Addison's disease (patient information)

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 * Associate Editors-In-Chief: Priyamvada Singh, MBBS [mailto:psingh@perfuse.org]; AssistantEditor-In-Chief: Meagan E. Doherty, B.S.

Overview
Addison's disease is an endocrine or hormonal disorder that occurs in all age groups and afflicts men and women equally. The disease is characterized by weight loss, muscle weakness, fatigue, low blood pressure, and sometimes darkening of the skin in both exposed and nonexposed parts of the body. Addison's disease occurs when the adrenal glands do not produce enough of the hormone cortisol and, in some cases, the hormone aldosterone. The disease is also called adrenal insufficiency, or hypocortisolism.

What are the symptoms of Addison's disease?
'''The symptoms of adrenal insufficiency usually begin gradually. Characteristics of the disease are:'''
 * chronic, worsening fatigue
 * muscle weakness
 * loss of appetite
 * weight loss

About 50 percent of the time, one will notice:
 * nausea
 * vomiting
 * diarrhea

Other symptoms include:
 * 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

Addison's disease can cause irritability and depression. Because of salt loss, a craving for salty foods also is common. Hypoglycemia, or low blood glucose, is more severe in children than in adults. In women, menstrual periods may become irregular or stop. 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 addisonian crisis, or acute adrenal insufficiency. In most cases, symptoms are severe enough that patients seek medical treatment before a crisis occurs. However, in about 25 percent of patients, symptoms first appear during an addisonian crisis.

Symptoms of an addisonian crisis include:
 * sudden penetrating pain in the lower back, abdomen, or legs
 * severe vomiting and diarrhea
 * dehydration
 * low blood pressure
 * loss of consciousness

Left untreated, an addisonian crisis can be fatal.

What causes Addison's disease?
Failure to produce adequate levels of cortisol can occur for different reasons. 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).

Primary Adrenal Insufficiency
Addison's disease affects about 1 in 100,000 people. Most cases are caused by the gradual destruction of the adrenal cortex, the outer layer of the adrenal glands, by the body's own immune system. 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. Adrenal insufficiency occurs when at least 90 percent of the adrenal cortex has been destroyed. As a result, often both glucocorticoid (cortisol) and mineralocorticoid (aldostertone) hormones are lacking. Sometimes only the adrenal gland is affected, as in idiopathic adrenal insufficiency; sometimes other glands also are affected, as in the polyendocrine deficiency syndrome.

Polyendocrine Deficiency Syndrome
The polyendocrine deficiency syndrome is classified into two separate forms, referred to as type I and type II. Type I occurs in children, and adrenal insufficiency may be accompanied by
 * underactive parathyroid glands
 * slow sexual development
 * pernicious anemia
 * chronic candida infections
 * chronic active hepatitis
 * hair loss (in very rare cases)

'''Type II, often called Schmidt's syndrome, usually afflicts young adults. Features of type II may include'''
 * an underactive thyroid gland
 * slow sexual development
 * diabetes
 * vitiligo
 * loss of pigment on areas of the skin

Scientists think that the polyendocrine deficiency syndrome is inherited because frequently more than one family member tends to have one or more endocrine deficiencies.

Tuberculosis
Tuberculosis (TB), an infection which can destroy the adrenal glands, accounts for about 20 percent of cases of primary adrenal insufficiency in developed countries. When adrenal insufficiency was first identified by Dr. Thomas Addison in 1849, TB was found at autopsy in 70 to 90 percent of cases. As the treatment for TB improved, however, the incidence of adrenal insufficiency due to TB of the adrenal glands has greatly decreased.

Other Causes
Less common causes of primary adrenal insufficiency are
 * chronic infection, mainly fungal infections
 * cancer cells spreading from other parts of the body to the adrenal glands
 * amyloidosis
 * surgical removal of the adrenal glands

Secondary Adrenal Insufficiency
This form of adrenal insufficiency is much more common than primary adrenal insufficiency and can be traced to a lack of ACTH. Without ACTH to stimulate the adrenals, the adrenal glands' production of cortisol drops, but not aldosterone. 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, asthma, or ulcerative colitis, 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. 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 replacement hormone must be taken until normal ACTH and cortisol production resumes. Less commonly, adrenal insufficiency occurs when the pituitary gland either decreases in size or stops producing ACTH. These events can result from
 * tumors or infections of the area
 * loss of blood flow to the pituitary
 * radiation for the treatment of pituitary tumors
 * surgical removal of parts of the hypothalamus
 * surgical removal of the pituitary gland

Diagnosis
In its early stages, 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.

ACTH Stimulation Test
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 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 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.

When to seek urgent medical care?
It is important to seek medical care if you show signs of any of the symptoms associated with Addison's disease. This is especially important if you experience any of the symptoms of addisonian crisis, as this can be fatal if not treated immediately.

Treatment options
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. During an addisonian 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.

Diseases with similar symptoms

 * diarrhea
 * gastrointestinal disease/illness
 * hepatitis
 * cancer

Where to find medical care for Addison's disease?
Directions to Hospitals Treating Addison's Disease

What to expect (Outlook/Prognosis)?
If you don't treat Addison's disease, it can be fatal. You will need to take hormone pills for the rest of your life. If you have Addison's disease, you should carry an emergency ID. It should say that you have the disease, list your medicines and say how much you need in an emergency.

As long as the proper dose of replacement medication is taken every day, an Addisonian can have a normal crisis-free life. There are no specific physical or occupational restrictions. Routine care includes regular physician visits, avoidance of dehydration, and the use of extra medication during illness. Pregnancy is possible, but will require extra monitoring of the replacement medication. Every Addisonian should wear an identification bracelet or preferably a necklace stating that he or she has the disease, to insure proper emergency treatment. An identification card outlining treatment is also suggested.