Thyroid physiology

10 min read Last updated April 8, 2026

Clinical relevance for anaesthesia

  • Thyroid hormones affect baseline metabolic rate, cardiovascular function, ventilatory drive, thermogenesis, GI motility, neuromuscular function, and drug handling.
    • Hyperthyroidism: ↑ CO, ↓ SVR, arrhythmias (AF), ↑ O2 consumption, heat intolerance, catabolism; risk of thyroid storm with stress/surgery.
    • Hypothyroidism: ↓ CO, ↑ SVR (often diastolic HTN), bradycardia, hypoventilation/OSA, hypothermia, ileus, hyponatraemia; severe form = myxoedema coma.
  • Perioperative interpretation of thyroid function tests: TSH is the most sensitive screening test in primary thyroid disease; acute illness/critical care can cause non-thyroidal illness syndrome (low T3 ± low/normal T4, TSH variable).
    • Do not diagnose hypothyroidism solely on low T3 in critical illness; correlate with TSH and clinical context.
  • Surgery/anaesthesia considerations: airway (goitre, tracheal deviation/compression), recurrent laryngeal nerve palsy risk, calcium monitoring post-thyroidectomy (hypocalcaemia from hypoparathyroidism).
    • Large goitre: consider CT/flow-volume loop history; plan for awake fibreoptic/intubation strategy if symptomatic compression/stridor.
    • Post-thyroidectomy hypocalcaemia: perioral tingling, tetany, prolonged QT; treat with IV calcium (e.g., calcium gluconate) and address magnesium.

Anatomy and cellular organisation

  • Thyroid gland composed of follicles lined by follicular cells surrounding colloid (thyroglobulin). Parafollicular (C) cells secrete calcitonin.
    • Follicular cell: synthesises T4/T3; has basolateral Na+/I− symporter (NIS) and apical thyroid peroxidase (TPO).
    • C cells: calcitonin (minor role in adult Ca2+ homeostasis; clinically relevant in medullary thyroid carcinoma).

Iodine handling and hormone synthesis (steps)

  • 1) Iodide trapping: I− transported into follicular cell via basolateral NIS (Na+/I− symporter), driven by Na+/K+ ATPase.
    • Inhibited by perchlorate, thiocyanate; stimulated by TSH.
  • 2) Apical transport into colloid via pendrin (Cl−/I− exchanger).
    • Pendred syndrome: defective pendrin → goitre + sensorineural deafness.
  • 3) Oxidation and organification: TPO oxidises I− and iodinates tyrosyl residues on thyroglobulin → MIT and DIT.
    • Inhibited by thionamides (carbimazole/methimazole, propylthiouracil).
  • 4) Coupling (TPO-mediated): DIT+DIT → T4; MIT+DIT → T3 (still within thyroglobulin).
    • Thyroid secretes mainly T4 (prohormone) and smaller amounts of T3 (more potent).
  • 5) Storage: iodinated thyroglobulin stored in colloid (large reserve: weeks).
    • This explains delayed onset/offset of many thyroid therapies and resilience to brief iodine deprivation.
  • 6) Release: TSH stimulates endocytosis of colloid → lysosomal proteolysis → free T4/T3 released to blood; MIT/DIT deiodinated intracellularly to recycle iodine.
    • Iodotyrosine deiodinase defects can cause iodine loss and goitre.

Transport in blood and free vs bound hormone

  • Most circulating thyroid hormone is protein-bound: thyroxine-binding globulin (TBG) > transthyretin (TTR) > albumin. Only free hormone is biologically active.
    • Approx free fraction: T4 ~0.02–0.03%; T3 ~0.3%.
    • Changes in binding proteins alter total T4/T3 but not free levels (and not clinical thyroid status) if axis intact.
  • TBG increased by oestrogen (pregnancy, OCP), hepatitis; decreased by androgens, nephrotic syndrome, severe illness. This changes total T4/T3 and can mislead if free hormone not measured.
    • Pregnancy: ↑ TBG → ↑ total T4/T3; free T4 often normal (assay-dependent); TSH reference ranges are trimester-specific.

Peripheral conversion and deiodinases

  • T4 is converted to T3 (active) or reverse T3 (inactive) by deiodinases.
    • Type 1 (D1): liver, kidney, thyroid; contributes to circulating T3; inhibited by propylthiouracil (PTU).
    • Type 2 (D2): brain, pituitary, brown fat, skeletal muscle; local intracellular T3 generation (important for feedback).
    • Type 3 (D3): placenta, brain, fetal tissues; inactivates T4→rT3 and T3→T2; increased in critical illness and fetal life.
  • Non-thyroidal illness: typically low T3 (reduced T4→T3), increased rT3; TSH often normal/low early, may rise during recovery.
    • Mechanisms: altered deiodinase activity, cytokines, reduced binding, altered hypothalamic-pituitary set-point.

Mechanism of action (cellular)

  • T3 enters cells (transporters e.g., MCT8) and binds nuclear thyroid hormone receptors (TRα, TRβ) → heterodimer with RXR → binds thyroid response elements → altered gene transcription.
    • Long latency (hours–days) for many effects due to transcription/translation; some rapid non-genomic effects also described (e.g., membrane/mitochondrial).

Hypothalamic–pituitary–thyroid axis and regulation

  • Hypothalamus secretes TRH → anterior pituitary thyrotrophs secrete TSH → thyroid hormone synthesis and release.
    • TSH acts via GPCR (Gs) → ↑ cAMP; trophic effects: thyroid growth and vascularity.
  • Negative feedback: free T3 (and T4 via local conversion to T3) inhibits TRH and TSH synthesis/release.
    • Pituitary D2 generates local T3: explains why TSH is sensitive to small changes in circulating T4.
  • Other modulators: cold exposure (especially neonates) increases TRH/TSH; stress, glucocorticoids, dopamine, somatostatin reduce TSH secretion.
    • Clinical: dopamine infusions and high-dose steroids in ICU can suppress TSH (interpret TFTs cautiously).
  • Iodine autoregulation: acute iodine load causes transient inhibition of organification and hormone release (Wolff–Chaikoff effect); escape occurs after ~2–3 days in normal thyroid.
    • Jod–Basedow phenomenon: iodine load can precipitate hyperthyroidism in autonomous nodular goitre/latent Graves’.
    • Sources of iodine load: iodinated contrast, amiodarone, topical povidone-iodine (large burns).

Physiological effects of thyroid hormones (system-based)

  • Metabolic: ↑ basal metabolic rate, ↑ O2 consumption and heat production (calorigenic effect), ↑ Na+/K+ ATPase activity, ↑ mitochondrial biogenesis.
    • Carbohydrate: ↑ gluconeogenesis, ↑ glycogenolysis, ↑ intestinal glucose absorption.
    • Lipid: ↑ lipolysis; ↓ LDL cholesterol via ↑ LDL receptor expression (hypothyroidism → hypercholesterolaemia).
    • Protein: physiological levels support growth; excess causes net catabolism and muscle wasting.
  • Cardiovascular: ↑ heart rate, ↑ contractility, ↑ stroke volume, ↑ cardiac output; ↓ systemic vascular resistance (vasodilation) → widened pulse pressure; ↑ blood volume via RAAS activation.
    • Mechanisms: ↑ β1 receptor expression/sensitivity, ↑ SERCA and myosin heavy chain α, enhanced diastolic relaxation; direct vascular smooth muscle effects.
    • Hyperthyroidism predisposes to atrial fibrillation and high-output heart failure; hypothyroidism predisposes to bradycardia, pericardial effusion, reduced exercise tolerance.
  • Respiratory: maintains ventilatory drive and respiratory muscle function. Hyperthyroidism may cause dyspnoea from increased CO2 production; hypothyroidism causes hypoventilation, reduced response to hypoxia/hypercapnia, OSA risk, pleural effusions.
    • Anaesthetic implication: hypothyroid patients may be more sensitive to sedatives/opioids and prone to CO2 retention.
  • CNS: essential for brain development (myelination, synaptogenesis). Adults: hyperthyroid → anxiety, tremor; hypothyroid → cognitive slowing, depression, somnolence.
    • Congenital hypothyroidism untreated → irreversible intellectual disability; newborn screening is critical.
  • GI: ↑ gut motility and secretion (hyperthyroid → diarrhoea; hypothyroid → constipation/ileus).
  • Musculoskeletal: permissive for growth hormone and normal bone turnover. Hyperthyroid → proximal myopathy, osteoporosis; hypothyroid → myalgia, delayed reflex relaxation, carpal tunnel.
  • Haematology: hypothyroidism can cause normocytic or macrocytic anaemia; hyperthyroidism may cause mild normocytic anaemia; thyroid hormones influence 2,3-DPG and tissue oxygen delivery.
  • Renal/water balance: hypothyroidism can impair free water clearance → hyponatraemia (ADH excess, reduced GFR/CO).
  • Reproductive: required for normal fertility; thyroid dysfunction can cause menstrual disturbance and subfertility; pregnancy increases thyroid hormone requirement in hypothyroid patients.

Laboratory patterns and interpretation (physiology focus)

  • Primary hypothyroidism: ↑ TSH, ↓ free T4 (T3 may be normal early).
  • Primary hyperthyroidism: ↓ TSH, ↑ free T4 and/or ↑ free T3 (T3-toxicosis possible).
  • Secondary (pituitary) hypothyroidism: low/normal TSH with low free T4 (TSH may be biologically inactive).
  • Thyroid hormone resistance: high free T4/T3 with non-suppressed TSH; differentiate from TSH-secreting pituitary adenoma (clinical, SHBG, alpha-subunit, imaging).
Describe the synthesis, storage and release of thyroid hormones.

Aim for a stepwise answer from iodide uptake to secretion, naming key transporters/enzymes and drug targets.

  • Iodide trapping into follicular cell via basolateral Na+/I− symporter (NIS), driven by Na+/K+ ATPase; stimulated by TSH.
  • Apical iodide transport into colloid via pendrin.
  • Oxidation and organification by thyroid peroxidase (TPO): iodination of thyroglobulin tyrosines → MIT and DIT.
  • Coupling (TPO-mediated): DIT+DIT→T4; MIT+DIT→T3; stored in colloid as iodinated thyroglobulin (weeks of reserve).
  • TSH stimulates endocytosis of colloid; lysosomal proteolysis releases T4/T3; secretion into blood; intracellular deiodination of MIT/DIT recycles iodide.
  • Drug targets: thionamides inhibit TPO (organification/coupling); PTU also inhibits peripheral T4→T3 (D1); perchlorate blocks NIS; iodide acutely inhibits release/organification (Wolff–Chaikoff).
Explain how thyroid hormones are transported in blood and why free hormone matters.

Examiners want: binding proteins, free fractions, and clinical implications of altered binding.

  • Most T4/T3 is bound to proteins: TBG (major), transthyretin, albumin; only free hormone is biologically active and available for tissue uptake.
  • Free fractions: T4 ~0.02–0.03%; T3 ~0.3%.
  • Changes in TBG alter total T4/T3 without necessarily changing free hormone (and thus thyroid status) if the axis is intact.
  • TBG increased by oestrogen (pregnancy/OCP) → increased total T4; TBG decreased by nephrotic syndrome/androgens → reduced total T4; interpret with free T4 and TSH.
Describe the hypothalamic–pituitary–thyroid axis and feedback control.

Structure your answer: TRH → TSH → thyroid; then negative feedback; then modulators.

  • TRH from hypothalamus stimulates anterior pituitary thyrotrophs to secrete TSH.
  • TSH (GPCR, Gs/cAMP) stimulates iodide uptake, TPO activity, thyroglobulin synthesis, endocytosis/release; also trophic → gland growth/vascularity.
  • Negative feedback: free T3 (and T4 via conversion to T3) inhibits TRH and TSH synthesis/release; pituitary D2 amplifies sensitivity to circulating T4.
  • Modulators: cold (neonates) increases TRH/TSH; dopamine, somatostatin, glucocorticoids suppress TSH (important in ICU).
What are the main physiological actions of thyroid hormones on the cardiovascular system? Explain mechanisms.

Give haemodynamic changes, then receptor/genomic mechanisms, then clinical correlates.

  • Net effects: ↑ HR, ↑ contractility, ↑ SV, ↑ CO; ↓ SVR (vasodilation) → widened pulse pressure; ↑ blood volume (RAAS).
  • Mechanisms: ↑ β1 receptor expression/sensitivity; ↑ calcium handling proteins (e.g., SERCA) and contractile protein isoforms; improved diastolic relaxation; direct vascular smooth muscle effects.
  • Clinical correlates: hyperthyroidism → AF, high-output failure; hypothyroidism → bradycardia, reduced contractility, pericardial effusion, diastolic hypertension.
Explain peripheral conversion of T4 and the significance of reverse T3.

Mention deiodinase types, tissue distribution, and critical illness pattern.

  • T4 is a prohormone; converted to active T3 by deiodinases (D1, D2).
  • D1 (liver/kidney/thyroid) contributes to circulating T3; inhibited by PTU.
  • D2 (brain/pituitary/muscle/brown fat) generates local T3 for tissue needs and feedback control.
  • D3 inactivates: T4→reverse T3 (rT3) and T3→T2; increased in fetal life and critical illness.
  • Non-thyroidal illness: low T3 with increased rT3; TSH often normal/low early; avoid misdiagnosing hypothyroidism without supportive TSH/free T4 pattern.
Describe the Wolff–Chaikoff effect and Jod–Basedow phenomenon. Give clinical examples relevant to anaesthesia.

This is commonly examined: define both and link to iodine exposure perioperatively.

  • Wolff–Chaikoff: acute iodine load transiently inhibits organification and hormone release; normal thyroid escapes after ~2–3 days.
  • Jod–Basedow: iodine load precipitates hyperthyroidism in autonomous thyroid tissue (multinodular goitre, latent Graves’).
  • Anaesthetic/ICU sources of iodine: iodinated contrast (CT angiography), amiodarone, topical povidone-iodine (large wounds/burns).
Interpret these thyroid function tests: (a) ↑TSH, ↓FT4; (b) ↓TSH, ↑FT4; (c) low/normal TSH with ↓FT4; (d) low T3 with normal/low T4 and variable TSH in ICU.

State diagnosis pattern and key differentials/contexts.

  • (a) Primary hypothyroidism (thyroid failure).
  • (b) Primary hyperthyroidism (e.g., Graves’, toxic nodular goitre).
  • (c) Secondary/tertiary hypothyroidism (pituitary/hypothalamic); TSH may be inappropriately normal or low; assess other pituitary axes.
  • (d) Non-thyroidal illness syndrome: reduced T4→T3 conversion and increased rT3; interpret cautiously and avoid reflex thyroid replacement without clear primary disease.
How do thyroid hormones influence thermoregulation and metabolic rate?

Link cellular mechanisms to whole-body heat production and clinical consequences.

  • Increase basal metabolic rate via increased Na+/K+ ATPase activity, mitochondrial number/function, and substrate cycling → increased O2 consumption and heat production.
  • Enhance catecholamine responsiveness (permissive effects) contributing to thermogenesis and cardiovascular changes.
  • Clinical: hyperthyroid heat intolerance and weight loss; hypothyroid cold intolerance, weight gain, hypothermia risk perioperatively.
Explain why TSH is usually the best screening test for thyroid dysfunction, and when it may be misleading.

Examiners want physiology of feedback plus exceptions (central disease, ICU, drugs).

  • TSH responds logarithmically to small changes in free T4 due to tight negative feedback and pituitary D2 conversion to T3, making it highly sensitive in primary thyroid disease.
  • Misleading situations: central hypothyroidism (TSH low/normal but inappropriate), non-thyroidal illness, pregnancy (different reference ranges), and drugs suppressing TSH (dopamine, high-dose glucocorticoids).
Describe the mechanism of action of thyroid hormones at a cellular level and relate this to onset/offset of clinical effects.

Mention transport, nuclear receptor, gene transcription, and time course.

  • T3 enters cells via transporters (e.g., MCT8) and binds nuclear thyroid hormone receptors (TRα/TRβ) → altered gene transcription via thyroid response elements.
  • Many effects have delayed onset (hours–days) due to transcription/translation; prolonged offset due to protein-bound hormone and colloid stores.

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