MANAGEMENT OF ENDOCRINE DISEASE: Clinical management of paragangliomas

Abstract

Paragangliomas (PGLs) are rare vascular, neuroendocrine tumors of paraganglia, which are associated with either sympathetic tissue in adrenal (pheochromocytomas (PCCs)) and extraadrenal (sympathetic paraganglioma (sPGLs)) locations or parasympathetic tissue of the head and neck paragangliomas (HNPGLs). As 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/PCCs produces 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/PCCs are based on measurement of plasma and/or 24-h urinary excretion of (fractionated) metanephrines and methoxytyramine (MT). sPGL/PCCs can subsequently be localized by anatomical (computed tomography and/or magnetic resonance imaging) and functional imaging studies ( 123 I-metaiodobenzylguanidine-scintigraphy, 111 In-pentetreotide scintigraphy, or positron emission tomography with radiolabeled dopamine or dihydroxyphenylalanine). Although most PGL/PCCs are benign, factors such as genetic background, tumor size, tumor location, and high MT 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/PCCs have a strong genetic background, with at least one-third of all cases linked with germline mutations in 11 susceptibility genes. As genetic testing becomes more widely available, the diagnosis of PGL/PCCs 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 operation.

Primary functioning hepatic paraganglioma mimicking hepatocellular carcinoma

“…Symptoms of catecholamine excess are a characteristic manifestation of sPGLs, although approximately 10% to 15% of sPGLs are asymptomatic. [ 3 ] In this case, the patient suffered from hyperglycemia and was diagnosed as having diabetes for 6 years before surgery, and levels of blood glucose were gradually turned into normal after the operation, which suggested that hyperglycemia is induced by catecholamine release. In the reported 11 HPGL cases, 2 showed headache, 1 showed both headache and palpitation, and 1 female patient showed abnormal menstruation.…”

“…[ 2 ] According to the World Health Organization (WHO), tumors which are related to sympathetic tissues in the adrenal gland should be named as pheochromocytomas (PCCs), whereas tumors related to extraadrenal sympathetic tissues should be named as sympathetic paragangliomas (sPGLs). [ 3 ] sPGL often occurs along the axis of the body, from skull-base to the pelvic floor and corresponds to the distribution of the sympathetic nerve. [ 4 ] In summary, PGLs include sPGLs and HNPGLs.…”

Monitoring the Secretory Behavior of the Rat Adrenal Medulla by High-Performance Liquid Chromatography-Based Catecholamine Assay from Slice Supernatants

“…In basic research, the secretory behavior of the adrenal glands is usually examined through the determination of CA (and/or their metabolites) levels in the systemic blood circulation or in the urines. In clinical medicine, measurements of plasma and urinary CA and/or their metabolite levels can be used to for the diagnosis and the follow-up of several neuroendocrine tumors, such as neuroblastoma ( 8 ), paragangliomas ( 9 ), pheochromocytomas ( 10 – 12 ), early arterial hypertension ( 13 , 14 ), and also for evaluating hemodynamic and sympathoadrenal functions in patients in intensive cares ( 15 – 17 ).…”

Malignant extra-adrenal pelvic paraganglioma in a paediatric patient

“…Of these, approximately 12% are considered malignant [ 1 – 3 ]. Accordingly, the only widely accepted criterion is the presence of metastases in organs where normally there are no chromaffin cells, as is the case of lymph nodes [ 3 , 4 ]. Extra-adrenal paragangliomas are usually diagnosed in the retroperitoneum, head, and neck.…”

“…Those located in the abdomen and pelvis are associated with the sympathetic nervous system, with catecholamine hypersecretions being the cause of the signs and symptoms during the clinical presentation, as well as the possible effects of mass on neighbouring organs [ 5 , 6 ]. The treatment of choice for this type of neoplasm is surgical resection and eventually, tumour embolisation prior to surgery or the administration of combined chemotherapy [ 3 , 4 ].…”