Introduction: Who Should Undergo Diagnostics

Diagnosing hyperadrenocorticism, commonly called Cushing’s syndrome, can be a long and complex process, but it is essential for getting the right treatment. If you notice symptoms that have appeared slowly over time, such as unexplained weight gain especially around your face and midsection, increased thirst and urination, or thinning skin with easy bruising, it may be time to talk to your doctor about testing for this condition.^[1]

People who are most likely to need diagnostic testing for hyperadrenocorticism include adults aged 25 to 50 years, although children and people outside this age range can also develop the condition. Women are diagnosed with Cushing’s syndrome about three times as often as men.^[3][6] You should seek medical advice if you experience symptoms like a rounded face, a fatty hump between your shoulders, purple stretch marks on your skin, muscle weakness, fatigue, or high blood pressure.^[1]

Those who take glucocorticoid medications—steroid medicines used to treat conditions like asthma, rheumatoid arthritis, or other inflammatory diseases—are especially vulnerable to developing this syndrome. Glucocorticoids are similar to cortisol and can cause the same problems when taken in high doses over long periods.^[6] If you have been using steroid pills, injections, creams, or inhalers for an extended time and notice any symptoms, your doctor should evaluate your medication use first before ordering additional tests.^[8]

People who have type 2 diabetes along with blood sugar levels that remain too high over time and high blood pressure may also benefit from testing for Cushing’s syndrome, as this hormonal imbalance could be an underlying cause of their metabolic problems.^[3]

Diagnostic Methods: Identifying the Condition

When Cushing syndrome is suspected, diagnosing it requires careful evaluation because other illnesses can have similar symptoms. You will likely need to see a specialist called an endocrinologist—a doctor who specializes in hormonal diseases—to get a proper diagnosis.^[8][6]

Physical Examination

Your endocrinologist will begin by performing a physical examination, looking for visible signs of Cushing’s syndrome such as a round, moon-shaped face, a fatty hump on the back of your neck, thin and bruised skin with stretch marks, and weight gain in the trunk area while your arms and legs appear thin.^[8][1] This physical assessment helps the doctor decide which laboratory and imaging tests will be most helpful.

Urine and Blood Tests

If you haven’t been using glucocorticoid medicine, your doctor will order tests to measure hormone levels in your body. These tests check whether your body is making too much cortisol.^[8][15]

One common test is a 24-hour urine collection. You will be asked to collect all your urine over a full day, and the laboratory will measure the amount of cortisol and other hormones in it. Blood tests can also be performed to measure cortisol and ACTH (adrenocorticotropic hormone)—a hormone produced by the pituitary gland that tells the adrenal glands to make cortisol—in your bloodstream.^[8]

Your healthcare provider may also recommend specialized tests that measure cortisol levels before and after you take certain hormone medicines that trigger or block cortisol production. These additional tests help confirm whether the problem lies in your body’s natural cortisol regulation.^[8]

Saliva Test

Cortisol levels in healthy people typically rise and fall throughout the day. In the evening, cortisol normally drops to very low levels. A saliva test involves collecting a small sample of your saliva late at night, and the lab checks whether your cortisol levels are too high at a time when they should be low. This simple test can reveal whether your body’s natural cortisol rhythm is disrupted.^[8][15]

Imaging Tests

Once blood or urine tests confirm that you have too much cortisol, imaging tests are used to find out where the problem is coming from. Your doctor may order a CT scan (computed tomography) or MRI scan (magnetic resonance imaging) to take detailed pictures of your pituitary gland in your brain or your adrenal glands near your kidneys. These scans can show whether there is a tumor or abnormal growth causing the extra cortisol production.^[8][15]

Abdominal ultrasound is another imaging technique that can be especially helpful. It uses sound waves to create images of your adrenal glands and can identify whether one or both glands are enlarged or have tumors.^[6]

Tests to Differentiate the Cause

Because Cushing’s syndrome can have different causes, additional tests are needed to determine whether the problem is in your pituitary gland (called Cushing’s disease) or in your adrenal glands (adrenal-dependent hyperadrenocorticism). Knowing the exact cause is important for choosing the most effective treatment.^[6]

One test used for this purpose is measuring plasma ACTH concentration. In people with tumors in the adrenal glands, ACTH levels in the blood are very low because the tumor produces cortisol on its own, without needing signals from the pituitary gland. In contrast, people with pituitary tumors have high or high-normal ACTH levels because the pituitary is producing too much ACTH, which then stimulates the adrenal glands to make too much cortisol.^[6]

Another test that can help distinguish between causes is the high-dose dexamethasone suppression test. Dexamethasone is a synthetic steroid that normally should shut down the pituitary gland’s production of ACTH through a natural feedback system. In people with pituitary-dependent Cushing’s disease, the high dose of dexamethasone can suppress cortisol production, at least temporarily. However, in people with adrenal tumors, cortisol production continues because the tumor acts independently and doesn’t respond to feedback signals.^[6]

This test, however, is not perfect. About 20 to 30 percent of people with pituitary-dependent Cushing’s disease will not show suppression of cortisol with this test, and it does not tell the difference between benign and cancerous adrenal tumors.^[6]

Diagnostics for Clinical Trial Qualification

Clinical trials for Cushing’s syndrome typically require specific diagnostic criteria to confirm that participants truly have the condition and to determine its underlying cause. These criteria ensure that researchers are studying patients with similar disease characteristics, which helps generate reliable and meaningful results.

Standard diagnostic tests used to qualify patients for clinical trials often include the same tests used in routine clinical care, such as urine and blood cortisol measurements, saliva tests for late-night cortisol, and ACTH stimulation tests to evaluate how the adrenal glands respond to hormonal signals.^[8][15]

Imaging studies like CT or MRI scans are also commonly required in clinical trial protocols. These scans help investigators confirm whether participants have pituitary tumors (Cushing’s disease) or adrenal gland tumors (adrenal-dependent hyperadrenocorticism), as trials may focus on one specific type of the condition.^[8]

In addition to these standard tests, some clinical trials may request specialized blood tests or additional imaging to gather more detailed information about disease severity and how the body is responding to excess cortisol. Trial protocols may also require participants to undergo baseline measurements of blood pressure, blood sugar levels, bone density, and other health markers that can be affected by hyperadrenocorticism, to track changes over time during the study.^[3]

Some research studies may also use screening tests to assess the general health of potential participants and to check for other medical conditions that could affect the trial results or put participants at risk. These can include routine blood tests to check kidney and liver function, as well as tests for diabetes or heart disease complications.^[3]

Because clinical trials are research studies designed to test new treatments or gather more information about diseases, they often have strict inclusion and exclusion criteria. This means that not everyone with Cushing’s syndrome will qualify for every trial. However, participating in a clinical trial can provide access to new treatments and contribute to advancing medical knowledge that may help future patients.