Thyroid Hormone and its Measurement Flashcards
(26 cards)
What are the full names of T3 and T4?
T3: triiodothyrosine
T4: thyroxine
What is the function of the thyroid follicle in hormone production?
Traps circulating iodine and synthesises thyroglobulin, which is stored in colloid
What type of receptors are the TSH receptors on thyrotrophs?
G-protein coupled receptors
What is the first stage of thyroid hormone synthesis?
Iodide trapping
What happens during iodide trapping?
Dietary iodine absorbed in stomach and upper SI, then transported to thyroid in blood
Most of it is excreted in urine
Uptake by Na-I symporter to follicular cells, stimulated by TSH
(this is the rate-limiting step in thyroid hormone synthesis)
What is the second stage of synthesis?
Iodination of thyroglobulin
What are the steps in thyroglobulin iodination?
TPO (thyroid peroxidase) oxidates iodine, which is incorporated by TPO into thyroglobulin Tyr residues to form DIT and MIT “organification of iodide”
What is the 3rd stage of thyroid hormone synthesis?
MIT and DIT coupling to form precursors
How do MIT/DIT couple?
Iodinated thyroglobulin is taken into the colloid and TPO catalyses coupling between thyroglobulin molecules.
Condensation reaction allows 2x DIT or 1x DIT and 1x MIT to couple, forming T4 and T3 respectively.
Hormone precursors are stored in the colloid within thyroglobulin
Why is iodination so important?
We get hypothyroidism from I or TPO deficiency (anti-TPO antibodies in Hashimoto’s etc.)
Na/I symporter can’t tell the difference between normal and radioactive iodide which is good for imaging and therapy
How are thyroid hormone precursors released from thyroglobulin?
Stimulated by TSH secretion
- Pinocytosis of colloid droplets
- Droplets fuse with lysosomes in follicular cells and Tg is digested, releasing T3/4
- Tg released to blood as a by-product (can be measured later)
- MIT/DIT released back to follicular cell and deiodinated
How does TSH fit into all this?
TSH receptors (GPCR) on follicular cells causes gene expression that stimulates iodine trapping, thyroid hormone synthesis and release + affects thyroid cell proliferation/differentiation - Mutations in receptors can cause thyroid adenoma
Which is secreted more: T3 or T4?
T4 by far! All the body’s T4 is made in the thyroid but only a small amount of its T3, as most comes from deiodination of T4 in extra-thyroidal tissue (this is because T4 has a longer half-life but T3 is more active)
How do T3/4 circulate?
99% bound to carrier proteins, mostly thyroxine-binding globulin and some to albumin and transthyretin
1% free and metabolically active
Why are these carrier proteins important?
Free thyroid hormone needs to be kept at an appropriate level - pregnancy, hereditary effects and drugs/disease etc. can all affect carrier protein levels
How is T4 converted to T3?
In peripheral tissues, mainly the liver
Done by deiodinase enzymes that remove one I
How does T3 exert its effect on cells?
Facilitated diffusion through membrane by MCT8
T4 -> T3 by intracellular deiodinases
Free T3 binds to intracellular receptors and activates genes (thyroid and retinoid X receptors)
What are the physiological effects of T3?
- Needed for normal brain development
- Cell growth and differentiation
- Increases basal metabolic rate (increases oxygen and energy consumption, increases heart rate, sympathetic sensitivity, mineral turnover in bone)
What are the half-lives of T3 and T4?
T3: 1-1.5 days
T4: 6-7 days
How are T3 and T4 metabolised in the periphery?
T4 converted to T3 or inactive rT3 as needed (dynamic process)
T3/rT3 are converted to inactive T2, and some are conjugated in the liver and excreted by the kidneys
Deiodination is catalysed y tissue-specific selenoenzymes (with selenium as a cofactor)
What type of relationship exists between free T4 and TSH?
Inverse linear/log relationship
Which changes first in hypo/hyper-thyroidism: TSH or free hormones?
TSH
What is the use of testing thyroid autoantibodies?
Autoantibodies can help diagnose Graves’ (anti-TSH receptor) , AI thyroid disease (Anti-TPO antibodies) and thyroiditis (anti-Tg antibodies)
What does TRH stimulation test?
Should increase TSH levels so used to test pituitary function
