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| Addison's Disease |
Addison's disease is an endocrine or hormonal disorder
characterized by weight loss, muscle weakness, fatigue, low
blood pressure, and sometimes darkening of the skin in both
exposed and non-exposed 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 underactive parathyroid glands, slow sexual
development. pernicious anemia, chronic candida infections,
chronic active hepatitis and 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 and
loss of pigment on areas of the skin.
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 and 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 and 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 and weight loss.
About 50 percent of the time, one will notice nausea,vomiting
and 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 and loss of
consciousness
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.
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.
Treatment
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.
Content Source NIDDK.NIH
characterized by weight loss, muscle weakness, fatigue, low
blood pressure, and sometimes darkening of the skin in both
exposed and non-exposed 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 underactive parathyroid glands, slow sexual
development. pernicious anemia, chronic candida infections,
chronic active hepatitis and 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 and
loss of pigment on areas of the skin.
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 and 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 and 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 and weight loss.
About 50 percent of the time, one will notice nausea,vomiting
and 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 and loss of
consciousness
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.
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.
Treatment
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.
Content Source NIDDK.NIH
| MEDICAL NOTES |