Hereditary Pheochromocytoma and Multiple Endocrine Neoplasia Type 2 (MEN2)

This chapter focuses on pheochromocytomas which are rare neural crest-derived tumors of the adrenal medulla and multiple endocrine neoplasia type 2 (MEN2). Pheochromocytomas results in hypersecretion of catecholamines that causes headache, palpitations, hypertension and excessive perspiration. Paragangliomas are stated to be extra-adrenal pheochromocytomas and they are histologically identical, but occur outside of the adrenal medulla either in sympathetic or parasympathetic paraganglia. The hereditary cases of pheochromocytoma and paraganglioma most commonly include multiple endocrine neoplasia type 2A and 2B, von Hippel-Lindau syndrome (VHL) and familial paraganglioma. Multiple endocrine neoplasia type 2 (MEN2) is characterized by a high risk of developing medullary thyroid carcinoma (MTC). MEN2 is inherited in an autosomal dominant manner and results from a germline mutation in the RET proto-oncogene. VHL is caused by germline inactivating mutations of the VHL tumor suppressor gene located on chromosome 3p25. Another disorder associated with hereditary pheochromocytoma is mentioned to be neurofibromatosis type 1 and the diagnosis is done on the physical manifestations by physical examination and genetic testing is generally not necessary.