Därr, Roland (37101227300)Roland (37101227300)DärrNambuba, Joan (57127225100)Joan (57127225100)NambubaDel Rivero, Jaydira (42361055400)Jaydira (42361055400)Del RiveroJanssen, Ingo (56884059400)Ingo (56884059400)JanssenMerino, Maria (9333497500)Maria (9333497500)MerinoTodorovic, Milena (23010544100)Milena (23010544100)TodorovicBalint, Bela (7005347355)Bela (7005347355)BalintJochmanova, Ivana (37101759000)Ivana (37101759000)JochmanovaPrchal, Josef T (7103030279)Josef T (7103030279)PrchalLechan, Ronald M (7005636129)Ronald M (7005636129)LechanTischler, Arthur S (7005414826)Arthur S (7005414826)TischlerPopovic, Vera (35451450900)Vera (35451450900)PopovicMiljic, Dragana (6505968542)Dragana (6505968542)MiljicAdams, Karen T (8357491300)Karen T (8357491300)AdamsPrall, F Ryan (57095726900)F Ryan (57095726900)PrallLing, Alexander (7102194533)Alexander (7102194533)LingGolomb, Meredith R (7004518624)Meredith R (7004518624)GolombFerguson, Michael (56861701400)Michael (56861701400)FergusonNilubol, Naris (15848795800)Naris (15848795800)NilubolChen, Clara C (8054736800)Clara C (8054736800)ChenChew, Emily (7102013764)Emily (7102013764)ChewTaïeb, David (13606337500)David (13606337500)TaïebStratakis, Constantine A (7006596684)Constantine A (7006596684)StratakisFojo, Tito (7005480840)Tito (7005480840)FojoYang, Chunzhang (36836399700)Chunzhang (36836399700)YangKebebew, Electron (7003372219)Electron (7003372219)KebebewZhuang, Zhengping (7203003412)Zhengping (7203003412)ZhuangPacak, Karel (56911173300)Karel (56911173300)Pacak2025-06-122025-06-122016https://doi.org/10.1530/ERC-16-0231https://www.scopus.com/inward/record.uri?eid=2-s2.0-84997787320&doi=10.1530%2fERC-16-0231&partnerID=40&md5=2fec82d500c8afa9cd3cb0531de55608https://remedy.med.bg.ac.rs/handle/123456789/7383Worldwide, the syndromes of paraganglioma (PGL), somatostatinoma (SOM) and early childhood polycythemia are described in only a few patients with somatic mutations in the hypoxia-inducible factor 2 alpha (HIF2A). This study provides detailed information about the clinical aspects and course of 7 patients with this syndrome and brings into perspective these experiences with the pertinent literature. Six females and one male presented at a median age of 28 years (range 11-46). Two were found to have HIF2A somatic mosaicism. No relatives were affected. All patients were diagnosed with polycythemia before age 8 and before PGL/SOM developed. PGLs were found at a median age of 17 years (range 8-38) and SOMs at 29 years (range 22-38). PGLs were multiple, recurrent and metastatic in 100, 100 and 29% of all cases, and SOMs in 40, 40 and 60%, respectively. All PGLs were primarily norepinephrine-producing. All patients had abnormal ophthalmologic findings and those with SOMs had gallbladder disease. Computed tomography (CT) and magnetic resonance imaging revealed cystic lesions at multiple sites and hemangiomas in 4 patients (57%), previously thought to be pathognomonic for von Hippel-Lindau disease. The most accurate radiopharmaceutical to detect PGL appeared to be [18F]-fluorodihydroxyphenylalanine ([18F]-FDOPA). Therefore, [18F]-FDOPA PET/CT, not [68Ga]-(DOTA)-[Tyr3]-octreotate ([68Ga]-DOTATATE) PET/CT is recommended for tumor localization and aftercare in this syndrome. The longterm prognosis of the syndrome is unknown. However, to date no deaths occurred after 6 years follow-up. Physicians should be aware of this unique syndrome and its diagnostic and therapeutic challenges. © 2016 Society for Endocrinology.HIF2A mutationParagangliomaPheochromocytomaPolycythemiaSomatostatinoma