T4 is deiodinated either to the active metabolite T3 or to a biologically inactive metabolite known as reverse T3 (rT3) (Fig. 15.10). Three types of T4 5' deiodinase have been described. Type I is a widely distributed selenoprotein that is responsible for generation of the majority of T3. It has reduced activity in starvation or severe illness and is inhibited by propylthiouracil. Type II is present in the brain and pituitary. It is important for local generation of T3 in these areas and has increased activity in hypothyroidism. In healthy individuals, T4 is converted equally to T3 and rT3, but in severely ill people suffering from a variety of acute and chronic non thyroidal illnesses, less T3 is produced and high levels of rT3 accumulate. T3 and rT3 are usually subsequently further deiodinated or conjugated into metabolically inactive compounds.
