Pheochromocytoma Diagnosis and Management

Clinical Presentation and Diagnosis

The European Society of Endocrinology recommends measuring plasma free metanefrines as the most sensitive and specific test for diagnosing pheochromocytoma in clinically suspected cases 2
If plasma tests are equivocal, a 24-hour urine collection for catecholamines and metanefrines should be performed 2
Additional measurement of plasma methoxytyramine provides useful information for evaluating the likelihood of malignancy 2
In patients with head and neck paragangliomas (HNPGL), particularly with SDHD pathogenic variants, clinical evaluation and biochemical measurements (plasma or urine metanefrines and plasma methoxytyramine) are recommended 3, 4

After positive biochemical tests, localization using CT or MRI of the abdomen is recommended 2
For patients with HNPGL, MRI of the head/neck is recommended as the first modality to evaluate multifocality and tumor extension 3, 4
For whole-body screening for pheochromocytoma/paraganglioma, anatomical imaging of the whole body along with positron emission tomography (PET) is recommended, preferably with radiolabeled somatostatin analogs 3, 4

The European Society of Medical Oncology recommends complete surgical resection (R0 resection) as the potentially curative treatment for pheochromocytoma 2, 5
For malignant pheochromocytoma, cytoreductive surgery may be considered 2, 5
An open approach is recommended for treating masses larger than 5 cm, consistent with adrenocortical carcinoma 6

Biochemical tests should be performed approximately 14 days after surgery to verify residual disease 2, 5
Long-term follow-up includes clinical evaluation (adrenergic symptoms and blood pressure levels) and biochemical testing (metanefrine, normetanefrine, chromogranin A, and methoxytyramine) 5
Biochemical tests should be repeated every 3-4 months for 2-3 years, and then every 6 months 5
Lifetime follow-up is recommended in proven malignant disease, SDHB mutation, primary extra-adrenal disease, and rare cases of pheochromocytoma/paraganglioma without relevant preoperative hormonal secretion 5

Tumor size ≥5 cm 2
Extra-adrenal paraganglioma 2
Germline SDHB mutation 2
Elevated plasma methoxytyramine (>3 times the upper limit) 2
Malignancy is defined solely by the presence of metastatic lesions in sites where chromaffin cells are not normally found 2