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)
which thianomide drug crosses the placenta more readily
carbimazole more than PTU
how long is treatment plan with thionamides?
18 month plan (stops after that)
review patient frequently for relapse or remission
what beta blocker is given
propanolol
non selective beta blocker until the other drugs take clinical effect
when is KI used?
preparation for hypothyroid patient for surgery
also in severe cases e.g. thyroid storm
mechanism of action of potassium iodide
inhibits iodination of TG
inhibits hydrogen peroxide generation
what is the Wolf-Chaikoff effect?
presumed reduction in thyroid hormone levels caused by ingestion of a large amount of iodine (KI) which blocks iodine production
symptoms reduce in 1-2 days
size of glands reduce in 10-14 days
unwanted reactions of KI
allergic reactions
pharmacokinetics of KI
orally active
Lugol’s solution
when is radio iodine used?
how does it target cells?
I[131] thyroid cancers and hyperthyroidism
emits beta particles that destroy follicular cells
dosage of treatment
radioiodine - high dose
technetium 99 pertechnetate- lose dose
dosage of radio iodine for Graves and Thyroid cancer
graves ~500 MBq
cancer ~3000 MBq
radioactive half life of radio iodine
8 days
radioactivity negligible after 2 months
precautions that need to be taken for those taking radio iodine
- avoid contact with small children for several weeks
- contraindicated in pregnancy and breast feeding
what are some investigations for hyperthyroidism?
- blood test for T4, TSH and antibodies
- uptake scan (radioiodine)
what does carbimazole do?
block synthesis of thyroxine
NB avoid in pregnancy
what is used to treat symptoms of hyperthyroidism?
beta blockers
what occurs in thyroid crises?
1) myxoedema coma
2) thyroid storm
what occurs in myxoedema coma?
- hypothermia
- hypotension
- hypoglycaemia
- hypoarousal
how is myxoedema coma (thyroid crisis) treated?
IV liothyronine (synthetic T3)
what occurs in thyroid storm?
- hypertension
- hyperthermia
- tachycardia and arrhythmia
- diarrhoea and vomiting
how is thyroid storm treated?
- IV beta blockers (for tachycardia)
- Lugoi’s iodine (KI)
what effect does Lugol’s iodine work in treating thyroid storm?
Wolff-Chaikoffs effect
–> increased iodine consumption decreases thyroxine production
what cells do medullary thyroid cancers arise from?
parafollicular cells
what is a fatal side effect of thionamides?
agranulocytosis
what is the main issue in Grave’s?
autoimmune stimulation
anti-TSH receptor antibodies
what symptoms are specific to Graves?
- pretibial myxoedema
- exophthalmos
- thyroid acropachy
(digital clubbing, soft tissue swelling of the hands and feet, and periosteal new bone formation.)
