thyroxine

Thyroxine, or T4, is a thyroid hormone produced primarily by the thyroid's follicular cells. It is the main hormone secreted by the gland, with smaller amounts of triiodothyronine (T3). In the bloodstream, most T4 is bound to transport proteins; only a small fraction circulates freely to act on tissues. T4 serves largely as a prohormone that is converted to the biologically active T3 in peripheral tissues.

Synthesis and transport: T4 and T3 are produced by iodination of tyrosine residues on thyroglobulin in the thyroid colloid. Iodine intake is essential. In plasma, T4 binds mainly to thyroxine-binding globulin (TBG) and, to a lesser extent, transthyretin and albumin; the free fraction is small but biologically important. Peripheral deiodinases convert most T4 to T3, which then activates nuclear receptors to regulate gene expression.

Regulation and role: The hypothalamic–pituitary–thyroid axis controls production via TRH and TSH; circulating T4 and T3 provide negative feedback. Thyroxine regulates metabolism, growth, and development and is particularly crucial for fetal and early postnatal CNS maturation.

Clinical use and monitoring: The standard replacement therapy for hypothyroidism is synthetic levothyroxine (L-thyroxine). Dosing is individualized and guided by TSH and free T4 measurements. Pharmacokinetics: oral absorption is ~60–80% and is influenced by food and gastric pH; the half-life is about 7 days in adults. Drugs and nutrients such as calcium, iron, and bile acid sequestrants can reduce absorption; estrogen raises TBG and total T4. Diagnosis relies on TSH with free T4; subclinical disease presents with abnormal TSH but normal free T4.

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