The natural history of autoimmune Addison's disease from the detection of autoantibodies to development of the disease: a long-term follow-up study on 143 patients.

Abstract

BACKGROUND:

Adrenal cortex autoantibodies (ACAs) and/or 21-hydroxylase (21OHAb) are markers of autoimmune Addison's disease (AAD) and progression to overt AAD. The reported cumulative risk of developing AAD varies from 0 to 90% in different studies.

AIM:

To assess the predictive value of different parameters in the progression toward AAD in patients with ACA and/or 21OHAb-positive patients with autoimmune polyendocrine syndromes (APS).

MATERIALS AND METHODS:

Twenty-nine patients with APS-1 and 114 patients with APS-2 or APS-4 were followed up for a median of 10 years (range 6 months to 33 years) and were assessed using ACTH test. The risk of AAD was estimated according to age, gender, stage of adrenal dysfunction, associated diseases and antibody titer. Univariate and multivariate Cox proportional hazard models were used for statistical analysis.

RESULTS:

The cumulative risk (CR) of developing AAD was higher in APS-1 patients (94.2%) than in patients with APS-2/APS-4 (38.7%). The CR was high in both male and female APS-1 patients, while in patients with APS-2/APS-4 it was high only in males. Stage 1 (increased plasma renin) for patients with APS-1 and Stage 2 (no response of cortisol to ACTH test) for patients with APS-2/APS-4 were established as the points of no return in the progression to AAD. Adjusted hazard ratio analyses by multivariate Cox model for AAD showed that gender, diseases and adrenal function were independent risk factors for developing clinical AAD. The risk of developing clinical AAD appears to subside after 19 years of follow-up.

CONCLUSIONS:

A model for estimating the probability to survive free of AAD has been developed and should be a useful tool in designing appropriate follow-up intervals and future therapeutic strategies.

• Authors: Lara Naletto, Anna Chiara Frigo, Filippo Ceccato, Chiara Sabbadin, Riccardo Scarpa, Fabio Presotto, Miriam Dalla Costa, Diego Faggian, Mario Plebani, Simona Censi, Jacopo Manso, Jadwiga Furmaniak, Shu Chen, Bernard Rees Smith, Stefano Masiero, Francesca Pigliaru, Marco Boscaro, Carla Scaroni, Corrado Betterle
• Journal: European journal of endocrinology (Eur J Endocrinol) Vol. 180 Issue 3 Pg. 223-234 (Mar 2019) ISSN: 1479-683X [Electronic] England
• PMID: 30608902 (Publication Type: Journal Article)