Thyroid hormone synthesis requires oxidation of dietary iodine, followed by iodination of tyrosine to mono- and diiodotyrosine; coupling of iodotyrosines leads to formation of the active molecules, tetraiodo-tyrosine, (T4 or L-thyroxine) and triiodotyrosine (T3 or L-thyronine).
These active thyroid hormones are stored in the gland within the molecule of thyroglobulin, a major component of the intrafollicular colloid. They are released into the circulation following reuptake of the colloid by the apical cells and proteolysis. The main circulating thyroid hormone is T4. About 80% of the released T4 is deiodinated in the peripheral tissues to the biologically active T3 (30-35%) and biologically inactive reverse T3 (45-50%); thus most circulating T3 is derived from T4. Further deiodi-nation, largely in the liver, leads to loss of activity.
In the blood both T4 and T3 are extensively (99.9%) bound to plasma proteins (thyroxine-binding globulin, TBG, and thyroxine-binding prealbumin, TBPA). The concentration of TBG is raised by oestrogens (including doses used in oral contraceptives), prolonged use of neuroleptics, and in pregnancy. The concentration of TBG is lowered by adrenocortical and androgen (including anabolic steroid) therapy and by urinary protein loss in nephrotic syndrome. Phenytoin and salicylates compete with thyroid hormone for TBG binding sites. Effects such as these would interfere with the assessment of the clinical significance of measure ments of total thyroid hormone concentration but the availability of free thyroid hormone assay (free thyroxine index) largely avoids such complicating factors. Normal values are: free T4 9-25 pmol/1, free T3 3-9 pmol/1.
T4 and T3 are well absorbed from the gut, except in myxoedema coma when parenteral therapy is required.
T4 (levothyroxine): a single dose reaches its maximum effect in about 10 days (its binding to plasma proteins is strong as well as extensive) and passes off in 2-3 weeks (tJ/2 7 d in euthyroid subjects; 14 d in hypothyroid; 3 d in hyperthyroid).
T3 (liothyronine) is about 5 times as biologically potent as T4; a single dose reaches its maximum effect in about 24 h (its binding to plasma proteins is weak) and passes off in one week (t'/2 2d in euthyroid subjects).
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