Hyperthyroidism

Question 1

State causes of hyperthyroidism. (2)

Answer 1

Common causes:
- Grave's disease
- Plummer's disease 
But also ... 
- Early stages of De Quervain's thyroiditis

Question 2

What is Grave’s disease? (2)

Answer 2

• An autoimmune disease
• An autoimmune antibody is produced that behaves like TSH and binds to the TSH receptor on the thyroid gland
• Antibody stimulates thyroid hormone production

Question 3

What does a thyroid gland look like in Graves’ Disease? (1)

Answer 3

Diffuse goitre: the thyroid gland is smoothly enlarged and the whole gland is active

Question 4

State some features of Graves’ Disease. (4)

Answer 4

Anything from diagram on page 18 is fine
Rapid pulse 
Warm (heat-intolerance)
Localised pretibial myxoedema 
Exophthalmos 
Lid lag
Excitability/nervousness/tremor
Loss of weight 
Muscle wasting 
Oligomenorrhoea/amenorrhoea/diarrhoea

Question 5

How does Grave’s disease give rise to pretibial myxoedema and exophthalmos? (2)

Answer 5

• Antibodies that bind to growth receptors

- Promote growth of soft tissue e.g. in the shins or behind the eye leading to bulging

Question 6

What are two defining features of Graves’ and what is it caused by? (2)

Answer 6

• Localised pretibial myxoedema
• Exophthalmos
  Antibodies cause both of these

Question 7

What is decompensation in the context of Grave’s disease? (1)

Answer 7

Initially patients have increased cognitive speed, more active, losing weight, but eventually decompensate, because cannot sleep so constantly feel tired, leading to emotional instability and lose ability to focus

Question 8

Describe the appearance of a thyroid gland of a Graves’ patient in a thyroid scan using radioactive iodine. (1)

Answer 8

The whole gland is smoothly enlarged and the whole gland is overactive

Question 9

What can be used instead of iodine in the production of thyroid scintigrams? (1)

Answer 9

Technetium (cheaper)

Question 10

Describe the levels of TSH and T3/T4 in Grave’s disease. (1)

Answer 10

High T3/T4 (OBVIOUSLY)

Low TSH

Question 11

What is Plummer’s disease? (1)

Answer 11

A benign adenoma of the thyroid that is overactive at making thyroxine

Question 12

How does Plummer’s disease differ from Graves’? (2)

Answer 12

• No autoimmune antibodies
• No pretibial myxoedema
• No exophthalmos
• On a scinitigram in Plummer’s observe a hot nodule as it is only a specific part of the thyroid gland that is overactive
• Histology different (e.g. diffuse hyperplasia in Grave’s whereas outside of the adenoma in Plummer’s get involution of the gland)

Question 13

What will a technetium or iodine scan of the thyroid show in a patient with Plummer’s Disease? (1)

Answer 13

All the iodine will be taken up by the overactive, tumorous part of the thyroid so you will see a hot nodule appear
The rest of the thyroid gland will not be seen because the high thyroxine production will decrease TSH release from the anterior pituitary and so the rest of the thyroid gland that is responding to TSH will not produce any thyroxine and will not take up iodine

Question 14

Describe the effects of thyroxine on the sympathetic nervous system. (2)

Answer 14

• Thyroxine sensitises beta adrenoceptors to ambient levels of adrenaline and noradrenaline. So you get symptoms of having high adrenaline (or sympathetic over-activation)
• Tachycardia, lid-lag and palpitations all arise due to sensitivity to adrenaline
• Exercise: small amounts of exercise = small increases in adrenaline, as a result get huge amount of anxiety, massive increase in heart rate

Question 15

What is thyroid storm? (1)

Answer 15

A rare medical emergency - potentially life threatening complication of hyperthyroidism (50% mortality if untreated)

Question 16

What are the biochemical features of thyroid storm? (3)

Answer 16

• Hyperpyrexia > 41oC (pyrexia = fever)
• Accelerated tachycardia / arrhythmia (i.e. fast and irregular heart beat)
• Cardiac failure (when the heart is unable to pump sufficiently to meet body needs)
• Delirium / frank psychosis
• Hepatocellular dysfunction; jaundice

Question 17

How is thyroid storm treated? (2)

Answer 17

• Surgery
• Radioiodine
• Drugs

Question 18

What is viral (de Quervain’s) thyroiditis? (2)

Answer 18

• Virus takes over thyroid gland: release of all stored thyroxine
• But because cell machinery now dedicated to producing viral particles no more uptake of iodine
• Goes from hyperthyroid to hypothyroid after ~4 weeks as thyroxine stores are depleted

Question 19

How can viral thyroiditis be distinguished from Grave’s disease? (3)

Answer 19

• Thyroid gland does not show any iodine or technetium uptake
• Patients complain of pain
• General features of inflammation
• Eventually developing hypothyroidis
• Lack of TSH antibody (cf. Grave’s)

Question 20

List the key clinical features of viral thyroiditis. (2)

Answer 20

• Hyperpyrexia
• Painful dysphagia
• Raised ESR

Question 21

State the classes of drugs used in the treatment of hyperthyroidism. (2)

Answer 21

• Thionamides
• Potassium iodide
• Radioiodine
• Beta blockers (improves symptoms - the other 3 block thyroxine production)

Question 22

Name two thionamides. (1)

Answer 22

Carbimazole & propylthiouracil

Question 23

When are thionamides used? (3)

Answer 23

• In hyperthyroidism:
• 1) Daily management of disease
• 2) Prior to surgery
• 3) Reduction of symptoms whilst waiting for other treatment to come in

Question 24

What is the mechanism of action of thionamides? (3)

Answer 24

• i) Inhibition of thyroid peroxidase
• :. no oxidation of iodide to atomic iodine (a free radical) nor does the coupling reaction (also catalysed by thyroperoxidase) take place
• ii) may suppress antibody production in Grave’s disease
• iii) Reduces conversion of T4 to T3

Question 25

Why do thionamides have a delayed effect on thyroid hormone levels? (2)

Answer 25

- Thionamides are quick in inhibiting synthesis of thyroid hormone but it does nothing to the thyroid hormone that has already been synthesised and is stored in the colloid ready for release - So there is a big delay between the biochemical effects (hours) and the clinical effects (weeks)

Question 26

What would you give the patient temporarily whilst waiting for thethionamides to have their clinical effect? (1)

Answer 26

Non-selective beta-blockers e.g. propanolol | This will reduce the effects of beta sensitisation by thyroxine

Question 27

State some unwanted effects of thionamides. (1)

Answer 27

Agranulocytosis | Rashes

Question 28

Carbimazole is a pro-drug. What is it converted to become active? (1)

Answer 28

Methimazole

Question 29

In what circumstances are propylthiouracil preferred to carbimazole? (1)

Answer 29

Breast-feeding mothers/pregnancy | PTU crosses placenta/concentrates in breastmilk much less

Question 30

What is the mechanism of action of potassium iodide treatment? (1)

Answer 30

If you give a massive dose of iodine it can turn off the thyroid gland It inhibits the iodination of thyroglobulin and inhibits the production of hydrogen peroxide

Question 31

What is the Wolff-Chaikoff effect? (1)

Answer 31

The temporary reduction in thyroid hormones following ingestion of a large amount of iodine

Question 32

When is potassium iodide used in hyperthyroidism? (1)

Answer 32

In hyperthyroidism to reduce the size/vascularity of the thyroid gland in preparation for surgery OR in thyroid storm (severe thyrotoxicosis)

Question 33

State some unwanted actions of potassium iodide. (1)

Answer 33

Rashes Fever Angioedema

Question 34

What is the mechanism of action of radioiodine treatment in hyperthyroidism? (1)

Answer 34

Taken up by the follicular cells and transported to the colloid where it accumulates; consequently emits ß-particles destroying follicular cells

Question 35

What cautions need to be taken with radioiodine treatment? (2)

Answer 35

Avoid close contact with small children for several weeks after receiving radioiodine Contra-indicated in pregnancy and breast-feeding Be wary when travelling