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Addison's disease in Italy: mortality and survival by etiology.

Carlotta Keiko Vedolin, Chiara Sabbadin, Alessandro Mondin, Stefano Masiero, Mattia Barbot, Elisabetta Cavedon, Valentina Camozzi, Caterina Mian, et al. (43 authors)

Journal of endocrinological investigation · 2026-05

Abstract

BACKGROUND: Data on survival and mortality in Addison's disease (AD) are contradictory: some studies suggest a mortality rate two times higher than in the general population, but this is not consistently reported in other studies.

METHODS: We evaluated survival and mortality in 1,826 Italian adult patients with AD of different etiologies, collected from 1947 to 2024 across 30 Endocrine Units. These outcomes were compared to those of the age- and sex-matched Italian reference population using a standardized mortality ratio (SMR) in a subgroup of 1,575 cases.

RESULTS: Sex and age adjusted survival analysis showed increased mortality in genetic AD, cancer-related-AD and cases with type 1 autoimmune polyendocrine syndrome (APS-1) compared to other etiologies. The SMR analysis demonstrated a significantly increased mortality risk of the overall patients with AD compared to the general population (SMR 1.34, p&#x2009;<&#x2009;0.01). However, 4 etiologies presented survival similar to the general population: patients with type 2 or type 4 APS or isolated autoimmune AD (SMR 0.91, p&#x2009;=&#x2009;0,57), vascular/post-tuberculosis AD (SMR 0.90, p&#x2009;=&#x2009;0.69), bilateral adrenalectomy due to benign endocrine diseases (SMR 0.91. p&#x2009;=&#x2009;0.64) and not defined AD (SMR 1.06, p&#x2009;=&#x2009;0.93). These groups included 1,188 patients, representing 75.4% of the population. On the contrary, a significantly increased mortality risk compared to the general population was reported in the following 3 groups: patients with APS-1 (SMR 5.98, p&#x2009;<&#x2009;0.01), genetic AD (SMR 5.09, p&#x2009;<&#x2009;0.01), and cancer-related AD (SMR 4.64, p&#x2009;<&#x2009;0.01), accounting for 387 patients (24.5%).

CONCLUSION: Our study has shown that in adult patients with AD there is a large difference in survival and mortality based on the various etiological forms. In order to evaluate survival and mortality each form of AD must be considered separately and compared with an age- and sex-matched population.