From the Guidelines
To diagnose Cushing syndrome, initial screening tests should include 24-hour urinary free cortisol, late-night salivary cortisol, and the overnight 1-mg dexamethasone suppression test. These tests are recommended based on the most recent and highest quality study available, which is the 2024 guideline for the diagnosis and management of pituitary adenomas in childhood and adolescence 1. The 24-hour urinary free cortisol measures cortisol excretion over a full day, with values exceeding the normal range (typically >50-100 μg/24h) suggesting hypercortisolism. Late-night salivary cortisol assesses disruption of the normal diurnal cortisol rhythm, with elevated levels (>0.2 μg/dL) indicating potential Cushing syndrome. The overnight dexamethasone suppression test involves administering 1 mg of dexamethasone at 11 PM and measuring serum cortisol at 8 AM the next morning; failure to suppress cortisol below 1.8 μg/dL suggests Cushing syndrome.
Some key points to consider when ordering these tests include:
- The sensitivity and specificity of each test, with the overnight dexamethasone suppression test and late-night salivary cortisol having the highest sensitivity and specificity, respectively 1
- The importance of using a combination of tests to confirm the diagnosis, as no single test is 100% sensitive or specific 1
- The need to consider the clinical context and patient symptoms when interpreting test results, as Cushing syndrome can present with a range of symptoms and signs 1
If screening tests are positive, confirmatory testing should include the 2-day low-dose dexamethasone suppression test (0.5 mg every 6 hours for 48 hours) and/or the dexamethasone-CRH stimulation test. Once Cushing syndrome is confirmed, additional tests like plasma ACTH levels, high-dose dexamethasone suppression test, and imaging studies (pituitary MRI, adrenal CT/MRI) help determine the specific cause, whether it's pituitary, adrenal, or ectopic ACTH production 1.
It's also important to note that Cushing syndrome is a rare condition, and the diagnosis should be made based on a combination of clinical suspicion, laboratory tests, and imaging studies. The treatment and management of Cushing syndrome depend on the underlying cause and may involve surgery, medication, or a combination of both 1.
From the Research
What is Cushing Syndrome
Cushing syndrome is a rare disorder caused by excess levels of cortisol in the body [(2,3,4,5,6)].
Laboratory Tests for Cushing Syndrome
The following laboratory tests can be ordered to diagnose Cushing syndrome:
- 24-hour urine free cortisol (UFC) [(2,3,5,6)]
- Overnight 1 mg dexamethasone suppression test (DST) [(2,3)]
- Late-night salivary cortisol (LNSC) [(2,4)]
- Late-night salivary cortisone (LNS cortisone) 4
- Plasma adrenocorticotropin (ACTH) levels [(3,5,6)]
- Low-dose and high-dose dexamethasone suppression tests [(3,5,6)]
- Corticotropin-releasing hormone (CRH) stimulatory test [(5,6)]
- Insulin tolerance test 3
- Metyrapone test 3
- 17-hydroxycorticosteroids and 17-ketogenic steroids 3
Key Points to Consider
- A single test may not be sufficient to diagnose Cushing syndrome, and multiple samples (urine/saliva) and tests may be needed [(2,3,4,5,6)].
- The choice of test may depend on the clinical presentation and suspected etiology of Cushing syndrome [(3,5,6)].
- Imaging studies, such as MRI or CT scans, may be necessary to localize the source of excess cortisol production [(2,5)].
- Inferior petrosal sinus sampling may be used to confirm the diagnosis and determine the source of excess ACTH production [(2,5)].