Thyroid Flashcards
What type of receptor is the thyrotropin receptor (TSHR)?
GPCR
Where do TSHRs receive signals from?
Pituitary
How are thyroid hormones synthesised?
- thyroglobulin is synthesised in the RER, follows a secretory pathway and enters the colloid via exocytosis
- Simultaneously, Na+/I- symporter (NIS) pumps iodide actively into the cell
- iodide enters the follicular lumen (colloid) from the cytoplasm by the transporter pendrin
- Colloid: iodide – TPO –> iodine
- TPO = thyroid peroxidase - iodine iodinates the thyroglobulin (at tyrosyl residues)
- thyroglobulin reenters the follicular cell by endocytosis
- proteolysis liberates thyroxine and triiodothyronine
What ion inhibits T4 release? In what situation/condition might this occur? How is this treated?
- T4 inhibited by iodide
- can occur in thyrotoxicosis
- use Lugol’s iodine or potassium iodide as treatment
What effect does TSH have on the thyroid?
increases NIS, TPO, thyroglobulin, H2O2 (oxidising agent), T4 and T3
- also increases thyroid blood flow and thyroid follicular cell hyperplasia
What are the different forms of deiodinase and what is their role?
D1, D2, D3 = iodothyronine deiodinase
Release iodine from thyronine hormones
Explain the control of thyroid function from the level fo the hypothalamus.
Hypothalamus – TRH –> pituitary – TSH –> Thyroid –> T3 and T4
- T4 —> T3 + rT3
What stimulates TRH release from the hypothalamus?
- cold
- acute psychosis
- circadian rhythm
What inhibits TRH release from the hypothalamus?
- somatostatin
- stress
- excess TRH
- T3
What stimulates TSH release from the pituitary?
- TRH
What inhibits TSH release from the pituitary?
- corticosteroids
- dopamine
- excess TSH
- T3
What stimulates thyronine hormone release from the thyroid?
TSH
What stimulates thyronine hormone release from the thyroid?
- excess iodine
What hypothyroidism and how is it treated?
Lack of thyroid hormone
Treat with levothyroxine
Should the dose of levothyroxine change if a woman is pregnant? If so, why?
Dose should INCREASE
- oestrogen binds to thyroid binding globulin which binds to free thyroid
- this reduced free T4 (=hypothyroidism)
- in pregnancy, there is more oestrogen therefore more levothyroxine is needed
Which transporters mediate the entry of T4 and T3 into cells?
ATP-requiring Transporters: - MCT8 - MCT10 - OATP1c1
What changes occur once thyroid hormones enter cells?
- can have a genomic effect –> means they can directly influence gene transcription and translation
- thyroid hormone bind to the thyroid response element
- T3 binds to the co-repressor, displacing it from the receptor/DNA complex
- this causes the TRs to cleave
- retinoid X receptor monomers bind on (new TR/RXR dimer)
- this causes CoA to bind
- transcription is activated
What are the effects of thyroid hormones on the body?
- increases BMR
- increases O2 consumption
- increases the rate of ATP hydrolysis
- increases fat mobilisation
- enhances fat oxidation
- reduces/controls LDL cholesterol
- increases gluconeogneeiss
- increases glycogenolysis
- increases glucose uptake
- causes vasodilation –> enhances blood flow to organs
What is the difference between hyperthyroidism and thyroidtoxicosis?
Hyperthyroidism = due to excessive production of thyroid hormone by the thyroid gland
Thyrotoxicosis = excessive thyroid hormone of any cause - include hyperthyroid
Give an example of a condition causing hyperthyroidism?
Graves’ disease
- due to autoantibodies against TPO, thyroglobulin and TSHR
What are the risk factors for Graves’ disease?
- HLA status (esp DR3)
- Infection
- Female
- Stress (cortisol + CRF)
How can Graves’ disease affect the eyes?
- lymphocytes release IFN-gamma
- fibroblasts secrete glycosaminoglycans
- eyes become fibrotic
- local hypoxia and increase inflammation (if smoking)
result = exophthalmos and lid lag mostly
What is the effect of excess thyroid hormone on the cardiovascular system?
- need to dissipate excess heat (underdress)
- increases alpha:beta myosin = increased inotropy
- increased nitric oxide = reduced peripheral resistance
- widened pulse pressure = palpitations
- AF
What is the effect of excess thyroid hormone on the nervous system?
- nervousness
- tremors
- seizures
