthy cells and tissues and launches an immune response against them. TPO antibodies indicate an aberrant thyroid-specific autoimmune response where the immune system mistakenly identifies TPO as non-self.
TPO antibodies are made by a type of white blood cell called B cells. Once produced, TPO antibodies travel to the thyroid gland and attach to TPO. TPO antibodies act like flags to recruit other immune cells to the area to destroy what they believe is a threat. Over time, this inflammatory immune response can cause chronic inflammation in the thyroid gland, destroy thyroid cells, and disrupt normal thyroid hormone production.
How Thyroid Peroxidase Antibodies Affect Thyroid Function
TPO antibodies can trigger the development of AITD and may be detectable in the blood anywhere from 3 months to 19 years before clinical symptoms appear. For example, approximately 50% of individuals with TPO antibodies will develop overt hypothyroidism within 20 years.
Hashimoto's Thyroiditis
Hashimoto's thyroiditis is the most common form of hypothyroidism. It is an autoimmune disorder in which the immune system mistakenly attacks and damages the thyroid, impairing its ability to produce sufficient amounts of hormones.
TPO antibodies are detected in 90% of all patients with Hashimoto's thyroiditis.
Grave's Disease
Graves' disease is another type of AITD and the most common type of hyperthyroidism. In this condition, the immune system attacks the thyroid and stimulates it to overproduce hormones.
Studies have shown that 57% to 85% of patients with Graves' disease have positive TPO antibodies at the time of their diagnosis.
Causes and Risk Factors
While the exact cause of autoimmunity is not fully understood, several factors may influence the immune system's production of TPO antibodies.
Genetic Predisposition
Research demonstrates that autoimmune diseases can run in families, suggesting a genetic predisposition to these conditions. Children and siblings of individuals with AITD are 16 times and 15 times more likely, respectively, to develop AITD themselves.
Variations in certain genes, such as those in the human leukocyte antigen (HLA) complex, cytotoxic T lymphocyte antigen-4 (CTLA-4), protein tyrosine phosphatase nonreceptor-type 22 (PTPN22), TG, and thyroid-stimulating hormone (TSH) receptor genes, have been associated with an increased risk for developing AITD.
Environmental Triggers
Environmental factors can trigger the autoimmune response in genetically susceptible individuals. Major environmental triggers that have been identified for AITD include:
- Iodine
- Medications, such as amiodarone and interferon-alpha
- Bacterial and viral infections, including Yersinia enterocolitica, Coxsackie B virus, retroviruses, Helicobacter pylori, and hepatitis C virus
- Smoking
- Stress
Other Risk Factors
Females are more likely to make TPO antibodies than males. This female predominance in thyroid autoimmunity is postulated to be associated with immunological variations between the sexes, particularly due to the effects of estrogen on the immune system.
Individuals with other autoimmune diseases also have a higher prevalence of TPO antibodies. This association suggests a shared genetic and immunologic basis for these conditions. Examples of other autoimmune diseases that often coexist with AITD include:
Symptoms and Diagnosis
During the preclinical stages of AITD, a patient has positive thyroid antibodies without changes to thyroid hormone levels. Research demonstrates that patients with elevated TPO antibodies often experience a range of symptoms even when thyroid hormone levels are normal. TPO antibodies are associated with increased inflammation, symptoms of thyroid disease, and reductions in health-related quality of life.
In addition to the symptoms listed below, patients with AITD may develop an enlarged thyroid gland (goiter) due to chronic inflammation. If goiters become large enough, they may cause symptoms like fullness in the neck, difficulty swallowing, and hoarseness of voice.
Hypothyroid Symptoms
Symptoms of hypothyroidism reflect a state of slowed metabolism:
- Fatigue
- Weight gain
- Headaches
- Hair loss
- Brittle nails
- Dry skin
- Decreased body temperature
- Irregular periods
- Constipation
- Depression
- Brain fog
- Joint pain
- Muscle weakness
Hyperthyroid Symptoms
Hyperthyroid symptoms reflect a hypermetabolic state:
- Weight loss
- Increased appetite
- Fast and irregular heart rate and rhythm
- Anxiety
- Irritability
- Insomnia
- Tremors
- Muscle weakness
- Hot flashes and sweating
- Skin thinning
- Fine, thinning hair
- Diarrhea
- Reduced bone density
- Bulging of the eyes
Diagnostic Tests
TPO antibodies can be measured in the blood and are typically ordered as part of a comprehensive thyroid panel to assess thyroid health and function, which includes:
- TSH
- Free and total T4
- Free and total T3
- Reverse T3
- TPO antibody
- Thyroglobulin antibody
- Thyroid-stimulating immunoglobulin (also called thyrotropin receptor antibody)
Interpreting Test Results
TPO antibodies ("Anti-TPO") may be positive with or without overt thyroid disease.
Hashimoto's thyroiditis is diagnosed when:
- TSH is elevated above the standard reference range
- T3 and/or T4 are below the standard reference range
- TPO antibodies are positive
Grave's disease is diagnosed when:
- TSH is below the standard reference range
- T3 and/or T4 are above the standard reference range
- Thyroid-stimulating immunoglobulin is positive
- TPO antibodies may or may not be elevated
The table below lists standard and optimal reference ranges for each component of a comprehensive thyroid panel.
Treatment and Management
Standard medical guidelines focus on treating overt thyroid disease with interventions to normalize thyroid hormones, but they do not emphasize the management of thyroid antibodies.
Medical Management of Hypothyroidism
Clinical hypothyroidism is treated with thyroid hormone replacement to normalize TSH levels and alleviate disease symptoms. Medications that may be prescribed include:
- Levothyroxine (T4)
- Liothyronine (T3)
- Porcine-derived desiccated thyroid (a fixed ratio of T4 and T3)
Medical Management of Hyperthyroidism
Depending on the patient's age, symptoms, comorbidities, and personal preference, clinical hyperthyroidism may be treated with antithyroid medications, radioactive iodine therapy, or surgical removal of part or all of the thyroid gland (thyroidectomy).
Strategies to Lower Thyroid Peroxidase Antibody Levels
While medical management of thyroid disease can effectively normalize thyroid hormones and improve patient quality of life, it does not address the underlying cause of thyroid dysfunction.
Integrative strategies can complement medical treatments by helping to lower TPO antibody levels, slow disease progression, and preserve thyroid function.
- A systematic review and meta-analysis found that selenium supplementation significantly reduced TPO antibody levels in patients with Hashimoto's thyroiditis. The typical dosage used in these studies was 200 μg/day of selenium.
- A meta-analysis indicated that vitamin D supplementation significantly reduced TPO antibody titers in patients with Hashimoto's thyroiditis. However, the effect size and consistency across studies are less robust compared to selenium.
- A 2023 meta-analysis examined the effect of a gluten-free diet (GFD) on TPO antibody levels in patients with Hashimoto's thyroiditis who did not have celiac disease and found a reduction in TPO antibody levels. However, this reduction was not statistically significant, and the authors concluded that current evidence is insufficient to recommend a GFD for all patients with Hashimoto's thyroiditis.
- Stress management strategies may help lower TPO antibody levels. According to one study, the total number of major life events correlated with higher TPO antibody levels, suggesting that stress could indirectly influence TPO antibody levels by affecting the immune response.
Monitoring and Follow-Up
Routine monitoring of thyroid function is an important aspect of managing thyroid disease. Retesting at regular intervals allows one to track changes in thyroid function and adjust treatments as needed.
- Thyroid hormone levels (e.g., TSH and free T4) should be checked every 4-6 weeks after initiating or adjusting thyroid hormone therapy in hypo- and hyperthyroid patients until stable thyroid status is achieved.
- Once stable, TSH levels should be monitored every 6-12 months.
- Per standard medical guidelines, routine monitoring of TPO antibody levels is generally not recommended. However, you can measure changes within 3-6 months of implementing antibody-lowering interventions.
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Key Takeaways
- TPO antibodies are immune proteins that target thyroid peroxidase, an enzyme involved in thyroid hormone production. They are a diagnostic marker for AITD, like Hashimoto's thyroiditis and Graves' disease, where the immune system attacks the thyroid, leading to dysfunction.
- While thyroid antibodies are not given significant attention in standard medical guidelines for screening and treating AITD, their presence is a risk factor for developing overt thyroid disease in the future.
- Given their role in thyroid dysfunction, TPO antibodies should be included in a comprehensive thyroid panel alongside TSH, T3, and T4 for a more complete understanding of thyroid health and disease progression.
- An integrative treatment plan for AITD should incorporate evidence-based therapies to reduce anti-TPO levels, supporting efforts to normalize thyroid hormone levels, slow disease progression, and preserve long-term thyroid function.
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