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.
Diagnosis & workup
Diagnostics & workup: - First-line screening (need ≥2 positive): 24-hr UFC, late-night salivary cortisol (2 collections), 1 mg overnight DST; consider 48-hr low-dose DST for equivocal results - Pseudo-Cushing differentiation: CRH-DST (dexamethasone + CRH stimulation) -- in true Cushing, cortisol rises after CRH despite dexamethasone; in pseudo-Cushing, cortisol remains suppressed - ACTH measurement: drawn at 8 AM (ACTH has diurnal variation); <5 pg/mL = ACTH-independent (adrenal); >20 pg/mL = ACTH-dependent (pituitary or ectopic); 5-20 = equivocal (repeat with CRH stimulation) - High-dose DST (8 mg): pituitary adenoma typically suppresses cortisol >50% (retains partial feedback sensitivity); ectopic typically does NOT suppress (no feedback mechanism); not 100% reliable (some ectopic tumors do suppress) - IPSS: gold standard for pituitary vs ectopic differentiation when imaging is equivocal; central:peripheral ACTH ratio ≥2 baseline or ≥3 post-CRH = pituitary; sensitivity 94%, specificity 100% - Pituitary MRI: only ~60% of Cushing disease pituitary adenomas are visible on MRI (many are microadenomas <6mm); a negative MRI does NOT exclude Cushing disease -- proceed to IPSS