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 then 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 include [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 may also help identify chronic fatigue syndrome or even depression.

Chronic fatigue syndrome (or CFS) is a poorly-understood disorder 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].

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; their suppression response to dexamethasone likely lasts 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.

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 tell 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

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 11:00pm between 12:00am. Your blood will then be drawn and cortisol measured between 8:00am and 9:00am the next morning.

What do the Results Mean?

In normal 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 done to check for tumors.

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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 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

Jimmy Julajak, MSc

MS (Psychology)

Jimmy got his MSc from the University of Copenhagen.

Jimmy is a psychologist and researcher. He is particularly interested in the workings of the brain and strategies for improving brain health. He believes that people shouldn't hand over the responsibility for their health only to their doctors. His aim is to empower each person with easy-to-understand, science-based health knowledge.

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