3.6 - Hyperthyroidism

Question 1

How does TSH work on the thyroid gland to produce T3 (triiodothyronine) and T4 (thyroxine)?

Answer 1

1. TSH binds to TSH-R on basolateral membrane of follicular cell
2. stimulates activation of Na-I cotransporter and Na+ and I- ions enter cell
3. I- move into colloid where they are oxidised to iodine (iodination)
4. TSH binding causes production of thyroglobulin (prohormone) which is secreted into colloid
5. TSH binding also causes activation of TPO enzyme which along with H2O2 catalyses iodination reactions
6. iodine from before added to thyroglobulin through iodination to produce MIT + DIT
7. coupling reaction results in production of T3 and T4 attached to thyroglobulin
8. thyroglobulin removed at lysosome and T3 and T4 released into bloodstream

Question 2

How is production of thyroid hormone controlled?

Answer 2

• TRH from hypothalamus stimulates TSH from APG, stimulating T3 and T4 from thyroid
• T3 and T4 have negative feedback effects on TRH and TSH

Question 3

How do we control thyroid replacement?

Answer 3

Monitor TSH level and increase thyroid replacement dose until TSH falls to normal

Question 4

What happens in Grave’s disease?

Answer 4

• autoimmune disease where antibodies bind to and stimulate the TSH receptor in the thyroid
• causes smooth goitre and hyperthyroidism
• other antibodies bind to muscles behind the eye and cause exophthalmos
• other antibodies cause pretibial myxoedema

Question 5

What is pretibial myxoedema?

Answer 5

• other antibodies cause pretibial myxoedema (hypertrophy) - growth of soft tissue
• pretibial - in front of tibia (shins)
• myxoedema - swelling of lower limb
• swelling is non-pitting as it is solid
• not to be confused with myxoedema –> HYPOthyroidism

Question 6

What are some symptoms of Grave’s disease? (18)

Answer 6

• perspiration
• facial flushing
• muscle wasting and weakness
• shortness of breath
• breast enlargement / gynecomastia in males
• weight loss
• rapid pulse, tachycardia, palpitation
• warm, moist palms
• oligomenorrhoea / amenorrhoea
• pretibial myxoedema
• nervousness, excitability, restlessness, emotional instability, insomnia
• exophthalmos
• goitre
• warm, velvety skin
• increased appetite
• diarrhoea
• tremor
• clubbing of fingers

Question 7

What does the thyroid gland look like in Grave’s disease?

Answer 7

Diffuse enlargement and engorgement of thyroid gland, diffuse goitre of moderate size

Question 8

What does a radioiodine uptake scan of the thyroid gland look like in Grave’s disease?

Answer 8

Uniform radioiodine uptake (V-shape) as whole gland is overactive so takes up the iodine

Question 9

What is toxic nodular thyroid disease?

AKA Plummer’s disease

Answer 9

• single toxic nodule/multiple toxic nodules (multinodular goitre)
• not autoimmune
• benign adenoma(s) overactive at making thyroxine

Question 10

What features are present in Grave’s disease but not present in toxic nodular thyroid disease?

Answer 10

• no pretibial myxoedema
• no exophthalmos
• as not autoimmune so antibodies not involved

Question 11

What does the thyroid look like in toxic nodular thyroid disease?

Answer 11

• asymmetrical lump
• one cell has grown a lot on one side of the thyroid so that side is large
• this makes a lot of thyroxine which suppresses TSH
• lack of TSH means the normal side of the gland atrophies and gets smaller

Question 12

What does a radioiodine uptake scan of the thyroid look like in toxic nodular thyroid disease?

Answer 12

Black ‘hot nodule’ on one side of the scintigram (rest of gland off)

Question 13

What are the effects of thyroxine on the sympathetic nervous system?

Answer 13

• sensitises beta adrenoceptors to ambient levels of adrenaline and noradrenaline
• thus there is apparent sympathetic activation
• tachycardia, palpitations, tremor in hands, lid lag etc

Question 14

What are the symptoms of hyperthyroidism? (7)

Answer 14

• weight loss despite increased appetite
• breathlessness
• palpitations, tachycardia
• sweating
• heat intolerance - feel hot in winter
• diarrhoea
• lid lag and other sympathetic features

Question 15

What is a thyroid storm?

Answer 15

• medical emergency - 50% mortality untreated
• blood results confirm hyperthyroidism
• need aggressive treatment (propranolol, potassium iodide, high-dose thionamides)

Question 16

What is the criteria for a thyroid storm? (5)

Answer 16

• hyperpyrexia >41oC
• accelerated tachycardia/arrhythmia
• cardiac failure
• delirium/frank psychosis
• hepatocellular dysfunction; jaundice

Question 17

What are the main types of treatment options for hyperthyroidism? (3)

Answer 17

• drugs
• surgery (thyroidectomy)
• radioiodine

Question 18

What are the classes of drugs to treat hyperthyroidism? (3)

Answer 18

• thionamides (thiourylenes; anti-thyroid drugs)
• potassium iodide
• beta blockers

Question 19

Which drugs reduce thyroid synthesis and which help with symptoms?

Answer 19

• thionamides and potassium iodide reduce hormone synthesis
• beta blockers help with symptoms

Question 20

What are two examples of thionamides?

Answer 20

• propylthiouracil (PTU)
• carbimazole (CBZ)

Question 21

How do thionamides work?

Answer 21

• good for daily treatment of hyperthyroid conditions e.g. Grave’s, toxic thyroid nodule/multinodular goitre
• block thyroid peroxidase enzyme to stop making T3 and T4

Question 22

How long do thionamides take to have a biochemical and clinical effect?

Answer 22

• biochemical effect - hours
• clinical effect - weeks (since previously stored thyroxine from needs to be used up)

Question 23

What are some unwanted side effects of thionamides?

Answer 23

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

Question 24

What can we give to patient while waiting for clinical effect of thionamides?

Answer 24

Treatment may include propranolol beta blocker to rapidly reduce tremor and tachycardia while waiting for effect to take place

Question 25

When do we follow up patients taking thionamides?

Answer 25

- usually aim to stop anti-thyroid drug treatment after 18 months - review patient periodically including thyroid function tests for remission/relapse

Question 26

What is the role of beta blockers in thyrotoxicosis?

Answer 26

- several weeks for anti-thyroid drugs to have clinical effects e.g. reduced tremor, slower heart rate, less anxiety - helps with sympathetic symptoms - usually works immediately - can use non-selective (i.e. beta-1 and beta-2) beta blocker e.g. propranolol - achieves these effects in the interim

Question 27

What is potassium iodide used for?

Answer 27

- preparation of hyperthyroid patients for surgery - severe thyrotoxic crisis (thyroid storm) - NB not used in patients opting for medical treatment of Grave's

Question 28

What is the dosage of potassium iodide given?

Answer 28

Doses at least 30x the average daily requirement

Question 29

How does potassium iodide work?

Answer 29

- inhibits iodination of thyroglobulin - inhibits H2O2 generation and TPO - overall inhibition of thyroid hormone synthesis and secretion - Wolff-Chaikoff effect (presumed autoregulatory effect)

Question 30

What effects does potassium iodide have and after how many days?

Answer 30

- hyperthyroid symptoms reduce within 1-2 days - vascularity and size of gland reduce within 10-14 days (makes gland easier to remove)

Question 31

What are the problems with surgery (thyroidectomy)? (4)

Answer 31

- risk of voice change (recurrent laryngeal nerve damage) - risk of also losing parathyroid glands - scar - need anaesthetic

Question 32

How does radioiodine work?

Answer 32

- swallow a capsule containing 370 MBq (10 mCi) of the isotope I(131) - taken up by thyroid gland and emits beta radiation to switch off thyroid gland permanently

Question 33

Who should not use radioiodine?

Answer 33

- do not use if pregnant or child - must avoid children and pregnant mums for a few days

Question 34

What substance can we use for scans only and not treatment?

Answer 34

99-Tc pertechnetate

Question 35

What are the symptoms of viral (de Quervain's) thyroiditis? (8)

Answer 35

- painful dysphagia - hyperthyroidism - pyrexia - thyroid inflammation - (malaise) - (pain radiating to ear) - (tender and palpable thyroid gland) - (thyroid gland visibly enlarged on one side)

Question 36

What happens in viral thyroiditis?

Answer 36

- virus attacks thyroid gland causing pain and tenderness - thyroid stops making thyroxine and makes viruses instead - thus no iodine uptake - scan would show up empty - stored thyroxine released (fT4 increases and TSH drops) so there is one month of hyperthyroidism - four weeks later, stored thyroxine exhausted, so hypothyroid - after another month, resolution occurs (like in all viral disease) - patient becomes euthryoid again

Question 37

How is postpartum thyroiditis different to viral thyroiditis?

Answer 37

Similar but no pain and only occurs after pregnancy - immune system modulated during pregnancy