Management of Elevated Metanephrines Suggestive of Pheochromocytoma or Paraganglioma

Initial Biochemical Assessment

Plasma free metanephrines is the preferred first-line test for suspected pheochromocytoma/paraganglioma due to its superior diagnostic performance (sensitivity 96-100%, specificity 89-98%) 1
Plasma free metanephrines should ideally be collected from an indwelling venous catheter, after the patient has been lying supine for 30 minutes to limit false positive results 1, 2
Plasma methoxytyramine measurement can help assess the likelihood of malignant disease 1, 2

For levels ≥4 times the upper limit of normal, results are highly consistent with pheochromocytoma/paraganglioma and immediate imaging is indicated 1, 2
For levels 2-4 times the upper limit of normal, repeat testing in 2 months and consider genetic testing, especially in younger patients 1, 2
For marginally elevated levels (1-2 times upper limit), consider repeat testing in 6 months and clonidine suppression test (100% specificity, 96% sensitivity) 1

MRI is preferred for suspected pheochromocytoma due to risk of hypertensive crisis with IV contrast for CT 1, 2
For head/neck paragangliomas, MRI with angiography sequences is recommended as the first modality to assess multifocality and tumor extension 3
Whole-body MRI should be performed at least every 2–3 years to detect new PPGLs, metastases, or progression in patients with known disease 4, 5

For functional PPGLs, preoperative alpha-blockade with phenoxybenzamine is recommended to prevent perioperative hemodynamic instability 5
Metyrosine and calcium channel blockers can be used as adjuncts to alpha-blockade 5

Patients with PPGL should undergo annual blood pressure measurements, clinical assessment, and biochemical measurements 4, 5
Measurement of plasma or urine metanephrines should be performed by 8 weeks post-treatment for functional PPGLs 5
Patients with SDHB mutations require more intensive surveillance due to higher risk of malignancy 1, 2

All decisions in patients with PPGLs should be discussed and managed by an expert interdisciplinary tumor team 3
Avoid fine needle biopsy of suspected pheochromocytoma as it is contraindicated due to risk of hypertensive crisis 1, 2
For patients with metastatic disease, targeted radionuclide therapy is recommended as first-line systemic therapy for SSTR- or MIBG-positive metastatic tumors 4