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The Dexamethasone Suppression Test for Cushing Syndrome

Written by Puya Yazdi, MD | Last updated:
Jonathan Ritter
Medically reviewed by
Jonathan Ritter, PharmD, PhD (Pharmacology) | Written by Puya Yazdi, MD | Last updated:

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dexamethasone suppression test

If you suffer from high cortisol levels, your doctor may ask you to do a dexamethasone suppression test. But what is that, and how is the test performed? Read on to learn what to expect, and how to prepare for the test.

What is Dexamethasone?

Dexamethasone is a corticosteroid, a drug that acts similarly to the stress hormone cortisol [1].

Cortisol is released from the adrenal gland in response to stressful events. It promotes energy production so that an animal (or a human) can stay in a state of high alert for a period of hours or even days [2, 3].

Cortisol is also required to maintain blood sugar at normal, healthy levels [2].

Dexamethasone is a synthetic hormone closely related to cortisol. Like other corticosteroids, it reduces inflammation and dampens the immune system. It is most often used to treat diseases caused by an overactive immune system, including rheumatoid arthritis, inflammatory bowel disease, asthma, allergies, and others [1, 4, 5].

However, dexamethasone has another interesting application: it can be used to evaluate the body’s ability to regulate cortisol.

Why the Dexamethasone Suppression Test?

How Does it Work?

This test measures whether your ACTH levels respond to steroid signals. If the pituitary gland works correctly, it should turn down (suppress) the release of ACTH when you receive dexamethasone. This will subsequently reduce the release of cortisol [6].

In healthy people, the pituitary gland senses when cortisol rises and consequently turns down the release of ACTH. But, in people with certain health conditions, this doesn’t happen. Instead, the pituitary keeps pumping out ACTH, which stimulates the adrenal glands to keep producing cortisol [7].

Cushing Syndrome

In a condition known as Cushing syndrome, the body produces too much cortisol. It is most often caused by a tumor, usually in the pituitary gland. The pituitary tumors release far too much adrenocorticotropic hormone (ACTH), which then stimulates the release of cortisol from the adrenal gland [8].

Over a period of months or years, elevated cortisol causes the classic symptoms of Cushing syndrome, including [9, 10]:

  • Round face (moon face)
  • Fatty pad on the neck (buffalo hump)
  • Thin arms and legs
  • Fat gain around the waist
  • Thin skin, stretch marks
  • Type 2 diabetes
  • High blood pressure
  • Increased cholesterol and triglycerides
People with Cushing syndrome produce too much cortisol, often due to a pituitary tumor.

Chronic Fatigue Syndrome

While Cushing syndrome is the most common clinical application of the dexamethasone suppression test, it has more recently been used to try to identify chronic fatigue syndrome or even depression.

Chronic fatigue syndrome (or CFS) is a poorly-understood and often controversial condition that causes a person to be exhausted to the point of disability. People with CFS often have difficulties just getting out of bed and completing everyday tasks like eating and showering. CFS sometimes causes joint pain and cognitive difficulties as well [11].

Some researchers believe that people with CFS may have prolonged suppression of cortisol in response to dexamethasone; where people with Cushing have unusually high cortisol, people with CFS may have unusually low cortisol for a long time after the dexamethasone challenge [12, 13].

People with chronic fatigue syndrome may not produce enough cortisol; in clinical studies, their suppression response to dexamethasone lasted longer than normal.

Depression

Many cases of depression may be caused by long-term stress, which in turn causes elevated cortisol. For several decades, researchers investigated the link between cortisol and depression; they found that people with a poor response to the dexamethasone suppression test were less likely to respond to antidepressants and talk therapy [14].

The relationship between dexamethasone suppression and depression appears to be complex. Some depressed people have abnormal suppression responses, while others seem healthy [15].

Future studies will probably shed more light on how cortisol contributes to depression and whether the dexamethasone suppression test is helpful in its diagnosis. For the time being, this test is not used to detect mental illness because the results cannot be consistently mapped to cases of depression.

Some cases of depression are probably caused by long-term stress, which may involve chronically high cortisol levels. The relationship between cortisol and depression is complex and poorly understood.

How to Prepare for the Test

Your doctor may instruct you to stop taking certain medicines before the test. These include [6]:

  • Antibiotics
  • Anti-seizure drugs
  • Corticosteroids (e.g. hydrocortisone, prednisone)
  • Estrogen
  • Birth control pills
  • Diuretics

Be sure to follow your doctor’s instructions precisely on the day of the test to avoid any inaccurate results.

How the Test is Performed

There are a few different ways of performing the dexamethasone suppression test. Most commonly, you will receive 1, 1.5, or 2 mg of dexamethasone orally between 11:00 pm and 12:00 am. Your blood will then be drawn and cortisol measured between 8:00 am and 9:00 am the following morning.

What do the Results Mean?

In healthy patients, dexamethasone suppresses morning cortisol to below 1.8 μg/mL. If your cortisol levels are higher in the morning after receiving dexamethasone, the test is positive for Cushing syndrome [16].

Other Tests Your Doctor May Order

Usually, a few other tests are done to confirm the diagnosis of Cushing syndrome. These include [16]:

  • Free cortisol in the urine
  • Cortisol levels in blood or saliva
  • Blood ACTH levels

If the diagnosis is confirmed, CT or MRI scans may be conducted to check for tumors.

Takeaway

Dexamethasone is a synthetic steroid closely related to the stress hormone cortisol. In the dexamethasone suppression test, a health professional gives a person dexamethasone and measures whether the person’s pituitary gland stops producing cortisol in response.

Failure to suppress cortisol most often means that the person has Cushing syndrome, a condition that causes a typical round “moon face,” fatty hump on the back, and other signs of poor metabolism.

The dexamethasone suppression test may yet offer insights into chronic fatigue syndrome and depression, but we don’t yet fully understand the relationship between cortisol and these conditions.

About the Author

Puya Yazdi

Puya Yazdi

MD
Dr. Puya Yazdi is a physician-scientist with 14+ years of experience in clinical medicine, life sciences, biotechnology, and nutraceuticals.
As a physician-scientist with expertise in genomics, biotechnology, and nutraceuticals, he has made it his mission to bring precision medicine to the bedside and help transform healthcare in the 21st century.He received his undergraduate education at the University of California at Irvine, a Medical Doctorate from the University of Southern California, and was a Resident Physician at Stanford University. He then proceeded to serve as a Clinical Fellow of The California Institute of Regenerative Medicine at The University of California at Irvine, where he conducted research of stem cells, epigenetics, and genomics. He was also a Medical Director for Cyvex Nutrition before serving as president of Systomic Health, a biotechnology consulting agency, where he served as an expert on genomics and other high-throughput technologies. His previous clients include Allergan, Caladrius Biosciences, and Omega Protein. He has a history of peer-reviewed publications, intellectual property discoveries (patents, etc.), clinical trial design, and a thorough knowledge of the regulatory landscape in biotechnology.He is leading our entire scientific and medical team in order to ensure accuracy and scientific validity of our content and products.

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