title: Outcome after surgery for primary hyperaldosteronism may depend on KCNJ5 tumor mutation status: a population-based study from Western Norway.
abstract: BACKGROUND
  Primary aldosteronism (PA) is a frequent cause (about 10 %) of hypertension. Some cases of PA were recently found to be caused by mutations in the potassium channel KCNJ5. Our objective was to determine the mutation status of KCNJ5 and seven additional candidate genes for tumorigenesis: YY1, FZD4, ARHGAP9, ZFP37, KDM5C, LRP1B, and PDE9A and, furthermore, the surgical outcome of PA patients who underwent surgery in Western Norway.
  
  
  METHODS
  Twenty-eight consecutive patients with aldosterone-producing adrenal tumors (20 patients with single adenoma, 8 patients with unilateral multiple adenomas or hyperplasia) who underwent surgery were included in this study. All patients were operated on by uncomplicated laparoscopic total adrenalectomy. Genomic DNA was isolated from tumor and non-tumor adrenocortical tissue, and DNA sequencing revealed the mutation status.
  
  
  RESULTS
  Ten out of 28 (36 %) patients with PA displayed tumor mutations in KCNJ5 (p. G151R and L168R) while none were found in the corresponding non-tumor samples. No mutations were found in the other seven candidate genes screened. The presence of KCNJ5 mutations was associated with lower blood pressure and a higher chance for cure by surgery when compared to patients harboring the KCNJ5 wild type.
  
  
  CONCLUSIONS
  KCNJ5 mutations are associated with a better surgical outcome. Preoperative identification of the mutation status might have impact on surgical strategy (total vs. subtotal adrenalectomy).
authors.affiliation: Department of Surgery, Haukeland University Hospital, 5021 Bergen, Norway.
authors.forename: Thomas
authors.initials: T
authors.lastname: Arnesen
authors.forename: Nina
authors.initials: N
authors.lastname: Glomnes
authors.forename: Siri
authors.initials: S
authors.lastname: Strømsøy
authors.forename: Stian
authors.initials: S
authors.lastname: Knappskog
authors.forename: Anette
authors.initials: A
authors.lastname: Heie
authors.forename: Lars A
authors.initials: LA
authors.lastname: Akslen
authors.forename: Marianne
authors.initials: M
authors.lastname: Grytaas
authors.forename: Jan Erik
authors.initials: JE
authors.lastname: Varhaug
authors.forename: Oliver
authors.initials: O
authors.lastname: Gimm
authors.forename: Michael
authors.initials: M
authors.lastname: Brauckhoff
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000235:genetics* / Q000503:physiopathology / Q000601:surgery*; D000315:Adrenalectomy / Q000009:adverse effects / Q000379:methods; D000328:Adult; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D006929:Hyperaldosteronism / Q000235:genetics* / Q000503:physiopathology / Q000601:surgery*; D010535:Laparoscopy / Q000009:adverse effects / Q000379:methods; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009664:Norway; D011183:Postoperative Complications / Q000235:genetics / Q000503:physiopathology; D012189:Retrospective Studies; D018570:Risk Assessment; D016896:Treatment Outcome
chemical_list: D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C484274:KCNJ5 protein, human