Flashcards in 2. The Thyroid Gland Deck (24):
Where is the thyroid gland?
-lies against and around the front larynx and trachea
-below the thyroid cartilage (Adams apple)
-isthmus extends from the 2nd to 3rd rings of the trachea
How is the thyroid derived embryologically?
- first endocrine organ to develop
- at 3-4 weeks gestation the thyroid appears as an epithelial proliferation in floor of the pharynx at base of tongue and takes several weeks to migrate to final position
-1st descends as diverticulum through the thyroglossal duct
-during migration remains connected to the tongue by thyroglossal duct which subsequently degenerates
-detracted thyroid then continues to its final position over following 2 weeks
Describe the histology of the thyroid tissue
-thyroid tissue is composed of follicular cells arranged in spheres known as thyroid follicles
-follicles are filled with colloid - deposit of thyroglobulin
-colloid is extracellular even though it is inside the follicle
What is secreted by the cells of the thyroid?
-thyroid follicular cells produce thyroid hormone
-thyroid parafollicular cells produce calcitonin
In the parathyroid gland, which cells produce parathyroid hormone?
The parathyroid principal also called chief cells
How is thyroid hormone synthesised?
-thyroid hormone consists of tyrosine residues which are iodinated (iodine group added to them)
- 1 iodine : MIT :monoiodotyrosine
-2 iodines: DIT : diiodotyrosine
MIT + DIT = triiodothyronine (T3)
DIT + DIT = tetraiodothyronine (T4) AKA thyroxine
What is thyroglobulin?
Thyroglobulin acts as a scaffold on which thyroid hormones are formed.
Thyroglobulin contains 134 tyrosine, although only a handful of these are actually used to syntehsise T3 and T4
What is thyroid peroxidase?
Membrane bound enzyme which regulates 3 separate reactions involving iodide.
1. Oxidation - iodide become iodine
2. Addition of iodine - to tyrosine acceptor residues o the protein thyroglobulin
3. Coupling - of MIT or DIT to generate thyroid hormones with the thyroglobulin protein
What happens to dietary iodine?
-dietary iodine is reduced to iodide before absorption principally in the small intestine before absorption
-thyroid hormones and precursors are the only molecules in the human body that contain iodine
-thyroid gland 95% iodine
How is iodide taken up?
-iodide taken up from the blood by thyroid epithelial cells which have a sodium iodide symporter or 'iodine trap'
What are the common sources of iodine?
- dairy products, grains, meat, eggs
What is the major form of thyroid hormone which is secreted?
-90% of thyroid hormone secreted is T$
-biological activity of T3 is 4 times that of T4
-most T4 will be converted to T3 in the liver and the kidneys
- 80% of circulating T3 is from T4
- T3 and T4 are transported in the blood bound to the protein thyroxine - binding globulin
How is thyroid hormone secretion regulated?
- via negative feedback
-thyroid hormone has effects on metabolism and also on growth and development
- Hypothalamus releases Thyrotropin releasing hormone (TRH)
-Anterior pituitary releases Thyroid stimulating hormone (TSH)
- thyroid gland will release thyroid hormone (TH)
What is the structure of TSH?
-glycoproteins composed of 2 non covalenty bound subunits (alpha and beta)
-the alpha subunit is also present in FSH and LH
-The beta subunit provides unique biological activity
What does TSH do to trigger thyroid hormone release?
-prteolysis of thyroglobulin
Which pathways is TSH coupled?
The TSH receptor can be coupled to GaS and also Gaq.
What are the general effects of the thyroid hormone?
- increase in BMR and heat production
-stimulation of metabolic pathways - mainly catabolic
What are the effects of thyroid hormone on the CVS system?
- increase hearts responsiveness to catecholamines
-increased cardiac output, increase in heart rate and increase in force of contraction
-increase in peripheral vasodilation to carry extra heat to body surface
What is the role of thyroid hormone in the nervous system?
-essential for both development and adult function
-myelination of nerve and development of neurones
What are the thyroid hormone receptors?
-hormone activated transcription factors
-modulate gene expression
-when there is no hormone, the TH receptor binds to DNA leading to transcriptional repression
-when hormone binds, conformational change - transcriptional activator
What happens when thyroid hormone binds to an intracellular receptor?
-lipid soluble and enters cell through thyroid hormone transporter
-TH receptor is pre bound to the hormone response element on DNA
-when TH enters nucleus and binds to TH receptor it relieves repression and gene expression
-examples of TH activated genes included PEPCKL
-expression of new protein mediates the effects of thyroid hormone
Normal plasma levels of thyroid hormones
Free T4 : 0.7-2.1
Free T3 : 0.2 -0.5
TSH - 0.3 - 4.0
Free means that the hormone is not bound to plasma protein
What is thyroid scintigraphy?
-technetium 99m used for isotope scanning of the thyroid with a gamma camera
-most commonly used medical radioisotope
-biological half life 1 day
-low radiation exposure
-also used for brain scans, myocardial perfusion imaging and brain imaging