Overview
Clinical Meaning
Cushing syndrome results from prolonged exposure to supraphysiologic levels of cortisol from any source.
Cushing syndrome results from prolonged exposure to supraphysiologic levels of cortisol from any source. The diagnostic evaluation follows a systematic algorithm: (1) SCREENING — at least two positive screening tests are required to confirm hypercortisolism: 24-hour urine free cortisol (UFC >3x upper limit of normal is virtually diagnostic), late-night salivary cortisol (elevated >2 occasions; exploits the loss of normal diurnal cortisol nadir), and 1-mg overnight dexamethasone suppression test (DST — normal suppression: 8 AM cortisol <1.8 mcg/dL; failure to suppress indicates autonomous cortisol production). (2) LOCALIZATION — once hypercortisolism is confirmed: measure plasma ACTH. ACTH-dependent (ACTH >15 pg/mL): pituitary adenoma (Cushing disease — 70%), ectopic ACTH (lung carcinoid, SCLC — 15%). ACTH-independent (ACTH <5 pg/mL): adrenal adenoma, adrenal carcinoma, bilateral adrenal hyperplasia. (3) DIFFERENTIATION of ACTH-dependent sources: high-dose DST (8 mg overnight or 2-day test — pituitary adenomas suppress cortisol by >50%; ectopic sources do not), CRH stimulation test (pituitary adenomas respond with ACTH increase; ectopic sources do not), pituitary MRI (microadenoma in 50-60% of Cushing disease), and inferior petrosal sinus sampling (IPSS — gold standard for confirming pituitary source...