5. Hyperthyroidism

Question 1

what are the 2 causes of hyperthyroidism?

Answer 1

1. Grave’s disease

2. nodular goitre (Plummer’s disease)

Question 2

describe grave’s disease

Answer 2

an autoimmune disease where the whole gland is smoothly enlarged and the whole gland is overactive

Question 3

how does grave’s disease trigger hyperthyroidism?

Answer 3

the immune system produces an antibody pretending to be TSH which binds to the TSH receptor and the thyroid gland becomes overactive

Question 4

what are the 2 major symptoms of grave’s disease?

Answer 4

1. exophthalmos

2. pretibial myxoedema

Question 5

describe exophthalmos

Answer 5

thyroxine makes b-receptors more sensitive and makes your eyes wider than normal and other antibodies bind the muscles behind the eye, pushing the eye forward

Question 6

describe pretibial myxoedema

Answer 6

antibodies stimulate the growth of soft tissue on the skin (hypertrophy)

Question 7

how might a patient present with grave’s disease?

Answer 7

• exophthalmos
• localised myxoedema
• lid lag
• perspiration
• facial flush
• muscle wasting
• shortness of breath
• loss of weight
• rapid pulse
• warm, moist palms
• increased appetite
• tremor
• clubbing of fingers
• muscular weakness/fatigue

Question 8

what is a scintigram?

Answer 8

a scan where radioactive iodine is given. the thyroid gland takes up iodine and can be visualised on the scan

Question 9

describe plummer’s disease

Answer 9

toxic nodular goitre which is not autoimmune but the result of a benign adenoma that is overactive and produces too much thyroxine

Question 10

what are the main differences you can see between grave’s disease and plummer’s disease?

Answer 10

in plummer’s disease there will only be a lump on one side not a smoothly enlarged thyroid

there are no autoimmune features (pretibial myxodeoma/exophthalmos) in plummer’s disease

the scintigram will show a hot nodule as opposed to the whole thyroid gland being enlarged

Question 11

what are some clinical features of plummer’s disease due to the actions of throxine?

Answer 11

• increased BMR
• weight loss
• overheating
• increased sensitivity of the sympathetic NS

Question 12

what are the effects of thyroxine on the sympathetic NS?

Answer 12

sensitises beta adrenoreceptors to low levels of adrenaline and NA so there is more sympathetic activation even when small amounts of adrenaline are released

Question 13

what is thyroid storm?

Answer 13

hyperthyroidism when it becomes life threatening (medical emergency)

Question 14

what are the features of thyroid storm?

Answer 14

• hyperpyrexia (temperature >41 degrees C)
• accelerated tachycardia (>170bpm)
• cardiac failure
• delirium/psychosis
• hepatocellular dysfunction, jaundice

2 or more symptoms are necessary for it to be a medical emergency

Question 15

what are the aggressive treatment options for thyroid storm?

Answer 15

• surgery (thyroidectomy)
• radioiodine
• drugs

Question 16

what drugs are used in the treatment of hyperthyroidism?

Answer 16

1. thionamides (1st line treatment) e.g. propylthiouracil (PTU) and carbimazole (CBZ)
2. potassium iodide
3. radioiodine
4. beta-blockers (to help symptoms)

Question 17

why might drugs be given for reasons other than direct treatment?

Answer 17

• to prepare a patient for a thyroidectomy (lower heart rate)
• to reduce symptoms while waiting for radioactive iodine to act

Question 18

what is the role of thyroid peroxidase in the production of thyroid hormones?

Answer 18

iodinates thyroglobulin and is involved in the coupling of mono/di-iodothyronines to make T3 or T4

Question 19

how do thionamides work?

Answer 19

they inhibit thyroperoxidase enzyme, preventing the thyroid gland from making hormones

Question 20

why do the clinical effects of thionamides take so long to show?

Answer 20

there is a store of thyroid hormones in the colloid so the biochemical effect takes hours and clinical effects are seen after several weeks

Question 21

what is given to reduce side effects in the short-term?

Answer 21

propranolol (non-selective beta blocker) to reduce tremor and tachycardia

a cardio-selective beta blocker would only overcome palpitations, not the tremor

Question 22

what are the other mechanisms of propylthiouracil (thionamide)?

Answer 22

• suppresses anti-TSH antibody production in Grave’s disease
• reduces the conversion of T4 to T3 in peripheral tissues

Question 23

what are the unwanted actions of thionamides?

Answer 23

• agranulocytosis - fall in WBC count (usually reduction in neutrophils) however is rare and reversible
• rashes

Question 24

describe the pharmacokinetics of thionamides

Answer 24

• drugs are in tablet form and are orally active
• carbimazole is a pro-drug so must be converted to methimazole first
• grave’s disease affects young people so women of reproductive age should be warned against pregnancy until dose is low because thionamides cross the placenta and are secreted in breast milk
• aim is to stop treatment after 18months

Question 25

why is iodide (usually in the form of potassium iodide) given in the treatment of hyperthyroidism?

Answer 25

in preparation for surgery and in severe thyrotoxic crisis (thyroid storm) inorganic iodide inhibits iodothyronine release (wolff-chaikoff effect) and reduces hyperthyroid symptoms within 1-2 days. it also reduces the size and vascularity of the thyroid gland

Question 26

what is hypothesised as the way KI switches off thyroid hormone production?

Answer 26

1. inhibiting iodination of tyrosine residues on thyroglobulin 2. inhibiting thyroid peroxidase with hydrogen peroxide

Question 27

what is the wolff-chaikoff effect?

Answer 27

inhibition of thyroid hormone synthesis and secretion

Question 28

what are the unwanted actions of KI?

Answer 28

allergic reactions e.g. rashes, fever

Question 29

describe the pharmacokinetics of KI

Answer 29

- given orally as tablets or lugol's solution (aq. iodine) | - maximum effects are seen after 10 days continuous administration

Question 30

why might radioiodine be given in the treatment of hyperthyroidism?

Answer 30

to treat hyperthyroidism or thyroid cancer radioiodine accumulates in the colloid and emits beta particles (beta radiation) which destroys thyroid follicular cells so the thyroid gland is effectively switched off. thyroxine can then be given as a supplement

Question 31

how is radioiodine given, in what dose is it given and what must be done before giving it?

Answer 31

given as a tablet graves disease: 500MBg, thyroid cancer: 3000MBg discontinue anti-thyroid drugs 7-10 days prior to treatment so the thyroid gland sucks up all the radioiodine

Question 32

what must you be cautious of with radioiodine?

Answer 32

avoid close contact with small children for several weeks after receiving treatment

Question 33

how can radioiodine be used in scintigraphy?

Answer 33

to map out the thyroid gland administered intravenously, has a negligible cytotoxicity

Question 34

what is viral (de Quervain's) thyroiditis?

Answer 34

thyroid gland is infected by a virus resulting in painful dysphagia (difficulty swallowing) damage to the thyroid follicles leading to a huge release of thyroxine (hyperthyroidism) as well as an immune response leading to pyrexia (fever)

Question 35

what is the main clinical feature of viral (de Quervain's) thyroiditis?

Answer 35

raised erythrocyte sedimentation rate (ESR)

Question 36

what does a scintigram of someone with viral thyroiditis show and why?

Answer 36

blank scintigram the virus hijacks the follicular cells and the cells make viruses instead of thyroxine. the patient has released the stored thyroxine and become hyperthyroid quickly but is not making any new thyroxine to store in the colloid so there is 0 iodine uptake

Question 37

how can you tell the difference between viral thyroiditis and graves disease?

Answer 37

in viral thyroiditis the thyroid gland is painful in viral thyroiditis the hyperthyroid is short-term, in 3-4 weeks the patient will become hypothyroid (cold and lethargic) because the stored thyroxine is exhausted