Physiology of Thyroid Hormone Production and Regulation
The thyroid gland is an endocrine organ located in the anterior neck, essential for regulating metabolism, thermogenesis, growth, and development through the production of thyroid hormones — thyroxine (T₄) and triiodothyronine (T₃).
🔷 1. Overview of Thyroid Hormones
Hormone | Secreted by | Circulating Form | Biologic Potency | Half-life |
T₄ (Thyroxine) | Thyroid gland | ~90% | Low | ~7 days |
T₃ (Triiodothyronine) | Thyroid gland & peripheral tissues (via deiodination of T₄) | ~10% | High (3–4x more potent than T₄) | ~1 day |
Reverse T₃ (rT₃) | Inactive metabolite | Peripheral tissues | Inactive | — |
🔷 2. Synthesis of Thyroid Hormones
Occurs in the follicular cells of the thyroid gland and involves several key steps:
Step-by-step Mechanism:
Step | Description |
1. Iodide Trapping | Active uptake of iodide (I⁻) from blood via Na⁺/I⁻ symporter (NIS) in the basal membrane of follicular cells |
2. Oxidation | Iodide (I⁻) is oxidized to iodine (I₂) by thyroid peroxidase (TPO) at the apical membrane |
3. Organification | Iodine binds to tyrosine residues on thyroglobulin to form MIT (monoiodotyrosine) and DIT(diiodotyrosine) |
4. Coupling | MIT + DIT → T₃ and DIT + DIT → T₄, catalyzed by TPO |
5. Storage | T₃ and T₄ remain bound to thyroglobulin in the colloid inside the follicular lumen |
6. Release | On stimulation by TSH, colloid is endocytosed; proteolysis releases T₃ and T₄ into circulation |
7. Peripheral Conversion | ~80% of T₃ is produced by 5’-deiodinase conversion of T₄ in liver, kidney, and muscle |
🔷 3. Regulation of Thyroid Hormone Secretion
The Hypothalamic-Pituitary-Thyroid (HPT) Axis governs thyroid function:
🔁 Feedback Loop:
- Hypothalamus → releases Thyrotropin-releasing hormone (TRH)
- Anterior pituitary → secretes Thyroid-stimulating hormone (TSH) in response to TRH
- Thyroid gland → stimulated by TSH to produce T₄ and T₃
- Negative Feedback → T₄ and T₃ inhibit TRH and TSH release
TSH Actions:
- Stimulates NIS expression, TPO activity, thyroglobulin production
- Increases iodide uptake, hormone synthesis and secretion
- Promotes follicular cell growth and vascularity
🔷 4. Transport of Thyroid Hormones
Thyroid hormones are lipophilic and mostly protein-bound in plasma:
Binding Protein | % Bound | Affinity |
Thyroxine-binding globulin (TBG) | ~70% | High |
Transthyretin (TTR) | ~20% | Moderate |
Albumin | ~10% | Low |
Only free T₃ and T₄ are biologically active and regulate feedback.
🔷 5. Physiological Actions of Thyroid Hormones
System | Effects |
Metabolic | ↑ Basal metabolic rate, oxygen consumption, glucose and lipid metabolism |
Cardiovascular | ↑ HR, contractility, cardiac output (↑ β₁-receptor sensitivity) |
GI | ↑ Motility (→ diarrhea in hyperthyroidism) |
CNS | Essential for brain development, alertness, mood |
Musculoskeletal | Growth, bone maturation, muscle strength |
Thermoregulation | Heat production (calorigenesis) |
Reproductive | Required for normal menstruation, fertility |
🔷 6. Thyroid Function Tests (TFTs)
Test | Normal Range | Interpretation |
TSH | 0.5–4.5 mIU/L | Best screening test |
Free T₄ | 0.8–1.8 ng/dL | Low in hypothyroid |
Free T₃ | 2.3–4.2 pg/mL | More specific for hyperthyroidism |
Total T₄ / T₃ | Affected by binding proteins |
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TBG | Useful if altered protein binding suspected |
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🔷 7. Factors Affecting Thyroid Function
↑ TBG (↑ Total T₄) | ↓ TBG (↓ Total T₄) |
Pregnancy | Liver failure |
Estrogen therapy | Androgens |
Hepatitis | Nephrotic syndrome |
🔷 8. Relevance to Anesthesia
Condition | Implication |
Hyperthyroidism | Risk of thyroid storm, tachyarrhythmia, heat intolerance; avoid sympathetic surges |
Hypothyroidism | Bradycardia, hypotension, hypothermia, drug sensitivity, delayed recovery |
TSH-producing adenoma | May cause thyrotoxicosis |