Adrenal Pathophysiology Flashcards
What are three main hallmarks of Cushing’s syndrome?
- Loss of diurnal variation of cortisol secretion
- Autonomy from “central” ACTH control (loss of response to feedback inhibition)
- Excess cortisol secretion
What are two broad categories of of Cushing’s syndrome?
ACTH-dependent and ACTH independent
What is most common cause os Cushing’s Syndrome?
Exogenous use of glucocorticoids
Next is Cushing’s disease (ACTH producing pituitary adenoma)
What are basic metabolic derangements due to excess corticosteroids? (3)
Stimulates gluconeogensis: hyperglycemia
Increases lipogenesis, insulin resistance: increased FFA
Increased gluconeogenesis results in catabolism of proteins
Signs and symptoms of Cushing’s Syndrome: Effects of fat metabolism (4)
Dewlap (neck)/round face
Supraclavicular fat pads
Buffalo hump
Skinny limbs with big stomach
Other effects of cortisol excess: immunity, hematopoetic, eyes and musculoskeletal (3)
Impaired immunity
Hypercoagulability
Cataract formation
MS: proximal myopathy, osteoperosis, redistribution of body fat
What are cardiovascular effects of cortisol excess? (3)
Hypertension, cardiomyopathy, increased thromboembolic events (atherosclerosis, strokes, PE, etc)
What are dermatological effects of cortisol excess? (6)
Thin skin Easy bruisability Striae Acne Hyperpigmentation Hirsutism
What are CNS effects of cortisol excess? (2)
Pyschiatric disturbances
Cognition/psychosocial functioning
What are mineralocorticoid and androgen effects of excess cortisol? (4)
HTN and hypokalemia (hk more associated with ectopic ACTH production)
Testosterone increased in females
Abnormal menses
Marked virilization worrisome for malignant adrenal tumor
ACTH-dependent Cushing’s is characterized by ______
Bilateral adrenal hyperplasia
What hormone levels do we observe in ACTH-independent Cushing’s? Why?
High cortisol; low ACTH
This is because cortisol is providing negative feedback on ACTH
How do you measure loss of diurnal variation of cortisol secretion?
Late night salivary cortisol: measures free cortisol and can be easily collected at home
Dexamethasone suppression: what it does….why do you do it?
Exogenous dexamethasone substitutes for ACTH in suppressing ACTH release
Should have low cortisol….if not, it indicates inappropriate cortisol secretion
24 hour urinary free cortisol: what indicates Cushing’s?
If cortisol > 3x upper limit of normal
How do you localize source of problem?
Look at plasma ACTH– if low, Cushing’s is from adrenal source….if high, Cushing’s from pituitary or ectopic ACTH source….also if exogenous, ACTH is low
Treatment of Cushing’s: Unilateral adrenal adenoma
Adrenalectomy
Treatment for pituitary adenoma
Hypophysectomy
How long do symptoms of hypercortisolism take to resolve?
Up to 12 months
Not all sequelae completely resolve (especially psych ones0
Primary adrenal failure (Addison’s disease): main features (4)
90% of cortex destroyed before presentation
Elevated ACTH
Usually indolent course
Can lose adrenal hormones
Symptoms of primary adrenal failure are consistent with ____ and _____ deficiency, and include _____ (3)
Mineralocorticoid and glucocorticoid deficiency
Hyponatremia, hyperkalmeia, hypotension
Clinical characteristics of primary adrenal failure: (6)
Hyperpigmentation Weight loss Muscle/joint pains Fatigue Nausea, abdominal pain Hypoglycemia (reduced gluconeogenesis)
Etiologies of Addison’s Disease (5)
Autoimmune destruction (60%) Infectious: TB, fungus, HIV Bilateral hemorrhage/infarct Metastatic cancer Drugs: aminoglutethimide, ketoconazole, etomidate, rifampin, phenytoin
Diagnosis of Addison’s disease (2)
Early AM cortisol/ACTH concentration: look for low cortisol and high ACTH
Cosyntropin stimulation testing: look at IM injection of synthetic ACTH and measure cortisol
What is an adrenal crisis? What are the clinical characteristics? (big list)
Acute deficiency in cortisol/mineralocorticoids
Hypotension, shock, fatigue, weakness, malaise, fever, lethargy, abdominal pain/nausea/vomiting, anorexia, hypoglycemia
Etiologies of Adrenal Crisis (4)
New primary adrenal failure
Known adrenal insufficiency with acute illness or under-replacement of meds
Acute withdrawal of high dose glucocorticoids
Pituitary apoplexy
Treatment of Adrenal Crisis (3)
Rehydration: saline IV and electrolytes
Dexamethasone
Monitor BP
Autoimmune adrenalitis are associated with _____
Other autoimmune disorders– polyglandular syndromes
Type 1: hypoparathyroidism, candidiasis, primary hypogonadism
Type 2: T1DM, autimmune thyroiditis, vitiligo, hypogonadism
Primary Hyperaldosteronism: Findings (5)
Mineralocorticoid excess:
Hypertension, hypokalemia, hypernatremia, metabolic alkalosis, muscle weakness
Who should be screened for primary hyperaldosteronism? (4)
Pts under 30 with HTN, no obesity or family history
Pts with unexplained hypokalemia and hypertension
Pts with resistant HTN
Ptts with adrenal incidentaloma/HTN
Dx of Primary Hyperaldosteronism
Look at aldosterone: renin ratio
> 20 suggestive, but not diagnostic
What do you do for hyperaldosteronism patients over 35? Why?
Sample adrenal vein prior to surgery– differentiate between unilateral adenoma and bilateral adrenal hyperplasia
How do you distinguish unilateral adenoma vs. bilateral hyperplasia?
Lateral disease has aldosterone concentration 4x greater than the contralateral side
How do you treat unilateral adenoma vs. bilateral hyperplasia?
Unilateral aldosterone-secreting adenoma: surgical resection
Bilateral adrenal hyperplasia: mineralocorticoid antagonist
