Pheochromocytoma
A rare adrenal tumor that secretes excessive adrenaline and noradrenaline, causing dangerous spikes in blood pressure, headaches, sweating, and palpitations.
Emergency Management: Hypertensive crisis due to pheochromocytoma requires IV Phentolamine (1-5 mg IV bolus) or Sodium Nitroprusside (0.25-10 mcg/kg/min infusion). Never use beta-blockers as first-line for this crisis.
A pheochromocytoma is a rare, catecholamine-secreting neuroendocrine tumor arising from the chromaffin cells of the adrenal medulla. Tumors arising from extra-adrenal sympathetic ganglia are termed paragangliomas. They are characterized by the episodic release of epinephrine, norepinephrine, and occasionally dopamine.
Detailed Overview
These tumors cause severe, secondary hypertension that can be sustained or paroxysmal. The classic triad of episodic headache, sweating, and tachycardia is highly suggestive but not universally present. Because of the excessive catecholamine release, patients are at high risk for fatal hypertensive crises, arrhythmias, or myocardial infarction, especially during surgery or induction of anesthesia. Genetic testing is now recommended for all diagnosed patients due to high rates of familial syndromes.
Epidemiology & Demographics
Incidence is 2-8 per million persons per year. Peaks between the 3rd and 5th decades of life. Found in about 0.2% of patients with hypertension.
Etiological Mechanism
Approximately 60% are sporadic. The remaining 40% are associated with germline mutations in susceptibility genes (RET, VHL, NF1, SDHx).
Primary Causes
Neoplastic proliferation of chromaffin cells in the adrenal medulla (90%) or extra-adrenal paraganglia (10%), commonly driven by genetic mutations (e.g., Multiple Endocrine Neoplasia type 2, von Hippel-Lindau disease, Neurofibromatosis type 1).
Chromaffin cells synthesize catecholamines from tyrosine. In pheochromocytoma, autonomous and uncontrolled secretion of norepinephrine (binds alpha-1 receptors causing profound vasoconstriction and hypertension) and epinephrine (binds beta-1 receptors causing tachycardia and increased cardiac output) occurs. The release is often episodic due to changes in tumor blood flow, physical compression, or induction by drugs. Sustained high catecholamine levels lead to alpha-receptor downregulation and chronic volume depletion, making patients paradoxically susceptible to severe hypotension after tumor removal.
Diagnostic Criteria & Guidelines
Biochemical confirmation of catecholamine excess followed by anatomical localization. Diagnosis requires significantly elevated levels (usually >2-3 times the upper limit of normal) of plasma free metanephrines or 24-hour urine fractionated metanephrines.
Medical blockade is mandatory prior to surgery. Alpha-adrenergic blockade first: Phenoxybenzamine (initially 10 mg PO BID, up-titrated to 10-100 mg BID) or Doxazosin (1 mg PO daily, up-titrated to 16 mg daily) for 10-14 days. After adequate alpha blockade (target BP <130/80 and asymptomatic), initiate beta-blockade (e.g., Propranolol 10-40 mg PO TID) to control tachycardia.
Second-Line & Adjunctive Therapy
Metyrosine (250 mg PO QID up to 4g/day) inhibits tyrosine hydroxylase, reducing catecholamine synthesis; used for pre-op optimization in extensive/metastatic disease or if standard blockade is ineffective.
Surgical & Procedural Management
Laparoscopic adrenalectomy is the definitive treatment for localized tumors. Open adrenalectomy is reserved for large (>6 cm) or likely malignant tumors. Extreme hemodynamic monitoring during surgery is required.
Patient Counseling & Advice
Warn the patient that initiating beta-blockers before alpha-blockers is strictly prohibited, as it can cause unopposed alpha-adrenergic stimulation, leading to a fatal hypertensive crisis. Genetic counseling is essential post-diagnosis.
Follow-Up & Monitoring Schedule
Recheck plasma or urine metanephrines 2-6 weeks post-operatively to confirm cure. Annual biochemical screening for at least 10 years, and lifelong for those with genetic mutations or extra-adrenal tumors.
Preventive Strategies
No primary prevention exists. Secondary prevention relies on prophylactic screening of family members in cases of known hereditary syndromes (e.g., checking plasma metanephrines yearly in MEN2 gene carriers).
The 5-year survival rate for localized completely resected pheochromocytoma is >95%. For metastatic disease, 5-year survival is highly variable (40-60%). Hypertension resolves post-operatively in about 70% of patients.