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TOPIC: Addison's Disease

Addison's Disease 27 Jan 2009 17:36 #697

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From: The National Endocrine and Metabolic Disease Information Services

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.

Cortisol

Cortisol is normally produced by the adrenal glands, located just above the kidneys. It belongs to a class of hormones called glucocorticoids, which affect almost every organ and tissue in the body. Scientists think that cortisol has possibly hundreds of effects in the body. Cortisol's most important job is to help the body respond to stress. Among its other vital tasks, cortisol
  • helps maintain blood pressure and cardiovascular function
  • helps slow the immune system's inflammatory response
  • helps balance the effects of insulin in breaking down sugar for energy
  • helps regulate the metabolism of proteins, carbohydrates, and fats
  • helps 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.

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.

Causes


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
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  • 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
Symptoms


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.

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.

http://www.endocrine.niddk.nih.gov/pubs/addison/addison.htm

 
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