Flashcards in MEH - The Thyroid Deck (37)
Where is the thyroid gland located?
Against and around the front larynx and trachea, below the thyroid cartilage. The isthmus extends from the 2nd to the 3rd rings of the trachea.
Describe the embryological development of the thyroid
- first endocrine gland to develop
- at 3-4 weeks gestation, appears as an epithelial proliferation in floor of pharynx at base of tongue
- descends as diverticulum through thyroglossal duct and migrates downwards, passing in front of the hyoid bone
- remains connected to the tongue by the thyroglossal duct which subsequently degenerates
- detached thyroid then continues to its final position over next two weeks
What are thyroid follicles made of?
Follicular cells arranged in spheres, filled with 'colloid' - a deposit of thyroglobulin
What do thyroid follicular cells produce?
What do thyroid parafollicular cells produce?
What are the histological differences between the parathyroid gland and the thyroid gland?
Parathyroid gland tissue appears denser, lots of small cells stuck together. Thyroid gland tissue has spaces in it, and is made of thyroid follicles which have colloid in them
At a molecular level, what are thyroid hormones formed from?
2 tyrosine linked together, with iodine at three or four positions on the aromatic rings
What is the difference between T3 and T4?
T3 (triiodothyronine) is formed from monoiodotyrosine and diiodotyrosine, while T4 (tetraiodothyronine/thyroxine) is formed from two diiodotyrosine molecules
What is the role of thyroglobulin in thyroid hormone formation?
It acts as a scaffold, stabilising tyrosine residues while they are iodinated and coupled
What are the three reactions regulated by thyroid peroxidase?
1) oxidation of iodide to iodine (requires hydrogen peroxide)
2) addition of iodine to tyrosine acceptor residues on thyroglobulin
3) coupling of MIT or DIT to generate thyroid hormones within thyroglobulin protein
How does dietary iodine reach the thyroid gland, where 95% of the iodine in the body is stored?
- reduced to iodide before absorption in the small intestine
- iodide is taken up from the blood by thyroid epithelial cells, which have a sodium-iodide symporter
What form is most of the thyroid hormone secreted by the body?
90% is T4.
Where is T4 converted to T3?
Liver and kidneys
Which is stronger, T3 or T4?
T3 is three times stronger than T4
How are T3 and T4 transported in the blood?
They are transported bound to the protein thyroxine-binding globulin
How is thyroid hormone secretion regulated?
Via negative feedback of thyroid hormone to the hypothalamus and anterior pituitary
What is thyroid stimulating hormone (TSH)?
A glycoprotein hormone composed of two non-covalently bound subunits (alpha and beta). The alpha subunit is also present in FSH and LH but the beta subunit is unique. It triggers thyroid hormone release.
Give some examples of things stimulated by TSH
- iodide uptake and oxidation
- thyroglobulin synthesis and iodination
- colloid pinocytosis into the cell
- proteolysis of thyroglobulin
- cell metabolism and growth
What are the two TSH induced second messenger pathways?
- can stimulate G alpha-S, increasing adenylyl cyclase and cAMP, producing more PKA leading to stimulation of thyroid hormone synthesis and release
- can stimulate G alpha-Q, increasing phospholipase C and therefore DAG and IP3. This leads to more Ca2+ release via the IP3 receptor, and PKC activation. This stimulates more thyroid hormone synthesis and release
How do thyroid hormones stimulate the metabolic rate?
- increase number/size of mitochondria
- stimulate the synthesis of enzymes in the respiratory chain
- stimulates lipolysis and beta-oxidation of fatty acids
- stimulates insulin-dependent entry of glucose into cells and increases gluconeogenesis and glycogenolysis
What are the sympathomimetic effects of thyroid hormone?
Increases target cell response to catecholamines by increasing receptor number on target cells
What are the effects of thyroid hormone on the cardiovascular system?
- increases heart's responsiveness to catecholamines
- increases cardiac output (higher heart rate and force of contraction)
- increase in peripheral vasodilation to carry extra heat to body surface
What are the effects of thyroid hormone on the nervous system
Increases myelination of nerves and development of neurons
True or false - thyroid hormone receptors are nuclear receptors?
How do thyroid hormone receptors work?
- lipid soluble hormone enters cell through thyroid hormone transporters
- thyroid hormone receptor is pre-bound to hormone response elements in promoter region of thyroid hormone regulated genes
- hormone enters nucleus and bind to thyroid hormone receptor on DNA, relieving repression of gene transcription and allowing gene to be expressed
- expression of new protein mediates effects of thyroid hormone
What unit is used when referring to normal plasma levels of thyroid hormones?
What is goitre?
Enlargement of the thyroid gland which often develops when the thyroid gland is overstimulated
Give some general symptoms of hypothyroidism
- intolerance to cold
- dry skin
- hoarse voice
- slow reflexes
- low T3, low T4 and elevated TSH
Give some symptoms of cretinism
- dwarfed stature
- mental deficiency
- poor bone development
- slow pulse
- muscle weakness
- GI disturbances