thyroid Flashcards
hyperthyroidism: list the causes of hyperthyroidism; recall the clinical features, explain the diagnosis, explain treatment options including mechanism of action, side effects, interactions and special circumstances (e.g. pregnancy); explain how to differentiate between Graves' disease and other causes of hyperthyroidism; recall the clinical features of a thyroid storm
4 classes of drugs used in treatment of hyperthyroidism
thionamides (thiourylenes; anti-thyoid drug), potassium iodide, radioiodine, B-blockers
2 examples of thionamides
propylthiouracil (PTU), carbimazole (CBZ)
what do thionamides (thiourylenes; anti-thyoid drug), potassium iodide and radioiodine classes attempt to do
reduce thyroid hormone symptoms
what does B-blocker class attempt to do
help with symptoms
3 clinical uses of thionamides
daily treatment of hyperthyroid conditions, treatment prior to surgery, reduction of symptoms while waiting for radioactive iodine to act
2 causes of hyperthyroidism
Graves’ disease, toxic thyroid nodule (Plummer’s disease)/toxic multinodular goitre
thyroid hormone synthesis
I- enters thyroid follicular cell from blood and passes into colloid via active transport -> coupling reaction occurs using peroxidase transaminase -> iodination of thryoglobulin occurs using thyroperoxidase and H2O2 -> T3 and T4 stored in colloid -> endocytosed and secreted
how do thionamides work to prevent T3 and T4 synthesis and secretion
inhibit thyroid peroxidase
thionamides: biochemical effect duration
hours
thionamides: clinical effect duration
weeks (colloid contains stored thyroxine)
thionamides: why might the treatment regimen include propranolol (B-blocker)
rapidly reduces tremor and tachycardia before clinical effect of thionamide
2 mechanisms of action of thionamides
may suppress antibody production in Graves’ disease, reduces conversion fo T4 to T3 in peripheral tissues (specifically propylthiouracil (PTU))
2 unwanted actions of thionamides
agranulocytosis (usually reduction in neutrophils; rare and reversible on withdrawal of drug), rashes (relatively common)
4 pharmacokinetic features of thionamides
orally active, carbimazole is pro-drug so must first be converted to methimazole, can cross placenta (pregnancy relevant) and are secreted in breastmilk (carbimazole (CBZ) more so than propylthiouracil (PTU)), metabolised in liver and excreted in urine
thionamides: follow up (duration and review)
usually aim to stop anti-thyroid drug treatment after 18 months, review patient periodically including thyroid function tests for remission (euthyroid) or relapse
anti-thyroid drug clinical effects
reduced tumour, slower heart rate, less anxiety
duration before anti-thyroid drugs have clinical effects
several weeks
what is used to achieve same clinical effects in interim before anti-thyoid drugs have clinical effect
non-selective (B1 and B2) B-blockers e.g. propranolol so all symptoms treated; less so with selective B1 blockers e.g. atenolol which only slow heart rate
when is iodide (usually KI, with doses x30 average daily requirement) used (2 conditions)
preparation of hyperthyroid patients for surgery, severe thyrotoxic crisis (thyroid storm) so quicker action required
2 KI mechanisms of action
inhibits iodination of thyroglobulin; inhibits H202 generation and thyroperoxidase (Wolff-Chaikoff effect)
what is the Wolff-Chaikoff effect
autoregulatory effect when thyroid hormone synthesis and secretion are both inhibited in presence of large doses of iodine
with KI, when do hyperthyroid symptoms reduce within
1-2 days
with KI, when does vascularity and size of thyroid gland reduce within
10-14 days
KI unwanted action
allergic reaction e.g. rashes, fever, angio-oedema
pharmacokinetic feature of KI (administration and duration before maximal effects)
given orally (Lugol’s solution; aqueous iodine), with maximum effects after 10 days of continuous administration
what is radioiodine chemically
131 I in high doses
what 2 things does radioiodine treat
hyperthyroidism, thyroid cancers
how does radioiodine work
accumulates in colloid, emiting B particles and destroying follicular cells; switches it off for good (e.g. 6 months before pregnancy so don’t have to take anti-thyroid drugs during pregnancy or for 18 months); then treat with thyroxine as if they were hypothyroid
prior to radioiodine treatment what must happen
anti-thyroid drugs must be discontinued for 7-10 days
how is radioiodine administered a) for Graves’ disease and b) for thyroid cancer
both as a single oral dose, but Graves’ disease: approx 500 MBq, and thyroid cancer: approx 3000 MBq
what is radioiodine’s radioactive half life, and when is it’s radioactivity negligible after
8 days half life, with radioactivity negligible after 2 months
2 cautions when using radioiodine
avoid close contact with small children for several weeks after receiving radioiodine; contra-indicated in pregnancy and breast feeding
what version of radioiodine is used at very low, tracer doses
technetium 99 pertechnetate
how is thryoid gland pathology (e.g. toxic nodule, thyroiditis vs Graves’) tested (2 tests)
administer i.v., negligible cytotoxicity
Graves’ disease: type and pathophysiology
autoimmune; antibodies bind to and stimulate TSH receptor in thyroid
2 effects of Graves’ disease
goitre (smooth thyroid) and hyperthyroidism (which causes lid lag)
signs and symptoms of Graves’ disease
makes B receptors more sensitive: pretibial myxoedema, exophthalmos, goitre (smooth swellling of neck due to diffuse enlargement and engorgement of thyroid gland by antibodies binding)
how does Graves’ disease cause exophthalmos
antibodies bind to muscles behind the eye (measure antibodies to confirm diagnosis); can get double vision or lose vision due to swelling and pressure on optic nerves; approx. 1 year after goitre
in Graves’ disease, what else can other antibodies cause
pretibial myxoedema (hypertrophy)
what is pretibial myxoedema
swelling (non-pitting) that occurs on shins due to growth of soft tissue caused by antibody binding (NOT MYXOEDEMA - that’s primary hypothyroidism)
thyroid scan in Graves’ disease
very big with smoothly increased uptake of radioactive iodine
what is Plummer’s disease and pathophysiology
toxic nodular goitre (not smooth so lump on one side) due to overactive thyroxine-making benign adenoma
Plummer’s disease vs Graves’ disease
not autoimmune, no pretibial myxoedema, no exophthalmos
histology of Plummer’s disease
hyperfunctioning adenoma; pituitary therefore doesn’t make TSH so rest of thyroid shrinks, but adenoma continues to grow
thyroid scan in Plummer’s disease
hot nodule
how does thryoxine cause apparent sympathetic activation
sensitises beta adrenoceptors to ambient levels of adrenaline and noradrenaline
clinical effects of thyroxine due to sentisation of beta adrenoceptors
tachycardia, palpitations, tremor in hands, lid lag
what is lid lag
where upper eyelid is higher than normal with globe in downgaze; eyelid is delayed when eyeball goes down (see white of eye above iris, as adrenaline holds back eyelid)
clinical presentation of hyperthyroidism
weight loss despite increased appetite, breathlessness, palpitations, tachycardia, sweating, heat intolerance, diarrhoea, lid lag and other sympathetic features; family history
thyroid storm: what is it, mortality if untreated and blood results
very high thyroxine level; 50% mortality if untreated; bood results confirm hyperthyroidism
5 clinical features of a thyroid storm (2 on top of thyroxine = thryoid storm)
hyperpyrexia > 41°C (increased basal metabolic rate); accelerated tachycardia/arrhythmia, cardiac failure, delirium/frank psychosis, hepatocellular dysfunction; jaundice
3 treatment options for thyroid storm
surgery (thyroidectomy), radioiodine, drugs
4 features of viral (de Quervain’s) thyroiditis
painful dysphagia, hyperthyroidism, pyrexia, raised erythrocyte sedimentation rate (ESR)
5 clinical presentations of viral (de Quervain’s) thyroiditis
malaise, dysphagia, pain radiating to ear, thyroid gland visible enlarged (more on one side) whilst being tender and palpable, tender pretracheal lymph nodes
natural history of viral (de Quervain’s) thyroiditis
virus attacks thyroid gland causing pain and tenderness -> thyroid stops making thyroxine and makes viruses instead -> no iodine uptake
effect of viral (de Quervain’s) thyroiditis on stored thyroxine
as radioiodine uptake is zero, stored thyroxine is released, so is toxic with zero uptake; after 4 weeks, stored thyroxine is exhausted, so hypothyroid
what happens after a further month of having viral (de Quervain’s) thyroiditis, after hypothyroid
resolution occurs (as with all viral diseases), so patient becomes euthyroid again
