Hypothyroid Disorders

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

Question 2

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

Answer 2

T3 and T4

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

Describe the mechanism of action of thyroxine.

Answer 4

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 5

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

Answer 5

T4 replacement – Levothyroxine Sodium

T3 replacement – Liothyronine Sodium

Question 6

What is thyroxine replacement used to treat?

Answer 6

Autoimmune primary hypothyroidism

Iatrogenic primary hypothyroidism

Question 7

How often is the tablet taken and what measurement is taken toguide the dose?

Answer 7

Once daily

TSH is measured and the aim is to use thyroxine replacement to suppress TSH so that it is within the reference range

Question 8

Describe the levels of thyroxine and TSH in someone with primary thyroid failure.

Answer 8

Thyroxine = LOW 
TSH = HIGH

Question 9

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

Answer 9

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 10

What is the clinical use of liothyronine sodium?

Answer 10

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 11

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

Answer 11

Some patients don’t feel better with T4 replacement alone though their
TSH may be normal

Question 12

What is the problem with giving T3 replacement?

Answer 12

T3 is very potent so it is difficult to get the dose right

Too high a dose can lead to patients complaining of thyrotoxicosis type symptoms: palpitations, tremor, anxiety

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 dysrhythmia 
Beta-adrenergic activity 
 Tremor  
 Nervousness

Question 14

What are the half-lives of T3 and T4?

Answer 14

T3 = 2-5 hours 
T4 = 6 days

Question 15

What plasma protein is T3 and T4 mainly bound to?

Answer 15

Thyroxine binding globulin

Question 16

What can cause an increase in the production of plasma proteins?

Answer 16

Pregnancy

Prolonged treatment with oestrogen and phenothiazines

Question 17

What can cause a decrease in the amounts of the plasma proteins?

Answer 17

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