title: Familial SDHA mutation associated with pituitary adenoma and pheochromocytoma/paraganglioma.
abstract: BACKGROUND
  Reports of the coexistence of pituitary adenomas and pheochromocytoma/paraganglioma are uncommon. Recently germline mutations in 2 of the genes encoding succinate dehydrogenase, SDHC and SDHD, were associated with pituitary tumors.
  
  
  OBJECTIVE
  Our aim was to determine whether the development of a pituitary adenoma was associated with SDHA mutation.
  
  
  METHODS
  A 46-year-old female presented with carotid body paraganglioma (proband). Subsequently the proband's son was diagnosed with a nonfunctioning pituitary macroadenoma at age 30 years.
  
  
  RESULTS
  An immunohistochemical analysis of the resected paraganglioma and pituitary adenoma revealed the loss of succinate dehydrogenase subunit B and succinate dehydrogenase subunit A (SDHA) expression in both tumors, with the preservation of staining in nonneoplastic tissue. Mutation analysis showed a novel SDHA mutation (c.1873C>T, p.His625Tyr) in the germline of the proband as well as in the proband's son. In the paraganglioma of the proband, in addition to the germline mutation, a somatic mutation was observed (c.1865G>A, p.Trp622*). In the pituitary adenoma of the proband's son, loss of SDHA immunoreactivity was paradoxically accompanied by loss of the mutant allele.
  
  
  CONCLUSIONS
  This is the first report of a pituitary adenoma arising in the setting of germline SDHA mutation. The loss of SDHA protein expression in both the paraganglioma (proband) and pituitary adenoma (proband's son) argues strongly for a causative role of SDHA mutation. This report further strengthens the link between pituitary neoplasia and germline SDH mutation. Although pituitary adenomas appear rare among patients carrying SDH subunit mutations, they may have been underrecognized due to the low penetrance of disease and lack of systematic surveillance.
authors: Cancer Genetics, Hormones and Cancer Group, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, New South Wales 2065, Australia. trisha.dwight@sydney.edu.au
authors: Trisha
authors: T
authors: Dwight
authors: Kirsty
authors: K
authors: Mann
authors: Diana E
authors: DE
authors: Benn
authors: Bruce G
authors: BG
authors: Robinson
authors: Penny
authors: P
authors: McKelvie
authors: Anthony J
authors: AJ
authors: Gill
authors: Ingrid
authors: I
authors: Winship
authors: Roderick J
authors: RJ
authors: Clifton-Bligh
mesh_terms: D000236:Adenoma / Q000235:genetics*; D000310:Adrenal Gland Neoplasms / Q000235:genetics*; D000328:Adult; D042963:Electron Transport Complex II / Q000235:genetics*; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010673:Pheochromocytoma / Q000235:genetics*; D010911:Pituitary Neoplasms / Q000235:genetics*
chemical_list: D042963:Electron Transport Complex II; C511268:SDHA protein, human