Diagnosis is based on a review of a person’s medical history, a physical examination, and laboratory tests. X rays of the adrenal or pituitary glands can be useful in locating tumors
No single lab test is perfect and usually several are needed. The three most common tests used to diagnose Cushing’s syndrome are the 24-hour urinary free cortisol test, measurement of midnight plasma cortisol or late-night salivary cortisol, and the low-dose dexamethasone suppression test. Another test, the dexamethasone-corticotropin-releasing hormone test, may be needed to distinguish Cushing’s syndrome from other causes of excess cortisol.
• 24-hour urinary free cortisol level
In this test, a person’s urine is collected several times over a 24-hour period and tested for cortisol. Levels higher than 50 to 100 micrograms a day for an adult suggest Cushing’s syndrome. The normal upper limit varies in different laboratories, depending on which measurement technique is used.
• Midnight plasma cortisol and late-night salivary cortisol measurements
The midnight plasma cortisol test measures cortisol concentrations in the blood. Cortisol production is normally suppressed at night, but in Cushing’s syndrome, this suppression doesn’t occur. If the cortisol level is more than 50 nanomoles per liter (nmol/L), Cushing’s syndrome is suspected. The test generally requires a 48-hour hospital stay to avoid falsely elevated cortisol levels due to stress.
However, a late-night or bedtime saliva sample can be obtained at home, then tested to determine the cortisol level. Diagnostic ranges vary, depending on the measurement technique used.
• Low-dose dexamethasone suppression test (LDDST)
In the LDDST, a person is given a low dose of dexamethasone, a synthetic glucocorticoid, by mouth every 6 hours for 2 days. Urine is collected before dexamethasone is administered and several times on each day of the test. A modified LDDST uses a onetime overnight dose.
Cortisol and other glucocorticoids signal the pituitary to release less ACTH, so the normal response after taking dexamethasone is a drop in blood and urine cortisol levels. If cortisol levels do not drop, Cushing’s syndrome is suspected.
The LDDST may not show a drop in cortisol levels in people with depression, alcoholism, high estrogen levels, acute illness, or stress, falsely indicating Cushing’s syndrome. On the other hand, drugs such as phenytoin and phenobarbital may cause cortisol levels to drop, falsely indicating that Cushing’s is not present in people who actually have the syndrome. For this reason, physicians usually advise their patients to stop taking these drugs at least 1 week before the test.
• Dexamethasone-corticotropin-releasing hormone (CRH) test
Some people have high cortisol levels but do not develop the progressive effects of Cushing’s syndrome, such as muscle weakness, fractures, and thinning of the skin. These people may have pseudo-Cushing’s syndrome, a condition sometimes found in people who have depression or anxiety disorders, drink excess alcohol, have poorly controlled diabetes, or are severely obese. Pseudo-Cushing’s does not have the same long-term effects on health as Cushing’s syndrome and does not require treatment directed at the endocrine glands.
The dexamethasone-CRH test rapidly distinguishes pseudo-Cushing’s from mild cases of Cushing’s. This test combines the LDDST and a CRH stimulation test. ...
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