Autoimmunity to Steroid-Producing Cells

Addison’s disease, named after the English physician who provided its full description in 1855, is the result of the destruction or impaired function of adrenocortical cells. Of the 11 cases described by Addison, 10 were likely subsequent to an infiltrative disease (the most common being the secondary localization of Mycobacterium tuberculosis to the adrenal gland) and 1 was clinically idiopathic (likely of an autoimmune origin, on the basis of the current knowledge of disease mechanisms). In recent years the ethiologic spectrum of the disease has considerably expanded to include genetic causes not present in the 11 cases described by Thomas Addison. Accordingly, the definition of primary adrenal insufficiency (PAI) appears today more correct. Nevertheless, Autoimmune Addison’s Disease (AAD) and posttuberculosis Addison’s disease are still adequate definitions according to the clinical characteristics of the cases described in 1855. Prevalence of PAI is estimated at 120-160 cases per million in western countries, corresponding to 1 case every 7,000-7,500 individuals (Laureti et al, 1999; Løvås et al, 2002). The clinical manifestations of the disease result from the glucorticoid, mineralcorticoid and androgen deficiency (Oelkers, 1996). In western countries and Japan, an autoimmune process is responsible for the destruction of the adrenocortical cells and for the clinical manifestations of PAI in around 70-90% of cases (Betterle et al, 2002; Nomura et al, 1994). AAD occurs frequently in concomitance with other organ-specific and non-organ-specific autoimmune diseases in the so-called autoimmune polyendocrine syndromes (APS). Since at least two-thirds of patients with AAD have one or more other manifestations of an ongoing autoimmune process against other endocrine glands or different tissues, AAD can be considered a paradigmatic disease for the study of endocrine autoimmunity. On the basis of the type of diseases present in the same patient, different APSs are recognized. APS 1 is caused by mutations of the AIRE (AutoImmune REgulator) gene, which is located on chromosome 21 (The Finnish-German APECED Consortium, 1997). This syndrome is characterized by the concomitant presence of at least two of three diseases: chronic mucocutaneous candidiasis, hypoparathyroidism and AAD. In first-degree relatives of APS1 patients a single disease manifestation is sufficient to formulate the diagnosis. No general agreement exists for the classification of the remaining APSs. Some authors discriminate APS 2, APS 3 and APS 4 according to the different combination of autoimmune diseases present in the same patients. With this classification, APS 2 would identify the association of clinical or pre-clinical AAD with thyroid autoimmune diseases