Physiology chapters
Thyroid hormones
How the thyroid makes T4 and T3 from iodine and thyroglobulin, how they are stored, carried and controlled by TSH, what they do to metabolism, the heart and growth, and the features of hyper- and hypothyroidism.
- The thyroid traps iodide (Na+/I− symporter), oxidises it and attaches it to tyrosines on thyroglobulin (thyroid peroxidase), then couples them into T4 and T3, stored in the colloid.
- Mostly T4 is released, but T3 is the active form (about 4 times more potent), made from T4 in tissues by deiodinases; over 99% circulates protein-bound, mainly to TBG.
- TRH → TSH → T4/T3 with negative feedback; thyroid hormone raises metabolic rate, heart rate and is essential for brain development and growth.
On this page
Overview
The thyroid gland makes two iodine-containing hormones: thyroxine (T4) and triiodothyronine (T3). They set the body's metabolic rate and are essential for normal growth and brain development.
The thyroid also makes calcitonin from its parafollicular (C) cells, which lowers blood calcium slightly.
Structure
The gland is made of follicles: spheres of follicular cells around a store of colloid, which is mostly thyroglobulin, a large protein carrying the hormones.
Synthesis
| Step | What happens | Blocked by |
|---|---|---|
| 1. Iodide trapping | Iodide is pumped into follicular cells by the sodium-iodide symporter (secondary active transport), up to about 30 times its blood level | Perchlorate, thiocyanate |
| 2. Thyroglobulin made | Made in the cell and released into the colloid; contains many tyrosines | |
| 3. Oxidation | Iodide → iodine by thyroid peroxidase | Carbimazole, propylthiouracil |
| 4. Organification (iodination) | Iodine joins tyrosines on thyroglobulin: MIT (one iodine) and DIT (two) | Carbimazole, PTU |
| 5. Coupling | DIT + DIT = T4; MIT + DIT = T3 | Carbimazole, PTU |
| 6. Storage | Hormones stay attached to thyroglobulin in the colloid | |
| 7. Release | Colloid is taken back into the cell by endocytosis; enzymes free T4 and T3 into the blood | High-dose iodide (briefly) |
Thyroid peroxidase does oxidation, organification and coupling. Carbimazole and propylthiouracil block it.
Storage
The thyroid is unusual among endocrine glands in storing a large amount of hormone: enough for about 2–3 months. So symptoms of deficiency appear slowly after synthesis stops.
Wolff-Chaikoff effect
A large dose of iodide temporarily reduces hormone synthesis and release. This is used before thyroid surgery to make the gland smaller and less vascular.
Circulation
- About 90% of secreted hormone is T4, about 10% T3.
- In the blood, more than 99% is bound: mainly to thyroxine-binding globulin (TBG), plus transthyretin and albumin.
- Only about 0.03% of T4 and 0.3% of T3 are free, and only free hormone acts.
- T4 has a half-life of about 6–7 days; T3 about a day.
Conversion of T4 to T3
In tissues (liver, kidney, muscle), 5'-deiodinase removes one iodine from T4 to make T3, the active hormone (about four times more potent). An inner-ring deiodinase makes inactive reverse T3.
In serious illness and starvation, more reverse T3 is made (sick euthyroid).
T4 is the main secreted form; T3 is the main active form. T4 acts largely as a prohormone.
In pregnancy and with the oral contraceptive pill, TBG rises, so total T4 rises, but free T4 is normal and the person is euthyroid.
Regulation
Hypothalamus (TRH) → anterior pituitary (TSH) → thyroid (T4, T3)
- TSH acts through cAMP and increases every step: iodide trapping, synthesis, release and growth of the gland.
- Free T4 and T3 feed back on the pituitary (and hypothalamus) to reduce TSH.
- Cold increases TRH in infants; stress and somatostatin reduce TSH.
Actions of thyroid hormone
Thyroid hormone enters cells and acts on nuclear receptors, changing the activity of many genes.
| System | Effect |
|---|---|
| Metabolism | ↑ Basal metabolic rate, O2 use and heat production (more Na+/K+-ATPase, more and larger mitochondria) |
| Carbohydrate | ↑ Glucose absorption, uptake, glycolysis and gluconeogenesis |
| Fat | ↑ Fat breakdown; ↓ plasma cholesterol (more LDL receptors in the liver) |
| Protein | ↑ Synthesis and breakdown |
| Heart | ↑ Heart rate, force and cardiac output (more β1 receptors); ↓ peripheral resistance |
| Breathing | ↑ Rate and depth (more O2 needed) |
| Gut | ↑ Appetite and motility |
| Nervous system | Essential for brain development in the fetus and infancy; ↑ alertness; brisk reflexes |
| Growth | Needed for normal growth and bone maturation; permissive for GH |
| Reproduction | Needed for normal menstruation and fertility |
Thyroid hormone increases β-adrenergic receptors, so hyperthyroid patients look adrenergic (tremor, fast heart). Beta-blockers control these symptoms.
Clinical relevance
Hyperthyroidism
Commonest cause: Graves' disease, in which TSH receptor-stimulating antibodies drive the gland. TSH is low.
What you see: weight loss despite good appetite, heat intolerance, sweating, tremor, palpitations (atrial fibrillation in older people), anxiety, diarrhoea, light periods, a diffuse goitre; in Graves' disease also exophthalmos and pretibial myxoedema.
Hypothyroidism
Common causes: Hashimoto's thyroiditis (autoimmune), iodine deficiency (still seen in parts of northern Pakistan), surgery or radioiodine.
What you see in adults: tiredness, cold intolerance, weight gain, constipation, dry skin, hoarse voice, slow reflexes, heavy periods, high cholesterol, myxoedema (non-pitting swelling).
Congenital hypothyroidism (cretinism)
How it happens: lack of thyroid hormone in fetal or early infant life.
What you see: intellectual disability, short stature with short limbs (disproportionate), a large tongue, umbilical hernia and coarse face. Newborn screening and early treatment prevent this.
Goitre
Enlargement of the thyroid. It can occur with high, normal or low hormone levels. In iodine deficiency, low hormone raises TSH, which enlarges the gland.
Expect: the steps of synthesis and the drugs that block each (perchlorate, carbimazole and PTU), coupling of MIT and DIT, storage in colloid, T4 vs T3 (secreted vs active), deiodinase, TBG and free hormone (and pregnancy), TRH-TSH feedback, actions on metabolism and the heart, and the features of Graves' disease, hypothyroidism and cretinism.
Quick revision
- Trapping (Na+/I− symporter) → oxidation, organification, coupling (thyroid peroxidase).
- DIT + DIT = T4; MIT + DIT = T3.
- Store of 2–3 months in colloid.
- 90% T4 secreted; T3 active (5'-deiodinase in tissues).
- Over 99% bound (mainly TBG); only free hormone acts.
- TRH → TSH (cAMP) → T4/T3; negative feedback.
- Actions: ↑ BMR, Na+/K+-ATPase, β-receptors, heart rate; brain development.
Written by The House Job from standard physiology references (Guyton and Hall Textbook of Medical Physiology; BRS Physiology).
FAQ
Which form of thyroid hormone is most active?
T3, which is about four times more potent than T4.
What does thyroid peroxidase do?
It oxidises iodide, attaches iodine to tyrosine on thyroglobulin, and couples the iodinated tyrosines to form T3 and T4.
What is the main carrier protein for thyroid hormones?
Thyroxine-binding globulin (TBG).
Why does congenital hypothyroidism cause intellectual disability?
Thyroid hormone is essential for brain development in the fetus and early infancy.