Thyroid hormone: physiology, tests and hypothyroidism
How the thyroid makes its hormones, how they act on nearly every organ, how blood tests are read, and how an underactive thyroid is recognised and treated.
The thyroid makes T4 and a little T3 from iodine and tyrosine; tissues convert T4 to the active T3, which acts mainly through nuclear receptors. This page covers synthesis, transport, activation and regulation, the organ effects, thyroid function tests and hypothyroidism from the subclinical form to myxoedema coma. Antithyroid drugs and hormone preparations have their own pages.
Synthesis, storage and release
Thyroid cells concentrate iodide from blood through the sodium-iodide symporter. At the colloid surface, thyroid peroxidase oxidises it and attaches it to tyrosine residues in thyroglobulin, forming MIT and DIT, which couple into T4 and T3. Hormone is stored in the colloid and released when TSH stimulates uptake and breakdown of thyroglobulin. A large load of iodide acutely and transiently shuts down hormone synthesis (the Wolff-Chaikoff effect); most glands escape, but patients with underlying thyroid disease may not, and iodine-rich drugs such as amiodarone can then cause hypothyroidism.
Transport, activation and degradation
- Binding: thyroxine-binding globulin is the main carrier, with transthyretin and albumin; T4 binds more tightly than T3. Oestrogen and pregnancy raise TBG and total T4 without changing free hormone.
- Activation: D1 (liver, kidney, thyroid) and D2 (brain, pituitary, muscle) convert T4 to T3; propylthiouracil, amiodarone, glucocorticoids and beta blockers reduce conversion.
- Inactivation: D3, highest in brain and placenta, removes an inner-ring iodine to make inactive metabolites.
- Elimination: T4 has a long half-life of about a week, so changes in replacement take weeks to settle.
Regulation and mechanism of action
Hypothalamic TRH stimulates pituitary TSH, which drives the thyroid; T3 and T4 feed back to suppress both. Inside cells, T3 binds thyroid hormone receptors (TR alpha and TR beta) that sit on DNA response elements and switch target genes on or off. TR beta in the pituitary and hypothalamus mediates negative feedback; TR beta in liver mediates the cholesterol-lowering effect. Some actions are rapid and non-genomic, from receptors outside the nucleus.
Effects on the body
- Growth and development: essential for brain development and linear growth; untreated congenital hypothyroidism is a preventable cause of intellectual disability, which is why newborns are screened.
- Bone: needed for skeletal maturation; excess hormone speeds bone turnover and raises osteoporosis risk.
- Thermogenesis: raises basal heat production; deficiency causes cold intolerance.
- Heart: increases heart rate and contractility and lowers vascular resistance; excess can trigger atrial fibrillation, especially in older people.
- Lipids: increases hepatic LDL receptors, so hypothyroidism raises LDL cholesterol.
Reading thyroid function tests
TSH is the most sensitive screen for primary thyroid disease. A high TSH with low free T4 means overt primary hypothyroidism; a high TSH with normal free T4 is subclinical hypothyroidism. A low TSH with high free T4 or T3 means hyperthyroidism; a low TSH with normal hormones is subclinical hyperthyroidism. In pituitary or hypothalamic disease TSH can be low or normal despite low free T4, so free T4 is the guide. Antibody tests identify Hashimoto and Graves disease, and radioiodine uptake separates overproduction (high uptake) from leakage in thyroiditis (low uptake).
Hypothyroidism, subclinical disease and myxoedema coma
Hypothyroidism develops slowly with fatigue, weight gain, cold intolerance, dry skin, constipation, slow heart rate, heavy periods and depression. It is more common in women and after 60. Levothyroxine replaces the missing hormone; tests are repeated some weeks after each change because of the long half-life, and needs usually rise in pregnancy. Subclinical hypothyroidism is a laboratory finding; whether to treat depends on symptoms, TSH level, antibodies, pregnancy plans and age. Myxoedema coma is the rare extreme, often in older people in winter after infection or heart failure. It is treated with intravenous levothyroxine (sometimes with liothyronine), ventilatory and temperature support, and treatment of the trigger.
Test yourself
Think of the answer, then tap the question to see it.
Why is free T4 preferred over total T4 in pregnancy?
Oestrogen raises thyroxine-binding globulin, which raises total T4; free T4 reflects the active hormone and is not distorted by binding.
What do a high TSH and a normal free T4 indicate?
Subclinical hypothyroidism: the pituitary is pushing harder to keep hormone levels in the normal range.
What is the Wolff-Chaikoff effect?
An acute, transient shutdown of thyroid hormone synthesis by a large iodide load; glands with underlying disease may fail to escape it.
Which features define myxoedema coma?
Hypothermia, respiratory depression and reduced consciousness in long-standing severe hypothyroidism, often triggered by infection.
Example drugs
Connections
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Thyroid Tests (National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), 2026); Hypothyroidism (Underactive Thyroid) (National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), 2026).
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Representative model, for educational purposes only.