Canonical Question
Endo – Thyroid
Master answer
Thyroid Hormones
- 3 main thyroid hormones
- thyroxine (T4): 95%; ½ life 7 days; less active
- tri-iodothyronine (T3): 7%; ½ life 24hrs; 3-5x activity of T4
- reverse T3 (rT3): inactive
- T3 + T4 formed from iodination of aa tyrosine
- iodine obtained from diet in form of iodide + actively taken up into thyroid follicular cells (req 120-150ug/day)
- Release
- TRH from hypothalamus → stimulates TSH release → binds to R on cell membrane of follicular cells, GPCR → ↑cAMP → ↑AC →
- ↑iodine uptake into follicular cells
- ↑synthesis of T3 + T4 via ↑iodination + ↑rate coupling reactions
- ↑proteolysis of thyroglobulin within follicular cells → liberate T3 + T4
- MoA
- T3 + T4 highly protein bound (>99%) predominantly to thyroxine binding globulin, albumin, thyroxin binding pre-albumin
- Thyroid hormones enter cell → T3 binds to intracellular thyroid receptors (TR) → hormone receptor complex = transcription factors (bind to DNA via zinc fingers) → alter gene transcription → clinical effects
- T4 de-iodinated to T3
Production and Regulation
Synthesis
- Steps:
- dietary iodine converted to iodide for absorption
- iodide actively transported into follicular cells in thyroid (trapping) → oxidised to iodine (via thyroid peroxidase)
- iodine binds tyrosine in thyroglobulin molecule (iodinase) → forms mono-iodotyrosine then di-iodotyrosine (peroxidase)
- di-iodotyrosine + di-iodotyrosine = thyroxine (T4) (perixodase) → binds thyroxine binding globulin + thyroxine binding pre-albumin
- ↑activity with TSH of:
- iodide pump activity
- thyroid peroxidase
- iodinase
- peroxidase
- vesicular lysosomal activity
- thyroid hormones formed within thyroglobulin; synthesised in golgi apparatus
- thyroglobulin stored in follicular colloid → vesicular lysosomal activity breaks down thyroglobulin to release T3 + T4 which diffuse out of follicular cells and into circulation
Metabolism of thyroid homrones
- T4 deiodinated to T3/ rT3 (inactive compound 1:1) → deiodinated in liver, kidney, skeletal muscle to inactive compounds
Negative feedback
Physiological Action
| System | Action | Physiological + pathological effects |
|---|---|---|
| CNS | Development | – normal CNS development – ↓T → ↓CNS development → retardation, rigidity, deaf-mutism – sexual function |
| CVS | Chronotrope Inotrope Vasodilation | – ↑number β-adrenoceptors → ↑HR – ↑circulating catecholamines → ↑contractility + ↑CO – ↑T → ↑body temp → vasodilation → ↓SVR |
| Resp | Metabolic | – ↑T → ↑metabolic rate → ↑MV |
| Bone | Anabolic | – essential for normal bone growth |
| ANS | Stimulatory | – ↑T → synergy with circulating catecholamines → ↑SNS |
| Metabolic / endocrine | Cellular effect Feedback Anabolic/ catabolic | – ↑Na/K ATPase activity → ↑MR of cells + calorigenic – feedback inhibition → ↓TRH + ↓TSH ; ↑T → ↑GH release – CHO: ↑CHO absorption – Fat: ↑lipolysis; ↑LDL Rs → ↑ liver uptake circulating cholesterol – Protein: physiological amounts: ↑protein synthesis; excess amounts: protein breakdown (thyrotoxic myopathy) |
Kerr 2016
Exam appearances
| Exam | Exact wording | Relationship | Success |
|---|---|---|---|
| 2016A Q17 | Describe the physiology of the thyroid hormones. | historical_member | — |
| 2021B Q14 | Describe the production, action and regulation of thyroid hormones. | historical_member | — |