paragangliomapheochromocytoma

Paragangliomapheochromocytoma describes tumors arising from paraganglia outside the adrenal gland (paragangliomas) and from the adrenal medulla (pheochromocytoma). Together they form the pheochromocytoma-paraganglioma (PPGL) spectrum. Most PPGLs are neuroendocrine tumors that secrete catecholamines, causing hypertension, headaches, palpitations, and sweating; many are biochemically silent.

Location and genetics: Paragangliomas occur in the head and neck or along the sympathetic chain; pheochromocytomas are adrenal. About 30–40% of PPGLs are hereditary, with germline mutations in SDHx, VHL, RET, NF1, MAX, TMEM127 or EGLN1. SDHB mutations are linked to higher metastatic risk; genetic testing and counseling are recommended for patients and at-risk relatives.

Diagnosis: Biochemical testing uses plasma-free metanephrines or urinary fractionated metanephrines to detect catecholamine excess. Localization combines CT or MRI with functional imaging such as MIBG scintigraphy or PET using 68Ga-DOTATATE or 18F-FDOPA to identify disease sites and differentiate pheochromocytoma from paraganglioma.

Treatment and prognosis: The main treatment for localized disease is surgical resection after preoperative alpha-adrenergic blockade. Adrenal pheochromocytomas and extra-adrenal paragangliomas may require different surgical approaches. Metastatic or unresectable disease may be treated with radiopharmaceuticals (e.g., 177Lu-DOTATATE) or chemotherapy; ongoing surveillance and genetic counseling are advised. Prognosis depends on location, metastatic status and underlying mutation, with SDHB-associated tumors carrying higher risk of spread.