From the Guidelines
Thyroglobulin antibodies and thyroglobulin tests should be ordered together when monitoring thyroid cancer, as thyroglobulin antibodies can interfere with thyroglobulin measurement, potentially causing falsely low results 1. When evaluating thyroid function, it is essential to understand the differences between thyroglobulin antibodies (TgAb) and thyroglobulin (Tg) tests.
- Thyroglobulin antibodies measure autoantibodies that target thyroglobulin protein, indicating autoimmune thyroid disease like Hashimoto's thyroiditis.
- Thyroglobulin testing measures the actual thyroglobulin protein produced by thyroid cells, primarily used to monitor for recurrence in thyroid cancer patients after thyroidectomy. The presence of thyroglobulin antibodies can interfere with thyroglobulin measurement, potentially causing falsely low results, which can lead to missed cancer recurrence if antibodies are present but not tested for 1. TgAb levels above 20 IU/mL typically indicate significant interference with thyroglobulin measurement. For patients with known or suspected autoimmune thyroid disease without cancer, thyroglobulin antibody testing alone may be sufficient, while cancer surveillance requires both tests for accurate interpretation 1. The choice of further imaging depends on the response to therapy based upon results from serum thyroglobulin testing and US performed in the first year after definitive treatment. An excellent response to therapy is associated with a low recurrence risk (<5%) in patients with low- or intermediate-risk tumors. For these patients, if the serum thyroglobulin remains low, additional imaging is not indicated. For patients with thyroidectomy and RAI ablation, a low serum thyroglobulin is defined as a level of <0.2 ng/mL on thyroid hormone therapy in a sensitive assay or <1 ng/mL after TSH stimulation in patients who have undergone thyroidectomy and radioiodine ablation 1. The serum thyroglobulin is elevated above the appropriate cutoff or if thyroglobulin antibodies are present and especially if they are rising, additional surveillance imaging is performed. In summary, both thyroglobulin antibodies and thyroglobulin tests are essential in thyroid evaluation, and their combined use provides valuable diagnostic information about autoimmune thyroid conditions and cancer recurrence.
From the Research
Thyroglobulin Antibodies vs Plain Thyroglobulin
- Thyroglobulin (Tg) is a disease marker for differentiated thyroid cancer, but thyroglobulin-antibodies (Tg-Ab) can interfere with Tg measurement, leading to over or underestimation 2.
- The trend of Tg-Ab can be used as a surrogate marker for disease recurrence, with a rising trend warranting further investigation 2, 3.
- A significant decrease in Tg-Ab levels can represent a good prognostic sign, while stable or increasing Tg-Ab levels may indicate a risk for recurrence 3, 4.
- Tg-Ab can interfere with Tg measurement, especially when using immunometric assays, resulting in underestimated values of Tg 4, 5.
- Neck ultrasonography (US) should be performed in patients with detectable Tg-Ab and negative Tg-IMA, and significant elevation of Tg-Ab requires extended investigation 4.
Clinical Implications
- The presence or absence of Tg-Ab, as well as the trend of Tg-Ab levels, should be considered in the follow-up of patients with differentiated thyroid cancer 2, 3, 4.
- Patients with negative Tg-IMA and US without abnormalities who exhibit a reduction > 50% in Tg-Ab generally do not require investigation 4.
- The management and follow-up of patients with borderline Tg-Ab can probably be the same as those recommended for patients without Tg-Ab if Tg-2GIMA and US indicate an excellent response to therapy 4.
Laboratory Aspects
- Thyroglobulin measurement is a complex process with many pitfalls, and anti-thyroglobulin antibodies need to be assessed and dealt with appropriately 6, 5.
- The use of highly-sensitive thyroglobulin assays and TgAb measurement can improve the detection of recurrent disease 6, 4.
- Interference from TgAb can be minimized by using alternative assay methods, such as liquid chromatography/tandem mass spectrometry 4.