Adrenal autoimmunity and correlation with adrenal dysfunction

Primary adrenal insufficiency (Addison's disease) affects approximately 1 i n 8500 persons in the general population, In the western countries, 70-75% of cases of Addison's disease are caused by autoimmune destruction of the a drenal cortex. The presence of adrenal cortex autoantibodies (ACA), as dete cted by indirect immunofluorescence, is a good marker of adrenal autoimmuni ty. The enzyme steroid-21-hydroxylase (21OH) is a major target of ACA and 2 1OH autoantibodies (210HAb) have been found in 80-90% of subjects with clin ically idiopathic Addison's disease and in almost all cases with short dise ase duration. Autoantibodies to other steroidogenic enzymes, such as 17 alp ha-hydroxylase (17 alpha OHAb) and side chain cleavage enzyme (P450sccAb) a re often detected in patients with autoimmune polyglandular syndrome type I (APS I) or with APS II with gonadal insufficiency, but they are rarely fou nd in isolated Addison's or in APS IT without gonadal insufficiency. The ge netic risk for autoimmune Addison's disease is associated with HLA-DR3-DR2 and with the allere 5.1 of the MHC class I chain-related A (MIC-A) gene. Th e predictive value of genetic markers for Addison's disease is very low Adr enal autoantibodies are found in approximately 1-1.5% of subjects with othe r organ-specific autoimmune diseases. The predictive value of ACA/21OHAb is very high (90%) in children, but is not higher than 20-30% in adult subjec ts. This is probably related to a slow chronic process in adults that requi res longer follow-up periods, The level of adrenal autoantibodies correlate with the degree of adrenal dysfunction and, using immune and biochemical m arkers, the natural history of autoimmune Addison's is described in this re view The clinical applications of the adrenal autoantibody assays are discu ssed.