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Cushing Syndrome

What is Cushing syndrome? 

Cushing syndrome is a rare hormonal disorder. It’s also called Cushing's syndrome or hypercortisolism. In people who have it, their bodies make too much cortisol. That’s a hormone that helps control blood sugar levels, regulate your metabolism, assist with memory function and regulate inflammation. It’s named after Harvey Cushing, a neurosurgeon who discovered the link between pituitary tumors and cortisol while operating on brain tumors.

According to the National Institute of Diabetes and Digestive and Kidney Diseases, Cushing syndrome affects 40 to 70 out of every million people each year. It’s usually diagnosed in people between the ages of 30 to 50, but can be found in people outside that range, including children. It’s three times more common in women than in men.

What causes Cushing syndrome?

Cushing syndrome develops when you have too much of the hormone cortisol in your body. Cortisol is often referred to as the stress hormone. That’s because your adrenal glands release it to help you cope with stress. Cortisol also helps regulate blood pressure and blood sugar, regulate inflammation, support your memory and convert food into energy.

Cushing syndrome risk factors include long-term use of high doses of corticosteroid medications, such as prednisone. These drugs are similar to cortisol. They are often used to treat asthma, lupus and rheumatoid arthritis. They are also used after organ transplants to help suppress the immune system. Injectable versions of these medications treat joint pain and bursitis. This type of Cushing syndrome is called exogenous Cushing syndrome, meaning it’s caused by factors that come from outside of the body.

Cushing syndrome can also occur if you have:

  • Pituitary tumor. This noncancerous tumor is also called a pituitary adenoma. It grows on the pituitary gland, which is a pea-sized gland that sits at the base of the brain. When a tumor growth happens, you make too much adrenocorticotropic hormone (ACTH). This hormone triggers cortisol production in the adrenal glands. These tumors are usually very small and can be hard to spot.
  • Ectopic ACTH-producing tumor. These tumors cause the same problem as pituitary tumors. But they occur in other parts of the body. They could be in the lungs, pancreas, thyroid or thymus. They may be cancerous.
  • Adrenal tumor. These tumors are usually not cancerous. They grow on the adrenal gland.

These types are called endogenous Cushing syndrome because they are caused by factors within the body. The symptoms of exogenous and endogenous Cushing syndrome are the same.

Cushing syndrome vs. Cushing disease – What’s the difference? 

Cushing disease is a form of Cushing syndrome. It’s the type that’s caused by a noncancerous (benign) pituitary tumor. 

What are the signs and symptoms of Cushing syndrome? 

Cushing syndrome can be hard to spot. Not everyone has symptoms. And some symptoms could be related to other conditions. For example, polycystic ovary syndrome (PCOS) and metabolic syndrome can have similar symptoms to Cushing syndrome. 

If you have high cortisol levels for a long period of time, you’ll probably notice some of these signs of Cushing syndrome:

  • Dark (purple) stretch marks on the torso or extremities
  • Weight gain or obesity, especially in center of the body, mainly abdomen 
  • Obesity with thin arms and legs
  • Fat between your shoulders or at the base of your neck, sometimes called a buffalo hump
  • Moon face (a round face)
  • Feeling tired and as though your muscles are weak
  • High blood pressure and blood sugar
  • Easy bruising
  • Depression or anxiety
  • Headache
  • Trouble thinking or concentrating
  • Irregular menstrual periods in women
  • Excess facial and body hair in women
  • Decreased sex drive or erectile dysfunction in men

What complications are associated with Cushing syndrome?

One of the dangerous things about this condition is that it can cause other serious health issues. People with Cushing syndrome can have complications including:

  • High blood pressure and cholesterol levels
  • Heart attack and stroke
  • Blood clots
  • Osteoporosis or bone loss or fractures
  • Infection
  • Mental illnesses or mental health disorders, like depression
  • Memory loss or trouble concentrating
  • Insulin resistance, pre-diabetes or type 2 diabetes

It can be fatal if left untreated because of the many complications it can cause to your body.

How to diagnose Cushing syndrome

Speak with your primary care doctor if you think you have Cushing syndrome. Treating it early is essential. That way, you can reduce your risk of complications and recover more quickly.

Your doctor or a health care professional such as an endocrinologist (a doctor who specializes in hormonal disorders) will perform a physical exam and review your medical history. If you’re taking medication that might be causing Cushing syndrome, you may not need additional testing. That’s because the medication is likely the cause.

If not, these tests can evaluate your cortisol levels for a Cushing syndrome diagnosis:

  • Urine test: This test is also called a 24-hour urinary free cortisol test. You collect your urine samples over 24 hours to measure cortisol in your urine. Your cortisol levels rise and fall during the day - they are usually lowest around midnight. To take the test, typically, you’ll urinate normally first thing in the morning without collecting a sample. Then, over the course of the day, you’ll collect samples of your urine and store them in a cool place. The next day, you’ll collect a sample of your urine first thing in the morning. Then you’ll drop off the samples as directed by your doctor.
  • Saliva collection: This test is usually done late at night. That’s because cortisol levels typically drop at nighttime, so cortisol levels that are high at this time of day can be a sign of Cushing syndrome. For this test, you’ll collect saliva in a special tube between at your bedtime. You may be able to mail your sample to a lab for evaluation of salivary cortisol.
  • Blood test: You can have your blood tested after taking dexamethasone. That’s a drug that suppresses cortisol production. You’ll take a pill at night, usually at 11pm, and then have your blood taken between 8 and 9 a.m. to check your cortisol levels. If tests show you have Cushing syndrome, your cortisol levels will still be high even after taking this medication to lower them. A high dose dexamethasone suppression test (DST) can determine whether it’s your pituitary gland or an ACTH secreting tumor that’s causing your problems.
  • Imaging studies. Your doctor may order an MRI or CT scan if they suspect a tumor on your pituitary or adrenal glands.
  • If you have excess cortisol, you may need another test called the dexamethasone-corticotropin releasing hormone (CRH) test (Dex-CRH). It can test cortisol levels to help determine if Cushing syndrome or something else is the cause.

If you’re diagnosed with Cushing syndrome, your doctor may recommend additional blood tests and imaging studies to find out what’s causing it. Blood tests can compare cortisol levels with ACTH levels. 

Treatments for Cushing syndrome

Treating Cushing syndrome can return your cortisol levels to normal and help alleviate your symptoms.

Treatment depends on what’s causing the condition. Treatment options for a tumor include medication, radiation, chemotherapy and/or surgery

  • Pituitary tumors are usually removed surgically. Surgery to remove a pituitary tumor is usually effective. If not, radiation therapy might also be an option.
  • Tumors that produce ACTH can also be surgically removed. For cancerous ACTH-producing tumors, you might also need chemotherapy or radiation.
  • For adrenal tumors, it’s common to remove the adrenal gland with the tumor. 

Your high cortisol levels might be due to steroid medications you’re taking. In that case, your doctor may try to adjust those medications or take you off them entirely. Sometimes, you only need these medications for a short time. And in some cases, other drugs can replace them. 

Medications such as ketoconazole, mitotane (Lysodren), levoketoconazole (Recorlev), metyrapone (Metopirone), pasireotide (Signifor) and osilodrostat (Isturisa) are also effective in lowering cortisol levels. Mifepristone (Korlym, Mifeprex) may be used in people who have type 2 diabetes or high blood sugar. It limits the effects cortisol has in the body. 

Medications are often options when surgery and radiation don’t work. They may also be used before surgery in people who are very sick with Cushing syndrome. These medications can have serious side effects that affect the brain, nervous system or liver. 

There’s no Cushing syndrome diet that can cure the condition. But you can choose foods that help keep your cortisol levels in check. Cushing syndrome can lead to high blood glucose levels, so good choices that keep blood glucose more stable include fish, nuts, berries and non-starchy vegetables. Limit alcohol, refined carbohydrates and sodium.