Glucocorticoids Flashcards
What are the different zones of the adrenal cortex and what do each of them secrete?
Glomerulosa: aldosterone
Fasciculata: cortisol
Reticularis: testosterone, estrogen, cortisol
Describe the pathway of cortisol release.
The hypothalamus releases CRH –> CRH causes anterior pituitary to release ACTH –> ACTH causes the adrenal cortex to release cortisol.
What are the metabolic effects of cortisol? What is cortisol’s main purpose?
- Increase gluconeogenesis
- Release amino acids via muscle catabolism
- Inhibit peripheral glucose uptake
- Stimulate lipolysis.
All these things serve to maintain an adequate supply of glucose to the brain.
Describe the anti-inflammatory and immunosuppressive effects of glucocorticoids.
Upregulation of anti-inflammatory and downregulation of pro-inflammatory proteins.
Decreased leukocyte presence and function. Inhibition of lymphocyte mitosis.
How is cortisol prevented from binding to mineralocorticoid receptors?
Cortisol gets converted to cortisone by 11beta-HSD2.
What are 2 things that stimulate aldosterone release?
- Angiotensin II
2. High ECF potassium levels
Which corticosteroid has the longest duration of action?
Dexamethasone
Which corticosteroid has the strongest relative anti-inflammatory activity?
Dexamethasone
Which corticosteroid has the strongest relative mineralocorticoid activity?
Fludrocortisone
How can you distinguish primary and secondary adrenocortical insufficiencies?
Primary: high ACTH (due to anatomic destruction of adrenal gland) -leads to skin discoloration.
Secondary: low ACTH (due to decreased pituitary function) -cortisol is primarily affected (ACTH has minimal effect on aldosterone)
What are the signs/symptoms of an Adrenal Crisis (acute adrenal insufficiency)?
-Mineralocorticoid deficiency –> Hyperkalemia, hyponatremia, increased ADH, hypotension, nausea/vomiting
How do you treat Chronic Primary Adrenal Insufficiency?
Replace glucocorticoids with Hydrocortisone and mineralocorticoids with Fludrocortisone.
If a minor febrile illness occurs, increase the glucocorticoid dose.
In an emergency, inject dexamethasone.
How do you diagnose Cushing’s Syndrome?
Use a low-dose dexamethasone test. This will cause a decrease in cortisol release via negative feedback in a normal patient. Cushing’s patients will still have elevated cortisol the next morning.
If surgery is not an option, what treatments are available for Cushing’s Syndrome?
Aminoglutethimide, Ketoconazole, Mitotane, Metyrapone, Mifepristone
What does Aminoglutethimide do?
Blocks conversion of cholesterol to pregnenolone.
