4 - Hypothyroidism

Question 1

What is the role of thyroxine (T4)?

Answer 1

keeps the basal metabolic rate high

Question 2

How does TSH lead to the production of thyroxine?

Answer 2

TSH switches on the follicular cells in the thyroid gland and you release thyroxine into the bloodstream

Question 3

State some of the effects of hypothyroidism.

Answer 3

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

Question 4

What are the results the thyroid function test on someone who has primary hypothyroidism?

Answer 4

high TSH

low T3/T4

Question 5

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

Answer 5

T3 and T4
T3 is more active (it has the biological action) but most of the thyroid hormone released by the thyroid gland is in the T4 form
T4 is a pro hormone that gets converted into the active T3

Question 6

What converts T4 to T3?

Answer 6

Deiodinase

Question 7

Give the proportions of T3 that come from the thyroid directly and that are converted from T4

Answer 7

80% - deiodination of T4

20% - direct thyroidal secretion

Question 8

Describe the mechanism of action of thyroxine.

Answer 8

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 9

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

Answer 9

T4 replacement – Levothyroxine Sodium

T3 replacement – Liothyronine Sodium

Question 10

What is thyroxine (T4) replacement used to treat?

Answer 10

Autoimmune primary hypothyroidism

Iatrogenic primary hypothyroidism

Question 11

How often is the tablet for thyroxine therapy taken and what measurement is taken to guide the dose?

Answer 11

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 12

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

Answer 12

Thyroxine = LOW
TSH = HIGH

Question 13

What is secondary hypothyroidism?

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

Answer 13

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 levels and keeping it within the reference range

Question 14

What is the clinical use of liothyronine sodium (T3)?

Answer 14

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

T3 is given initially, then T4

Question 15

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

Answer 15

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

Question 16

What is the problem with giving T3 replacement?

Answer 16

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 17

What are the half-lives of T3 and T4?

Answer 17

T3 = 2.5 hours
T4 = 6 days

Question 18

What plasma protein is (99.7%) T3 and T4 mainly bound to?

Answer 18

Thyroxine binding globulin (TBG)

Question 19

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

Answer 19

Pregnancy

Prolonged treatment with oestrogen and phenothiazines

Question 20

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

Answer 20

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

Question 21

How long does it take for T3 and T4 to be cleared from the body (bile into urine)?

Answer 21

T3 - cleared in hours

T4 - cleared much slower (about 6 days)