Addison's disease

Definition

Addison's disease is a disorder involving disrupted functioning of the part of the adrenal gland called the cortex. This results in decreased production of two important chemicals (hormones) normally released by the adrenal cortex: cortisol and aldosterone.

Description

The adrenals are two glands, each perched on the upper part of the two kidneys. The outer part of the gland is known as the cortex; the inner part is known as the medulla. Each of these parts of the adrenal gland is responsible for producing different types of hormones.

Cortisol is a very potent hormone produced by the adrenal cortex. It is involved in regulating the functioning of nearly every type of organ and tissue throughout the body, and is considered to be one of the few hormones absolutely necessary for life. Cortisol is involved in:

• The very complex processing and utilization of many nutrients, including sugars (carbohydrates), fats, and proteins
• The normal functioning of the circulatory system and the heart
• The functioning of muscles
• Normal kidney function
• Production of blood cells
• The normal processes involved in maintaining the skeletal system
• Proper functioning of the brain and nerves
• The normal responses of the immune system.

Aldosterone, also produced by the adrenal cortex, plays a central role in maintaining the appropriate proportions of water and salts in the body. When this balance is upset, the volume of blood circulating throughout the body will fall dangerously low, accompanied by a drop in blood pressure.

Addison's disease is also called primary adrenocortical insufficiency. In other words, some process interferes directly with the ability of the adrenal cortex to produce its hormones. Levels of both cortisol and aldosterone drop, and numerous functions throughout the body are disrupted.

Addison's disease occurs in about four in every 100,000 people. It strikes both men and women of all ages.

Causes & symptoms

The most common cause of Addison's disease is the destruction and/or shrinking (atrophy) of the adrenal cortex. In about 70% of all cases, this atrophy is believed to occur due to an autoimmune disorder. In an autoimmune disorder, the immune system of the body, responsible for identifying foreign invaders such as viruses or bacteria and killing them, accidentally begins to identify the cells of the adrenal cortex as foreign, and destroy them. In about 20% of all cases, destruction of the adrenal cortex is caused by tuberculosis. The remaining cases of Addison's disease may be caused by fungal infections, such as histoplasmosis, coccidiomycosis, and cryptococcosis, which affect the adrenal gland by producing destructive, tumor-like masses called granulomas; a disease called amyloidosis, in which a starchy substance called amyloid is deposited in abnormal places throughout the body, interfering with the function of whatever structure it is present within; or invasion of the adrenal glands by cancer.

In about 75% of all patients, Addison's disease tends to be a very gradual, slowly developing disease. Significant symptoms are not noted until about 90% of the adrenal cortex has been destroyed. The most common symptoms include fatigue and loss of energy, decreased appetite, nausea, vomiting, diarrhea, abdominal pain, weight loss, muscle weakness, dizziness when standing, dehydration, unusual areas of darkened (pigmented) skin, and dark freckling. As the disease progresses, the patient may appear to have very tanned, or bronzed skin, with darkening of the lining of the mouth, vagina, and rectum, and dark pigmentation of the area around the nipples (aereola). As dehydration becomes more severe, the blood pressure will continue to drop and the patient will feel increasingly weak and light-headed. Some patients have psychiatric symptoms, including depression and irritability. Women lose pubic and underarm hair, and stop having normal menstrual periods.

When a patient becomes ill with an infection, or stressed by an injury, the disease may suddenly and rapidly progress, becoming life-threatening. Symptoms of this "Addisonian crisis" include abnormal heart rhythms, severe pain in the back and abdomen, uncontrollable nausea and vomiting, a drastic drop in blood pressure, kidney failure, and unconsciousness. About 25% of all Addison's disease patients are identified due to the development of Addisonian crisis.

Diagnosis

Many patients do not recognize the slow progression of symptoms and the disease is ultimately identified when a physician notices the areas of increased pigmentation of the skin. Once suspected, a number of blood tests can lead to the diagnosis of Addison's disease. It is not sufficient to demonstrate low blood cortisol levels, as normal levels of cortisol vary quite widely. Instead, patients are given a testing dose of another hormone called corticotropin (ACTH). ACTH is produced in the body by the pituitary gland, and normally acts by promoting growth within the adrenal cortex and stimulating the production and release of cortisol. In Addison's disease, even a dose of synthetic ACTH does not increase cortisol levels.

To distinguish between primary adrenocortical insufficiency (Addison's disease) and secondary adrenocortical insufficiency (caused by failure of the pituitary to produce enough ACTH), levels of ACTH in the blood are examined. Normal or high levels of ACTH indicate that the pituitary is working properly, but the adrenal cortex is not responding normally to the presence of ACTH. This confirms the diagnosis of Addison's disease.

Treatment

Treatment of Addison's disease involves replacing the missing or low levels of cortisol. In the case of Addisonian crisis, this will be achieved by injecting a potent form of steroid preparation through a needle placed in a vein (intravenous or IV). Dehydration and salt loss will also be treated by administering carefully balanced solutions through the IV. Dangerously low blood pressure may require special medications to safely elevate it until the steroids take effect.

Patients with Addison's disease will need to take a steroid preparation (hydrocortisone) and a replacement for aldosterone (fludrocortisone) by mouth for the rest of their lives. When a patient has an illness which causes nausea and vomiting (such that they cannot hold down their medications), he or she will need to enter a medical facility where IV medications can be administered. When a patient has any kind of infection or injury, the normal dose of hydrocortisone will need to be doubled.

Prognosis

Prognosis for patients appropriately treated with hydrocortisone and aldosterone is excellent. These patients can expect to enjoy a normal lifespan. Without treatment, or with substandard treatment, patients are always at risk of developing Addisonian crisis.

Key Terms

Gland

A collection of cells whose function is to release certain chemicals, or hormones, which are important to the functioning of other, sometimes distantly located, organs or body systems.

Hormone

A chemical produced in one part of the body, which travels to another part of the body in order to exert its effect.

Further Reading

For Your Information

Books

• Williams, Gordon H. and Robert G. Dluhy. "Hypofunction of the Adrenal Cortex." In Harrison's Principles of Internal Medicine, edited by Anthony S. Fauci, et al. New York: McGraw-Hill, 1998.

  Periodicals

• Brosnan, C.M. and N.F.C. Gowing. "Addison's Disease." British Medical Journal, 312 (7038) (April 27, 1996): 1085+.
• Oelkers, Wolfgang. "Adrenal Insufficiency." New England Journal of Medicine, 335 (16) (October 17, 1996): 1206+.

  Organizations

• National Adrenal Disease Foundation. 505 Northern Boulevard, Suite 200, Great Neck, NY 11021. (516)487-4992.

Gale Encyclopedia of Medicine. Gale Research, 1999.