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
    • Percholate
      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 T4 and T3 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
  • Highly protein bound to albumin and thyroxine-binding globulin
    • T4 has a t1/2 of 7 days
    • T3 has a t1/2 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:

System Effect
Resp MV due to ↑ CO2 production
CVS HR, ↑ inotropy, ↑ CO, ↓ SVR, ↓ DBP
CNS ↑ Excitability: Seizures, tremor
MSK ↑ Osteoblastic activity
GU Impotence (men), oligomenorrhoea (women)
GIT ↑ GIT motility
Metabolic BMR up to 100%, ↑ carbohydrate metabolism (↑ glucose uptake, ↑ glycolysis, ↑ gluconeogenesis), ↑ fat metabolism (↑ lipolysis, ↑ non-shivering thermogenesis, ↓ plasma cholesterol, ↓ plasma phospholipids, ↓ triglycerides), ↑ protein metabolism (↑ anabolism at physiological levels, ↑ catabolism at high levels)

References

  1. Kam P, Power I. Principles of Physiology for the Anaesthetist. 3rd Ed. Hodder Education. 2012.
  2. CICM September/November 2008
Last updated 2017-09-22

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