EXAM #2: CUSHING SYNDROME Flashcards
What is the most common cause of Cushing’s Syndrome?
Iatrogenic use of oral glucocorticoids for a non-endocrine illness e.g.
- COPD
- RA
How is Iatrogenic Cushing’s Syndrome categorized?
ACTH-independent
What causes ACTH-dependent Cushing’s Syndrome?
1) Pituitary tumor (adenoma) or “Cushing’s Disease”
2) Ectopic ACTH (e.g. small cell lung cancer)
3) Ectopic CRH
How does the clinical presentation of Cushing’s from ectopic ACTH differ from pituitary adenoma or iatrogenic?
1) Rapid onset
2) Hirsutism
3) Hyperpigmentation
*Generally, the presentation is more rapid and dramatic
What is the most common cause of ACTH-independent Cushing’s (non-iatrogenic)?
Adrenal adenoma overproducing cortisol
*Could be a carcinoma, which is usually large/irregular–poor prognosis
What are the steps to diagnosing Cushing’s Syndrome?
1) Confirm hypercortisolemia
2) Determine subtype
3) Localize source
In what setting are patients evaluated for Cushing’s Syndrome?
Outpatient–need to avoid stress of hospitalization
How is hypercortisolemia confirmed?
1) 24 hour urine sample
2) 11 pm salivary or serum cortisol (should be low)
3) Low dose dexamethasone suppression test (DST)
What is the mechanism of the DST?
- Dexamethasone should suppress ACTH
- Sample collected following day should normally show low cortisol
In a 24 hour urine sample, what is normal cortisol and what is likely to be Cushing’s?
- Less than 50mcg = normal*****
- Greater than 150 mcg= Cushing’s
*Note that a normal test does NOT exclude the diganosis; it must be repeated numerous times
What is Pseudo-Cushing’s Syndrome?
Elevated cortisol from condition/illness that activates the HPA-axis
- E.g. depression, trauma…etc.
What should you do if you suspect Pseudo-Cushing?
1) Delay testing
2) Avoid 24 hour urine and do a DST instead
What values for a midnight salivary cortisol level would indicate a normal test? Positive for Cushing’s?
- Normal= less than 5 mcg/dL
- Cushing’s= greater than 7.5 mcg/dL
What values for a DST would indicate a normal test? Positive for Cushing’s?
- Normal= less than 2 mcg/dL
- Cushing’s= greater than 10 mcg/dL
If 24 hr urine is greater than 300 mcg/dL, how does this impact your decision making?
No need for further confirmatory testing
*If 50-150, need additional
You order an ACTH test and it comes back high. How would you image the pituitary, hypothalamus, adrenal glands, and chest to determine etiology?
Brain= MRI Adrenal= Abdominal CT Ectopic= Chest CT
How is an adrenocortical adenoma treated?
- Surgical removal (6cm is the cut off for laprascopic vs. open laparotomy)
- Follow-up with steroid taper*
*Atrophy of contralateral adrenal gland will require hormone replacement for some time.
How is an adrenocortical carcinoma treated?
Symptomatic relief with drugs/chemo/rad/surgery
How can you differentiate between a pituitary adenoma and ectopic ACTH if brain MRI is normal or equivocal?
1) IPSS= inferior petrosal sinus sampling
2) High dose DST
What are the expected results of high dose DST for pituitary adenoma and ectopic ACTH?
Pituitary= partial suppression
Ectopic= no suppression
What is the significance of the petrosal sinus?
Pituitary gland drains into the petrosal sinus
What levels are being compared in IPSS? What are the steps of the test?
Sinus ACTH levels and peripheral ACTH
*CRH is given; a 2:1 ratio of sinus to periphery= pituitary source
When is pituitary radiation indicated for a pituitary adenoma?
1) TSS failure
2) Recurrence
3) Residual disease
In the setting of Cushing’s Disease, what procedure is indicated with failed TSS and pituitary radiation?
Bilateral adrenalectomy
What three drugs are used to reduce cortisol levels for symptomatic relief of Cushing’s Disease?
1) Aminoglutethimide
2) Ketoconazole
3) Mitotane
How is ectopic ACTH treated?
1) Surgical resection
2) Chemo/rad
3) Bilateral adrenalectomy
4) Meds
