When circulating in the body, most of the T4 and T3 is bound to several different types of transporter proteins. When the thyroid hormones enter a cell they can bind at a number of different sites which can lead to gene activation or other cell-specific effects. Only a small proportion of T4 (around 0.2%) is free and unbound in the blood.[⁴]

T4 is considered mainly inactive but is a prohormone being converted to the active form T3. This is done by D1 (or DIO1) and D2 (or DIO2) type deiodinase enzymes removing an iodine atom. Another deiodinase enzyme, the D3 (or DIO3) type, inactivates T3 and T4 thyroid hormones by removing an iodine elsewhere on the T3/T4 molecular ring structure.[^5,6]

D2 deiodinase activity occurs in cells and tissues throughout the body, especially in the liver. The liver is also the main route for eliminating thyroid hormones from the body. The body’s ability to balance D2 and D3 activity according to need is influenced by endogenous and environmental factors and is one of the core processes in tightly controlling thyroid hormone levels.[^4,5,6]

Subclinical thyroid dysfunction describes patients having abnormal thyroid-stimulating hormone (TSH) levels but ‘normal’ levels of circulating free T4 and T3. Symptoms may or may not be present.[⁷]