What is the appropriate diagnostic and treatment approach for pheochromocytosis (adrenal gland tumor)?

From the Guidelines

The appropriate diagnostic approach for pheochromocytoma begins with biochemical testing, specifically measuring plasma free metanephrines or 24-hour urinary metanephrines and catecholamines, as recommended by the American Heart Association in 2018 1. This approach is crucial due to the high morbidity and mortality associated with untreated pheochromocytoma, as well as the potential for a 3-year delay in diagnosis. The screening test of choice is measurement of circulating catecholamine metabolites, with plasma free metanephrines offering a sensitivity of 96%−100% and specificity of 89%−98%, and urinary fractionated metanephrines providing a sensitivity of 86%−97% and specificity of 86%−95% 1. Imaging studies such as CT or MRI of the abdomen and pelvis should be performed to localize the tumor only after biochemical evidence for a pheochromocytoma has been obtained, with functional imaging like MIBG scan or PET/CT used for metastatic disease evaluation.

Key Considerations in Diagnosis and Treatment

• Biochemical testing is the first step in diagnosis, with plasma free metanephrines or 24-hour urinary metanephrines and catecholamines being the preferred tests.
• Imaging studies are used to localize the tumor after biochemical confirmation.
• Treatment is primarily surgical resection of the tumor, with proper preoperative management including alpha-adrenergic blockade and beta-blockers to prevent hypertensive crisis.
• Preoperative volume expansion and careful monitoring of blood pressure fluctuations during surgery are also critical.
• Postoperative follow-up should include lifelong monitoring for recurrence, with annual biochemical testing for at least 10 years, and consideration of genetic testing to identify hereditary syndromes.

Preoperative Management

• Alpha-adrenergic blockade with phenoxybenzamine or doxazosin is essential for 1-2 weeks before surgery to control blood pressure and prevent hypertensive crises, as supported by guidelines from the American Heart Association and other studies 1.
• Beta-blockers should be added only after adequate alpha-blockade.
• Preoperative volume expansion with increased salt intake and IV fluids is also important to prevent hypotension after tumor removal.

Surgical Considerations

• Surgery should be performed in centers with experience in adrenal surgery, as recommended by the European Society of Medical Oncology in 2012 1.
• The goal is to achieve a margin-free complete resection (R0 resection), which provides the best chance for long-term survival.
• Locoregional lymphadenectomy may improve tumor staging and outcome.

Postoperative Care

• Lifelong follow-up is necessary to monitor for recurrence, with annual biochemical testing for at least 10 years.
• Genetic testing should be considered to identify hereditary syndromes, which would necessitate screening of family members and surveillance for other associated tumors.

From the FDA Drug Label

INDICATION AND USAGE Phenoxybenzamine hydrochloride capsules are indicated in the treatment of pheochromocytoma, to control episodes of hypertension and sweating. If tachycardia is excessive, it may be necessary to use a beta-blocking agent concomitantly. The appropriate diagnostic approach for pheochromocytosis is not directly stated in the provided drug label. However, for treatment, phenoxybenzamine is indicated to control episodes of hypertension and sweating.

• Key points in treatment approach:
  • Use phenoxybenzamine to control hypertension and sweating
  • Consider using a beta-blocking agent if tachycardia is excessive 2

From the Research

Diagnostic Approach for Pheochromocytosis

• The diagnosis of pheochromocytoma depends on biochemical evidence of catecholamine production by the tumor 3.
• Plasma free metanephrines and urinary fractionated metanephrines are the biochemical tests of choice for the diagnosis of pheochromocytoma due to their greater sensitivity and specificity than catecholamines for pheochromocytoma detection 3, 4.
• The sensitivity of plasma free metanephrines (99%) and urinary fractionated metanephrines (97%) is higher than that of other tests such as plasma catecholamines, urinary catecholamines, urinary total metanephrines, and urinary vanillylmandelic acid 3.
• Specificity is highest for urinary vanillylmandelic acid (95%) and urinary total metanephrines (93%), and lowest for urinary fractionated metanephrines (69%) 3.

Treatment Approach for Pheochromocytosis

• After biochemical diagnosis, imaging studies such as computed tomography (CT), magnetic resonance imaging (MRI), and metaiodobenzylguanidine (MIBG) scintigraphy can be used to localize the tumor 5, 6.
• MIBG scintigraphy is recommended as the initial localizing study of choice, especially for the detection of extraadrenal disease and postoperative recurrence 6.
• Surgical excision of the tumor is the treatment of choice for pheochromocytoma, and adequate preoperative treatment is necessary to control blood pressure and prevent complications 5.

Special Considerations

• Preanalytical factors such as drug interference can influence metanephrine measurement and cause false positive results, highlighting the importance of careful patient medication review and consideration of alternative testing methods such as liquid chromatography tandem mass spectrometry (LC-MS/MS) 4.
• In rare cases, pheochromocytoma may not be associated with elevated urine catecholamines and metanephrines, and plasma free metanephrines or functional nuclear medicine studies such as MIBG may be necessary to confirm the diagnosis 5.
• Enzyme immunoassay (EIA) for free plasma metanephrines may be a suitable alternative to high-performance liquid chromatography with electrochemical detection (HPLC-ECD) for the diagnosis of pheochromocytoma, with comparable diagnostic performance to MIBG whole body scan 7.