## Clinical Context This patient has biochemically confirmed Cushing syndrome (elevated 24-hour UFC and non-suppressed cortisol on low-dose dexamethasone suppression test). The next diagnostic step is to determine the etiology: ACTH-dependent (pituitary or ectopic) versus ACTH-independent (adrenal). ## High-Dose Dexamethasone Suppression Test (HDST) **Key Point:** The HDST is the gold standard second-line test to differentiate the cause of confirmed Cushing syndrome. **High-Yield:** HDST interpretation: - **Cortisol suppression to <50% of baseline** → Cushing disease (pituitary ACTH-secreting adenoma) - **No suppression (>50% of baseline)** → Ectopic ACTH or adrenal source **Clinical Pearl:** Before HDST, ACTH level should be measured. If ACTH is suppressed (<5 pg/mL), the source is adrenal and HDST is unnecessary — proceed directly to adrenal imaging (CT/MRI). ## Why HDST is the Next Step 1. Biochemical confirmation is complete (elevated UFC + non-suppressed LDST) 2. ACTH level (not mentioned in stem but implied as part of workup) guides interpretation 3. HDST result directs further imaging and management: - If suppression → pituitary MRI - If no suppression → adrenal CT/MRI or ACTH source imaging ## Algorithm Overview ```mermaid flowchart TD A[Cushing syndrome suspected]:::outcome --> B[24h UFC + LDST]:::action B --> C{Both elevated?}:::decision C -->|Yes| D[Measure ACTH]:::action D --> E{ACTH level?}:::decision E -->|Suppressed <5| F[Adrenal source]:::outcome E -->|Normal/elevated| G[HDST 8 mg]:::action G --> H{Suppression?}:::decision H -->|Yes <50%| I[Cushing disease - Pituitary MRI]:::action H -->|No| J[Ectopic ACTH or adrenal - Imaging]:::action F --> K[Adrenal CT/MRI]:::action ``` [cite:Harrison 21e Ch 375] 
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