title: The role of diabetes in acromegaly associated neoplasia.
abstract: BACKGROUND
  The risk and mortality due to cancer in patients with acromegaly have been previously investigated. Although GH/IGF-1 excess provides a probable pathophysiological explanation, the degree of IGF-1 excess and the role in acromegaly-associated neoplasms of diabetes, a common comorbidity in acromegaly with known association with cancer, remains unclear.
  
  
  METHODS
  Acromegalic patients treated in three Canadian referral centers (Toronto, Montreal, Edmonton) were included. All available clinical information was recorded including: age, initial and last percentage of the upper limit of normal (%ULN) IGF-1 levels, comorbidities and other neoplasms (benign and malignant).
  
  
  RESULTS
  408 cases were assessed. 185 were women (45.3%), 126 (30.9%) developed extra-pituitary neoplasms: 55 malignant and 71 benign. The most frequent anatomic site was the gastrointestinal tract (46 [11.3%]), followed by head and neck (36 [8.8%]) and multiple locations (14 [3.4%]). 106 (26.0%) cases had diabetes. Initial IGF-1 was significantly higher in men older than 50 (380.15 vs. 284.78, p = 0.001) when compared to men younger than 50. Diabetics showed significantly higher initial IGF-1 (389.38 vs. 285.27, p = 0.009), as did diabetics older than 50 compared with those without diabetes. 45.3% (48/106) of cases with diabetes developed extra-pituitary neoplasms vs. 24.3% (71/292) without diabetes (p = 0.001, OR: 2.576 95%CI 1.615-4.108). 22.6% (24/106) of cases with diabetes developed malignant tumors vs. 9.2% (27/292), (p < 0.001, OR 2.873, 95%CI 1.572-5.250).
  
  
  CONCLUSIONS
  These data suggest that acromegalic patients with diabetes are more likely to develop extra-pituitary neoplasms and their initial IGF-1 levels are higher. The contribution of IGF-1 vs. diabetes alone or in combination in the development of extra-pituitary neoplasms warrants further investigation.
authors.affiliation: Department of Medicine, Division of Endocrinology and Metabolism, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Sonia
authors.initials: S
authors.lastname: Cheng
authors.affiliation: Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Karen
authors.initials: K
authors.lastname: Gomez
authors.affiliation: Department of Medicine, University of Montreal, Montréal, Québec, Canada.
authors.forename: Omar
authors.initials: O
authors.lastname: Serri
authors.affiliation: Department of Medicine, Division of Endocrinology and Metabolism, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Constance
authors.initials: C
authors.lastname: Chik
authors.affiliation: Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Shereen
authors.initials: S
authors.lastname: Ezzat
mesh_terms: D000172:Acromegaly / Q000150:complications*; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D002170:Canada / Q000453:epidemiology; D015897:Comorbidity; D003920:Diabetes Mellitus; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology* / Q000209:etiology*; D010911:Pituitary Neoplasms / Q000453:epidemiology / Q000209:etiology; D012306:Risk; D012737:Sex Factors; D055815:Young Adult
chemical_list: D007334:Insulin-Like Growth Factor I