Cushing Syndrome

What is It, Causes, Treatment, and More

Author:Corinne Tarantino, MPH

Editors:Alyssa Haag,Ahaana Singh,Emily Miao, PharmD

Illustrator:Jillian Dunbar

Copyeditor:David Walker

What is Cushing syndrome?

Cushing syndrome, also called hypercortisolism, is a set of symptoms resulting from exposure to high levels of the stress hormone cortisol. Cortisol, a hormone in the body that is typically produced in response to stress, helps regulate blood pressure and blood sugar, reduce inflammation, and metabolize food. 

Cortisol production and release is stimulated by a series of hormone interactions. First, the hypothalamus secretes corticotropin-releasing hormone, known as CRH. CRH stimulates the anterior pituitary gland to produce adrenocorticotropic hormone (ACTH). Ultimately, ACTH signals cortisol production of the adrenal glands, which are small glands located on top of each kidney.

What is the difference between Cushing disease and Cushing syndrome?

Cushing disease occurs when Cushing syndrome is caused by an ACTH-producing pituitary tumor, whereas Cushing syndrome is the set of symptoms that results when there is a surplus of cortisol in the body. In other words, Cushing syndrome can be caused by any exposure to surplus cortisol whether it be endogenous (from the body) or exogenous (from outside the body), while Cushing disease can only be caused by increased cortisol levels resulting from an ACTH-producing pituitary tumor (a specific endogenous cause). High levels of ACTH with Cushing disease signals the adrenal gland to increase cortisol production, leading to the elevated cortisol levels found in Cushing syndrome.

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What causes Cushing syndrome?

There are many potential causes of Cushing syndrome. The most common cause is long-term use of glucocorticoids to treat inflammatory disorders, like asthma, rheumatoid arthritis, or lupus. Glucocorticoids resemble cortisol and, thus, can be utilized in the body as excess cortisol.

Less frequently, Cushing syndrome may develop due to a tumor that affects the hormones involved in stimulating cortisol production. Pituitary tumors that produce ACTH in excess, as seen in Cushing disease, are the most common tumor type. Sometimes, ectopic ACTH-producing tumors (i.e. tumors that secrete ACTH outside of the pituitary gland) may occur, such as in the lungs or pancreas, and are often cancerous. Cushing syndrome can rarely be caused by an adrenal tumor, which is typically benign, or non-cancerous.

What are the signs and symptoms of Cushing syndrome?

Most early signs and symptoms of Cushing syndrome are general and non-specific, including fatigue, diabetes, high blood pressure, and depression. Over time, most individuals with undiagnosed Cushing syndrome develop weight gain, leading to obesity with characteristic features, such as a moon face (i.e., a rounded face shape), a buffalo hump (i.e., a bump behind the shoulders), and thin extremities. The skin may become more frail, leading to easy bruising and stretch marks. Individuals assigned female at birth who are experiencing Cushing syndrome commonly present with decreased libido; menstrual changes; and hirsutism, or thick hair growth in unexpected areas, such as on the face or back. Rarely, individuals may also experience proximal myopathy, or muscle weakness, in the legs and arms, which may be evidenced by difficulty standing up or climbing stairs. 

How is Cushing syndrome diagnosed?

Cushing syndrome is often diagnosed after a thorough medical examination investigating the individual’s medical history and conducting a physical exam. Subsequently, multiple laboratory tests (e.g., 24-hour urinary free-cortisol test, overnight low-dose dexamethasone suppression test, or late-night salivary cortisol test) are typically performed, which require samples of bodily fluids, such as urine, saliva, or blood. Oftentimes, the diagnosis of Cushing syndrome is only confirmed after two or more tests demonstrate elevated levels of ACTH and cortisol.

Further testing, including imaging tests (e.g., CT or MRI), may be used to assess whether a tumor is the underlying cause of the individual’s Cushing syndrome. Some pituitary tumors are too small to appear on imaging and, instead, require petrosal sinus (i.e. small sinus veins that drain from the pituitary) blood samples.

How is Cushing syndrome treated?

The treatment of Cushing syndrome varies depending on the underlying cause. If the disease was caused by the use of a glucocorticoid medication, treatment typically involves lowering the glucocorticoid dose or changing the medication to another steroid class or anti-inflammatory. If the medication is lowered or changed, it will be slowly tapered to avoid adrenal crisis caused by a sudden reduction of cortisol. When Cushing syndrome results from a tumor, the tumor is often surgically removed. If surgery is not a viable option (e.g., the tumor has metastasized) or does not relieve symptoms, radiation therapy may be utilized. After a pituitary tumor is removed, about 6-18 months of cortisol supplementation will typically follow the surgery. If both adrenal glands are removed, cortisol and other hormone supplementation will be needed for the duration of the individual’s life.

Can Cushing syndrome be cured?

Most of the time, Cushing syndrome can be cured since it typically results from long-term glucocorticoid use. However, despite appropriate treatment, many individuals experience residual symptoms from Cushing syndrome, including muscle weakness or cognitive impairment

Individuals with successful surgeries of benign pituitary, adrenal, or ectopic tumors have a 5 year survival rate of 95% and 10 year survival rate of 90%. Unlike the benign tumors, depending on the stage of an adrenocortical carcinoma, five year survival rates for malignant tumors range from 50-81%.

What are the most important facts to know about Cushing syndrome?

Cushing syndrome is a set of symptoms that result from high cortisol levels. Cushing syndrome has many causes, most commonly glucocorticoid medication use. When Cushing syndrome is caused by an ACTH-producing pituitary tumor, it is called Cushing disease. There are a wide range of Cushing syndrome symptoms, including obesity, diabetes, high blood pressure, fatigue, and depression. The condition is diagnosed after a medical evaluation and diagnostic laboratory testing. Treatment varies depending on the underlying cause but may include either decreasing or discontinuing glucocorticoid medications as well as surgically or radioactively removing the tumor. Typically, Cushing syndrome can be cured, although some symptoms, such as muscle weakness, may never completely resolve.

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Related links

Cushing syndrome
Cushing syndrome: Clinical practice
Cushing syndrome and Cushing disease: Pathology review

Resources for research and reference

Arlt, W (2018). Disorders of the adrenal cortex. In Jameson J, & Fauci A.S., & Kasper D.L., & Hauser S.L., & Longo D.L., & Loscalzo J(Eds.), Harrison's Principles of Internal Medicine, 20e. McGraw Hill.

Chaudhry, H.S. & Singh, G. (2021). Cushing Syndrome. In: StatPearls. StatPearls Publishing. Retrieved from: 

Fitzgerald, P.A. (2022). Cushing syndrome (hypercortisolism). In Papadakis M.A., & McPhee S.J., & Rabow M.W., & McQuaid K.R.(Eds.), Current Medical Diagnosis & Treatment 2022. McGraw Hill.

National Institute of Diabetes and Digestive and Kidney Diseases. (2018). Cushing's Syndrome. Retrieved, August 19, 2021, from: