No endocrinologic findings yield a 100% accuracy rate in the diagnosis of Cushing disease. The evaluation of patients suspected of having this condition should start with verification of sustained hypercortisolism. Morning and evening levels of serum cortisol as well as a 24-hour urine collection with measurement of urinary free cortisol levels should be determined. The diagnosis can generally be established by the demonstration of nonsuppressibility of corticosteroids in serum or urine after administration of low-dose dexamethasone but at least 50% suppressibility after administration of high-dose (8 mg) dexamethasone. A lack of suppression with high-dose dexamethasone can be seen in cases of macroadenoma and thus does not necessarily rule out an adrenocorticotropic hormone (ACTH)–secreting adenoma.41 An elevated serum ACTH level in the presence of hypercortisolism provides additional supportive evidence.

Percutaneous transfemoral selective inferior petrosal venous sampling for ACTH before and after the administration of corticotropin-releasing factor has also been of help in equivocal cases.42 If the diagnosis is uncertain and a paraneoplastic (“ectopic”) source of ACTH secretion is suggested, selective venous sampling to determine a cephalic plasma ACTH gradient has proved to be diagnostically definitive.5 When the samples have been obtained from the inferior petrosal sinus, no misleading results have been found. Sampling of another pituitary hormone along with ACTH is helpful to reduce confusion about results from various sites (see Chap. 74, Chap. 75 and Chap. 219). Such sampling can be taken directly from the cavernous sinus, using a superselective microcatheterization technique.43