Addison's DiseaseAdrenal Insufficiency and Adrenal Crisis

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

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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. Thehypothalamus produces corticotropin-releasing hormone, triggering the pituitary gland to secrete corticotropin, which regulates the productionof 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, PDFmyURL.com

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 donot produce enough of the hormone cortisol and, in some cases, the hormone aldosterone. Aldosterone belongs to a class of hormones calledmineralocorticoids, also produced by the adrenal glands. It helps maintain blood pressure and water and salt balance in the body by helping thekidney retain sodium and excrete potassium. When aldosterone production falls too low, the kidneys are not able to regulate salt and waterbalance, 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, muscleweakness, 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 becomeunable 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 shockmay 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 primaryadrenal 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 thanprimary adrenal insufficiency and can be traced to a lack of ACTH due to many causes. Without ACTH to stimulate the adrenals, the adrenalglands' 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 ACTHby 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 bycontrolling 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 patientsand 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 cantake 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 thepituitary 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 orinfections; 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, aredeficient.

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 asPrednisone 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 bothcorticotropin-releasing hormone (CRH) and ACTH. Normally, CRH instructs the pituitary gland to release ACTH. If CRH levels drop, thepituitary 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 adrenalinsufficiency usually begin gradually.

In either case the characteristics of AI are:

chronic, worsening fatiguemuscle weaknessloss of appetiteweight lossheadacheslow, sluggish, lethargic movementdehydrationhigh feverchills, shakingconfusion or comarapid heart ratejoint painabdominal painunintentional weight lossrapid respiratory rateunusual and excessive sweating on face and/or palmspossible skin rash or lesionflank painirritability and depressiona craving for salty foods due to salt lossHypoglycemia, or low blood glucose, is more severe in children than in adults

About 50 percent of the time, one will notice:

nauseavomitingdiarrhea

Other symptoms may include:

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low blood pressure that falls further when standing, causing dizziness or faintingskin changes in Addison's disease, with areas of hyperpigmentation, or dark tanning, covering exposed and nonexposed parts of thebody.

This darkening of the skin is most visible on scars; skin folds; pressure points such as the elbows, knees, knuckles, and toes; lips; andmucous membranes.menstrual periods may become irregular or stop

Adrenal Crisis / Addison Crisis

Because the symptoms progress slowly, they are usually ignored until astressful 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 medicaltreatment before a crisis occurs.

In about 25 percent of patients, symptoms first appear during an AdrenalCrisis.

Symptoms of an Adrenal Crisis include:

sudden penetrating pain in the lower back, abdomen, or legssevere vomiting and diarrheadehydrationlow blood pressureloss 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 theMedic 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 relativecontact 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 withAddison's disease, or as the first sign of adrenal insufficiency. More uncommonly, it may be caused by a pituitary gland disorder. It may alsobe caused by sudden withdrawal of corticosteroids, removal or injury of the adrenal glands, or destruction of the pituitary gland. Risk factorsare 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 itto occur suddenly and unexpectedly). Most people with Addison's disease are taught to give themselves an emergency injection ofhydrocortisone 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 cardshould alert emergency personnel about the need to inject 100 mg of cortisol if its bearer is found severely injured or unable to answerquestions.

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 mayneed 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 addisoniancrisis. 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 ofcompanies 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 yourdoctor 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 therapyinvolves 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. Ifaldosterone 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 replacedorally with hydrocortisone tablets, a synthetic glucocorticoid, taken once or twice a day. If aldosterone is also deficient, it is replaced withoral doses of a mineralocorticoid called fludrocortisone acetate (Florinef), which is taken once a day. Patients receiving aldosteronereplacement therapy are usually advised by a doctor to increase their salt intake. Because patients with secondary adrenal insufficiencynormally maintain aldosterone production, they do not require aldosterone replacement therapy. The doses of each of these medications areadjusted 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 adrenalcortex 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 antibodiesthat 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 adrenalinsufficiency 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 otherparts 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 areinsufficient 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 thistest, blood cortisol, urine cortisol, or both are measured before and after a synthetic form of ACTH is given by injection. In the so-called 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 adrenalinsufficiency 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 determinethe 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 ACTHresponse 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 glucocorticoidhormones immediately. Although a reliable diagnosis is not possible while the patient is being treated for the crisis, measurement ofblood ACTH and cortisol during the crisis and before glucocorticoids are given is enough to make the diagnosis. Once the crisis iscontrolled 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 cortisoldecreased serum sodiumelevated serum potassium

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This disease may also alter the results of the following tests:sodium, urine17-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 anysigns 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 ofthe 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:

shockcomaseizures

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 hydrocortisoneand 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 inearly 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 bymouth 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 Addisoniansto survive major surgery. There was substantial secrecy surrounding his health during his years as president, and the 25th amendment tothe U.S. constitution was introduced at least in part as a result of this secrecy.Helen Reddy, Popular singerEugene 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 thekey symptoms, such as "low blood pressure, weight loss, muscle fatigue, stomach irritability, sharp back pains, dehydration, and anabnormal 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 PDFmyURL.com

Cortisol, a hormone produced by the adrenal glands, also belongs to a class of hormones called glucocorticoids. These hormones affectalmost 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 maintain blood pressure and cardiovascular functionhelps slow the immune system's inflammatory responsehelps balance the effects of insulin in breaking down sugar for energyhelps regulate the metabolism of proteins, carbohydrates, and fatshelps 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 pituitarygland, a bean-sized organ at the base of the brain.

First, the hypothalamus sends "releasing hormones" to the pituitary gland. The pituitary responds bysecreting hormones that regulate growth and thyroid and adrenal function, and sex hormones suchas estrogen and testosterone.

One of the pituitary's main functions is to secrete ACTH (adrenocorticotropin), a hormone thatstimulates the adrenal glands.

When the adrenals receive the pituitary's signal in the form of ACTH, they respond by producingcortisol. 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 andcontact info for support groups.

Addison's forum

Addison HelpAddison News

E-mail: Joan Hoffman

Adrenal Clinical TrialsAdrenal Crisis / Insufficiency

Adrenal HyperplasiaAustralian Addison's Disease NewsDutch/International Addison's and Cushing SocietyNew Zealand Addison's Network

Organizations

National Adrenal Diseases Foundation505 Northern BoulevardGreat Neck, NY 11021Telephone: (516) 487-4992e-mail: nadf@aol.comHome Page: www.NADF.US

NIH/National Digestive Diseases Information Clearinghouse2 Information WayBethesda, MD 20892--3570Telephone: (301) 654-3810

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Toll free: (800) 891-5389

NIH/National Institute of Child Health and Human Development9000 Rockville PikeBuilding 31, Room 2A32MSC2425Bethesda, MD 20892Telephone: (301) 496-5133Home Page: http://www.nichd.nih.gov/

National Organization for Rare Disorders, Inc. (NORD)P.O. Box 8923New Fairfield, CT 06812-8923Telephone: (203) 746-6518Fax: (203) 746-6481Toll free: (800) 999-6673TDD: (203) 746-6927e-mail: orphan@rarediseases.orgHome Page: http://www.rarediseases.org

Comments

Interesting article.

Great art icle. Easy to read with broad considerations, and the endocrine system is fascinating. Regards, -JB

Jack Byrom - Jan 30, 2011

Thanks!

This helped me with my post on my blog - http://nursingninjas.com/nursingschoolblog. Thanks! Freedom ofInformation sure is liberating!

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