Drug effects of the hypothalamo-pituitary axis

Question 1

What is GH insensitivity?

Answer 1

When GH doesn’t properly elicit production of IGF-1

Question 1

What is deficit and cause of Hashimoto’s disease?

Answer 1

Deficient production of thyroid hormones

Autoimmune attack of the thyroid gland

Question 2

What effect does thyroxin binding protein have on thyroxin pharmacokinetics?

Answer 2

Increases in half-life

Question 3

What does carbimazole do?

Answer 3

Inhibits thyroid peroxidase required for the production of T4

Question 4

What are the three options for treatment of acromegaly?

Answer 4

Remove tumour (if applicable)

Reduce GH release - somatostatin

Inhibit GH action - GH antagonist

Question 5

Laron dwarfism is due to what?

Answer 5

GH insensitivity

Question 5

What can you give prophylactically in the event of a nuclear disaster?

Answer 5

Stable iodine that will out compete the radioactive iodine

Question 7

High GH and low IGF-1 is indicative of what condition?

Answer 7

GH insensitivity

Question 8

For which condition does one of its treating drugs cause agranulocytosis?

Answer 8

Hyperthyroidism

Question 9

Which is acromegaly due to?

Answer 9

Too much GH

Question 10

Which areas of the body are preferentially enlarged with acromegaly?

Answer 10

Hands, ears, nose, lips, jaw, feet

Question 10

What effect does radioactive I have on the thyroid gland?

Answer 10

Ablates it

Question 11

What is liothyronine?

Answer 11

T3

Question 12

Why was PEGylation required for the GH antagonist?

Answer 12

To increase its size therefore reduce its elimination in the kidneys

Question 13

What effect does ghrelin have on GH production?

Answer 13

Stimulates it production

• acts in synergy with GHRH

Question 14

What is the best treatment for hypothyroidism?

Answer 14

Thyroxine

Question 16

Do ghrelin and GHRH stimulate GH release via the same mechanism?

Answer 16

No, ghrelin increases Ca while GHRH elevates cAMP

Question 17

What was the trade off made in the creation of the optimal GH antagonist?

Answer 17

Increase its half-life at the cost of its GH receptor binding affinity

Question 20

What is the important stimulator of GH production?

Answer 20

GH releasing hormone (GHRH)

Question 20

What does IGF-1 do to appetite?

Answer 20

Stimulates it

Question 21

What are the analogues of somatostatin with longer half-lives called?

Answer 21

Octreotide and Lanreotide

Question 22

How does the GH antagonist work at the receptor?

Answer 22

Binds to its first receptor thereby preventing GH from binding but it doesn’t bind to the second site due to it lacking a lysine.

Question 23

The brain not stimulating enough GH production is a secondary or tertiary deficiency?

Answer 23

Tertiary

Question 24

If I inhibit thyroid peroxidase and the conversation of T4 to T3, which drug am I?

Answer 24

Propylthiouracil

Question 25

How can you image GH tumours?

Answer 25

Fluorescently labelled somatostatin is internalised when bound to somatostatin receptors on the tumour > will light up

Question 26

What is a problem with somatostatin as a treatment for GH tumours?

Answer 26

Short half-life

Only administered parenterally

Can reduce TSH too

Question 27

How was the problem of somatostatin’s short half-life alleviated?

Answer 27

Added some D- amino acids that aren’t easily broken down by enzymes

Question 28

What effect does somatostatin have on GH production?

Answer 28

Downregulates its production

Question 29

The pituitary not producing enough GH is a secondary or tertiary deficiency?

Answer 29

Secondary

Question 30

What is the mechanism of administration for GH treatment?

Answer 30

Parenteral (not GIT)

Question 31

What must you do when commencing someone on GH treatment?

Answer 31

Titrate the dose

Question 32

What is the most important downstream mediator of GH’s effect?

Answer 32

Insulin-like growth factor 1 (IGF-1)

Question 33

When is IGF-1 a useful treatment?

Answer 33

For GH insensitivity and when anti-GH antibodies are present