AUA Summit - What is Cushing’s Syndrome?


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What is Cushing’s Syndrome?

Cushing’s syndrome (CS) is a rare problem caused when the adrenal gland(s) makes too much of a hormone called cortisol. CS is most often due to a tumor or mass found in the pituitary gland, but can also be caused by tumors in the adrenal glands themselves.

People with Cushing's syndrome may see their face get round ("moon face"), they gain weight in unusual ways, bruise easily or feel weak, tired and sad. Women and men may also notice fertility and other problems. CS is most often found in adults between the ages of 20 and 50.

What Happens Under Normal Conditions?

The adrenal glands are found above each kidney. They are triangle-shaped, and measure about half an inch in height and 3 inches in length. Each adrenal gland has 2 layers.

  • The adrenal medulla (inner part) makes epinephrine (also called adrenaline).
  • The adrenal cortex (outer part) makes steroid hormones (such as cortisone and aldosterone).

The adrenal glands control many processes in the body. Their job is to keep the body in balance by making various hormones that are critical for maintaining good health.

These hormones do many important things. For example, they help regulate fluid and salt levels in the body that affect blood volume and blood pressure. They also help the body react to stress and change. They cause a faster heart rate and boost other systems that help you to react quickly with a burst of energy when needed. Problems in the cortex or the medulla, then, can result in high blood pressure.

Cortisol levels are controlled by the pituitary gland, which is found at the base of the brain. The hypothalamus of the brain makes the corticotropin-releasing hormone (CRH). CRH tells the pituitary gland to release signals that control how much cortisol the adrenal glands make. The pituitary gland signal is called corticotropin or adrenocorticotropic hormone (ACTH).

The pituitary detects when cortisol levels are high enough, then it stops sending signals. This feedback system acts like a thermostat to balance cortisol levels. It is highly controlled system.


The signs of CS appear slowly over time. Some people may only have a few signs while others show greater changes. Common symptoms of CS are:

  • "Moon face" (round and full face)
  • "Buffalo hump" (fat bulge between the shoulders)
  • Gaining weight around your belly
  • Skin becomes thin. You may bruise easily and find pink or purple stretch marks on your belly
  • High blood pressure
  • High blood sugar
  • Fatigue and trouble sleeping (cortisol is released based on normal sleep patterns)
  • Mood swings and sadness
  • Lack of muscle strength (difficulty standing up from a seated position)
  • Bone density loss
  • Sexual abnormalities
  • More body hair
  • Menstrual changes in women
  • Women may also see their appearance change and become more masculine (virilization)

The signs of CS often appear slowly. A series of pictures of a person’s appearance may be the best way to show the changes.

Doctors sometimes describe patients with CS as having "Cushingoid" features. These features are also side effects of cortisone related drugs such as prednisone and prednisolone.


Benign Pituitary Tumor (Adenoma)

This is the most common cause of CS. Almost 75 out of 100 to 85 out of 100 all Cushing's syndrome cases are this type. Corticotropin (CRH) is normally made by the pituitary gland. It is a hormone that stimulates the adrenal gland to release cortisol, especially in times of stress. A pituitary tumor causes too much corticotropin (also called ACTH) to be made. ACTH is a kind of pituitary control switch that manages the growth and activity of the adrenal glands. Too much corticotropin causes the adrenal gland to make too much cortisol. Too much cortisol can cause CS.

Adrenal Tumor

This important cause of CS is when a tumor is found in the adrenal gland. The tumor may or may not be cancerous.

Ectopic (Abnormal) ACTH

This is when CS is caused by tumors that make ACTH in other organs. For example, tumors found in the chest on the lung or thymus can make ACTH.


Steroids that are used at high doses and for long periods of time may cause CS. For example, the use of prednisone.

It is normal to find high levels of cortisol in the body from stress. This does not lead to Cushing's syndrome.

In very rare cases, there is a hereditary link to an endocrine tumor that could cause CS. Most cases of CS are not passed down.


The signs are hard to see and may be masked by other health problems. You will need to see your health care provider to find out if CS is a possibility. A diagnosis is based on:

  • Your health history
  • A physical exam
  • Lab tests for cortisol levels

Dexamethasone Suppression Test

Dexamethasone (steroid) pill is given by mouth for this test. Then blood is collected to measure cortisol levels in the body. Normally, the extra steroid would make the body stop making cortisol. In a person with CS, the levels of cortisol will stay very high.

24-Hour Urinary Free Cortisol Test

Urine testing is sometimes used to test cortisol levels. Urine samples are collected for a full period of 24 hours, and tested. To diagnose adrenal problems, more tests would be needed.

Further Tests

Once CS has been diagnosed, imaging and other tests may be used to find the cause. Blood tests and imaging tests can find unwanted tumors. In blood tests, doctors will look for:

  1. Very low levels of corticotropin, which suggests an adrenal tumor. CT scan or MRI usually confirms the diagnosis.
  2. Slightly high levels of corticotropin, which suggests a pituitary tumor. MRI of the brain can often confirm this diagnosis. More tests may be needed if the pituitary tumor is too small to be seen with an MRI.
  3. Very high levels of ACTH suggest an ectopic ACTH. More tests would be needed to confirm this.

Imaging Tests

A CT scan or MRI can often find pituitary or adrenal tumors. These tests show different views of the body in detail. They are painless, accurate and quick.


Treatment depends on what is causing the excess cortisol. If the cause is from steroid use over time, your doctor may tell you to stop taking the drug or give you less. If the cause is a benign or cancerous adrenal tumor, you will need surgery to remove it.

If Caused by Steroid Use

Often, stopping the use of drugs like prednisone will allow the body to go back to normal. But, to cut or stop steroid use depends on the type of disease being treated and how your body reacts.

If Caused by a Pituitary Tumor

Pituitary tumors can be treated with surgery. Usually an operation can be done through the nose (transsphenoidal surgery) by a neurosurgeon.

If Caused by an Adrenal Tumor

Adrenal tumors can be removed by a urologist. When the adrenal tumor is small (less than 4-6 cm), the tumor is more likely not cancer. It can be removed with a small cut through laparoscopic or robotic surgery. Sometimes part of the adrenal gland is removed (a partial adrenalectomy) to leave the healthy portion of the gland behind. When laparoscopic surgery is not possible, an “open” operation is used. Open surgery is used for larger or more difficult tumors. If the mass is larger than 4-6 cm, it is more likely to be cancer. Nearby organs (the spleen, kidney or a part of the colon) may also need to be removed or reduced to remove the entire tumor.

After Treatment

How well you feel after treatment, is linked to the cause of excess cortisol. Treatment mostly helps patients feel better and can often cure the problem. In very rare cases of adrenal cancer, less than 50 out of 100 people will be cured. However, the most important thing to know is that treatment for an adrenal adenoma (non-cancerous tumor) is very successful.

Overall, the quality of life for a person with CS depends on:

  • How much extra cortisol is in your system
  • How long the disease has lasted
  • How healthy you are in general
  • How easily the type of CS can be cured

If CS is cured, all of the symptoms of the disease will go away. This may take as long as 2 to 18 months after treatment. The slow improvement can be hard to take, but you will feel better. As you improve, you will need frequent calls and visits to your health care provider.

If the CS is not curable, or if you still have CS from steroids, you may have to cope with the signs mentioned earlier. (Things like: fatigue, muscle weakness, abdominal and facial weight gain, depression, mood swings.) Drugs can help with these ongoing symptoms. You will need regular visits to your health care provider for exams, blood tests, and treatment of side effects.

After Adrenal Tumor Surgery

Most people feel better quickly after laparoscopic surgery. You can often leave the hospital within 1 or 2 days with no restrictions. Often patients feel back-to-normal in about 3 to 5 weeks. Recovery from open surgery will take longer. You may stay in the hospital between 5 and 10 days. Full healing takes up to 8 weeks.

When one adrenal gland gives off too much cortisol, the other gland may shut-down. After surgery, you may need steroids to avoid a deficiency while the gland recovers. This may take up to a year. Rarely the adrenal gland that shut-down won't recover. In this case, steroids may be needed as replacement therapy.

It's important to know that adrenal surgery is complex. It helps to choose a surgeon who has significant experience with surgery in the area around the kidneys and adrenal glands. Talk with a few surgeons before you choose one to work with.

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