Etiology: ↑ cortisol due to:- Exogenous corticosteroids: result in ↓ ACTH, bilateral adrenal atrophy. Most common cause.- Primary adrenal adenoma, hyperplasia, or carcinoma – result in ↓ ACTH, atrophy of uninvolved adrenal gland.- ACTH-secreting pituitary adenoma (Cushing disease); paraneoplastic ACTH secretion (eg, small cell lung cancer, bronchial carcinoids) – result in ↑ ACTH, bilateral adrenal hyperplasia.Cushing disease is responsible for the majority of endogenous cases of Cushing syndrome.

Findings: Hypertension, weight gain, moon facies, abdominal striae and truncal obesity, buffalo hump, skin changes (eg, thinning, striae), hirsutism, osteoporosis, hyperglycemia (insulin resistance), amenorrhea, immunosuppression. Can also present with pseudohyperaldosteronism.

Diagnosis: - Screening tests: ↑ free cortisol on 24-hr urinalysis, ↑ midnight salivary cortisol, and no suppression with overnight low-dose dexamethasone test. - Measure serum ACTH:→ If ↓, suspect adrenal tumor or exogenous glucocorticoids. → If ↑, distinguish between Cushing disease and ectopic ACTH secretion with a high-dose (8 mg) dexamethasone suppression test. - Ectopic secretion will not decrease with dexamethasone because the source is resistant to negative feedback. - Ectopic secretion will not increase with CRH because pituitary ACTH is suppressed.