Cushing's Disease Flashcards
what is Cushing’s syndrome
- any excess cortisol state
what is Cushing’s disease
- Cushing’s syndrome due to ACTH producing pituitary adenoma
causes of Cushing’s syndrome
- Cushing’s disease (pituitary adenoma)
- ectopic ACTH production
- adrenal cortical adenoma
Cushing’s syndrome due to pituitary ACTH producing tumor (Cushing’s disease)
hormone levels:
CRH:
ACTH:
cortisol:
size of the adrenal glands
treatment
hormone levels:
CRH: low (negative feedback)
ACTH: high
cortisol: high
- hyperplastic
- transphenoidal surgery
- block ACTH secretion by the tumor or block steroid synthesis
Cushing’s syndrome due to adrenal tumor making cortisol
hormone levels:
CRH:
ACTH:
cortisol:
treatment (successful for/not)
hormone levels:
CRH: low
ACTH: low
cortisol: high
- surgery (successful for adenomas/not for carcinoma (cancer usually too invasive)
- block steroid biosynthesis
Cushing’s syndrome due to ectopic ACTH-producing tumor
hormone levels:
CRH:
ACTH:
cortisol:
what will pituitary ACTH levels be
treatment
- hormone levels:
CRH: low
ACTH: high
cortisol: high - pituitary ACTH levels will be low
- find malignancy and remove (surgery, radiation)
- block steroid biosynthesis
glucocorticoid excess features of Cushing’s syndrome
- muscle wasting
- easy bruising or poor wound healing
- osteoporosis or fractures
- central obesity
- glucose intolerance, hyperglycemia
- psychiatric disturbances
what symptoms are present in most cases of cortisol excess
- psychiatric disturbances
- metabolic alkalosis
mineralocorticoid excess symptoms in Cushing’s syndrome
- salt retention, hypertension, edema
- hypokalemia
- metabolic alkalosis
- excess cortisol cross-reacts with aldosterone/androgen receptors (mineralocorticoid) producing these symptoms
androgen excess symptoms in Cushing’s syndrome
why do you get androgen symptoms
- hirsutism, acne
- amenorrhea
- excess cortisol cross-reacts with aldosterone/androgen receptors producing these symptoms
steps in evaluating Cushing’s syndrome
- confirm hypercortisolism
2. localize source by measuring ACTH
how do you confirm hypercortisolism
- 24 hour urinary free cortisol
- low-dose demethasone suppression test
- salivary free cortisol
normally demethasone suppression test suppresses cortisol to what level
< 1.8 mcg/dL
watch out for demethasone suppression test in patients taking what
- estrogen containing birth control
in localizing the source, ACTH will be high when
ACTH will be low when
- ACTH-dependent Cushing’s
- ACTH-independent Cushing’s
if ACTH dependent, must differentiate between
how do you do this
which will respond
how much do you give
level to know it responds
- pituitary and ectopic ACTH
- high dose dexamethasone suppression test
- inferior petrosal sinus sampling test
- pituitary ACTH will respond and decrease
- 8 mg dexamethasone
- cortisol suppression by 50% or < 5 mcg/L
if ACTH independent, what is the source
what do you do
usual cause (benign/malignant)
size
- adrenal gland
- adrenal imaging
- adrenal adenoma (benign)
- contralateral side is atrophic due to decreased ACTH
MOA of mifepristone in treating hypercortisolism
- inhibits glucocorticoid receptors
MOA of spironolactone in treating hypercortisolism
- inhibits mineralocorticoid receptors
MOA of ketoconazole in treating hypercortisolism
importance of this drug
- inhibits steroidogenesis
- rapid onset of action
MOA of aminoglutethimide in treating hypercortisolism
- inhibits steroidogenesis
MOA of Cabergoline and Pasireotide in treating hypercortisolism
- decreased ACTH secretion by tumor
factors determining the severity of glucocorticoids causing Cushing’s syndrome
- effective dose (lowest dose you can give)
- how long the drug acts
- duration of treatment (shorter is better)
- tissue distribution (stay localized if you can with topical)
- AVOID ANTI-INFLAM AND IMMUNOSUPPRESANT DRUGS IF YOU CAN
between hydrocortisone, prednisone, and dexamethasone, which has the longest half life
- dexamethasone
