Thyroid

Describe the control, secretions and functions of the thyroid.

The thyroid gland:

• Produces and secretes two hormones in response to TSH:
  • T₄ (thyroxine, 93%)
  • T₃ (tri-iodothyronine, 7%)
• Secretions are controlled via a negative-feedback loop on the hypothalamic-pituitary-thyroid axis
  Increased TSH results in:
  • Increased iodine uptake
  • Increased iodination to form T₄ and T₃
  • Increased proteolysis of thyroglobulin, which releases T₄ and T₃
• Secretions are decreased with decreased iodine uptake
  • Perchlorate
    Blocks Na⁺/I^- symporter.
  • Wolff-Chaikoff effect
    A reduction in thyroid hormone production due to a high circulating [iodide].

Synthesis

Thyroid hormones are:

• Synthesised in follicles
  A follicle is formed of a single layer of cuboidal epithelium around a central lumen (follicular cavity) containing thyroglobulin.
  • Iodide is transported into follicular cells via a secondary active transport mechanism
    Na⁺/I^- co-transporter.
  • Iodide is then oxidised to iodine
  • Thyroglobulin is synthesised in the endoplasmic reticulum of the follicular cell and excreted into the follicular cavity
  • Iodine is excreted into the follicular cavity using a chloride exchange pump
  • In the follicular cavity:
    • Thyroid peroxidase catalyses the iodination of thyroglobulin, forming mono-iodotyrosine and di-iodotyrosine
    • These are subsequently oxidised, forming T₃ and T₄ respectively

In summary:

• Iodide is taken into the thyroid follicles by secondary active transport, and oxidised to iodine
• Thyroglobulin is synthesised in the follicle, and excreted into the follicular cavity
• Iodine is secreted into the follicular cavity, where it combines with thyroglobulin to produce T₄ and T₃

Secretion and Metabolism

Thyroid hormones are:

• Secreted in vesicles via endocytosis into the surrounding capillaries
  • Colloid enters thyroid cell via pinocytosis at the apical membrane
  • Vesicles then fuse with lysosomes
  • Thyroid hormone cleaved from thyroglobulin by proteases
  • Free T₃ and T₄ diffuse through the base of the thyroid cell into surrounding capillaries
• Highly protein bound to albumin and thyroxine-binding globulin
  • T₄ has a t_1/2 of 7 days
  • T₃ has a t_1/2 of 24 hours
  • Both are deiodinated in the liver, kidney, and muscle
    • 55% of T₄ will be first deiodinated to T₃

Physiological Effects

Thyroid hormones:

• Act on thyroid receptors in the cell nucleus
  Increasing gene transcription, protein synthesis, and mitochondria size and number.
• T₃ is 3-5x more active than T₄

Effects of thyroid hormone are predominantly metabolic:

References

1. Kam P, Power I. Principles of Physiology for the Anaesthetist. 3rd Ed. Hodder Education. 2012.
2. CICM September/November 2008