Acromegaly is associated with an increased incidence of primary malignant tumors: data from a national study in Sweden

CONTEXT: Growth hormone (GH) excess and elevated insulin-like growth factor-1 (IGF-1) in acromegaly are considered to promote cancer development. OBJECTIVE: To investigate cancer incidence and outcome in patients with acromegaly in relation to biochemical control. METHODS: Matched cohort study in patients with acromegaly diagnosed from 1991 to 2018 and ten controls per case from the Swedish population. Cancer diagnoses and fatalities were obtained from the Swedish Pituitary and National Patient Registers. Adjusted hazard ratio (HR) and 95% confidence intervals (CIs) for cancer incidence and death were estimated using a Cox proportional hazard regression model adjusted for age, sex, and comorbidity. RESULTS: We included 1035 patients with acromegaly (49.5% female; median age 52.0 years) and 10,261 matched controls. Patients had higher adjusted HR (95% CI) for all cancer (1.28, 1.11-1.49), colorectal cancer (1.84, 1.28-2.64), lung cancer (1.95, 1.22-3.11), hematologic cancer (1.68, 1.03-2.73), and breast cancer in women (1.46, 1.02-2.11) from 5 years before acromegaly diagnosis. Second cancers after diagnosis tended to be increased (1.54, 0.98-2.44). Death from cancer was only significantly elevated in patients 40-60 years of age (1.48, 1.19-1.85). Patients with persistently elevated IGF-1 had a higher overall mortality rate (1.50, 1.10-2.01) but no increase in cancer incidence nor cancer-related mortality compared to biochemically controlled patients. CONCLUSIONS: This nationwide, matched cohort study showed an increased risk of cancer in patients with acromegaly, underscoring the importance of vigilance for early signs of cancer after acromegaly diagnosis. Biochemical control had minor effects on increased cancer development, indicating an effect beyond GH hypersecretion.