The thyroid gland is a ductless alveolar gland found in the neck. It has two lobes connected by what’s known as the isthmus and wraps around the trachea. You are not usually able to feel your thyroid gland. The thyroid is supplied by the superior and inferior thyroid arteries and is drained via 3 veins; superior, middle and inferior thyroid veins.
Thyroid epithelia form follicles filled with colloid, a protein rich reservoir of materials which are needed for the production of thyroid hormones. Between the follicles are parafollicular cells which secrete calcitonin. This calcitonin is involved in the regulation of calcium metabolism within the body.
The main function of the thyroid gland is to produce and store thyroid hormones, which are involved in the rate of metabolism. High levels of thyroid hormone speed up metabolism by acting on nuclear receptors in target tissues and initiating various metabolic pathways. There are a number of these pathways that thyroid hormones speed up such as gluconeogenesis, lipogenesis, basal metabolic rate.
Thyroid hormone synthesis can be split into 6 steps, which I like to remember using TEA ICE.
- T = thyroglobulin – a large protein is formed in follicular ribosomes and placed into a secretory vesicle, this is rich in tyrosine
- E = exocytosis – the thyroglobulin is exocytosed into the follicle lumen where it is stored as colloid. Thyroglobulin is a scaffold for which thyroid hormones are synthesised.
- A = active transport – iodide is actively transported into the follicular cell via a sodium-iodine symporter. For this to occur a sodium gradient is maintained by sodium-potassium ATPase.
- I = iondination – iodine is made reactive by the enzyme thyroid peroxidase and binds to the thyroglobulin at tyrosine amino acids. When one iodine binds it forms monoiodotryosin (MIT) and then diiodotyrosine (DIT)
- C = coupling - MIT and DIT can couple together to for triiodothyronine (T3) hormone or two DITs can couple together to form tetraiodothyronine (T4) hormone (thyroxine).
- E = endocytosis – the thyroglobulin undergoes proteolysis in lysosomes so that the T3 and T4 are cleaved off the larger protein. The free T3 and T4 are then release, leaving the thyroglobulin scaffold to be recycled.
T3 and T4 are mostly carried by plasma proteins within the blood, thyronine binding globulin and albumin. T3 is more potent than T4 however it has a shorted half-life as it has low affinity for binding proteins. In the peripheries T4 is deiodinated to form the more active T3. The liver and kidneys metabolise T3 and T4 by removing the iodine.
This whole system of production of thyroid hormones is under control of the hypothalamic-pituitary-thyroid axis. This is where thyroid releasing hormone (TRH) is produced by the hypothalamus which stimulates the pituitary gland to produce thyroid stimulating hormone (TSH) which promotes the production of T3 and T4. This have a negative feedback loop in order to stop the over production of T3 and T4. T3 and T4 inhibit both the pituitary gland and the hypothalamus so they do not produce as much TSH or TRH.
In our next blog we will look at what happens when this system goes wrong