Autoimmune Mechanisms in Endocrine Disease

Autoimmune endocrine disease develops when immune cells lose tolerance to a self-tissue and begin treating a hormone-producing gland as a target. The clinical result depends on what the immune response does to that gland. Some antibodies stimulate a receptor. In Graves disease, thyroid-stimulating immunoglobulins activate the thyroid-stimulating hormone receptor, driving excess thyroid hormone production even when pituitary TSH is suppressed. Other autoimmune processes progressively destroy tissue. Type 1 diabetes results from T-cell-mediated destruction of pancreatic beta cells. Hashimoto thyroiditis destroys thyroid tissue over time, and autoimmune adrenal insufficiency damages the adrenal cortex. The patient then develops disease because the gland can no longer produce enough hormone. Autoantibodies are useful clues, but they do not always cause the injury directly. In type 1 diabetes, islet autoantibodies identify an autoimmune process; T cells are the principal cells destroying beta cells. This distinction explains why a person may have positive antibodies for years before hyperglycemia appears. Autoimmune endocrine disorders cluster because the same susceptibility to immune dysregulation can affect several organs. A patient with type 1 diabetes may later develop autoimmune thyroid disease,...