The thyroid hormones, thyroxine (T4) and triiodothyronine (T3), are tyrosine-based hormones produced by the thyroid gland. They act on the body to increase the basal metabolic rate, affect protein synthesis and increase the body's sensitivity to catecholamines (such as adrenaline). An important component in the synthesis is iodine.

The major form of thyroid hormone in the blood is thyroxine (T4). This is converted to the active T3 within cells by deiodinases.

Most of the thyroid hormone circulating in the blood is bound to transport proteins :

• Thyroxine-binding globulin (TBG)
• Thyroid binding prealbumin (TBPA) - this protein is also responsible for the transport of retinol, and so now has the preferred name of transthyretin (TTR)
• albumin

Only a very small fraction of the circulating hormone is free (unbound) - T₄ 0.03% and T₃ 0.3%. This free fraction is biologically active, hence measuring concentrations of free thyroid hormones is of great diagnostic value. These values are referred to as fT₄ and fT₃. Another critical diagnostic tool is the amount of thyroid-stimulating hormone that is present.

When thyroid hormone is bound, it is not active, so the amount of free T3/T4 is what is important. For this reason, measuring total thyroxine in the blood can be misleading.

The thyroid hormones are essential to proper development and differentiation of all cells of human body. To various extents they regulate protein, fat and carbohydrate metabolism. But they have their most pronounced effects on how human cells use engergetic compounds.

Numerous physiological and pathological stimuli influence thyroid hormone synthesis.

Thyrotoxicosis or hyperthyroidism is the clinical syndrome caused by an excess of circulating free thyroxine, free triiodothyronine, or both. It is a common disorder that affects approximately 2% of women and 0.2% of men.

Structure and production of the thyroid hormones

Thyroxine (3:5,3':5' tetra­iodothyronine) is produced by follicular cells of the thyroid gland. It is produced as the precursor thyroglobulin (this is not the same as TBG), which is cleaved by enzymes to produce active T4.

Thyroxine is produced by attaching iodine atoms to the ring structures of tyrosine molecules. Thyroxine contains four iodine atoms. Triiodothyronine is identical to T4, but it has one less iodine atom per molecule.

Iodide is actively absorbed from the bloodstream and concentrated in the thyroid follicles. (If there is a deficiency of dietary iodine, the thyroid enlarges in an attempt to trap more iodine, resulting in goitre.) Via a reaction with the enzyme thyroperoxidase, iodine is covalently bound to tyrosine residues in the thyroglobulin molecules, forming monoiodotyrosine (MIT) and diiodotyrosine (DIT). By linking two moieties of DIT we have thyroxine. Combining one particle of MIT and one particle of DIT produces triiodothyronine.

MIT + DIT = triiodothyronine (usually referred to as T₃) DIT + DIT = thyroxine (referred to as T₄)

Proteases digest iodinated thyroglobulin, releasing the hormones T4 and T3, the biologically active agents central to metabolic regulation. Thyroxine is supposedly a prohormone and a reservoir for the most active and main thyroid hormone T₃. T₄ is converted as required in the tissues by deiodinases.

Medical use of thyroid hormones

Both T3 and T4 are used to treat thyroid hormone deficiency (hypothyroidism). They are both absorbed well by the gut, so can be given orally.

External links

• Discussion of thyroxine treatment.