Polyglandular autoimmunity

Although target tissues or glands differ, several common threads have begun to emerge that link the diseases of the autoimmune endocrine syndromes. In the polyglandular syndrome type II, a defect resides in one of the genes of the major histocompatibility locus which, in concert with other gene(s), results in susceptibility. Genetic susceptibility is necessary but not sufficient to produce the disorder. This is illustrated by the lack of 100% concordance of disease in identical twins. This lack of concordance has led to the search for environmental influences or "triggers" of the autoimmune process. These "triggers" have not been well defined, but may include amiodarone or other iodine-containing medications for thyroid autoimmunity and congenital rubella for some patients with diabetes and thyroiditis. The autoimmune destruction of most target glands appears to be a slow process with a long preclinical prodrome that may last for years. During this period, autoantibodies, lymphocyte abnormalities, and subclinical endocrine defects are usually present. As knowledge of target antigens has progressed, it appears that despite polyendocrine disease, within each gland specific antigens are the targets of the autoimmune process. When the genetic defect(s) and environmental influences of organ specific autoimmunity are better understood, it may be possible to devise specific "replacement" or corrective therapies. In the absence of this knowledge, therapies directed at partial immunosuppression are currently being studied in Type I diabetes and Graves' ophthalmopathy. Given the similar features of many of the organ-specific autoimmune disorders, it is likely that if immunotherapeutic modalities are successful in one disease, they may be of benefit in related disorders.