[1] Thyroxine and its active metabolites are essential for regulating metabolic rate, supporting heart and muscle function, promoting brain development, and maintaining bone health.

[5][6][4] The process begins with the active uptake of iodide from the bloodstream by thyroid follicular cells through the sodium/iodide symporter (NIS) located in the basolateral membrane.

Once inside the cell, iodide is transported to the follicular lumen, where it undergoes oxidation by the enzyme thyroid peroxidase (TPO) in the presence of hydrogen peroxide generated by the NADPH oxidase DUOX2.

[5] This process, known as organification, results in the formation of monoiodotyrosine (MIT) and diiodotyrosine (DIT) residues within the Tg molecule.

[6][4] The final step in thyroxine synthesis involves the free radical mediated coupling of two DIT residues, catalyzed by TPO, to form T4 while still attached to the Tg backbone.