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.

Addison's disease: a survey on 633 patients in Padova

“…All adrenal antibody-positive patients had normal or atrophic glands on imaging and only one of the 240 patients examined showed a slight increase in adrenal volume, probably related to inflammatory infiltration of the glands. This is consistent with the observations that detection of ACA/21-OHAbs is the test of choice for identifying the autoimmune nature of AD while adrenal imaging provides no additional value for the diagnosis (13). For these reasons, adrenal imaging was no longer performed in ACA/21-OHAbs-positive patients recruited more recently in our study.…”

“…For these reasons, adrenal imaging was no longer performed in ACA/21-OHAbs-positive patients recruited more recently in our study. However, adrenal imaging may be necessary in clarifying the nature of AD in adrenal antibody-negative patients (13).…”

“…Autoimmune AD (A-AD) is currently the most common form of adrenal failure in adults (1,7,8,12,13,14,15), while it is less frequent in children where genetic forms, mainly congenital adrenal hyperplasia, are the most common causes (16,17,18).…”

Retrovirus-Like Long-Terminal Repeat DQ-LTR13 and Genetic Susceptibility to Type 1 Diabetes and Autoimmune Addison’s Disease

“…According to a recent update of diagnostic criteria, based on autoantibody levels, imaging data, and biochemical parameters (22), 217 cases (69%) were classified as AAD. Of these 217 cases, DNA was available for 166.…”

Autoimmunity to Steroid-Producing Cells

“…Autoantibody titer is also important, because the presence of low titre adrenal autoantibodies does not enable the unequivocal diagnosis of AAD in all cases (Falorni et al, 2004). ACA and 21OHAb have sporadically been found also in patients with unequivocal post-tuberculosis Addison's disease (Nomura et al, 1994;do Carmo Silva et al, 2000).…”