From the Guidelines
Thyroid peroxidase (TPO) is a crucial enzyme in thyroid hormone production and a common target for autoantibodies in autoimmune thyroid diseases, making it significant in the diagnosis and management of thyroid dysfunction, particularly in individuals with type 1 diabetes, as indicated by the most recent study 1.
Clinical Significance of TPO
The clinical significance of TPO lies in its role as a target for autoantibodies in autoimmune thyroid diseases, such as Hashimoto's thyroiditis and Graves' disease. The presence of anti-TPO antibodies is a standard diagnostic tool for evaluating thyroid dysfunction and can predict future thyroid dysfunction, even when thyroid function tests are normal.
TPO in Autoimmune Thyroid Diseases
Autoimmune thyroid disease is the most common autoimmune disorder associated with diabetes, occurring in 17–30% of individuals with type 1 diabetes 1. At the time of diagnosis, 25% of children with type 1 diabetes have thyroid autoantibodies, which are predictive of thyroid dysfunction, most commonly hypothyroidism, although hyperthyroidism occurs in 0.5% of people with type 1 diabetes.
Recommendations for TPO Testing
The most recent guidelines recommend assessing for additional autoimmune conditions, including thyroid dysfunction, soon after the diagnosis of type 1 diabetes and if symptoms develop 1. For thyroid autoantibodies, anti-thyroid peroxidase antibodies were found to be more predictive than antithyroglobulin antibodies in multivariate analysis, highlighting the importance of TPO in the diagnosis and management of autoimmune thyroid diseases.
Implications for Patient Care
Understanding the significance of TPO in thyroid hormone production and autoimmune thyroid diseases is essential for explaining the pathophysiology of these disorders and the mechanism of action for certain antithyroid medications that inhibit this enzyme. The presence of elevated anti-TPO antibodies indicates autoimmune thyroid disease and may predict future thyroid dysfunction, allowing for early intervention and management to improve patient outcomes.
From the Research
Significance of Thyroid Peroxidase (TPO)
- Thyroid peroxidase (TPO) is an enzyme that participates in thyroid hormone biosynthesis 2, 3, 4, 5.
- TPO is also a major autoantigen in autoimmune thyroid diseases (AITD) such as Hashimoto's disease and Graves' disease 2, 3, 4, 6.
- Autoantibodies to TPO (TPOAbs) are a hallmark of autoimmune thyroid disease (AITD) and are directed predominantly to two immunodominant determinants (IDR) termed IDR-A and IDR-B regions 4.
- TPO undergoes complex post-translational modifications as a dimer in endoplasmic reticulum during secretory pathway to apical membrane of thyrocytes 4.
- The enzyme has a dual active site and plays a crucial role in thyroid hormone synthesis, with autoantibodies to TPO being a significant factor in autoimmune thyroid disease 4, 5.
Role of TPO in Autoimmune Thyroid Disease
- Autoimmunity to TPO is characterized by autoantibodies and T cell reactivity in Hashimoto's disease and Graves' disease 4.
- Strong genetic risk has been shown to be associated with TPOAbs for AITD development 4.
- A different antibody with unusual features of bispecificity for both TPO and thyroglobulin may play a protective role in Hashimoto's disease 4.
Structural and Functional Aspects of TPO
- TPO can exist as both a monomer and a dimer, with the monomer being the preferred form for binding to autoantibodies 3.
- The enzyme has two active site regions and autoantigenic determinants, which are important for its function and interaction with autoantibodies 3, 4.
- TPO and hydrogen peroxide generating DUOX and caveolin-1 form a complex known as thyroxisome to bring together in close proximity the components of hormone synthesis in apical membrane 4.