title: ACTH deficiency, higher doses of hydrocortisone replacement, and radiotherapy are independent predictors of mortality in patients with acromegaly.
abstract: BACKGROUND
  A number of retrospective studies report that patients with acromegaly have increased morbidity and premature mortality, with standardized mortality ratios (SMR) of 1.3-3. Many patients with acromegaly develop hypopituitarism as a result of the pituitary adenoma itself or therapies such as surgery and radiotherapy. Pituitary radiotherapy and hypopituitarism have also been associated with an increased SMR.
  
  
  METHODS
  Using the West MIDLANDS: Acromegaly database (n = 501; 275 female), we assessed the influence of prior radiotherapy and hypopituitarism (and replacement therapy) on mortality in patients with acromegaly. Median duration of follow-up was 14.0 yr (interquartile range, 7.9-21 yr).
  
  
  RESULTS
  All-cause mortality was elevated [SMR, 1.7 (1.4, 2.0); P < 0.001]. On external analysis, prior radiotherapy, ACTH, and gonadotropin deficiency were associated with an elevated SMR [radiotherapy SMR, 2.1 (1.7-2.6); P = 0.006; ACTH deficiency SMR, 2.5 (1.9-3.2); P < 0.0005; and gonadotropin deficiency SMR, 2.1 (1.6-2.7); P = 0.037]. On internal analysis, the relative risk (RR) of mortality was increased in the radiotherapy [RR, 1.8 (1.2-2.8); P = 0.008] and ACTH-deficiency groups [RR, 1.7 (1.2-2.5); P = 0.004], but not in the gonadotropin- or TSH-deficiency groups. In the ACTH-deficient group, increased replacement doses of hydrocortisone greater than 25 mg/d were associated with increased mortality compared to lower doses.
  
  
  CONCLUSIONS
  Radiotherapy and ACTH deficiency are significantly associated with increased mortality in patients with acromegaly. In ACTH-deficient patients, a daily dose of more than 25 mg hydrocortisone is associated with increased mortality compared to lower doses. These results have important implications for the treatment of patients with acromegaly and also raise issues as to the optimum hydrocortisone treatment regimens for ACTH-deficient patients.
authors.affiliation: Centre for Endocrinology, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TH, United Kingdom.
authors.forename: M
authors.initials: M
authors.lastname: Sherlock
authors.forename: R C
authors.initials: RC
authors.lastname: Reulen
authors.forename: A Aragon
authors.initials: AA
authors.lastname: Alonso
authors.forename: J
authors.initials: J
authors.lastname: Ayuk
authors.forename: R N
authors.initials: RN
authors.lastname: Clayton
authors.forename: M C
authors.initials: MC
authors.lastname: Sheppard
authors.forename: M M
authors.initials: MM
authors.lastname: Hawkins
authors.forename: A S
authors.initials: AS
authors.lastname: Bates
authors.forename: P M
authors.initials: PM
authors.lastname: Stewart
mesh_terms: D000172:Acromegaly / Q000150:complications* / Q000188:drug therapy / Q000401:mortality* / Q000532:radiotherapy; D000324:Adrenocorticotropic Hormone / Q000172:deficiency*; D002318:Cardiovascular Diseases / Q000401:mortality; D002423:Cause of Death; D005260:Female; D005500:Follow-Up Studies; D020249:Hormone Replacement Therapy / Q000009:adverse effects; D006801:Humans; D006854:Hydrocortisone / Q000627:therapeutic use*; D008297:Male; D009369:Neoplasms / Q000401:mortality; D011237:Predictive Value of Tests; D011878:Radiotherapy / Q000009:adverse effects; D012140:Respiratory Tract Diseases / Q000401:mortality; D013997:Time Factors
chemical_list: D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone