Pheochromocytoma and paraganglioma: optimizing surveillance and diagnostic strategies

Pheochromocytomas (PCC) and paragangliomas (PGL), together referred to as PPGLs, are rare neuroendocrine tumors derived from the paraganglion system. Sympathetic PGL and PCC can secrete catecholamines, which can lead to severe cardiovascular complications. Establishing an increased concentration of the metabolites of these catecholamines: metanephrines, is an essential step in the diagnosis of PCC and sympathetic PGL. Paraganglioma derived from parasympathetic paraganglia, mostly located in head and neck region (HNPGL) rarely secrete catecholamines and can give rise to complaints due to compression of cranial nerves. The diagnosis of HNPGL is based on imaging techniques. PPGLs have a high heritability rate as 40% of patients carry germline mutations, requiring regular surveillance.
This thesis aimed to optimize the surveillance of patients and carriers of germline mutations predisposing to PPGLs, and improve the biochemical strategies for diagnosing these tumors. We have focused on optimizing surveillance programs by calculating the cumulative risk of disease in SDHB mutation carriers, proposing an older age to start screening for HNPGL, and extending screening intervals. We have also gained more insights into new susceptibility genes and reviewed the phenotype of TMEM127 mutation, as required for establishing surveillance programs for carriers of this mutation. We have focused on optimizing diagnostics by assessing the accuracy of a new patient-friendly tool, salivary metanephrines, for diagnosing PCC and sympathetic PGL. Furthermore, we have explored a method to decrease stress-related false-positive results in the biochemical diagnosis of PCC and sympathetic PGL, and looked for a new biomarker for HNPGL.