How do you diagnose Cushing syndrome?

From the Guidelines

Cushing syndrome is diagnosed through a combination of clinical evaluation, laboratory tests, and imaging studies, with the most recent and highest quality study recommending a stepwise approach starting with screening tests such as 24-hour urinary free cortisol, late-night salivary cortisol, or an overnight dexamethasone suppression test 1. The diagnosis of Cushing syndrome typically begins with recognizing characteristic symptoms such as central obesity, rounded face, purple stretch marks, muscle weakness, high blood pressure, and elevated blood glucose.

• Laboratory testing is essential and typically follows a stepwise approach, with the initial screening tests including:
  • 24-hour urinary free cortisol
  • Late-night salivary cortisol
  • Overnight dexamethasone suppression test (1 mg dexamethasone given at 11 PM with cortisol measured at 8 AM the next day; normal response is cortisol below 1.8 μg/dL) 1
• If screening tests are positive, confirmatory tests are performed, such as the low-dose dexamethasone suppression test (0.5 mg every 6 hours for 48 hours) or the midnight serum cortisol measurement.
• Once hypercortisolism is confirmed, determining the cause requires measuring ACTH levels, with high ACTH suggesting an ACTH-producing tumor (pituitary or ectopic), and low ACTH indicating an adrenal cause 1.
• Further localization involves imaging studies, including:
  • MRI of the pituitary for Cushing's disease
  • CT or MRI of the adrenal glands for adrenal tumors
  • Chest/abdominal imaging for ectopic ACTH sources
• In difficult cases, specialized tests like inferior petrosal sinus sampling may be needed to differentiate between pituitary and ectopic ACTH sources, as recommended by the most recent consensus guidelines 1. This systematic approach is necessary because Cushing syndrome can have serious complications if left untreated, and the recent guidelines emphasize the importance of accurate diagnosis and personalized care 1.

From the Research

Diagnosis of Cushing Syndrome

To diagnose Cushing syndrome, several tests can be used, including:

• 24-hour urine free cortisol (UFC) measurement 2, 3, 4, 5
• Overnight 1 mg dexamethasone suppression test (DST) 2, 3, 4, 5
• Late-night salivary cortisol measurement 2, 3, 4, 5, 6
• Measurement of plasma ACTH concentrations to differentiate between ACTH-dependent and ACTH-independent causes 3, 5
• Imaging modalities such as magnetic resonance imaging (MRI) of the pituitary or computer tomography scan of the abdomen 2, 3, 5
• Bilateral inferior petrosal sinus sampling to further pinpoint the cause of Cushing's syndrome 2, 5

Interpretation of Test Results

The interpretation of test results can be difficult due to individual patient characteristics and the limitations of each test 2, 5. For example:

• A normal UFC or late-night salivary cortisol does not exclude mild Cushing syndrome 2
• The sensitivity and specificity of each test can vary, and multiple samples and tests may be needed to make a diagnosis 2, 4, 5
• The diagnosis of Cushing syndrome requires a combination of clinical evaluation and laboratory testing 3, 4, 5

Screening for Cushing Syndrome

Screening for Cushing syndrome should start with excluding local and systemic corticosteroid use 5. First-line screening tests, including the 1-mg dexamethasone suppression test, 24-hour urinary free cortisol excretion, and late-night salivary cortisol measurement, should be performed to screen for endogenous Cushing syndrome 3, 4, 5. Scalp-hair cortisol/cortisone analysis can also be used to assess long-term glucocorticoid exposure and detect transient periods of hypercortisolism 5.