Reference:

• Chapter 48, "SYNTHESIS OF THYROID HORMONES" in: Walter F., PhD. Boron (2003) Medical Physiology: A Cellular And Molecular Approach, Elsevier/Saunders, pp. 1,300 ISBN: 1-4160-2328-3.

• Thyroglobulin is synthesized in the rough endoplasmic reticulum and follows the secretory pathway to enter the colloid in the lumen of the thyroid follicle by exocytosis.
• Meanwhile, a sodium-iodide (Na/I) symporter pumps iodide (I^-) actively into the cell, which previously has crossed the endothelium by largely unknown mechanisms.
• This iodide enters the follicular lumen from the cytoplasm by the transporter pendrin, in a purportedly passive manner.^[1]
• In the colloid, iodide (I^-) is oxidized to iodine (I⁰) by an enzyme called thyroid peroxidase.
• Iodine (I⁰) is very reactive and iodinates the thyroglobulin at tyrosyl residues in its protein chain (in total containing approximately 120 tyrosyl residues).
• In conjugation, adjacent tyrosyl residues are paired together.
• The entire complex re-enters the follicular cell by endocytosis.
• Proteolysis by various proteases liberates thyroxine and triiodothyronine molecules, which enter the blood by largely unknown mechanisms.