The adrenal glands are hormone-producing organs located on top of each kidney. The outer part of the adrenal is called the cortex. The cortex makes three types of hormones: glucocorticoid hormones, mineralocorticoid hormones and sex hormones.

Glucocorticoids are hormones that help the body fight infection, regulate blood sugar and deal with stressful situations. Cortisol is the best known of the glucocorticoids. Mineralocorticoids (including aldosterone) regulate water and salt balance and help control blood pressure and volume. The sex hormones made in the adrenal cortex contribute to some secondary sex characteristics.

Adrenal insufficiency occurs when there is decreased production of some or all of these hormones produced by the adrenal cortex. Clinically the most important hormones are cortisol and aldosterone.

Many different problems can cause adrenal insufficiency. There may be a disorder of the adrenal glands themselves. This is known as "primary adrenal insufficiency." The adrenal glands can be damaged by the body’s own immune system mistakenly attacking the gland. They also can be damaged by infections, hemorrhage or tumors.

Adrenal insufficiency can also occur when the pituitary gland, located in the base of the brain, is damaged. The pituitary helps regulate the function of the adrenals. A pituitary problem can lead to decreased production of cortisol by the adrenal glands. This is referred to as "secondary adrenal insufficiency." Aldosterone production by the adrenal glands is not impaired in this form of adrenal insufficiency. Damage to the pituitary can be caused by a tumor or surgery. Long-term use of certain medications such as prednisone can affect the way the pituitary controls the adrenal glands, and can cause temporary adrenal insufficiency.

Tertiary adrenal insufficiency is due to a problem in the hypothalamus. This part of the brain helps regulate the pituitary. A hypothalamic problem can impair the pituitary’s ability to regulate the adrenal glands' production of cortisol.

Lacking adrenal hormones can lead to many different symptoms. The clinical picture will depend on the cause of the problem, the speed at which the condition develops, and the amount of hormones actually produced.

Primary adrenal insufficiency is characterized by fatigue, weight loss, low blood pressure, and weakness. People also may have nausea and vomiting, joint and muscle pains, darkening of the skin, and cravings for salt. Rarely, adrenal "crisis" develops, with very low blood pressure, fever, and vomiting and abdominal pain. The symptoms of secondary and tertiary adrenal insufficiency are similar. However, darkening of the skin and dehydration are not seen with these forms. Of course, there may be other symptoms depending on the cause of the adrenal insufficiency.

Adrenal insufficiency does not involve the pancreas. However, there is a clinical syndrome known as Schmidt’s syndrome, which is a "polyendocrine syndrome" and can be associated with both adrenal insufficiency and diabetes.