title: The role of cumulative growth hormone exposure in determining mortality and morbidity in acromegaly: a single centre study.
abstract: OBJECTIVE
  Acromegaly has traditionally been associated with significant mortality and cardiovascular morbidity. The aim of this study was to assess the overall mortality and improvement in mortality and morbidity in acromegaly and correlate these with cumulative growth hormone exposure.
  
  
  METHODS
  All patients treated for acromegaly at our centre until 2012 were analysed in this retrospective observational study. Baseline demographic details such as age at diagnoses, radiological features and pituitary status were obtained on these 167 patients. Cumulative GH levels (GHy) were calculated as a sum of average of GH readings in consecutive years. Mortality rates and development of new diabetes, hypertension and cardiovascular events (stroke, congestive cardiac failure and ischaemic heart disease) were assessed.
  
  
  RESULTS
  The SMR for overall cohort was 1.6. There has been a significant improvement in SMR over the past two decades (SMR until 1992 2.5; SMR since 1992 1.0). Cumulative GH exposure was significantly high in patients who died (35.2 vs 24.1, p < 0.01) and in those with incident metabolic or vascular events during follow up (51.6 vs 24.4, p = 0.0001). The cardiovascular event rate of the 'new' cohort was significantly better than the 'old' cohort (8.0 vs. 29.1 %, p < 0.001).
  
  
  CONCLUSIONS
  There has been significant improvement in mortality and morbidity associated with acromegaly, in the setting of routine care in a specialized endocrine unit. Early and effective treatment to 'control' acromegaly could reduce GH exposure and hence vascular comorbidities.
authors.affiliation: Department of Diabetes and Endocrinology, Royal Stoke University Hospital, University Hospitals of North Midlands NHS Trust, Stoke-on-Trent, ST4 6QG, UK. laks.varadhan@gmail.com.
authors.forename: Lakshminarayanan
authors.initials: L
authors.lastname: Varadhan
authors.affiliation: Department of Public Health and Epidemiology, Centre for Childhood Cancer Survivor Studies, University of Birmingham, Birmingham, UK.
authors.forename: Raoul C
authors.initials: RC
authors.lastname: Reulen
authors.affiliation: Department of Diabetes and Endocrinology, Royal Stoke University Hospital, University Hospitals of North Midlands NHS Trust, Stoke-on-Trent, ST4 6QG, UK.
authors.forename: Maureen
authors.initials: M
authors.lastname: Brown
authors.affiliation: Department of Diabetes and Endocrinology, Royal Stoke University Hospital, University Hospitals of North Midlands NHS Trust, Stoke-on-Trent, ST4 6QG, UK.
authors.forename: Richard N
authors.initials: RN
authors.lastname: Clayton
mesh_terms: D000236:Adenoma / Q000453:epidemiology* / Q000378:metabolism / Q000628:therapy; D000328:Adult; D000368:Aged; D002318:Cardiovascular Diseases / Q000453:epidemiology*; D002423:Cause of Death; D003920:Diabetes Mellitus / Q000453:epidemiology*; D005260:Female; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000453:epidemiology* / Q000378:metabolism / Q000628:therapy; D006333:Heart Failure / Q000453:epidemiology; D019382:Human Growth Hormone / Q000378:metabolism*; D006801:Humans; D006973:Hypertension / Q000453:epidemiology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000453:epidemiology; D012189:Retrospective Studies; D020521:Stroke / Q000453:epidemiology; D013997:Time Factors; D055815:Young Adult
chemical_list: D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I
keywords: Acromegaly; Cumulative growth hormone; Mortality