# Thyroid Hormone Action and Regulation > Thyroid hormone action and regulation in MBBS Physiology: receptor effects, deiodinases, TSH control and the Wolff-Chaikoff effect. - Canonical URL: https://prepelephant.com/topics/mbbs/physiology/thyroid-hormone-action-regulation - Exam / course: MBBS · Subject: Physiology - Publisher: PrepElephant (https://prepelephant.com) — Prepared and reviewed by the PrepElephant Academic Review Team - First published: 2026-10-02 - Last updated: 2026-10-02 - How to cite: "Thyroid Hormone Action and Regulation", PrepElephant, https://prepelephant.com/topics/mbbs/physiology/thyroid-hormone-action-regulation ## Direct answer Thyroid hormones act through nuclear T3 receptors (TR alpha and TR beta) that bind thyroid-response elements and modulate gene transcription, producing their hallmark effects: raised basal metabolic rate through Na-K ATPase induction and mitochondrial uncoupling, heightened catecholamine sensitivity of the heart, cholesterol lowering via increased hepatic LDL receptors, and obligatory roles in infant brain myelination and linear growth. About 93% of secreted output is T4, a prohormone with a 6-7 day half-life, converted at target tissues by deiodinases to T3 (three to five times more potent, half-life about one day) or inactivated to reverse T3. Regulation runs through the hypothalamic TRH-pituitary TSH axis plus intrathyroidal autoregulation, of which the Wolff-Chaikoff effect — transient organification block by iodide excess — is the exam favourite. ## What you must remember - **Secretion ratio:** roughly 93% T4 to 7% T3; free hormone is the active fraction, with 99.98% of T4 bound (70% to thyroxine-binding globulin, the rest to transthyretin and albumin). - **Deiodinase map:** type 1 in liver and kidney generates most circulating T3 (and clears reverse T3); type 2 in brain, pituitary and brown fat makes local T3 (the pituitary's own sensor); type 3 in placenta, fetus and brain inactivates hormone (T4 to reverse T3, T3 to T2). - **Metabolic actions:** oxygen consumption and BMR rise in all tissues except brain, testis, uterus, lymph nodes and spleen, through Na-K ATPase induction and mitochondrial biogenesis; heart rate, contractility and pulse pressure rise from beta-receptor up-regulation. - **Growth and nervous system:** permissive for GH action on bone and essential for myelination in the first 2-3 years — untreated congenital hypothyroidism causes irreversible intellectual disability, which is why newborn TSH screening exists. - **Regulation:** TRH (hypothalamus) drives TSH; T3 from intrapituitary D2 conversion is the main negative-feedback signal; TSH stimulates every step from trapping (NIS) to release and also has a trophic effect on the gland (goitre when chronic). - **Wolff-Chaikoff effect:** a large iodide load transiently inhibits organification and hormone release, with escape in about 48 hours in normal glands (via NIS down-regulation); non-escape underlies iodide-induced hypothyroidism in Hashimoto disease, and the effect is exploited pre-operatively in Graves disease with Lugol's iodine. ## How to work through thyroid function tests A 35-year-old with palpitations, weight loss and a diffuse goitre: TSH suppressed below the assay floor, free T4 high — primary hyperthyroidism, the periphery flooded by T4 that target-tissue D2 converts to T3. The pituitary's own D2 conversion raised its intracellular T3, shutting off TSH — proving that feedback samples local, not just plasma, hormone. Conversely, a pregnant patient on amiodarone (37% iodine by weight, and a D1 inhibitor) can swing either way: the iodide load can trigger Wolff-Chaikoff hypothyroidism in an autoimmune gland, or a Jod-Basedow hyperthyroidism in a nodular gland — the same drug, opposite directions, decided by the gland's underlying autonomy. In severe non-thyroidal illness, total T3 falls, reverse T3 rises, and T4 may fall late (sick euthyroid syndrome) because D1 activity drops and D3 rises, shunting hormone to inactive pathways; treating the illness, not the numbers, is the rule. For replacement, levothyroxine (T4) is chosen over liothyronine (T3) precisely because of its long half-life and steady T3 generation by peripheral D2 — and absorption is impaired by calcium and iron tablets taken together, a practical counselling point. ## Where students slip Students call T4 the active hormone because it dominates secretion; T3 is the biologically active ligand at the receptor, and T4 is largely a prohormone and reservoir — which is also why T3 poisoning presents faster and clears faster. The second recurring error is labelling reverse T3 simply as "another hormone"; it is functionally inactive, the D3 shunt product, and its rise in illness is a protective down-regulation. Finally, candidates forget that thyroid hormone passes into cells and the pituitary via specific transporters (MCT8 mutations cause Allan-Herndon-Dudley syndrome with high free T4 but low T3 and neurodevelopmental delay) — the rare-disease viva that separates a reader from a memoriser. ## Frequently asked questions ### Which form of thyroid hormone is active at the receptor? T3, generated about 80% peripherally from T4 by deiodinases; T4 is mainly a prohormone with a much longer half-life and larger pool. ### What is the Wolff-Chaikoff effect and when does it fail? Acute iodide excess transiently blocks thyroid hormone synthesis; normal glands escape in about 48 hours by down-regulating iodide transport, but glands with Hashimoto disease or Graves may not escape, becoming hypothyroid — exploited deliberately with preoperative Lugol's iodine. ### Why does the heart become catecholamine-sensitive in thyrotoxicosis? T3 increases beta-adrenergic receptor density and coupling along with myosin isoform switching, so normal catecholamine levels produce tachycardia and a hyperdynamic circulation; beta-blockers relieve symptoms while definitive therapy works. ### How do the deiodinases differ in function? D1 supplies blood T3 from T4 in liver and kidney, D2 provides local intracellular T3 (notably in pituitary and brain), and D3 inactivates hormone, protecting the fetus and placenta from excess exposure. ### Why does untreated congenital hypothyroidism cause permanent brain damage? T3 is required for myelination, dendritic arborisation and synaptogenesis in the first two to three years, a window that does not reopen; newborn TSH screening and prompt levothyroxine prevent the intellectual disability of cretinism.