From the Guidelines
The diagnosis of Cushing's syndrome should be performed using a systematic approach, starting with screening tests such as 24-hour urinary free cortisol measurement, late-night salivary cortisol testing, or the overnight 1-mg dexamethasone suppression test, as recommended by the most recent guideline update 1. The initial screening tests are crucial in identifying patients with Cushing's syndrome, and the choice of test depends on the clinical presentation and patient factors.
- 24-hour urinary free cortisol measurement is a useful screening test, with values >193 nmol/24 h (>70 μg/m2) suggesting Cushing's syndrome 1.
- Late-night salivary cortisol testing is also a sensitive screening test, with elevated levels on two separate occasions indicating possible Cushing's syndrome 1.
- The overnight 1-mg dexamethasone suppression test involves administering 1 mg of dexamethasone at 11 PM and measuring serum cortisol at 8 AM the next morning; cortisol levels above 1.8 μg/dL suggest Cushing's syndrome 1. If screening tests are positive, confirmatory testing is necessary, which may include the low-dose dexamethasone suppression test (0.5 mg every 6 hours for 48 hours) or the dexamethasone-CRH test 1. Once Cushing's syndrome is confirmed, determining the etiology is crucial through ACTH level measurement, with high ACTH levels suggesting ectopic ACTH production or pituitary adenoma, and low levels indicating adrenal causes 1. Additional testing such as high-dose dexamethasone suppression test, pituitary MRI, inferior petrosal sinus sampling, or adrenal imaging may be needed to pinpoint the exact cause 1. This stepwise approach is necessary because Cushing's syndrome can present with variable clinical features and laboratory findings, requiring careful differentiation from conditions that can mimic hypercortisolism 1. It is essential to follow the most recent guideline update, which provides recommendations for the diagnosis and management of Cushing's syndrome, including the use of laboratory tests, imaging, and treatment options 1. The guideline update also highlights the importance of considering patient- and disease-specific factors for personalized care 1. In summary, the diagnosis of Cushing's syndrome requires a systematic approach, starting with screening tests, followed by confirmatory testing, and determining the etiology through ACTH level measurement and additional testing as needed, as recommended by the most recent guideline update 1.
From the Research
Diagnostic Tests for Cushing's Syndrome
To perform the diagnosis of Cushing's syndrome, several tests can be utilized, including:
- Overnight 1-mg dexamethasone suppression test (DST) 2
- 24-hour urinary free cortisol (UFC) 2, 3, 4, 5
- Late-night salivary cortisol (LNSC) 6, 4
- Midnight serum cortisol (MSC) 4
- Dexamethasone-suppressed CRH (dex-CRH) and desmopressin (dex-DDAVP) tests 4
Test Sensitivity and Specificity
The sensitivity and specificity of these tests vary, with:
- DST: 98.6% sensitivity, 90.6% specificity 4
- 24-hour UFC: 94.0% sensitivity, 93.0% specificity 4
- LNSC: 95.8% sensitivity, 93.4% specificity 4
- MSC: 96.1% sensitivity, 93.2% specificity 4
- Dex-CRH: 98.6% sensitivity, 85.9% specificity 4
Comparison of Tests
Comparing the efficacy of serum cortisol and 24-hour UFC in combined dexamethasone suppression tests, studies have found:
- Serum cortisol <50 nmol/L had a higher sensitivity than 24-hour UFC <32 nmol in combined low-dose DST 5
- Suppression rate of 24-hour UFC ≥50% had better sensitivity and specificity than serum cortisol in differentiating the etiology of Cushing's syndrome in high-dose DST 5
Urinary Cortisol/Creatinine Ratio
The 24-hour urinary cortisol/urinary creatinine ratio (24hUCor/Cr) has been investigated as a potential diagnostic tool, with: