title: The effects of long-term growth hormone and insulin-like growth factor-1 exposure on the development of cardiovascular, cerebrovascular and metabolic co-morbidities in treated patients with acromegaly.
abstract: BACKGROUND
  Acromegaly is characterized by the hypersecretion of growth hormone (GH) and insulin-like growth factor-1 (IGF-1). This leads to an increased cardiovascular, cerebrovascular and metabolic morbidity resulting in excess mortality. There is controversy over which biomarker, GH or IGF-1, better predicts this increased morbidity and mortality. The relationship between the cumulative exposure to GH and IGF-1 with co-morbidities in acromegaly has not previously been reported.
  
  
  OBJECTIVE
  To investigate the relationship between the cumulative exposure to GH and IGF-1 with cardiovascular, cerebrovascular and metabolic co-morbidities.
  
  
  METHODS
  Records of 116 acromegalic patients were retrospectively examined. Cardiovascular and cerebrovascular histories, serum GH and IGF-1, fasting glucose and oral glucose tolerance test results, were reviewed for the duration of follow-up. IGF-1 index was calculated by dividing each serum IGF-1 value by the upper limit of reference range for IGF-1. GH and IGF-1 burdens were calculated for each patient by multiplying known disease duration (in years) by mean level of basal GH or IGF-1 index recorded during the patients' entire follow-up.
  
  
  RESULTS
  Patients with abnormal glucose tolerance had a significantly higher mean GH burden compared with euglycaemic patients (P = 0·005). Ischaemic heart disease was also associated with a higher GH burden (P = 0·009) whereas cerebrovascular disease and cardiomyopathy were associated with a significantly higher mean IGF-1 burden (P = 0·018, P = 0·011 respectively).
  
  
  CONCLUSIONS
  This study identifies associations of raised GH and IGF-1 burden with cardiovascular, cerebrovascular and metabolic complications of acromegaly. Results from this study therefore suggest that consideration of the overall level of GH and IGF-1 exposure may provide important information for the management and surveillance of patients with treated acromegaly.
authors.affiliation: Department of Endocrinology, Imperial College London, Faculty of Medicine, Hammersmith Hospital, London, UK.
authors.forename: C N
authors.initials: CN
authors.lastname: Jayasena
authors.forename: A N
authors.initials: AN
authors.lastname: Comninos
authors.forename: H
authors.initials: H
authors.lastname: Clarke
authors.forename: M
authors.initials: M
authors.lastname: Donaldson
authors.forename: K
authors.initials: K
authors.lastname: Meeran
authors.forename: W S
authors.initials: WS
authors.lastname: Dhillo
mesh_terms: D000172:Acromegaly / Q000150:complications* / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology*; D002561:Cerebrovascular Disorders / Q000097:blood / Q000209:etiology*; D002648:Child; D002675:Child, Preschool; D015897:Comorbidity; D005260:Female; D005500:Follow-Up Studies; D018149:Glucose Intolerance / Q000097:blood / Q000209:etiology*; D019382:Human Growth Hormone / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000378:metabolism*; D008297:Male; D008659:Metabolic Diseases / Q000097:blood / Q000209:etiology; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000097:blood / Q000209:etiology; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I