Common Conditions: Cushing's Disease (and Addisons, can't avoid it)

[liveonearth]

ETIOLOGY
excessive glucocorticoid steroids from the adrenal cortex
mbdt anterior pituatary neoplasm
exogenous corticosteroids

SYMPTOMS
obesity esp in upper thorax and face
"moon face", accelerated hair growth
HTN

fat deposition over upper thoracic spine creating "buffalo hump"
purple striae on abdomen and axillae

OSSEOUS CHANGES
visible on X-ray
osteoposis, thinned cortices, low density
vertebrae have biconcave endplates

osteonecrosis of femoral and humeral head, distal femora & talus
ischemic vert bodies may collapse following steroid meds
recognized by "intravertebral vacuum cleft sign"



here's a teenager with the typical Cushing's body shape:

and adults, notice the purple striations:


--pets can have it too




CUSHING'S SYNDROME
excess cortisol from any cause
95% show elevation in urine cortisol
hyperglycemia (cortisol-->gluconeogenesis and glycogenolysis)
negative nitrogen balance-->osteoporosis, muscle wasting, reduced fibrogenesis, thin skin, easy bruising

salt and water retention-->tendency to CHF with hypokalemia
reduced immune response-->more infx
abnormal fat metabolism-->central deposition, loss in extremities
suppression of ACTH
NEUTROPHILIA
mental effects: depression, confusion, occ frank psychosis
one common etio: exogenous glucocorticoids

ADRENOCORTICOTROPIC HORMONE = ACTH
test this to eval anterior pituitary function
affords greatest insight into cause of Cushing's or Addison's
normal levels show diurnal variation
am: 15-100 pg/ml
pm: < 50 pg/ml
low in Cushing's syndrome and w/ hypopituitary
high in Cushing's dz and Addison's dz
INCREASE ETIO: Addisons = primary adrenal insufficiency, adrenogenital syndrome = congential adrenal hypoplasia (CAH);, Cushing's DZ (pituitary dependent adrenal hyperplasia, ectopic ACTH syndrome (tumor in lung, pancreas, thymus or ovary), stress
DECREASE ETIO: Cushing's syndrome (exogenous cortisol intake, overproduction, any hypercortisolemia), adrenal adenoma or carcinoma, exogenous steroid administration, hypotituitarism-->secondary adrenal insufficiency

DEXAMETHASONE SUPPRESSION TEST
used to evaluate pts presenting with glucocorticosteroid excess
many other medical uses:
anti-inflammatory (for RA), immunosuppressant in autoimmune dz, multiple myeloma tx,
in preg to promote fetal pulmonary maturation, for high altitude cerebral edema,
for side effects of chemo, in cases of CA compression of spinal cord, and lots more
--20-30 times more potent than hydrocortisone and 4-5 times prednisone
--a synthetic steroid
--suppresses ACTH secretion in normal people
--normally results in reduced stimulation to adrenal glands
--plasma cortisol levels should drop 50% (or >)
--this feedback system does not function properly in pts with Cushing's syndrome (cortisol production is not suppressed)
--pts with Cushing's dz relatively resistant to suppression: high dose will suppress
--imp in dx of adrenal hyperfx: Cushing's
--helps distinguish cause of hyperfunction: pituitary or ectopic ACTH?
--DS test based on pituitary ACTH secretion, dependence on plasma cortisol feedback mechanism
--increased plasma cortisol level suppress ACTH secretion
--decreased cortisol levels stimulate ACTH secretion
--HIGH DOSE DEX results in cases of Cushing's syndrome:
----if dt bilateral adrenal hyperplasia-->50% reduction in plasma cort.
----dt adrenal adenoma or CA, ectopic ACTH producing tumor or exogenous glucocorticoids-->no change in cortisol
----Cushing's dz + high dose dex --> 50% decrease in plasma cort or urinary free cortisol

SCREENING
use 24 hour free cortisol

Cushings: high cortisol, low ACTH
Addisons: low cortisol, high ACTH

Basic Metabolic Profile
Cushings: high chloride, glucose, sodium; low potassium and calcium
Addisons: low chloride, glucose, sodium; high potassium and calcium

Cardiology from Milner notes:
Cushings: high dopamine, NE, epi-->tachcardia
Addisons: bradycardia, conduction delays (1st and 2nd degree blocks)

SOURCES:
Stecher DI notes
Milner Cardio notes