Hyperthyroidism

Question 1

What inhibits TRH and therefore TSH?

Answer 1

T4 and T3

Question 2

What is Graves’ disease?

Answer 2

• Autoimmune
• TSH receptor antibodies (TRAb) bind and stimulate the TSH receptor in the thyroid
• Causing a smooth goitre and hyperthyroidism

Question 3

What are distinctive symptoms of Graves’ disease?

Answer 3

• Exophthalmos
• Pretibial myxoedema

Question 4

What causes exophthalmos in people with Graves’ disease?

Answer 4

Antibodies binding to the muscles behind the eye

Question 5

What is pretibial myxoedema?

Answer 5

The swelling (non-pitting) that occurs on the shins of patients with Graves' disease (growth of soft tissue)
associated with hyperthyroidism NOT hypothyroidism

Question 6

Describe the goitre caused by Graves’ disease.

Answer 6

• Diffuse enlargement and engorgement of the thyroid gland
• with uniform radioiodine uptake

Question 7

What is the difference between toxic nodular thyroid disease and Graves’ disease?

Answer 7

Toxic nodular thyroid disease =

• not autoimmune
• no pretibial myxoedema
• no exophthalmos
• non-symmetrical and non-diffuse goitre
• possible sore throat

Question 8

What is toxic nodular thyroid disease?

Answer 8

Characterised by:

• toxic nodular nodule or multinodular goitre
• benign adenoma produces excess thyroxine

Question 9

How does thyroxine impact the sympathetic nervous system?

Answer 9

• sensitises beta adrenoreceptors to the ambient levels of adrenaline and noradrenaline
• causes apparent sympathetic activation without adrenaline increasing

Question 10

How does the impact of thyroxine on the sympathetic nervous system present?

Answer 10

• tachycardia
• palpitations
• tremor in the hands
• lid lag

Question 11

What are the symptoms of hyperthyroidism?

Answer 11

• weight loss (despite increased appetite)
• breathlessness
• palpitations
• tachycardia
• sweating
• heat intolerance
• diarrhoea
• lid lag (+ other sympathetic features)

Question 12

What is a thyroid storm?

Answer 12

A medical emergency resulting in a 50% mortality if untreated
(aggressive treatment is required)

Question 13

What are the characteristics of a thyroid strom?

Answer 13

• Hyperpyrexia (>41C)
• accelerated tachycardia/arrhythmia
• cardiac failure
• delirium/frank psychosis
• hepatocellular dysfunction; jaundice

Question 14

What are the possible treatments for hyperthyroidism?

Answer 14

• surgery (thyroidectomy)
• radioiodine
• drugs

Question 15

What are the 4 classes of drugs involved in the treatment of hyperthyroidism?

Answer 15

Thionamides (thiourylenes; anti-thyroid drugs)
- propylthiouracil (PTU)
- carbimazole (CBZ)
Potassium Iodide
Radioiodine
Beta-Blockers

Question 16

What is the aim of thionamides, potassium iodide and radioiodine?

Answer 16

To reduce thyroid hormone synthesis

Question 17

What is the aim of Beta-blockers?

Answer 17

To help with the symptoms associated with hyperthyroidism

Question 18

What are the 2 main enzymes involves in thyroid hormone synthesis?

Answer 18

• Thyroid peroxidase (TPO)
• Peroxidase transaminase

Question 19

What is the mechanism of action of thionamides?

Answer 19

The inhibition of thyroid peroxidase and therefore T3/4 synthesis and secretion

Question 20

How long does it take for thionamides to come into effect?

Answer 20

• biochemical effect: hours
• clinical effect: weeks

Question 21

What drug often accompanies thionamides in a treatment plan?

Answer 21

• Propanolol (beta-blocker)
• rapidly reduces tremors and tachycardia

Question 22

Describe the synthesis of thyroid hormones

Answer 22

• Uptake of iodide via active transport
• Iodination of thyroglobulin (TG) into MIT and DIT
• Coupling reaction of MIT and DIT into T3 and T4: storage in the colloid
• Endocytosis and secretion

Question 23

What are the unwanted actions of thionamides?

Answer 23

• rashes (common)
• Agranulocytosis (normally a reduction in neutrophils) - rare, and reversible by stopping the drug

Question 24

How to follow up on the patient using drugs to treat hyperthyroidism?

Answer 24

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

Question 25

Why are beta-blockers like propanolol involved in treatment plans with anti-thyroid drugs?

Answer 25

Anti-thyroid drugs take several weeks to have clinical effects, therefore non-selective beta-blockers do so in the interim.

Question 26

When is potassium iodide used?

Answer 26

- in preparation for surgery - during a thyroid storm (severe thyrotoxic crisis) - usually in doses >30x daily requirement * NOT used in patients opting for medical treatment of Graves'

Question 27

What is the mechanism of action of potassium iodide?

Answer 27

- Actual mechanism is unknown - Inhibits the iodination of thyroglobulin - Inhibits hydrogen peroxide generation and thyroperoxidase

Question 28

What is the impact of potassium iodide in hyperthyroidism?

Answer 28

- inhibition of thyroid hormone synthesis and secretion - Wolff-Chaikoff effect - hyperthyroid symptoms reduce in 1-2 days - vascularity and size of the gland reduce in 10-14 days

Question 29

What is the Wolff-Chaikoff effect?

Answer 29

presumed reduction in thyroid hormone levels caused by ingestion of a large amount of iodine

Question 30

What are the risks involved in surgery/thyroidectomy?

Answer 30

- risk of voice change - risk of parathyroid gland loss - scarring - risk involved in anaesthesia

Question 31

What do people taking radioiodine need to do?

Answer 31

need to avoid children and pregnant women for a few days

Question 32

When is radioiodine contrindicated?

Answer 32

Pregnancy

Question 33

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

Answer 33

- painful dysphagia - hyperthyroidism - pyrexia - thyroid inflammation - one-sided visible enlargement of the thyroid gland

Question 34

What causes Viral (de Quervain's) thyroiditis?

Answer 34

- virus attacks the thyroid gland causing pain and tenderness - thyroid stops making thyroxine and makes viruses instead - therefore no iodine uptake (ZERO) - stored thyroxine is released - thus, thyrotoxic with 0 reuptake - 4 weeks later, stores are exhausted > hypothyroidism - 8 weeks later, resolution occurs - patient becomes euthyroid

Question 35

How does Viral (de Quervain's) thyroiditis present?

Answer 35

- painful neck - all stored thyroxine is released - fT4 levels rise - TSH levels drop - 1 month of hyperthyroidism - no new thyroxine synthesis - fT4 slowly falls - patients becomes hypothyroid (thyroid just replicates the virus) lasts another month - after 3 months, slow recovery

Question 36

What is the difference between viral (de Quervain's) thyroiditis and postpartum thyroiditis?

Answer 36

postpartum thyroiditis has no pain, and only occurs post pregnancy

Question 37

What are thionamides used to treat?

Answer 37

- Grave's disease - Toxic nodular thyroid disease