Cushing Syndrome

Cushing's syndrome Description: A disorder resulting from increased adrenocortical secretion of cortisol, due to any one of several sources: ACTH-dependent adrenocortical hyperplasia or tumor, ectopic ACTH-secreting tumor, or excessive administrations of steroids; characterized by trunkal obesity, moon face, acne, abdominal striae, hypertension, decreased carbohydrate tolerance, protein catabolism, psychiatric disturbances, and osteoporosis, amenorrhea, and hirsutism in females; when associated with an ACTH-producing adenoma, called Cushing disease. Syn: Cushing basophilism. Alternative Name: Hypercortisolism. Cushing's syndrome is a rare disorder that develops when the body is exposed to too much of the hormone cortisol. Cushing's syndrome is also known as hypercortisolism. Normally, cortisol levels increase through a chain reaction of hormones. The brain's hypothalamus produces corticotropin-releasing hormone (CRH), which stimulates the pituitary gland to make adrenocorticotropic hormone (ACTH). Then, ACTH stimulates the adrenal glands to produce cortisol. Cortisol affects almost every area of the body and is particularly important in regulating blood pressure and metabolism. But if your body makes too much cortisol-or if you take certain medicines that act like cortisol-you may develop one or more symptoms. Cushing's syndrome may cause weight gain, skin changes, and fatigue and lead to such serious conditions as diabetes, high blood pressure, depression, and osteoporosis. If untreated, Cushing's syndrome can cause death. Cushing's syndrome can affect anyone, but it is most frequently seen in adults between the ages of 20 to 50 and is more common in women than men. Rarely, a patient may have an inherited gene mutation, such as Multiple Endocrine Neoplasia Type 1 or MEN-1, that increases her risk of developing tumors throughout the endocrine system, including pituitary and adrenal tumors. Symptoms: Signs and symptoms of Cushing's syndrome vary, but most people with the disorder have upper body obesity, a rounded face, increased fat around the neck, and relatively slender arms and legs. Children tend to be obese with slowed growth rates. Other signs appear in the skin, which becomes fragile and thin, bruises easily, and heals poorly. Purple or 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 and rib or spinal column fractures. Women with Cushing's syndrome usually have excess hair growth on their face, neck, chest, abdomen, and thighs. Their menstrual periods may become irregular or stop. Men may have decreased fertility with diminished or absent desire for sex and, sometimes, erectile dysfunction. Other common signs and symptoms includeCushing's syndrome Severe fatigue.
  • Weak muscles.
  • High blood pressure.
  • High blood glucose.
  • Increased thirst and urination.
  • Irritability, anxiety, or depression.
  • A fatty hump between the shoulders.
Causes and Risk factors: Cushing's syndrome occurs when the body's tissues are exposed to high levels of cortisol for too long. Many people develop Cushing's syndrome because they take glucocorticoids—steroid hormones that are chemically similar to naturally produced cortisol—such as prednisone for asthma, rheumatoid arthritis, lupus, and other inflammatory diseases. Glucocorticoids are also used to suppress the immune system after transplantation to keep the body from rejecting the new organ or tissue. Other people develop Cushing's syndrome because their bodies produce too much cortisol. Normally, the production of cortisol follows a precise chain of events. First, the hypothalamus, a part of the brain about the size of a small sugar cube, sends corticotropin-releasing hormone (CRH) to the pituitary gland. CRH causes the pituitary to secrete adrenocorticotropin hormone (ACTH), which 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. 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, or 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 process ensures 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 the regulating switches in the pituitary gland or hypothalamus, cortisol production can go awry. Pituitary adenomas cause 70 percent of Cushing's syndrome cases, excluding those caused by glucocorticoid use. These benign, or noncancerous, tumors of the pituitary gland secrete extra ACTH. Most people with the disorder have a single adenoma. This form of the syndrome, known as Cushing's disease, affects women five times more often than men. In rare cases, an abnormality of the adrenal glands, most often an adrenal tumor, causes Cushing's syndrome. Adrenal tumors are four to five times more common in women than men, and the average age of onset is about 40. Most of these cases involve noncancerous tumors of adrenal tissue called adrenal adenomas, which release excess cortisol into the blood. Adrenocortical carcinomas—adrenal cancers—are the least common cause of Cushing's syndrome. With adrenocortical carcinomas, cancer cells secrete excess levels of several adrenocortical hormones, including cortisol and adrenal androgens, a type of male hormone. Adrenocortical carcinomas usually cause very high hormone levels and rapid development of symptoms. Most cases of Cushing's syndrome are not inherited. Rarely, however, Cushing's syndrome results from an inherited tendency to develop tumors of one or more endocrine glands. Endocrine glands release hormones into the bloodstream. With primary pigmented micronodular adrenal disease, children or young adults develop small cortisol-producing tumors of the adrenal glands. With multiple endocrine neoplasia type 1 (MEN1), hormone-secreting tumors of the parathyroid glands, pancreas, and pituitary develop; Cushing's syndrome in MEN1 may be due to pituitary, ectopic, or adrenal tumors. Diagnosis: Diagnosis is based on a review of a person's medical history, a physical examination, and laboratory tests. X rays of the adrenal or pituitary glands can be useful in locating tumors. 24-hour urinary free cortisol level: In this test, a person's urine is collected several times over a 24-hour period and tested for cortisol. Levels higher than 50 to 100 micrograms a day for an adult suggest Cushing's syndrome. The normal upper limit varies in different laboratories, depending on which measurement technique is used. Midnight plasma cortisol and late-night salivary cortisol measurements: The midnight plasma cortisol test measures cortisol concentrations in the blood. Cortisol production is normally suppressed at night, but in Cushing's syndrome, this suppression doesn't occur. If the cortisol level is more than 50 nanomoles per liter (nmol/L), Cushing's syndrome is suspected. The test generally requires a 48-hour hospital stay to avoid falsely elevated cortisol levels due to stress. Low-dose dexamethasone suppression test (LDDST): In the LDDST, a person is given a low dose of dexamethasone, a synthetic glucocorticoid, by mouth every 6 hours for 2 days. Urine is collected before dexamethasone is administered and several times on each day of the test. A modified LDDST uses a onetime overnight dose. Cortisol and other glucocorticoids signal the pituitary to release less ACTH, so the normal response after taking dexamethasone is a drop in blood and urine cortisol levels. If cortisol levels do not drop, Cushing's syndrome is suspected. The LDDST may not show a drop in cortisol levels in people with depression, alcoholism, high estrogen levels, acute illness, or stress, falsely indicating Cushing's syndrome. On the other hand, drugs such as phenytoin and phenobarbital may cause cortisol levels to drop, falsely indicating that Cushing's is not present in people who actually have the syndrome. For this reason, physicians usually advise their patients to stop taking these drugs at least 1 week before the test. Dexamethasone-corticotropin-releasing hormone (CRH) test: Some people have high cortisol levels but do not develop the progressive effects of Cushing's syndrome, such as muscle weakness, fractures, and thinning of the skin. These people may have pseudo-Cushing's syndrome, a condition sometimes found in people who have depression or anxiety disorders, drink excess alcohol, have poorly controlled diabetes, or are severely obese. Pseudo-Cushing's does not have the same long-term effects on health as Cushing's syndrome and does not require treatment directed at the endocrine glands. The dexamethasone-CRH test rapidly distinguishes pseudo-Cushing's from mild cases of Cushing's. This test combines the LDDST and a CRH stimulation test. In the CRH stimulation test, an injection of CRH causes the pituitary to secrete ACTH. Pretreatment with dexamethasone prevents CRH from causing an increase in cortisol in people with pseudo-Cushing's. Elevations of cortisol during this test suggest Cushing's syndrome. Petrosal sinus sampling: This test is not always required, but in many cases, it is the best way to distinguish pituitary from ectopic causes of Cushing's syndrome. Samples of blood are drawn from the petrosal sinuses—veins that drain the pituitary—by inserting tiny tubes through a vein in the upper thigh or groin region. A local anesthetic and mild sedation are given, and x rays are taken to confirm the correct position of the tubes. Often CRH, the hormone that causes the pituitary to release ACTH, is given during this test to improve diagnostic accuracy. Levels of ACTH in the petrosal sinuses are measured and compared with ACTH levels in a forearm vein. Higher levels of ACTH in the sinuses than in the forearm vein indicate a pituitary adenoma. Similar levels of ACTH in the petrosal sinuses and the forearm suggest ectopic ACTH syndrome. Radiologic Imaging: Direct visualization of the endocrine glands. Imaging tests reveal the size and shape of the pituitary and adrenal glands and help determine if a tumor is present. The most common imaging tests are the computerized tomography (CT) scan and magnetic resonance imaging (MRI). A CT scan produces a series of x-ray pictures giving a cross-sectional image of a body part. MRI also produces images of internal organs but without exposing patients to ionizing radiation. Imaging procedures are used to find a tumor after a diagnosis has been made. Imaging is not used to make the diagnosis of Cushing's syndrome because benign tumors are commonly found in the pituitary and adrenal glands. These tumors, sometimes called incidentalomas, do not produce hormones in quantities that are harmful. They are not removed unless blood tests show they are a cause of symptoms or they are unusually large. Conversely, pituitary tumors may not be detectable by imaging in almost half of people who ultimately need pituitary surgery for Cushing's syndrome. Treatment: Treatment for Cushing's syndrome depends on the cause. For Cushing's syndrome caused by long-term corticosteroid medicine use: Never stop taking corticosteroid medicine on your own because it might lead to a life-threatening adrenal crisis. When you take steroids, your adrenal glands stop making cortisol. If you suddenly stop taking your medicine, your adrenal glands may not be able to start making cortisol quickly enough. This can lead to an adrenal crisis and a severe drop in blood pressure. To avoid this, your doctor will want to gradually reduce and then stop your medicine. Your doctor may change your corticosteroid medicine from a longer-acting steroid (such as prednisone) to a shorter-acting one (such as hydrocortisone). Sometimes corticosteroid medicines can be taken every other day. Either way, the body's normal production of cortisol returns gradually. If you must continue taking corticosteroid medicine to control another condition, the dosage can sometimes be lowered to reduce symptoms and the risk of complications. If your doctor and you are trying to reduce the dosage of your medicine and you become ill, contact your doctor immediately. If reducing the dosage does not make Cushing's syndrome go away, your doctor will perform more tests to look for another cause of your condition. For Cushing's syndrome caused by pituitary tumors (Cushing's disease): If you are well enough to have surgery, surgical removal of the pituitary tumor offers the best chance for recovery. The surgery (transsphenoidal adenomectomy) requires great skill and should be performed at a major medical center where teams of doctors specialize in pituitary surgery. Transsphenoidal adenomectomy is successful: About 85% of the time if the tumor is less than 1cm in diameter.
  • About 25% of the time if the tumor is 1cm in diameter or larger.
  • Cushing's disease returns in about 2% of adults and up to 40% of children who have the operation.2 Surgery can be repeated, often with good results.
Gamma knife radiosurgery has recently been introduced in the United States. In this technique, many small beams of radiation are focused on the tumor to shrink and destroy it. It does not involve a surgical incision (there is no "knife" involved), and there is minimal damage to surrounding tissue. It can be done as an outpatient and with local anesthesia. Few centers in the United States have gamma knife facilities. Medicine therapies may be tried if surgery is not possible or has failed. For Cushing's syndrome caused by adrenal tumors: Doctors almost always recommend surgery to remove benign adrenal tumors that are producing hormones. If a tumor is cancerous, the affected adrenal gland is removed. Although chemotherapy is usually advised, there is no proven long-term treatment for adrenal cancer. On rare occasions, both adrenal glands must be removed. In this case, you would take daily long-term hormone replacement. Surgery is usually successful if the tumor is not cancerous. But surgery is not as successful for a cancerous tumor if the cancer has spread to other parts of the body. If surgery is not possible, medicine therapy may be tried to reduce the tumor's production of cortisol. This includes using ketoconazole (Nizoral), mitotane (Lysodren), and aminoglutethimide (Cytadren). These medicines also are sometimes used before surgery in people with severe Cushing's syndrome. Pregnant women with Cushing's disease can take aminoglutethimide. If left untreated for a long time, Cushing's syndrome may cause serious problems, including complications from high blood pressure (such as a heart attack or stroke), osteoporosis, or diabetes. The condition also can cause death. Because of these risks, treatment usually begins as soon as possible. Home Treatment: Home treatment for Cushing's syndrome consists of lifestyle changes to prevent weight gain, strengthen muscles and bones, and prevent complications. Eat a low-calorie, nutritious diet high in protein and calcium. This can help prevent muscle and bone loss caused by the high cortisol levels in your body. Take calcium and vitamin D supplements to decrease bone loss. Ask your doctor whether you need medicine to help slow bone loss.
  • Limit salt (sodium) in your diet. This is especially important if you have high blood pressure, a complication of Cushing's syndrome.
  • Get regular exercise to help maintain muscles and bone mass and prevent weight gain. To maintain muscle and bone mass, try weight-bearing exercises such as push-ups, sit-ups, or lifting weights. To prevent weight gain, try aerobic exercise to increase your heart rate. Examples of aerobic exercise include fast walking, jogging, cycling, and swimming. Consult your doctor before beginning any exercise program. \
  • Avoid possible falls by removing loose rugs and other hazards from your home. Falling may lead to broken bones and other injuries.
  • Get regular eye exams to check for glaucoma and cataracts.
Medicine and medications: As an option, there are medication therapies that are used to control the production of cortisol. Ketoconazole and Metyrapone are just some of the drugs used to block the effects of too much cortisol in the body. However, levels of success in using them vary from patient to patient. One good way of preventing Cushing's syndrome from happening is simply minding over your drug intake. Some anti-inflammatory steroids, especially those taken for asthma and arthritis, may have side effects that cause this problem. To be safe, make sure that you consult your doctor about the intake of any of those kinds of drugs. DISCLAIMER: This information should not substitute for seeking responsible, professional medical care.

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