Is there a salivary cortisol test for Cushing's syndrome or hyperaldosteronism?

Late-Night Salivary Cortisol Testing for Cushing's Syndrome Diagnosis

Yes, late-night salivary cortisol (LNSC) testing is an established, highly reliable screening test for Cushing's syndrome, but there is no salivary test specifically for hyperaldosteronism.

Salivary Cortisol Testing for Cushing's Syndrome

Diagnostic Value and Accuracy

• LNSC is one of the first-line screening tests for Cushing's syndrome with excellent diagnostic accuracy 1
• LNSC has superior sensitivity (95%) and specificity (91-100%) compared to other screening methods 2
• The test is based on the principle that patients with Cushing's syndrome lose the normal circadian nadir of cortisol secretion that typically occurs late at night 1

Clinical Implementation

• At least 2-3 LNSC tests are recommended for proper diagnosis 1
• Samples are collected at bedtime or between 22:00-24:00 hours 1
• The test is non-invasive and can be performed at home, increasing patient compliance 2
• LNSC is particularly useful for:
  • Detecting mild cases of Cushing's syndrome
  • Longitudinal surveillance of patients with suspected cyclic Cushing's syndrome 1
  • Screening high-risk populations (e.g., patients with diabetes mellitus) 3

Advantages Over Other Tests

• More convenient than 24-hour urinary free cortisol (UFC) collection
• More specific than the overnight dexamethasone suppression test (DST) 1
• Measures free (bioactive) cortisol, which is in equilibrium with plasma free cortisol 3
• Not affected by changes in cortisol-binding globulin levels 1

Recent Advancements

• Combined measurement of LNSC and late-night salivary cortisone has shown to further improve diagnostic accuracy 2
• With an optimal cut-off for salivary cortisone of >14.5 nmol/L, sensitivity reaches 95.2% with 100% specificity 2

Important Caveats and Limitations

• LNSC should not be performed in patients with disrupted day/night cycles (e.g., night-shift workers) 1
• False positives can occur with:
  • Severe obesity
  • Uncontrolled diabetes
  • Pregnancy
  • Depression
  • Alcoholism 1
• Multiple samples are needed for mild Cushing's syndrome as a single normal result doesn't exclude the diagnosis 4
• Laboratory-specific cut-off values should be established for optimal diagnostic accuracy 5

Hyperaldosteronism Testing

For hyperaldosteronism (primary aldosteronism), there is no established salivary test for diagnosis 1. The standard diagnostic approach includes:

1. Measuring plasma aldosterone and renin activity (aldosterone-to-renin ratio >30 suggests primary hyperaldosteronism)
2. Confirmatory testing with saline suppression test or salt loading test
3. Adrenal vein sampling to distinguish between unilateral adenoma and bilateral hyperplasia 1

Diagnostic Algorithm for Cushing's Syndrome

1. Initial screening with LNSC (at least 2-3 samples on consecutive days)
2. If LNSC is elevated, proceed with additional tests:
   • 24-hour UFC collection (2-3 samples)
   • Overnight 1-mg dexamethasone suppression test
3. If at least two screening tests are abnormal, measure ACTH levels to determine if Cushing's is ACTH-dependent or independent
4. Proceed with appropriate imaging based on ACTH results:
   • Low ACTH: Adrenal CT/MRI
   • Normal/high ACTH: Pituitary MRI 1

LNSC has become a cornerstone in the diagnosis of Cushing's syndrome due to its excellent diagnostic performance, ease of collection, and patient convenience. However, for hyperaldosteronism, traditional plasma and urine tests remain the standard of care.