Cushing's Syndrome

Definition
Cushing's syndrome is a condition that occurs when the body is exposed to high levels
of the hormone cortisol for a long time. The most common cause of Cushing's
syndrome, sometimes called hypercortisolism, is the use of oral corticosteroid
medication. The condition can also occur when the body makes too much cortisol.

Too much cortisol can produce some of the hallmark signs of Cushing's syndrome —
a fatty hump between the shoulders, a rounded face, and pink or purple stretch marks
on the skin. Cushing's syndrome can also result in high blood pressure, bone loss and,
on occasion, diabetes.

Treatments for Cushing's syndrome can return the body's cortisol production to
normal and noticeably improve the symptoms. The earlier treatment begins, the better
the chances for recovery.

Symptoms

Cushing's syndrome

Common Cushing's syndrome symptoms include:

 Weight gain, particularly around your midsection and upper back

  Fatigue
 Muscle weakness
 Rounding of your face (moon face)
 Facial flushing
 Fatty pad or hump between your shoulders (buffalo hump)
 Pink or purple stretch marks (striae) on the skin of your abdomen, thighs, breasts and arms
 Thin and fragile skin that bruises easily
 Slow healing of cuts, insect bites and infections
 Depression, anxiety and irritability
 Loss of emotional control
 Thicker or more visible body and facial hair (hirsutism)
 Acne
 Irregular or absent menstrual periods in females
 Decreased libido
 Erectile dysfunction in males
 New or worsened high blood pressure
 Glucose intolerance that may lead to diabetes
 Headache
 Bone loss, leading to fractures over time

When to see a doctor

If you're taking corticosteroid medications to treat a condition, such as asthma,
arthritis or inflammatory bowel disease, and experience signs and symptoms that may
indicate Cushing's syndrome, see your doctor for an evaluation. Even if you're not
using these drugs and you have symptoms that suggest the possible presence of
Cushing's syndrome, contact your doctor.

Causes

Adrenal glands
 Endocrine system

Your endocrine system consists of glands that produce hormones, which regulate
processes throughout your body. These glands include the adrenal glands, pituitary
gland, thyroid gland, parathyroid glands, pancreas, ovaries (in females) and testicles
(in men).

Your adrenal glands produce a number of hormones, including cortisol. Cortisol plays
a variety of roles in your body. For example, cortisol helps regulate your blood
pressure and keeps your cardiovascular system functioning normally. It also helps
your body respond to stress and regulates the way you convert (metabolize) proteins,
carbohydrates and fats in your diet into usable energy. However, when the level of
cortisol is too high in your body, you may develop Cushing's syndrome.

The role of corticosteroids

Cushing's syndrome can develop from a cause that originates outside of your body
(exogenous Cushing's syndrome). Taking corticosteroid medications in high doses
over an extended period of time may result in Cushing's syndrome. These
medications, such as prednisone, dexamethasone (Decadron) and methylprednisolone
(Medrol), have the same effects as does the cortisol produced by your body.

Your doctor may prescribe corticosteroids to treat inflammatory diseases, such as

rheumatoid arthritis, lupus and asthma, or to prevent your body from rejecting a
transplanted organ. Because the doses required to treat these conditions are often
higher than the amount of cortisol your body normally needs each day, the effects of
excess cortisol can occur.

People can also develop Cushing's from injectable corticosteroids — for example,
repeated injections for joint pain, bursitis and back pain. While certain inhaled steroid
medicines (taken for asthma) and steroid skin creams (for skin disorders such as
eczema) are in the same general category of drugs, they're generally not implicated in
Cushing's syndrome unless taken in very high doses.

Your body's own overproduction

The condition may also be due to your body's own overproduction of cortisol
(endogenous Cushing's syndrome). This may occur from excess production by one or
both adrenal glands, or overproduction of the adrenocorticotropic hormone (ACTH),
which normally regulates cortisol production. In these cases, Cushing's syndrome may
be related to:

 A pituitary gland tumor. A noncancerous (benign) tumor of the pituitary gland, located at
the base of the brain, secretes an excess amount of ACTH, which in turn stimulates the
adrenal glands to make more cortisol. When this form of the syndrome develops, it's called
Cushing's disease. It occurs much more often in women and is the most common form of
endogenous Cushing's syndrome.
 An ectopic ACTH-secreting tumor. Rarely, when a tumor develops in an organ that normally
does not produce ACTH, the tumor will begin to secrete this hormone in excess, resulting in
Cushing's syndrome. These tumors, which can be noncancerous (benign) or cancerous
(malignant), are usually found in the lung, pancreas, thyroid or thymus gland.
 A primary adrenal gland disease. In some people, the cause of Cushing's syndrome is excess
cortisol secretion that doesn't depend on stimulation from ACTH and is associated with
disorders of the adrenal glands. The most common of these disorders is a noncancerous
tumor of the adrenal cortex, called an adrenal adenoma. Cancerous tumors of the adrenal
cortex are rare, but they can cause Cushing's syndrome as well. Occasionally, benign,
nodular enlargement of both adrenal glands can result in Cushing's syndrome.

Complications
If you don't receive prompt treatment for Cushing's syndrome, other complications
may occur, such as:

 Bone loss (osteoporosis), due to the damaging effects of excess cortisol

 High blood pressure (hypertension)
 Kidney stones
 Diabetes
 Frequent or unusual infections
 Loss of muscle mass and strength

When the cause of Cushing's syndrome is a pituitary tumor (Cushing's disease), it can
sometimes lead to other problems, such as interfering with the production of other
hormones that the pituitary controls.

Preparing for your appointment

You're likely to start by first seeing your family doctor or a general practitioner.
However, in some cases when you call to set up an appointment, you may be referred
immediately to a doctor who specializes in endocrine disorders (endocrinologist).

It's a good idea to prepare for your appointment so that you can make the most of your
time with your doctor. Here's some information to help you get ready, and what to
expect from your doctor.

What you can do

 Be aware of any pre-appointment restrictions. At the time you make the

appointment, be sure to ask if there's anything you need to do in advance to
prepare for diagnostic tests.
 Write down any symptoms you're experiencing, including any that may
seem unrelated to the reason for which you scheduled the appointment. For
example, if you've had headaches more frequently or if you've been feeling
down or more tired than usual, this is important information to share with your
doctor. Also tell your doctor about changes in your physical appearance, such
as weight gain, new acne or increased body hair.
 Write down key personal information, including any changes in your
personal relationships and in your sex life. Let your doctor know if the people
closest to you have noticed that you seem irritable or that you seem to have
more mood swings than in the past.
 Make a list of all medications, as well as any vitamins, creams or
supplements, that you are currently taking or have used in the past. Include on
your list the specific name, dose and dates of any steroid medications you've
taken in the past, such as cortisone injections.
 Take a family member or friend along, if possible. Sometimes it can be
difficult to soak up all the information provided to you during an appointment.
Someone who accompanies you may remember something that you missed or
forgot.
 Write down questions to ask your doctor.

Your time with your doctor is limited, so preparing a list of questions will help you
make the most of your time together. List your questions from most important to least
important in case time runs out. For Cushing's syndrome, some basic questions to ask
your doctor include:

 What is likely causing my symptoms or condition?

 Are there other possible causes for my symptoms or condition?
 What kinds of diagnostic tests do I need? How are these tests performed?
 What are my treatment options?
 How noticeably will my physical signs and symptoms improve with
treatment? Will I see a difference in my appearance as well as in the way I
feel?
 Will treatment help make me feel more emotionally stable?
 What long-term impact could each treatment option have? Will there be an
impact on my ability to have children?
 How will you follow my response to treatment over time?
 Are there any alternatives to the primary approach that you're suggesting?
  I have these other health conditions. How can I best manage them together?
 Are there any restrictions that I need to follow?
 Should I see a specialist? What will that cost, and will my insurance cover
seeing a specialist?
 Is there a generic alternative to the medicine you're prescribing me?
 Are there any brochures or other printed material that I can take home with
me? What Web sites do you recommend visiting?

In addition to the questions that you've prepared to ask your doctor, don't hesitate to
ask questions during your appointment at any time that you don't understand
something.

What to expect from your doctor

Your doctor is likely to ask you a number of questions. Being ready to answer them
may reserve time to go over any points you want to spend more time on. Your doctor
may ask:

 When did you first begin experiencing symptoms?

 Have your symptoms been continuous, or occasional? Have they gotten worse
over time?
 Have you noticed any changes in your sexual performance or your interest in
sex?
 For women, has your menstrual cycle changed, or have you stopped having
your period?
 Have you gained weight? On what part of your body?
 Have your emotions become more unpredictable?
 Have you noticed that you bruise more easily, or that wounds and infections
take longer to heal than in the past?
 Do you feel more physically weak than in the past?
 Have you developed new acne or more body or facial hair?
 Have you been taking a corticosteroid medication? For how long?
 What, if anything, seems either to improve or worsen your symptoms?

Diagnosing Cushing's syndrome can be a long and extensive process. You may not
have any firm answers about your condition until you've had a series of medical
appointments.

Tests and diagnosis

Cushing's syndrome can be difficult to diagnose, particularly endogenous Cushing's,
because other conditions share the same signs and symptoms.

Your doctor will conduct a physical exam, looking for signs of Cushing's syndrome.
He or she may suspect Cushing's syndrome if you have signs such as rounding of the
face (moon face), a pad of fatty tissue at the shoulders and neck (buffalo hump), and
thin skin with bruises and stretch marks.

If you've been taking a corticosteroid medication long term, your doctor may suspect
that you've developed Cushing's syndrome as a result of this medication. If you
haven't been using a corticosteroid medication, these diagnostic tests may help
pinpoint the cause:

 Urine and blood tests. These tests measure hormone levels in your urine and
blood and show whether your body is producing excessive cortisol. For the
urine test, you may be asked to collect a sample of your urine over a 24-hour
period. Both the urine and blood samples will be sent to a laboratory to be
analyzed for cortisol levels.

Your doctor might also recommend other specialized tests that evaluate the
blood and urine to help determine if Cushing's syndrome is present and to help
identify the underlying source of any excess production. These tests often
involve measuring cortisol levels before and after stimulation or suppression
with other hormone medications.

 Saliva test. Cortisol levels normally rise and fall throughout the day. In people
without Cushing's syndrome, levels of cortisol drop significantly overnight.
By analyzing cortisol levels from a small sample of saliva collected late at
night, doctors can see if cortisol levels are too high, indicating a diagnosis of
Cushing's.
 Imaging tests. Computerized tomography (CT) scans or magnetic resonance
imaging (MRI) scans can provide images of your pituitary and adrenal glands
to locate abnormalities, such as tumors.

As these tests help your doctor diagnose Cushing's syndrome, they may also rule out
medical conditions with similar signs and symptoms. For example, polycystic ovary
syndrome — a hormone disorder in women with enlarged ovaries — shares some of
the same signs and symptoms as Cushing's has, such as excessive hair growth and
irregular menstrual periods. Depression, eating disorders and alcoholism also can
partially mimic Cushing's syndrome.

Treatments and drugs

Treatments for Cushing's syndrome are designed to lower the high level of cortisol in
your body. The best treatment for you depends on the cause of the syndrome.
Treatment options include:

 Reducing corticosteroid use. If the cause of Cushing's syndrome is long-term

use of corticosteroid medications, your doctor may be able to keep your
Cushing's signs and symptoms under control by reducing the dosage of the
drug over a period of time, while still adequately managing your asthma,
arthritis or other condition. For many of these medical problems, your doctor
can prescribe noncorticosteroid drugs, which will allow him or her to reduce
the dosage or eliminate the use of corticosteroids altogether.

Don't reduce the dose of corticosteroid drugs or stop taking them on your own.
Do so only under your doctor's supervision. Abruptly discontinuing these
medications could lead to deficient cortisol levels. Slowly tapering off
corticosteroid drugs allows your body to resume normal cortisol production.
  Surgery. If the cause of Cushing's syndrome is a tumor, your doctor may
recommend complete surgical removal. Pituitary tumors are typically removed
by a neurosurgeon, who may perform the procedure through your nose. If a
tumor is present in the adrenal glands, lung or pancreas, the surgeon can
remove it through a standard operation or in some cases by using minimally
invasive surgical techniques, with smaller incisions.

After the operation, you'll need to take cortisol replacement medications to

provide your body with the correct amount of cortisol. In most cases, you'll
eventually experience a return of normal adrenal hormone production, and
your doctor can taper off the replacement drugs. However, this process can
take up to a year or longer. In some instances, people with Cushing's
syndrome never experience a resumption of normal adrenal function; they then
need lifelong replacement therapy.

 Radiation therapy. If the surgeon can't totally remove the pituitary tumor, he
or she will usually prescribe radiation therapy to be used in conjunction with
the operation. Additionally, radiation may be used for people who aren't
suitable candidates for surgery. Radiation can be given in small doses over a
six-week period, or by a technique called stereotactic radiosurgery or gamma-
knife radiation. In the latter procedure, administered as a single treatment, a
large dose of radiation is delivered to the tumor, and the radiation exposure to
surrounding tissues is minimized.
 Medications. In some situations, when surgery and radiation don't produce a
normalization of cortisol production, your doctor may advise drug therapy.
Medications to control excessive production of cortisol include ketoconazole
(Nizoral), mitotane (Lysodren) and metyrapone (Metopirone). Drugs also are
sometimes prescribed before surgery for people who are very sick. Doing so
may improve their signs and symptoms and minimize their surgical risk.

In some cases, the tumor or its treatment will cause other hormones produced
by the pituitary or adrenal gland to become deficient and your doctor will
recommend hormone replacement medications.

If none of these treatment options is effective, your doctor may recommend surgical
removal of your adrenal glands (bilateral adrenalectomy). This procedure will cure
excess production of cortisol. However, your ACTH levels will remain high, possibly
causing excess pigmentation of your skin.

Left untreated, Cushing's syndrome can lead to death. However, most often,
treatments improve signs and symptoms and normalize cortisol levels.