Thyroid Physiology

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Thyroid Hormone Synthesis - Glandular Goodness

  • Iodide Trapping: Follicular cells trap I- via Na+/I- symporter (NIS); achieve 20-40x concentration gradient.
  • Oxidation: Thyroid Peroxidase (TPO) oxidizes I- to reactive iodine (I2) using H2O2.

    ⭐ Dual oxidase (DUOX) on apical membrane generates H2O2 for TPO.

  • Organification: TPO incorporates iodine into tyrosine residues on thyroglobulin (Tg) → forming MIT & DIT.
  • Coupling: TPO couples iodotyrosines on Tg: $DIT + DIT \rightarrow T_4$; $MIT + DIT \rightarrow T_3$.
  • Storage: Hormones stored within follicular colloid, still attached to Tg.
  • Release: Colloid endocytosis, lysosomal proteolysis of Tg liberates T3 & T4 into circulation.

Thyroid hormone synthesis pathway diagram

Regulation of Secretion - Control Central

HPT Axis Diagram

  • HPT Axis: Hypothalamus (TRH) → Ant. Pituitary (TSH) → Thyroid ($T_3$/$T_4$). TRH stimulates TSH; TSH stimulates thyroid hormone synthesis/release.
  • Negative Feedback: ↑ $T_3$/$T_4$ inhibits TRH (hypothalamus) & TSH (pituitary) secretion, maintaining homeostasis.
  • TSH: Glycoprotein: common α-subunit (shared: LH, FSH, hCG); specific β-subunit (confers specificity).
  • Influencers:
    • TSH Inhibition: Somatostatin, Dopamine, Glucocorticoids.
    • Iodine: Wolff-Chaikoff effect (excess iodine ↓ synthesis); Jod-Basedow phenomenon (iodine-induced hyperthyroidism in susceptible glands).

⭐ TSH receptor: Gs (major, adenylyl cyclase) & Gq protein-coupled receptor.

Transport & Metabolism - Journey & Makeover

  • Transport: >99% TH protein-bound; free form active.
    • Binding Proteins:
      Protein% T4 BoundAffinity
      TBG~70-75%Highest
      TTR~15-20%Medium
      Albumin~5-10%Low
  • Metabolism: T4 converted to T3 (active, 3-4x potent) by deiodinases.
    • Deiodinases:
      TypeLocation(s)ActionSubstrate
      D1Liver, KidneyT4→T3; T4→rT3 (peripheral)T4, T3
      D2Pituitary, CNST4→T3 (local T3 supply)T4
      D3Placenta, CNS, SkinT4→rT3; T3→T2 (inactivation)T4, T3
  • TBG: ↑ Estrogen (preg), OCPs. ↓ Androgens, steroids, illness.

⭐ Pregnancy: ↑TBG → ↑Total T4/T3. Free T4/T3 normal. Clinically euthyroid.

Thyroid hormone transport and metabolism

Thyroid Hormone Actions - Systemic Spark

Thyroid hormone effects on the cardiovascular system

  • Mechanism: Nuclear receptors (TRα, TRβ) → alter gene expression.
  • Effects:
    • ↑ Basal Metabolic Rate (BMR), O₂ consumption, heat (calorigenic).
    • Growth & Development: Synergistic with GH for skeletal maturation; vital for CNS development.
    • Cardiovascular: ↑ Heart rate, contractility, cardiac output (via ↑ β-adrenergic receptors).
    • Metabolic: ↑ Glucose absorption, glycogenolysis, gluconeogenesis, lipolysis, protein turnover.
    • Permissive: Potentiates catecholamine effects.

⭐ Thyroid hormones are essential for brain development, particularly myelination, in fetal and neonatal life.

Applied Physiology Snippets - Test & Tell Tales

  • Key Tests: TSH (most sensitive for primary disorders), Free T4 (fT4), Free T3 (fT3).
  • Patterns:
    • Primary Hypothyroidism: ↑TSH, ↓fT4.
    • Primary Hyperthyroidism: ↓TSH, ↑fT4/fT3.
  • Iodine Effects: Wolff-Chaikoff (excess iodine temporarily inhibits hormone synthesis); Jod-Basedow (iodine induces hyperthyroidism in susceptible individuals).
  • Key Antibodies: Anti-TPO (TPOAb) in Hashimoto's; TRAb (TSH receptor antibody) in Graves'.

⭐ Subclinical hypothyroidism: Elevated TSH with normal free T4 levels.

Hypothyroidism Diagnostic Algorithm

High‑Yield Points - ⚡ Biggest Takeaways

  • TSH from anterior pituitary controls thyroid hormone synthesis and release.
  • Iodine trapping by NIS (Na+/I- symporter) is crucial for thyroid hormone production.
  • T4 (thyroxine) is the major circulating hormone; T3 (triiodothyronine) is more potent, mainly from peripheral T4 conversion by deiodinases.
  • The Wolff-Chaikoff effect describes transient inhibition of hormone synthesis by excess iodine.
  • Thyroid hormones significantly ↑ Basal Metabolic Rate (BMR) and sensitize tissues to catecholamines.
  • TBG (Thyroxine-binding globulin) is the primary plasma transport protein for thyroid hormones.

Practice Questions: Thyroid Physiology

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Regarding thyroid hormone all are true except:

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Flashcards: Thyroid Physiology

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The main functions of thyroid hormone can be remembered with the "6 B's"?1. _____2. Bone growth3. 1-adrenergic effects 4. Basal metabolic rate (increased) 5. Blood sugar6. Break down lipids

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The main functions of thyroid hormone can be remembered with the "6 B's"?1. _____2. Bone growth3. 1-adrenergic effects 4. Basal metabolic rate (increased) 5. Blood sugar6. Break down lipids

Brain maturation

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