What are the risks of not surgically removing an asymptomatic pheochromocytoma in a patient?

Risks of Not Treating Asymptomatic Pheochromocytoma

Even asymptomatic pheochromocytomas carry substantial mortality risk from sudden catecholamine surges causing hypertensive crises, cardiovascular complications, and death—surgical resection should be strongly recommended for all patients who are surgical candidates. 1

Life-Threatening Cardiovascular Risks

The primary danger of leaving an asymptomatic pheochromocytoma untreated is sudden death from cardiovascular complications:

• Hypertensive crises can occur unpredictably, even in patients without baseline symptoms, triggered by physical stress, anesthesia for unrelated procedures, or spontaneous catecholamine surges 1, 2
• Cardiac arrhythmias and myocardial infarction from catecholamine excess represent immediate life-threatening risks 1, 3
• A significant number of patients with pheochromocytoma die specifically from hormone-related complications including uncontrolled hypertension 1
• The tumor is "almost always lethal unless recognized and appropriately treated" 2

Malignant Transformation and Metastatic Disease

Risk of malignancy ranges from 4.5% to 10%, with no reliable way to predict which tumors will become malignant:

• Approximately 10% of pheochromocytomas are malignant, defined by the presence of metastases 1, 2
• For SDHD-associated tumors specifically, metastatic rates range between 4.5% and 7.7% 1
• Malignant recurrence can occur decades after initial diagnosis—benign recurrence or malignant transformation has been reported up to 41 years after initial detection 3
• Once metastatic, treatment options are limited to palliative measures with poor outcomes 1

Tumor Growth and Local Complications

Untreated pheochromocytomas progressively enlarge and become more difficult to resect:

• Larger tumors (>5-6 cm) require open surgery rather than minimally invasive approaches, increasing surgical morbidity 1
• Growing tumors can become locally invasive, involving major vessels (inferior vena cava, aorta, renal vein, superior mesenteric vessels), necessitating complex vascular reconstruction 1
• Mass effect from enlarging tumors can cause debilitating pain and compression of surrounding structures 1

Surgical Risk Increases Over Time

Delaying surgery makes the procedure progressively more dangerous:

• Complete (R0) resection becomes less achievable as tumors grow and invade adjacent structures 1
• Incomplete resection is associated with significantly worse prognosis and higher recurrence rates 1
• Patients may develop medical comorbidities from chronic catecholamine excess (diabetes, cardiomyopathy) that increase surgical risk 1

The "Asymptomatic" Designation is Misleading

Many patients labeled as asymptomatic actually have subclinical disease:

• Biochemical evidence of catecholamine excess typically precedes clinical manifestations when tumors recur or progress 3
• Patients may have normalized their symptoms or attribute them to other causes (stress, anxiety, aging) 2
• Even biochemically "silent" tumors can suddenly begin secreting catecholamines unpredictably 1

Guideline-Based Recommendation

The ESMO guidelines explicitly state that complete surgical excision (R0 resection) should be performed for localized pheochromocytomas when complete tumor removal is possible 1. The only exception is for patients with:

• Low tumor burden, asymptomatic malignant (metastatic) pheochromocytoma—where a "wait and see" policy is recommended 1
• Absolute contraindications to surgery due to severe comorbidities 1

For non-metastatic, localized pheochromocytomas (even if asymptomatic), surgery should be offered to all appropriate surgical candidates 1.

Critical Pitfall to Avoid

Never assume an "asymptomatic" pheochromocytoma is safe to observe—the unpredictable nature of catecholamine release means patients are at constant risk of life-threatening complications, and surgical outcomes are optimal when tumors are smaller and non-invasive 1, 2.