Does an asymptomatic patient with very high thyroglobulin antibody (TgAb) levels and normal thyroid function require an ultrasound to rule out thyroid cancer?

From the Guidelines

Yes, an ultrasound is generally recommended for asymptomatic patients with very high thyroglobulin antibodies and normal thyroid function to rule out thyroid cancer. The patient should undergo a thyroid ultrasound examination, which is a non-invasive imaging test that can detect nodules or other abnormalities in the thyroid gland. This should be performed by a qualified radiologist or endocrinologist experienced in thyroid imaging, as suggested by the American College of Radiology 1. While high thyroglobulin antibodies alone do not necessarily indicate cancer, they can be associated with autoimmune thyroid conditions or, less commonly, thyroid malignancies. An ultrasound can help identify any suspicious nodules or structural changes that may require further investigation, such as a fine-needle aspiration biopsy, as recommended by the European Society for Medical Oncology 1. Some key points to consider when evaluating thyroid nodules include:

• Thyroid ultrasound (US) is a widespread technique used as a first-line diagnostic procedure for detecting and characterizing nodular thyroid disease.
• US features associated with malignancy include hypoechogenicity, microcalcifications, absence of peripheral halo, irregular borders, solid aspect, intranodular blood flow, and shape (taller than wide).
• Fine-needle aspiration cytology (FNAC) should be performed in any thyroid nodule >1 cm and in those <1 cm if there is any clinical or ultrasonographic suspicion of malignancy. The ultrasound results, combined with the antibody levels and thyroid function tests, will guide the next steps in management. If the ultrasound is normal, regular monitoring of thyroid function and antibody levels may be sufficient. If abnormalities are found, further testing or referral to an endocrinologist may be necessary. This approach is justified because early detection of thyroid cancer, if present, can lead to more effective treatment and better outcomes, as noted in the guidelines for diagnosis, treatment, and follow-up of thyroid cancer 1. Additionally, ruling out cancer can provide reassurance to the patient and help determine the appropriate follow-up strategy for their thyroid health.

From the Research

Thyroglobulin Antibody (TgAb) Levels and Thyroid Cancer Risk

• High levels of TgAb can interfere with thyroglobulin measurement, making it challenging to monitor patients for residual or recurrent disease 2, 3
• The presence of TgAb is associated with an increased risk of thyroid cancer in patients with thyroid nodules, with a positive TgAb test being an independent predictor for thyroid malignancy 4
• TgAb levels can be used to guide investigation and management of patients with differentiated thyroid cancer, with rising levels potentially indicating persistent, recurrent, or progressive disease 5, 3

Ultrasound Examination in Patients with High TgAb Levels

• Neck ultrasonography (US) is recommended in patients with detectable TgAb levels more than 6 months after initial therapy, even if thyroglobulin levels are undetectable by immunometric assay (IMA) 5
• Significant elevation of TgAb requires extended investigation, including ultrasound examination, to rule out thyroid cancer 5
• Patients with negative Tg-IMA and US without abnormalities who exhibit a reduction > 50% in TgAb generally do not require further investigation 5

Clinical Implications

• Asymptomatic patients with very high TgAb levels and normal thyroid function may require an ultrasound examination to rule out thyroid cancer, especially if TgAb levels are rising or persisting over time 5, 4, 3
• The presence of high TgAb levels should prompt further investigation, including ultrasound examination, to assess the risk of thyroid cancer and guide management decisions 5, 4, 3