A 38-year-old woman presents with a 6-month history of progressive headaches and palpitations. On examination, blood pressure is 168/104 mmHg bilaterally, heart rate 92/min regular, and there is a palpable abdominal mass in the left flank. Serum electrolytes show K⁺ 3.2 mEq/L (normal 3.5–5.0). Plasma metanephrines are elevated at 1.8 nmol/L (normal <0.9). 24-hour urine catecholamines are 850 µg/24 h (normal <100). CT abdomen shows a 4 cm left adrenal mass with heterogeneous enhancement. What is the most likely diagnosis?

Explanation

## Clinical Diagnosis: Pheochromocytoma ### Key Clinical Features **Key Point:** The triad of episodic headaches, diaphoresis, and palpitations in a hypertensive patient with an adrenal mass and elevated plasma metanephrines is pathognomonic for pheochromocytoma. ### Diagnostic Criteria Met | Feature | Patient Finding | Significance | |---------|-----------------|-------------| | **Symptoms** | Headaches, palpitations | Classic catecholamine excess | | **Hypertension** | 168/104 mmHg | Sustained or paroxysmal | | **Imaging** | 4 cm left adrenal mass | Typical location (90% adrenal) | | **Biochemistry** | ↑ Plasma metanephrines | Gold standard screening test | | **24-h urine catecholamines** | 850 µg/24 h (8.5× normal) | Confirms catecholamine excess | | **Hypokalemia** | K⁺ 3.2 mEq/L | From α₂-adrenergic inhibition of insulin | ### Pathophysiology 1. Catecholamine-secreting tumor arises from chromaffin cells of adrenal medulla (90%) or sympathetic chain (10%) 2. Episodic release of norepinephrine and epinephrine → paroxysmal hypertension, headache, sweating 3. Chronic catecholamine exposure → left ventricular hypertrophy, cardiomyopathy risk 4. α-Adrenergic effects dominate → vasoconstriction; β-effects → tachycardia, arrhythmias ### Diagnostic Algorithm ```mermaid flowchart TD A["Hypertension + Headaches/Palpitations/Diaphoresis"]:::outcome --> B["Plasma metanephrines or 24-h urine catecholamines"]:::action B --> C{"Elevated?"}:::decision C -->|"Yes"| D["Imaging: CT/MRI abdomen"]:::action C -->|"No"| E["Pheochromocytoma unlikely"]:::outcome D --> F{"Adrenal mass?"}:::decision F -->|"Yes"| G["Confirm with clonidine suppression test if needed"]:::action F -->|"No"| H["Extra-adrenal paraganglioma - search neck/chest/abdomen"]:::action G --> I["Genetic screening: RET, SDH, VHL, NF1"]:::action I --> J["Preoperative α-blockade (phenoxybenzamine)"]:::action J --> K["Then β-blockade (after α-control)"]:::action K --> L["Surgical resection"]:::action ``` **High-Yield:** Plasma free metanephrines are the **single best screening test** — superior sensitivity (96–99%) and specificity (85–89%) compared to 24-hour urine catecholamines. Always measure metanephrines BEFORE imaging. **Clinical Pearl:** The "rule of 10s" is outdated; modern series show malignancy in ~30–40%, familial syndromes in ~30–40%, and bilateral disease in ~10%. Always screen for MEN2A/2B, NF1, SDH mutations, and VHL. **Mnemonic: PHEO** — **P**ressure (hypertension), **H**eadache, **E**xcessive sweating, **O**rthostatic hypotension (from volume depletion). ### Why Plasma Metanephrines Are Superior - Metabolites of catecholamines; produced continuously even between paroxysmal episodes - Not affected by stress, medications, or dietary tyramine (unlike plasma catecholamines) - 24-hour urine catecholamines miss ~10% of cases due to episodic secretion ### Management Principles 1. **Preoperative α-blockade:** Phenoxybenzamine 10 mg BD, titrate to 80–320 mg/day over 7–10 days 2. **Then β-blockade:** Propranolol 20–40 mg TDS (NEVER β-block before α-blockade — risk of hypertensive crisis) 3. **Surgical resection** under anesthesia with intraoperative monitoring 4. **Genetic counseling** for familial syndromes [cite:Harrison 21e Ch 405]