title: Italian addison network study: update of diagnostic criteria for the etiological classification of primary adrenal insufficiency.
abstract: Primary adrenal insufficiency (PAI) is clinically evident in one in 8000 individuals. A correct etiological classification is critical for correct disease management. To update the diagnostic criteria for the etiological classification of PAI, a multicentric network was established in Italy, and 222 patients with PAI were studied. Both 21-hydroxylase and adrenal cortex autoantibodies (21OHAb and ACA, respectively) were tested in two independent laboratories on coded samples and found in 65-66% and 58-61% of cases, respectively. Autoimmune polyendocrine syndrome I was diagnosed in 11 of the 222 patients. Of the remaining 211 patients, 38 (18%) had a nonautoimmune form of PAI. In 145 subjects (65%), the presence of adrenal autoantibodies, without signs of other forms of PAI, led to a diagnosis of autoimmune Addison's disease. In six cases (3%), PAI remained idiopathic. Logistic regression analysis showed a 92.2-92.7% probability of correct reclassification for the two 21OHAb assays and 84.5-85.9% for the ACA assays. We conclude that the simultaneous presence of both 21OHAb and ACA permits unambiguous diagnosis of autoimmune Addison's, whereas subjects with low antibody titers should undergo both instrumental and biochemical tests to exclude other causes of PAI. Lastly, we developed a comprehensive flowchart for the classification of PAI for use in routine clinical practice.
authors.affiliation: Department of Internal Medicine, University of Perugia, 06126 Perugia, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Falorni
authors.forename: Stefano
authors.initials: S
authors.lastname: Laureti
authors.forename: Annamaria
authors.initials: A
authors.lastname: De Bellis
authors.forename: Renato
authors.initials: R
authors.lastname: Zanchetta
authors.forename: Claudio
authors.initials: C
authors.lastname: Tiberti
authors.forename: Giorgio
authors.initials: G
authors.lastname: Arnaldi
authors.forename: Vittorio
authors.initials: V
authors.lastname: Bini
authors.forename: Paolo
authors.initials: P
authors.lastname: Beck-Peccoz
authors.forename: Antonio
authors.initials: A
authors.lastname: Bizzarro
authors.forename: Francesco
authors.initials: F
authors.lastname: Dotta
authors.forename: Franco
authors.initials: F
authors.lastname: Mantero
authors.forename: Antonio
authors.initials: A
authors.lastname: Bellastella
authors.forename: Corrado
authors.initials: C
authors.lastname: Betterle
authors.forename: Fausto
authors.initials: F
authors.lastname: Santeusanio
mesh_terms: D000224:Addison Disease / Q000175:diagnosis* / Q000209:etiology / Q000276:immunology*; D000293:Adolescent; D000302:Adrenal Cortex / Q000276:immunology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000032:analysis*; D002648:Child; D005260:Female; D006801:Humans; D007159:Immunologic Tests; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D013255:Steroid 21-Hydroxylase / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D013255:Steroid 21-Hydroxylase