24. The thyroid

Question 1

What is the structure of the thyroid gland?

Answer 1

Bilobed gland - occasionally has a pyramidal lobe in the middle of it
Right gland is usually larger
Blood supply to the gland is the highest in the body

Question 2

What are the thyroid hormones and why are they named like this?

Answer 2

Thyroid hormones are named for their number of iodine residues
T4 - Thyroxine
T3 - Triiodothyronine/Liothyronine

Question 3

What stimulates the release of thyroid hormones?

Answer 3

Thyroid stimulating hormone (TSH) binding to a TSH receptor

Question 4

Briefly describe how the roles of T4 and T3 differ to one another

Answer 4

T4 - Major form of thyroid hormone secreted from the thyroid gland - is metabolised into T3
T3 - Active thyroid hormone - 3/4 times more potent than T4 - has metabolic effects on almost every tissue in the body

Question 5

How are the thyroid hormones synthesised? (mechanism)

Answer 5

TSH binds to TSHR on the thyroid follicular cell of the thyroid gland
Causes activation of protein symporter channels through which iodine enter the thyroid follicular cell, along with sodium
Iodines bind to thyro-globulin
Used for the production ofT4

Question 6

How is T4 converted to T3?

Answer 6

Via a deiodinase enzyme - removes an iodine

Question 7

Give the roles of the different deiodinase enzymes

Answer 7

D1 and D2 convert T4 to T3
D3 then acts to inactivate T4
D3 can also inactivate T3 if required and can produce T2 (T2 has no function)

Question 8

Where is the majority of T4 converted to T3?

Answer 8

In the liver

Question 9

Why are there so many expressions of these deiodinase enzymes?

Answer 9

Not all of the T4 needs to be activated at the same time (remember T3 has an effect on almost every tissue) SO allows for finer regulation and control
Some tissues will have a very high level of D1/D2 and some will have low levels

Question 10

Where is D1 expressed?

Answer 10

In the peripheries

Question 11

Where is D2 expressed?

Answer 11

In the brain and in the pituitary gland

Question 12

What is the relevance of the brain to the conversion of T4 to T3?

Answer 12

The brain requires relatively constant levels of exposure to T3
Does this via the expression of the enzyme D2

Question 13

What happens to the levels of T4 and D2 during hypothyroidism?

IMPORTANT FOR EXAMS

Answer 13

During hypothyroidism, T4 levels go down

D2 gets upregulated SO more T4 is converted into T3

Question 14

What happens to the levels of T4 and D2 during hyperthyroidism?

IMPORTANT FOR EXAMS

Answer 14

In hyperthyroidism, there are very high levels of T4

D2 gets down regulated so the brain converts less T4 to T3

Question 15

What is thyroid binding globulin?

Answer 15

Globulin that binds thyroid hormones

Question 16

What is the significance of a raised thyroid binding globulin?

Answer 16

The more thyroid binding globulin you have, the more thyroid hormones are bound to this rather than are free in the bloodstream SO the thyroid gland needs to work harder to increase the levels of free T4

Question 17

When might the levels of thyroid binding globulin increase?

Answer 17

During pregnancy

Question 18

Describe the thyroid hormone receptor

Answer 18

Sits on the DNA in the nucleus - has an affect on transcription
T3 binds to it and activates transcription
Homodimer - the same on both sides

Question 19

What is hyperthyroidism and what state does it lead to?

Answer 19

This is a state of over-activity of the thyroid gland
Leads to thyrotoxicosis i.e. state of too much thyroxine (T4) release in the blood
The overdose of T4 results in inflammation and a release of stored thyroid hormones - makes matters even worse (lymphoid follicles are present)

Question 20

What is the relation of hyperthyroidism to the metabolic rate and what is the significance of this?

Answer 20

Hyperthyroidism - increases the metabolic rate
Leads to excess production of heat - patients have heat intolerance
Attempt to remove excess heat - increased heart rate
Increased appetite - to provide for increased energy for the raised BMR
Degradation of proteins and lipids (myopathy) to gain increased levels of energy - weight loss (also degradation of bones, leading to osteoporosis)
Accelerated insulin turnover - insulin is being digested quicker due to raised BMR and so insulin has less time to work - hyperglycaemia

Question 21

What is the effect of hyperthyroidism on the nervous system?

Answer 21

Damage to the nervous system leading to seizures and nervousness

Question 22

What is the effect of hyperthyroidism on the eyes?

Answer 22

Eyes widen - lid retraction and lid lag
Ptosis can occur due to Grave’s disease
Proptosis - large number of TSHR behind the eye - causes the swells to swell up and get inflamed

Question 23

What is hypothyroidism and what is it’s effect on BMR?

Answer 23

Lack of thyroid hormone production

Causes a reduction in the BMR

Question 24

What are the symptoms of hypothyroidism?

Answer 24

Lowered BMR 
Reduced appetite but increased weight - not burning it off (overweight)
Skin becomes dry 
Hair is brittle and starts falling out
Reduced heart rate
More sensitive to the cold
Reduced libido 
Erectile dysfunction

Question 25

What is a common cause of hypothyroidism?

Answer 25

Hashimoto’s disease - autoimmune condition via the production of autoantibodies
There will be lymphocytic infiltration of the thyroid gland - lymphoid follicles
High TSH levels but low T4 levels

Question 26

How is hypothyroidism treated?

Answer 26

Drugs Levothyroxine/Liothyronine (T3)