Cheng Sonia, Gomez Karen, Serri Omar, Chik Constance, Ezzat Shereen
Department of Medicine, Division of Endocrinology and Metabolism, University of Alberta, Edmonton, Alberta, Canada.
Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
PLoS One. 2015 May 21;10(5):e0127276. doi: 10.1371/journal.pone.0127276. eCollection 2015.
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.
既往已对肢端肥大症患者患癌的风险及死亡率进行了研究。尽管生长激素/胰岛素样生长因子-1（GH/IGF-1）过量提供了一种可能的病理生理学解释，但IGF-1过量的程度以及糖尿病（肢端肥大症常见的合并症且已知与癌症有关联）在肢端肥大症相关肿瘤中的作用仍不明确。
纳入在加拿大三个转诊中心（多伦多、蒙特利尔、埃德蒙顿）接受治疗的肢端肥大症患者。记录所有可用的临床信息，包括：年龄、IGF-1水平初始及末次相对于正常上限的百分比（%ULN）、合并症及其他肿瘤（良性和恶性）。
共评估了408例病例。185例为女性（45.3%），126例（30.9%）发生了垂体外肿瘤：55例为恶性，71例为良性。最常见的解剖部位是胃肠道（46例[11.3%]），其次是头颈部（36例[8.8%]）和多个部位（14例[3.4%]）。106例（26.0%）病例患有糖尿病。50岁以上男性的初始IGF-1显著高于50岁以下男性（380.15对284.78，p = 0.001）。糖尿病患者的初始IGF-1显著更高（389.38对285.27，p = 0.009），50岁以上的糖尿病患者与无糖尿病患者相比也是如此。糖尿病患者中有45.3%（48/106）发生了垂体外肿瘤，而无糖尿病患者中这一比例为24.3%（71/292）（p = 0.001，比值比：2.576，95%置信区间1.615 - 4.108）。糖尿病患者中有22.6%（24/106）发生了恶性肿瘤，而无糖尿病患者中这一比例为9.2%（27/292）（p < 0.001，比值比2.873，9%置信区间1.572 - 5.250）。
这些数据表明，患有糖尿病的肢端肥大症患者更易发生垂体外肿瘤，且其初始IGF-1水平更高。IGF-1单独或与糖尿病共同在垂体外肿瘤发生中的作用值得进一步研究。
