MANAGEMENT OF ENDOCRINE DISEASE: Clinical management of paragangliomas

Paragangliomas (PGLs) are rare vascular, neuroendocrine tumors of paraganglia, which derive from either sympathetic tissue in adrenal (pheochromocytomas or PCCs) and extraadrenal (sPGLs) locations, or parasympathetic tissue of the head and neck (HNPGLs). Since HNPGLs are usually benign and most tumors grow slowly, a wait-and-scan policy is often advised. However, their location in the close proximity to cranial nerves and vasculature may result in considerable morbidity due to compression or infiltration of the adjacent structures, necessitating balanced decisions between a wait-and-see policy and active treatment. The main treatment options for HNPGL are surgery and radiotherapy. In contrast to HNPGLs, the majority of sPGL/PCC produce catecholamines, in advanced cases resulting in typical symptoms and signs such as palpitations, headache, diaphoresis and hypertension. The state-of-the-art diagnosis and localization of sPGL/PCC is based on measurement of plasma and/or 24 h urinary excretion of (fractionated) metanephrines and methoxytyramine. sPGL/PCC can subsequently be localized by anatomical (computed tomography and/or magnetic resonance imaging) and functional imaging studies (123I-MIBG-scintigraphy, 111In-pentetreotide scintigraphy, or positron emission tomography with radiolabelled dopamine or dihydroxyphenylalanine). Although most PGL/PCC are benign, factors such as genetic background, tumor size, tumor location, and high methoxytyramine levels are associated with higher rates of metastatic disease. Surgery is the only curative treatment. Treatment options for patients with metastatic disease are limited. PGL/PCC have a strong genetic background, with at least one third of all cases linked to germline mutations in 11 susceptibility genes. As genetic testing becomes more widely available, the diagnosis of PGL/PCC will be made earlier due to routine screening of at-risk patients. Early detection of a familial PGL allows early detection of potentially malignant PGLs and early surgical treatment, reducing the complication rates of this operatio