{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T17:29:13Z","timestamp":1790270953226,"version":"4.1.0"},"reference-count":0,"publisher":"Oxford University Press (OUP)","issue":"4","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:sec>\n<jats:title><jats:italic>Background:<\/jats:italic><\/jats:title>\n<jats:p>The \u20183PAs\u2019 syndrome, associating pituitary adenoma (PA) and pheochromocytoma\/paraganglioma (PPGL), is sometimes associated with mutations in PPGL-predisposing genes, such as <jats:italic>SDHx<\/jats:italic> or <jats:italic>MAX<\/jats:italic>. In \u20193PAs\u2019 syndrome, PAs can occur before PPGL, suggesting a new gateway into <jats:italic>SDHx\/MAX-<\/jats:italic>related diseases.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title><jats:italic>Objective:<\/jats:italic><\/jats:title>\n<jats:p>To determine the <jats:italic>SDHx\/MAX<\/jats:italic> mutation prevalence in patients with isolated PAs and characterize PAs of patients with <jats:italic>SDHx\/MAX<\/jats:italic> mutations.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title><jats:italic>Design:<\/jats:italic><\/jats:title>\n<jats:p>Genes involved in PAs (<jats:italic>AIP\/MEN1\/CDKN1B<\/jats:italic>) or PPGLs (<jats:italic>SDHx\/MAX<\/jats:italic>) were sequenced in patients with isolated PAs. We then conducted a review of cases of PA in the setting of \u20193PAs\u2019 syndrome.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title><jats:italic>Results:<\/jats:italic><\/jats:title>\n<jats:p>A total of 263 patients were recruited. Seven (likely) pathogenic variants were found in <jats:italic>AIP<\/jats:italic>, two in <jats:italic>MEN1<\/jats:italic>, two in <jats:italic>SDHA<\/jats:italic>, and one in <jats:italic>SDHC<\/jats:italic>. The prevalence of <jats:italic>SDHx<\/jats:italic> mutations reached 1.1% (3\/263). Of 31 reported patients with PAs harboring <jats:italic>SDHx\/MAX<\/jats:italic> mutations (28 published cases and 3 cases reported here), 6\/31 (19%) developed PA before PPGL and 8\/31 (26%) had isolated PA. The age of onset was later than in patients with <jats:italic>AIP\/MEN1<\/jats:italic> mutations. PAs were mainly macroprolactinomas and showed intracytoplasmic vacuoles seen on histopathology.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title><jats:italic>Conclusions:<\/jats:italic><\/jats:title>\n<jats:p>We discovered <jats:italic>SDHx<\/jats:italic> mutations in patients bearing PA who had no familial or personal history of PPGL. However, the question of incidental association remains unresolved and data to determine the benefit of <jats:italic>SDHx\/MAX<\/jats:italic> screening in these patients are lacking. We recommend that patients with isolated PA should be carefully examined for a family history of PPGLs. A family history of PPGL, as well as the presence of intracytoplasmic vacuoles in PA, requires <jats:italic>SDHx\/MAX<\/jats:italic> genetic testing of patients.<\/jats:p>\n<\/jats:sec>","DOI":"10.1530\/eje-20-0054","type":"journal-article","created":{"date-parts":[[2020,7,3]],"date-time":"2020-07-03T17:09:19Z","timestamp":1593796159000},"page":"369-379","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-7","source":"Crossref","is-referenced-by-count":27,"title":["Germinal defects of SDHx genes in patients with isolated pituitary adenoma"],"prefix":"10.1093","volume":"183","author":[{"given":"Gr\u00e9gory","family":"Mougel","sequence":"first","affiliation":[{"name":"1Aix Marseille Univ, APHM, INSERM, MMG, Hospital La Conception, Laboratory of Molecular Biology, Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaud","family":"Lagarde","sequence":"additional","affiliation":[{"name":"1Aix Marseille Univ, APHM, INSERM, MMG, Hospital La Conception, Laboratory of Molecular Biology, Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9rique","family":"Albarel","sequence":"additional","affiliation":[{"name":"2Department of Endocrinology, Hospital La Conception, APHM, Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wassim","family":"Essamet","sequence":"additional","affiliation":[{"name":"3Department of Pathology, Hospital La Timone, APHM, Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Perrine","family":"Luigi","sequence":"additional","affiliation":[{"name":"4Department of Endocrinology, Hospital Lapeyronie, CHU Montpellier, Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Mouly","sequence":"additional","affiliation":[{"name":"5Department of Endocrinology, Hospital Larrey, CHU Toulouse, Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magaly","family":"Vialon","sequence":"additional","affiliation":[{"name":"5Department of Endocrinology, Hospital Larrey, CHU Toulouse, Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Cuny","sequence":"additional","affiliation":[{"name":"6Aix Marseille University, APHM, INSERM, MMG, Hospital La Conception, Department of Endocrinology, Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Castinetti","sequence":"additional","affiliation":[{"name":"6Aix Marseille University, APHM, INSERM, MMG, Hospital La Conception, Department of Endocrinology, Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandru","family":"Saveanu","sequence":"additional","affiliation":[{"name":"1Aix Marseille Univ, APHM, INSERM, MMG, Hospital La Conception, Laboratory of Molecular Biology, Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Brue","sequence":"additional","affiliation":[{"name":"6Aix Marseille University, APHM, INSERM, MMG, Hospital La Conception, Department of Endocrinology, Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Barlier","sequence":"additional","affiliation":[{"name":"1Aix Marseille Univ, APHM, INSERM, MMG, Hospital La Conception, Laboratory of Molecular Biology, Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pauline","family":"Romanet","sequence":"additional","affiliation":[{"name":"1Aix Marseille Univ, APHM, INSERM, MMG, Hospital La Conception, Laboratory of Molecular Biology, Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","container-title":["European Journal of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/183\/4\/EJE-20-0054.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/eje.bioscientifica.com\/downloadpdf\/journals\/eje\/183\/4\/EJE-20-0054.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T16:14:29Z","timestamp":1676391269000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ejendo\/article\/183\/4\/369\/6653749"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10]]},"references-count":0,"journal-issue":{"issue":"4"},"URL":"https:\/\/doi.org\/10.1530\/eje-20-0054","relation":{},"ISSN":["0804-4643","1479-683X"],"issn-type":[{"value":"0804-4643","type":"print"},{"value":"1479-683X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10]]}}}