Hyperthyroidism

Question 1

What are the causes of Grave’s disease? What are the features of Grave’s disease?

Answer 1

autoimmune - antibodies bind to and stimulate TSH receptors in thyroid gland.

The stimulation of the gland causes growth and form a SMOOTH goitre.

Also causes lid lag

Other antibodies bind to growth factor receptors in muscles behind the eyes and causes an exophthalmos.

Other antibodies cause pretibial myxoedema (hypertrophy) – growth of soft tissue on the shins.
o NON-pitting oedema

more likely to have family history

Question 2

What are the signs and symptoms of general hyperthyroidism?

Answer 2

• Weight loss despite increased appetite.
• Dyspnoea.
• Palpitations, tachycardia.
• Sweating and heat intolerance.
• Diarrhoea.
• Lid lag and other SNS features - Thyroxine sensitises beta-adrenoceptors to ambient levels of adrenaline and noradrenaline (NOT more adrenaline, just more sensitive receptors) ->Leads to apparent SNS activation ->tachycardia, lid lag, etc.

Question 3

What are the causes and features of Plummer’s disease?

Answer 3

NOT autoimmune but a benign adenoma.

Toxic nodular goitre.

NO pretibial myxoedema.

NO exophthalmos.

Also called a “Hot Nodule” on a thyroid uptake scan

tachycardia

lid lag

Question 4

What are the features of a thyroid storm? What is the treatment for it?

Answer 4

• Hyperpyrexia – high fever (>41).
• Accelerated tachycardia/arrhythmia.
• Cardiac failure.
• Delirium/frank psychosis.
• Hepatocellular dysfunction, jaundice.

Requires aggressive treatment:

• Surgery (thyroidectomy).
• Radioiodine.
• Drugs.

Question 5

What types of drugs are used to treat hyperthyroidism?

Answer 5

1. Thionamides (thiourylenes; anti-thyroid drugs):
   Propylthiouracil (PTU) / Carbimazole (CBZ)
2. Potassium iodide
3. Radioiodine
4. Beta-blockers (combats symptoms)

The first 3 inhibit thyroxine synthesis

Question 6

What are the clinical uses of thionamides?

Answer 6

Daily treatment of hyperthyroid conditions – e.g. Graves’, Toxic thyroid nodule

Treatment prior to surgery

Reduction of symptoms while waiting for radioactive iodine to act

Question 7

Outline the mechanism of action of thionamides?

Answer 7

Inhibits TPO and peroxidase transaminase

Supress antibody production in Graves’

Reduce T4 -> T3 in peripheral tissues (PTU)

Question 8

How long does it take to see a clinical effect of thionamides?

What are some unwanted side effects?

Answer 8

There is a biochemical effect in hours but no clinical effect until a week or so has passed as there is a large store of normal thyroxine in the thyroid gland that is released for a while.

• It takes several weeks for ATDs to have a clinical effect so a NON-cardio selective beta blocker is given (e.g. propranolol), to achieve symptom relief in the interim (works on tremors as well as palpitations)

The treatment regimen may include propranolol (beta-blocker) to rapidly reduce tremor and tachycardia.

Unwanted actions:
- Agranulocytosis – reduction or absence of granular leukocytes.

-Rashes.

Question 9

Describe the pharmokinetic properties of thionamides

Answer 9

• Orally active.
• Carbimazole is a pro-drug (first is converted to methimazole).
• Plasma half-life of 6-15 hours.
• Crosses placenta (secreted in breast milk) – Carbimazole more so than PTU
• Metabolised in liver and secreted in urine

Question 10

What is the follow up after thionamides?

Answer 10

Stop anti-thyroid treatment after 18 months

Review patient frequently

**50% chance of relapse

Question 11

When is potassium iodide used? What are some unwanted reactions?

Answer 11

Preparation of hyperthyroid patients for surgery

In severe thyroid storm crisis patients

unwanted reaction:
allergic reaction

Question 12

What is the mechanism of action of iodide treatment?

Describe the pharmacokinetics

Answer 12

Inhibits iodination of TG.

Inhibits hydrogen peroxide generation.

WOLF-CHAIKOFF EFFECT (presumed autoregulatory - large does of iodine shuts of TSH production)

• Symptoms reduce in 1-2 days.
• Size of gland reduce in 10-14 days

Pharmacokinetics
Orally active – Lugol’s solution with maximum effect after 10 days’ continuous administration

Question 13

What are the features of HIGH DOSE radioiodine (mechanism of action, pharmacokinetics, caution)?

Answer 13

Treats hyperthyroidism and thyroid cancers.

Mechanism of action:
- Radioiodine accumulates in thyroid and emits beta particles which destroy follicular cells.

Pharmacokinetics:
- Discontinued anti-thyroid drugs 7-10 days’ prior so radioiodine is taken up by thyroid as much as possible.
- Administered as a single dose orally:
Graves – approx. 500 MBq.
Thyroid cancer – approx. 3000 MBq.

• Radioactive half-life of 8 days.
• Radioactivity negligible after 2 months.

Cautions:

• Contact with small children avoided for several weeks after receiving.
• CONTRA-indicated in pregnancy and breast feeding.

Question 14

What are the causes of viral thyroiditis?

Answer 14

• Painful/tender dysphagia.
• Hyperthyroidism (WITH ZERO IODINE UPTAKE ON SCAN)
• Pyrexia – fever.
• Raised ESR – Erythrocyte sedimentation rate.

hyperthyroidism -> hypothyroidism

• Virus attacks thyroid gland causing pain and tenderness -> Virus then lyses the cell and so thyroxine spills out into the blood (hyperthyroidism) and then the thyroid is not creating thyroxine so the hyperthyroidism becomes hypothyroidism after around a month.
• After a further month, patient is healthy again.