Iodothyronine deiodinase (peripheral T4 to T3 conversion)

Peripheral T4 to T3 conversion refers to the enzymatic process by which the prohormone thyroxine (T4) is converted into the biologically active triiodothyronine (T3) outside the thyroid gland, primarily in tissues such as liver, gut, kidney, brain, and skeletal muscle. This reaction is catalyzed by a family of enzymes known as iodothyronine deiodinases—mainly type I and type II deiodinases. Type III deiodinase instead converts T4 into reverse-T3 (rT3), an inactive form that can act as a competitive inhibitor at thyroid hormone receptors[2][4][6]. The majority of circulating active thyroid hormone arises from this peripheral conversion rather than direct secretion from the thyroid gland itself. The efficiency and regulation of this process are critical for maintaining normal metabolism; it can be impaired by factors such as stress, inflammation, liver dysfunction, certain drugs like amiodarone or propylthiouracil, chronic illness, or nutrient deficiencies including selenium and iron[2][5]. Disruption in this pathway contributes to various clinical syndromes including hypothyroidism—even when serum thyroxine levels are normal—and non-thyroidal illness syndrome. While "peripheral T4 to T3 conversion" describes a crucial biological process targeted therapeutically in some contexts—such as with antithyroid drugs—it does not refer to a single molecular entity but rather an enzymatic activity carried out by specific proteins. Therefore it is not strictly correct as a canonical target name; instead "Iodothyronine deiodinase" or its subtypes should be used for structured data purposes[2][6].

Other names

Peripheral deiodinaseDeiodinase type I (D1)Deiodinase type II (D2)5'-deiodinase

Inhibition of deiodinases to reduce T3 production from T4, lowering active thyroid hormone levels in tissues[5].