In the diagnosis of Cushing syndrome, which single test has the highest sensitivity and specificity for detecting hypercortisolism?

Explanation

## Diagnostic Tests for Cushing Syndrome **Key Point:** The 24-hour urinary free cortisol (UFC) is the gold standard screening test for Cushing syndrome, with sensitivity and specificity both >90% when properly collected. ### Screening Tests Comparison | Test | Sensitivity | Specificity | Notes | |------|-------------|-------------|-------| | 24-hour UFC | 90–95% | 90–98% | Gold standard; requires 3 collections for confirmation | | Late-night salivary cortisol | 90–95% | 95–98% | Convenient; good for outpatient screening | | Midnight serum cortisol | 85–90% | 85–90% | Requires hospitalization; less practical | | Morning serum cortisol | 60–70% | 70–80% | Low specificity; affected by stress, diurnal variation | | Random plasma ACTH | Variable | Variable | Not a screening test; used for classification | **High-Yield:** A normal 24-hour UFC essentially excludes Cushing syndrome. Elevated UFC on 3 separate collections confirms hypercortisolism. This is the most reliable single test for initial diagnosis. **Clinical Pearl:** Late-night salivary cortisol has emerged as an equally sensitive and specific screening tool and is increasingly preferred in clinical practice due to patient convenience, but UFC remains the reference standard in most guidelines. **Warning:** A single elevated 24-hour UFC can occur in pseudo-Cushing states (depression, alcoholism, obesity). Confirmation with a second test (late-night salivary cortisol or low-dose dexamethasone suppression test) is recommended before proceeding to further investigation. ### Why Other Tests Are Inferior - **Morning serum cortisol:** Affected by stress, diurnal rhythm, and individual variation; low specificity. - **Midnight serum cortisol:** Requires hospitalization and patient cooperation; less practical but useful when available. - **Random plasma ACTH:** Used for differential diagnosis (ACTH-dependent vs. independent) after hypercortisolism is confirmed, not for screening. [cite:Harrison 21e Ch 375]