The reasoning: binding, deiodination, nuclear action
- Binding: TBG (~70%), transthyretin, albumin; free fractions ≈ T4 0.02–0.03%, T3 0.2–0.3%. Half‑life: T4 ~7 days, T3 ~1 day. Oestrogen/pregnancy ↑ TBG (total ↑, free normal); androgens, nephrotic syndrome, severe illness ↓ TBG.
- Deiodinases: D1 (liver, kidney, thyroid — outer ring, clearance), D2 (brain, pituitary, brown fat, muscle — local T3 production; key to pituitary feedback), D3 (placenta, brain, illness — inner ring → rT3/T2, inactivation).
- Action: T3 binds TRα/TRβ with RXR on thyroid response elements → transcription: ↑ Na⁺/K⁺‑ATPase, ↑ β₁‑receptors, ↑ SERCA2a/↓ phospholamban, ↑ α‑MHC (heart); uncoupling proteins and thermogenesis; brain development (myelination); bone maturation; ↑ LDL receptors (↓ cholesterol); ↑ glucose absorption and turnover.