Regarding the diagnostic approach to Cushing syndrome, all of the following statements are correct EXCEPT:

Explanation

## Cushing Syndrome Diagnosis: Screening and Confirmation ### Overview Diagnosis of Cushing syndrome requires demonstration of autonomous cortisol excess using sensitive screening tests, followed by subtype differentiation. ### Correct Answer: Normal 24-Hour UFC Does NOT Exclude Cushing Syndrome **Key Point:** A single normal 24-hour urinary free cortisol (UFC) does **NOT** reliably exclude Cushing syndrome. Cortisol secretion is episodic and pulsatile; mild cases may have borderline or intermittently normal UFC values. **Multiple measurements (ideally 2–3 separate 24-hour collections) are required** for adequate sensitivity. **High-Yield:** This is a critical NEET PG concept. A negative screening test does not rule out disease; repeat testing or alternative screening modalities (late-night salivary cortisol, midnight serum cortisol) are necessary if clinical suspicion remains high. **Warning:** Relying on a single normal UFC to exclude Cushing syndrome is a diagnostic pitfall that can delay diagnosis in patients with mild or episodic hypercortisolism. ### Why the Other Options Are Correct | Statement | Evidence | Clinical Use | |-----------|----------|---------------| | **Late-night salivary cortisol >90% sensitivity/specificity** | Loss of normal circadian rhythm is hallmark of Cushing syndrome | Excellent screening test; non-invasive, repeatable | | **DST (1 mg overnight) useful but lower specificity in obesity** | Obesity, depression, and other conditions cause false positives | Screening tool; requires confirmation with UFC or late-night cortisol | | **Midnight serum cortisol >7.5 μg/dL or UFC >4× ULN confirms autonomous secretion** | These thresholds indicate significant autonomous cortisol production | Diagnostic criteria per Endocrine Society guidelines | ### Diagnostic Algorithm ```mermaid flowchart TD A[Clinical suspicion of Cushing syndrome]:::outcome --> B[Screen with 2-3 of:<br/>24h UFC, Late-night salivary cortisol,<br/>Midnight serum cortisol, or DST]:::action B --> C{All tests normal?}:::decision C -->|Yes| D[Cushing syndrome unlikely]:::outcome C -->|No| E{≥2 tests abnormal?}:::decision E -->|Yes| F[Cushing syndrome confirmed]:::outcome E -->|No| G[Repeat testing or consider<br/>alternative diagnosis]:::action F --> H[Determine etiology:<br/>ACTH level]:::action H --> I{ACTH suppressed?}:::decision I -->|Yes| J[Adrenal Cushing<br/>Imaging: CT/MRI adrenal]:::action I -->|No| K[ACTH-dependent Cushing<br/>CRH stimulation, HDDST, Pituitary MRI]:::action ``` **Mnemonic — Screening Tests for Cushing Syndrome: "DULL"** - **D**examethasone suppression test (1 mg overnight) - **U**rinary free cortisol (24-hour, ×2–3) - **L**ate-night salivary cortisol - **L**ate-night serum cortisol (midnight) ### Clinical Pearl **Endocrine Society Diagnostic Approach:** At least one abnormal screening test warrants further evaluation. If clinical suspicion is high and initial screening is borderline, **repeat testing is mandatory** rather than dismissing the diagnosis based on a single normal result. [cite:Harrison 21e Ch 375; Endocrine Society Clinical Practice Guidelines 2023]