In Cushing syndrome, the level of cortisol is excessive, usually due to taking steroid medications or overproduction by the adrenal glands.
Cushing syndrome usually results from taking steroids (sometimes called glucocorticoids or corticosteroids) to treat a medical disorder or from a tumor in the pituitary or adrenal gland that causes the adrenal glands to produce excessive cortisol.
Cushing syndrome can also result from tumors in other locations (such as the lungs).
People with Cushing syndrome usually develop excessive fat throughout the torso and have a large, round face and thin skin.
Doctors measure the level of cortisol and do other tests to detect Cushing syndrome.
Surgery or radiation therapy is often needed to remove a tumor.
(See also Overview of the Adrenal Glands.)
The adrenal glands may overproduce cortisol because of a problem in the adrenal glands or because of too much stimulation from the pituitary gland, which controls the adrenal glands and other endocrine glands. An abnormality in the pituitary gland, such as a tumor, can cause the pituitary to produce large amounts of adrenocorticotropic hormone (ACTH, also known as corticotropin), the hormone that stimulates the production of cortisol by the adrenal glands (a condition known as Cushing disease). Tumors outside the pituitary gland, such as small cell lung cancer or a neuroendocrine tumor in the lungs or elsewhere in the body, can produce ACTH as well (a condition called ectopic ACTH syndrome).
Sometimes a noncancerous tumor (adenoma) develops in the adrenal glands, which causes them to overproduce cortisol. Adrenal adenomas are extremely common. About 10% of all people have them by the age of 70 years. Only a small fraction of adenomas produce excess hormone, however. Cancerous tumors of the adrenal glands are very rare, but some of them also produce excess hormone.
Taking steroids
Cushing syndrome can also develop in people who must take large doses of steroid medications (such as prednisone or dexamethasone) because of a serious medical condition. These are synthetic forms of glucocorticoids that are often used to treat many inflammatory, Cushing syndrome can also develop in people who must take large doses of steroid medications (such as prednisone or dexamethasone) because of a serious medical condition. These are synthetic forms of glucocorticoids that are often used to treat many inflammatory,allergic, and autoimmune disorders. Common examples include asthma, rheumatoid arthritis, systemic lupus erythematosus, many skin disorders, and numerous other conditions. People who must take large doses have the same symptoms as people whose body produces too much cortisol. The symptoms can occasionally occur even if the steroids are inhaled, as for asthma, or are used topically for a skin condition.
In addition to causing Cushing syndrome, taking large doses of steroids also can suppress the function of the adrenal glands (adrenal insufficiency). This suppression occurs because steroids signal the hypothalamus and pituitary gland to stop producing the hormones that normally stimulate adrenal function. Thus, if the person abruptly stops taking steroids, the body cannot restore adrenal function quickly enough, and temporary adrenal insufficiency results. Also, when stress occurs, the body is not able to stimulate production of the additional cortisol that is needed.
Therefore, doctors never stop the use of steroids abruptly if people have been taking them for more than 2 or 3 weeks. Instead, doctors gradually reduce (taper) the dose over weeks and sometimes months.
Also, the dose of steroids may need to be increased in people who become ill or otherwise severely stressed while taking steroids. Steroid use may need to be resumed in people who become ill or otherwise severely stressed within weeks of having the steroid tapered and stopped.
Cushing disease
Cushing disease is a term given specifically to Cushing syndrome caused by overstimulation of the adrenal glands because of a pituitary tumor. In this disorder, the adrenal glands are overactive because the pituitary gland is overstimulating them, and not because the adrenal glands are abnormal. Symptoms of Cushing disease are similar to those of Cushing syndrome.
Cushing disease is diagnosed by blood tests, or sometimes also with tests of urine and saliva. Imaging tests such as magnetic resonance imaging (MRI) or computed tomography (CT) may be done of the pituitary gland area.
Cushing disease is treated with surgery or radiation therapy to remove the pituitary tumor. If removal of the pituitary tumor cannot be done or is unsuccessful, the adrenal glands can be removed surgically, or medications can be given to reduce ACTH production or block the production or effects of the excess cortisol on tissues.
Symptoms of Cushing Syndrome
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Excess glucocorticoid hormones alter the amount and distribution of body fat. Excessive fat develops throughout the torso and may be particularly noticeable at the top of the back (sometimes called a buffalo hump). A person with Cushing syndrome usually has a large, round face (moon face). The arms and legs are usually slender in proportion to the thickened trunk. Muscles lose their bulk, leading to weakness. The skin becomes thin, bruises easily, and heals poorly when bruised or cut. Streaks that look like stretch marks (striae) may develop over the abdomen and chest. People with Cushing syndrome tend to tire easily.
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Over time, high glucocorticoid levels raise the blood pressure (hypertension), weaken bones (osteoporosis), and diminish resistance to infections. The risk of developing kidney stones, diabetes, and blood clots in veins is increased, and mental disturbances, including depression and hallucinations, may occur.
Women usually have an irregular menstrual cycle. In some people, the adrenal glands also produce large amounts of male sex hormones (testosterone and similar hormones), leading to increased facial and body hair, and balding in women.
Children with Cushing syndrome grow slowly, and their height is likely to be shorter than average.
Diagnosis of Cushing Syndrome
Measure the level of cortisol in the urine, saliva, or blood
Other blood tests
Imaging tests
When doctors suspect Cushing syndrome, they measure the level of cortisol, the main glucocorticoid hormone. Normally, cortisol levels are high in the morning and lower late in the day. In people who have Cushing syndrome, cortisol levels are usually very high throughout the day. Cortisol levels may be checked by testing the urine, the saliva, or the blood.
If the cortisol levels are high, doctors may recommend a dexamethasone suppression test in which doctors give a dose of dexamethasone at night or over several days and then measure the level of suppression test in which doctors give a dose of dexamethasone at night or over several days and then measure the level ofcortisol in the morning. Dexamethasone is a synthetic glucocorticoid that normally suppresses the secretion of corticotropin by the pituitary gland and should lead to suppression of cortisol secretion by the adrenal glands. If Cushing syndrome is caused by too much pituitary stimulation (Cushing disease), the blood level of cortisol will fall to some extent, although not as much as in people who do not have Cushing syndrome. A high ACTH level further suggests overstimulation of the adrenal gland by the pituitary.
If Cushing syndrome has another cause, the level of cortisol will remain high after giving dexamethasone. For example, if a tumor in an adrenal gland produces too much will remain high after giving dexamethasone. For example, if a tumor in an adrenal gland produces too muchcortisol, the level of corticotropin from the pituitary is already suppressed, and dexamethasone does not decrease the blood level of cortisol. Sometimes, other types of tumors elsewhere in the body produce corticotropin-like substances that stimulate the adrenal glands to produce excess cortisol, but this stimulation is not suppressed by dexamethasone.
Imaging tests may be needed to determine the exact cause, including a computed tomography (CT) or magnetic resonance imaging (MRI) scan of the pituitary gland or the adrenal glands and a CT scan of the lungs or the abdomen. However, these imaging tests may occasionally fail to find the tumor. There are also radionuclide scans, which may be helpful.
When overproduction of ACTH is thought to be the cause, blood samples may sometimes need to be taken from the veins that drain the pituitary to see if that is the source.
Treatment of Cushing Syndrome
Diet high in protein and potassium
Medications that decrease cortisol levels or block the effects of cortisol
Surgery or radiation therapy
Treatment depends on whether the problem is in the adrenal glands, the pituitary gland, or elsewhere.
If the problem is caused by taking steroids, doctors weigh the benefit of the medication against the harm of having Cushing syndrome. Some people need to continue taking the steroid even though they have Cushing syndrome. If not, doctors gradually reduce (taper) the dose over weeks and sometimes months. During the tapering, the dose may need to be temporarily increased if people become ill or otherwise severely physically stressed. Even for weeks to months after steroids have been stopped, people who become ill may need to resume taking them because their adrenal glands have not fully recovered from suppression by the steroids.
The first step people can take in the treatment of Cushing syndrome is to support their general condition by following a diet that is high in protein and potassium. Sometimes, medications that increase potassium or lower blood glucose (sugar) levels are necessary. Any increase in blood pressure needs to be treated. Because people with Cushing syndrome are also at increased risk of blood clots in their veins, blood thinners are routinely used in most cases. These people are also especially likely to develop infections, which may be life-threatening.
Surgery or radiation therapy (including proton beam therapy, if available) may be needed to remove or destroy a pituitary tumor.
Tumors of the adrenal glands (usually benign adenomas) can often be removed surgically.
Both adrenal glands may have to be removed if tumors are present in both adrenal glands, attempted removal of a pituitary or other ACTH-secreting tumor is not effective, or blood levels of ACTH are high but an ACTH-secreting tumor cannot be found. People who have both adrenal glands removed, and many people who have part of their adrenal glands removed, must take steroids for life.
Tumors outside the pituitary and adrenal glands that secrete excess hormones are usually surgically removed if possible.
Certain medications, such as metyrapone or ketoconazole, or newer agents such as osilodrostat or levoketoconazole, can lower Certain medications, such as metyrapone or ketoconazole, or newer agents such as osilodrostat or levoketoconazole, can lowercortisol levels and can be used while awaiting more definitive treatment such as surgery. Mifepristone, which can block the effects of levels and can be used while awaiting more definitive treatment such as surgery. Mifepristone, which can block the effects ofcortisol, can also be used. People with mild cases of persistent or recurrent disease may benefit from pasireotide, although this will tend to cause or worsen , can also be used. People with mild cases of persistent or recurrent disease may benefit from pasireotide, although this will tend to cause or worsendiabetes. Cabergoline may also occasionally be useful. . Cabergoline may also occasionally be useful.Pasireotide and cabergoline decrease the level of ACTH to stimulate production of cortisol by the adrenal glands.
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