19 - Thyroid Gland Flashcards
What is the location and macroscopic structure of the thyroid?
- 2 lateral lobes joined by isthmus
- Bow tie shape
What is the blood supply to the thyroid?
High vascular as three arteries supplying and three veins draining:
- Superior
- Middle
- Inferior
What is the risk when carrying out thyroid surgery?
- Thyroid in close proximity to recurrent laryngeal and external branch of superior laryngeal nerve. These supply the larynx and are involved in speech so must be avoided
What is the embryological origin of the thyroid?
- First gland to develop at 3-4 weeks
- Epithelial proliferation in floor of pharynx at base of tongue
- Descends as diverticulum through thyroglossal duct and migrates down in front of hyoid bone
- Remains connected to tongue by thyroglossal duct which then degenerates as the thyroid descends to final position
What is the microscopic appearance of the thyroid gland?
- Follicle and parafollicular (C-cells)
- Follicles separated by CT and C cells within the CT
- Follicles are spherical and lined with epithelial cells surround lumen of colloid which contains thyroglobulin
What do each of the cells in the thyroid produce?
Follicular –> Thyroid hormone. T3 (Thyroxine) and T4 (triiodothyronine)
Parafollicular –> calcitonin
What are T3 and T4 made up of?
- Amino acid tyrosine x 2
- Iodine
What are the steps in the synthesis of T3 and T4?
- Iodide transported into epithelial cells against conc grad
- Tyrosine rich protein (Thyroglobulin) made in epithelial cells
- Exocytosis of thyroglobulin into colloid in lumen
- Iodide oxidised to produce iodinating species
- Iodination of side chains of tyrosine in thyroglobulin to form MIT and DIT
- Coupling of DIT with MIT or DIT within thyroglobulin to form T3 and T4 in ratio 1:10
What is the enzyme involved in T3 and T4 synthesis?
Thyroid Peroxidase
How is iodine obtained for thyroid hormone synthesis?
- Dietary iodine reduced to iodide before absorption in SI
- Iodide taken up from blood by thyroid epithelial cells by sodium-iodide symporter (iodine trap)
- Most iodine in body in thyroid
Where are T3 and T4 stored and how is it secreted?
- In lumen of colloid as part of thyroglobulin and large amount stored that can last a few months
- Thyroglobulin taken into epithelial cells from lumen by endocytosis. Proteolytic cleavage of the proteins occurs to release T3 and T4 and then they diffuse from cells to blood
What thyroid hormone is released from the thyroid gland the most and how is it transported in the blood?
- T4 and it is converted to T3 in kidneys and liver
- Activity of T3 is 4 times that of T4
- T3 and T4 bound to thyroxine-binding globulin, pre-albumin or albumin as hydrophobic
How is the secretion of thyroid hormone regulated?
- TRH released from hypothalamus from cells in dorsomedial nucleus in response to T3/T4 levels, stress (increases release) and temperature (low temp increases release)
- TRH travels in hypothalamo-hypophyseal portal to anterior pituitary which stimulates secretion of TSH from thyrotropes.
- TSH travels to blood and acts on follicular cells
What type of hormone is TSH and what levels will it appear at in the blood at different times in the day?
- High levels during the night and this decreases into the early hours of the morning
What does TSH stimulate and what type of receptor does it act on?
- Can act on GPCR S or Q
- Trophic effects on gland as it increases vascularity and increases size and number of follicle cells. Can result in enlarged gland
Why might you have a goitre with hypothyroidism?
High levels of TSH, which has a trophic effect on the follicle cells causing gland to increase in size
What is the difference in the half-life of T3 and T4 and why?
T3 only 2 days but T4 is 8 days as T3 has lower affinity for transport proteins so there is more free T3 hormone
Why might you have hyperthyroidism induced by pregnancy?
- Oestrogen increases in pregnant women and this stimulates more production of TBG
- Less free T3 and T4 so more TRH and TSH produced to combat the lack of free T3 and T4 in the blood, even though there is still lots bound
What are the actions of T3 and T4 on the body in general?
- Takes a few days/weeks to manifest activity on tissue
- Stimulate glucose uptake, mobilisation and oxidation of fatty acids and stimulate protein metabolism. Increases BMR, heat production and oxygen consumption
What are some tissue specific effects of thyroid hormone?
Heart: increases synthesis of heart muscle protein and stimulate hormone and neurotransmitter receptor synthesis to increase responsiveness of tissues so can produce tachycardia
GI: increase motility by increasing receptor synthesis
CNS: development of nerve cells, hyperplasia of cortical neurons and myelination of nerve fibres
Pituitary: without thyroid hormone ovulation fails as no FSH and LH
Why might someone with hypothyroidism struggle to get pregnant?
Thyroid hormones involved in production of FSH and LH so without them then then ovulation cannot occur
What can a lack of thyroid hormone cause in children and adults?
Children: from birth to puberty if low thyroid can have cretinism where child is mentally and physically retarded as cannot develop cellular processes of nerve cells and myelination. If not corrected a few weeks after birth change is irreversible
Adults: poor concentration, poor memory, lack of initiative
What action does the thyroid hormone have on it’s target cell in regards to the receptor it uses?
- Nuclear receptor
- Crosses plasma membrane of target cell and binds to high affinity receptors on nuclei and mitochondria. 10 fold affinity greater for T3
- Increase the rate of transcription of specific gene so increased protein synthesis
- Increase in protein synthesis stimulates oxidative energy metabolism to provide the energy for synthesis and to provide energy for increased cell activity
What are normal levels of T3, T4 and TSH in the blood, and what can cause variations in the readings?
‘Free’ = hormone not bond to plasma proteins
How is T4 converted into T3?
- Removal of 5’-iodide
- Removing 3’-iodide produces inactive reverse T3, which can bind to thyroid hormone receptors but not activate them so blocks activity of T3
