Thyroxine (T4) and triiodothyronine (T3)

End hormone or mediator · T4 prohormone D2 makes T3 Nuclear receptor

T4 is the prohormone, with a 7-day half-life and over 99.9% protein binding; T3 is the active ligand at the nuclear receptor. About 80% of circulating T3 is generated outside the thyroid by 5'-deiodination.

Traced from the start

  1. Thyrotrophin-releasing hormone (paraventricular nucleus)
  2. Thyrotroph — thyroid-stimulating hormone
  3. Thyroid follicular cell
  4. Thyroxine (T4) and triiodothyronine (T3)

Detail

Deiodinases
D1 in liver and kidney supplies plasma T3; D2 in pituitary, brain and brown fat makes T3 locally, so the thyrotroph effectively senses T4; D3 inactivates T4 to reverse T3
Binding
Thyroxine-binding globulin carries most of it, so oestrogen raises total T4 while free T4 stays normal
Effects
Raises basal metabolic rate and thermogenesis, up-regulates beta-adrenergic receptors, and is essential for fetal and infant brain development and for linear growth
Conversion blockers
Propranolol, propylthiouracil, glucocorticoids, amiodarone and severe illness all reduce T4 to T3 conversion

When it goes wrong

Severe non-thyroidal illness (sick euthyroid syndrome)

Low T3 with normal or low TSH and later a low T4; thyroid function should not be tested in acute illness and this pattern should not be treated

Untreated congenital hypothyroidism

Irreversible intellectual disability and growth failure — the justification for newborn screening and thyroxine within the first two weeks

Practise this structure

4 questions in the bank tagged Thyroid.