From the Guidelines
High thyroglobulin antibodies (TgAb) are primarily caused by autoimmune thyroid disorders, particularly Hashimoto's thyroiditis, as indicated by the most recent and highest quality study available 1.
Causes of High Thyroglobulin Antibodies
These antibodies develop when the body's immune system identifies thyroglobulin (a protein produced by the thyroid) as foreign and mounts an immune response against it. Several factors contribute to this autoimmune reaction, including:
- Genetic predisposition, with a family history of autoimmune disorders increasing risk
- Environmental triggers such as excessive iodine intake, radiation exposure, certain medications, viral infections, and stress
- Women are more susceptible than men, and the condition often appears during periods of hormonal fluctuation
- Other autoimmune conditions like rheumatoid arthritis or lupus may increase the likelihood of developing thyroid antibodies
Diagnosis and Management
Treatment typically focuses on managing the underlying thyroid dysfunction rather than directly targeting the antibodies, often involving thyroid hormone replacement therapy like levothyroxine when hypothyroidism develops, as recommended by 1. Regular monitoring of thyroid function is essential, as antibody levels may fluctuate over time and can indicate disease progression. The presence of thyroid autoantibodies (antithyroid peroxidase [TPO] and antithyroglobulin [TG]) identifies patients at increased risk for thyroid autoimmunity, as noted in 1.
Key Considerations
The American Thyroid Association risk categories of recurrence help to guide imaging and treatment decisions for patients with suspected recurrence of differentiated thyroid cancer, as outlined in 1 and 1. In general, more imaging modalities are used to pursue recurrence in high-risk patients because distant metastases are more likely in these patients and negatively impact survival. Recurrence with a structural abnormality can be treated with neck dissection, repeat RAI therapy, external beam radiotherapy, and systemic therapy.
Monitoring and Follow-Up
The serum TSH test is the primary screening test for thyroid dysfunction, and multiple tests should be done over a 3- to 6-month interval to confirm or rule out abnormal findings, as recommended by 1 and 1. Follow-up testing of serum T4 levels in persons with persistently abnormal TSH levels can differentiate between subclinical (normal T4 levels) and “overt” (abnormal T4 levels) thyroid dysfunction. The optimal screening interval for thyroid dysfunction is unknown, but clinicians should be aware of subtle signs of thyroid dysfunction, particularly among those at high risk, including the elderly, postpartum women, those with high levels of radiation exposure, and patients with Down syndrome.
From the Research
Causes of High Thyroglobulin Antibodies
- High thyroglobulin antibodies can be caused by autoimmune thyroid diseases, such as Hashimoto's thyroiditis and Graves' disease 2, 3, 4, 5.
- In Hashimoto's thyroiditis, the immune system attacks the thyroid gland, leading to inflammation and damage, which can result in high levels of thyroglobulin antibodies 2, 3.
- Graves' disease, on the other hand, is characterized by the presence of autoantibodies that stimulate the TSH receptor, leading to hyperthyroidism, and can also be associated with high levels of thyroglobulin antibodies 4, 5.
- The shift from Graves' disease to Hashimoto's thyroiditis has been reported in the literature, and it is thought that the immune system's response to the thyroid gland can change over time, leading to different autoimmune diseases 5.
- Autoimmuno-dominant thyroglobulin epitopes have been characterized, and it is thought that these epitopes play a role in the development of autoimmune thyroid diseases 6.
- The presence of high levels of thyroglobulin antibodies can interfere with the measurement of anti-thyroglobulin antibody using highly sensitive assays, and can also be associated with thyroid lymphocytic infiltrates and hypothyroidism 2, 3.