CUSHING'S
SYNDROME
Cushing's syndrome is a
hormonal disorder caused by prolonged exposure of the body's
tissues to high levels of the hormone cortisol. Sometimes called
"hypercortisolism," it is relatively rare and most commonly
affects adults aged 20 to 50. An estimated 10 to15 of every
million people are affected each year.
What are the
Symptoms?
Symptoms vary, but most
people have upper body obesity, rounded face, increased fat
around the neck, and thinning arms and legs. Children tend to be
obese with slowed growth rates. Other symptoms appear in the
skin, which becomes fragile and thin. It bruises easily and
heals poorly. Purplish pink stretch marks may appear on the
abdomen, thighs, buttocks, arms and breasts. The bones are
weakened, and routine activities such as bending, lifting or
rising from a chair may lead to backaches, rib and spinal column
fractures. Most people have severe fatigue, weak muscles, high
blood pressure and high blood sugar. Irritability, anxiety and
depression are common. Women usually have excess hair growth on
their faces, necks, chests, abdomens, and thighs. Their
menstrual periods may become irregular or stop. Men have
decreased fertility with diminished or absent desire for sex. If
Cushing’ syndrome is not treated, patients face a shortened
lifespan.
What Causes
Cushing's Syndrome?
Cushing's syndrome
occurs when the body's tissues are exposed to excessive levels
of cortisol for long periods of time. Many people suffer the
symptoms of Cushing's syndrome because they take glucocorticoid
hormones such as prednisone for asthma, rheumatoid arthritis,
lupus or other inflammatory diseases. Others develop Cushing's
syndrome because of overproduction of cortisol by the body.
Normally, the production of cortisol follows a precise chain of
events. First, the hypothalamus, a part of the brain which is
about the size of a small sugar cube, sends corticotropin
releasing hormone (CRH) to the pituitary gland. CRH causes the
pituitary to secrete ACTH (adrenocorticotropin), a hormone that
stimulates the adrenal glands. When the adrenals, which are
located just above the kidneys, receive the ACTH, they respond
by releasing cortisol into the bloodstream. Cortisol performs
vital tasks in the body. It helps maintain blood pressure and
cardiovascular function, reduces the immune system's
inflammatory response, balances the effects of insulin in
breaking down sugar for energy, and regulates the metabolism of
proteins, carbohydrates, and fats. One of cortisol's most
important jobs is to help the body respond to stress. For this
reason, women in their last 3 months of pregnancy and highly
trained athletes normally have high levels of the hormone.
People suffering from depression, alcoholism, malnutrition and
panic disorders also have increased cortisol levels.
When the amount of
cortisol in the blood is adequate, the hypothalamus and
pituitary release less CRH and ACTH. This ensures that the
amount of cortisol released by the adrenal glands is precisely
balanced to meet the body's daily needs. However, if something
goes wrong with the adrenals or their regulating switches in the
pituitary gland or the hypothalamus, cortisol production can go
awry.
Pituitary Adenomas
Pituitary adenomas cause
most cases of Cushing's syndrome. They are benign, or
non-cancerous, tumors of the pituitary gland which secrete
increased amounts of ACTH. Most patients have a single adenoma.
This form of the syndrome, known as "Cushing's disease," affects
women five times more frequently than men.
Ectopic ACTH Syndrome
Some benign or malignant
(cancerous) tumors that arise outside the pituitary can produce
ACTH. This condition is known as ectopic ACTH syndrome. Lung
tumors cause over 50 percent of these cases. Men are affected 3
times more frequently than women. The most common forms of
ACTH-producing tumors are oat cell, or small cell lung cancer,
which accounts for about 25 percent of all lung cancer cases,
and carcinoid tumors. Other less common types of tumors that can
produce ACTH are thymomas, pancreatic islet cell tumors, and
medullary carcinomas of the thyroid.
Adrenal Tumors
Sometimes, an
abnormality of the adrenal glands, most often an adrenal tumor,
causes Cushing's syndrome. The average age of onset is about 40
years. Most of these cases involve non-cancerous tumors of
adrenal tissue, called adrenal adenomas, which release excess
cortisol into the blood.
Adrenocortical
carcinomas, or adrenal cancers, are the least common cause of
Cushing's syndrome. Cancer cells secrete excess levels of
several adrenal cortical hormones, including cortisol and
adrenal androgens. Adrenocortical carcinomas usually cause very
high hormone levels and rapid development of symptoms.
How Is
Cushing's Syndrome Diagnosed?
Diagnosis is based on a
review of the patient's medical history, physical examination
and laboratory tests. Often CT or MRI
exams of the adrenal or pituitary glands are useful for locating
tumors. These tests help to determine if excess levels of
cortisol are present and why. Lab tests include both
blood and urine tests.
How Is
Cushing's Syndrome Treated?
Treatment depends on the
specific reason for cortisol excess and may include surgery,
radiation, chemotherapy or the use of cortisol-inhibiting drugs.
If the cause is long-term use of glucocorticoid hormones to
treat another disorder, the doctor will gradually reduce the
dosage to the lowest dose adequate for control of that disorder.
Once control is established, the daily dose of glucocorticoid
hormones may be doubled and given on alternate days to lessen
side effects.
Pituitary Adenomas
Several therapies are
available to treat the ACTH-secreting pituitary adenomas of
Cushing's disease. The most widely used treatment is surgical
removal of the tumor, known as transsphenoidal adenomectomy.
Using a special microscope and very fine instruments, the
surgeon approaches the pituitary gland through a nostril or an
opening made below the upper lip. Because this is an extremely
delicate procedure, patients are often referred to centers
specializing in this type of surgery. The success, or cure, rate
of this procedure is over 80 percent when performed by a surgeon
with extensive experience. If surgery fails, or only produces a
temporary cure, surgery can be repeated, often with good
results. After curative pituitary surgery, the production of
ACTH drops two levels below normal. This is a natural, but
temporary, drop in ACTH production, and patients are given a
synthetic form of cortisol (such as hydrocortisone or
prednisolone). Most patients can stop this replacement therapy
in less than a year.
For patients in whom
transsphenoidal surgery has failed or who are not suitable
candidates for surgery, radiotherapy is another possible
treatment. Radiation to the pituitary gland is given over a
6-week period, with improvement occurring in 40 to 50 percent of
adults and up to 80 percent of children. It may take several
months or years before patients feel better from radiation
treatment alone. Drugs used alone or
in combination to control the production of excess cortisol are
mitotane, aminoglutethimide,
metyrapone, trilostane and ketoconazole. Each has its own side
effects that doctors consider when prescribing therapy for
individual patients.
Ectopic ACTH Syndrome
To cure the
overproduction of cortisol caused by ectopic ACTH syndrome, it
is necessary to eliminate all of the cancerous tissue that is
secreting ACTH. The choice of cancer treatment - surgery,
radiotherapy, chemotherapy, immunotherapy, or a combination of
these treatments - depends on the type of cancer and how far it
has spread. Since ACTH-secreting tumors (for example, small cell
lung cancer) may be very small or widespread at the time of
diagnosis, cortisol-inhibiting drugs, like mitotane, are an
important part of treatment. In some cases, if pituitary surgery
is not successful, surgical removal of the adrenal glands
(bilateral adrenalectomy) may take the place of drug therapy.
Adrenal Tumors
Surgery is the mainstay
of treatment for benign as well as cancerous tumors of the
adrenal glands. |