SM151 Adrenal Cortex Pathophysiology Flashcards
What are the 3 types of steroids made in the cortex and where are they made?
Glucocorticoids (C-21) - zona fasciculata
Mineralcorticoids (C-21) - zona glomerulosa Androgens (C-19) - zona reticularis
What precursor protein does ACTH come from? What tissues is it expressed in? What else is made from this precursor?
POMC cascade. Also produces a-MSH (responsible for pigmentation).
ACTH is expressed in anterior pituitary and skin, MSH is expressed in skin only.
How do you test for ACTH insufficiency?
ACTH stimulation test (should see rise in cortisol production)
Insulin tolerance test (causes release of ACTH and GH)
CRH stimulation test (hypothalamic hormone that releases ACTH)
How do you test for aldosterone insufficiency?
Administer low salt diet, upright posture, or diuretic and check for increased production of aldosterone
How do you test for an excess ACTH state?
Dexamethasone suppression test: normally endogenous production is suppressed to almost 0 with dex administration.
How do you test for an excess aldosterone state?
Give high salt diet or supine posture and check for decreased production of aldosterone
Effects of cortisol?
BBIIG mnemonic
Blood pressure (up-regulates alpha receptors) Bone formation is stopped Immunosuppression/anti-inflammation Insulin resistance (diabetogenic) Gluconeogenesis, lipolysis, proteolysis
Effects of mineralocorticoids?
Na+ retention, K+ excretion, H+ excretion
Effects of androgens?
Hair growth, temporal balding, sebum production (acne), anabolism (more muscle mass), penile/clitoral growth, erythropoiesis, anti-estrogen effects
Etiologies of adrenal insufficiency?
Primary (adrenal problem): autoimmune (Addison’s), infectious/granuloma (TB), hemorrhage, metastases, ACTH-R or MRAP mutations
Secondary (ACTH problem): pituitary dx (tumor, granuloma, autoimmune, hemorrhage)
Congenital adrenal hyperplasia (mixed hypo- and hyper- syndrome). Defect in the cortisol synthesis pathway. Get a build up of whatever comes before the enzyme that is mutated
Clinical features of cortisol insufficiency?
Anorexia, weakness, hypoglycemia, hyponatremia, hyperkalemia, dehydration, death if let untreated
Clinical features of aldosterone insufficiency?
Hyponatremia, hyperkalemia, dehydration, hypotension
Clinical features of androgen insufficiency?
Axillary and pubic hair loss, loss of libido (women only - no testes supplementation)
Clinical features of ACTH excess?
Primary: pigmentation, secondary: no pigmentation
What do you see in isolated hypoaldosteronism? What is the most common cause of this?
Cortisol levels are normal, aldosterone is low Hyporeninemic hypoaldosteronism (complication of diabetes)
Clinical features of glucocorticoid excess/Cushing’s syndrome?
Weight gain, redistribution of fat to face and trunk, buffalo hump, moon facies
HTN: Na+/fluid retention, hypokalemia
Hyperglycemia, (insulin resistance)
Derm: ruddy complexion, purple striae
Osteoporosis, amenorrhea, immune suppression
Clinical features of androgen excess?
Hirsutism, acne, temporal balding
Ruddy complexion, purple striae
Increased RBC mass
Irregular menstruation
Etiologies of Cushing’s syndrome?
Exogenous steroids (most common)
Pituitary adenoma (this is Cushing’s disease)
Adrenal tumor
Nodular adrenal hyperplasia
Ectopic ACTH syndrome (small cell carcinoma)
Etiologies of Cushing’s syndrome?
Pituitary adenoma (this is Cushing’s disease)
Adrenal tumor
Nodular adrenal hyperplasia
Ectopic ACTH syndrome (small cell carcinoma)
Exogenous steroid administration (most common)
What are the hallmarks of adrenal insufficiency vs. excess?
Insufficiency: non-stimulability
Excess: non-suppressibility
How do people with Cushing’s disease test on dexamethasone suppression?
Start at higher cortisol levels than normal. Can be suppressed, but require higher levels of dex than normal.
Note: ectopic ACTH-tumors and cortisol tumors are never suppressed by dex suppression
How do people with Cushing’s disease test on dexamethasone suppression?
Start at higher cortisol levels than normal. Can be suppressed, but require higher levels of dex than normal.
Etiologies of mineralocorticoid excess?
Primary: aldosterone-producing adenoma, bilateral nodular hyperplasia
Secondary: renin overproduction due to hypovolemia
Etiologies of mineralocorticoid excess?
Primary: aldosterone-producing adenoma, bilateral nodular hyperplasia (aldosterone synthase or KCNJ5 mutations)
Secondary: renin overproduction due to hypovolemia
How can you distinguish primary and secondary mineralocorticoid excess?
Primary: renin low, aldosterone high. Renin can’t be stimulated (by Na+/volume depletion or standing up). Aldosterone not suppressible (by Na+ loading or high volume)
Secondary: renin and aldosterone both high, both suppressible
How can you distinguish primary and secondary mineralocorticoid excess?
Primary: renin low, aldosterone high. Renin can’t be stimulated (by Na+/volume depletion or standing up). Aldosterone not suppressible (by Na+ loading)
Secondary: renin and aldosterone both high. Renin and aldosterone both suppressible (by Na+ loading or high volume)
Clinical signs of congenital adrenal hyperlasia?
Ambiguous genitalia, short stature, tomboyish, hirsutism, amenorrhea
