Hypothyroidism

Question 1

State some of the effects of hypothyroidism.

Answer 1

Reduced basal metabolic rate – everything slows down 
Cold intolerance 
Deep voice 
Weight gain 
Loss of appetite 
Depression 
Lethargy 
Speech slows down 
Bradycardia 
Constipation

High TSH, Low T4

Question 2

What are the main thyroid hormones? Which is more active?

Answer 2

T3 (half-life 2-5 hours) and T4 (half-life 6 days)

T3 is more active but most of the thyroid hormone released by the thyroid gland is in the T4 form

Question 3

What converts T4 to T3?

Answer 3

Deiodinase

Question 4

What plasma protein is T3 and T4 mainly bound to?

Answer 4

Thyroxine binding globulin (99.97% of T4 bound 99.7% T3)

Question 5

What can change the production of plasma proteins?

Answer 5

Increased production:
Pregnancy
Prolonged treatment with oestrogen and phenothiazines

Decreased production:
Liver failure (most plasma proteins are produced by the liver)
Severe malnourishment

Question 6

Describe the mechanism of action of thyroxine.

Answer 6

Thyroxine enters the target cell and is converted to T3 by deiodinase
T3 then binds to a thyroid hormone receptor in the nucleus and then heterodimerises with a retinoid X receptor
This complex then binds to a thyroid response element, which causes a change in gene expression

Question 7

What are the two main drugs that are used as thyroxine and T3 replacement?

Answer 7

T4 replacement – Levothyroxine Sodium
T3 replacement – Liothyronine Sodium (Very rarely used as expensive and can cause toxicity – palpitation, tremor, anxiety etc and has no better outcome)

Question 8

What is thyroxine replacement used to treat?

Answer 8

Autoimmune primary hypothyroidism

Iatrogenic primary hypothyroidism (caused by prior treatment)

Question 9

How often is the tablet taken and how is correct dosage decided?

Answer 9

Daily tablet

TSH levels are monitored and once they fall to within normal range, correct dosage has been found

Question 10

What is secondary hypothyroidism? What measurement is used to guide the dose in this case?

Answer 10

This is a problem with TSH production by the adenohypophysis, there is no problem with the thyroid gland itself

As there is no TSH production, thyroxine replacement therapy is monitored by measuring free T4 (fT4) levels and keeping it within the reference range

Question 11

What is the clinical use of liothyronine sodium?

Answer 11

Treatment of myxoedema coma (very rare complication of hypothyroidism)
You give IV liothyronine sodium because the onset of action is faster than levothyroxine sodium

Question 12

Why would you give a patient combined thyroid hormone replacement (T3+T4)?

Answer 12

Some patients don’t feel better with T4 replacement alone though their TSH may be normal (although combined treatment in contentious and suppresses TSH)

Question 13

Describe some adverse effects of thyroid hormone over-replacement.

Answer 13

Skeletal
Increased bone turnover
Reduced bone mineral density
Risk of osteoporosis

Metabolic
Increased energy expenditure
Weight loss

Cardiac
Tachycardia
Risk of arrhythmia

Beta-adrenergic activity
Tremor
Nervousness