A 52-year-old man from Delhi presents to the emergency department with acute onset severe headache, palpitations, and profuse sweating for the past 2 hours. His blood pressure is 210/130 mmHg, heart rate 118/min, and respiratory rate 24/min. On examination, he appears anxious and tremulous. His pupils are dilated. Serum glucose is 280 mg/dL. A 24-hour urine metanephrine is markedly elevated. Which of the following best explains the constellation of symptoms and signs in this patient?

Explanation

## Clinical Diagnosis: Pheochromocytoma Crisis ### Pathophysiology of Catecholamine Excess **Key Point:** Pheochromocytoma is a chromaffin cell tumor that releases massive amounts of norepinephrine and epinephrine, causing unopposed α-adrenergic (vasoconstriction, hypertension) and β-adrenergic (tachycardia, tremor, anxiety) effects. ### Clinical Triad Recognition | Feature | Mechanism | Finding in this case | |---------|-----------|---------------------| | **Hypertension (often paroxysmal)** | α-adrenergic vasoconstriction | BP 210/130 mmHg | | **Palpitations & tachycardia** | β-adrenergic cardiac stimulation | HR 118/min | | **Diaphoresis & anxiety** | Sympathetic overdrive | Profuse sweating, tremor | | **Hyperglycemia** | β-adrenergic inhibition of insulin secretion | Glucose 280 mg/dL | | **Mydriasis** | α-adrenergic pupillary dilation | Dilated pupils | **High-Yield:** The **classic triad** of pheochromocytoma is: 1. Episodic headache 2. Profuse diaphoresis 3. Palpitations ### Diagnostic Confirmation **Clinical Pearl:** Elevated 24-hour urine metanephrine (or plasma free metanephrine) is the **gold standard screening test**. Metanephrines are the O-methylated metabolites of catecholamines and are more stable than catecholamines themselves. **Key Point:** The diagnosis is confirmed by: - Elevated plasma or urine metanephrines (>4× upper limit of normal is highly specific) - Imaging: CT/MRI abdomen (most commonly adrenal origin, 90% of cases) - MIBG scintigraphy or PET-CT for metastatic disease ### Autonomic Mechanism The sympathetic nervous system is hyperactivated due to tumor catecholamine release. Unlike normal sympathetic stimulation (which involves acetylcholine at preganglionic terminals), the tumor directly dumps catecholamines into the bloodstream, bypassing normal neural regulation and causing unopposed receptor activation. ### Management Approach ```mermaid flowchart TD A[Pheochromocytoma Crisis]:::urgent --> B[α-blockade first]:::action B -->|Phenoxybenzamine or doxazosin| C[Control hypertension] C --> D[Then add β-blockade]:::action D -->|Propranolol or atenolol| E[Control tachycardia] E --> F[Definitive: Surgical resection]:::action F --> G[Complete resolution expected]:::outcome ``` **Warning:** Never give β-blockers before α-blockade — unopposed α-adrenergic effects will cause severe hypertension and coronary vasospasm. **Mnemonic:** **PHEOCHROMOCYTOMA** → **PHE**o = **PHE**noxybenzamine (α-blocker) first [cite:Harrison 21e Ch 405]