Hyperthyroidism Flashcards
what is Grave’s Disease?
autoimmune stimulation of TSH receptors in thyroid gland (by antibodies)
how does goitre in graves look like?
smooth, symmetrical enlargement
what is lid lag?
what is the mechanism behind this?
delay of eyelid when following the pupil
thyroxine sensitises beta adrenoreceptors to ambient levels of adrenaline and noradrenaline (not more adrenaline, but increases sensitivity of receptors)
SNS activation is slowed down in the oculomotor nerve so the eyelid lags
what is the cause of exophthalmos?
antibodies attack muscles behind the eyes
what is pretibial myxoedema?
growth of soft tissue in shins due to other antibodies
non-pitting, solid oedema
what is the difference between Plummer’s and Grave’s?
Plummer’s is not autoimmune
No exopthalamos shown
No pretibial myxoedema
what is Nodular Goitre?
aka Plummers
- not autoimmune
- benign adenoma causing toxic nodular goitre secreting T4
- NO pretibial myxoedema
- NO exophthalamos
produces “hot nodules” on thyroid uptake scan (toxic multinodular goitre)
what are the signs and symptoms of general hyperthyroidism?
- weight loss, increased appetite
- sweating
- tachycardia
- palpitations
- diarrhoea (overactive bowels)
- lid lag
- dyspnoea
Viral thyroiditis as a cause of hyperthyroidism
- de Quervain’s thyroiditis is of viral orgin
- causes hyperthyroidism but eventually lead to hypothyroidism
what are the symptoms of thyroiditis?
- painful/tender dysphagia: viral attack of gland
- hyperthyroidism
- pyrexia (fever)
- raised erythrocyte sedimentation rate
what causes the eventual hypothyroidism in viral thyroiditis?
the virus lyse the thyroid cells causing a release in thyroxine into the blood (hyperthyroidism)
thyroid doe not create more thyroxine leading to hypothyroidism after a month
how much uptake is seen on the scan for thyroiditis?
zero uptake
what is a thyroid storm?
medical emergency with 50% mortality
requires aggressive treatment of surgery, radio iodine and drugs
what are the features of thyroid storm?
- hyperpyrexia (>41 degrees)
- accelerated tachycardia/arrhythmia
- cardiac failure
- delirium/ frank psychosis
- heptacellular dysfunction, jaundice
what are the 4 classes of drugs used to treat hyperthyroidism?
1) thionamides
2) potassium iodide
3) radioiodine
4) beta blockers (symptom treatment)
what is thionamide?
affects thyroxine synthesis by preventing iodination of tyrosine residues on thyroglobulin and the coupling reaction
consists of thiourylenes, anti-thyroid drugs
e. g. propylthiouracil (PTU)
e. g. carbimazole (CBZ)
what are the uses of thionamides?
e.g. propothiouricil, carbimazole
- daily for Graves nodules
- treatment prior to surgery
- reduction of symptoms while waiting for radio iodine to act
what are the actions of thioamides?
- inhibits thyroperoxidase and peroxidase transaminase
- supresses antibody production in Grave’s
- reduces T4 conversion to T3 in peripheral tissues
remember: tyrosine residues of thyroglobulin are iodinated
biochemical and clinical effect of thionamides/thionureylenes
why does the clinical effect take longer
biochemical effect in hours
clinical effect takes weeks
due to large store of thyroxine already present in the thyroid that needs to be removed
why are beta blockers used despite not having effects on thyroxine synthesis?
treat symptoms of tachycardia and reduce tremor
unwanted action of thionamides
- agranulocytosis (rare and reversible)
- rashes (common)
what thionamide drug is preferentially used
carbimazole due to its weaker side effect profile
PTU is potent
however in pregancy, PTU is used over Carbimazole (which crosses the placenta readily)
pharmacokinetics of the thionamides
- orally active
- carbimazole is a prodrug
- half life of 6-15 hours
- crosses placenta (secreted in breastmilk)
- metabolised in the liver and excreted in the urine
what is the prodrug carbimazole converted into?
converted to methimazole first (administered in the USA)
