Adrenal autoantibodies in primary adrenal insufficiency [Autoanticorpi anti-surrene nell’insufficienza corticosurrenalica primitiva]

Autoimmune Addison’s disease (AAD) is caused by the immuno-mediated destruction of adrenocortical cells. AAD may be isolated or a component of the autoimmune polyendocrine syndromes type 1 (APS1) and type 2 (APS2). APS1 is caused by mutations of the AutoImmune Regulator (AIRE) gene which encodes an activator of transcription, Aire, that induces expression of autoantigens in thymic medullary epithelial cells and promotes immunological tolerance. Isolated AAD and APS2 are complex genetic pathologies caused by a T-cell mediated destruction of adrenocortical cells, with major contribution of HLA genes. The target cells in the adrenal cortex participate in the immune reaction by releasing chemokines, such as CXCL-10, that are attracting Th1 cells. The major immune marker of the adrenal autoimmune process is the presence of circulating autoantibodies against the steroidogenic enzyme 21-hydroxylase (21OHAb). Determination of 21OHAb is clinically useful to discriminate AAD from other causes of primary adrenal insufficiency. 21OHAb are also the best immune marker for identification of autoimmune oophoritis in women with primary ovarian insufficiency. Appearance of 21OHAb in patients with endocrine autoimmune diseases defines the so-called pre-clinical AAD. An impaired response to an ACTH stimulation test predicts progression towards clinical AAD in over 80% of cases.