Internal Medicine

0521779407-C04 CUNY1086/Karliner 0 521 77940 7 June 14, 2007 20:37

Cushing’s Syndrome 437

May be normal or elevated in pituitary corticotrophic ade-

noma

Normal to marked elevation in ectopic ACTH

■High-dose (8 mg) dexamethasone suppression test: useful to distin-

guish between pituitary vs. ectopic source of ACTH in established

case of ACTH-dependent CS; suppression of ACTH, serum and 24-

hr urine cortisol in pituitary adenoma; may be given as a 2-day test

or as an overnight test

■Inferior petrosal sinus (IPS) sampling:

➣In ACTH-dependent CS, pituitary vs. ectopic source of ACTH

➣Not useful in distinguishing CS from normal or pseudo-Cushing

or normal from pituitary corticotrophic adenoma

➣Primary utility is to distinguish between pituitary (Cushing’s dis-

ease) or ectopic source of ACTH in established case of ACTH-

dependent CS, especially when MRI of sella is negative

➣May be useful in lateralizing corticotroph adenoma in pituitary

(Cushing’s disease)

Imaging

■ACTH-independent CS: abdominal CT/MRI

■ACTH-dependent, pituitary adenoma: MRI of sella; often due to

microadenoma (often not visualized)

■Ectopic (nonpituitary) Cushing: CXR, chest CT, 111-Indium-

ocreotide (Octrescan), FDG-PET scan

differential diagnosis

■Pseudo-Cushing’s: may be associated with depression, alcoholism,

intercurrent stress

■ACTH-independent:adrenal adenoma or carcinoma, nodular hy-

perplasia, exogenous glucocorticoid administration

■ACTH-dependent:

➣Pituitary corticotroph adenoma (Cushing’s disease,CD)

➣Plasma ACTH levels may be normal or elevated

■Ectopic ACTH:

➣Often in setting of known malignancy

➣Small cell carcinoma of the lung

➣Carcinoid tumors (bronchial, thymic, islet, gut)

➣Other neuroendocrine tumors (e.g. pheochromocytoma, medu-

llary CA of thyroid)

➣Plasma ACTH and UFC levels may be dramatically elevated

➣Syndrome of mineralocorticoid excess (hypokalemia, alkalosis,

edema) may dominate