title: Glucocorticoid replacement and mortality in patients with nonfunctioning pituitary adenoma.
abstract: BACKGROUND
  Current treatment guidelines generally suggest using lower and weight-adjusted glucocorticoid replacement doses in patients with insufficiency of the hypothalamic-pituitary-adrenal (HPA) axis. Although data in patients with acromegaly revealed a positive association between glucocorticoid dose and mortality, no comparable results exist in patients with nonfunctioning pituitary adenomas (NFPA).
  
  
  OBJECTIVE
  Our objective was to assess whether higher glucocorticoid replacement doses are associated with increased mortality in patients with NFPA and HPA axis insufficiency.
  
  
  METHODS
  We included 105 patients receiving glucocorticoid replacement after pituitary surgery due to NFPA and concomitant HPA axis insufficiency. Patients were grouped according weight-adapted and absolute hydrocortisone (HC) replacement doses. Mortality was assessed using Kaplan-Meier methodology as well as multivariable Cox regression models.
  
  
  METHODS
  This was a retrospective analysis conducted at a tertiary referral center.
  
  
  RESULTS
  We evaluated overall mortality based on HC replacement doses.
  
  
  RESULTS
  Average age at inclusion was 58.9±14.8 yr, and mean follow-up was 12.7±9.4 yr. The groups did not differ according to age, follow-up time, pattern of hypopituitarism, and comorbidities. Kaplan-Meier survival probabilities differed significantly when comparing individuals with differing weight-adjusted HC dose (P=0.001) as well as absolute HC dose (5-19, 20-29, and ≥30 mg, P=0.009). Hazard ratios for mortality increased from 1 (0.05-0.24 mg/kg) to 2.62 (0.25-0.34 mg/kg) to 4.56 (≥0.35 mg/kg, P for trend=0.006) and from 1 (5-19 mg) to 2.03 (20-29 mg) to 4 (≥30 mg, P for trend=0.029), respectively.
  
  
  CONCLUSIONS
  Higher glucocorticoid replacement doses are associated with increased overall mortality in patients with NFPA and insufficiency of HPA axis. This further substantiates the importance of a balanced and adjusted glucocorticoid replacement therapy in these patients.
authors.affiliation: Division of Endocrinology, Diabetes, and Clinical Nutrition, Inselspital, Bern University Hospital, and Institute of Social and Preventive Medicine, University of Bern, CH-3010 Bern, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Zueger
authors.forename: Paul
authors.initials: P
authors.lastname: Kirchner
authors.forename: Coline
authors.initials: C
authors.lastname: Herren
authors.forename: Stefan
authors.initials: S
authors.lastname: Fischli
authors.forename: Marcel
authors.initials: M
authors.lastname: Zwahlen
authors.forename: Emanuel
authors.initials: E
authors.lastname: Christ
authors.forename: Christoph
authors.initials: C
authors.lastname: Stettler
mesh_terms: D000236:Adenoma / Q000188:drug therapy* / Q000401:mortality*; D000328:Adult; D000368:Aged; D015897:Comorbidity; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D005938:Glucocorticoids / Q000008:administration & dosage*; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000188:drug therapy / Q000401:mortality; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010911:Pituitary Neoplasms / Q000188:drug therapy* / Q000401:mortality*; D010913:Pituitary-Adrenal System / Q000187:drug effects; D012189:Retrospective Studies; D062606:Tertiary Care Centers / Q000706:statistics & numerical data
chemical_list: D005938:Glucocorticoids; D006854:Hydrocortisone