Cushing's Syndrome

Cushing's syndrome is a condition that occurs when your body is exposed to high levels of the hormone cortisol for a prolonged period of time. Sometimes called hypercortisolism, Cushing's syndrome can occur when your adrenal glands, located above your kidneys, make too much cortisol. It may also develop if you're taking high doses of cortisol-like medications (corticosteroids) for a prolonged period.

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

The most common cause of Cushing's syndrome is the use of oral corticosteroid medication. By contrast, it's rare for the cause to be excess cortisol production by your body. The syndrome is named after Harvey Cushing, an American surgeon who first identified the condition in 1932.

Treatments for Cushing's syndrome are designed to return your body's cortisol production to normal. By normalizing or even markedly lowering cortisol levels, you'll experience noticeable improvements in your signs and symptoms. Left untreated, however, Cushing's syndrome can eventually lead to death.

Causes:
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.

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. 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.

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 five times as often in women as in men 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 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.

Symptoms:
Common signs and symptoms of Cushing's syndrome 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.
* Thicker or more visible body and facial hair (hirsutism).
* Acne.
* Irregular or absent menstrual periods in females.
* Erectile dysfunction in males.
* High blood pressure.

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. Your doctor may ask you about signs and symptoms such as fatigue, depression and weight change.

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 drug. 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.

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 between 11 p.m. and midnight, 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.

Treatment:
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.

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.

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.

Medical therapy- In some situations, when surgery and radiation don't produce a normalization of cortisol production, your doctor may advise medical therapy. Medications to control excessive production of cortisol include ketoconazole (Nizoral), mitotane (Lysodren) and metyrapone (Metopirone). Medical therapy is also sometimes used 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.

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