Hyperthyroidism

Question 1

What are the 2 common causes of hyperthyroidism?

Answer 1

Graves' disease (autoimmune)
Nodular goitre (Plummer's disease)- this is a benign tumour that produces thyroxine.

Question 2

What is Graves’ disease?

Answer 2

An autoimmune disease involving antibodies binding to and stimulating the TSH receptor in the thyroid. This causes smooth enlargement (goitre) of the thyroid and hyperthyroidism.

Question 3

What are the signs and symptoms of Graves’ disease?

Answer 3

Lid-lag, exophthalmos and pretibial myxoedema caused by antibodies.
Anxious and energetic, rapid pulse, raised metabolic rate, weight loss and sweating, etc.

Question 4

How is imaging used to diagnose Graves’ disease?

Answer 4

Radioactive iodine can be used to visualise the thyroid. It will show up on the scintigram, showing that the iodine is going into the thyroid gland and the whole gland is active.

Question 5

What is Plummer’s disease?

Answer 5

Toxic nodular goitre.
Not autoimmune.
Benign adenoma that is overactive at making thyroxine.
There is no pretibial myxoedema and no exophthalmos (caused by antibodies).

Question 6

How is imaging used to diagnose Plummer’s disease?

Answer 6

A technetium or iodine scan may be used. The scan will show iodine going into the hot tumour. As there is too much thyroxine coming from the tumour part of the thyroid, the pituitary will stop making TSH and the normal part of the thyroid will slowly shrink and stop making thyroxine. This means that in the thyroid scan you will just see a hot nodule and the rest of the thyroid will not be seen.

Question 7

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

Answer 7

Sensitises beta adrenoceptors to ambient levels of adrenaline and noradrenaline.
Apparent sympathetic activation.
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 a thyroid storm?

Answer 9

A rare but severe complication of hyperthyroidism- medical emergency, 50% mortality if untreated.
May die of heart failure or arrhythmia.
Blood results will confirm hyperthyroidism.

Question 10

What are the symptoms of a thyroid storm?

Answer 10

Hyperpyrexia >41 degrees
Accelerated tachycardia/arrhythmia
Cardiac failure
Delirium/ frank psychosis
Hepatocellular dysfunction; jaundice

Question 11

What are the treatment options for a thyroid storm?

Answer 11

Surgery (thyroidectomy)
Radioiodine
Drugs

Question 12

What classes of drugs are used to treat hyperthyroidism?

Answer 12

Thionamides (thiourylenes, anti-thyroid drugs) e.g. propylthiouracil (PTU), carbimazole (CBZ).
Potassium iodide- blocks thyroxine synthesis.
Radioiodine- blocks thyroxine synthesis.
Beta blockers- help with symptoms.

Question 13

What are the clinical uses of thionamides?

Answer 13

Daily treatment of hyperthyroid conditions (Graves’ and Plummer’s).
Treatment prior to surgery (thyroidectomy).
Reduction of symptoms while waiting for radioactive iodine to act.

Question 14

How is thyroid hormone synthesised?

Answer 14

Iodine is taken up into the follicular cells.
Under the action of thyroperoxidase with hydrogen peroxide there is iodination of tyrosine residues in the thyroglobulin.
There is coupling of monoiodotyrosine and diiodotyrosine to form T3 and T4.
This is taken up and then released by the cells into the circulation.

Question 15

What is the mechanism of action of thionamides?

Answer 15

Inhibition of thyroperoxidase and hence T3/T4 synthesis and secretion.
The biochemical effects of inhibition with thionamides occurs in hours but it takes weeks before the clinical effects can be seen. This is because there is a lot of stored thyroid hormone in the lumen of thyroid follicles.

Question 16

What are the unwanted actions of thionamides?

Answer 16

Agranulocytosis/ granulocytopenia (reduction or absence of granular leukocytes like neutrophils)- rare and reversible on withdrawal of drug.
Rashes (relatively common)

Question 17

Discuss pharmacokinetics of thionamides.

Answer 17

Orally active.
Carbimazole is a prodrug which first has to be converted to methimazole. Crosses placenta and is secreted in breastmilk (PTU

Question 18

What is the follow-up procedure for thionamides?

Answer 18

Usually aim to stop antithyroid drug treatment after 18 months. Review patient periodically including thyroid function tests for remission/relapse.

Question 19

What is the role of beta blockers in thyrotoxicosis?

Answer 19

It takes several weeks for antithyroid drugs to have clinical effects, e.g. reduced tremor, slower heart rate, less anxiety. Non-selective beta blockers achieve these effects in the interim, e.g. propranolol.

Question 20

What is iodide treatment used for?

Answer 20

Usually potassium iodide, doses at least 30 times the average daily requirement.
Preparation of hyperthyroid patients for surgery.
Severe thyrotoxic crisis (thyroid storm).

Question 21

What is the mechanism of action of potassium iodide?

Answer 21

Inhibition of thyroid hormone synthesis and secretion: inhibits iodination of thyroglobulin; inhibits hydrogen peroxide generation.
Wolff-Chaikoff effect- the temporary reduction in thyroid hormones following ingestion of large amounts of iodine.
Hyperthyroid symptoms reduce within 1-2 days.
Vascularity and size of gland reduce within 10-14 days.

Question 22

What are the unwanted actions of KI?

Answer 22

Allergic reaction: rashes, fever, angioedema.

Question 23

Discuss the pharmacokinetics of KI.

Answer 23

Orally administered, given as Lugol’s solution or aqueous iodine. Maximum effect after 10 days of continuous administration.

Question 24

What are high doses of radioiodine (131) used for?

Answer 24

Treatment of Graves’, Plummer’s, and thyroid cancer. Permanently switches off thyroid without surgery.

Question 25

How does radioiodine work?

Answer 25

Relies on the fact that the thyroid gland takes up iodine to make thyroid hormone. Thyroid follicular cells take up the iodine and it accumulates in the colloid.
From the colloid it emits beta particles of radiation that destroy the follicular cells.

Question 26

Discuss the pharmacokinetics of radioiodine.

Answer 26

Discontinue antithyroid drugs 7-10 days prior to radioiodine treatment.
Administer as a single oral dose- 500MBq for Graves’, 3000MBq for thyroid cancer.
Radioactive half-life of 8 days.
Radioactivity negligible after 2 months.

Question 27

What are the cautions of radioiodine?

Answer 27

Avoid close contact with small children for several weeks after receiving radioiodine.
Contraindicated in pregnancy and breastfeeding.

Question 28

What is viral (de Quervain’s) thyroiditis?

Answer 28

Painful dysphagia
Hyperthyroidism
Pyrexia
Raised ESR
Virus attacks thyroid gland causing pain and tenderness. Thyroid stops making thyroxine and makes viruses instead, thus zero iodine uptake. Stored thyroxine is released- toxic with zero uptake. Four weeks later, stored thyroxine exhausted, so hypothyroid. After a further month, resolution occurs- euthyroid.