Heterogeneous genetic background of the association of pheochromocytoma/paraganglioma and pituitary adenoma: results from a large patient cohort

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 DuttaRajesh 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, Márta Korbonits

Research output: Contribution to journalArticle (Academic Journal)peer-review

131 Citations (Scopus)


CONTEXT: Pituitary 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.

OBJECTIVE: The objective of the investigation was to study the possible coexistence of pituitary adenoma and pheo/PGL.

DESIGN: Thirty-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.

SETTING: The study was conducted at university hospitals.

PATIENTS: Thirty-nine patients with sporadic of familial pituitary adenoma and pheo/PGL participated in the study.

OUTCOME: Outcomes included genetic screening and clinical characteristics.

RESULTS: Eleven 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.

CONCLUSIONS: Mutations 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.

Original languageEnglish
Pages (from-to)E531-41
JournalJournal of Clinical Endocrinology and Metabolism
Issue number3
Publication statusPublished - Mar 2015


  • Adenoma/epidemiology
  • Adrenal Gland Neoplasms/epidemiology
  • Adult
  • Cohort Studies
  • Female
  • Genetic Association Studies
  • Genetic Heterogeneity
  • Genetic Predisposition to Disease
  • Genetic Testing
  • Humans
  • Male
  • Middle Aged
  • Paraganglioma/epidemiology
  • Pheochromocytoma/epidemiology
  • Pituitary Neoplasms/epidemiology
  • Young Adult


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