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
What is the effect of excess thyroid hormone on the reproductive system?
- disordered GnRH pulse
- oligomenorrhoea/amenorrhoea
- gynaecomastia (androgen –> oestrogen)
- erectile dysfunction (androgen –> oestrogen)
- miscarriage
What is the effect of excess thyroid hormone on the metabolism?
- increased BMR
- increased appetite
- heat intolerant
- increased protein and lipid degradation = weight loss and myopathy
- increased insulin turnover = hyperglycaemia
- reduced gluconeogenesis
- reduced insulin secretion
What is the effect of excess thyroid hormone on the skin?
- warm, moist, sweating - vasodilation
- plummer’s nail - uneven, black lines
- vitiligo - pigmentation lost
- pretibial myxoedema
What is the effect of excess thyroid hormone on the GIT?
- increased appetite
- reduced weight
- increased motility (reduced fat absorption)
- increased transaminase in serum
What is the effect of excess thyroid hormone on the blood?
- pernicious anaemia
- B12 deficiency
What is the effect of excess thyroid hormone on the eyes?
- exophthalmos/proptosis - eyes bulge out
- eyelid retraction + inflammation of soft orbital tissue
- lid lag
What is the effect of excess thyroid hormone on the bones?
- increased osteoclast activity (T3)
- hypercalcaemia - osteoporosis
What are the other causes of thyrotoxicosis?
- toxic multinodular goitre
- toxic adenoma
- excess iodine
- amiodarone
- HGC thyroiditis
- TSHoma
- Struma ovarii
- Hamburger thyrotoxicosis
How should hyperthyroid conditions be managed?
- Technetium or iodine uptake scans
- thyroidectomy
- thionamide drugs (propylthio-uracil, carbimazole)
- radioactive iodine
Give an example of a condition causing hypothyroidism?
Hashimoto’s
- due to antibodies to TPO
- apoptotic follicular cell destruction
What is the effect of hypothyroidism on the cardiovascular system?
- reduced cutaneous circulation - (overdressed)
- sinus bradycardia
- increased LDL cholesterol - fatty plaques in arteries
- J waves of hypothermia
What is the effect of hypothyroidism on the renal and haematological system?
- reduced GFR
- hyponatraemia - water retention
- reduced reabsorptive and secretory capacity
- normochromic and normocytic anaemia
What is the effect of hypothyroidism on the endocrine system and metabolism?
- delayed puberty
- reduced libido
- erectile dysfunction
- reduced BMR
- reduced GLUT4 stimulation
What is the effect of hypothyroidism on the GIT?
- reduced appetite
- reduced peristalsis –> constipation
- increased weight - fluid retention
What is the effect of hypothyroidism on the nerves, muscle and bone?
- impaired foetal brain development
- dementia
- slow relaxing reflexes - may be jittery
- growth retardation
- loss of initiative and memory
- stiffness and muscle aches (worse in the cold)
- epiphyseal dysgenesis - impaired linear growth (dwarfism)
How does Hashimoto’s cause goitre (swelling of thyroid gland)?
TSH trophic effects
Apart from Hashimoto’s, what are the causes of hypothyroidism?
- endemic goitre - iodine deficiency
- hypopituitarism
- Pendred’s syndrome
- infiltrate disease
- lithium (inhibits TSH release)
How are hyper and hypothyroidism diagnosed?
Hyper:
- increased T3, T4
- low TSH
Hypo:
- high TSH
- low T4
How is hypothyroidism managed?
Levothyroxine and liothyronine
