SFEBES2013 Oral Communications Pituitary and neoplasia (8 abstracts)
Pituitary adenoma and phaeochromocytoma/paraganglioma – a novel syndrome with a heterogeneous genetic background
Judit Dénes 1 , Francesca Swords 2 , Eleanor Rattenberry 3 , Paraskevi Xekouki 4 , Ajith Kumar 5 , Christopher Wassif 6 , Naomi Fersht 7 , Stephanie Baldeweg 8 , Damian Morris 9 , Stafford Lightman 10 , Chris J Thompson 11 , Amar Agha 11 , Aled Rees 12 , Maralyn Druce 1 , Joan Grieve 13 , Michael Powell 13 , Cesar Luiz Boguszewski 14 , Claire Higham 15 , Julian Davis 15 , Cristina Preda 16 , Jacqueline Trouillas 17 , Nadezhda Dalantaeva 18 , Antônio Ribeiro-Oliveira 19 , Pinaki Dutta 20 , Federico Roncaroli 21 , Rajesh V Thakker 22 , Mark Stevenson 22 , Brendan O’Sullivan 23 , Phillipe Taniere 23 , Kassiani Skordilis 23 , Plamena Gabrovska 1 , Anne Barlier 24 , Sian Ellard 25 , Karen Stals 25 , Constantine A. Stratakis 4 , Ashley B. Grossman 26 , Eamonn Maher 3 & Márta Korbonits 1
1Department of Endocrinology, Barts and the London School of Medicine, Queen Mary University of London, London, UK; 2Diabetes, Endocrinology and General Medicine, Norfolk and Norwich University Hospital, Norwich, UK; 3Medical and Molecular Genetics, University of Birmingham, Birmingham, UK; 4Section Endocrinology and Genetics, Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States; 5Clinical Genetics Department, Great Ormond Street Hospital, London, UK; 6Section on Molecular Dysmorphology, Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States; 7Department of Oncology, University College London Hospitals, London, UK; 8Department of Endocrinology, University College London Hospitals, London, UK; 9Department of Diabetes and Endocrinology, The Ipswich Hospital NHS Trust, Ipswich, UK; 10Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Bristol, UK; 11Department of Endocrinology, Beaumont Hospital, Dublin, Ireland; 12Department of Endocrinolgy and Diabetes, Cardiff University School of Medicine, Cardiff, UK; 13Department of Neurosurgery, National Hospital for Neurology and Neurosurgery, London, UK; 14Servico de Endocrinologia e Metabologia Hospital de Clinicas, Universidade Federal do Parana, Curitiba Brazil; 15Department of Endocrinology, Central Manchester University Hospitals, Manchester, UK; 16University of Medecine and Pharmacy “Gr.T.Popa” Iasi, Romania; 17Centre de Pathologie Est, Hospices Civils de Lyon, Lyon, France; 18Endocrinolgy Research Centre, Lomonosov Moscow State University, Moscow, Russia; 19Hospital das Clinicas da Universidade Federal de Minas Gerais, Belo Horizonte, Brazil; 20Department of Endocrinology, Post Graduate Institute of Medical Education and Research, Chandigarh, India; 21Neuropathology Unit, Imperial College, London, UK; 22Academic Endocrine Unit, University of Oxford, Oxford, UK; 23Histopathology - University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK; 24Laboratoire de Biologie Moléculaire, Hôpital de la conception, Marseille, France; 25Department of Molecular Genetics, Royal Devon and Exeter NHS Hospital, Exeter, UK; 26Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.
Pituitary adenomas and phaeochromocytoma/paragangliomas (PHAEO/PGL) can very rarely occur in the same patient or in the same family. Together, they are not known to be part of any classical endocrine neoplasia syndromes. In some caes the pathogenetic mechanism may be secondary to a PHAEO secreting GHRH leading to somatotroph hyperplasia and clinical acromegaly. However, we suggest several other mechanisms which could lead to the development of pituitary and PHAEO/PGL together: a known PHAEO/PGL gene which also causes pituitary adenoma formation, a known pituitary tumour gene which also causes PHAEO/PGL, digenic disease, a new gene(s) causing both diseases, and one must not exclude the possibility that the development of the two tumours together might be coincidence. We found 52 cases in the literature with this combination of diseases, although only 15 of them had a confirmed diagnosis.
We studied 25 patients with the combination of pituitary adenoma and a PHAEO/PGL. Recognised PHAEO/PGL causing genes (SDH A-D, SDHAF2, RET, VHL, TMEM127, MAX) and pituitary adenoma genes (MEN1, AIP, CDKN1B) were sequenced using next generation or Sanger sequencing, and loss of heterozygosity was studied in the tumours, where available.
We identified mutations in SDHB, SDHC, SDHD, MEN1, RET and VHL in some patients and families with PHAEO/PGL and pituitary adenomas (1 SDHA variant of unknown significance, 1 MEN1 variant with unknown pathogenicity and several mutations; 4 SDHB, 1 VHL, 1 SDHC, 1 SDHD and 1 MEN1). Loss of heterozygosity for the relevant gene was shown in all the cases where pituitary tissue was available. In addition, we noted that pituitary adenomas in patients affected by SDH mutations have unique histology.
These data suggest that mutations in some PHAEO/PGL and pituitary genes can affect both these tissue types.
Volume 31
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Endocrine Abstracts
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