Project title
游離腎上腺素在嗜鉻細胞瘤與副神經節瘤的診斷、臨床表型、預後和基因學之應用
Internal ID
109-2314-B-002-190-
Principal Investigator
Start Date
August 1, 2020
End Date
July 31, 2021
Investigators
Organizations
Partner Organizations
Free Metanephrines Implications on Diagnosis, Phenotype, Prognosis and Genetics of Pheochromocytomas and Paragangliomas (Ppgls) = 游離腎上腺素在嗜鉻細胞瘤與副神經節瘤的診斷、臨床表型、預後和基因學之應用
Keywords
Free Metanephrines
Pheochromocytomas and Paragangliomas (PPGLs)
Diagnosis
Phenotype
Prognosis
Genetics
Description
Pheochromocytoma-paraganglioma (PPGLs) are rare neuroendocrine tumors characterized by excessive secretion of catecholamines. If not accurate diagnosed or left untreated, it can cause serious complications and even death. PPGLs also have the opportunity to be cured by surgery. Therefore, timely diagnosis and appropriate treatment are essential. However, the symptoms of PPGLs are "great mimickers" and the diagnosis depends on reliable biochemical tests, which step is really challenging. Traditional 24-hr urine VMA & catecholamines had inadequate sensitivity, which lead to false negative results and miss diagnose PPGLs. Plasma free metanephrines (PFMs) measured by liquid chromatography tandem mass spectrometry (HPLC-MS / MS) provides highest diagnostic accuracy and became the recommended screening and diagnostic tool. However, this test is not common applied in clinical practice in Taiwan.Unfortunately, reference intervals for PFMs are all too often inappropriately established, and use of inappropriately high upper cutoffs of PFMs leads to lower diagnostic sensitivity. Diagnostic specificity should also be enhanced to minimize false-positive results and avoid unnecessary surgery. The reference intervals and upper cutoffs are different in different laboratories, which most of them reported from Europe and America. There is no relevant research in Taiwan. This study will collect reference populations and PPGLs patients to establish the Taiwan reference intervals and appropriate upper cutoffs of "PFMs" to improve the diagnosis accuracy of PPGLs (Aim A).In addition, most PPGLs have a benign course and can be successfully treated by surgery. About 15% of PPGLs are malignant or aggressive (rapid growth or multiple relapses), which was lack of appropriate treatment options. The predictive factors to differential benign course, aggressiveness, or metastasis are limited and imprecise. Search for the reliable predictors to distinguish true benign PPGLs from those eventually develop malignant or aggressive diseases is important. Tumor size and location have been proven to be predictors of PPGLs malignant risk. Secretion pattern of catecholamines can be used as indirect tumor localization markers, and its metabolites metanephrines are more faithfully reflect tumor secretion patterns. This study will explore the relationship between "PFMs" and the position, size, and clinical behavior of PPGLs, and apply them to predict the clinical phenotype, aggressiveness, and prognosis of PPGLs (Aim B).The last, PPGLs are highest hereditary tumors in all human tumors, with about 40% of familial diseases and 30-40% of somatic mutations. PPGLs are genetically heterogeneous tumors, and currently 34 genes have been reported. Genetic test is recommended for all the PPGLs to provide appropriate treatment strategy. However, with the increasing list of the potential gene mutations, and the genotype is not always predicted well by phenotype, these makes genetic test a time- and resource-consuming process. This study will explore the correlation between "PFMs" and PPGLs gene mutation patterns, and provide further information to guide targeted gene screening protocol (Aim C).