## Diagnostic Approach to Pheochromocytoma **Key Point:** Plasma free metanephrines or 24-hour urine metanephrines are the gold-standard biochemical screening tests for pheochromocytoma. They have >95% sensitivity and are the first-line investigation before imaging. ### Why Metanephrines? Metanephrines are the O-methylated metabolites of catecholamines (epinephrine and norepinephrine). They are: - **More stable** than catecholamines in blood and urine - **Continuously produced** by the tumor, not just during paroxysmal episodes - **More specific** for pheochromocytoma than catecholamines alone ### Diagnostic Algorithm for Secondary Hypertension ```mermaid flowchart TD A[Hypertensive crisis + Palpitations + Diaphoresis]:::outcome --> B{Clinical suspicion for pheochromocytoma?}:::decision B -->|Yes| C[Measure plasma free metanephrines or 24-hour urine metanephrines]:::action C --> D{Elevated?}:::decision D -->|Yes| E[Imaging: CT/MRI abdomen + pelvis]:::action D -->|No| F[Pheochromocytoma ruled out]:::outcome E --> G[Locate tumor]:::outcome G --> H[Surgical resection after alpha-blockade]:::action ``` **High-Yield:** Plasma free metanephrines are preferred over 24-hour urine metanephrines in many centers because they: - Require only a single blood draw - Have slightly higher sensitivity in some studies - Avoid collection errors **Mnemonic:** **PUMA** — **P**lasma/Urine **M**etanephrines for **A**drenergic tumors (pheochromocytoma). **Warning:** Do NOT order imaging (CT/MRI) before biochemical confirmation. Imaging is used to **localize** the tumor once biochemistry confirms the diagnosis. Imaging without biochemical evidence can lead to unnecessary procedures and false positives. **Clinical Pearl:** The classic triad of palpitations, diaphoresis, and headache during a hypertensive crisis is highly suggestive of pheochromocytoma. Biochemical testing must precede imaging. [cite:Harrison 21e Ch 297]
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