EXAM #2: CUSHING SYNDROME

Question 1

What is the most common cause of Cushing’s Syndrome?

Answer 1

Iatrogenic use of oral glucocorticoids for a non-endocrine illness e.g.

• COPD
• RA

Question 2

How is Iatrogenic Cushing’s Syndrome categorized?

Answer 2

ACTH-independent

Question 3

What causes ACTH-dependent Cushing’s Syndrome?

Answer 3

1) Pituitary tumor (adenoma) or “Cushing’s Disease”
2) Ectopic ACTH (e.g. small cell lung cancer)
3) Ectopic CRH

Question 4

How does the clinical presentation of Cushing’s from ectopic ACTH differ from pituitary adenoma or iatrogenic?

Answer 4

1) Rapid onset
2) Hirsutism
3) Hyperpigmentation

*Generally, the presentation is more rapid and dramatic

Question 5

What is the most common cause of ACTH-independent Cushing’s (non-iatrogenic)?

Answer 5

Adrenal adenoma overproducing cortisol

*Could be a carcinoma, which is usually large/irregular–poor prognosis

Question 6

What are the steps to diagnosing Cushing’s Syndrome?

Answer 6

1) Confirm hypercortisolemia
2) Determine subtype
3) Localize source

Question 7

In what setting are patients evaluated for Cushing’s Syndrome?

Answer 7

Outpatient–need to avoid stress of hospitalization

Question 8

How is hypercortisolemia confirmed?

Answer 8

1) 24 hour urine sample
2) 11 pm salivary or serum cortisol (should be low)
3) Low dose dexamethasone suppression test (DST)

Question 9

What is the mechanism of the DST?

Answer 9

• Dexamethasone should suppress ACTH

- Sample collected following day should normally show low cortisol

Question 10

In a 24 hour urine sample, what is normal cortisol and what is likely to be Cushing’s?

Answer 10

• 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

Question 11

What is Pseudo-Cushing’s Syndrome?

Answer 11

Elevated cortisol from condition/illness that activates the HPA-axis
- E.g. depression, trauma…etc.

Question 12

What should you do if you suspect Pseudo-Cushing?

Answer 12

1) Delay testing

2) Avoid 24 hour urine and do a DST instead

Question 13

What values for a midnight salivary cortisol level would indicate a normal test? Positive for Cushing’s?

Answer 13

• Normal= less than 5 mcg/dL

- Cushing’s= greater than 7.5 mcg/dL

Question 14

What values for a DST would indicate a normal test? Positive for Cushing’s?

Answer 14

• Normal= less than 2 mcg/dL

- Cushing’s= greater than 10 mcg/dL

Question 15

If 24 hr urine is greater than 300 mcg/dL, how does this impact your decision making?

Answer 15

No need for further confirmatory testing

*If 50-150, need additional

Question 16

You order an ACTH test and it comes back high. How would you image the pituitary, hypothalamus, adrenal glands, and chest to determine etiology?

Answer 16

Brain= MRI 
Adrenal= Abdominal CT 
Ectopic= Chest CT

Question 17

How is an adrenocortical adenoma treated?

Answer 17

• 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.

Question 18

How is an adrenocortical carcinoma treated?

Answer 18

Symptomatic relief with drugs/chemo/rad/surgery

Question 19

How can you differentiate between a pituitary adenoma and ectopic ACTH if brain MRI is normal or equivocal?

Answer 19

1) IPSS= inferior petrosal sinus sampling

2) High dose DST

Question 20

What are the expected results of high dose DST for pituitary adenoma and ectopic ACTH?

Answer 20

Pituitary= partial suppression

Ectopic= no suppression

Question 21

What is the significance of the petrosal sinus?

Answer 21

Pituitary gland drains into the petrosal sinus

Question 22

What levels are being compared in IPSS? What are the steps of the test?

Answer 22

Sinus ACTH levels and peripheral ACTH

*CRH is given; a 2:1 ratio of sinus to periphery= pituitary source

Question 23

When is pituitary radiation indicated for a pituitary adenoma?

Answer 23

1) TSS failure
2) Recurrence
3) Residual disease

Question 24

In the setting of Cushing’s Disease, what procedure is indicated with failed TSS and pituitary radiation?

Answer 24

Bilateral adrenalectomy

Question 25

What three drugs are used to reduce cortisol levels for symptomatic relief of Cushing’s Disease?

Answer 25

1) Aminoglutethimide
2) Ketoconazole
3) Mitotane

Question 26

How is ectopic ACTH treated?

Answer 26

1) Surgical resection
2) Chemo/rad
3) Bilateral adrenalectomy
4) Meds