Pheochromocytoma and paraganglioma Diagnosis and management Metanephrine assays Obtain plasma free metanephrines or urinary fractionated metanephrines as part of the initial biochemical testing for pheochromocytoma or paraganglioma. A Consider using liquid chromatography with mass spectrometric or electrochemical detection methods rather than other laboratory methods to establish a biochemical diagnosis of pheochromocytoma and paraganglioma. C Consider drawing blood for measurements of plasma metanephrines with the patient in the supine position and using reference intervals established in the same position. C Diagnostic imaging Obtain imaging to locate pheochromocytoma or paraganglioma in patients displaying biochemical evidence of these diseases. B Consider obtaining CT rather than MRI as the initial imaging modality because of its excellent spatial resolution. C Obtain MRI in the following situations: metastatic pheochromocytoma or paraganglioma surgical clips causing artifacts on CT allergy to CT contrast limiting radiation exposure is warranted including pediatric and pregnant patients, recent excessive radiation exposure, and known germline mutations. B Obtain MRI to detect skull base and neck paragangliomas. B Consider obtaining positron emission tomography/CT scanning (rather I- metaiodobenzylguanidine scintigraphy) as the first-line imaging modality in patients with known metastatic pheochromocytoma or paraganglioma. C Consider obtaining I-metaiodobenzylguanidine scintigraphy as a functional imaging modality in patients with metastatic pheochromocytoma or paraganglioma detected by other imaging modalities when radiotherapy using I-metaiodobenzylguanidine scintigraphy is planned. C Consider obtaining I-metaiodobenzylguanidine scintigraphy selectively in some patients with an increased risk for metastatic disease due to the large size of the primary tumor or to extra-adrenal, multifocal (excluding skull base and neck primaries), or recurrent disease. C Genetic testing Engage all patients in shared decision-making for genetic testing. B Use a clinical feature-drive algorithm to establish priorities for specific genetic testing in patients with suspected germline mutations. B Consider testing for succinate dehydrogenase mutations in patients with paraganglioma, and testing for succinate dehydrogenase subunit B (SDHB) mutations in patients with metastatic disease. C Provide pre- and post-test counseling to all patients undergoing genetic testing. Preoperartive alpha-blockers ES Q Does the patient have hormonally functional disease? Yes Administer preoperative adrenergic blockade to prevent cardiovascular complications in patients with hormonally functional disease. B Consider preferring alpha-blockers as the first-line choice for the adrenergic blockade. B Continue treatment for 7-14 days preoperatively to allow adequate time to normalize BP and HR. B Advise a high-sodium diet and liberal fluid intake preoperatively to reverse catecholamine-induced blood volume contraction and prevent severe hypotension after tumor removal. B No Choice of surgical approach Perform minimally invasive adrenalectomy (such as laparoscopic) as the treatment of choice in most patients with adrenal pheochromocytoma. B Perform open adrenalectomy in patients with large (> 6 cm) or invasive pheochromocytoma. B Consider performing open resection in patients with paragangliomas, while consider performing laparoscopic resection in patients with small, noninvasive paragangliomas in surgically favorable locations. C Indications for adrenalectomy ES Q Does the patient have a small tumor? Q Has the patient already undergone contralateral complete adrenalectomy? Q Does the patient have hereditary pheochromocytoma? No to any Yes to all Indications for adrenalectomy ES Q Does the patient have a small tumor? Q Has the patient already undergone contralateral complete adrenalectomy? Q Does the patient have hereditary pheochromocytoma? Yes Consider performing partial adrenalectomy in selected patients (hereditary pheochromocytoma, small tumors undergone contralateral complete adrenalectomy), in order to spare the adrenal cortex and prevent permanent hypocortisolism. C No Perioperative monitoring ES Q Has the patient undergone surgical resection? Yes Monitor BP, HR, and blood glucose levels, and adjust therapy accordingly in the immediate postoperative period. B No Follow-up, laboratory Consider measuring plasma or urine levels of metanephrines on the follow-up to diagnose persistent disease. C