The Dexamethasone Suppression Test for Cushing Syndrome

What Is an Overnight Dexamethasone Suppression Test?

The Dexamethasone Suppression Test for Cushing Syndrome

Some illnesses have clear signs that tell you what they are, the bull’s-eye rash of Lyme disease or the high-pitched whoop of whooping cough. But others, such as Cushing syndrome, make you work to figure it out.

When you have Cushing syndrome, you have high levels of cortisol. That’s a hormone made by your adrenal glands. It affects everything from blood pressure to memory.

The challenge with Cushing syndrome is that the signs and symptoms can look a lot many other diseases. So doctors typically do more than one test to make sure you have it.

One of those tests has a mouthful of a name — it’s an “overnight dexamethasone suppression test.” It can help you learn whether you have Cushing syndrome and what’s causing it if you do.

You get this syndrome when you have high levels of cortisol for a long time. It can cause weight gain, thining skin, easy bruising, and other issues. Longer term, it can lead to conditions such as:

  • Type 2 diabetes
  • High blood pressure
  • Bone loss (osteoporosis)

When your body makes too much cortisol, it’s often because of a tumor. In some cases, these tumors are cancerous, but usually they’re not.

A tumor on your pituitary gland is the most common one that causes Cushing syndrome. It’s not cancer, but it causes the pituitary to make too much adrenocorticotropic hormone (ACTH), which controls how much cortisol your body makes. More ACTH means more cortisol.

Adrenal tumors are the second most common cause of Cushing syndrome. The may or may not be cancerous.

You can also get tumors on other organs where the tumor itself makes ACTH. This is called an ectopic ACTH-secreting hormone. Again, it leads to too much cortisol.

Dexamethasone is a manmade version of cortisol. After you take a dose of it, your body should make less cortisol. That’s the idea behind the test — take some dexamethasone and see whether your cortisol level drops. Usually, the test is done overnight, but it can also be done over 2 days.

There are two doses you can take for the test: low dose and high dose. The low-dose test helps you find out if you have Cushing syndrome or not. You typically get 1 mg of dexamethasone.

You’d get the high-dose test once you know you have Cushing syndrome. It’s done to find out whether it’s caused by a tumor on your pituitary gland. The high dose is typically 8 mg.

You’d get this test if you show signs and symptoms of Cushing syndrome, bruising easily, weight gain around your belly, and a very round face. Your doctor might also order this test if you have problems that aren't typical for your age but could mean you have Cushing syndrome: For example, if you’re young but have weak bones (osteoporosis), high blood pressure, or diabetes.

This test isn’t ideal for everyone. For example, pregnancy and seizure medicines can both affect your results, so you’d ly get one of the other tests for Cushing syndrome.

Your doctor may tell you to avoid taking any food or drink 10 to 12 hours before the morning blood test, but that’s about it.

Make sure to tell your doctor about any medicines and supplements you’re taking — some medications, such as birth control pills and seizure medicine, can affect your results.

Between 11 p.m. and midnight the night before, you’ll take the dexamethasone. That’s all you need to do until the next morning. Between 8 a.m. and 9 a.m., you’ll get a blood draw to measure your cortisol level.

A blood draw takes just a few minutes. Your doctor will:

  • Clean the skin where the needle goes in
  • Wrap a rubber strap around your upper arm — this creates pressure to make your veins swell with blood
  • Put a thin needle into a vein, usually on the inside of your arm at your elbow or in the back of your hand
  • Draw the blood
  • Remove the rubber strap and put a bandage on your arm or hand

Results can vary with different labs, so be sure to talk to your doctor to learn exactly what your numbers mean and what your next steps are.

For a low-dose test, a healthy cortisol level is below 1.8 mcg/dL (micrograms per deciliter) or 50 nmol/L (nanomoles per liter). These two numbers say the same thing, they just have different units — just 12 inches is the same as 1 foot. If your result is higher than that, there’s a good chance you have Cushing syndrome. If it’s lower, something else may be triggering high cortisol levels.

For a high-dose test, your doctor looks for a 50% drop in cortisol. If your level drops, it’s ly that a pituitary tumor is causing Cushing syndrome. If your level doesn’t drop, you may have a tumor somewhere else.

You may get other tests to check for Cushing syndrome and what’s causing it, such as:

  • Corticotrophin releasing hormone (CRH) stimulation test to learn more about the possible causes of Cushing syndrome
  • Imaging, such as CT or MRI, to look for tumors
  • Late-night saliva cortisol or 24-hour urine free cortisol tests to check cortisol level
  • 24-hour urinary cortisol excretion test


CDC: “Lyme Disease,” “Pertussis (Whooping Cough).”

Hormone Health Network: “Diagnosis of Cushing Syndrome,” “What Does Cortisol Do?”

Lab Test Online: “Cushing Syndrome.”

UpToDate: “Dexamethasone Suppression Tests.”

Mayo Clinic: “Cushing Syndrome.”

Dartmouth-Hitchcock: “Dexamethasone Suppression Test.”

KidsHealth: “Blood Test: Partial Thromboplastin Time (PTT).”

University of Rochester Medical Center: “Activated Partial Thromboplastin Clotting Time.”

American Board of Internal Medicine: “ABIM Laboratory Test Reference Ranges ̶ August 2018” (pdf).

© 2019 WebMD, LLC. All rights reserved.


What You Should Know About the Dexamethasone Suppression Test

The Dexamethasone Suppression Test for Cushing Syndrome

You may have been told that you need to have a dexamethasone suppression test if your doctor suspects you have a condition known as Cushing's syndrome. The test evaluates your body’s ability to respond normally to a type of hormone known as glucocorticoids. A dexamethasone suppression test can help your doctor diagnose Cushing's syndrome, or eliminate it as a possibility.

To more deeply understand the purpose of the dexamethasone suppression test, you have to first learn about glucocorticoids and how they are regulated in your body. 

Glucocorticoids are a group of compounds all with similar chemical structures and similar characteristics. They are members of a larger class of hormones called steroid hormones and members of a smaller steroid group called corticosteroids.

Glucocorticoids bind to glucocorticoid receptors, which are found in many cells in the body.

There, they have many different effects, including influencing how your body uses nutrients, modulating the immune system, and helping your body deal with stress.

Cortisol is a type of glucocorticoid naturally produced in your body by the adrenal gland (near the kidneys). Dexamethasone is another type of glucocorticoid that is very similar to cortisol in structure. However, it is made synthetically and not found naturally in the body. Various glucocorticoids are also sometimes given as medical treatments.

Your body works to maintain a balance of glucocorticoids in the body. That’s important because either too much or too little can cause problems.

The pituitary gland (found at the base of the brain) helps regulate how much cortisol is produced. It produces another hormone called ACTH. This hormone travels through the bloodstream and signals your adrenal gland to produce cortisol.

Various factors control how much ACTH the body produces. Normally, high amounts of cortisol will travel back in the bloodstream to the pituitary gland and inhibit the release of ACTH. In other words, because cortisol is already high, the body downregulates the secretion of ACTH. That helps prevent cortisol levels from getting too high in the body.

Normally, cortisol levels should also decrease if the body is exposed to another corticosteroid ( dexamethasone). The dexamethasone travels to the pituitary and causes the pituitary to downregulate the secretion of ACTH. That leads to lower secretion of cortisol and lower levels of cortisol in blood tests. If that doesn’t happen, it’s a sign of some sort of problem in the body.

Cushing's syndrome describes a group of related medical conditions.

Cushing's syndrome occurs when the body is exposed to abnormally high levels of glucocorticoid hormones over a prolonged period.

That leads to the symptoms of Cushing's syndrome, which can include abdominal obesity, rounding of the face, elevated blood pressure, muscle weakness, increased blood glucose levels, and others.

The most common medical cause of Cushing's syndrome is a specific subtype: Cushing's disease. These sound very similar, but not everyone with “Cushing's syndrome” has “Cushing's disease.

” Cushing's disease is caused specifically by a pituitary adenoma (a tumor that arises from the pituitary gland). This can cause the pituitary to release abnormally high amounts of ACTH and not respond to feedback in the right way.

So, the adenoma might continue releasing ACTH even when the body is exposed to the glucocorticoid dexamethasone.

Cushing's syndrome also has other causes. For example, it can also occur when a person is given large doses of corticosteroids as a medical treatment.

A variety of other problems can either cause the body to make too much ACTH (and therefore too much cortisol) or make too much cortisol even if ACTH is not high. Many of these types of Cushing's syndrome arise from specific kinds of cancer.

For example, certain kinds of lung cancer or cancer of the adrenal glands can lead to Cushing's syndrome.

If you are diagnosed with Cushing's syndrome, your doctor may need to do other tests to find out the exact cause of your problem. This might be Cushing's disease (from a pituitary adenoma) or it might have another source. There are various types of treatment available, depending on the source of the disease.

You might need a dexamethasone suppression test if you have some of the symptoms of Cushing's syndrome and your doctor wants to screen you for the disease. The test can be used to help diagnose the disease or help eliminate it as a possibility.

Many of the symptoms of Cushing's disease ( high blood pressure) are quite common in people who don’t have the disease. The dexamethasone suppression test can help pick out people who are having symptoms because of Cushing's syndrome. Your regular doctor or an endocrinologist might first suggest the test.

In some cases, the dexamethasone suppression test can be used if you already know you have Cushing's syndrome but your doctor is trying to figure out the exact source of your problem.

In some cases, yes. If your doctor is worried about the possibility of Cushing's syndrome, you might be able to have a test that assesses the cortisol in your saliva. Or you might be able to have a test in which you assess the amount of cortisol in your urine over a 24-hour period. You can talk to your doctor about these other possibilities.

The dexamethasone suppression test is generally a very safe test for most people. It can be given to pregnant women and people with many different health conditions. The low dose version of the test, in particular, is very unly to cause any problems. However, be sure to discuss all of your health conditions with your health provider before you have the test. 

The dexamethasone suppression test is relatively simple to perform. It does not require medical imaging.

In the test, a person takes a dose of dexamethasone orally at a specific time. Often, this can be done as an outpatient. Usually, there are no special preparations to make ahead of time. You can eat and drink normally unless your doctor tells you otherwise. Many people don't notice anything at all, or you might experience a mild response to the dexamethasone, a headache.

The dexamethasone acts in the body very similarly to cortisol. After a period of time (often overnight), the amount of cortisol in your body is assessed. This could be through blood or urine samples taken once or a few times, so you might come into an outpatient clinic to have your blood drawn. The sample is then analyzed for the amount of cortisol.

In a normal person, the pituitary gland responds to the extra dexamethasone by decreasing the secretion of ACTH. This decreases the amount of cortisol found in the blood or urine. If cortisol doesn’t decrease as much as expected, then the patient may have a form of Cushing's syndrome.

In some versions of the test, you might need to take multiple doses of dexamethasone. Your doctor can let you know what to expect in your particular situation.

In the high-dose dexamethasone suppression test, you receive a higher amount of dexamethasone. In the low-dose version of the test, you would receive a somewhat lower dose.

Typically, the low-dose test is the version given if Cushing's syndrome is suspected. For example, with a low-dose test, people with all different types of Cushing's syndrome will show no suppression of cortisol (e.g., cortisol will be higher than it is in normal people). That’s why it is often used as an initial screening test.

The high-dose test is more ly to be given if Cushing's syndrome has already been diagnosed, to help identify the specific cause of the problem. With a high-dose test, people with different types of Cushing's syndrome can have different responses. This can help doctors tease apart the underlying cause of your Cushing's syndrome.

There are several existing protocols for the dexamethasone suppression test. Both the low dose and the high dose version can be given either overnight (more commonly) or as part of a two-day test.

There generally aren't any special precautions to follow after having your dexamethasone suppression test.

There can be side effects from receiving high doses of corticosteroids over the long-term. However, in the most common version of the test, you receive only a single low dose of dexamethasone. In this case, you are unly to experience side effects.

If present, they are ly to be mild and temporary (e.g., poor sleep the night of the test, headache), and they are ly to go away without intervention. If you have severe symptoms such as chest pain, contact a healthcare professional right away.


Because the dexamethasone suppression test most often relies on a simple blood test of cortisol levels, results are usually available relatively quickly. 

Healthy people show suppression of cortisol release as part of the dexamethasone suppression test.

That is, in response to the dexamethasone which they receive, their body downregulates the amount of cortisol it releases.

In people with Cushing's syndrome, there is no suppression of cortisol or only limited suppression. Cortisol levels remain high, even though the body received a dose of the dexamethasone. 

Interpreting the results of the dexamethasone suppression test can be complicated. Exact levels of cortisol will vary the version of the test you have. However, for the low-dose overnight version of the test, serum cortisol of fewer than 1.8 micrograms per deciliter is considered normal.

Yes. A false positive might happen when a person’s cortisol does not appear to go down normally, but they don’t really have Cushing's syndrome. This might happen, for example, with:

  • Women taking contraceptive medications
  • People taking certain other medications ( phenytoin)

Other times, the test might have a false negative. In other words, the person might really have Cushing's syndrome, but the test doesn’t pick it up. For example, this might happen, for example, with:

  • People with kidney problems
  • People with liver problems
  • People taking other medications ( fluoxetine and certain HIV medications)

You also might have incorrect results if you don’t follow the instructions correctly. For example, it is important to take the dexamethasone at exactly the time that your doctor instructs, or you can have incorrect results. Be sure to talk to your doctor about all your medications before you have your test. That will help make sure that your test can be interpreted correctly. 

You might need other tests after having a dexamethasone suppression test, especially if your test result is abnormal. Cushing's syndrome can be challenging to diagnose. Even once you are diagnosed with Cushing's syndrome, your doctor might request follow-up tests to diagnose the specific cause. Some additional tests you might need include:

  • CT scan of the abdomen
  • Salivary tests for cortisol
  • Blood tests ( for levels of ACTH)
  • MRI of the brain
  • Repeat low-dose dexamethasone test
  • High-dose dexamethasone test (after an initial low-dose test)

The dexamethasone suppression test is generally a very safe test that requires little preparation on your part. You should be able to discuss the results of your test relatively soon.

If you have Cushing's syndrome, your doctor may need to do follow up tests to evaluate the cause.

Though it can be anxiety-provoking to wait for your results, know that there are many people available to help you through your potential diagnosis and beyond.


Diagnostic Testing for Cushing’s Syndrome

The Dexamethasone Suppression Test for Cushing Syndrome

By Dr. James Findling, Spring, 2014

A screening laboratory evaluation for Cushing’s syndrome should be considered in any patient with signs and symptoms of excessive cortisol secretion. Abnormal weight gain, particularly in the central part of the body, accompanied by hypertension, diabetes, or hyperlipidemia should signal the possibility of Cushing’s syndrome.

Many patients with this disorder will also have facial rounding with the so-called “moon facies.” Accumulations of fat above the clavicles or behind the neck are also common features of excessive cortisol secretion. Some patients will also present with osteoporosis and some have muscle weakness.

The presence of wide purplish striae (stretch marks) in the abdomen or elsewhere can also be a symptom of Cushing’s syndrome. The majority of patients with Cushing’s syndrome have some type of neuropsychiatric problem (particularly depression) or even some cognitive impairment. Fatigue is almost always present in patients with Cushing’s usually related to very poor sleep quality.

Mild Cushing’s syndrome is sometimes detected in patients in whom an adrenal nodule is incidentally discovered during CT imaging of the abdomen.

The diagnostic approach to patients with suspected Cushing’s syndrome has been published in an evidence-based guideline by the Endocrine Society.

Three diagnostic studies are currently recommended: late-night salivary cortisol, 24 hour urine free cortisol, low-dose dexamethasone suppression.

If any of these tests is abnormal, a referral to an endocrinologist is strongly encouraged. These three tests are summarized in Figure 1.

Perform 1 or 2 of the following studies
11 pm Salivary CortisolNormal range varies depending on the laboratory used. Most reference labs in the US report a normal range of less than 3.0-4.0 nmol/L or 0.10-0.15 ug/dL24-hour Urine Free Cortisol(normal < 40 – 50 ug/d)Upper limits of normal may also vary depending on the laboratory used.Overnight 1 mg Dex Suppression(normal < 1.8 ug/dl)1mg dexamethasone at 2300, obtain serum cortisol before 0900 the following day
NormalDx probably excludedRepeat if high index of suspicionAbnormalConsult Endocrinologist

Late-Night Salivary Cortisol

Late-night salivary cortisol is one of the most sensitive diagnostic tests for Cushing’s syndrome. Elevated cortisol between 11:00 p.m. and midnight appears to be the earliest detectable abnormality in many patients with this disorder.

Cortisol secretion is usually very low at this time of the day, but in patients with Cushing’s syndrome, the value is usually elevated.

It is the most widely studied single test for the diagnosis of Cushing’s syndrome with many studies from all over the world demonstrating a sensitivity of 93-100% for the diagnosis of Cushing’s syndrome; however, all the tests for Cushing’s syndrome there are many things which may cause a false positive result and additional testing is always needed. Collection of saliva requires special sampling tubes; however, this is a very easy test for patients to perform and can be done on multiple occasions. Salivary cortisol is very stable at room temperature and the samples can actually be mailed to a reference laboratory. This test is now widely available. Normal levels of late-night salivary cortisol usually exclude the diagnosis of Cushing’s syndrome due to an ACTH secreting tumor; however, some patients with Cushing’s caused by an adrenal tumor will have normal late-night salivary cortisol levels.

Urine Free Cortisol

Urine free cortisol has been used for many years for the diagnosis of Cushing’s syndrome. A 24 hour urine free cortisol level does reflect the cortisol secretion throughout an entire day.

Although the majority of patients with Cushing’s have elevated levels of urine free cortisol, it is becoming increasingly evident that many patients with mild Cushing’s syndrome will actually have normal levels of urine free cortisol.

It is estimated that 20-25% of patients with Cushing’s syndrome may have a normal urine cortisol. In other words, a normal 24 hour urine free cortisol does not exclude the diagnosis of Cushing’s syndrome and additional testing is usually needed.

In addition, there are many conditions which may increase urine free cortisol that are not Cushing’s syndrome including depression, chronic alcoholism, and eating disorders.

Low-Dose Dexamethasone Suppression Testing

The low-dose dexamethasone suppression testing has been used for four decades as a diagnostic tool in the evaluation of patients with suspected Cushing’s syndrome.

Dexamethasone is a synthetic steroid that should suppress the cortisol production in normal subjects to a very low level. Currently, the most widely used test is the administration of a small dose of dexamethasone (1 mg) at 11:00 p.m.

followed by a measurement of serum cortisol early the following morning. Normal subjects should suppress their cortisol level to a very low level (


Vanderbilt Pituitary Center – Dexamethasone Suppression CRH Stimulation Test – Vanderbilt Health Nashville, TN

The Dexamethasone Suppression Test for Cushing Syndrome

Dexamethasone suppression tests have been used for more than 30 years in the evaluation of patients with Cushing's syndrome. It was Dr. Grant Liddle of Vanderbilt who first reported on the usefulness of the classical test in 1960.

The adrenal glands produce cortisol, the major glucocorticoid hormone, in response to signals provided by the pituitary gland. Dexamethasone is a synthetic glucocorticoid hormone. In normal subjects, daily doses of Dexamethasone in excess of 0.5-0.

75 mg, can suppress the coordinated functions of the hypothalamus pituitary and adrenal glands. In patients with Cushing's disease, Dexamethasone often fails to suppress the function of the hypothalamus, pituitary, and adrenal glands.

These observations form the basis for the five different Dexamethasone suppression tests:

  • Overnight 1 mg low dose Dexamethasone Suppression Test
  • Formal low dose Dexamethasone Suppression Test
  • Dexamethasone-Suppressed CRH Stimulation Test
  • Overnight high dose 8 mg Dexamethasone Suppression Test
  • Formal two-day high dose Dexamethasone Suppression Test

Overnight 1 mg low dose Dexamethasone Suppression Test
This test is a reasonable screening test for Cushing's syndrome. Dexamethasone 1.0 mg should be taken by mouth at 11:00 PM.

A snack can be consumed with the medication.

The patient then reports to the specified laboratory or physician's office at 8:00 AM the very next morning so that a sample of blood can be drawn in order to determine the serum cortisol level.

Formal low dose Dexamethasone Suppression Test
This procedure is often used in the diagnosis of Cushing's syndrome.

Proper performance of the test requires proper timing and collection of urine samples as well as the ingestion of Dexamethasone at specified time intervals.

Your physician may request that you collect several “basal” (or baseline) 24-hour urine samples for determination of:

  • free cortisol
  • 17-hydroxycorticosteroids
  • creatinine

The test begins on day one with the administration of the first 8 doses of Dexamethasone. You may be asked to take the first dose at 6:00 AM.

If so, subsequent doses should be at 12:00 Noon, 6:00 PM, and 12:00 Midnight on day one, and then 6:00 AM, 12:00 Noon, 6:00 PM, and 12:00 Midnight on day 2. You may be asked to begin the medication at some other time.

If so, you will be given explicit guidelines so that you understand when to take the subsequent doses of the medication. The most important thing to remember is that the medication should be taken every 6 hours for a total of 8 doses.

You should begin the 24-hour urine collection at 6:00 AM on day 2, coinciding with the 5th dose of the medication. Then complete the urine collection on 6:00 AM on day 3.

Please review the instructions for the 24-hour urine collection. Contact your physician if you have any questions.

Dexamethasone-Suppressed CRH Stimulation TestThis test is often used in the diagnosis of Cushing's syndrome. It is rather unique because it combines suppression and stimulation of the pituitary gland. It does this to gain additional information about the altered functions of the hypothalamus, pituitary, and adrenal glands in patients with probable Cushing's syndrome.

A formal low dose Dexamethasone suppression test is performed as specified above, except that a 9th dose of Dexamethasone is taken at 6:00 AM on day 3. You should report to your physician's office by 8:00 AM for a CRH Stimulation Test on day 3. This test involves placement of an i.v.

, followed by injection of the hypothalamic hormone CRH, then sampling of blood for cortisol 15 minutes later.

Overnight high dose 8 mg Dexamethasone Suppression Test
This test is often used in the differential diagnosis of Cushing's syndrome. It can help distinguish between Cushing's syndrome caused by pituitary tumors and non-pituitary tumors.

You should report to the specified laboratory or other location to have blood drawn. This blood will be tested to measure serum cortisol and ACTH at 8:00 AM on day 1. Then, take Dexamethasone, 8 mg., by mouth at 11:00 PM on day 1.

Return to the same facility at 8:00 AM on day 2 to have another blood sample drawn for measurement of serum cortisol and ACTH.

Formal two-day high dose Dexamethasone Suppression Test
This test is often used in the differential diagnosis of Cushing's syndrome. It has largely been replaced by the high dose 8 mg overnight Dexamethasone suppression test (described above). The schedule is as follows:

  • Day 1: Begin a 24-hour urine collection at 6:00 AM.
  • Day 2: Finish the first urine collection at 6:00 AM and start the second 24-hour urine collection.
  • Day 3: Finish the second 24-hour urine collection at 6:00 AM and start the third collection. Start Dexamethasone 0.5 mg. at 6:00 AM and take subsequent doses at 12:00 Noon, 6:00 PM, and 12:00 Midnight.
  • Day 4: Finish the third 24-hour urine collection at 6:00 AM and start the fourth collection. Continue Dexamethasone 0.5 mg. at 6:00 AM, 12:00 Noon, 6:00 PM, and 12:00 Midnight.
  • Day 5: Complete the fourth 24-hour urine collection at 6:00 AM and start the fifth collection. Begin Dexamethasone 2.0 mg. at 6:00 AM and take subsequent doses at 12:00 Noon, 6:00 PM, and 12:00 Midnight.
  • Day 6: Finish the fifth 24-hour urine collection at 6:00 AM and begin the sixth collection. Continue Dexamethasone 2.0 mg at 6:00 AM, 12:00 Noon, 6:00 PM, and 12:00 Midnight.
  • Day 7: Complete the sixth 24-hour urine collection at 6:00 AM. Transport the specimens to the designated facility for testing.

You should make sure that all collection bottles are labeled with your name and start date of the collection. As an extra precaution, it's a good idea to indicate the day of the collection (day 1, day 2, etc.)


Dexamethasone Suppression Test: Reference Range, Interpretation, Collection and Panels

The Dexamethasone Suppression Test for Cushing Syndrome

Dexamethasone is a synthetic glucocorticoid that does not interact with cortisol measurement. [2, 3, 4, 5]

Low-dose dexamethasone suppression tests

In a subject with a normal hypothalamic–pituitary–adrenal (HPA) axis, a supraphysiological dose of dexamethasone can inhibit ACTH secretion by the pituitary leading to drop in cortisol level in serum, urine and saliva; such inhibition does not occur in patients with Cushing syndrome.

  • Overnight suppression test: Administer 1 mg oral dexamethasone between 11 pm and midnight. Test cortisol level between 8 am and 9 am the next morning.

  • Standard 2-day dexamethasone suppression test: Administer 0.5 mg oral dexamethasone every 6 hours for 48 hours (9 am, 3 pm, 9 pm, and 3 am). Measure cortisol level 6 hours (9 am) after the last dose. Other protocols suggest starting dexamethasone 0.5 mg orally every 6 hours starting at noon for 48 hours and checking cortisol level 2 hours (8 am) after the last dose.

The 24-hour urine free cortisol test may be used during the second day of the standard test as an end point; however, data suggest that serum cortisol has higher diagnostic accuracy and conducting both tests is not recommended. [6]

High-dose dexamethasone suppression test

In subjects with Cushing disease, a higher dose of dexamethasone (usually 8 mg) is required to suppress ACTH secretion and drop cortisol level in serum, urine, and saliva.

  • Standard 2-day dexamethasone suppression test: Serum cortisol level and/or 24-hour urinary free cortisol is measured as a baseline, and then dexamethasone 2 mg orally is taken every 6 hours for 48 hours; urine for free cortisol is collected during the test and serum cortisol is checked 6 hours after the last dose.

  • Overnight suppression test: Serum cortisol is checked at baseline, then dexamethasone (typically 8 mg) is given orally between 11 pm and midnight. Cortisol level is then checked between 8 am and 9 am the next morning.

  • Intravenous dexamethasone suppression test: Serum cortisol is checked at baseline, followed by continuous infusion of intravenous dexamethasone at a rate of 1 mg/h for 5-7 hours.

The low-dose dexamethasone suppression test is one of the screening tests for Cushing syndrome.

Four highly sensitive tests are recommended by the Endocrine Society for the screening of Cushing syndrome: 24-hour urinary free cortisol, late-night salivary cortisol, overnight dexamethasone suppression test, and sta  ndard 2-day dexamethasone suppression test.

[7] If Cushing syndrome is suspected, the physician should perform at least two 24-hour urinary free cortisol tests, at least 2 late-night salivary cortisol tests, or one dexamethasone suppression test. If this initial evaluation is positive, then another set of tests should be performed.

The high-dose dexamethasone suppression test is used in patients with confirmed Cushing syndrome when further workup is needed to identify the etiology.

The first step is to differentiate between ACTH-dependent Cushing syndrome (ectopic ACTH and Cushing disease) and ACTH-independent Cushing syndrome (adrenal disorders).

Once the Cushing syndrome is confirmed to be ACTH-dependent, a high-dose dexamethasone suppression test is performed to differentiate between Cushing disease (suppression) and ectopic ACTH.

The causes of ACTH-dependent Cushing syndrome are as follows:

The causes of ACTH-independent Cushing syndrome are as follows:

Pseudo-Cushing syndrome can occur as a result of the following conditions:

  • Depression, anxiety disorder, obsessive compulsive disorder

  • Poorly controlled diabetes mellitus

These conditions can overactivate the HPA axis, causing a physiological increase in circulating cortisol and leading to erroneous dexamethasone suppression test results and/or elevated 24-hour urinary free cortisol levels suggestive of Cushing syndrome.

The standard 2-day low-dose dexamethasone suppression test followed by corticotropin-releasing hormone (CRH) was designed to differentiate between Cushing syndrome and pseudo-Cushing syndrome.

The test is performed by administering 0.5 mg dexamethasone orally every 6 hours for 48 hours followed by IV CRH (1µg/kg) 2 hours after the last dose of dexamethasone; then cortisol level is measured about 15 minutes after IV CRH administration. Patients with Cushing syndrome do not suppress, whereas patients with pseudo-Cushing syndrome do suppress their cortisol level.

According to The Endocrine Society, this test can be useful in patients with equivocal 24-hour urinary free cortisol results, and a dexamethasone level should be measured at the time of CRH administration to exclude a false-positive result. [7]