What are the findings of a Cushing's syndrome (Cushing's) exam?

From the Guidelines

To diagnose Cushing's syndrome, a comprehensive evaluation is necessary, beginning with screening tests followed by confirmatory tests, as recommended by the most recent guideline update 1. The initial screening should include a combination of tests to assess cortisol secretory status, such as late-night salivary cortisol (LNSC), overnight 1-mg dexamethasone suppression test (DST), and 24-hour urinary free cortisol (UFC) 1.

• The sensitivity of these tests is above 90%, with the highest rates seen with DST and LNSC, and the lowest with UFC 1.
• The specificity is somewhat lower, with LNSC being the most specific and DST and UFC being the least specific 1. The diagnostic approach should consider the clinical suspicion for Cushing's syndrome, and the patient's history of exogenous glucocorticoid (GC) use, as outlined in the guideline update 1.
• If the patient takes exogenous GC, it should be stopped if possible, and the clinical likelihood of endogenous Cushing's syndrome should be assessed 1.
• The guideline recommends using two to three screening tests, including LNSC, 24-hour UFC, and overnight 1-mg DST, to confirm the diagnosis 1. Once Cushing's syndrome is confirmed, determining the cause requires measuring adrenocorticotropic hormone (ACTH) levels, high-dose dexamethasone suppression testing, pituitary MRI, and possibly inferior petrosal sinus sampling, as recommended by the guideline update 1.
• The measurement of ACTH levels helps to differentiate between ACTH-dependent and ACTH-independent Cushing's syndrome 1.
• The guideline also recommends using adrenal CT or MRI for ACTH-independent Cushing's syndrome, and pituitary MRI for ACTH-dependent Cushing's syndrome 1.

From the Research

Cushing's Syndrome Diagnosis

The diagnosis of Cushing's syndrome involves a complex diagnostic assessment, with several tests recommended for screening and diagnosis.

• The recommended diagnostic tests are:
  • 24-h urinary free cortisol
  • 1-mg overnight dexamethasone suppression test
  • Late-night salivary cortisol 2, 3, 4, 5
• These tests are used to screen for endogenous Cushing's syndrome and to differentiate between ACTH-dependent and ACTH-independent causes.

Screening Tests

The screening tests for Cushing's syndrome have varying degrees of sensitivity and specificity.

• The 1-mg dexamethasone suppression test has a high specificity (97%) but may not be as sensitive for mild cases of Cushing's syndrome 3, 6
• Urinary free cortisol measurement has a high sensitivity (97%) and specificity (91%) when measured by liquid chromatography tandem-mass spectrometry 3
• Late-night salivary cortisol measurement has a sensitivity of 84% and specificity of 89% 3

Diagnostic Challenges

The diagnosis of Cushing's syndrome can be challenging due to its nonspecific presentation and the limitations of diagnostic tests.

• Mild cases of Cushing's syndrome may have normal or mildly elevated urinary free cortisol levels, making diagnosis more difficult 6
• Individual patient characteristics and test limitations must be considered when interpreting results 5
• Multiple samples and tests may be needed to make a diagnosis of mild Cushing's syndrome 6

Further Assessment

Once endogenous Cushing's syndrome is established, further assessment is needed to differentiate between ACTH-dependent and ACTH-independent causes.

• Measurement of plasma ACTH concentrations can help differentiate between ACTH-dependent (80%-85%) and ACTH-independent (15%-20%) causes 2, 5
• Imaging modalities and dynamic biochemical testing, including bilateral inferior petrosal sinus sampling, can help further pinpoint the cause of Cushing's syndrome 2, 5