What is the appropriate management and treatment approach for a patient suspected of having pheochromocytoma?

Pheochromocytoma Management and Treatment

Diagnostic Workup

All patients suspected of having pheochromocytoma must undergo biochemical confirmation before any intervention, as unrecognized tumors can cause life-threatening hypertensive crises. 1

Initial Biochemical Testing

• Plasma free metanephrines (normetanephrine and metanephrine) are the single best screening test with 99% sensitivity and 89% specificity, and should be performed under standardized conditions—supine position with an indwelling IV cannula after 30 minutes of rest. 1, 2

• If plasma testing is equivocal (less than fourfold elevation above the upper limit of normal), perform 24-hour urine collection for fractionated metanephrines and catecholamines. 1, 2

• For levels ≥4 times the upper limit of normal, proceed immediately to imaging as this degree of elevation is diagnostic for pheochromocytoma/paraganglioma. 2

• For levels 2-4 times the upper limit of normal, repeat testing in 2 months and consider genetic testing. 2

• For marginally elevated levels (1-2 times upper limit), repeat testing in 6 months or consider clonidine suppression testing, which has 100% specificity and 96% sensitivity. 2

Imaging Localization

• MRI is preferred over CT for suspected pheochromocytoma due to the risk of hypertensive crisis after IV contrast administration. 3, 2

• After biochemical confirmation, obtain CT or MRI of the abdomen, along with chest CT to screen for metastases. 3, 2

• For whole-body screening, use anatomic imaging together with PET, preferably with radiolabeled somatostatin analogs. 1, 2

• Never perform fine needle biopsy of a suspected pheochromocytoma before biochemical exclusion, as this can precipitate fatal hypertensive crisis. 3, 2

Preoperative Medical Management

Alpha-adrenergic blockade must be initiated at least 7-14 days before surgery with gradually increasing dosages until blood pressure targets are achieved. 1, 2

Alpha-Blockade Protocol

• Phenoxybenzamine is FDA-indicated for pheochromocytoma to control episodes of hypertension and sweating. 4

• Start alpha-blockade 7-14 days preoperatively with gradually increasing dosages. 1, 2, 5

• Beta-blockers should only be added AFTER adequate alpha-blockade is established to control tachyarrhythmias—monotherapy with beta-blockers can precipitate severe hypertensive crisis due to unopposed alpha-adrenergic stimulation and is contraindicated. 1, 2

• Calcium channel blockers can be used as adjuncts for refractory hypertension. 1

• Ensure adequate plasma volume expansion before surgery. 6

Important Preoperative Caveats

• Meticulous perioperative management of hormonal, glucose, electrolytes, cardiac, and fluid/blood pressure abnormalities is critical. 3

• In low-risk patients, omission of presurgical treatment could be considered only if surgery is performed in experienced centers with strict perioperative monitoring. 5

Surgical Treatment

Complete surgical extirpation (R0 resection) is the only curative treatment for pheochromocytoma and is successful in 90% of cases. 3, 1

Surgical Approach

• Laparoscopic adrenalectomy is the preferred surgical approach for tumors ≤6 cm in diameter and weighing <100 g, offering earlier mobilization, reduced morbidity, and lower mortality rates. 1, 6

• Larger tumors (>5 cm) should be removed by open surgery to ensure complete resection. 7, 6

• A thorough exploration of the entire abdominal cavity and both adrenal beds is essential, as 10% of tumors are extra-adrenal. 8

• Cytoreductive surgery might be considered in advanced cases. 3

Special Population: Pregnancy

• For pregnant patients diagnosed in the first 24 weeks of gestation, perform laparoscopic adrenalectomy after 10-14 days of alpha-blockade. 1

Malignant Disease Management

Malignant pheochromocytomas are defined by the presence of metastases, occurring in approximately 10% of cases. 3

Treatment Options for Malignant Disease

• Disease and symptom control is the main treatment goal for inoperable malignant pheochromocytoma. 3

• Radiopharmaceutical therapy with 131I-MIBG is a primary option for patients with positive MIBG uptake. 3

• Combination chemotherapy with cyclophosphamide, vincristine, and dacarbazine (CVD) or doxorubicin-containing regimens (CVDD or CDD) can be used in selected cases, with 40% of patients experiencing clinical benefits. 3

• A "wait and see" policy is recommended for low tumor burden and asymptomatic malignant disease. 3

• Locoregional ablative procedures may be considered for symptom control. 3

Genetic Testing and Surveillance

Approximately 40% of pheochromocytomas are hereditary, and genetic testing should be considered in all patients. 2, 5

Indications for Genetic Testing

• Extra-adrenal tumors and bilateral adrenal tumors are strong indications for genetic testing. 2

• SDHB mutations are associated with higher risk of aggressive behavior and metastatic disease, requiring more intensive surveillance. 2

• For pediatric patients with suspected von Hippel-Lindau syndrome, begin surveillance at age 2 years. 2

• For pediatric patients with suspected hereditary paraganglioma/pheochromocytoma syndromes, begin surveillance at age 6-8 years. 2

Long-Term Follow-Up

All patients require lifelong surveillance due to 10-15% recurrence risk and 10-12% malignancy rate. 1

Follow-Up Protocol

• Repeat biochemical testing 14 days post-surgery to confirm complete resection. 2

• Follow-up every 3-4 months for the first 2-3 years, then every 6 months thereafter. 2

• Continue surveillance for at least 10 years minimum, with lifelong surveillance favored for malignant disease. 3, 1

• Patients with SDHB mutations, extra-adrenal tumors, or tumors >5 cm require more intensive long-term monitoring. 2

• A PASS score ≥4, large primary tumor, and/or SDHB mutation should prompt extended and lifelong monitoring. 2