Addison's disease is caused by damage to the adrenal glands. The adrenal glands sit just above the kidneys. As part of the endocrine system, they make hormones that affect almost every organ and tissue in the body. Damage to these glands results in too little of the hormone cortisol and, often, the hormone aldosterone.
The adrenal glands are made up of two sections. The interior, called the medulla, makes adrenaline-like hormones. The outer layer, called the cortex, makes a group of hormones called corticosteroids. Corticosteroids include:
- Glucocorticoids. These hormones, including cortisol, affect the body's ability to turn food into energy. They also play a role in the immune system's inflammatory response and help the body respond to stress.
- Mineralocorticoids. These hormones, including aldosterone, balance the body's sodium and potassium to keep blood pressure in a healthy range.
- Androgens. In all people, the adrenal glands make small amounts of these sex hormones. They cause male sexual development. And they affect muscle mass, sex drive, known as libido, and a sense of well-being in all people.
Primary adrenal insufficiency
Sometimes, the outer layer of the adrenal glands, known as the cortex, is damaged. Then it can't make enough hormones, a condition called primary adrenal insufficiency. This is usually the result of an autoimmune disease, in which the body attacks itself. People with Addison's disease are more likely than are other people to have another autoimmune disease as well.
Other causes of adrenal gland failure may include:
- Tuberculosis.
- Other infections of the adrenal glands.
- Spread of cancer to the adrenal glands.
- Bleeding into the adrenal glands.
- Medicines that block the body's ability to make glucocorticoid, such as ketoconazole and etomidate (Amidate). Or medicines that block the action of glucocorticoid in the body, such as mifepristone (Mifeprex, Korlym).
- Treatment for cancer with medicines called checkpoint inhibitors.
Secondary adrenal insufficiency
The pituitary gland makes a hormone called adrenocorticotropic hormone (ACTH). ACTH in turn causes the adrenal cortex to make its hormones. Having pituitary tumors that aren't cancer, inflammation and pituitary surgery can cause the pituitary gland to make too little ACTH.
Too little ACTH can cause the adrenal glands to make too little glucocorticoids and androgens. This is called secondary adrenal insufficiency.
Most symptoms of secondary adrenal insufficiency are similar to those of primary adrenal insufficiency. However, people with secondary adrenal insufficiency don't have darkened skin and are less likely to have severe dehydration or low blood pressure. They're more likely to have low blood sugar.
A temporary cause of secondary adrenal insufficiency occurs when people who take corticosteroids, such as prednisone, to treat conditions such as asthma or arthritis, stop taking the medicine suddenly rather than tapering off.