## Investigation of Choice for Pheochromocytoma Diagnosis ### Why Plasma Free Metanephrines and 24-Hour Urinary Metanephrines? **Key Point:** Metanephrines (O-methylated metabolites of catecholamines) are the most sensitive and specific biochemical markers for pheochromocytoma diagnosis. They are more stable than catecholamines themselves and less subject to fluctuation. **High-Yield:** - Plasma free metanephrines have ~96% sensitivity and ~85% specificity - 24-hour urinary metanephrines have ~95% sensitivity and ~89% specificity - These tests should be performed BEFORE imaging (CT/MRI) to confirm biochemical excess - Catecholamine excess is mediated through α₁, α₂, and β₁ adrenergic receptors, causing the clinical presentation ### Biochemical Basis 1. Catecholamines (epinephrine, norepinephrine) are released from chromaffin cells 2. They are rapidly metabolized by catechol-O-methyltransferase (COMT) to metanephrines 3. Metanephrines are more stable and accumulate in plasma and urine 4. Detection of elevated metanephrines confirms autonomous catecholamine production **Clinical Pearl:** Even a single normal plasma free metanephrine level has >99% negative predictive value for excluding pheochromocytoma, making it an excellent screening test. ### Investigation Algorithm ```mermaid flowchart TD A[Suspected pheochromocytoma<br/>Clinical signs: HTN, palpitations, tremor]:::outcome A --> B[Plasma free metanephrines<br/>or 24-h urinary metanephrines]:::action B --> C{Elevated?}:::decision C -->|Yes| D[Confirm biochemical excess]:::outcome C -->|No| E[Pheochromocytoma unlikely<br/>Consider alternative diagnosis]:::outcome D --> F[Imaging: CT/MRI abdomen<br/>to localize tumor]:::action F --> G[Surgical planning/management]:::action ``` **Mnemonic:** **METH-HUNT** — Metanephrines (test), Epinephrine/norepinephrine (source), Tumor (pheochromocytoma), Hunt for biochemical evidence first, then imaging. 
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