Each thyroglobulin molecule contains approximately 16 tyrosine residues, but only around 10 of these are subject to iodination by thyroperoxidase in the follicular colloid.

[7] Newly synthesized thyroid hormones (T3 and T4) exist as prohormonal modified tyrosine residues of thyroglobulin, which comprise the colloid within the follicle.

When endosomes fuse with lysosomes in these cells, Tg is subsequently cleaved by proteases to release thyroglobulin from its T3 and T4 attachments.

The active forms of thyroid hormone (T3 and T4), are then released into circulation where they are either unbound or attached to plasma proteins.

[10] Iodine is recycled back into the follicular lumen where it can continue to serve as a substrate for thyroid hormone synthesis, while the non-modified residues of Tg reenter cellular metabolic pathways.

[11] In the clinical laboratory, thyroglobulin testing can be complicated by the presence of anti-thyroglobulin antibodies (ATAs, alternatively referred to as TgAb).