Adrenal Steroids Flashcards
What zones of the adrenal correspond the most with the production of aldosterone, cortisol, and androgens?
Aldosterone = zona glomerulosa Cortisol = zona fasciculata Androgens = zona reticularis
Describe the mechanism of glucocorticoids
- binds to cytosolic receptor, which then is internalized, activated, and allows release of heat shock protein
- receptor then dimerizes, enters nucleus, and affects gene transcription
What are the metabolic effects of glucocorticoids?
- increases gluconeogenesis
- releases amino acids through muscle catabolism
- inhibits peripheral glucose uptake
- stimulates lipolysis
- main goal: maintain adequate glucose for the brain
What are the anti-inflammatory effects of glucocorticoids?
- upregulation of anti-inflammatory proteins
- downregulation of pro-inflammatory proteins
- decrease of leukocyte presence and function at sites of inflammation
What are the effects of mineralocorticoids (aldosterone and deoxycorticosterone)?
- increases reabsorption of sodium
- increases reabsorption of water and expands extracellular fluid volume
- increases renal excretion of potassium
What enzyme is present in tissues changes cortisol to a product with reduced affinity for the aldosterone receptor, and what is the name of the product?
- cortisol is converted to cortisone by 11B-hydroxysteroid dehydrogenase type 2
- cortisone has a low affinity for the aldo receptor, allowing aldo to bind even though there is much more cortisone around
Which synthetic corticosteroid has the highest activity at the mineralocorticoid receptor?
fludrocortisone
Which synthetic corticosteroid has the highest anti-inflammatory activity?
dexamethasone
What is the difference between primary and secondary adrenocortical insufficiency?
- primary: anatomic destruction of adrenal gland (decreased cortisol but increased ACTH)
- secondary: decreased pituitary production of ACTH (decreased cortisol and decreased ACTH)
What are some causes of primary adrenocortical insufficiency?
- autoimmune adrenalitis (Addison’s)
- infection (TB, fungal, CMV, HIV)
- hemorrhage after menigococcal sepsis (Waterhouse-Friderichsen syndrome)
- metastatic tumor
- infiltrates (amyloid, hemochromatosis)
- adrenoleukodystrophies
What are the differentiating factors when comparing primary and secondary adrenal insufficiency?
- secondary AI has - no hyperpigmentation (ACTH levels not elevated), near normal aldosterone levels
What is the first step in testing suspected adrenal insufficiency?
- cosyntropin test (a synthetic ACTH)
- if cortisol does not increase, diagnosis of adrenal insufficiency is made
When treating a patient with chronic primary adrenal insufficiency, what are some guidelines/goals you want to follow?
- physiologic replacement (cortisol has a diurnal variation), so two daily doses of hydrocortisone with more in the morning
- with minor illness, increase glucocorticoid dose 2-3x
- for extremely stressful situations, increase doses even more (have prefilled syringe of steroids on hand for emergencies)
What are some signs and symptoms of Cushing syndrome (glucocorticoid excess)?
- weight gain (in trunk, thinning of arms)
- moon face, buffalo hump, red abdominal striae
- hypertension
- psych changes
- infections
etc etc etc
What test is used to diagnose Cushing syndrome?
- low dose dexamethasone administration, and if cortisol is not suppressed, this indicates Cushing syndrome, so then evaluate ACTH
- if ACTH is high, process is ACTH-dependent
- if ACTH is low, process is ACTH-independent
- if ACTH-dependent, administer high dose dexamethasone which would slow down a pituitary cause but would not affect an ectopic cause
