Pharmacology and testing in thyroid disease

Question 1

Where is the thyroid located?

Answer 1

2 lobes either side of the trachea, just below the larynx

Question 2

What are the 3 common disorders of the thyroid?

Answer 2

Hyperthyroidism
Hypothyroidism
Goitre - enlarged thyroid gland

Question 3

The only known use of which substance is used by the thyroid?

Answer 3

Iodine

Question 4

Thyroid hormones are based on which molecule?

Answer 4

Tyrosine

Question 5

What are the two main thyroid hormones?

Answer 5

T3 and T4

- T4 is in larger quantities, it is converted to T3 which is more biologically active

Question 6

How are thyroid hormones transported in the body?

Answer 6

In blood

- Fat soluble so need to be bound to a protein carrier

Question 7

What controls thyroid hormones and how?

Answer 7

HPA axis

• releasing hormones from the hypothalamus which affects the release of thyrotropin from the anterior pituitary
• TSH drives the production of thyroid hormone from the thyroid gland

Question 8

Give examples of the functions of thyroid hormone

Answer 8

1. Increases metabolic rate in all tissues (except brain, gonads and spleen)
2. Leads to an increase in oxygen consumption and thermogenesis
3. Required for normal growth and development
4. Promotes target responsiveness for the sympathetic NS
5. Promotes transmission of nerve impulses
6. Required for normal gonadal function
7. Required for normal development of the CNS

Question 9

What are some clinical signs of hypothyroidism?

Answer 9

• Weight gain with little change in appetite
• Lethargy
• Poor exercise tolerance
• Intolerance to cold
• Thinning of coat, bilateral hair loss, flaky skin
• Decreases HR
• Mental dullness

Question 10

What is the main cause of hyperthyroidism?

Answer 10

Benign but functional tumour on the thyroid gland

Question 11

What are the clinical signs of hyperthyroidism?

Answer 11

• Increased appetite and weight loss
• Hyperthermia
• Excitable, irritable, aggressive
• Increased HR

Question 12

What would be an indicator of hyperthyroidism on a blood test?

Answer 12

High serum total T4 (free and protein bound T4)

Question 13

What are the treatment options for hyperthyroidism?

Answer 13

• removal of thyroid tissue using surgery or radioactive iodide
• reduce synthesis of thyroid hormone from existing tissue

Question 14

How does radioactive iodine work in reducing the synthesis of thyroid hormone?

Answer 14

Destroys thyroid follicles so is an alternative to surgery

Question 15

What are possible adverse effects of removing thyroid tissues?

Answer 15

Hypothyroidism

Bilateral disease - damage to PTH glands

Question 16

Which drugs could you use in treatment of hyperthyroidism?

Answer 16

Thioureylenes

• Carbimazole
• Thiamazole

Question 17

What would you look for on a blood test as an indicator of hypothyroidism?

Answer 17

Serum level T4
Serum free T4
Endogenous TSH increased
Thyroglobulin autoantibodies

Question 18

What is the treatment method for hypothyroidism?

Answer 18

• Thyroid hormone replacement therapy: oral admission

Question 19

What are some adverse effects of thyroid hormone replacement therapy?

Answer 19

• Signs of hyperthyroidism
• Increase BMR
• Cardiovascular stimulant

Question 20

How and where are T3 and T4 synthesised?

Answer 20

By iodination of tyrosine residues on thyroglobulin within the lumen of the thyroid follicle

Question 21

Thyroid hormone synthesis and secretion is regulated by… and…?

Answer 21

Thyrotropin releasing hormone and thyroid stimulating hormone

Question 22

Compare the turnover rate and body concentrations of T3 and T4

Answer 22

T3: small pool, fast turnover rate, found intracellularly
T4: large pool, slow turnover rate, found in circulation

Question 23

How does T4 lead to regulation of gene transcription?

Answer 23

T4 is converted to T3 which bind with high affinity to nuclear receptors to regulate gene transcription

Question 24

Hyperthyroidism is a relatively common condition for?

Answer 24

Elderly cats

Question 25

Hypothyroidism is a relatively common condition for?

Answer 25

Dogs

Question 26

Dogs with primary hypothyroidism usually have elevated serum levels of what?

Answer 26

Thyroid stimulating hormone

Question 27

Which type of antibodies can be measured which indicate hypothyroidism?

Answer 27

Thyroglobulin autoantibodies

- immune destruction of the thyroid is a common cause of hypothyroidism

Question 28

Which test can be used to distinguish between euthyroid sick syndrome and genuine hypothyroidism?

Answer 28

Free T4 - concs of free T4 are rarely suppressed by non-thyroidal illness unless it is severe

Question 29

Which two drugs are available to treat hyperthyroidism?

Answer 29

Radioiodine

Thioureylenes

Question 30

Describe the mechanism of action of radioiodine

Answer 30

Injected - Rapidly and selectively taken up by the thyroid and damages cells. Emits B-radiation which only affects thyroid follicle cells. Serum T3 and T4 begin to normalise after 1-2 weeks

Question 31

Describe the mechanism of action of thioureylenes

Answer 31

Orally once daily -
Carbimazole is metabolised to methimazole
Methimazole inhibits the synthesis of thyroid hormones
Causes a gradual decrease in signs of hyperthyroidism over several weeks

Question 32

What 2 drugs are available for the treatment of hypothyroidism?

Answer 32

Levothyroxine

Liothyronine

Question 33

Describe the mechanism of action for levothyroxine/liothyronine

Answer 33

Given orally as a replacement therapy.
They are identical to their endogenous counterparts
Hormone is highly protein bound in circulation and only the free hormone is metabolically active