Thyroid hormones
Also known as: T3 and T4, thyroxine and triiodothyronine
Thyroid hormones are thyroxine (T4) and triiodothyronine (T3), iodine-containing hormones made by the thyroid gland that set the body's basal metabolic rate. They also support growth, brain development, and the cardiovascular response to catecholamines.
The thyroid follicular cells synthesize T4 and T3 by iodinating tyrosine residues on thyroglobulin and coupling them. The gland secretes mostly T4, which acts as a circulating reservoir; peripheral tissues then convert it to T3, the far more potent form, using deiodinase enzymes. Both hormones travel bound to thyroxine-binding globulin, and only the small unbound fraction is active — which is why free T4 is often more informative than total T4. Because iodine is a required substrate, dietary iodine deficiency limits synthesis and is a leading cause of goiter worldwide.
Production runs on a classic negative feedback axis. The hypothalamus releases TRH, which stimulates the anterior pituitary to release TSH, which stimulates thyroid growth and hormone output. Circulating T3 and T4 then suppress both TRH and TSH. The practical consequence is an inverse relationship clinicians rely on: in primary hypothyroidism, thyroid hormone is low and TSH is high; in primary hyperthyroidism, hormone is high and TSH is suppressed. When TSH moves in the same direction as T4, the problem lies in the pituitary or hypothalamus rather than the gland.
Thyroid hormone acts on nuclear receptors to change gene transcription in nearly every tissue. It raises basal metabolic rate and oxygen consumption, increases Na⁺/K⁺-ATPase activity and heat production, upregulates beta-adrenergic receptors so the heart responds more strongly to catecholamines, and is essential for normal skeletal growth and central nervous system maturation in infancy. Excess produces weight loss, heat intolerance, tachycardia, and tremor; deficiency produces fatigue, cold intolerance, bradycardia, weight gain, and constipation.
USMLE Step 1 tests synthesis steps, the feedback axis, and the interpretation of TSH and free T4 patterns. The MCAT covers thyroid hormones within the endocrine system, and the CSCS exam addresses hormonal responses to exercise, where thyroid hormone's metabolic role sits alongside testosterone, growth hormone, and cortisol.
Key takeaways
- The thyroid secretes mostly T4, which peripheral tissues convert to the more potent T3.
- Iodine is an essential substrate, and deficiency limits hormone synthesis.
- TRH and TSH drive production, and circulating thyroid hormone suppresses them through negative feedback.
- In primary thyroid disease, TSH moves opposite to T4; matching directions point to a pituitary or hypothalamic cause.
- Thyroid hormone raises basal metabolic rate and heat production and upregulates beta-adrenergic receptors.