What is the recommended approach for diagnosing pheochromocytoma (adrenal gland tumor)?

Recommended Approach for Diagnosing Pheochromocytoma

The diagnosis of pheochromocytoma should begin with measuring plasma free metanephrines, which is the most sensitive and specific test, followed by appropriate imaging studies including CT or MRI of the abdomen. 1, 2

Biochemical Testing

• Plasma free metanephrines (normetanephrine and metanephrine) measurement is the first-line diagnostic test with the highest sensitivity (99%) and good specificity (89%) for diagnosing pheochromocytoma 3, 4
• If plasma testing is equivocal (less than fourfold elevation), a 24-hour urine collection for fractionated metanephrines should be performed as a follow-up test 2, 5
• Additional measurement of plasma methoxytyramine (when available) provides useful information to assess the likelihood of malignancy 3, 1
• LC-MS/MS methods for measuring plasma metanephrines offer superior analytical sensitivity and specificity compared to immunoassay methods 6, 7

Imaging Studies

• After positive biochemical testing, localization of the tumor should be performed using CT or MRI of the abdomen 3
• CT is less expensive and should be the first choice in suspected pheochromocytoma, while MRI is preferred when there is a risk of hypertensive crisis from IV contrast 3
• Cross-sectional imaging of the chest, abdomen, and pelvis is required preoperatively to detect local invasion, tumor extension, and metastases 3
• For patients with suspected metastatic disease, functional imaging is recommended 3, 2

Functional Imaging Options

• FDG-PET is useful for distinguishing potentially malignant lesions from benign tumors and appears superior to MIBG scintigraphy, particularly in patients with SDHB mutations 3
• Other functional imaging options include MIBG scintigraphy, DOTA-TATE-PET, and FDOPA-PET, which help detect multifocal disease 1, 5

Important Considerations

• Fine needle biopsy of suspected pheochromocytoma is contraindicated due to the risk of hypertensive crisis 3, 5
• Malignancy in pheochromocytoma can only be determined by the presence of metastatic lesions at sites where chromaffin cells are normally absent 3, 1
• Risk factors for malignancy include tumor size ≥5 cm, extra-adrenal paraganglioma location, SDHB germline mutation, and plasma methoxytyramine more than threefold above the upper limit 3, 2

Diagnostic Algorithm

1. Initial biochemical testing: Measure plasma free metanephrines 1, 4
2. If equivocal: Perform 24-hour urine collection for fractionated metanephrines 2, 8
3. If biochemically positive: Proceed to anatomical imaging with CT or MRI of abdomen 3
4. For suspected metastatic disease: Add functional imaging (FDG-PET preferred) 3, 1
5. For high-risk patients: Consider genetic testing, especially with family history, young age at diagnosis, bilateral/multifocal disease, or extra-adrenal location 2

Follow-up After Treatment

• Biochemical testing should be performed approximately 14 days after surgery to verify complete resection 1, 2
• Long-term follow-up includes clinical evaluation (adrenergic symptoms and blood pressure) and biochemical testing every 3-4 months for 2-3 years, then every 6 months 1, 3
• Lifelong surveillance is recommended for patients with proven malignant disease, SDHB mutation, extra-adrenal primary disease, or pheochromocytoma without relevant preoperative hormone secretion 1, 3