Excess Mortality in Women and Young Adults With Nonfunctioning Pituitary Adenoma: A Swedish Nationwide Study

Context: Patients with hypopituitarism of various etiologies have excess mortality. The mortality in patients with nonfunctioning pituitary adenoma (NFPA), regardless of pituitary function, is less well studied. Objective: Our aim was to investigate mortality in patients with NFPA and to examine whether age at diagnosis, gender, tumor treatments, or hormonal deficiencies influence the outcome. Design: NFPA patients were identified and followed up in nationwide health registries in Sweden, 1987-2011. The criteria for identification were tested and validated in a subpopulation of the patients. Settings: This was a nationwide, population-based study. Patients: A total of 2795 unique patients with NFPA (1502 men, 1293 women) were identified and included in the study. Mean age at diagnosis was 58 years (men, 60 y; women, 56 y) and mean follow-up time was 7 years (range 0-25 y). Intervention: There were no interventions. Main Outcome Measures: Standardized mortality ratios (SMRs) and annual incidence rates were calculated using the Swedish population as reference and presented with 95% confidence intervals. Results: Annual incidence of NFPA was 20.3 (18.8-21.9) cases per 1 million inhabitants. During the observation period, 473 patients died against an expected 431, resulting in an SMR of 1.10 (1.00-1.20). Patients diagnosed at younger than 40 years of age had an increased SMR of 2.68 (1.23-5.09). The SMR for patients with hypopituitarism (n = 1500) was 1.06 (0.94-1.19), and for patients with diabetes insipidus (n = 145), it was 1.71 (1.07-2.58). The SMR was increased in women with NFPA (1.29; 1.11-1.48) but not in men (1.00; 0.88-1.12). Women, but not men, with a diagnosis of hypopituitarism and/or diabetes insipidus also had an increased mortality ratio. SMRs due to cerebrovascular (1.73; 1.34-2.19) and infectious diseases (2.08; 1.17-3.44) were increased, whereas the SMR for malignant tumors was decreased (0.76; 0.61-0.94). Conclusions: This nationwide study of patients with NFPA showed an overall excess mortality in women and in patients with a young age at diagnosis. Increased mortality was seen for cerebrovascular and infectious diseases.