Thyroglobulin (Tg) is a glycoprotein that is synthesized in large quantities by thyrocytes (thyroid cells) and secreted into the follicular lumen. It plays a crucial role in the synthesis of the thyroid hormones triiodothyronine (T3) and thyroxine (T4). Thyroglobulin contains approximately 132 tyrosine residues, about one-third of which can be iodinated to mono- and diiodotyrosine (MIT and DIT) with the help of thyroperoxidase and iodine. The subsequent coupling of MIT and DIT to form T3 and T4 also occurs within the thyroglobulin matrix with the involvement of thyroperoxidase.
The synthesis of T3 and T4 from thyroglobulin is regulated by thyroid-stimulating hormone (TSH), the level of iodine within the thyroid, and the presence of thyroid-stimulating immunoglobulins. During the synthesis of thyroglobulin by thyrocytes and its transfer to the follicles, small amounts of the protein can enter the bloodstream. Consequently, low concentrations of thyroglobulin can be detected in the blood.
Thyroglobulin levels in the blood can be high in a number of thyroid-related diseases.
The main causes of elevated thyroglobulin levels are:
• Thyroid cancer, particularly differentiated thyroid cancers (papillary and follicular types), where thyroglobulin is used as a tumor marker to detect residual, recurrent, or metastatic disease.
• Benign proliferative thyroid diseases, such as thyroid nodules, adenomas, and goiter, which increase the mass of thyroid tissue and thyroglobulin production.
• Autoimmune thyroid diseases, such as Hashimoto's thyroiditis and Graves' disease, which are associated with the destruction or inflammation of thyroid tissue.
• Thyroiditis (inflammation of the thyroid) and physical trauma to the thyroid gland.
• Hyperthyroidism, due to increased thyroid activity.
• Thyroglobulin levels can be temporarily high after thyroid surgery or injury to the thyroid tissue.
• Iodine deficiency or excess can also affect thyroglobulin levels.
The presence of anti-thyroglobulin antibodies (TgAb) can interfere with thyroglobulin measurement, which can lead to falsely high or falsely low thyroglobulin values. Therefore, it is recommended to simultaneously test for anti-thyroglobulin antibodies to rule out this interference.