Thyroglobulin: current aspects of its role in autoimmune thyroid disease and thyroid cancer

Thyroglobulin (Tg) is a large glycoprotein (molecular weight: 660000) with 2 polypeptide chains of approximately 2768 amino acids each. It functions both as a pro-hormone and storage hormone for thyroid hormones. The complete Tg gene sequence has been determined for human, rat and bovine species. Tg is one of the thyroid autoantigens recognised in patients with autoimmune thyroid disease (AITD). Antibodies to Tg (TgAb) are present in the serum of patients with AITD and are also sometimes present in healthy euthyroid subjects. Though at least 40 antigenic epitopes on human Tg have been identified, only 2 or 3 of these bind TgAb. Epitope mapping studies suggest that TgAb in AITD patients express a restricted binding pattern while TgAb in the serum of healthy individuals do not show such specific binding. There is evidence to suggest that iodination of Tg may alter these epitope binding patterns. TgAb IgG on the other hand, do not appear to be subclass restricted. Several Tg fragments capable of inducing a T-cell response have been described. Tg is routinely used in the postoperative monitoring of patients with differentiated thyroid cancer. Its use has been limited by problems with assay methods which include poor inter-laboratory standardisation, poor inter-assay variation, low functional sensitivity of the assays, hook effects, and interference from TgAb present in patients serum. The use of rh-TSH in stimulating Tg prior to testing has improved the sensitivity of Tg values in the suppressed state.