Thyroid Physiology

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.

Regulation of Secretion - Control Central

• 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 Bound	Affinity
    TBG	~70-75%	Highest
    TTR	~15-20%	Medium
    Albumin	~5-10%	Low

• Metabolism: T4 converted to T3 (active, 3-4x potent) by deiodinases.
  • Deiodinases:

    Type	Location(s)	Action	Substrate
    D1	Liver, Kidney	T4→T3; T4→rT3 (peripheral)	T4, T3
    D2	Pituitary, CNS	T4→T3 (local T3 supply)	T4
    D3	Placenta, CNS, Skin	T4→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 Actions - Systemic Spark

• 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.

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.