Estimated risk for developing autoimmune Addison's disease in patients with adrenal cortex autoantibodies.
BACKGROUND
Patients with adrenal cortex autoantibodies (ACA) without overt autoimmune Addison's disease (AAD) are at risk of adrenal failure.


METHODS
To assess the contribution of different clinical, immunological, genetic, and functional factors in the progression to AAD, we followed up 100 ACA-positive and 63 ACA-negative patients without AAD for a maximum of 21 yr (mean 6.0 yr, median 4.8). ACA were measured by immunofluorescence and 21-OH autoantibodies (Abs) by RIA. Adrenal function was assessed by measuring basal levels of cortisol, aldosterone, ACTH, renin activity, and cortisol response to ACTH. The risk of developing AAD was calculated using survival and multivariate analyses.


RESULTS
AAD developed in 31 ACA-positive patients and one ACA-negative patient. The cumulative risk of disease in ACA-positive patients was 48.5% [95% confidence interval (CI) 40.8-56.1]. The cumulative risk was higher in children than adults (100 vs. 31.9%; P < 0.0001), males than females (68.6 vs. 42.7%; P = 0.006), patients with subclinical rather than normal adrenal function at entry (87.4 vs. 30.1%; P < 0.0001), patients with hypoparathyroidism and/or candidiasis than patients with other autoimmune or nonautoimmune diseases (100 vs. 29.7%; P < 0.0001), and patients with high rather than low-medium ACA titers (62.8 vs. 41.2%; P = 0.12). The presence of human leukocyte antigen (HLA)-DRB1 did not appear to contribute to the prediction of AAD. Adjusted hazard ratios by Cox model for the development of AAD were 3.37 for males (CI 1.38-8.24), 5.23 for hypoparathyroidism and/or candidiasis (CI 1.53-17.92), 3.33 for high antibody titers (CI 1.43-7.78), and 6.15 for impaired adrenal function at entry (CI 2.79-13.57).


CONCLUSIONS
These results were used to construct a risk algorithm for estimating the probability of developing AAD from the combination of gender, age, adrenal function, antibody titer, and associated autoimmune disorders at entry. The values of estimated risk could be used to decide appropriate follow-up intervals and future immunointervention strategies.
Coco
Graziella
G
Endocrine Unit, University of Padua Medical School, Italy.
Dal Pra
Chiara
C
Presotto
Fabio
F
Albergoni
Maria Paola
MP
Canova
Cristina
C
Pedini
Beniamino
B
Zanchetta
Renato
R
Chen
Shu
S
Furmaniak
Jadwiga
J
Rees Smith
Bernard
B
Mantero
Franco
F
Betterle
Corrado
C
D000224:Addison Disease / Q000453:epidemiology* / Q000209:etiology / Q000276:immunology*; D000293:Adolescent; D000302:Adrenal Cortex / Q000276:immunology* / Q000503:physiopathology; D000305:Adrenal Cortex Hormones / Q000097:blood; D000328:Adult; D000368:Aged; D000465:Algorithms; D001323:Autoantibodies / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D005500:Follow-Up Studies; D015798:HLA-DR1 Antigen / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D015999:Multivariate Analysis; D012306:Risk; D016019:Survival Analysis
D000305:Adrenal Cortex Hormones; D001323:Autoantibodies; D015798:HLA-DR1 Antigen