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In Addison disease, the adrenal glands are underactive, resulting in a deficiency of adrenal hormones.
Addison disease can start at any age and affects males and females about equally. In 70% of people with Addison disease, the cause is not precisely known, but the adrenal glands are affected by an autoimmune reaction (see Allergic Reactions and Other Hypersensitivity Disorders: Autoimmune Disorders) in which the body's immune system attacks and destroys the adrenal cortex. In the other 30%, the adrenal glands are destroyed by cancer, an infection such as tuberculosis, or another identifiable disease. In infants and children, Addison disease may be due to a genetic abnormality of the adrenal glands.
Secondary adrenal insufficiency is a term given to a disorder that resembles Addison disease. In this disorder, the adrenal glands are underactive because the pituitary gland is not stimulating them, not because the adrenal glands have been destroyed or have otherwise directly failed.
When the adrenal glands become underactive, they tend to produce inadequate amounts of all of the adrenal hormones. Thus, Addison disease affects the balance of water, sodium, and potassium in the body, as well as the body's ability to control blood pressure and react to stress. In addition, loss of androgens, such as dehydroepiandrosterone (DHEA), may cause a loss of body hair in women. In men, testosterone from the testes more than makes up for this loss. DHEA may have additional effects that do not relate to androgens.
When the adrenal glands are destroyed by infection or cancer, the adrenal medulla and thus the source of epinephrine is lost. However, this loss does not cause symptoms.
A deficiency of aldosterone in particular causes the body to excrete large amounts of sodium and retain potassium, leading to low levels of sodium and high levels of potassium in the blood. The kidneys are not able to retain sodium easily, so when a person with Addison disease drinks too much water or loses too much sodium, the level of sodium in the blood falls, and the person becomes dehydrated. Severe dehydration and a low sodium level reduce blood volume and can lead to shock.
Corticosteroid deficiency leads to an extreme sensitivity to insulin so that the level of sugar in the blood may fall dangerously low (hypoglycemia). The deficiency prevents the body from manufacturing carbohydrates from protein, fighting infections properly, and controlling inflammation. Muscles weaken, and even the heart can become weak and unable to pump blood adequately. In addition, the blood pressure may become dangerously low.
People with Addison disease are not able to produce additional corticosteroids when they are stressed. They therefore are susceptible to serious symptoms and complications when confronted with illness, extreme fatigue, severe injury, surgery, or, possibly, severe psychologic stress.
In Addison disease, the pituitary gland produces more corticotropin in an attempt to stimulate the adrenal glands. Corticotropin also stimulates melanin production, so the skin and the lining of the mouth often develop a dark pigmentation.
Symptoms
Soon after developing Addison disease, a person feels weak, tired, and dizzy when standing up after sitting or lying down. These problems may develop gradually and insidiously. People with Addison disease develop patches of dark skin. The darkness may seem like tanning, but it appears on areas not even exposed to the sun. Even people with dark skin can develop excessive pigmentation, although the change may be harder to recognize. Black freckles may develop over the forehead, face, and shoulders, and a bluish black discoloration may develop around the nipples, lips, mouth, rectum, scrotum, or vagina.
Most people lose weight, become dehydrated, have no appetite, and develop muscle aches, nausea, vomiting, and diarrhea. Many become unable to tolerate cold. Unless the disease is severe, symptoms tend to become apparent only during times of stress. Periods of hypoglycemia, with nervousness and extreme hunger for salty foods, can occur, particularly in children.
If Addison disease is not treated, severe abdominal pain, profound weakness, extremely low blood pressure, kidney failure, and shock may occur (adrenal crisis). An adrenal crisis often occurs if the body is subjected to stress, such as an accident, injury, surgery, or severe infection. Death may quickly follow.
Diagnosis
Because the symptoms may start slowly and subtly, and because no single laboratory test may give definitive results in the early stages, doctors often do not suspect Addison disease at the outset. Sometimes a major stress makes the symptoms more obvious and precipitates a crisis.
Blood tests may show low sodium and high potassium levels and usually indicate that the kidneys are not working well. Doctors who suspect Addison disease measure cortisol levels, which may be low, and corticotropin levels, which may be high. However, doctors may need to confirm the diagnosis by measuring cortisol levels before and after an injection of corticotropin. If cortisol levels are low, further tests are needed to determine if the problem is Addison disease or secondary adrenal insufficiency.
Treatment
Regardless of the cause, Addison disease can be life threatening and must be treated with corticosteroids and intravenous fluids. Usually, treatment can be started with hydrocortisone or prednisone (a synthetic corticosteroid) taken by mouth. However, people who are severely ill may be given cortisol intravenously or intramuscularly at first and then hydrocortisone tablets. Because the body normally produces most cortisol in the morning, replacement hydrocortisone should also be taken in divided doses, with the largest dose in the morning. Hydrocortisone will need to be taken every day for the rest of the person's life. Larger doses of hydrocortisone are needed when the body is stressed, especially from an illness, and may need to be given by injection if the person has severe diarrhea or vomiting.
Most people also need to take fludrocortisone tablets every day to help restore the body's normal excretion of sodium and potassium. Supplemental testosterone is not usually needed, although there is some evidence that replacement with DHEA improves the quality of life. Although treatment must be continued for life, the outlook is excellent.
Last full review/revision September 2012 by Ashley B. Grossman, MD, FRCP, FMedSci
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