A 38-year-old woman with a 2-year history of hypertension (previously well-controlled on atenolol 50 mg daily) presents with acute worsening of blood pressure to 194/118 mmHg. She reports severe headache, palpitations, and profuse sweating for the past 4 hours. On examination, she is anxious, heart rate 112/min, and has cold, clammy skin. Fundoscopy reveals flame-shaped hemorrhages and cotton-wool spots. Serum creatinine is 1.6 mg/dL (baseline 0.9), and urinalysis shows 3+ proteinuria. 24-hour urine metanephrines are elevated at 2.5 times the upper limit of normal (reference < 90 μg/24 h). What is the most likely diagnosis?

Explanation

## Clinical Diagnosis: Pheochromocytoma with Hypertensive Crisis ### Diagnostic Triad **Key Point:** The classic triad of **episodic headache + profuse sweating + palpitations** in a patient with paroxysmal hypertension and elevated urine metanephrines is pathognomonic for pheochromocytoma. | Clinical Feature | Finding | Significance | |------------------|---------|---------------| | **Presentation** | Acute onset headache + diaphoresis + palpitations | Catecholamine surge (epinephrine > norepinephrine) | | **Vital signs** | HR 112, BP 194/118 | Sympathomimetic response | | **Skin** | Cold, clammy | Peripheral vasoconstriction from α-adrenergic excess | | **Anxiety** | Present | Psychological manifestation of catecholamine excess | | **Urine metanephrines** | 2.5× ULN (elevated) | **Gold standard test for pheochromocytoma** | | **Acute renal injury** | Creatinine 1.6 (baseline 0.9) | Hypertensive nephrosclerosis from catecholamine surge | | **Retinal findings** | Flame hemorrhages + cotton-wool spots | Grade 4 hypertensive retinopathy (hypertensive emergency) | | **Proteinuria** | 3+ | Acute glomerular injury from severe HTN | ### Pathophysiology of Pheochromocytoma Crisis 1. **Catecholamine release**: Tumor secretes excessive epinephrine and norepinephrine (metanephrines are their metabolites). 2. **α-adrenergic effects**: Intense vasoconstriction → severe hypertension, cold extremities, anxiety. 3. **β-adrenergic effects**: Tachycardia, palpitations, tremor. 4. **End-organ damage**: Acute hypertensive emergency with retinopathy, acute kidney injury, and potential stroke/MI. **High-Yield:** Urine metanephrines are the **most sensitive and specific screening test** for pheochromocytoma. Plasma free metanephrines are also acceptable but urine is preferred in many centers [cite:Harrison 21e Ch 405]. ### Why This Is NOT Essential HTN with Medication Non-Adherence - **Episodic symptoms**: True essential HTN does not cause acute headache + diaphoresis + palpitations in clusters. - **Elevated metanephrines**: This biochemical finding is diagnostic of catecholamine excess, not simple non-adherence. - **Acute kidney injury**: Suggests a paroxysmal, severe process, not chronic poor control. ### Next Steps in Management ```mermaid flowchart TD A[Pheochromocytoma suspected]:::outcome --> B[Confirm with imaging: CT/MRI abdomen]:::action B --> C[Localize tumor]:::action C --> D[Alpha blockade first: phenoxybenzamine or doxazosin]:::action D --> E[Then add beta blocker: propranolol]:::action E --> F[Surgical resection when stable]:::action A --> G[Avoid beta blockade alone]:::urgent G --> H[Risk: unopposed alpha → hypertensive crisis]:::urgent ``` **Clinical Pearl:** Always use **alpha blockade BEFORE beta blockade** in pheochromocytoma. Beta blockade alone causes unopposed α-adrenergic effects and worsens hypertension. [cite:Harrison 21e Ch 405]