What are the non-thyroidal effects of Thyroid Peroxidase (TPO) antibodies?

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Last updated: February 28, 2025View editorial policy

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From the Guidelines

Thyroid peroxidase (TPO) antibodies have been associated with non-thyroidal effects, including chronic spontaneous urticaria (CSU), where they may contribute to autoallergic or autoimmune-mediated skin mast cell activation, as indicated by the presence of IgG–anti-TPO and total IgE levels 1. The non-thyroidal effects of TPO antibodies can be seen in various conditions, such as:

  • Chronic spontaneous urticaria (CSU), where TPO antibodies may play a role in autoallergic or autoimmune-mediated skin mast cell activation, with a high ratio of IgG–anti-TPO to total IgE being a surrogate marker for autoimmune CSU 1
  • Reproductive issues, including recurrent pregnancy loss, infertility, and adverse pregnancy outcomes, although the evidence for this is not as strong as for CSU
  • Potential links to neuropsychiatric conditions, such as depression and anxiety, and certain autoimmune disorders outside the thyroid, including pernicious anemia, vitiligo, and rheumatoid arthritis, although more research is needed to confirm these associations The mechanism behind these non-thyroid effects likely involves systemic inflammation, cross-reactivity with non-thyroid tissues, and potential direct effects on target organs. Monitoring thyroid function in TPO antibody-positive individuals is crucial, even when thyroid function tests are initially normal, as these patients have an increased risk of developing thyroid dysfunction over time 1. It is essential to note that while TPO antibodies have been linked to various non-thyroidal effects, the evidence is not always strong, and more research is needed to fully understand the relationships between TPO antibodies and these conditions. In clinical practice, it is essential to consider the potential non-thyroidal effects of TPO antibodies and to monitor patients with these antibodies for signs of thyroid dysfunction and other related conditions.

From the Research

Non-Thyroidal Effects of Thyroid Peroxidase (TPO) Antibodies

  • TPO antibodies have been associated with various non-thyroidal effects, including increased risk of mortality, particularly in men 2
  • The presence of TPO antibodies has been linked to low-grade inflammation, which may contribute to the development of cardiovascular disease and cancer 2
  • TPO antibodies have also been found to be associated with other autoimmune diseases, such as pernicious anemia, connective tissue disorders, and diabetes 3
  • In addition, TPO antibodies have been linked to fertility-related problems, including miscarriage, infertility, and pre-term delivery 3
  • The presence of TPO antibodies may also be associated with mood disorders, such as depression 3

Determinants of TPO Antibodies

  • Female sex and current smoking have been identified as determinants of TPO antibody positivity and detectability 2
  • Higher age and alcohol consumption have been associated with lower odds of TPO antibody detectability 2
  • The presence of TPO antibodies has been found to be more prominent in men compared to women, particularly in relation to cardiovascular mortality 2

Clinical Implications of TPO Antibodies

  • The detection of TPO antibodies may be useful in identifying individuals at risk of developing hypothyroidism, particularly in women who wish to become pregnant and those with a history of autoimmune thyroid disease 4
  • TPO antibody levels may also be used to monitor the effectiveness of treatment for autoimmune thyroid disease 5
  • The clinical importance of detectable TPO antibody levels is illustrated by the association with an increased mortality risk, mainly in men 2

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Clinical and laboratory aspects of thyroid autoantibodies.

Annals of clinical biochemistry, 2006

Research

Thyroid peroxidase autoantibodies in euthyroid subjects.

Best practice & research. Clinical endocrinology & metabolism, 2005

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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