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.
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
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:
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.
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.
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.
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.
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.
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.
Surgery
Patients with chronic adrenal insufficiency who need 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
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 and the usual maintenance
doses of hydrocortisone and fludrocortisone acetate by mouth are reached by
about 10 days after childbirth.
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. 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.
The following materials can be found in medical libraries, many college and
university libraries, and through interlibrary loan in most public libraries.
Stewart PM. The adrenal cortex. In: Larsen P, ed. Williams Textbook of
Endocrinology. 10th ed. Philadelphia: Saunders; 2003: 491–551.
Chrousos GP. Glucocorticoid therapy. In: Felig P, Frohman L, eds. Endocrinology
and Metabolism. 4th ed. New York: McGraw-Hill; 2001: 609–632.
Miller W, Chrousos GP. The adrenal cortex. In: Felig P, Frohman L, eds. Endocrinology
and Metabolism. 4th ed. New York: McGraw-Hill; 2001: 387–524.
Ten S, New M, Maclaren N. Clinical Review 130: Addison's disease 2001. Journal
of Clinical Endocrinology & Metabolism. 2001;86(7):2909–2922.
Williams GH, Dluhy, RC. Disorders of the adrenal cortex. In: Braunwald E, ed.
Harrison's Principles of Internal Medicine. 15th ed. New York:
McGraw-Hill Professional; 2001: 2084–2105.
American Autoimmune Related Diseases Association
National Office
22100 Gratiot Avenue
East Detroit, MI 48021
Phone: 586.776.3900
Email: aarda@aarda.org
National Adrenal Disease Foundation
505 Northern Boulevard, Suite 200
Great Neck, NY 11021
Phone: 516.487.4992
Source: National Institutes of Health; National Institute of
Diabetes and Digestive and Kidney Diseases (NIH Publication No. 04–3054)
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This information is provided by the Cleveland Clinic and is not intended to replace the medical advice of your doctor or health care provider. Please consult your health care provider for advice about a specific medical condition. This document was last reviewed on: 6/1/2004...#5484
