ABSTRACT
Individual patients or multiple members of a pedigree may suffer from multiple autoimmune endocrinopathies, or autoimmune polyglandular syndromes (APS). The recognition of APS dates back to the initial description of Addsions’ disease, which is a major component disease for patients with APS. Addison’s disease was named after Thomas Addison, who initially recognized the co-existence of the clinical manifestations of the disease and adrenalitis and/or adrenal atrophy in 1849 (1). Almost 80 years later, destruction of the adrenal cortex, but not the medulla of adrenal gland, was found to be responsible for the clinical appearance of Addison’s disease (2). Adrenal cortical extracts were then demonstrated to be able to maintain the lives of adrenalecotmized animals (3), and be beneficial to patients with Addison’s disease (4,5). Adrenal tuberculosis was still the major cause of Addison’s disease in the early twentieth century, however, adrenal failure become increasingly recognized in patients without tuberculosis. Hashimoto in 1912 reported lymphocyte infiltration of thyroid gland (6), and Schmidt in 1926 observed simultaneous lymphocytic infiltrations of both adrenal cortices and thyroid gland in two patients (7). Schmidt’s syndrome, comprising Addison’s disease and Hashimoto’s thyroiditis, was expanded to include insulin dependent diabetes by Carpenter et al. in 1964 (8) In 1980, autoimmune polyglandular endocrinopathies were classified into three types, APS-I, II and III, based on clinical features of patients with APS (9,10). Recent studies have provided information on the genetics of Addison’s disease and APS, while many autoantigens involved in these autoimmunities have been identified. Autoantibodies to these autoantigens can be used as markers to either facilitate the diagnoses of the involved component diseases or to predict them. Studies on the subsets of T helper cells (Th1 and Th2) in autoimmune diseases, and the relative balance of polarized Th1/Th2 foundations in the outcome of autoimmunity, have increased our understanding of the pathogenic process of APS. In addition, a gene called autoimmune regulator (AIRE), responsible for APS-I, has recently been identified and multiple mutations have been found in patients with APS-I. Studies of the function of AIRE gene product should promote our understanding of the pathogenic process of APS-I, and perhaps autoimmune diseases in general. Accordingly, this Chapter will summarize the current knowledge on clinical, immunological and genetic underpinnings of Addison’s disease and the three types of APS.
