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.
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 and 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.
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.
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 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 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.
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, 1997.
National Adrenal Disease Foundation. 505 Northern Boulevard, Suite 200, Great Neck, NY 11021. (516) 487-4992.
Addison's disease , also called adrenocortical deficiency or primary adrenal hypofunction, is a rare condition caused by destruction of the cortex of the adrenal gland, one of several glands the endocrine system . Because Addison's disease is treatable, those who develop the illness can expect to have a normal life span.
The adrenal glands
The adrenal glands, also called suprarenal glands, sit like flat, triangular caps atop each kidney. They are divided into two distinct areas-the medulla at the center and cortex surrounding the outside. The cortex, which makes up about 80% of the adrenal gland, secretes three types of hormones—sex hormones , mineralocorticoids (principally aldosterone), and glucocorticoids (primarily cortisol or hydrocortisone). Scientists believe these hormones perform hundreds of regulatory functions in the body, including helping to regulate metabolism , blood pressure , the effects of insulin in the breakdown of sugars, and the inflammatory response of the immune system . Addison's disease results from an injury or disease that slowly destroys the adrenal cortex, therefore shutting down the production of these hormones.
The production of cortisol by the adrenal cortex is precisely metered by a control loop that begins in an area in the brain called the hypothalamus, a collection of specialized cells that control many of the functions of the body. When necessary, the hypothalamus secretes a releasing factor that tells the pituitary gland to secrete another hormone to stimulate the adrenal gland to release more cortisol. The increased cortisol levels signal the pituitary to stop producing the adrenal stimulant. This is a finely tuned loop, and if it is interrupted or shut down, as in Addison's disease, profound changes occur in the body.
History of Addison's disease
The disease is named for its discoverer, Dr. Thomas Addison, a British surgeon who described adrenal insufficiency in 1849, though endocrine functions had yet to be explained. Addison described the condition from autopsies he performed. At the time, there was no cure for adrenal insufficiency, so victims died after contracting it. Addison also noted that 70-90% of patients with adrenal insufficiency had tuberculosis as well.
Addison's disease is no longer a fatal illness if it is properly diagnosed. Today, doctors note that up to 70% of cases are the result of the adrenal cortex being destroyed by the body's own immune system, so Addison's is called an autoimmune disease. Those who have sustained an injury to the adrenal gland and people who have diabetes are at increased risk of Addison's disease. Tuberculosis is also linked to the disease, but since this disease can now be cured, Addison's disease is rarely caused by tuberculosis today.
The effects of adrenal insufficiency do not manifest themselves until more than 90% of the adrenal cortex has been lost. Then weakness and dizziness occur, and the skin darkens, especially on or near the elbows, knees, knuckles, lips, scars, and skin folds. These symptoms begin gradually and worsen over time.
The patient becomes irritable and depressed and often craves salty foods. Some people do not experience these progressive symptoms, but become aware of the disease during what is called an addisonian crisis. In this case, the symptoms appear suddenly and require immediate medical attention. Severe pain develops in the lower back, abdomen, or legs; vomiting and diarrhea leave the patient dehydrated. A person may become unconscious and may even die.
A doctor's examination reveals low blood pressure that becomes even lower when the patient rises from a sitting or lying position to a standing position. A blood test shows low blood sugar (hypoglycemia), low blood sodium (hyponatremia), and low levels of cortisol. Other tests are carried out to determine whether the condition is the result of adrenal insufficiency or if the low levels of cortisol are the result of problems with the hypothalamus or pituitary.
Once diagnosed, Addison's disease is treated by replacing the natural cortisol with an oral medication. The medicine is adjusted by a doctor to bring cortisol levels in the blood up to normal and maintain them. A patient also is advised to eat salty foods, not skip any meals, and carry a packet containing a syringe with cortisone to be injected in case of an emergency.
With the loss of the ability to secrete cortisol under stress , a patient must take extra medication when he undergoes dental treatments or surgery . Even though Addison's disease is not curable, a patient with this condition can expect to live a full life span.
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Addison's disease [for Thomas Addison], progressive disease brought about by atrophy of the outer layer, or cortex, of the adrenal gland; it is also called chronic adrenocortical insufficiency. The deterioration of this tissue causes a decrease in the secretion of steroid hormones, many of which are necessary for the maintenance of life. In many cases the cause of the wasting process is not known; in others the predominant cause is the formation and infiltration of tumors, inflammatory disease, or surgery. Symptoms are increasing weakness, abnormal pigmentation of the skin and mucous membranes, weight loss, low blood pressure, dehydration, and gastrointestinal upsets. Secondary Addison's disease is most commonly caused by acute withdrawal of steroids. Once considered inevitably fatal, Addison's disease can now be treated with injections of adrenocortical hormones.