Cushing Syndrome

When your healthcare provider suspects hypercortisolism, there are certain guidelines they may follow. They’ll ask questions, look at your medical history, perform a physical examination and then conduct some laboratory tests. They’ll likely continue to monitor you over time.

Cushing syndrome can sometimes be difficult to diagnose. If you tell your provider you have fatigue and weight gain, they might not immediately think of Cushing syndrome. These types of symptoms are common to many different kinds of diseases.

Cushing syndrome is also sometimes mistaken for polycystic ovary syndrome or metabolic syndrome. Your healthcare provider will have to go through a process of elimination to rule out other conditions.

What tests will be done to diagnose Cushing syndrome?

Your healthcare provider is likely to request some of the following tests:

• 24-hour urinary cortisol test: This test measures the amount of cortisol in micrograms (mcg) in your urine. Your healthcare provider will have you collect your urine (pee) over a period of 24 hours.
• Midnight salivary cortisol test: Typically, cortisol levels are very low late at night. This test checks cortisol levels between 11 p.m. and 12 a.m. If you have Cushing syndrome, your cortisol levels will be unusually high during that hour.
• Low-dose dexamethasone suppression test: Dexamethasone is a cortisol-like drug. For this test, you take one milligram (mg) of the drug by mouth at night and then measure cortisol levels between 8 a.m. and 9 a.m. This blood test determines if the adrenal glands responded to the dexamethasone by suppressing the amount of cortisol they secrete. If you have Cushing syndrome, your cortisol levels will remain high.
• Blood test: A blood test will measure the ACTH levels in your blood. An adrenal tumor might be there if the levels are low. If the levels are normal or high, there could be a pituitary or ectopic tumor.
• High-dose dexamethasone suppression test: This test is like the low-dose dexamethasone suppression test, but the dosage is 8 milligrams instead of one. A provider will typically perform this test after the low-dose test shows high levels of cortisol in the morning and when blood tests show high ACTH in the blood. This test can determine the source of Cushing syndrome, since it can tell the difference between a pituitary adenoma (Cushing disease) and a tumor elsewhere in your body (such as your lungs).

Once your healthcare provider has confirmed that you have Cushing syndrome, the next step is to determine why. Often it’s medication or a tumor. If you’re on glucocorticoids, that’s probably the cause, and your healthcare provider will likely decrease the dosage. If you’re not on glucocorticoids, that indicates there’s likely a tumor in your adrenal glands, pituitary gland or elsewhere. Your healthcare provider may recommend the following imaging studies to reveal the location of the tumor:

• CAT scan (CT scan) or MRI abdomen: Your provider may perform a CT scan or MRI to look for a tumor in your adrenal glands. The provider can do these scans with or without IV contrast. The tests are very sensitive at identifying adrenal tumors.
• Magnetic resonance imaging (MRI) pituitary: An MRI will take a picture of your pituitary gland to see if there’s a tumor. In some cases, the MRI won’t provide a perfect diagnosis. Fifty percent of those with Cushing syndrome will have a “normal” MRI and 10% will have tumors unrelated to the syndrome.
• Bilateral inferior petrosal sinus sampling (BIPPS): This test finds the source of ACTH secretion. ACTH and other pituitary hormones go into the bloodstream from the pituitary gland. An experienced interventional radiologist will go through two veins known as the inferior petrosal sinuses. This test has a 95% to 98% accuracy rate.
• CT scan chest: If your provider suspects an ectopic tumor, they’ll order a CT chest to look for possible lung cancer.