Regulation of thyroid function

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HPT Axis - The Body's Thermostat

Hypothalamic-Pituitary-Thyroid Axis and hormone regulation

  • Central Regulation: A classic negative feedback loop maintains thyroid hormone homeostasis, crucial for metabolism, growth, and thermoregulation.
  • Mechanism:T3/T4 levels inhibit TRH and TSH release.
  • Pathology: Disruption at any level (primary, secondary, tertiary) leads to hypo/hyperthyroidism.

⭐ In primary hypothyroidism, ↓T3/T4 leads to a compensatory ↑ in both TRH and TSH. The elevated TSH is the most sensitive initial marker.

Thyroid Kitchen - Cooking Up Hormones

Thyroid hormone regulation and effects

HPT Axis Regulation:

  • Synthesis Steps:
    • Trapping: Iodide ($I^−$) enters follicular cells via Na+/I− symporter (NIS).
    • Oxidation & Organification: Thyroid peroxidase (TPO) oxidizes $I^−$ to iodine ($I_2$) and adds it to thyroglobulin (TG) tyrosine residues → MIT & DIT.
    • Coupling: TPO couples residues: DIT + DIT → $T_4$; DIT + MIT → $T_3$.
    • Release: TSH stimulates proteolysis of TG, releasing $T_4$ and $T_3$ (ratio ~20:1).
  • Peripheral Conversion: $T_4$ is converted to more potent $T_3$ by 5′-deiodinase.

Wolff-Chaikoff Effect: High levels of iodide acutely inhibit TPO, ↓ hormone synthesis. This transient effect is used to treat thyroid storm.

On the Road - T4's Big Adventure

  • Transport: >99% of thyroid hormones are protein-bound in circulation.
    • Thyroxine-binding globulin (TBG): Binds ~70%.
    • Albumin: Binds ~15-20%.
    • Transthyretin (TTR): Binds ~10-15%.
  • Activation: Thyroxine (T4) is a prohormone.
    • Converted to triiodothyronine (T3), the more potent form, in peripheral tissues.
    • Enzyme: 5'-deiodinase.
  • Inactivation: T4 can also be converted to reverse T3 (rT3), which is metabolically inactive.
  • Free Hormone Hypothesis: Only unbound, free hormone (FT4, FT3) is biologically active.

Pathways of Thyroid Hormone Metabolism

⭐ Estrogen (e.g., in pregnancy or OCP use) ↑ TBG levels, leading to an ↑ in total T4 and T3, but free hormone levels remain normal.

Special Ops - Other Key Regulators

  • Central Inhibition: Somatostatin, dopamine, and high-dose glucocorticoids can suppress TSH release from the pituitary, acting as a brake on the HPT axis.
  • TBG Levels: Thyroid-binding globulin levels alter total T4/T3, but free hormone levels remain stable in a healthy individual.
    • ↑ TBG: Estrogen (e.g., pregnancy, OCPs) leads to ↑ total T4/T3.
    • ↓ TBG: Androgens, anabolic steroids, and protein-losing states (e.g., nephrotic syndrome).

⭐ Pregnancy elevates TBG, increasing total T4/T3. hCG can also weakly stimulate the TSH receptor.

High‑Yield Points - ⚡ Biggest Takeaways

  • TRH from the hypothalamus stimulates TSH release from the anterior pituitary.
  • TSH stimulates all steps of thyroid hormone synthesis and release.
  • Free T3/T4 exert negative feedback on the hypothalamus and pituitary, with T3 being more potent.
  • Most T3 is formed by peripheral conversion of T4 via 5'-deiodinase.
  • Wolff-Chaikoff effect: Excess iodide transiently inhibits thyroid peroxidase, decreasing hormone synthesis.
  • Jod-Basedow phenomenon: Iodide-induced hyperthyroidism in underlying thyroid disease.

Practice Questions: Regulation of thyroid function

Test your understanding with these related questions

A 27-year-old woman comes to the physician because of a 2-month history of palpitations, diaphoresis, and a 5-kg (11-lb) weight loss. Her pulse is 101/min and blood pressure is 141/84 mm Hg. Physical examination shows a fine tremor when the fingers are outstretched. After confirmation of the diagnosis, treatment is begun with an antithyroid medication. The physician emphasizes the need for adequate contraception because of the increased risk of severe fetal malformations associated with the use of this medication, which is why its use is discouraged in the first trimester of pregnancy. Which of the following best describes the mechanism of action of this drug?

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Flashcards: Regulation of thyroid function

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Thyroid-stimulating hormone (TSH) secretion is decreased in response to _____

TAP TO REVEAL ANSWER

Thyroid-stimulating hormone (TSH) secretion is decreased in response to _____

free T3/T4

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