hypothyroidism

Question 1

Draw a diagram to show the hypothalamo-pituitary-thyroid axis.

Answer 1

Question 2

How can primary hypothyroidism be diagnosed?

Answer 2

High TSH

Question 3

What is the role of TSH?

Answer 3

Control uptake of Iodide.

Control enzyme that catalyses thyroxine formation.

Question 4

Diagram to outline thyroxine synthesis.

Answer 4

Question 5

Diagram outlining thyroid axis, thyroxine production, thyroxine effects.

Answer 5

Question 6

What is the most common cause of primary hypothyroidism (myxoedema)?

Answer 6

autoimmune damage to the thyroid.

Question 7

Outline the pathology of primary hypothyroidism.

Answer 7

autoimmine damage to thyroid.

Thyroxine levels decline.

TSH levels rise.

Question 8

Give some symptoms and signs of primary hypothyroidism.

Answer 8

Deepening voice

Depression and tiredness

Cold intolerance

Weight gain and reduced appetite

Constipation.
Bradycardia.

Eventual myxoedema coma.

Question 9

How do T4 and T3 relate to each other?

Answer 9

T4 is a prohormone. Deiodinase enzyme converts T4 –> T3. T3 provides almost all thyroid hormone activity in target cells.

Question 10

What are the origins of circulating T3.

Answer 10

80% deiodination of T4.

20% direct thyroidal secretion.

Question 11

Outline the method of action of T3.

Answer 11

T3/T4 enter cell. T4 –> T3 (deiodinase).

T3 binds to retinoid x receptor and thyroid hormone receptor (hexodimer).

This grioup binds to Thyroid response element in DNA which modulates gene expression.

Question 12

How is primary hypothyroidism treated?

Answer 12

Thyroxine replacement (also called thyroxine sodium or levothyroxine sodium). T3 also given less commonly.

Question 13

List some causes of hypothyroidism.

Answer 13

Autoimmune, post-thyroidectomy, post-radioacrive iodine intake.

Question 14

How is thyroxine administered.

Answer 14

Normally orally.

Question 15

How is thyroxine dose for primary hypothyroidism controlled?

Answer 15

TSH used for guidance of dosage - aim to keep within reference range.

Question 16

What is secondary hypothyroidism?

Answer 16

Healthy thyroid - lack of TSH to stimulate it

Question 17

What are some causes of secondary hypothyroidism?

Answer 17

Pituitary tumour, post-pituitary surgery, radiotherapy.

Question 18

How is T4 dose controlled in secondary hypothyroidism?

Answer 18

Aim for free T4 levels in middle of reference range.

Question 19

Why might you give T3 instead of T4.

Answer 19

Treatment for myxoedema coma - faster acting + can be asdministered intravenously.

Question 20

What are the pros and cons of combination T3/T4 treatment?

Answer 20

Some have reported that combination improves well being (limited evidence)

However, can lead to palpitations, tremor, anziety and combination can lead to suppression of TSH.

Question 21

What is the difference in half-life between T4 and T3.

Answer 21

T4 - 6 days

T3 - 2.5 days

Question 22

What proportion of T3 and T4 is free?

Answer 22

0.03% (99.97% bound to PP).

Question 23

What is the primary binding protein for plasma T4 and T3?

Answer 23

Thyroxine Binding Globulin (TBG)

Question 24

How might TBG levels change and why?

Answer 24

Increase - in pregnancy or on prolonged oestrogen/phenothiazine treatment.

Decrease - malnutrition, liver dieases.

Certain drugs can compete for binding sites (e.g. phenytoin/salicylates).