Hypothyroidism

Question 1

Where and how does TSH act specifically?

Answer 1

It switches on follicular cells of the thyroid gland and release thyroxine into the bloodstream

Question 2

What does thyroxine do?

Answer 2

Keeps basal metabolic rate high and body temperature constant

Question 3

What is the most common cause of thyroid gland failure (primary hypothyroidism)?

Answer 3

Autoimmune disease of the thyroid

Question 4

What percentage of the population will be affected by thyroid gland failure?

Answer 4

5%

Question 5

Explain the biochemistry of primary hypothyroidism?

Answer 5

There is a fall in the level of the thyroxine- feel cold and tired
Pituitary detects fall and produces loads of TSH to compensate

Question 6

What are some common signs and symptoms of primary hypothyroidism?

Answer 6

Tongue gets thick
Speech slows down
Deepening of voice
BMR falls
Bradycardia
General weakness
Depression
Cold intolerance
Weight gain and reduced appetite
Constipation

Question 7

What are the two hormones that a healthy thyroid secretes?

Answer 7

T3 and T4

Question 8

Explain the relationship between T3 and T4?

Answer 8

T4 (thyroxine) is a pro-hormone that is converted to active T3 by deiodinase

Question 9

How is the majority of T3 in the circulation formed?

Answer 9

80% from the conversion of T4

20% from direct thyroidal secretion

Question 10

Describe the relationship between T3 and T4 in terms of thyroid hormone activity at target cells?

Answer 10

T3 provides almost all of the thyroid hormone activity

Question 11

Where is thyroxine converted to T3 by deiodinase?

Answer 11

In the target cell

Question 12

Where does T3 go once inside the target cell?

Answer 12

To the nucleus where it binds to the thyroid hormone receptor

Question 13

What happens after T3 has bound to thyroid hormone receptor?

Answer 13

The THR then heterodimerises with the retinoid x receptor. This complex then binds to the thyroid response element that causes a change in gene expression

Question 14

What is usually used as thyroxine replacement?

Answer 14

Levothyroxine sodium

Question 15

What is used as the guideline for thyroxine dose in primary?

Answer 15

TSH levels as it suppresses TSH by negative feedback

Question 16

Where is the problem in secondary hypothyroidism?

Answer 16

Pituitary gland

Question 17

What is used to treat secondary hypothyroidism?

Answer 17

Levothyroxine sodium

Question 18

What is used as the guideline for thyroxine dose in secondary?

Answer 18

They don’t produce TSH so this can’t be used, free T4 levels are used instead

Question 19

What is liothyronine sodium (T3) used for?

Answer 19

Myxoedema coma - very rare complication of hypothyroidism

I.V liothyronine is given as its onset is faster than T4

Question 20

What are the complications of T3 treatment?

Answer 20

Switch off TSH and patients may complain of symptoms of thyrotoxicosis:
palpitations, tremor and anxiety

Question 21

What are some adverse effects of thyroid hormone over-replacement?

Answer 21

Usually associated with low TSH
Skeletal-
Increased bone turnover
Reduction in bone mineral density
Risk of osteoporosis
Cardiac-
Tachycardia
Risk of dysrrythmia
Metabolism-
Increased energy expenditure
Weight loss
Increased beta-adrenergic sensitivity-
Tremor
Nervousness

Question 22

How do T4 and T3 normally exist in circulation?

Answer 22

Highly bound- 99.97% of circulating T4 and 99.7% of T3 are plasma protein bound

Question 23

Which plasma protein is T3 and T4 mainly bound to?

Answer 23

Thyroxine binding globulin

Question 24

When do plasma proteins increase?

Answer 24

Pregnancy and on prolonged treatment with oestrogen and phenothiazides

Question 25

When do plasma proteins decrease?

Answer 25

If you have liver disease or are severely malnourished

Question 26

In terms of quantity in the plasma, how do T3 an T4 compare?

Answer 26

10 times more T4 in plasma than T3

Question 27

How is T3 and T4 cleared?

Answer 27

Free and conjugated hormone is secreted into bile and urine:
T3 is cleared in hours
T4 is cleared in about 6 days