Adrenal autoimmunity and correlation with adrenal dysfunction

Primary adrenal insufficiency (Addison's disease) affects approximately 1 in 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 adrenal cortex. The presence of adrenal cortex autoantibodies (ACA), as detected by indirect immunofluorescence, is a good marker of adrenal autoimmunity. The enzyme steroid-21-hydroxylase (21OH) is a major target of ACA and 21OH autoantibodies (21OHAb) have been found in 80-90% of subjects with clinically idiopathic Addison's disease and in almost all cases with short disease duration. Autoantibodies to other steroidogenic enzymes, such as 17α-hydroxylase (17αOHAb) and side-chain cleavage enzyme (P450sccAb) are often detected in patients with autoimmune polyglandular syndrome type I (APS I) or with APS II with gonadal insufficiency, but they are rarely found in isolated Addison's or in APS II without gonadal insufficiency. The genetic risk for autoimmune Addison's disease is associated with HLA-DR3-DQ2 and with the allele 5.1 of the MHC class I chain-related A (MIC-A) gene. The predictive value of genetic markers for Addison's disease is very low. Adrenal autoantibodies are found in approximately 1-1.5% of subjects with other 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 subjects. This is probably related to a slow, chronic process in adults that requires longer follow-up periods. The level of adrenal autoantibodies correlate with the degree of adrenal dysfunction and, using immune and biochemical markers, the natural history of autoimmune Addison's is described in this review. The clinical applications of the adrenal autoantibody assays are discussed.