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Cushing Syndrome


Ashley B. Grossman

, MD, University of Oxford; Fellow, Green-Templeton College

Reviewed/Revised Feb 2024
Topic Resources

In Cushing syndrome, the level of corticosteroids is excessive, usually due to taking corticosteroid medications or overproduction by the adrenal glands.

  • Cushing syndrome usually results from taking corticosteroids to treat a medical disorder or from a tumor in the pituitary or adrenal gland that causes the adrenal glands to produce excessive corticosteroids.

  • 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.

The adrenal glands may overproduce corticosteroids because of a problem in the adrenal glands or because of too much stimulation from the pituitary gland Overview of the Pituitary Gland The pituitary is a pea-sized gland that is housed within a bony structure (sella turcica) at the base of the brain. The sella turcica protects the pituitary but allows very little room for expansion... read more , which controls the adrenal glands and other endocrine glands Endocrine Glands The endocrine system consists of a group of glands and organs that regulate and control various body functions by producing and secreting hormones. Hormones are chemical substances that affect... read more . 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 corticosteroids by the adrenal glands (a condition known as Cushing disease Cushing disease In Cushing syndrome, the level of corticosteroids is excessive, usually due to taking corticosteroid medications or overproduction by the adrenal glands. Cushing syndrome usually results from... read more Cushing disease ). Tumors outside the pituitary gland, such as small cell lung cancer or a carcinoid tumor Carcinoid Tumors and Carcinoid Syndrome Carcinoid tumors are noncancerous (benign) or cancerous (malignant) growths that sometimes produce excessive amounts of hormone-like substances (such as serotonin), resulting in the carcinoid... read more Carcinoid Tumors and Carcinoid Syndrome in the lungs or elsewhere in the body, can produce ACTH as well (a condition called ectopic ACTH syndrome).

The Adrenal Glands

Sometimes a noncancerous tumor (adenoma) develops in the adrenal glands, which causes them to overproduce corticosteroids. 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 corticosteroids

Cushing syndrome can also develop in people who must take large doses of corticosteroids (such as prednisone or dexamethasone) because of a serious medical condition. Corticosteroids are often used to treat many inflammatory, allergic Overview of Allergic Reactions Allergic reactions (hypersensitivity reactions) are inappropriate responses of the immune system to a normally harmless substance. Usually, allergies cause sneezing, watery and itchy eyes, a... read more Overview of Allergic Reactions , and autoimmune Autoimmune Disorders An autoimmune disorder is a malfunction of the body's immune system that causes the body to attack its own tissues. What triggers an autoimmune disorder is not known. Symptoms vary depending... read more disorders. Common examples include asthma Asthma Asthma is a condition in which the airways narrow—usually reversibly—in response to certain stimuli. Coughing, wheezing, and shortness of breath that occur in response to specific triggers are... read more Asthma , rheumatoid arthritis Rheumatoid Arthritis (RA) Rheumatoid arthritis is an inflammatory arthritis in which joints, usually including those of the hands and feet, are inflamed, resulting in swelling, pain, and often destruction of joints.... read more Rheumatoid Arthritis (RA) , systemic lupus erythematosus Systemic Lupus Erythematosus (SLE) Systemic lupus erythematosus is a chronic autoimmune inflammatory connective tissue disorder that can involve joints, kidneys, skin, mucous membranes, and blood vessel walls. Problems in the... read more Systemic Lupus Erythematosus (SLE) , many skin disorders, and numerous other conditions. Those who must take large doses have the same symptoms as those whose body produces too much of the hormone. The symptoms can occasionally occur even if the corticosteroids are inhaled, as for asthma Asthma Asthma is a condition in which the airways narrow—usually reversibly—in response to certain stimuli. Coughing, wheezing, and shortness of breath that occur in response to specific triggers are... read more Asthma , or are used topically for a skin condition.

In addition to causing Cushing syndrome, taking large doses of corticosteroids also can suppress the function of the adrenal glands (adrenal insufficiency Adrenal Insufficiency In adrenal insufficiency, the adrenal glands do not produce enough adrenal hormones. Adrenal insufficiency may be caused by a disorder of the adrenal glands, a disorder of the pituitary gland... read more Adrenal Insufficiency ). This suppression occurs because corticosteroids signal the hypothalamus and pituitary gland to stop producing the hormones that normally stimulate adrenal function. Thus, if the person abruptly stops taking corticosteroids, 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 corticosteroids that are needed.

Therefore, doctors never stop the use of corticosteroids 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 corticosteroids may need to be increased in people who become ill or otherwise severely stressed while taking corticosteroids. Corticosteroid use may need to be resumed in people who become ill or otherwise severely stressed within weeks of having the corticosteroid tapered and stopped.

Cushing disease

Cushing disease is a term given specifically to Cushing syndrome caused by overstimulation of the adrenal glands, usually because of a pituitary tumor Enlargement of the Pituitary Gland Enlargement of the pituitary gland is usually due to a tumor but may be due to bleeding into the gland or involvement by some other disease, such as tuberculosis or sarcoidosis. In some cases... read more . 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 MRI (magnetic resonance imaging) or CT (computed tomography) may be done of the pituitary gland area.

Cushing disease is treated with surgery or radiation to remove the pituitary tumor. If removal of the pituitary tumor can't 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

Corticosteroids 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.

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, and/or blood

  • Other blood tests

  • Imaging tests

When doctors suspect Cushing syndrome, they measure the level of cortisol, the main corticosteroid 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 cortisol in the morning. Dexamethasone 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 cortisol, 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 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 chest x-ray or CT scan of the lungs or the abdomen. However, these imaging tests may occasionally fail to find the tumor.

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 corticosteroids, doctors weigh the benefit of the medication against the harm of having Cushing syndrome. Some people need to continue taking the corticosteroid 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 corticosteroids 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 corticosteroids.

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, so blood thinners may be used. These people are also especially likely to develop infections, which may be life-threatening.

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 corticosteroids for life.

Tumors outside the pituitary and adrenal glands that secrete excess hormones are usually surgically removed.

Certain medications, such as metyrapone or ketoconazole, can lower cortisol levels and can be used while awaiting more definitive treatment such as surgery. Mifepristone, which can block the effects of cortisol, 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 diabetes Diabetes Mellitus (DM) Diabetes mellitus is a disorder in which the body does not produce enough or respond normally to insulin, causing blood sugar (glucose) levels to be abnormally high. Symptoms of diabetes may... read more . Cabergoline may also occasionally be useful. Pasireotide and cabergoline decrease the ability of ACTH to stimulate production of cortisol by the adrenal glands. Osilodrostat and levoketoconazole can also be used to lower cortisol levels; like metyrapone and ketoconazole, they block production of cortisol in the adrenal glands.

What Is Nelson Syndrome?

People who have both their adrenal glands removed as treatment for Cushing disease that did not resolve with surgery and/or radiation to the pituitary may develop Nelson syndrome.

In this disorder, the pituitary tumor that caused the Cushing disease continues to grow, producing large amounts of ACTH and leading to darkening of the skin. The enlarging pituitary tumor may compress nearby structures in the brain, causing headaches and defects in vision.

Some experts believe that this compression may be prevented, at least in some people, by radiation therapy to the pituitary gland. If necessary, Nelson syndrome can be treated with radiation therapy or surgical removal of the pituitary gland.

Drugs Mentioned In This Article

Generic Name Select Brand Names
Deltasone, Predone, RAYOS, Sterapred, Sterapred DS
AK-Dex, Baycadron, Dalalone, Dalalone D.P, Dalalone L.A, Decadron, Decadron-LA, Dexabliss, Dexacort PH Turbinaire, Dexacort Respihaler, DexPak Jr TaperPak, DexPak TaperPak, Dextenza, DEXYCU, DoubleDex, Dxevo, Hemady, HiDex, Maxidex, Ocu-Dex , Ozurdex, ReadySharp Dexamethasone, Simplist Dexamethasone, Solurex, TaperDex, ZCORT, Zema-Pak, ZoDex, ZonaCort 11 Day, ZonaCort 7 Day
Extina, Ketodan, Kuric, Nizoral, Nizoral A-D, Xolegel
Korlym, Mifeprex
Signifor, Signifor LAR
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