{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T04:45:45Z","timestamp":1771303545305,"version":"3.50.1"},"reference-count":19,"publisher":"The Endocrine Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Introduction: Malignant paragangliomas have been well described in carriers of mutations of the succinate dehydrogenase B (SDHB) gene, but have rarely been associated with mutations in the succinate dehydrogenase D (SDHD) gene.<\/jats:p>\n               <jats:p>Aim: The aim of the study was to report the different clinical expression patterns of malignant paragangliomas in five patients with SDHD (D92Y) mutations observed in approximately 200 SDHD (D92Y) mutation carriers followed in our institution.<\/jats:p>\n               <jats:p>Results: Metastasis and\/or local tumor invasion was documented 0 (n = 2), 1, 18, and 30 yr after the initial diagnosis of paraganglioma. Malignancy was proven by paraganglioma bone metastases (n = 2), intrathoracic paraganglioma with lymph node metastases, locally invasive head-and-neck paraganglioma with destruction of the petrosal bone, and locally invasive paraganglioma of the bladder with lymph node metastases. Four of the five patients developed catecholamine excess during follow-up due to intraadrenal paraganglioma (pheochromocytoma) (n = 1), extra adrenal paraganglioma (n = 2), and presumed subclinical disease (n = 1).<\/jats:p>\n               <jats:p>Conclusion: SDHD mutations (D92Y) are associated with malignant paragangliomas and catecholamine excess with remarkable interindividual variations despite the same mutation. We estimate that the prevalence of malignancy in carriers of D92Y mutations is at least 2.5%.<\/jats:p>","DOI":"10.1210\/jc.2006-1993","type":"journal-article","created":{"date-parts":[[2007,1,17]],"date-time":"2007-01-17T02:58:58Z","timestamp":1169002738000},"page":"1245-1248","source":"Crossref","is-referenced-by-count":58,"title":["Malignant Paragangliomas Associated with Mutations in the Succinate Dehydrogenase D Gene"],"prefix":"10.1210","volume":"92","author":[{"given":"B.","family":"Havekes","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolic Diseases (B.H., E.P.M.C., J.A.R.), Leiden University Medical Center, 2300 RC Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E. P. M.","family":"Corssmit","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolic Diseases (B.H., E.P.M.C., J.A.R.), Leiden University Medical Center, 2300 RC Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. C.","family":"Jansen","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology (J.C.J., A.G.L.v.d.M.), Leiden University Medical Center, 2300 RC Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. G. L.","family":"van der Mey","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology (J.C.J., A.G.L.v.d.M.), Leiden University Medical Center, 2300 RC Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. H. J. T.","family":"Vriends","sequence":"additional","affiliation":[{"name":"Center of Human and Clinical Genetics (A.H.J.T.V.), Leiden University Medical Center, 2300 RC Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. A.","family":"Romijn","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolic Diseases (B.H., E.P.M.C., J.A.R.), Leiden University Medical Center, 2300 RC Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","reference":[{"key":"2020071613421530300_R1","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1126\/science.287.5454.848","article-title":"Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma.","volume":"287","author":"Baysal","year":"2000","journal-title":"Science"},{"key":"2020071613421530300_R2","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1038\/81551","article-title":"Mutations in SDHC cause autosomal dominant paraganglioma, type 3.","volume":"26","author":"Niemann","year":"2000","journal-title":"Nat Genet"},{"key":"2020071613421530300_R3","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1086\/321282","article-title":"Gene mutations in the succinate dehydrogenase subunit SDHB cause susceptibility to familial pheochromocytoma and to familial paraganglioma.","volume":"69","author":"Astuti","year":"2001","journal-title":"Am J Hum Genet"},{"key":"2020071613421530300_R4","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/j.1749-6632.2002.tb04409.x","article-title":"New insights into the genetics of familial chromaffin cell tumors.","volume":"970","author":"Koch","year":"2002","journal-title":"Ann NY Acad Sci"},{"key":"2020071613421530300_R5","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1210\/jc.2005-1862","article-title":"Clinical presentation and penetrance of pheochromocytoma\/paraganglioma syndromes.","volume":"91","author":"Benn","year":"2006","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613421530300_R6","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1001\/jama.292.8.943","article-title":"Distinct clinical features of paraganglioma syndromes associated with SDHB and SDHD gene mutations.","volume":"292","author":"Neumann","year":"2004","journal-title":"JAMA"},{"key":"2020071613421530300_R7","doi-asserted-by":"crossref","first-page":"8812","DOI":"10.1200\/JCO.2005.03.1484","article-title":"Genetic testing in pheochromocytoma or functional paraganglioma.","volume":"23","author":"Amar","year":"2005","journal-title":"J Clin Oncol"},{"key":"2020071613421530300_R8","doi-asserted-by":"crossref","first-page":"4101","DOI":"10.1210\/jc.2002-020312","article-title":"Familial malignant catecholamine-secreting paraganglioma with prolonged survival associated with mutation in the succinate dehydrogenase B gene.","volume":"87","author":"Young","year":"2002","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613421530300_R9","doi-asserted-by":"crossref","first-page":"4505","DOI":"10.1210\/jc.2006-0423","article-title":"High frequency of SDHB germline mutations in patients with malignant catecholamine-producing paragangliomas: implications for genetic testing.","volume":"91","author":"Brouwers","year":"2006","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613421530300_R10","first-page":"6822","article-title":"Somatic and occult germ-line mutations in SDHD, a mitochondrial complex II gene, in nonfamilial pheochromocytoma.","volume":"60","author":"Gimm","year":"2000","journal-title":"Cancer Res"},{"key":"2020071613421530300_R11","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1002\/ajmg.1270","article-title":"Novel mutations and the emergence of a common mutation in the SDHD gene causing familial paraganglioma.","volume":"100","author":"Milunsky","year":"2001","journal-title":"Am J Med Genet"},{"key":"2020071613421530300_R12","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1007\/s00439-003-0969-6","article-title":"Altitude is a phenotypic modifier in hereditary paraganglioma type 1: evidence for an oxygen-sensing defect.","volume":"113","author":"Astrom","year":"2003","journal-title":"Hum Genet"},{"key":"2020071613421530300_R13","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1530\/eje.1.01833","article-title":"Increased prevalence of catecholamine excess and phaeochromocytomas in a well-defined Dutch population with SDHD-linked head and neck paragangliomas.","volume":"152","author":"Houtum","year":"2005","journal-title":"Eur J Endocrinol"},{"key":"2020071613421530300_R14","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1002\/gcc.1144","article-title":"Nearly all hereditary paragangliomas in the Netherlands are caused by two founder mutations in the SDHD gene.","volume":"31","author":"Taschner","year":"2001","journal-title":"Genes Chromosomes Cancer"},{"key":"2020071613421530300_R15","doi-asserted-by":"crossref","first-page":"2057","DOI":"10.1001\/jama.294.16.2057","article-title":"Predictors and prevalence of paraganglioma syndrome associated with mutations of the SDHC gene.","volume":"294","author":"Schiavi","year":"2005","journal-title":"JAMA"},{"key":"2020071613421530300_R16","first-page":"1599","article-title":"Effects of therapy with [177Lu-DOTA0, Tyr3]octreotate in patients with paraganglioma, meningioma, small cell lung carcinoma, and melanoma.","volume":"47","author":"Essen","year":"2006","journal-title":"J Nucl Med"},{"key":"2020071613421530300_R17","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1016\/S0090-4295(01)00966-9","article-title":"Pheochromocytoma.","volume":"57","author":"Klingler","year":"2001","journal-title":"Urology"},{"key":"2020071613421530300_R18","first-page":"1160","article-title":"Comparison of adrenal and extraadrenal pheochromocytomas.","volume":"114","author":"Pommier","year":"1993","journal-title":"Surgery"},{"key":"2020071613421530300_R19","doi-asserted-by":"crossref","first-page":"310","DOI":"10.4158\/EP.9.4.310","article-title":"Hypotension in a woman with a metastatic dopamine-secreting carotid body tumor.","volume":"9","author":"Koch","year":"2003","journal-title":"Endocr Pract"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/92\/4\/1245\/9051980\/jcem1245.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/92\/4\/1245\/9051980\/jcem1245.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,17]],"date-time":"2020-07-17T00:26:28Z","timestamp":1594945588000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/92\/4\/1245\/2596853"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,4,1]]},"references-count":19,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2007,4,1]]}},"URL":"https:\/\/doi.org\/10.1210\/jc.2006-1993","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,4,1]]}}}