Pheochromocytoma

Abstract

Pheochromocytomas are catecholamine-secreting tumors derived from chromaffin tissue of the adrenal medulla. Closely related tumors, called extra-adrenal paragangliomas, can arise at extra-adrenal sites. Catecholamine secretion from these tumors is often episodic, causing headache, perspiration, palpitations and hypertension. If not recognized and treated, pheochromocytoma and extra-adrenal paraganglioma(PPGL) can lead to arrhythmia, myocardial infarction, stroke, and death. Diagnosis of PPGL relies on biochemical evidence of excess catecholamine secretion and confirmation of tumor presence by imaging studies. While many different biochemical tests have historically been used in screening for PPGL, measurement of the catecholamine breakdown products metanephrine and normetanephrine in plasma or urine are now regarded as the first line tests. Florid elevations of either of these metabolites are associated with nearly a 100% probability of PPGL. However, it can be challenging to differentiate between true-positive and false positive results when metanephrine or normetanephrine concentrations are only slightly above the respective upper reference limit. Not too long ago, approximately 90% of PPGLs were thought to occur sporadically. However, germline mutations in 10 different genes have been shown to cause PPGLs, and at least 30% of these tumors are now known to be hereditary. Importantly, genotype-phenotype correlations have been elucidated: different mutations are associated with specific clinical features and sites of disease, the production of certain catecholamines, and varying frequency of malignancy. In this Q&A article, 5 experts discuss the current state of the art in the diagnosis, localization, and treatment of PPGL. They also provide their opinions on the role of genetic testing in the diagnosis and management of patients with these tumors.