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Tests to diagnose Cushing's syndrome and Cushing's disease

Tests to diagnose Cushing's syndrome

It is important that the diagnosis of Cushing's syndrome is confirmed. First a doctor will test you for Cushing's syndrome. Once glucocorticoid medicines have been ruled out, there are 4 types of tests that are generally used to find out if you have Cushing's syndrome. These tests measure the amount of cortisol in samples of urine, blood, or saliva to determine how much cortisol is circulating in your body. If the tests show that the level of cortisol is too high, it means you have Cushing's syndrome.¹ If the test is not positive for high levels of cortisol, then signs and symptoms should be closely watched. If your symptoms get worse, check back with your doctor in 6 months.¹

In certain cases, doctors recommend specific types of tests based on a person's medical history. Some of these recommendations are included below.

Special recommendations for Cushing's syndrome diagnostic testing¹
If you …	UFC test	Late-night salivary cortisol	DST
Are pregnant	Yes	*	No
Are taking medicine for seizures (for example, phenobarbital, phenytoin, or carbamazepine)	Yes	Yes	No
Have kidney failure	No	*	Yes (1 mg overnight)
Have an adrenal mass	No	Yes	Yes (1 mg overnight)

UFC=urine-free cortisol; DST=dexamethasone suppression test; *=No recommendation stated.

Following are brief descriptions of tests that are used to diagnose Cushing’s syndrome. However, complete information about these tests, along with instructions for patients, should be obtained from your doctor.

Urine-free cortisol (UFC) test^1,2

What it measures:

Cortisol in urine

Why it's used:

Almost all people with Cushing's syndrome have high urine cortisol levels
The UFC test only measures the type of cortisol that causes Cushing's syndrome, called "circulating, free cortisol." It does not measure "bound" cortisol, which increases in the blood from taking certain medicines such as estrogen, but does not cause Cushing's syndrome

How it's done:

Urine samples are collected at every opportunity throughout a 24-hour period. The samples are then given to a lab for testing

Special instructions:

During the 24-hour testing period, don't drink a lot of fluids or use glucocorticoid medicines or products, such as hemorrhoid or skin creams that contain steroids. This test needs to be done up to 3 times to be certain the results are accurate

Late-night salivary cortisol test^1,3

What it measures:

Cortisol in saliva

Why it's used:

Normally, the amount of cortisol in saliva is lowest late at night. However, Cushing's syndrome will cause there to be more cortisol than normal in saliva at this time

How it's done:

A saliva sample is obtained between 11 PM and midnight on 2 different nights. These are then given to a lab for testing

Special instructions:

Don't eat licorice, smoke cigarettes, or chew tobacco on the days when samples are obtained
Avoid situations that create extreme stress or excitement
If bedtime is usually well past midnight, obtain samples at bedtime

Late-night plasma cortisol test^3,4

What it measures:

Cortisol in blood

Why it's used:

Normally, the amount of cortisol in blood is lowest late at night. However, Cushing's syndrome will cause there to be more cortisol than normal in blood at this time

How it's done:

A blood sample is obtained at night while the patient is sleeping in a hospital.⁴ This is then given to a lab for testing

Dexamethasone suppression test (DST)^1,3

What it measures:

Cortisol in blood

Why it's used:

Normally, low doses of dexamethasone will reduce cortisol levels. However, if a person has Cushing's syndrome, these doses will not have an effect on cortisol levels

Overnight DST (short test)

How it's done:

A 1-mg dose of dexamethasone is taken between 11 AM and midnight
A blood sample is taken at the doctor's office between 8 AM and 9 AM the next morning

Special instructions:

Don't drink or eat anything for at least 10 hours before the blood test

48-hour DST (long test)

How it's done:

A 0.5-mg dose of dexamethasone is taken every 6 hours for 48 hours
A blood sample is taken at the doctor's office 6 hours following the last dose

Special instructions:

Be sure to take dexamethasone every 6 hours as instructed²

(Note: The longer DST is considered more accurate in determining whether high cortisol levels are caused by Cushing’s syndrome or some other condition.¹)

Tests to diagnosis Cushing’s disease

If a patient is diagnosed with Cushing’s syndrome after measuring the level of cortisol in his or her body, the next step is additional testing to diagnose if the cause of excess cortisol is Cushing’s disease (a pituitary tumor) or a different form of Cushing’s syndrome.¹

Tests to diagnose Cushing's disease
Tests to Diagnose Cushing’s Disease

ACTH measurement

What it measures:

Adrenocorticotropic hormone (ACTH) in the blood

How it's done:

A blood sample is obtained.⁴ This is then given to a lab for testing

Why it's used^4,5:

If ACTH levels are high, then Cushing's syndrome may be caused by a tumor in the pituitary (Cushing's disease) or somewhere other than the pituitary, most commonly on the lungs (ectopic Cushing's syndrome)
If ACTH levels are low, then Cushing's syndrome may be caused by a tumor in the adrenal glands or another area of the body

Imaging tests

What it measures:

Location of the tumor

How it's done:

Doctors use an MRI* or CT* machine to scan areas of the patient's body to look for a tumor based on ACTH testing
MRI scan of the pituitary gland if ACTH levels are high
MRI or CT scan of the adrenal gland if ACTH levels are low⁴

Corticotropin-releasing hormone (CRH) stimulation test

What it measures:

How CRH changes ACTH and cortisol levels^2,4,5

How it's done:

ACTH and cortisol levels are checked with a blood test, then a CRH intravenous injection is given^2,4
After the CRH injection, blood tests are repeated several times to recheck ACTH and Serum F levels^2,4
If these levels are higher, this helps to confirm that there is a pituitary tumor ^2,4

Why it's used:

The CRH test can be used to confirm that there is a pituitary tumor if either the ACTH measurement or the pituitary MRI is inconclusive⁵

*MRI=magnetic resonance imaging; CT=computerized tomography.

Other testing

If a pituitary tumor is suspected but not found on MRI, it may be because either the tumor is too small to see, or it is not a pituitary tumor, but rather an ACTH-producing tumor in another part of the body. Additional imaging and/or tests are then needed.²

A test called inferior petrosal sinus sampling (IPSS) test can be used to determine whether an ACTH-producing tumor is in the pituitary gland (Cushing’s disease).⁴

Once the doctor knows what is causing the level of cortisol to be too high, then he or she can determine the most appropriate treatment.

Next, learn about complications caused by Cushing’s disease

References: 1. Nieman LK, Biller BMK, Findling JW, et al. The diagnosis of Cushing’s syndrome: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2008;93:1526-1540. 2. Newell-Price J, Bertagna X, Grossman AB, Nieman LK. Cushing’s syndrome. Lancet. 2006;367:1605-1617. 3. The Hormone Foundation’s patient guide to the diagnosis of Cushing’s syndrome. The Hormone Foundation. http://www.hormone.org/resources/patient_guides/upload/mgmt-cushings-syndrome-070609.pdf. Accessed August 4, 2009. 4. Arnaldi G, Angeli A, Atkinson AB, et al. Diagnosis and complications of Cushing’s syndrome: a consensus statement. J Clin Endocrinol Metab. 2003;88:5593-5602. 5. Nieman LK, Ilias I. Evaluation and treatment of Cushing’s syndrome. Am J Med. 2005;118:1340-1346.

Tests to diagnose Cushing's syndrome and Cushing's disease