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.
What does ketoconazole do?
It is a potent, nonselective inhibitor of adrenal and gonadal steroid synthesis.
What does mitotane do?
It has a nonselective cytotoxic action on the adrenal cortex. Bad side effect profile.
How does metyrapone work?
Inhibits 11-hydroxylation, interfering with cortisol and corticosterone synthesis.
What is the metyrapone test?
It tests anterior pituitary function. The metyrapone results in decreased cortisol and corticosterone synthesis, which causes an increase in ACTH (in a normal patient) and 11-deoxycortisol (the precursor to cortisol).
How does mifepristone work?
It’s a glucocorticoid receptor antagonist.
What is the treatment plan for primary aldosteronism?
Surgery: unilateral adenoma
Spironolactone, eplerenone: bilateral adrenal hyperplasia
Describe what is going on in 21-hydroxylase deficiency (Congenital Adrenal Hyperplasia)
The absence of this enzyme shunts away from aldosterone and cortisol production to androgen production.
The decreased cortisol increases ACTH and the increased androgen causes hirsutism and virilization.
What is something very important to consider when ending steroid therapy?
NEVER stop abruptly. Always taper off.
How is 21-hydroxylase deficiency diagnosed?
Increased response of plasma 17-OH-Progesterone to ACTH stimulation (Cosyntropin stimulation test)
How is 21-hydroxylase deficiency treated?
Dexamethasone, prednisone or hydrocortisone.
If salt-wasting, add fludrocortisone.
