Normal overall mortality rate in Addison's disease, but young patients are at risk of premature death

Abstract

Context: Primary adrenal insufficiency (Addison's disease) is a rare autoimmune disease. Until recently, life expectancy in Addison's disease patients was considered normal. Objective: To determine the mortality rate in Addison's disease patients. Design and methods: i) Patients registered with Addison's disease in Norway during 1943-2005 were identified through search in hospital diagnosis registries. Scrutiny of the medical records provided diagnostic accuracy and age at diagnosis. ii) The patients who had died were identified from the National Directory of Residents. iii) Background mortality data were obtained from Statistics Norway, and standard mortality rate (SMR) calculated. iv) Death diagnoses were obtained from the Norwegian Death Cause Registry. Results: Totally 811 patients with Addison's disease were identified, of whom 147 were deceased. Overall SMR was 1.15 (95% confidence intervals (CI) 0.96-1.35), similar in females (1.18 (0.92-1.44)) and males (1.10 (0.80-1.39)). Patients diagnosed before the age of 40 had significantly elevated SMR at 1.50 (95% CI 1.09-2.01), most pronounced in males (2.03 (1.19-2.86)). Acute adrenal failure was a major cause of death; infection and sudden death were more common than in the general population. The mean ages at death for females (75.7 years) and males (64.8 years) were 3.2 and 11.2 years less than the estimated life expectancy. Conclusion: Addison's disease is still a potentially lethal condition, with excess mortality in acute adrenal failure, infection, and sudden death in patients diagnosed at young age. Otherwise, the prognosis is excellent for patients with Addison's disease.

Improvement of anthropometric and metabolic parameters, and quality of life following treatment with dual-release hydrocortisone in patients with Addison’s disease

“…The same for Norwegian patients with AD, particularly males, presenting with an increased risk of premature death due to infections, sudden death and acute adrenal failure [9].…”

“…Afterwards, it has become increasingly clear that, on the contrary, despite glucocorticoid replacement therapy, mortality rate and morbidity remain increased in patients with adrenal insufficiency as compared to the general population [7][8][9][10].…”

Adrenal Crisis: Still a Deadly Event in the 21st Century

“…Eight of these patients had a documented adrenal crisis, and 7 of these 8 died at home or upon arrival to the hospital. Sudden death occurring in young patients with adrenal insufficiency was noted in 2 other studies, 13,14 with adrenal crisis a likely cause in >50%, 13 and in many cases associated with trivial infections. 14 This highlights the importance of prevention and early treatment.…”

EXTENSIVE EXPERTISE IN ENDOCRINOLOGY: Adrenal crisis

“…Adrenal insufficiency accounted for 15% of deaths in a Norwegian study of 130 deceased patients with Addison's disease, most probably reflecting the adrenal crisis (25). Two Swedish registry analyses in patients with Addison's disease reported 'endocrine causes' as responsible for the death in 12.6 and 8.3%, respectively, also suggesting a role of adrenal crisis (20,21).…”