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Once considered, appropriate biochemical testing is key to diagnosis. Advances in understanding catecholamine metabolism have clarified why measurements of the O-methylated catecholamine metabolites rather than the catecholamines themselves are important for effective diagnosis. These metabolites, normetanephrine and metanephrine, produced respectively from norepinephrine and epinephrine, can be measured in plasma or urine, with choice according to available methods or presentation of patients. For patients with signs and symptoms of catecholamine excess, either test will invariably establish the diagnosis, whereas the plasma test provides higher sensitivity than urinary metanephrines for patients screened due to an incidentaloma or genetic predisposition, particularly for small tumors or in patients with an asymptomatic presentation. Additional measurements of plasma methoxytyramine can be important for some tumors, such as paragangliomas, and for surveillance of patients at risk of metastatic disease. Avoidance of false-positive test results is best achieved by plasma measurements with appropriate reference intervals and preanalytical precautions, including sampling blood in the fully supine position. Follow-up of positive results, including optimization of preanalytics for repeat tests or whether to proceed directly to anatomic imaging or confirmatory clonidine tests, depends on the test results, which can also suggest likely size, adrenal vs extra-adrenal location, underlying biology, or even metastatic involvement of a suspected tumor. Modern biochemical testing now makes diagnosis of PPGL relatively simple. Integration of artificial intelligence into the process should make it possible to fine-tune these advances.<\/jats:p>","DOI":"10.1210\/endrev\/bnad011","type":"journal-article","created":{"date-parts":[[2023,3,30]],"date-time":"2023-03-30T22:01:52Z","timestamp":1680213712000},"page":"862-909","source":"Crossref","is-referenced-by-count":113,"title":["Biochemical Assessment of Pheochromocytoma and Paraganglioma"],"prefix":"10.1210","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8601-9903","authenticated-orcid":false,"given":"Graeme","family":"Eisenhofer","sequence":"first","affiliation":[{"name":"Department of Internal Medicine III, University Hospital Carl Gustav Carus, Technische Universit\u00e4t Dresden , 01307 Dresden , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0772-1604","authenticated-orcid":false,"given":"Christina","family":"Pamporaki","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III, University Hospital Carl Gustav Carus, Technische Universit\u00e4t Dresden , 01307 Dresden , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7658-4466","authenticated-orcid":false,"given":"Jacques W M","family":"Lenders","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III, University Hospital Carl Gustav Carus, Technische Universit\u00e4t Dresden , 01307 Dresden , Germany"},{"name":"Department of Internal Medicine, Radboud University Medical Centre , 6500 HB Nijmegen , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2023,3,30]]},"reference":[{"issue":"8","key":"2023091509053197200_bnad011-B1","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1097\/HJH.0000000000002438","article-title":"Genetics, diagnosis, management and future directions of research of phaeochromocytoma and paraganglioma: a position statement and consensus of the working group on endocrine hypertension of the European Society of Hypertension","volume":"38","author":"Lenders","year":"2020","journal-title":"J Hypertens"},{"issue":"2","key":"2023091509053197200_bnad011-B2","doi-asserted-by":"crossref","DOI":"10.1016\/j.beem.2019.101346","article-title":"Pheochromocytoma: an approach to diagnosis","volume":"34","author":"Sbardella","year":"2020","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"issue":"6","key":"2023091509053197200_bnad011-B3","doi-asserted-by":"crossref","first-page":"2656","DOI":"10.1210\/jc.2002-030005","article-title":"Biochemical diagnosis of pheochromocytoma: how to distinguish true- from false-positive test results","volume":"88","author":"Eisenhofer","year":"2003","journal-title":"J Clin Endocrinol Metab"},{"issue":"9","key":"2023091509053197200_bnad011-B4","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1055\/s-0029-1237699","article-title":"False positive test results for pheochromocytoma from 2000 to 2008","volume":"118","author":"Yu","year":"2010","journal-title":"Exp Clin Endocrinol Diabetes"},{"key":"2023091509053197200_bnad011-B5","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.clinbiochem.2020.01.005","article-title":"Very high rate of false positive biochemical results when screening for pheochromocytoma in a large, undifferentiated population with variable indications for testing","volume":"77","author":"Kline","year":"2020","journal-title":"Clin Biochem"},{"issue":"2","key":"2023091509053197200_bnad011-B6","first-page":"637","article-title":"A survey on adrenal incidentaloma in Italy. 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