What is the management approach for a patient with positive thyroglobulin (TG) antibodies?

From the Guidelines

Patients with positive thyroglobulin (TG) antibodies require a specialized management approach that includes careful monitoring and the use of both thyroglobulin measurements and imaging studies for follow-up. The presence of TG antibodies interferes with standard thyroglobulin assays, making it difficult to reliably use thyroglobulin as a tumor marker for thyroid cancer surveillance 1. For these patients, I recommend using both thyroglobulin measurements and imaging studies for follow-up. Specifically, patients should undergo periodic neck ultrasounds every 6-12 months and, depending on their risk stratification, may require whole-body radioiodine scans. TG antibody levels themselves should be monitored as a surrogate tumor marker, as declining antibody levels often correlate with successful treatment while persistent or rising levels may indicate residual disease.

Key Considerations

• The presence of TG antibodies alone does not change the overall treatment approach but does alter the surveillance strategy 1.
• More sensitive thyroglobulin assays such as liquid chromatography-tandem mass spectrometry (LC-MS/MS) may be used as they are less affected by antibody interference.
• For patients with differentiated thyroid cancer, TSH suppression therapy with levothyroxine should be continued according to their risk category.
• The use of rhTSH-stimulated serum Tg measurement may still be informative in patients with basal serum Tg levels between 0.1-1.0 ng/ml, as it may detect those patients in whom serum Tg increases to >1 ng/ml 1.

Surveillance Strategy

• Patients with positive TG antibodies should be monitored closely, with regular assessments of their TG antibody levels and imaging studies as needed.
• The goal of surveillance is to detect any signs of disease recurrence or persistence, and to intervene early if necessary.
• The use of a combination of thyroglobulin measurements and imaging studies can help to identify patients who require more intensive follow-up or treatment.

From the Research

Management Approach for Patients with Positive Thyroglobulin Antibodies

The management of patients with positive thyroglobulin (TG) antibodies requires careful consideration of the potential impact on thyroid function tests and the risk of thyroid disease.

• The presence of anti-thyroglobulin antibodies (TgAb) can lead to underestimation of serum thyroglobulin (Tg) levels, making it challenging to interpret test results 2.
• In patients with differentiated thyroid cancer (DTC) who have undergone total thyroidectomy and radioactive iodine ablation, the American Thyroid Association does not recommend serum Tg testing after thyroid hormone withdrawal or recombinant human thyrotropin administration (stimulated Tg) and diagnostic whole-body scanning (DxWBS) in TgAb-positive patients with serum Tg values <1 ng/mL while on thyroxine (Tg-on-T4) 2.

Diagnostic Whole-Body Scanning and Serum Thyroglobulin Testing

• A study found that performing stimulated Tg and DxWBS at the same time can be useful in detecting persistent disease in DTC patients with TgAb who do not appear to have persistent disease, even when ultrasound is negative 2.
• The study suggested that stimulated Tg and DxWBS can reveal evidence of disease in a significant proportion of patients, highlighting the importance of considering these tests in the management of patients with positive TG antibodies 2.

Thyroid Hormone Autoantibodies

• Research has also explored the role of thyroid hormone autoantibodies (thAbs) in detecting early thyroid damage in patients with hematologic cancers receiving tyrosine kinase inhibitor or immunoregulatory drug treatments 3.
• The study found that thAbs were a reliable marker of early thyroid dysfunction, with a higher sensitivity than standard thyroid tests 3.

Reference Intervals for Thyroid Stimulating Hormone (TSH) and Free Thyroxine (FT4)

• The effect of thyroid antibody positivity on reference intervals for TSH and FT4 has been evaluated in an aged population 4.
• The study found that the exclusion of subjects with elevated thyroid antibodies had no significant effect on the FT4 reference interval in either gender or on the TSH reference interval in men, but it lowered the upper reference limit of TSH in women 4.

Levothyroxine Treatment in Subclinical Hypothyroidism

• A pooled analysis of two randomized controlled trials investigated the effects of levothyroxine treatment on subclinical hypothyroidism in older adults with and without positive anti-thyroid peroxidase (TPO) antibodies 5.
• The study found that positive anti-TPO antibodies were not associated with more benefits on clinical outcomes with levothyroxine treatment, suggesting that the presence of antibodies does not necessarily influence the response to treatment 5.