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What is Addison's disease?

Addison's disease (primary adrenocortical insufficiency) is a rare condition that develops when the adrenal glands, located above the kidneys, are not able to produce enough of the hormones cortisol and, less commonly, aldosterone.

Cortisol affects almost every organ in the body and is important for normal body function. The adrenal glands release cortisol to help the body cope with stress from illness, injury, surgery, childbirth, or other reasons. Aldosterone helps the body retain salt and maintain blood pressure.

Cortisol production by the adrenal glands is controlled by the brain's hypothalamus and in the pituitary gland below the brain. The hypothalamus signals the pituitary gland to produce adrenocorticotropic hormone (ACTH), which in turn stimulates the adrenal glands to produce cortisol. If the adrenal glands cannot produce enough cortisol, the condition is called primary adrenocortical insufficiency (hypocortisolism), or Addison's disease. When the hypothalamus or the pituitary gland is not working correctly to produce enough ACTH, the condition is called secondary adrenocortical insufficiency. This topic focuses on primary adrenocortical insufficiency.

What causes Addison's disease?

Addison's disease usually develops when the body's immune system destroys the part of the adrenal glands that produces cortisol and aldosterone. Addison's disease also can develop when the adrenal glands are destroyed by:

• Cancer that has spread to the adrenal glands. This is most commonly seen in lung cancer.
• Bleeding into the adrenal glands as a side effect of blood-thinning medicine.
• Infections, such as tuberculosis, HIV, or certain bacterial infections, such as meningococcemia (caused by meningococcal bacteria in the bloodstream).
• Some types of surgery or radiation treatments.
• Injury to the adrenal glands during the late stages of pregnancy or during the delivery of the baby. This is rare.
• Using certain medicines, such as high doses of ketoconazole.

Addison's disease can affect people at any age, including children. Addison's disease caused by the immune system destroying the adrenal gland is more frequent in women than in men, but when caused by tuberculosis, it is more frequent in men.¹ It can also develop if someone takes a cortisol-like medicine, such as prednisone, for a long period of time then suddenly stops the treatment.

What are the symptoms?

The most common symptoms of Addison's disease are fatigue, weakness, and unexpected weight loss. Your skin color also may become darker, a condition called hyperpigmentation. Other possible symptoms include lightheadedness; loss of appetite; nausea, vomiting, and diarrhea; and a craving for salt.² In people with diabetes mellitus, episodes of low blood sugar (hypoglycemia) often become more frequent and more severe.

Symptoms usually develop slowly and often are not obvious until an adrenal crisis (Addisonian crisis) occurs because of a stressful event, such as a severe infection, trauma, surgery, or dehydration. The body is not able to produce enough cortisol to cope with stress. If not treated, an adrenal crisis may be fatal because of shock from a steep drop in blood pressure.

In a few cases, Addison's disease develops rapidly. These people may already be in an adrenal crisis when they see a doctor. Symptoms of an adrenal crisis can include vomiting and diarrhea; weakness and lightheadedness; restlessness, confusion, or feeling fearful; difficulty staying awake; and a high fever.

How is Addison's disease diagnosed?

Addison's disease is diagnosed by taking your medical history, a physical examination, and laboratory tests. During the medical history, your doctor will ask about your symptoms, whether you have a family history of the condition, and whether you have had cancer, tuberculosis, or HIV infection. During the physical examination, your doctor will check for hyperpigmentation, low blood pressure, and dehydration.

Laboratory tests can show whether you have high potassium and low sodium levels in your blood—signs of possible Addison's disease. If your doctor suspects you have Addison's disease, he or she will check your blood cortisol and ACTH levels. If your ACTH level is very high, and your cortisol level is low, that may be enough to diagnose Addison's disease.

If the diagnosis is still not clear, an ACTH stimulation test may be done. You will be given a man-made form of ACTH to see whether your body creates cortisol. A low level of cortisol after an injection of ACTH indicates adrenal insufficiency. Further tests will show whether you have primary adrenocortical insufficiency (Addison's disease) or a related condition called secondary adrenocortical insufficiency. Your doctor may recommend imaging tests of the adrenal glands, the pituitary gland, or the hypothalamus, after the problem area is found.

Your doctor may start treatment during the testing if he or she thinks adrenocortical insufficiency is likely. If treatment is found to be unnecessary, it can be stopped after testing is complete.

How is it treated?

If you have Addison's disease (or adrenal failure from another cause), you need to take medicine for the rest of your life to replace the cortisol and aldosterone your body no longer produces. You may be given hydrocortisone, because it can function like both of these hormones. If you receive another steroid to replace cortisol, you also may take a medicine (usually fludrocortisone) to replace aldosterone. The dose of medicine may need to be increased during times of stress or illness. In addition, you may need to add extra salt to food during hot and humid weather to replace salt lost through sweating.

Any person with Addison's disease should always wear medical identification (such as a medical alert bracelet or necklace). If you are injured or ill and cannot tell medical personnel you have Addison's disease, low levels of cortisol could lead to death.

You can lead a long, healthy life by following treatment and preventing an adrenal crisis.

Frequently Asked Questions

Addison's disease develops when the adrenal glands, located above the kidneys, are not able to produce enough of the hormones cortisol and aldosterone. In most cases, the adrenal glands fail slowly and symptoms begin gradually. But symptoms may appear rapidly if the adrenal glands are destroyed suddenly, such as from trauma or severe bleeding (hemorrhage). The most obvious and common symptoms of Addison's disease include:

• Fatigue and muscle weakness that gradually get worse over time.
• Weight loss. Profound weight loss is a common symptom.
• Loss of appetite.

Other symptoms include:

• Darkening of the skin, or hyperpigmentation. This occurs especially:
  • Over new scars.
  • In skin folds.
  • On the lips and tissue lining the mouth and nose.
  • Over joints such as the elbows, knees, knuckles, and toes.
  • In the creases of the palms.
  • On the nipples and surrounding areas (areola).
• Lightheadedness or fainting when getting up from a sitting or lying position. This is called orthostatic hypotension.
• Nausea, vomiting, diarrhea, and belly pain.
• A craving for salty foods.
• Shakiness. People with Addison's disease sometimes have low blood sugar.
• Difficulty concentrating, increased irritability, and depression.

Because symptoms develop slowly, they often are not obvious until an adrenal crisis (Addisonian crisis) occurs. An adrenal crisis is caused by a stressful event, such as a severe infection, trauma, surgery, or dehydration. The body is not able to produce enough cortisol to cope with stress. If an adrenal crisis is not treated, you may die from shock caused by a serious drop in blood pressure. Symptoms of an adrenal crisis include:

• Severe vomiting and diarrhea that lead to a dangerous loss of body fluids (dehydration).
• Extreme weakness, lightheadedness, or feeling that you are going to pass out.
• Sudden pain in the belly, lower back, and legs.
• Abnormal behavior, such as restlessness, confusion, or feeling fearful.
• Changes in level of consciousness, such as having difficulty staying awake, or a total loss of consciousness.
• High fever.
• Pale face and blue lips and earlobes.

A wide range of illnesses—many of them not serious—can have symptoms similar to those of Addison's disease, although they are usually not as severe. Other conditions with similar symptoms range from diarrhea and other gastrointestinal problems to more serious illnesses such as hepatitis or cancer.

Addison's disease develops when the adrenal glands, located above the kidneys, are not able to produce enough of the hormones cortisol and aldosterone. Your doctor may suspect Addison's disease from your medical history, physical examination, and when blood tests show high potassium, low sodium, and high levels of certain types of white blood cells.

If your doctor suspects Addison's disease, you will have a blood test to determine your cortisol level.

Low blood cortisol levels do not always indicate Addison's disease. During a full day, cortisol levels are highest in the morning, drop during the afternoon, and are lowest overnight. Cortisol levels that are normal at one time of the day may be low at other times of the day. But the level of cortisol should be high when the body is physically or emotionally stressed. The diagnosis of Addison's disease is usually confirmed by doing an ACTH stimulation test, which helps show how your hormone levels react to stress. If your test results show you have high cortisol levels, when checked at random, or after the ACTH stimulation test, then you do not have adrenocortical disease.

• Low cortisol blood levels that fail to increase after an injection of ACTH indicate adrenal insufficiency.
• The levels of ACTH in the blood before an injection of ACTH indicate whether you have Addison's disease or secondary adrenocortical insufficiency, in which an inadequate amount of ACTH leads to low cortisol production. This may be caused by a problem with the pituitary gland, which controls hormone production.

X-rays, including computerized axial tomography (CAT scan) or magnetic resonance imaging (MRI), can also be used to check for damage to the adrenal glands.

If Addison's disease is diagnosed, your doctor will also look for thyroid problems, such as hyperthyroidism, hypothyroidism, and low production of parathyroid hormone, which causes a low calcium level in the blood. He or she will also look for other problems such as type 2 diabetes, pernicious anemia, and failure of the reproductive glands ( testes and ovaries). One or more of these conditions are present in about one-half of those with Addison's disease.¹ It is especially important for people with Addison's disease to know if they also have thyroid disease. In people with low thyroid, cortisol lasts longer in the blood. Correcting a low level of thyroid hormone can lead to low cortisol levels and an adrenal crisis.

You may need to see an endocrinologist if the diagnosis or treatment of Addison's disease is uncertain.

Addison's disease develops when the adrenal glands, located above the kidneys, are not able to produce enough of the hormones cortisol and aldosterone. Treatment is usually lifelong. After proper treatment is started, most people with Addison's disease can lead healthy lives.

Treatment includes:

• Medicines to replace the hormones cortisol and aldosterone. Many doctors use a short-acting medicine called hydrocortisone, given 2 or 3 times a day. In some people, long-acting medicines such as prednisone, methylprednisolone, or dexamethasone can be used. You may also need a medicine that can function like aldosterone (usually fludrocortisone). Hydrocortisone is used because it can function like both of these hormones, although some people still need to take additional fludrocortisone. You will need a higher dose of medicine during childbirth; when you have an injury, surgery, or a serious infection; or during severe stress, such as the death of a loved one.
• Increasing salt in the diet. Because people with adrenal failure tend to lose sodium, you will need extra salt (sodium chloride) in your diet, especially during hot and humid weather and vigorous exercise. But because people with Addison's disease retain potassium, you need to avoid salt substitutes, which usually contain potassium chloride salts.
• Regular medical checkups to monitor symptoms and blood pressure. Your doctor also may need to do lab tests to evaluate and monitor blood levels of potassium and sodium.

During a stressful event, such as a severe infection, trauma, surgery, childbirth, dehydration, or an emotional event such as the death of a loved one, you could develop an adrenal crisis. Your body is not able to produce enough cortisol for the stressful condition. If an adrenal crisis is not treated, you may die from shock caused by a serious drop in blood pressure. You would need treatment in the hospital.

Recent small studies suggest that women with Addison's disease may benefit from taking a hormone replacement called dehydroepiandrosterone (DHEA). Some women who take this medicine every day may experience a greater sense of well-being and improvement in depression, anxiety, sexuality, and sensitivity to insulin.^{3, 4} If you are considering DHEA, talk to your doctor.

Addison's disease develops when the adrenal glands, located above the kidneys, are not able to produce enough of the hormones cortisol and aldosterone. Home treatment is very important. If you have Addison's disease:

• Take your medicine daily as recommended. Medicine should be taken at the same times of day when your body would normally need the hormones (usually more in the morning and less in the evening). Let your doctor know how you are doing. For example, if your face is puffy or if you are gaining weight or bruising more easily or extensively than usual, the amount of your medicine may be too high. If you are still fatigued, have no appetite, or are feeling generally unwell, the amount of your medicine may be too low.
• Don't restrict salt in your diet. Your body needs a certain amount of salt. With Addison's disease, your body may lose too much salt. You may need to add extra salt to your food during hot and humid weather or when you are exercising and sweating.
• Seek medical help in an emergency. If you have symptoms of adrenal crisis, take your emergency medicine (such as dexamethasone) as directed and seek medical help immediately. An adrenal crisis is caused by a stressful event, such as a severe infection, trauma, surgery, or dehydration. Your body is not able to produce enough cortisol for the stressful condition. If this is not treated, you may die from shock caused by a serious drop in blood pressure. Have an injection of emergency medicine ready at your home, work or school, and in the car. Know when and how to give the medicine. Have instructions written out, and teach someone else how to give you the medicine in case you can't give it to yourself. Replace unused syringes of emergency medicine each year or if the solution begins to look cloudy or colored.
• Carry a medical identification card or bracelet (such as a medical alert bracelet) that states that you have Addison's disease. This information helps medical personnel decide whether to give you a cortisol shot if you are unconscious, severely injured, or unable to answer questions.
• Monitor your weight regularly, especially if your appetite has been poor or you have been vomiting. Weigh yourself at the same time of day and wearing the same amount of clothing. Ask when your doctor wants to be notified about weight loss or frequent vomiting.
• Monitor your blood pressure. High blood pressure and swelling may indicate that your medicine needs to be adjusted. Also, if you notice that you become lightheaded when you first get up in the morning, your blood pressure may be low. Sit on the edge of your bed for a while before standing. Let your doctor know if this problem becomes worse.

In addition, you need to be prepared for and deal with minor illness or stress. During illness or stress, you may need to:

• Increase your medicine dosage. Talk with your doctor about when and how much you should increase your medicine dosage during a minor illness or time of stress. Have clear instructions written out for which medicine should be increased and how much you should increase it.
• Know when to contact your doctor if you have either stress or a minor infection that won't go away. If you notice signs of a severe infection, such as high fever, frequent cough, or burning with urination, call right away.
• Contact your doctor right away if you are unable to take your cortisol medicine because of nausea or vomiting, or if you have ongoing diarrhea.

Organizations

Citations

1. Miller WL, Chrousus GP (2001). Primary adrenocortical insufficiency section of The adrenal cortex. In P Felig, LA Frohman, eds., Endocrinology and Metabolism, pp. 461–475. New York: McGraw-Hill.

2. Aron DC, et al. (2007). Disorders of adrenocortical insufficiency section of Glucocorticoids and adrenal androgens. In DG Gardner, D Shoback, eds., Greenspan's Basic and Clinical Endocrinology, 8th ed., pp. 367–378. New York: McGraw-Hill.

3. Dehydroepiandrosterone (DHEA) (2005). Medical Letter on Drugs and Therapeutics, 47(1208): 37–38.

4. Arlt W, et al. (1999). Dehydroepiandrosterone replacement in women with adrenal insuffieciency. New England Journal of Medicine, 341(14): 1013–1020.

Other Works Consulted

• Aron DC, et al. (2004). Glucocorticoids and adrenal androgens. In FS Greenspan et al., eds., Basic and Clinical Endocrinology, 8th ed., pp. 346–394. New York: McGraw-Hill.

• Dambro MR (2006). Addison disease. In Griffith's 5-Minute Clinical Consult, p. 14. Philadelphia: Lippincott Williams and Wilkins.

• Drincic A, Anderson RJ (2007). Adrenal insufficiency. In RE Rakel, ET Bope, eds., Conn's Current Therapy 2007, pp. 737–740. Philadelphia: Saunders Elsevier.

• Loriaux DL (2004). The adrenal. In DC Dale, DD Federman, eds., ACP Medicine, section 3, chap. 4. New York: WebMD.

• Miller M (2007). Selected endocrine problems. In LR Barker et al., eds., Principles of Ambulatory Medicine, 7th ed., pp. 1367–1394. Philadelphia: Lippincott Williams and Wilkins.

• Stewart PM (2003). Glucocorticoid deficiency section of The adrenal cortex. In PR Larsen et al., eds., Williams Textbook of Endocrinology, 10th ed., pp. 525–532. Philadelphia: Saunders.

Author:	Caroline Rea, RN, BS, MS	Last Updated: February 20, 2008
Medical Review:	Caroline S. Rhoads, MD - Internal Medicine Alan C. Dalkin, MD - Endocrinology
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