Hyperthyroidism - Toxic multinodular goitre

Question 1

Are TMGs typically benign or malignant?

Answer 1

Benign.

Question 2

Where are TMG rates higher?

Answer 2

In iodine-deficient regions.

Question 3

What is the pathophysiology of TMGs?

Answer 3

· Thyroid cell growth and function are mainly stimulated by TSH via the TSH receptor.
· TSH receptor activity is mediated through the alpha sub-unit of stimulation G protein and cAMP.
· In germline mutations, cAMP levels are increased, which causes growth and excess function of thyrocytes.

Question 4

What is the aetiology of TMGs?

Answer 4

· Contains multiple autonomously functioning nodules, resulting in hyperthyroidism.
· Most hyperfunctioning nodules have thyroid cell germline mutations that affect the TSH receptor.
· Patients usually have a hx of long-standing goitre.

Question 5

List the risk factors.

Answer 5

· Iodine deficiency.
· Age >40 years.
· Head and neck irradiation.

Question 6

What are the most common signs and symptoms?

Answer 6

· Goitre:
	- Irregular. 
	- Substernal extension. 
· Heat intolerance and weight loss. 
· Depression. 
· Nervousness or palpitations. 
· Tachycardia. 
· Fine resting tremor.

Question 7

What investigations would you request if you suspected a patient had a TMG?

Answer 7

· TSH.
· Free T4.
· Total T3.
· Thyroid scan and uptake.
· Thyroid USS. 
· U&Es and LFTs.
· FBC. 
· TSH receptor antibodies.

Question 8

What would the investigations typically show?

Answer 8

· TSH - suppressed.
· Free T4 - elevated.
· Total T3 - elevated.
· Thyroid scan and uptake - multiple hot and cold areas.
· Thyroid USS.
· U&Es and LFTs - possible hypercalcaemia.
· FBC.
· TSH receptor antibodies - negative (would be positive in Graves’ disease).

Question 9

Suggest some differentials.

Answer 9

· Graves’ disease. Younger people, diffuse goitre not nodular, positive TSH receptor antibodies.
· Toxic adenoma. Single, generally large nodule.
· Functional thyroid cancer.

Question 10

How would you treat a patient with TMG?

Answer 10

· 1st line - Radioactive iodine therapy (I-131).
· Adjunct - Pre-treatment anti-thyroid drugs, such as thiamazole.
· 2nd line - Thyroid surgery.
· Adjunct - Pre-surgical anti-thyroid drugs, such as thiamazole.
· 3rd line - Anti-thyroid drugs alone.
· If moderate/severe symptoms and/or increased cardiovascular risk - beta blockers.

Question 11

What complications can occur?

Answer 11

· Surgery-related recurrent laryngeal nerve damage.
· Surgery-related hypoparathyroidism. Transient post-op hypocalcaemia is common.
· Bone mineral loss.
· AF.
· Mass effect with large goitres, such as choking and dysphagia.
· Thyroid storm - weakness, severe tachycardia and fever.