title: Genetic basis of bilateral macronodular hyperplasia.
abstract: OBJECTIVE
  To review the genetic basis of bilateral macronodular hyperplasia (BMAH).
  
  
  METHODS
  Case presentation, review of literature, table, and bullet point conclusions.
  
  
  RESULTS
  BMAH, also known as adrenocorticotropic hormone (ACTH)-independent macronodular hyperplasia (AIMH), can cause Cushing syndrome or mild hypercortisolism. Recent studies have demonstrated that hyperplastic tissue reproduces ectopic ACTH, implying that BMAH is the more proper term, as the syndrome is not ACTH-independent. BMAH was thought to be sporadic, but recent data have shown that there is likely a genetic component in the majority of cases. Mutations in ARMC5, a putative suppressor gene, have been found in many familial cases of BMAH and are thought to be responsible for the disorder. As these nodules inefficiently produce cortisol, large nodules are required to produce a clinical syndrome. ARMC5 likely requires a second somatic mutation to become clinically apparent. Clinical manifestations are not generally noted until the fifth to sixth decades of life.
  
  
  CONCLUSIONS
  BMAH is an underrecognized genetic condition that can lead to Cushing syndrome and should be screened for in patients and susceptible family members.
authors.forename: Aarti
authors.initials: A
authors.lastname: Ravikumar
authors.forename: Alice C
authors.initials: AC
authors.lastname: Levine
mesh_terms: D051186:Armadillo Domain Proteins; D003480:Cushing Syndrome / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: C000590373:ARMC5 protein, human; D051186:Armadillo Domain Proteins; D025521:Tumor Suppressor Proteins