Thyroid - Pathology Flashcards
The thyroid gland develops from an invagination of what?
Pharyngeal epithelium
Where does the thyroid gland descend to and from?
From the foramen caecum of the tongue to the thyroglossal duct
What is known as when the thyroid gland fails to descend normally?
Lingual thyroid
If there is excessive descent of the thyroid, where does it end up?
Retrosternal in the mediastinum
What is the thyroid gland composed of?
Follicles
What cell type are the thyroid follicles surrounded by?
Cuboidal follicular epithelial cells
What is the area in the centre of each thyroid follicle known as?
Colloid
What does the thyroid colloid contain? What is this?
Thyroglobulin- this is the protein on which T3 and T4 are synthesised
What other cell type are found scattered among the thyroid follicles in the upper 2/3rds of the thyroid gland?
C-cells (parafollicular cells)
What do C-cells produce?
Calcitonin
What does calcitonin do?
Decrease serum calcium levels
Calcitonin is a good marker for what?
Medullary thyroid cancer
What three things does thyroid gland tissue secrete?
T3, T4 and calcitonin
What is required for the synthesis of thyroid hormones?
Iodine
What will happen if you live in an area where there is not enough iodine?
You won’t make enough thyroid hormones and hence will be hypothyroid
What is the difference, chemically, between T3 and T4?
1 iodine
Iodine is taken up by which cells?
Follicular cells
What does iodine attach to once it has been taken up? What does this form?
Iodine attaches to tyrosine units on thyroglobulin to form MIT and DIT units
How do carbimazole and PTU work?
They prevent iodination of tyrosine
What units need to be combined to form T3?
1 MIT and 1 DIT
What units need to be combined to form T4?
2 DITs
What happens to T3 and T4 molecules once they have been synthesised?
They are stored in colloid thyroglobulin until they are required
Which is the major biologically active thyroid hormone?
T3
Which thyroid hormone is produced in greater amounts?
T4
What happens to the majority of T4 produced?
It is converted to T3 in peripheral tissues
What chemical process changes T4 to T3?
5-monodeiodination (removal of 1 iodine)
What does 3-monodeiodination of T4 form?
rT3
Which family of enzymes regulates the conversion of T4 to T3?
Deiodinase enzymes
Where is deiodinase 1 found?
Liver and kidney
Which deiosinase enzyme is the major determinant of generating T3 from T4?
D2
Where is deiodinase 3 found?
Foetal tissue ad brain (except the pituitary gland)
What is the first step in releasing thyroid hormones?
TSH binds to its receptor on the surface of thyroid epithelial cells
What type of receptor is the TSH receptor?
GPCR
What happens when TSH has bound to its receptor?
GTP is converted to GDP and cAMP is produced
What allows T3 and T4 to be released from cells?
Increased cAMP
Where is most T3 and T4 found in the plasma? Why?
Bound to hormone binding proteins, since they are hydrophobic and lipophilic
What hormone binding protein is most of T3 and T4 bound to in the plasma?
Thyroxine binding globulin
What are the less used hormone binding proteins?
Thyroid-binding pre-albumin Albumin
Which thyroid hormone is bound less avidly to TBG?
T3
What type of T3 and T4 should be measured in a thyroid function test?
Free
What type of receptor is the T3 receptor?
Nuclear
How are thyroid hormones taken into cells?
A transmembrane transporter
What is the thyroid hormone receptor bound to?
Thyroid response element
Where are TRalpha thyroid receptors found?
Peripheral tissues
Where are TRbeta thyroid receptors found?
In the feedback loop
Resistance to which type of thyroid receptor causes the biggest problem?
TRbeta
What effect do thyroid hormones have on the basal metabolic rate?
Increase it
What are 3 ways that thyroid hormones increase basal metabolic rate?
- Increase the number of mitochondria - Increase oxygen use and rate of ATP hydrolysis - Increase synthesis of respiratory chain enzymes
What effect do thyroid hormones have on thermogenesis?
Increase it
Name two effects that thyroid hormones have on carbohydrate metabolism?
- Increase plasma glucose due to stimulation of glycogenolysis and gluconeogenesis - Increase insulin dependent glucose uptake into cells
Name two effects that thyroid hormones have on lipid metabolism?
- Mobilise fats from adipose tissue - Increase fatty acid oxidation in tissues
What two effects do thyroid hormones have on protein metabolism?
- Increased protein synthesis - Decreased plasma amino acids
What hormones relating to growth require thyroid hormones for their action?
GHRH and GH
How do thyroid hormones help to develop the foetal and neonatal brain?
They allow myelinogenesis and axonal growth
What can inadequately treated hypothyroidism in pregnancy cause?
Problems with cognitive development
What effect do thyroid hormones have on the sympathetic nervous system? What effect does this have on the CV system?
They increase responsiveness to adrenaline and noradrenaline by increasing the number of receptors. This increases cardiac rate and force of contraction.
What effect do low temperatures have on thyroid function in babies and young children?
Stimulate TRH release, hence TSH release, hence T3/4 release
What effect does stress have on thyroid function?
Inhibits TRH and TSH release
Describe the circadian rhythm of thyroid hormones?
Thyroid hormone levels are high at night and low in the morning
