From the Guidelines
Elevated thyroglobulin levels are primarily caused by thyroid cancer, thyroiditis, hyperthyroidism, goiter, or physical trauma to the thyroid gland, and management depends on the underlying cause, with the goal of achieving undetectable thyroglobulin levels in cancer patients through total thyroidectomy and radioactive iodine therapy 1. The causes of elevated thyroglobulin levels can be categorized into several groups, including:
- Thyroid cancer, particularly differentiated thyroid carcinoma
- Thyroiditis, an inflammatory condition of the thyroid gland
- Hyperthyroidism, a condition characterized by excessive production of thyroid hormones
- Goiter, an enlargement of the thyroid gland
- Physical trauma to the thyroid gland Management of elevated thyroglobulin levels depends on the underlying cause, and may involve:
- Total thyroidectomy followed by radioactive iodine (RAI) therapy for thyroid cancer patients, with doses of I-131 ranging from 30-200 mCi depending on disease extent 1
- Lifelong thyroid hormone replacement therapy with levothyroxine to suppress TSH levels in cancer patients
- Treatment of underlying inflammatory conditions, such as thyroiditis, with anti-inflammatory medications or observation
- Treatment of hyperthyroidism with antithyroid medications, radioactive iodine ablation, or surgery Regular monitoring of thyroglobulin levels every 6-12 months is essential for cancer surveillance, and the presence of anti-thyroglobulin antibodies can interfere with accurate measurement and should always be checked simultaneously 1. In patients with suspected recurrence of differentiated thyroid cancer, elevated thyroglobulin levels with structural disease or no detectable abnormality on imaging require further evaluation and management, which may include neck dissection, repeat RAI therapy, external beam radiotherapy, and systemic therapy 1.
From the Research
Causes of Elevated Thyroglobulin Levels
- Thyroid cancer, particularly papillary thyroid carcinoma, can cause elevated thyroglobulin levels 2, 3
- Lymph node metastasis of differentiated thyroid cancer can also lead to increased thyroglobulin levels 2
- Hashimoto's thyroiditis, an autoimmune condition, can cause elevated thyroglobulin levels 4, 2
- Thyroid nodules, especially those with suspicious ultrasound features, can be associated with elevated thyroglobulin levels 5, 6
- Serum thyroglobulin antibodies (sTgAb) can negatively correlate with fine-needle aspiration thyroglobulin (FNA-Tg) levels 2
Factors Influencing Thyroglobulin Levels
- Serum thyroglobulin (sTg) is positively correlated with FNA-Tg levels 2
- TNM stage, presence of large or high-volume lymph node metastasis, lymph node lateralization/suspicion ratio, ultrasound findings, and tumor size can impact FNA-Tg levels 2
- Presence of Hashimoto's thyroiditis, thyroid capsule invasion, and increased blood flow can also influence FNA-Tg levels 2
Management of Elevated Thyroglobulin Levels
- Fine-needle aspiration biopsy (FNAB) with thyroglobulin measurement can be used to diagnose metastatic cervical lymph nodes from papillary thyroid cancer 2, 3
- Ultrasound-guided FNAB can help detect thyroid cancer and lymph node metastasis 5, 4, 6
- Combined FNAB-Tg/cytology can increase sensitivity and accuracy in detecting metastatic nodes compared to FNAB-cytology alone 3