3.6 - Hyperthyroidism Flashcards
(37 cards)
How does TSH work on the thyroid gland to produce T3 (triiodothyronine) and T4 (thyroxine)?
- TSH binds to TSH-R on basolateral membrane of follicular cell
- stimulates activation of Na-I cotransporter and Na+ and I- ions enter cell
- I- move into colloid where they are oxidised to iodine (iodination)
- TSH binding causes production of thyroglobulin (prohormone) which is secreted into colloid
- TSH binding also causes activation of TPO enzyme which along with H2O2 catalyses iodination reactions
- iodine from before added to thyroglobulin through iodination to produce MIT + DIT
- coupling reaction results in production of T3 and T4 attached to thyroglobulin
- thyroglobulin removed at lysosome and T3 and T4 released into bloodstream
How is production of thyroid hormone controlled?
- TRH from hypothalamus stimulates TSH from APG, stimulating T3 and T4 from thyroid
- T3 and T4 have negative feedback effects on TRH and TSH
How do we control thyroid replacement?
Monitor TSH level and increase thyroid replacement dose until TSH falls to normal
What happens in Grave’s disease?
- autoimmune disease where antibodies bind to and stimulate the TSH receptor in the thyroid
- causes smooth goitre and hyperthyroidism
- other antibodies bind to muscles behind the eye and cause exophthalmos
- other antibodies cause pretibial myxoedema
What is pretibial myxoedema?
- other antibodies cause pretibial myxoedema (hypertrophy) - growth of soft tissue
- pretibial - in front of tibia (shins)
- myxoedema - swelling of lower limb
- swelling is non-pitting as it is solid
- not to be confused with myxoedema –> HYPOthyroidism
What are some symptoms of Grave’s disease? (18)
- perspiration
- facial flushing
- muscle wasting and weakness
- shortness of breath
- breast enlargement / gynecomastia in males
- weight loss
- rapid pulse, tachycardia, palpitation
- warm, moist palms
- oligomenorrhoea / amenorrhoea
- pretibial myxoedema
- nervousness, excitability, restlessness, emotional instability, insomnia
- exophthalmos
- goitre
- warm, velvety skin
- increased appetite
- diarrhoea
- tremor
- clubbing of fingers
What does the thyroid gland look like in Grave’s disease?
Diffuse enlargement and engorgement of thyroid gland, diffuse goitre of moderate size
What does a radioiodine uptake scan of the thyroid gland look like in Grave’s disease?
Uniform radioiodine uptake (V-shape) as whole gland is overactive so takes up the iodine
What is toxic nodular thyroid disease?
AKA Plummer’s disease
- single toxic nodule/multiple toxic nodules (multinodular goitre)
- not autoimmune
- benign adenoma(s) overactive at making thyroxine
What features are present in Grave’s disease but not present in toxic nodular thyroid disease?
- no pretibial myxoedema
- no exophthalmos
- as not autoimmune so antibodies not involved
What does the thyroid look like in toxic nodular thyroid disease?
- asymmetrical lump
- one cell has grown a lot on one side of the thyroid so that side is large
- this makes a lot of thyroxine which suppresses TSH
- lack of TSH means the normal side of the gland atrophies and gets smaller
What does a radioiodine uptake scan of the thyroid look like in toxic nodular thyroid disease?
Black ‘hot nodule’ on one side of the scintigram (rest of gland off)
What are the effects of thyroxine on the sympathetic nervous system?
- sensitises beta adrenoceptors to ambient levels of adrenaline and noradrenaline
- thus there is apparent sympathetic activation
- tachycardia, palpitations, tremor in hands, lid lag etc
What are the symptoms of hyperthyroidism? (7)
- weight loss despite increased appetite
- breathlessness
- palpitations, tachycardia
- sweating
- heat intolerance - feel hot in winter
- diarrhoea
- lid lag and other sympathetic features
What is a thyroid storm?
- medical emergency - 50% mortality untreated
- blood results confirm hyperthyroidism
- need aggressive treatment (propranolol, potassium iodide, high-dose thionamides)
What is the criteria for a thyroid storm? (5)
- hyperpyrexia >41oC
- accelerated tachycardia/arrhythmia
- cardiac failure
- delirium/frank psychosis
- hepatocellular dysfunction; jaundice
What are the main types of treatment options for hyperthyroidism? (3)
- drugs
- surgery (thyroidectomy)
- radioiodine
What are the classes of drugs to treat hyperthyroidism? (3)
- thionamides (thiourylenes; anti-thyroid drugs)
- potassium iodide
- beta blockers
Which drugs reduce thyroid synthesis and which help with symptoms?
- thionamides and potassium iodide reduce hormone synthesis
- beta blockers help with symptoms
What are two examples of thionamides?
- propylthiouracil (PTU)
- carbimazole (CBZ)
How do thionamides work?
- good for daily treatment of hyperthyroid conditions e.g. Grave’s, toxic thyroid nodule/multinodular goitre
- block thyroid peroxidase enzyme to stop making T3 and T4
How long do thionamides take to have a biochemical and clinical effect?
- biochemical effect - hours
- clinical effect - weeks (since previously stored thyroxine from needs to be used up)
What are some unwanted side effects of thionamides?
- agranulocytosis (usually reduction in neutrophils) - rare and reversible on withdrawal of drug
- rashes (relatively common)
What can we give to patient while waiting for clinical effect of thionamides?
Treatment may include propranolol beta blocker to rapidly reduce tremor and tachycardia while waiting for effect to take place
