[Autoimmune Addison's disease. Current knowledge and prospects]

Idiopathic Addison's disease (IAD) is a chronic organ-specific autoimmune disease sometimes associated with other autoimmune endocrine diseases. The prevalence is 50-100/million with an incidence of 5-6 cases/million/year. A genetic predisposition to this disease has been reported in subjects with phenotype HLA-DR3, -DR4, -A1, -B8 or HLA-A28, -B8; a phenotype HLA-B8 has been described in subjects with adrenal autoantibodies (AA) not progressing toward an overt disease. There is strong evidence that AA can play a pathogenic role or at least can be considered good immunological markers in IAD. AA may damage adrenal function by a cytotoxic process directed at adrenal cell surface or other intracellular antigens. An antigenic activity has been recently attributed to P450c enzymes and in particular to P450c21. Clinical manifestations of IAD can be preceded by a long period of subclinical adrenocortical impairment, characterized only by the presence of AA with or without adrenocortical function findings. In our experience, where AA titers were 1:8 or higher, progression of adrenal disease was likely with time. A spontaneous remission can indeed occur with lower titers, especially in early stages of subclinical adrenal insufficiency. Finally, a reversal of previously significant AA positive titers in patients in more advanced stages of subclinical adrenal insufficiency seems to be induced by corticosteroid therapy.