What is Cushing’s syndrome—and how is it treated?

Amy Schumer recently announced that she has been diagnosed with Cushing’s syndrome, a disorder that develops over time when there is too much cortisol in the body. Schumer went public with her health issue after receiving a flurry of critical social media comments about her “puffier than normal” face. The 42-year-old comedian says she shared her diagnosis to ‘advocate for women’s health,’ noting that the public’s outcry over the changes in her appearance helped her realize something was wrong.

What is Cushing’s syndrome?

Cushing’s syndrome (also called Cushing syndrome) is named after Harvey Cushing, a brain surgeon who first described patients with the condition in 1912. It can develop over time if the body produces too much cortisol—or if you get too much from an outside source, like medications.

Cortisol is a steroid hormone that is made and released by the adrenal glands, small, triangular-shaped glands located on top of each kidney. It plays a role in several essential jobs, including:

• Controlling the body’s response to stress
• Regulating the body’s blood sugar and metabolism
• Maintaining blood pressure
• Controlling bone formation
• Fighting infections and control inflammation
• Regulating the body’s sleep-wake cycle

So, the body needs cortisol but if levels of the hormone are too high for too long, it can affect your health.

What causes it and who is at greater risk?

Cushing syndrome is rare. In the U.S., only about 10 to 15 new cases per million people are diagnosed each year. It’s possible that this estimate is low since the condition may be underdiagnosed or be confused with other issues.

Anyone can develop it—even kids. But the condition usually affects adults ages 30 to 50. Cushing’s syndrome also affects almost three times as many women as men. High blood pressure or diabetes may also result from or be linked with Cushing’s.

The most common cause of Cushing’s is long-term use of medicines called glucocorticoids, a type of corticosteroid hormone that’s similar to cortisol. These drugs, which include hydrocortisone, prednisone pills, asthma inhalers and joint injections, are often used to manage a wide range of inflammatory and autoimmune diseases, including asthma, psoriasis, arthritis, lupus, and inflammatory bowel disease. Glucocorticoids are also used to suppress the immune system in people who’ve received an organ transplant.

This type of Cushing’s syndrome is called “exogenous,” which means it is caused by something outside the body. Schumer’s case was reportedly brought on by “getting steroid injections in high doses." It's unclear why she was receiving the injections, but the comedian has also revealed that she has endometriosis, a condition in which tissue similar to the lining of the uterus grows outside the uterus.

More rarely, some people develop “endogenous” Cushing’s. This means that something inside their body is causing the condition. Certain types of tumors can cause the body to produce too much cortisol, including:

• Pituitary tumors: The pituitary gland is a pea-sized glad located at the base of the brain. It makes a hormone called adrenocorticotropic hormone (ACTH), which signals the adrenal glands to produce cortisol. Tumors on the pituitary are rarely cancerous but they can cause the gland to make too much ACTH, which prompts the adrenal glands to make too much cortisol. These tumors account for most “endogenous” cases of high cortisol levels. These cases, in particular, are called Cushing’s disease.
• Ectopic ACTH-producing tumors: Sometimes tumors that develop in the lungs can also make ACTH and cause the adrenal glands to produce too much cortisol. These tumors, which may be cancerous, can also occur in the pancreas as well as the thyroid or thymus glands.
• Adrenal tumors: Tumors that occur on the adrenal glands themselves can trigger the overproduction of cortisol. These tumors may be cancerous, but they are usually not.

How do you know if you have it?

Having high cortisol levels for a long time can cause some obvious symptoms, including:

• Weight gain
• Purple stretch marks on the abdomen
• Muscle loss, particularly in the arms and legs
• A round or “puffy” face, also called “moon face”
• A build-up of fat on the back of the neck and shoulders, known as a "buffalo hump"
• Thinner skin that bruises more easily
• Slow-healing wounds
• Excessive body and facial hair (women)
• Acne
• Weakness and fatigue
• Blurry vision and dizziness
• Lower sex drive or sexual dysfunction
• Stopped or irregular menstrual periods

Children with Cushing’s syndrome tend to have stunted or slowed growth, compared to other kids. They are also more likely to have obesity.

But not everyone with Cushing’s syndrome experiences these symptoms. This can make the condition difficult to diagnose. And many of these tell-tale signs are also tied to other health issues, such as polyendocrine metabolic ovarian syndrome or metabolic syndrome.

In some cases, people may have high cortisol levels due to other causes, such as alcohol abuse, obesity, uncontrolled diabetes, depression, the eating disorder anorexia nervosa, or high estrogen levels. These cases are called “Pseudo-Cushing's” because they mimic the disorder.

Healthcare providers diagnose Cushing’s based on your medical history and whether you’re taking glucocorticoids or have had steroid injections as well as a physical exam and several lab tests.

If Cushing’s syndrome is suspected, one or more of the following tests may be ordered:

• 24-hour urinary cortisol test: This test measures the amount of cortisol in your urine over a 24-hour period.
• Midnight salivary cortisol test: This test checks the level of cortisol in your saliva late at night between 11 p.m. and 12 a.m. Normally, cortisol levels drop at night and are higher in the morning. For those with Cushing’s, their cortisol levels do not fall late in the evening.
• Low-dose dexamethasone suppression test: For this test, you take the cortisol-like drug dexamethasone by mouth at night. Cortisol levels are then measured between 8 a.m. and 9 a.m. in the morning to assess how the adrenal glands responded to the medication. Normally, the drug would reduce the amount of cortisol they secrete. For those with Cushing’s, their cortisol levels will remain high.
• Blood test: Measuring blood levels of ACTH can also help diagnose Cushing’s caused by a tumor. Low ACTH levels may signal an adrenal tumor, while high levels may indicate a pituitary or ectopic tumor.
• High-dose dexamethasone suppression test: This test is like the low-dose dexamethasone suppression test, but the dosage of the drug is higher. It may be ordered if the low-dose test reveals high cortisol levels in the morning and blood tests show high levels of ACTH. It can help tell the difference between a pituitary tumor and tumors in other parts of the body.

How is Cushing’s syndrome treated?

Once Cushing’s is diagnosed, treatment will depend on what is causing the condition.

For example, if you have been taking glucocorticoids, your dosage may be lowered to help manage your cortisol level. In some cases, people may be switched to a non-glucocorticoid medicine.

If you are not on one of these drugs, imaging tests may be ordered to identify a possible tumor that may be the cause. This may include CT scans or an MRI of the chest, abdomen, or pituitary gland.

Another test called a bilateral inferior petrosal sinus sampling (BIPPS) can help detect the source of ACTH, which may be driving up cortisol levels. For this test, while a patient is under general anesthesia, small tubes are inserted through the groin to the main veins that drain the pituitary gland (the inferior petrosal sinuses). Samples are taken from these veins and tested for ACTH. They are compared to samples taken from the main vein of the abdomen. The differences in ACTH levels can help pinpoint the location of a tumor that may be increasing cortisol levels.

When Cushing’s syndrome is caused by a tumor, treatment may involve one or more of the following:

• Medication: Reducing or eliminating drugs that increase cortisol levels is one approach. But there are also drugs, such as ketoconazole, that help slow down the production of the hormone as well.
• Surgery: In most cases, an operation to remove tumors on the pituitary or adrenal glands or other locations is performed to help restore cortisol levels to a normal level.
• Chemotherapy: For cancerous tumors that have spread, chemotherapy may be needed.
• Radiation: Some tumors, including those on the pituitary gland, may not be treatable surgically. In these cases, radiation can help shrink or get rid of them.

Unmanaged Cushing’s syndrome can lead to complications, such as:

• Heart attack or stroke
• Unhealthy cholesterol levels
• Blood clots in the legs and lungs
• Infection
• Bone loss and fractures
• High blood pressure
• Insulin resistance or type 2 diabetes
• Depression or changes in mood
• Memory loss or trouble concentrating
• Low levels of potassium in your blood

If Cushing’s syndrome is treated properly, it may be cured in two to 18 months. If left untreated, the condition can be fatal. If you are experiencing any signs or symptoms of the disorder, see your healthcare provider. You may be referred to a specialist called an endocrinologist who is trained to diagnose and treat hormone-related conditions and diseases.