When Addison's disease is the result of a problem with the adrenal glands themselves (primary adrenal insufficiency), the body's immune system mistakenly attacks the adrenal glands. This autoimmune assault destroys the outer layer of the glands. This happens in 70% of Addison cases.
Long-lasting infections -- such as tuberculosis, HIV, and some fungal infections -- can harm the adrenal glands. Cancer cells that spread from other parts of the body to the adrenal glands also can cause Addison's disease.
Less commonly, Addison's disease is due to secondary adrenal insufficiency, which can be caused by problems with the hypothalamus or pituitary gland, located in the center of the brain. These glands produces hormones that act as a switch and can turn on or off the production of hormones in the rest of the body. A pituitary hormone called ACTH is the switch that turns on cortisol production in the adrenal gland. If ACTH levels are too low, the adrenal glands stay in the off position.
Another cause of secondary adrenal insufficiency is prolonged or improper use of steroid hormones such as prednisone. Less common causes include pituitary tumors and damage to the pituitary gland during surgery or radiation.
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