Cushing's syndrome
Introduction
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 to 15 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.
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 and other inflammatory diseases, or for
immunosuppression after transplantation.
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.
Familial Cushing's Syndrome
Most cases of Cushing's syndrome are not
inherited. Rarely, however, some individuals
have special causes of Cushing's syndrome due to
an inherited tendency to develop tumors of one
or more endocrine glands. In Primary Pigmented
Micronodular Adrenal Disease, children or young
adults develop small cortisol-producing tumors
of the adrenal glands. In Multiple Endocrine
Neoplasia Type I (MEN I), hormone secreting
tumors of the parathyroid glands, pancreas and
pituitary occur. Cushing's syndrome in MEN I may
be due to pituitary, ectopic or adrenal tumors.
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.
