Addison's Disease

Adrenal Insufficiency and Adrenal Crisis

Addison's Disease (also called adrenal insufficiency, AI, or hypocort isolism) is an endocrine disorder t hat occurs when t he adrenal glands do not produce enough of t he hormone cort isol.

Authors
M aryO CushingsHelp

Published Creat ive Commons At t ribut ion 3.0 License Version 45 Last edit ed: Aug 12, 2008 Export ed: Aug 11, 2012 Original URL: ht t p://knol.google.com/k/-/-/r4frzuit dsa4/2

What are the Adrenal Glands?

The human body has two adrenal glands, one on the top of each kidney, like the stocking cap on a newborn baby. The adrenal glands are part of a very complex endocrine system which produces many hormones that interact with each other. The hypothalamus produces corticotropin-releasing hormone, triggering the pituitary gland to secrete corticotropin, which regulates the production of corticosteroids by the adrenal glands. (see image below) The inner part, or the medulla, of the adrenal glands secretes hormones such as adrenaline (epinephrine) that affect blood pressure, heart rate,
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sweating, and other activities also regulated by the sympathetic nervous system. The outer part (cortex) secretes many different hormones, including cortisone-like hormones (corticosteroids), androgens (male hormones), and mineralocorticoids, which control blood pressure and the levels of salt and potassium in the body. Adrenal glands may stop functioning when either the pituitary or hypothalamus fails to produce enough of the appropriate hormones. Underproduction or overproduction of any adrenal hormones can lead to serious illness such as Addison's Disease.

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Addison's Disease
Addison's Disease (also called adrenal insufficiency, AI, or hypocortisolism) is an endocrine disorder that occurs when the adrenal glands do not produce enough of the hormone cortisol and, in some cases, the hormone aldosterone. Aldosterone belongs to a class of hormones called mineralocorticoids, also produced by the adrenal glands. It helps maintain blood pressure and water and salt balance in the body by helping the kidney retain sodium and excrete potassium. When aldosterone production falls too low, the kidneys are not able to regulate salt and water balance, causing blood volume and blood pressure to drop. Addison's can occur in any age group and afflicts both males and females equally. The disease is characterized by weight loss, muscle weakness, fatigue, low blood pressure, dizziness and sometimes darkening of the skin in both exposed and nonexposed parts of the body. Black freckles may develop over the forehead, face, and shoulders; a bluish-black discoloration may develop around the nipples, lips, mouth, rectum, scrotum, or vagina. Most people with Addison's 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 more apparent during times of stress. If Addison's Disease isn't treated , severe abdominal pains, profound weakness, extremely low blood pressure, kidney failure, and shock may occur, especially if the body is subjected to stress such as an injury, surgery, or severe infection. Death may quickly follow. Naturally occurring adrenal insufficiency is also known as " primary adrenal insufficiency ". Because there are fewer individuals with primary adrenal insufficiency, there is more information about that near the end of this article. The focus of this article is for individuals with secondary adrenal insufficiency. Secondary adrenal insufficiency is much more common than primary adrenal insufficiency and can be traced to a lack of ACTH due to many causes. Without ACTH to stimulate the adrenals, the adrenal glands' production of cortisol drops, but not aldosterone.

The Causes of Addison's Disease

Besides the causes I mentioned above with Cushing's patients, there are several other reasons that the body fails to produce enough cortisol. The problem may be due to a disorder of the adrenal glands themselves (primary adrenal insufficiency) or to inadequate secretion of ACTH by the pituitary gland (secondary adrenal insufficiency).
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ACTH is the abbreviation for Adrenocorticotropic Hormone. ACTH is a normal by-product of the anterior pituitary gland. It acts by controlling the secretion of the adrenal hormone, cortisol.

Secondary Adrenal Insufficiency

Addison's Disease / Adrenal Insufficiency can be caused when the adrenal glands are removed. This is often the case with Cushing's patients and why I have come to learn about it. Many times after a pituitary Cushing's patient has had two or three failed surgeries, it becomes apparent that surgical treatment will not work. The patient may even try gamma knife or stereotactic radiotherapy to cure his/her Cushing's. Gamma knife and stereotactic radiotherapy can take up to a year to work so they aren't always good options for a patient who may have already been sick for 10 or more years. Having a bilateral adrenalectomy (BLA) will almost always cure the patient of his/her Cushing's. In addition to developing Addison's Disease, the pituitary patient who has had a BLA may also find that s/he has Nelson's Syndrome but that's a subject for another article. Another cause of secondary adrenal insufficiency is the surgical removal of benign, or noncancerous, ACTH-producing tumors of the pituitary gland (Cushing's disease). In this case, the source of ACTH is suddenly removed, and a replacement hormone such as Cortef (hydrocortisone) must be taken until normal ACTH and cortisol production resumes. AI can also occur when the pituitary gland either decreases in size or stops producing ACTH. These changes can result from tumors or infections; loss of blood flow to the pituitary; radiation for the treatment of pituitary tumors; surgical removal of parts of the hypothalamus; or surgical removal of the entire pituitary gland. Other patients who have had only one adrenal gland removed my find that the remaining gland doesn't pick up the slack so they, too, are deficient. Even rarer are people like myself. I had a successful pituitary surgery but developed scar tissue on my pituitary gland. The scar tissue caused my adrenal glands not to work at full capacity. Then, during a nephrectomy (kidney removal), my left adrenal gland was removed, making my already weak adrenal system even weaker. A temporary form of secondary adrenal insufficiency may occur when a person who has been receiving a glucocorticoid hormone such as Prednisone for a long time abruptly stops or interrupts taking the medication. Glucocorticoid hormones, which are often used to treat inflammatory illnesses like rheumatoid arthritis or asthma block the release of both corticotropin-releasing hormone (CRH) and ACTH. Normally, CRH instructs the pituitary gland to release ACTH. If CRH levels drop, the pituitary is not stimulated to release ACTH, and the adrenals then fail to secrete sufficient levels of cortisol. In addition to having an adrenal tumor removed due to Cushing's Disease, the adrenals themselves can develop their own adenomas, tumors, or hyperplasia.
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Symptoms of Adrenal Insufficiency (AI)

In patients with secondary AI, these symptoms often occur immediately. In people with primary insufficiency the symptoms of adrenal insufficiency usually begin gradually. In either case the characteristics of AI are: chronic, worsening fatigue muscle weakness loss of appetite weight loss headache slow, sluggish, lethargic movement dehydration high fever chills, shaking confusion or coma rapid heart rate joint pain abdominal pain unintentional weight loss rapid respiratory rate unusual and excessive sweating on face and/or palms possible skin rash or lesion flank pain irritability and depression a craving for salty foods due to salt loss Hypoglycemia, or low blood glucose, is more severe in children than in adults About 50 percent of the time, one will notice: nausea vomiting diarrhea Other symptoms may include:
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low blood pressure that falls further when standing, causing dizziness or fainting skin changes in Addison's disease, with areas of hyperpigmentation, or dark tanning, covering exposed and nonexposed parts of the body. This darkening of the skin is most visible on scars; skin folds; pressure points such as the elbows, knees, knuckles, and toes; lips; and mucous membranes. menstrual periods may become irregular or stop

Adrenal Crisis / Addison Crisis

Because the symptoms progress slowly, they are usually ignored until a stressful event like an illness or an accident causes them to become worse. This is called an Adrenal Crisis, or acute adrenal insufficiency. In most cases, symptoms are severe enough that patients seek medical treatment before a crisis occurs. In about 25 percent of patients, symptoms first appear during an Adrenal Crisis. Symptoms of an Adrenal Crisis include: sudden penetrating pain in the lower back, abdomen, or legs severe vomiting and diarrhea dehydration low blood pressure loss of consciousness For more personal experiences, see these message boards

Prevention
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Left untreated, an Addison's Crisis can be fatal.

It is important for the individual with Addison's disease to always carry a medical identification card such as those produced by the Medic Alert Foundation. These cards state the type of medication and the proper dose needed in case of an emergency as well as doctor and close relative contact information. Never omit medication. If unable to retain medication due to vomiting, notify the health care provider. Acute adrenal crisis is an emergency caused by decreased cortisol (more about cortisol below). The crisis may occur in a person with Addison's disease, or as the first sign of adrenal insufficiency. More uncommonly, it may be caused by a pituitary gland disorder. It may also be caused by sudden withdrawal of corticosteroids, removal or injury of the adrenal glands, or destruction of the pituitary gland. Risk factors are stress, trauma, surgery, or infection in a person with Addison's disease, or injury or trauma to the adrenal glands or the pituitary gland. People who have Addison's disease should be taught to recognize signs of potential stress that may precipitate an acute adrenal crisis (cause it to occur suddenly and unexpectedly). Most people with Addison's disease are taught to give themselves an emergency injection of hydrocortisone in times of stress.

What You Can Do

A person who has adrenal insufficiency should always carry identification stating his or her condition in case of an emergency. The card should alert emergency personnel about the need to inject 100 mg of cortisol if its bearer is found severely injured or unable to answer questions. The card should also include the doctor's name and telephone number and the name and telephone number of the nearest relative to be notified. When traveling, a needle, syringe, and an injectable form of cortisol should be carried for emergencies. If traveling by airplane, you may need a letter from your doctor explaining the medical necessity for carrying this equipment. A person with Addison's disease also should know how to increase medication during periods of stress or mild upper respiratory infections. Immediate medical attention is needed when severe infections, vomiting, or diarrhea occur. These conditions can precipitate an addisonian crisis. A patient who is vomiting may require injections of hydrocortisone. People with medical problems may wish to wear a descriptive warning bracelet or neck chain to alert emergency personnel. A number of companies manufacture medical identification products.

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Treatment
In adrenal crisis, an intravenous or intramuscular injection of hydrocortisone (an injectable corticosteroid) must be given immediately. If your doctor gave you a prescription for injectable hydrocortisone, use that immediately and have someone get you to the hospital. During an Adrenal Crisis, low blood pressure, low blood glucose, and high levels of potassium can be life threatening. Standard therapy involves intravenous injections of hydrocortisone, saline (salt water), and dextrose (sugar). This treatment usually brings rapid improvement. When the patient can take fluids and medications by mouth, the amount of hydrocortisone is decreased until a maintenance dose is achieved. If aldosterone is deficient, maintenance therapy also includes oral doses of fludrocortisone acetate. Treatment of Addison's disease involves replacing, or substituting, the hormones that the adrenal glands are not making. Cortisol is replaced orally with hydrocortisone tablets, a synthetic glucocorticoid, taken once or twice a day. If aldosterone is also deficient, it is replaced with oral doses of a mineralocorticoid called fludrocortisone acetate (Florinef), which is taken once a day. Patients receiving aldosterone replacement therapy are usually advised by a doctor to increase their salt intake. Because patients with secondary adrenal insufficiency normally maintain aldosterone production, they do not require aldosterone replacement therapy. The doses of each of these medications are adjusted to meet the needs of individual patients.

Primary Adrenal Insufficiency

Primary AI Causes
Most cases of Addison's Disease are caused by the gradual destruction of the adrenal cortex by the body's own immune system. The adrenal cortex is the outer layer of the adrenal gland and it secretes various hormones including cortisone, estrogen, testosterone, cortisol, androgen, aldosterone and progesterone. Adrenal insufficiency occurs when at least 90 percent of the adrenal cortex has been destroyed. As a result of this adrenal cortex damage, often both glucocorticoid (cortisol) and mineralocorticoid (aldostertone) hormones are lacking. Sometimes only the adrenal gland is affected; sometimes other glands also are affected, as in the polyendocrine deficiency syndrome. About 70 percent of reported cases of Addison's disease are caused by autoimmune disorders, in which the immune system makes antibodies that attack the body's own tissues or organs and slowly destroy them.
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Tuberculosis (TB) is an infection which can destroy the adrenal glands. As the treatment for TB improves, however, the incidence of adrenal insufficiency due to TB of the adrenal glands has greatly decreased. Less common causes of primary adrenal insufficiency are chronic infection (usually fungal infections), cancer cells spreading from other parts of the body to the adrenal glands and amyloidosis.

Primary Adrenal Insufficiency Diagnosis

In its early stages, primary adrenal insufficiency can be difficult to diagnose. A review of a patient's medical history based on the symptoms, especially the dark tanning of the skin, will lead a doctor to suspect Addison's disease. A diagnosis of Addison's disease is made by laboratory tests. The aim of these tests is first to determine whether levels of cortisol are insufficient and then to establish the cause. X-ray exams of the adrenal and pituitary glands also are useful in helping to establish the cause.

Signs and tests

An ACTH (cortrosyn) stimulation test shows low cortisol. This is the most specific test for diagnosing Addison's disease. In this test, blood cortisol, urine cortisol, or both are measured before and after a synthetic form of ACTH is given by injection. In the socalled short, or rapid, ACTH test, measurement of cortisol in blood is repeated 30 to 60 minutes after an intravenous ACTH injection. The normal response after an injection of ACTH is a rise in blood and urine cortisol levels. Patients with either form of adrenal insufficiency respond poorly or do not respond at all. CRH stimulation test. When the response to the short ACTH test is abnormal, a "long" CRH stimulation test is required to determine the cause of adrenal insufficiency. In this test, synthetic CRH is injected intravenously and blood cortisol is measured before and 30, 60, 90, and 120 minutes after the injection. Patients with primary adrenal insufficiency have high ACTHs but do not produce cortisol. Patients with secondary adrenal insufficiency have deficient cortisol responses but absent or delayed ACTH responses. Absent ACTH response points to the pituitary as the cause; a delayed ACTH response points to the hypothalamus as the cause. In patients suspected of having an addisonian crisis, the doctor must begin treatment with injections of salt, fluids, and glucocorticoid hormones immediately. Although a reliable diagnosis is not possible while the patient is being treated for the crisis, measurement of blood ACTH and cortisol during the crisis and before glucocorticoids are given is enough to make the diagnosis. Once the crisis is controlled and medication has been stopped, the doctor will delay further testing for up to 1 month to obtain an accurate diagnosis. The fasting blood sugar may be low. low cortisol decreased serum sodium elevated serum potassium
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This disease may also alter the results of the following tests: sodium, urine 17-hydroxycorticosteroids

Other Tests
Once a diagnosis of primary adrenal insufficiency has been made, x-ray exams of the abdomen may be taken to see if the adrenals have any signs of calcium deposits. Calcium deposits may indicate TB. A tuberculin skin test also may be used. If secondary adrenal insufficiency is the cause, doctors may use different imaging tools to reveal the size and shape of the pituitary gland. The most common is the CT scan, which produces a series of x-ray pictures giving a cross-sectional image of a body part. The function of the pituitary and its ability to produce other hormones also are tested.

Expectations (prognosis)
Death may occur due to overwhelming shock if early treatment is not provided.

Complications:
shock coma seizures

Special Problems for Anyone with Adrenal Insufficiency

Surgery
Patients with chronic adrenal insufficiency who need any type surgery with general anesthesia are treated with injections of hydrocortisone and saline. Injections begin on the evening before surgery and continue until the patient is fully awake and able to take medication by mouth. The dosage is adjusted until the maintenance dosage given before surgery is reached.

Pregnancy
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Women with primary adrenal insufficiency who become pregnant are treated with standard replacement therapy. If nausea and vomiting in early pregnancy interfere with oral medication, injections of the hormone may be necessary. During delivery, treatment is similar to that of patients needing surgery. Following delivery, the dose is gradually tapered (weaning) and the usual maintenance doses of hydrocortisone and fludrocortisone acetate by mouth are reached by about 10 days after childbirth.

Famous Addisonians
US President John F. Kennedy was one of the best-known Addison's disease sufferers. He was possibly one of the first Addisonians to survive major surgery. There was substantial secrecy surrounding his health during his years as president, and the 25th amendment to the U.S. constitution was introduced at least in part as a result of this secrecy. Helen Reddy, Popular singer Eugene Merle Shoemaker, scientist and co-discoverer of the Comet Shoemaker-Levy 9. Blessed Elizabeth of the Trinity, French Carmelite nun and religious writer

Possible Addisonians

Some have suggested that Jane Austen, but others have disputed this. According to Dr. Carl Abbott, a Canadian medical researcher, Charles Dickens may also have been affected. Osama bin- Laden may be an Addisonian. Lawrence Wright ( The Looming Tower , 2006, p. 139) notes that bin-Laden manifests all the key symptoms, such as "low blood pressure, weight loss, muscle fatigue, stomach irritability, sharp back pains, dehydration, and an abnormal craving for salt". Bin-Laden is known to have been consuming large amounts of the drug Arcalion to treat his symptoms.

Cortisol
Cortisol, a hormone produced by the adrenal glands, also belongs to a class of hormones called glucocorticoids. These hormones affect
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Cortisol, a hormone produced by the adrenal glands, also belongs to a class of hormones called glucocorticoids. These hormones affect almost every organ and tissue in the body. A Cushing's patient can tell that every organ is affected by the wide range of symptoms s/he has. Cortisol helps the body respond to stress. It's part of the "fight or flight" syndrome. Among its other vital tasks, cortisol helps helps helps helps helps maintain blood pressure and cardiovascular function slow the immune system's inflammatory response balance the effects of insulin in breaking down sugar for energy regulate the metabolism of proteins, carbohydrates, and fats maintain proper arousal and sense of well-being

Because cortisol is so vital to health, the amount of cortisol produced by the adrenals is precisely balanced. Like many other hormones, cortisol is regulated by the brain's hypothalamus and the pituitary gland, a bean-sized organ at the base of the brain. First, the hypothalamus sends "releasing hormones" to the pituitary gland. The pituitary responds by secreting hormones that regulate growth and thyroid and adrenal function, and sex hormones such as estrogen and testosterone. One of the pituitary's main functions is to secrete ACTH (adrenocorticotropin), a hormone that stimulates the adrenal glands. When the adrenals receive the pituitary's signal in the form of ACTH, they respond by producing cortisol. Completing the cycle, cortisol then signals the pituitary to lower secretion of ACTH.

For More Information on Addison's Disease and Adrenal Insufficiency

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On the Web

Addison and Cushing International Federation (ACIF) Information on Addison's Disease, Cushing's syndrome, and Acromegaly. Includes the personal stories of two Cushing's patients and contact info for support groups. Addison's forum Addison Help Addison News E-mail: Joan Hoffman Adrenal Clinical Trials Adrenal Crisis / Insufficiency Adrenal Hyperplasia Australian Addison's Disease News Dutch/International Addison's and Cushing Society New Zealand Addison's Network

Organizations
National Adrenal Diseases Foundation 505 Northern Boulevard Great Neck, NY 11021 Telephone: (516) 487-4992 e-mail: nadf@aol.com Home Page: www.NADF.US NIH/National Digestive Diseases Information Clearinghouse 2 Information Way Bethesda, MD 20892--3570 Telephone: (301) 654-3810
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Toll free: (800) 891-5389 NIH/National Institute of Child Health and Human Development 9000 Rockville Pike Building 31, Room 2A32 MSC2425 Bethesda, MD 20892 Telephone: (301) 496-5133 Home Page: http://www.nichd.nih.gov/ National Organiz ation for Rare Disorders, Inc. (NORD) P.O. Box 8923 New Fairfield, CT 06812-8923 Telephone: (203) 746-6518 Fax: (203) 746-6481 Toll free: (800) 999-6673 TDD: (203) 746-6927 e-mail: orphan@rarediseases.org Home Page: http://www.rarediseases.org

Comments

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