{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T11:01:59Z","timestamp":1788519719682,"version":"build-2803163510"},"reference-count":111,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2019,5,24]],"date-time":"2019-05-24T00:00:00Z","timestamp":1558656000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Malignant pheochromocytomas (PCs) and paragangliomas (PGLs) are rare neuroendocrine neoplasms defined by the presence of distant metastases. There is currently a relatively paucity of data regarding the natural history of PCs\/PGLs and the optimal approach to their treatment. We retrospectively analyzed the clinical, biochemical, imaging, genetic and histopathological characteristics of fourteen patients with metastatic PCs\/PGLs diagnosed over 15 years, along with their response to treatment. Patients were followed-up for a median of six years (range: 1\u201314 years). Six patients had synchronous metastases and the remaining developed metastases after a median of four years (range 2\u201310 years). Genetic analysis of seven patients revealed that three harbored succinate dehydrogenase subunit B\/D gene (SDHB\/D) mutations. Hormonal hypersecretion occurred in 70% of patients; normetanephrine, either alone or with other concomitant hormones, was the most frequent secretory component. Patients were administered multiple first and subsequent treatments including surgery (n = 12), chemotherapy (n = 7), radionuclide therapy (n = 2) and radiopeptides (n = 5). Seven patients had stable disease, four had progressive disease and three died. Ectopic hormonal secretion is rare and commonly encountered in benign PCs. Ectopic secretion of interleukin-6 in one of our patients, prompted a literature review of ectopic hormonal secretion, particularly from metastatic PCs\/PGLs. Only four cases of metastatic PC\/PGLs with confirmed ectopic secretion of hormones or peptides have been described so far.<\/jats:p>","DOI":"10.3390\/cancers11050724","type":"journal-article","created":{"date-parts":[[2019,5,24]],"date-time":"2019-05-24T11:20:46Z","timestamp":1558696846000},"page":"724","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Malignant Pheochromocytomas\/Paragangliomas and Ectopic Hormonal Secretion: A Case Series and Review of the Literature"],"prefix":"10.3390","volume":"11","author":[{"given":"Anna","family":"Angelousi","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Unit of Endocrinology, National and Kapodistrian University of Athens, Laiko hospital, Goudi, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melpomeni","family":"Peppa","sequence":"additional","affiliation":[{"name":"Endocrine Unit, 2nd Department of Internal Medicine Propaedeutic, Research Institute and Diabetes Center, National and Kapodistrian University of Athens, Attikon University Hospital, 12462 Haidari, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Chrisoulidou","sequence":"additional","affiliation":[{"name":"Unit of Endocrinology, Theagenio Cancer Hospital, 2 Al Simeonidi Str., 54007 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2398-6768","authenticated-orcid":false,"given":"Krystallenia","family":"Alexandraki","sequence":"additional","affiliation":[{"name":"1st Department of Propaedeutic Internal Medicine, National and Kapodistrian University of Athens, Laiko hospital, Goudi, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5576-9525","authenticated-orcid":false,"given":"Annabel","family":"Berthon","sequence":"additional","affiliation":[{"name":"Section on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio Rueda","family":"Faucz","sequence":"additional","affiliation":[{"name":"Section on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Kassi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Unit of Endocrinology, National and Kapodistrian University of Athens, Laiko hospital, Goudi, 11527 Athens, Greece"},{"name":"Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Goudi, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Kaltsas","sequence":"additional","affiliation":[{"name":"1st Department of Propaedeutic Internal Medicine, National and Kapodistrian University of Athens, Laiko hospital, Goudi, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,5,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/S0140-6736(05)67139-5","article-title":"Phaeochromocytoma","volume":"366","author":"Lenders","year":"2005","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1677\/ERC-07-0074","article-title":"The diagnosis and management of malignant phaeochromocytoma and paraganglioma","volume":"14","author":"Chrisoulidou","year":"2007","journal-title":"Endocr. 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