Pathophysiology
Clinical meaning
At the NP level, Cushing syndrome evaluation requires sophisticated application of the diagnostic algorithm and nuanced management decisions. The 1 mg overnight dexamethasone suppression test (DST) has ~95% sensitivity but only ~80% specificity -- false positives occur with depression, alcoholism, obesity, OCP use (estrogen increases cortisol-binding globulin, elevating total cortisol), and CYP3A4 inducers (phenytoin, carbamazepine accelerate dexamethasone metabolism, causing inadequate suppression). The 48-hour low-dose DST (2 mg/day × 2 days) improves specificity. Late-night salivary cortisol measures FREE cortisol and is not affected by CBG levels. The inferior petrosal sinus sampling (IPSS) with CRH stimulation is the gold standard to distinguish pituitary from ectopic ACTH: a central-to-peripheral ACTH ratio ≥2 (baseline) or ≥3 (post-CRH) confirms pituitary source.