The role of diabetes in acromegaly associated neoplasia

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. 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). 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). 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.