Hypothalamic & Pituitary Flashcards
What is the MOA of growth hormone receptor, what does it lead to and where does growth hormone comes from?
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
What are the effects of IGF1 on the body?
- 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
What are the 3 clinical uses of exogenous GH?
- 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).
What can be another potential cause of short stature other than GH deficiency?
IGF1 deficiency or a defective IGF1 receptor
What is the name of recombinant IGF1?
Mecasermin
When is Mecasermin used?
For patients that have resistance to GH therapy, Mecasermin (recombinant IGF-1) can be used instead
What does GH secreting pituitary adenomas can cause and how that can be treated?
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
What is the MOA and indications for octeotride
Somatostatin analog, inhibits GH secretion so it can be used to treat gigantism and acromegaly
What are the functions of somatostatin in the body?
Reduces intestinal and pancreatic secretion, slows down GI motility, and inhibits some pituitary hormones
What other conditions can be treated with octeotride?
Octreotide treats VIPoma (neuroendocrine tumor secreting Vasoactive Intestinal Peptide) and Carcinoid tumor (ileal tumor with hepatic metastasis secreting serotonin).
What 3 other endocrine tumors can be treated with octeotride?
Insulinoma, glucagonoma and gastronome (Zollinger Ellison syndrome)
How does glucagonoma presents as?
Presents as weight loss and a necrolytic migratory erythema
How does octeotride treat symptoms of portal hypertension?
Octreotide can control bleeding of esophageal varices by decreasing portal blood flow and variceal pressure (mechanism is poorly understood).
What are the AE of octeotride?
Octeotride decrease pancreas and gall bladder contractility so it can cause steatorrhea along with GI symptoms.
Name D2 receptor agonists
Cabergoline and Bromocriptine
What are D2 receptor agonists used for?
Inhibit GH secretion and prolactin secretion from the pituitary, can be used for a variety of conditions
Name a direct GH antagonist
Pegvisomant
What are its effects and side effects?
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
Where is ADH released from?
Posterior pituitary
MOA and effects of ADH
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)
Where are extra V2 receptors found?
Extra V2 receptors are found on the vascular endothelium and cause the secretion of von Willebrand Factor and Factor VIII
Explain diabetes insipidus
Patient cannot concentrate their urine, either because they cannot produce ADH (central DI) or because they cannot respond to ADH (nephrogenic DI).
What is the most common cause of nephrogenic DI
Lithium, present in bipolar disorder drugs
What drugs can we use to treat nephrogenic DI
Thiazides and amiloride, caution thiazides increase lithium levels by decreasing its clearence
How does NSAIDs treat nephrogenic DI?
NSAIDs (e.g. indomethacin) treat nephrogenic DI by decreasing the production of prostaglandins that antagonize the effects of ADH
What drug can be used in central DI?
Desmopressin, its an exogenous ADH
What other condition can be treated with desmopressin?
Nocturnal urination (bed wetting)
What is the role of desmopressin in treating portal hypertension?
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.
How do we treat SIADH?
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
What tetracycline can also be used for SIADH?
Demeclocycline, though ‘vaptans’ are 1st-line.
What are the adverse effects of V2 antagonists?
May cause hypernatremia or central pontine myelinolysis by causing too much free water excretion by the kidney, CPM is irreversible.
