thyroid

Question 1

4 classes of drugs used in treatment of hyperthyroidism

Answer 1

thionamides (thiourylenes; anti-thyoid drug), potassium iodide, radioiodine, B-blockers

Question 2

2 examples of thionamides

Answer 2

propylthiouracil (PTU), carbimazole (CBZ)

Question 3

what do thionamides (thiourylenes; anti-thyoid drug), potassium iodide and radioiodine classes attempt to do

Answer 3

reduce thyroid hormone symptoms

Question 4

what does B-blocker class attempt to do

Answer 4

help with symptoms

Question 5

3 clinical uses of thionamides

Answer 5

daily treatment of hyperthyroid conditions, treatment prior to surgery, reduction of symptoms while waiting for radioactive iodine to act

Question 6

2 causes of hyperthyroidism

Answer 6

Graves’ disease, toxic thyroid nodule (Plummer’s disease)/toxic multinodular goitre

Question 7

thyroid hormone synthesis

Answer 7

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

Question 8

how do thionamides work to prevent T3 and T4 synthesis and secretion

Answer 8

inhibit thyroid peroxidase

Question 9

thionamides: biochemical effect duration

Answer 9

hours

Question 10

thionamides: clinical effect duration

Answer 10

weeks (colloid contains stored thyroxine)

Question 11

thionamides: why might the treatment regimen include propranolol (B-blocker)

Answer 11

rapidly reduces tremor and tachycardia before clinical effect of thionamide

Question 12

2 mechanisms of action of thionamides

Answer 12

may suppress antibody production in Graves’ disease, reduces conversion fo T4 to T3 in peripheral tissues (specifically propylthiouracil (PTU))

Question 13

2 unwanted actions of thionamides

Answer 13

agranulocytosis (usually reduction in neutrophils; rare and reversible on withdrawal of drug), rashes (relatively common)

Question 14

4 pharmacokinetic features of thionamides

Answer 14

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

Question 15

thionamides: follow up (duration and review)

Answer 15

usually aim to stop anti-thyroid drug treatment after 18 months, review patient periodically including thyroid function tests for remission (euthyroid) or relapse

Question 16

anti-thyroid drug clinical effects

Answer 16

reduced tumour, slower heart rate, less anxiety

Question 17

duration before anti-thyroid drugs have clinical effects

Answer 17

several weeks

Question 18

what is used to achieve same clinical effects in interim before anti-thyoid drugs have clinical effect

Answer 18

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

Question 19

when is iodide (usually KI, with doses x30 average daily requirement) used (2 conditions)

Answer 19

preparation of hyperthyroid patients for surgery, severe thyrotoxic crisis (thyroid storm) so quicker action required

Question 20

2 KI mechanisms of action

Answer 20

inhibits iodination of thyroglobulin; inhibits H202 generation and thyroperoxidase (Wolff-Chaikoff effect)

Question 21

what is the Wolff-Chaikoff effect

Answer 21

autoregulatory effect when thyroid hormone synthesis and secretion are both inhibited in presence of large doses of iodine

Question 22

with KI, when do hyperthyroid symptoms reduce within

Answer 22

1-2 days

Question 23

with KI, when does vascularity and size of thyroid gland reduce within

Answer 23

10-14 days

Question 24

KI unwanted action

Answer 24

allergic reaction e.g. rashes, fever, angio-oedema

Question 25

pharmacokinetic feature of KI (administration and duration before maximal effects)

Answer 25

given orally (Lugol's solution; aqueous iodine), with maximum effects after 10 days of continuous administration

Question 26

what is radioiodine chemically

Answer 26

131 I in high doses

Question 27

what 2 things does radioiodine treat

Answer 27

hyperthyroidism, thyroid cancers

Question 28

how does radioiodine work

Answer 28

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

Question 29

prior to radioiodine treatment what must happen

Answer 29

anti-thyroid drugs must be discontinued for 7-10 days

Question 30

how is radioiodine administered a) for Graves' disease and b) for thyroid cancer

Answer 30

both as a single oral dose, but Graves' disease: approx 500 MBq, and thyroid cancer: approx 3000 MBq

Question 31

what is radioiodine's radioactive half life, and when is it's radioactivity negligible after

Answer 31

8 days half life, with radioactivity negligible after 2 months

Question 32

2 cautions when using radioiodine

Answer 32

avoid close contact with small children for several weeks after receiving radioiodine; contra-indicated in pregnancy and breast feeding

Question 33

what version of radioiodine is used at very low, tracer doses

Answer 33

technetium 99 pertechnetate

Question 34

how is thryoid gland pathology (e.g. toxic nodule, thyroiditis vs Graves') tested (2 tests)

Answer 34

administer i.v., negligible cytotoxicity

Question 35

Graves' disease: type and pathophysiology

Answer 35

autoimmune; antibodies bind to and stimulate TSH receptor in thyroid

Question 36

2 effects of Graves' disease

Answer 36

goitre (smooth thyroid) and hyperthyroidism (which causes lid lag)

Question 37

signs and symptoms of Graves' disease

Answer 37

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)

Question 38

how does Graves' disease cause exophthalmos

Answer 38

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

Question 39

in Graves' disease, what else can other antibodies cause

Answer 39

pretibial myxoedema (hypertrophy)

Question 40

what is pretibial myxoedema

Answer 40

swelling (non-pitting) that occurs on shins due to growth of soft tissue caused by antibody binding (NOT MYXOEDEMA - that's primary hypothyroidism)

Question 41

thyroid scan in Graves' disease

Answer 41

very big with smoothly increased uptake of radioactive iodine

Question 42

what is Plummer's disease and pathophysiology

Answer 42

toxic nodular goitre (not smooth so lump on one side) due to overactive thyroxine-making benign adenoma

Question 43

Plummer's disease vs Graves' disease

Answer 43

not autoimmune, no pretibial myxoedema, no exophthalmos

Question 44

histology of Plummer's disease

Answer 44

hyperfunctioning adenoma; pituitary therefore doesn't make TSH so rest of thyroid shrinks, but adenoma continues to grow

Question 45

thyroid scan in Plummer's disease

Answer 45

hot nodule

Question 46

how does thryoxine cause apparent sympathetic activation

Answer 46

sensitises beta adrenoceptors to ambient levels of adrenaline and noradrenaline

Question 47

clinical effects of thyroxine due to sentisation of beta adrenoceptors

Answer 47

tachycardia, palpitations, tremor in hands, lid lag

Question 48

what is lid lag

Answer 48

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)

Question 49

clinical presentation of hyperthyroidism

Answer 49

weight loss despite increased appetite, breathlessness, palpitations, tachycardia, sweating, heat intolerance, diarrhoea, lid lag and other sympathetic features; family history

Question 50

thyroid storm: what is it, mortality if untreated and blood results

Answer 50

very high thyroxine level; 50% mortality if untreated; bood results confirm hyperthyroidism

Question 51

5 clinical features of a thyroid storm (2 on top of thyroxine = thryoid storm)

Answer 51

hyperpyrexia > 41°C (increased basal metabolic rate); accelerated tachycardia/arrhythmia, cardiac failure, delirium/frank psychosis, hepatocellular dysfunction; jaundice

Question 52

3 treatment options for thyroid storm

Answer 52

surgery (thyroidectomy), radioiodine, drugs

Question 53

4 features of viral (de Quervain's) thyroiditis

Answer 53

painful dysphagia, hyperthyroidism, pyrexia, raised erythrocyte sedimentation rate (ESR)

Question 54

5 clinical presentations of viral (de Quervain's) thyroiditis

Answer 54

malaise, dysphagia, pain radiating to ear, thyroid gland visible enlarged (more on one side) whilst being tender and palpable, tender pretracheal lymph nodes

Question 55

natural history of viral (de Quervain's) thyroiditis

Answer 55

virus attacks thyroid gland causing pain and tenderness -> thyroid stops making thyroxine and makes viruses instead -> no iodine uptake

Question 56

effect of viral (de Quervain's) thyroiditis on stored thyroxine

Answer 56

as radioiodine uptake is zero, stored thyroxine is released, so is toxic with zero uptake; after 4 weeks, stored thyroxine is exhausted, so hypothyroid

Question 57

what happens after a further month of having viral (de Quervain's) thyroiditis, after hypothyroid

Answer 57

resolution occurs (as with all viral diseases), so patient becomes euthyroid again