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

Controls uptake of i- which makes thyroxine stores
Controls enzyme that causes release of Thyroxine

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+Tiredness
Cold intolerance
Weight gain and reduced appetite
Constipation
Eventual myxoedema coma

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, located in nucleus, that causes a change in gene expression

Question 14

What is usually used for primary hypothyroidism

-rimary hypothyroidism due to

Answer 14

Levothyroxine sodium–oral admin

-Autoimmune, iatrogenic-post thyroidectomy, post-radioactive iodine

Question 15

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

Answer 15

TSH levels as it suppresses TSH by negative feedback back into its reference range

Question 16

Where is the problem in secondary hypothyroidism?

Answer 16

Pituitary gland– tumour, surgery, radiotherapy

Question 17

What is used to treat secondary hypothyroidism?

Answer 17

Levothyroxine–oral admin

NOT LEVOTHYROXINE SODIUM – PRIMARY

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 – active, not hormone bound levels are used instead

Question 19

What is liothyronine sodium used for?

Answer 19

liothyronine sodium (T3)
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 combined T4T3 treatment?

Answer 20

Some reported improvement in well being

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

Question 21

Pharmocokinetics how is T4 and T3 horm usually adminstered drug name

Comparison of half life

Answer 21

T4–Levothryoxine Sodium for primary hypothyroidism
Levothyroxine for secondary
both administered orally

T3 Liothyronine sodium administered as IV

T4- Plasma half life of 6 days
T3 plasma half life of 2.5 days

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

Thyroglobulin -glycoprotein in colloid in thyrofollicular cells that contain I2 and T3/T4

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

-Certain co-administered drugs e.g phenytoin, salicylates, compete for protein binding sites