From the Guidelines
The presence of Thyroid Peroxidase (TPO) antibodies is indicative of autoimmune thyroid disease, particularly Hashimoto's thyroiditis, and is recommended for diagnosis in patients with symptoms of hypothyroidism, an enlarged thyroid gland, or abnormal thyroid function tests.
Diagnosis and Recommendations
The test should be ordered when a patient presents with symptoms of hypothyroidism, an enlarged thyroid gland, or abnormal thyroid function tests, as stated in the 2023 standards of care in diabetes 1. A positive TPO antibody result (typically >35 IU/mL, though reference ranges vary by laboratory) indicates autoimmune thyroid disease. This test is particularly useful when thyroid function tests show subclinical hypothyroidism (elevated TSH with normal T4) to determine if the condition has an autoimmune etiology. TPO antibodies are present in over 90% of Hashimoto's thyroiditis cases and about 75% of Graves' disease cases. The presence of these antibodies indicates that the immune system is attacking the thyroid gland, specifically targeting the enzyme thyroid peroxidase which is essential for thyroid hormone production. While a positive result confirms autoimmunity, treatment decisions should be based on thyroid function and clinical presentation rather than antibody levels alone, as suggested by the 2021 standards of medical care in diabetes 1. TPO antibody testing is not typically used for monitoring treatment response as levels may remain elevated despite successful management of thyroid function.
Key Points to Consider
- Autoimmune thyroid disease is the most common autoimmune disorder associated with diabetes, occurring in 17–30% of patients with type 1 diabetes 1.
- At the time of diagnosis, about 25% of children with type 1 diabetes have thyroid autoantibodies, the presence of which is predictive of thyroid dysfunction—most commonly hypothyroidism, although hyperthyroidism occurs in <0.5% of patients with type 1 diabetes 1.
- Thyroid function tests may be misleading (euthyroid sick syndrome) if performed at the time of diagnosis owing to the effect of previous hyperglycemia, ketosis or ketoacidosis, weight loss, etc., and should be repeated soon after a period of metabolic stability and good glycemic control 1.
From the Research
Diagnosis of Thyroid Peroxidase (TPO) Antibody Presence
The presence of Thyroid Peroxidase (TPO) antibodies is a key indicator of autoimmune thyroid diseases. The diagnosis of TPO antibody presence involves the use of sensitive and specific assays to detect the antibodies in serum.
- The assay of anti-TPO with third-generation ultrasensitive methods is considered the main test for the diagnosis of autoimmune thyroid diseases 2.
- The presence of TPO antibodies is a clear risk factor for hypothyroidism, and measuring TPO antibodies in euthyroid subjects can be used to identify subjects with increased risk for hypothyroidism 3.
- A cut-off point of 200 units/ml can be used to diagnose Hashimoto's thyroiditis and Graves' disease, with a sensitivity of 96% and 59%, respectively, and a specificity of 100% 4.
Clinical Validity of TPO Antibody Assays
The clinical validity of TPO antibody assays has been evaluated in several studies.
- Clearly elevated anti-TPO values (> 500 units/ml) were found in 59% of patients with thyroiditis, but in none of the controls or patients with non-thyroidal illness 4.
- The mean anti-TPO levels in controls and patients with non-thyroidal illness were 26 +/- 31 units/ml and 39 +/- 34 units/ml, respectively 4.
- The highest frequency of positive results (88%) was obtained in patients with auto-immune hypothyroidism (clinical diagnosis: Hashimoto's thyroiditis) followed by patients with Graves' disease (53%) 4.
Analytical Aspects of TPO Antibody Estimation
The estimation of TPO antibodies involves several technical difficulties, including the development of a humoral response to the antigens and the detection and measurement of their concentrations.
- Multiple antigen configurations of thyroglobulin (TG) are produced when it is iodinated, resulting in functionally active but immunologically distinct molecules 5.
- Thyroid peroxidase (TPO) is present on the apical surface of thyroid follicular cells and is the antigen most closely involved in cell-mediated cytotoxicity 5.
- The aetiology and mechanics of the autoimmune cellular and antibody responses involve a combination of HLA linkage, genetics, and environmental factors to determine the initial and subsequent stages of the development of autoimmune thyroid disease 5.