Hyperthyroidism

Question 1

What are two types of hyperthyroidism?

Answer 1

Graves' disease
Nodular Goitre (Plummer's disease)

Question 2

Describe Graves’ disease

Answer 2

Autoimmune disease where the antibodies bind to TSH receptors in the thyroid and stimulate it. It produces more thyroxine and also causes the thyroid gland to grow.
Graves’ disease can be thought of as 3 things:

Goitre (smooth enlarged thyroid gland) caused by hyperthyroidism. Eyelid lag (the eye lid is closing is delayed)
Other antibodies bind to muscles behind the eyes causing exopthalmos.
Other antibodies causes pretibial myxoedema (hypertrophy of the shins)

Question 3

What is pretibial myxoedema?

Answer 3

The swelling (non-pitting) that occurs on the shins of patients with graves disease: growth of soft tissue

Question 4

What is Plummer’s disease?

Answer 4

This is not an autoimmune disease. Benign adenoma that is overactive at making thyroxine. Because it is not an autoimmune disease no antibodies are being produced = No exophthalmos, No pretibial myxoedema

See notes - normal side of the thyroid gland shrinks decrease in TSH from the high levels of T4 produced from the benign adenoma

Question 5

How can diagnose graves disease?

Answer 5

See notes

Palpitation, radioactive iodine (or technetium cheaper)

Question 6

How can you differentiate between graves and plummers?

Answer 6

See notes

Palpitations, scans

Question 7

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

Answer 7

Sensitises beta adrenoreceptors to ambient levels of adrenaline. see notes
Tachycardia, palpitations, tremor in hands, lid lag

Question 8

What are the symptoms of hyperthyroidism?

Answer 8

Weight loss despite = increased appetite
Breathlessness
Palpitations, tachycardia
Sweating
Heat intolerance
Diarrhoea
Lid lag and other sympathetic features

Question 9

What is thyroid storm?

Answer 9

A medical emergency where you have extreme hyperthyroidism. 50% mortality if left untreated.
See notes for features of thyroid storm
Aggressive treatment

Question 10

What are the treatment options for hyperthyroidism?

Answer 10

Surgery (thyroidectomy)
Radioiodine
Drugs

Question 11

What are the classes of drugs used to treat hyperthyroidism?

Answer 11

1) Thionamides (thiourylenes; anti-thyroid drugs) - short term treatment
Propylthiouracil (PTU), carbimazole (CBZ)
2) Potassium iodide
3) Radioiodine
4) B-blockers

1,2 and 3 all reduce thyroid hormone synthesis. 4 helps with symptoms

Question 12

How are thionamides used?

Answer 12

Daily treatment of Graves’ and Plummer’s disease
Treatment prior to surgery
Reduction of symptoms while waiting for radioactive iodine to act

See notes for reasons why

Question 13

How is thyroxine synthesised?

Answer 13

See notes - its about the main steps which drugs can act on

Question 14

Describe the mechanism of action of thionamides

Answer 14

Thionamides inhibit thyroperoxidase which is involved in the iodination of thyroglobulin and in the coupling reaction = reduction in the synthesis and secretion of thyroxine
Suppresses antibody production in graves’ disease
Reduces deiodination of T4 to T3 in peripheral tissue (PTU)

Usually aim to stop thionamides after 18 months, review patient. 50% chance of relapse

Question 15

What is a problem with thionamides?

Answer 15

See notes - time of action vs clinical effects seen
non-selective b-blocker required to manage symptoms

Agranulocytosis - rare; urgent full blood count
Rashes

Question 16

Describe the pharmacokinetics of thionamides

Answer 16

Carbimazole (prodrug) converted to methimazole
Plasma half life of 6-15 hours
PTU crosses the placenta less than CBZ. (And is secreted in the milk)

Question 17

What is carbimazole converted to?

Answer 17

A prodrug converted to methimazole

Question 18

Role of betablockers during thyrotoxicosis

Answer 18

It takes several weeks before clinical effects can be seen following the use of thionamides so you use b-blockers to manage the symptoms of tachycardia and tremors. You use non-selective betablockers (propanolol) so it can remove all the effects of excess stimulation to of beta adrenoreceptors.

Question 19

What is the role of iodide treatment?

Answer 19

KI - dose that is 30 times the average daily requirement. This huge dose turns the thyroid gland off. You do this when you want the effect to take place quickly.

1) Preparation of hyperthyroid patients for surgery
2) Severe thyrotoxic crisis (thyroid storm)

Question 20

Describe the pharmacokinetics of KI

Answer 20

Wolff-Chaikoff Effect = the temporary reduction in thyroid hormones following ingestion of large amounts of iodine. Autoregulatory phenomenon
The large amounts of KI causes the inhibition of iodination thyroglobulin and the generation of H2O2.
Works faster than anti-thyroid drugs (thionamides)

Given orally (lugol's solution; aqueous iodine) 
Maximum effect after 10 days' of continuous administration - short term because afterwards there is a sudden increase in thyroid hormones

Question 21

What happens after the KI is administered?

Answer 21

Hyperthyroid symptoms are reduced within in 1-2 days

Vascularity and size of the gland also reduces within 10-14 days

Question 22

What are unwanted action of KI?

Answer 22

Allergic reaction eg. Rashes, fever, angio-oedema

Question 23

What does radioiodine treat and how?

Answer 23

It treats hyperthyroidism and thyroid cancers
Radioactive iodine accumulates in the colloid once it is taken in and emits beta particles of radiation which destroys the follicular cells.

Question 24

Describe the pharmacokinetics and cautions of radioiodine

Answer 24

Discontinue anti thyroid drugs 7-10 days prior to radioiodine - ensures that the thyroid gland can become really active to suck up the radioiodine.

Single oral dose

Radioactive half life of 8 days
Radioactivity is negligible after 2 months

Question 25

How can you diagnose viral thyroiditis?

Answer 25

If you see a hyperthyroid patient with no uptake of radioiodine then they have viral thyroiditis - stored thyroxine is released. Four weeks later the stored thyroxine exhausted so they become hypothyroid. A month later resolution - they recover and become euthyroid again. No treatment required