Overview
Definition:
Pheochromocytoma is a catecholamine-secreting tumor of the adrenal medulla or sympathetic nervous system, leading to paroxysmal or sustained hypertension and other symptoms due to excess hormone production
Preoperative optimization is crucial to mitigate the significant risks associated with surgical resection.
Epidemiology:
Rare tumors, occurring in about 2-8 per million population annually
Can occur at any age but are most common in the third to fifth decades of life
Approximately 10% are malignant, and 10% are associated with inherited syndromes like MEN2A, MEN2B, neurofibromatosis type 1, and von Hippel-Lindau disease.
Clinical Significance:
Uncontrolled pheochromocytoma poses a high risk of perioperative cardiovascular events including hypertensive crisis, myocardial infarction, stroke, arrhythmias, and pulmonary edema
Optimal medical management before surgery significantly reduces this morbidity and mortality, making it a cornerstone of surgical preparation.
Clinical Presentation
Symptoms:
Classic triad: episodic headaches, palpitations, and diaphoresis (sweating)
Other symptoms include: significant hypertension (often sustained or paroxysmal), anxiety, tremor, nausea, vomiting, pallor, dyspnea, chest pain, and abdominal pain
Symptoms can be triggered by physical exertion, palpation of the tumor, or certain medications.
Signs:
Hypertension (systolic >140 mmHg and/or diastolic >90 mmHg, often with labile fluctuations)
Tachycardia or bradycardia
Postural hypotension (due to volume depletion)
Pallor
Tremor
Proptosis
Funduscopic findings of hypertensive retinopathy
Abdominal mass (rare).
Diagnostic Criteria:
Diagnosis is confirmed by biochemical evidence of excess catecholamine or metanephrine excretion
Criteria include: plasma free metanephrines > normal range, 24-hour urinary fractionated metanephrines and catecholamines > upper limit of normal
Clonidine suppression test can be helpful in equivocal cases
Imaging (CT, MRI, MIBG scan) is used for localization.
Preoperative Preparation
Medical Management Goals:
To control hypertension, prevent catecholamine surges, and restore intravascular volume
The primary aim is to block the effects of circulating catecholamines on alpha and beta adrenergic receptors.
Alpha Adrenergic Blockade:
Initiated first, typically 10-14 days preoperatively
Phenoxybenzamine (non-selective, irreversible alpha-blocker) is often preferred
Start with 10 mg PO daily, titrated upwards to achieve postural hypotension and control hypertension
Prazosin or terazosin (selective alpha-1 blockers) can be used if side effects with phenoxybenzamine are problematic, but require careful titration
Target blood pressure: systolic >90-100 mmHg, diastolic >50-60 mmHg, with postural drop of <20 mmHg systolic.
Beta Adrenergic Blockade:
Initiated ONLY AFTER adequate alpha-blockade is established, typically 2-3 days before surgery
If initiated before alpha-blockade, it can precipitate unopposed alpha-stimulation leading to severe hypertension and pulmonary edema
Propranolol (non-selective beta-blocker) is commonly used
Start with 20 mg PO TID, titrated to control tachycardia (heart rate 60-80 bpm).
Volume Expansion:
Intravenous fluid resuscitation is essential to restore depleted intravascular volume, especially with phenoxybenzamine use
Normal saline is typically used
Adequate hydration is vital to prevent hypotension during anesthesia and tumor manipulation.
Calcium Channel Blockers:
May be used as adjuncts if hypertension is refractory to alpha and beta blockade
Examples: nifedipine or nicardipine
Used cautiously to avoid excessive vasodilation and hypotension.
Dietary Considerations:
High salt intake is encouraged to help expand intravascular volume, particularly during phenoxybenzamine therapy.
Management During Surgery
Anesthetic Considerations:
General anesthesia is preferred
Avoid agents that can trigger catecholamine release (e.g., succinylcholine)
Monitor arterial pressure, central venous pressure, ECG, oxygen saturation, and urine output closely.
Intraoperative Monitoring:
Continuous invasive arterial blood pressure monitoring is mandatory
Central venous pressure monitoring is recommended
ECG for arrhythmias
Pulse oximetry
Capnography.
Pharmacological Interventions:
Lidocaine or esmolol for ventricular arrhythmias
Sodium nitroprusside or nicardipine infusion for rapid control of hypertensive crises
Phenylephrine or norepinephrine for hypotension
Volume replacement with crystalloids and colloids.
Tumor Manipulation:
The anesthetic team should be alerted before any manipulation of the tumor
Complete tumor resection with control of venous and arterial supply is crucial to prevent catecholamine release
Ligature of the feeding vessels should be done meticulously.
Post Ligation Hypotension:
Sudden hypotension can occur after tumor ligation due to withdrawal of circulating catecholamines
Aggressive fluid resuscitation and vasopressor support may be required.
Postoperative Care
Immediate Postoperative Period:
Close monitoring of blood pressure, heart rate, and fluid balance is critical
Patients may require continued intravenous fluids and vasopressors if hypotension persists.
Arrhythmia Management:
Monitor for arrhythmias and treat promptly
Beta-blockers may be continued or reinstituted as needed.
Glycemic Control:
Monitor blood glucose levels as pheochromocytomas can cause hyperglycemia
Insulin may be required.
Hypertension Resolution:
Blood pressure typically normalizes within a few days of surgery, but may take longer
Continued outpatient antihypertensive medication may be necessary in some patients.
Discharge Planning:
Discharge planning includes patient education on signs of recurrence, importance of follow-up, and lifestyle modifications
Patients are typically discharged when hemodynamically stable and tolerating oral intake.
Complications
Perioperative Hypertensive Crisis:
Risk significantly reduced by adequate alpha-blockade
Can occur during induction, tumor manipulation, or after ligation.
Hypotension:
Can occur due to anesthetic agents, tumor ligation leading to catecholamine withdrawal, or volume depletion.
Cardiac Arrhythmias:
Atrial and ventricular arrhythmias are common due to excess catecholamines
Ventricular tachycardia and fibrillation are life-threatening.
Myocardial Infarction:
Can occur due to coronary artery spasm or increased myocardial oxygen demand.
Stroke:
Related to severe hypertension and potential coagulopathy.
Pulmonary Edema:
Can occur with severe hypertension, left ventricular dysfunction, or fluid overload.
Renal Insufficiency:
Due to severe hypertension or prolonged hypotension.
Adrenal Insufficiency:
Rare with unilateral adrenalectomy if the contralateral adrenal gland is healthy.
Key Points
Exam Focus:
The hallmark of pheochromocytoma management is preoperative medical optimization using alpha-blockade followed by beta-blockade
Understand the drug classes, sequence of administration, and target parameters for BP and HR.
Clinical Pearls:
Always rule out pheochromocytoma in patients with unexplained hypertension, especially if accompanied by headaches, palpitations, or sweating
Be vigilant for labile hypertension
Never initiate beta-blockers before adequate alpha-blockade.
Common Mistakes:
Administering beta-blockers before alpha-blockers
inadequate medical preparation leading to perioperative hypertensive crises
insufficient volume expansion
delaying surgery due to fear of complications rather than optimizing for them.