A 21 year old student is found to have hyperthyroidism. She is counselled on treatment options including radioactive iodine and antithyroid medications. Carbimazole acts on which part of the thyroid hormone synthesis pathway?
Iodide is actively transported into follicular cells by a sodium/iodide transporter (Fig. 18.6). Pendrin is found at the apical membrane, where it transports iodide into colloid. A defect in this transporter underlies Pend red's syndrome (congenital hypothyroidism and deafness). Thyroid peroxidase catalyses the conversion of iodide ions into organic iodine and couples it with tyrosine to form MIT and DIT. This later step is inhibited by thionamides such as carbimazole. DIT and MIT combine forming T4 and T3. The organification of iodide and coupling of iodinated tyrosine molecules occurs on the surface of thyroglobulin. This is subsequently cleaved, releasing thyroid hormone. Uncoupled iodinated tyrosine can be dehalogenated, allowing recycling of the iodine. The majority of T4 circulates bound to thyroxine-binding globulin (TBG).
Cleavage of thyroglobulin by proteolysis
Coupling of monoiodotyrosine (MIT) and diiodotyrosine (DIT) forming triiodothyronine CTsl and thyroxine (T4)
Dehalogenation of iodinated tyrosine to recycle iodide
Organification of iodide by thyroid peroxidase incorporating tyrosine forming MIT and DIT