• Judit Dénes, Francesca Swords, Eleanor Rattenberry, Karen Stals, Martina Owens, Treena Cranston, Paraskevi Xekouki, Linda Moran, Ajith Kumar, Christopher Wassif, Naomi Fersht, Stephanie E Baldeweg, Damian Morris, Stafford Lightman, Amar Agha, Aled Rees, Joan Grieve, Michael Powell, Cesar Luiz Boguszewski, Pinaki Dutta, Rajesh V Thakker, Umasuthan Srirangalingam, Chris J Thompson, Maralyn Druce, Claire Higham, Julian Davis, Rosalind Eeles, Mark Stevenson, Brendan O'Sullivan, Phillipe Taniere, Kassiani Skordilis, Plamena Gabrovska, Anne Barlier, Susan M Webb, Anna Aulinas, William M Drake, John S Bevan, Cristina Preda, Nadezhda Dalantaeva, Antônio Ribeiro-Oliveira, Isabel Tena Garcia, Galina Yordanova, Violeta Iotova, Jane Evanson, Ashley B Grossman, Jacqueline Trouillas, Sian Ellard, Constantine A Stratakis, Eamonn R Maher, Federico Roncaroli, and Márta Korbonits.
• Department of Endocrinology (J.D., U.S., M.D., P.G., W.M.D., M.K.), Barts and the London School of Medicine, Queen Mary University of London, London EC1M 6BQ, United Kingdom; Semmelweis University, School of PhD studies, Doctoral School of Clinical Medicine, Budapest, Hungary (J.D.), Endocrinology Directorate (F.S.), Norfolk and Norwich University Hospital, Norwich NR4 7UZ, United Kingdom; Department of Medical and Molecular Genetics (E.R., E.R.M.), University of Birmingham, Birmingham B15 2TT, United Kingdom; Department of Molecular Genetics (K.S., M.O., S.E.), Royal Devon and Exeter National Health Service Foundation Trust, Exeter EX2 5DW, United Kingdom; University of Exeter Medical School (S.E.), Exeter EX4 4PY, United Kingdom; Oxford Medical Genetics Laboratories (T.C.), Oxford University Hospitals National Health Service Trust, The Churchill Hospital, Oxford OX3 7LJ, United Kingdom; Section on Endocrinology and Genetics (P.X., C.A.S.) and Section on Molecular Dysmorphology (C.W.), Eunice Kennedy Shriver Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892; Electron Microscopy Unit (L.M.), Department Histopathology, Charing Cross Hospital, Imperial College Healthcare National Health Service Trust, London W6 8RF, United Kingdom; Department of Clinical Genetics (A.K.), Great Ormond Street Hospital, London WC1N 1LE, United Kingdom; Departments of Oncology (N.F.) and Endocrinology (S.E.B.), University College London Hospitals, London WC1E 6BT, United Kingdom; Department of Diabetes and Endocrinology (D.M.), The Ipswich Hospital National Health Service Trust, Ipswich IP4 5PD, United Kingdom; Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology (S.L.), University of Bristol, Bristol BS1 3NY, United Kingdom; Department of Endocrinology (A.Ag., C.J.T.), Beaumont Hospital, Dublin 9, Ireland; Institute of Molecular and Experimental Medicine (A.R.), Cardiff University, Cardiff CF10 3US, United Kingd
• J. Clin. Endocrinol. Metab. 2015 Mar 1; 100 (3): E531-41.

ContextPituitary adenomas and pheochromocytomas/paragangliomas (pheo/PGL) can occur in the same patient or in the same family. Coexistence of the two diseases could be due to either a common pathogenic mechanism or a coincidence.ObjectiveThe objective of the investigation was to study the possible coexistence of pituitary adenoma and pheo/PGL.DesignThirty-nine cases of sporadic or familial pheo/PGL and pituitary adenomas were investigated. Known pheo/PGL genes (SDHA-D, SDHAF2, RET, VHL, TMEM127, MAX, FH) and pituitary adenoma genes (MEN1, AIP, CDKN1B) were sequenced using next generation or Sanger sequencing. Loss of heterozygosity study and pathological studies were performed on the available tumor samples.SettingThe study was conducted at university hospitals.PatientsThirty-nine patients with sporadic of familial pituitary adenoma and pheo/PGL participated in the study.OutcomeOutcomes included genetic screening and clinical characteristics.ResultsEleven germline mutations (five SDHB, one SDHC, one SDHD, two VHL, and two MEN1) and four variants of unknown significance (two SDHA, one SDHB, and one SDHAF2) were identified in the studied genes in our patient cohort. Tumor tissue analysis identified LOH at the SDHB locus in three pituitary adenomas and loss of heterozygosity at the MEN1 locus in two pheochromocytomas. All the pituitary adenomas of patients affected by SDHX alterations have a unique histological feature not previously described in this context.ConclusionsMutations in the genes known to cause pheo/PGL can rarely be associated with pituitary adenomas, whereas mutation in a gene predisposing to pituitary adenomas (MEN1) can be associated with pheo/PGL. Our findings suggest that genetic testing should be considered in all patients or families with the constellation of pheo/PGL and a pituitary adenoma.

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