Increased death risk and altered cancer incidence pattern in patients with isolated or combined autoimmune primary adrenocortical insufficiency

Objectives Primary adrenocortical insufficiency is mostly caused by an autoimmune destruction of the adrenal cortex. The disease may appear isolated or as a part of an autoimmune polyendocrine syndrome (APS). APS1 is a rare hereditary disorder with a broad spectrum of clinical manifestations. In APS2, primary adrenocortical insufficiency is often combined with autoimmune thyroid disease and/or type 1 diabetes. We analysed mortality and cancer incidence in primary adrenocortical insufficiency patients during 40 years. Data were compared with the general Swedish population. Design and patients A population based cohort study including all patients with autoimmune primary adrenocortical insufficiency (3299) admitted to Swedish hospitals 1964-2004. Measurements Mortality risk was calculated as the standardized mortality ratio (SMR) and cancer incidence as the standardized incidence ratio (SIR). Results A more than 2-fold increased mortality risk was observed in both women (SMR 2.9, 95% CI 2.7-3.0) and men (SMR 2.5, 95% CI 2.3-2.7). Highest risks were observed in patients diagnosed in childhood. SMR was higher in APS1 patients (SMR 4.6, 95% CI 3.5-6.0) compared with patients with APS2 (SMR 2.1, 95% CI 1.9-2.4). Cancer incidence was increased (SIR 1.3, 95% CI 1.2-1.5). When tumours observed during the first year of follow-up were excluded, only the cancer risk among APS1 patients remained increased. Cause-specific cancer incidence analysis revealed significantly higher incidences of oral cancer, nonmelanoma skin cancer, and male genital system cancer among patients. Breast cancer incidence was lower than in the general population. Conclusions Our study shows a reduced life expectancy and altered cancer incidence pattern in patients with autoimmune primary adrenocortical insufficiency.