Thyroid Hormones (T3 and T4)

T4 and T3 are tyrosine-derived hormones distinguished by iodine count, four atoms against three. The thyroid secretes mostly T4, which behaves largely as a circulating prohormone: most active T3 is produced outside the gland by type 1 and type 2 deiodinases removing an outer-ring iodine, while type 3 deiodinase inactivates hormone by generating reverse T3 instead. T3 binds the nuclear thyroid hormone receptor with roughly ten-fold greater affinity than T4, and that receptor works as a transcription factor.

Almost all circulating hormone is protein-bound, to thyroxine-binding globulin, transthyretin and albumin, leaving free fractions well under one percent - which is why free rather than total hormone is measured. The half-lives differ sharply: T4 persists about a week, T3 about a day. That long T4 half-life is what makes once-daily levothyroxine viable and what forces a wait of roughly six weeks before rechecking after a dose change.

The division of labour between gland and periphery is the reason T4 monotherapy remains standard. Deiodinase activity adjusts local T3 supply tissue by tissue, something a fixed exogenous T3 dose cannot reproduce, and randomised comparisons of combined T4 plus T3 against T4 alone have generally failed to show consistent benefit. The same machinery explains why acute illness lowers T3 and raises reverse T3 with no thyroid disease present, the non-thyroidal illness pattern.

Two misreadings are common. The first treats a low T3 in a sick or energy-restricted patient as hypothyroidism needing T3; it is a regulated adaptation, and correcting the number has not been shown to help. The second is assay interference: high-dose biotin supplements distort many immunoassays, producing a spuriously high free T4 alongside a low TSH that mimics thyrotoxicosis and resolves once the supplement is withheld for a few days.