Pharm: GH, mecasermin, octreotide, pegvisomant

Question 1

GH’s recombinant form is _________.

Answer 1

somatotropin (think of the the magic growing beans)

Question 2

______ has significant homology to GH.

Answer 2

PRL

Question 3

What cellular pathway is GH associated with?

Answer 3

Jak-STAT

Jak is a tyrosine kinase which phosphorylates STATs to change transcription (think of the tire swing in front of Jak’s house)

Question 4

What mediates the growth promoting effects of GH?

Answer 4

IGF-1- insulin-like growth factor 1 (think of the welcome INSIDE mat)

Like insulin IGF-1 binds to the EGFRs which is a tyrosine kinase (that phosphorylates itself)

Question 5

What is IGF-1 responsible for?

Answer 5

long bone growth

Question 6

Where is IGF-1 produced?

Answer 6

liver (think of the liver-shaped rock where the “welcome INSIDE” mat used to be

Question 7

What is GH responsible for?

Answer 7

1. anabolic effects in muscle (think of the striated muscle leaf)
2. catabolic effects in AT- lipolysis (think of the donuts spilling out of a jar)

Question 8

When can GH be administered exogenously for treatment?

Answer 8

1. child with GH deficiency or idiopathic short stature- latter is more controversial (think of the short kid)
2. Prader-Willi: AD disease, growth failure, obesity, carb intolerance (think of Padre Willi- missing dad’s genes)
3. Turner’s syndrome (think of the Turning-cartwheeling “X” girl)

Question 9

What is another cause of growth failure (not from GH deficiency)?

Answer 9

IGF-1 deficiency (not responsive to GH therapy)

Question 10

What is mecasermin?

Answer 10

Recombinant IGF-1 (think of the “sermon” sign in front of the church with the welcome INSIDE mat)

Question 11

What is a side effect of mecasermin?

Answer 11

Insulin-like growth factor 1 is insulin like and therefore causes HYPOGLYCEMIA

Question 12

Why does exogenous GH administration not cause hypoglycemia?

Answer 12

By itself, GH causes insulin resistance which is GH itself does not cause hypoglycemia. Both GH and insulin is needed to release IGF-1

Question 13

What does excess GH from a GH pituitary adenoma cause?

Answer 13

Acromegaly: in adults
Gigantism: in children

Question 14

What are the signs of acromegaly?

Answer 14

Deep voice, large hands and feet, coarse facial features, insulin resistance, increased risk of CRC

Question 15

What is the first-line therapy for GH adenomas?

Answer 15

Surgical resection

Question 16

What are medical treatments that inhibit GH secretion?

Answer 16

1. octreotide- SST analog (think of the lady holding a STOP sign)
2. D2 receptor agonists- cabergoline and bromocriptine (think of BuRGLer holding a BROoMstiCk going down the Double rope ladder)
3. Pegvisomant - GH receptor antagonist (think of the ANTs on the Tyr swing)

Note: Pegvisomant prevents activation of GH-receptor but GH levels may increase in response and the tumor may grow

Question 17

What are all the things that octreotide can be used to treat?

Answer 17

1. VIPoma - secretory diarrhea
2. Carcinoid tumor (secreting 5HT) - secretory diarrhea, wheezing, flushing
3. GH tumors - acromegaly
4. Insulinoma - fasting hypoglycemia
5. Glucagonoma - weight loss, necrolytic migratory erythema (esp skin surrounding lips)
6. Gastrinoma (Zollinger-Ellison syndrome)
7. Esophageal varices

Question 18

What are the physiological actions of somatostatin?

Answer 18

1. Decrease release of a lot of hormones and digestive (and pancreatic) enzymes
2. Decrease portal blood flow (thus variceal pressure)
3. Decrease GI motility

Question 19

What are the side effects of octreotide?

Answer 19

1. N/V
2. abd cramps
3. steatorrhea (think of the naustead town’s person on the yellow STOOL)