Prospective, Longitudinal Study of Cancer Predictors and Rates in a New York City Cohort of 598 Patients With Acromegaly

Abstract Context Long-term growth hormone/insulin-like growth factor-1 (GH/IGF-1) excess could increase the risk of cancer in acromegaly, but individual levels of these hormones do not relate to this risk. Objective We newly investigated longitudinally-measured IGF-1 levels as a potential predictor of cancer in a large New York City acromegaly cohort. Methods We conducted a prospective, longitudinal study of 598 acromegaly (309 men, 289 women) and 292 clinically nonfunctioning pituitary adenoma (CNFPA) (140 women, 152 men) patients from the same underlying population. GH and IGF-1 levels were measured longitudinally and outcomes were observed during long-term follow-up. Cumulative exposure to IGF-1 excess was tested as a predictor of cancer. We compared cancer prevalence in acromegaly and CNFPA cohorts and incidence in each to that expected from Surveillance, Epidemiology, and End Results (SEER) data. Results Cancer prevalence by last follow-up was 22.6% in acromegaly and 12.7% in CNFPAs (odds ratio [OR] = 1.99 [95% CI, 1.34-2.97]) (P = .0005). Overall standardized incidence ratio for cancer was 1.78 (1.51-1.81) in the acromegaly and 1.26 (0.89-1.70) in the CNFPA cohorts. Cumulative exposure to IGF-1 excess, OR = 1.278 (1.060-1.541) (P = .01), years from acromegaly diagnosis to cancer or last follow-up, OR = 1.03 (1.004-1.057) (P = .024), and age at follow up, OR = 1.064 (1.047-1.082) (P < .001), were predictors of cancer. Conclusion Cancer risk is increased in acromegaly, but not in CNFPA patients. Cumulative exposure to IGF-1 excess is a predictor of cancer in acromegaly. Our data suggest that cancer risk in acromegaly relates to the degree and duration of IGF-1 excess and that full appreciation of this risk requires long-term follow up.