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Thyroglobulin (TG) is a large dimeric glycoprotein synthesized by thyroid follicular cells and secreted into the follicular lumen (UniProt P01266). It serves as the primary substrate for thyroid hormone synthesis, where specific tyrosine residues within its structure are iodinated by the enzyme thyroid peroxidase at the apical membrane (StatPearls, Physiology, Thyroid Hormone). These iodinated tyrosines, specifically monoiodotyrosine (MIT) and diiodotyrosine (DIT), undergo oxidative coupling to form the active hormones thyroxine (T4) and triiodothyronine (T3) (NCBI, Thyroglobulin: Structure, Function and Clinical Application). Beyond its role as a precursor, thyroglobulin acts as a storage reservoir for iodine and thyroid hormones within the thyroid colloid (PubMed, PMID: 25607115). In clinical practice, serum thyroglobulin levels are utilized as a highly sensitive biomarker for detecting residual or recurrent disease in patients with differentiated thyroid cancer (American Thyroid Association). Pharmacological agents like radioactive iodine (I-131) target these sites of iodination to selectively destroy thyroid tissue in hyperthyroidism or malignancy (NIH, Radioactive Iodine (I-131) Therapy). Autoantibodies against thyroglobulin are also significant in the pathogenesis of autoimmune thyroid diseases such as Hashimoto's thyroiditis (StatPearls, Hashimoto Thyroiditis).
Iodination of specific tyrosine residues by thyroid peroxidase followed by the oxidative coupling of iodotyrosines to form T3 and T4.
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