Hypothalamic & Pituitary

Question 1

What is the MOA of growth hormone receptor, what does it lead to and where does growth hormone comes from?

Answer 1

GH is released from anterior pituitary, enters the circulation and binds to GH receptors that are JAK tyrosine kinase, this causes activation of JAK STAT pathway.It leads to the production of insulin like growth factor 1, IGF1 then has several effects

Question 2

What are the effects of IGF1 on the body?

Answer 2

1. Insulin like effects, but GH causes increase in glucose levels so they’re effects are balanced out2. Growth promoting effects: growth of long bones, catabolic effects on adipose tissue, anabolic effect on muscles

Question 3

What are the 3 clinical uses of exogenous GH?

Answer 3

1. GH therapy is useful in GH deficiency (patients gain normal height) and idiopathic short stature (controversial). 2. - GH therapy is useful for increasing growth in Prader-Willi syndrome (AD inheritance due to missing genetic contribution from the father).3. - GH therapy is useful for increasing growth in Turner syndrome (XO genotype).

Question 4

What can be another potential cause of short stature other than GH deficiency?

Answer 4

IGF1 deficiency or a defective IGF1 receptor

Question 5

What is the name of recombinant IGF1?

Answer 5

Mecasermin

Question 6

When is Mecasermin used?

Answer 6

For patients that have resistance to GH therapy, Mecasermin (recombinant IGF-1) can be used instead

Question 7

What does GH secreting pituitary adenomas can cause and how that can be treated?

Answer 7

GH-secreting pituitary adenoma causes acromegaly (in adults) or gigantism (in children) and an increased risk of colorectal tumors/polypsThe initial therapy of choice for a GH-secreting pituitary adenoma is Transphenoidal resection. If GH-hypersecretion persists, GH-antagonists are used

Question 8

What is the MOA and indications for octeotride

Answer 8

Somatostatin analog, inhibits GH secretion so it can be used to treat gigantism and acromegaly

Question 9

What are the functions of somatostatin in the body?

Answer 9

Reduces intestinal and pancreatic secretion, slows down GI motility, and inhibits some pituitary hormones

Question 10

What other conditions can be treated with octeotride?

Answer 10

Octreotide treats VIPoma (neuroendocrine tumor secreting Vasoactive Intestinal Peptide) and Carcinoid tumor (ileal tumor with hepatic metastasis secreting serotonin).

Question 11

What 3 other endocrine tumors can be treated with octeotride?

Answer 11

Insulinoma, glucagonoma and gastronome (Zollinger Ellison syndrome)

Question 12

How does glucagonoma presents as?

Answer 12

Presents as weight loss and a necrolytic migratory erythema

Question 13

How does octeotride treat symptoms of portal hypertension?

Answer 13

Octreotide can control bleeding of esophageal varices by decreasing portal blood flow and variceal pressure (mechanism is poorly understood).

Question 14

What are the AE of octeotride?

Answer 14

Octeotride decrease pancreas and gall bladder contractility so it can cause steatorrhea along with GI symptoms.

Question 15

Name D2 receptor agonists

Answer 15

Cabergoline and Bromocriptine

Question 16

What are D2 receptor agonists used for?

Answer 16

Inhibit GH secretion and prolactin secretion from the pituitary, can be used for a variety of conditions

Question 17

Name a direct GH antagonist

Answer 17

Pegvisomant

Question 18

What are its effects and side effects?

Answer 18

Since Pegvisomant (a direct GH receptor antagonist) inhibits GH-receptor activation but does not inhibit GH secretion, it causes elevated serum GH levels and can even cause increased pituitary adenoma growth!Can be used to treat acromegaly

Question 19

Where is ADH released from?

Answer 19

Posterior pituitary

Question 20

MOA and effects of ADH

Answer 20

V1 receptor found in capillaries, causes vasoconstriction, coupled to Gq (IP3, DAG, increase in Ca)V2 in kidneys, recruits acquporins in the collecting duct, coupled to Gs (increase in cAMP)

Question 21

Where are extra V2 receptors found?

Answer 21

Extra V2 receptors are found on the vascular endothelium and cause the secretion of von Willebrand Factor and Factor VIII

Question 22

Explain diabetes insipidus

Answer 22

Patient cannot concentrate their urine, either because they cannot produce ADH (central DI) or because they cannot respond to ADH (nephrogenic DI).

Question 23

What is the most common cause of nephrogenic DI

Answer 23

Lithium, present in bipolar disorder drugs

Question 24

What drugs can we use to treat nephrogenic DI

Answer 24

Thiazides and amiloride, caution thiazides increase lithium levels by decreasing its clearence

Question 25

How does NSAIDs treat nephrogenic DI?

Answer 25

NSAIDs (e.g. indomethacin) treat nephrogenic DI by decreasing the production of prostaglandins that antagonize the effects of ADH

Question 26

What drug can be used in central DI?

Answer 26

Desmopressin, its an exogenous ADH

Question 27

What other condition can be treated with desmopressin?

Answer 27

Nocturnal urination (bed wetting)

Question 28

What is the role of desmopressin in treating portal hypertension?

Answer 28

Exogenous ADH (that binds to V1) is useful in the management of esophageal variceal vein bleeding via constriction of mesenteric arterioles causing reduced portal pressure -> less blood flow to esophageal variceal veins.

Question 29

How do we treat SIADH?

Answer 29

Syndrome of Inappropriate ADH (SIADH) is caused by the overproduction of ADH. SIADH can be caused by ectopic secretion of ADH by cancer.”-vaptan” suffix of V2 ADH receptor antagonists (e.g. conivaptan, tolvaptain) used to treat SIADH. V2 ADH receptor antagonists (e.g. conivaptan, tolvaptain) are used to treat SIADH and promote free water excretion

Question 30

What tetracycline can also be used for SIADH?

Answer 30

Demeclocycline, though ‘vaptans’ are 1st-line.

Question 31

What are the adverse effects of V2 antagonists?

Answer 31

May cause hypernatremia or central pontine myelinolysis by causing too much free water excretion by the kidney, CPM is irreversible.