What does a saliva cortisol level of 166 ng/mL indicate?

Interpretation of Salivary Cortisol 166 ng/mL

A salivary cortisol level of 166 ng/mL (16.6 nmol/L) collected at late night (bedtime) is highly suggestive of Cushing's syndrome and requires immediate confirmatory testing and endocrinology referral.

Critical Context: When Was This Sample Collected?

The interpretation of this result depends entirely on the timing of collection:

If Collected at Late Night/Bedtime (Most Likely Scenario)

This result is markedly abnormal and strongly indicates Cushing's syndrome. 1

• Normal late-night salivary cortisol should be <3.6 nmol/L (<36 ng/dL or approximately <3.6 ng/mL) 2
• Your value of 166 ng/mL is approximately 46 times the upper limit of normal 2
• Late-night salivary cortisol has 92-100% sensitivity and 93-100% specificity for Cushing's syndrome 3, 4

If Collected in the Morning (Less Likely)

• Morning values up to 27.3 nmol/L (approximately 27 ng/mL) can be normal 5
• A value of 166 ng/mL in the morning would still be elevated (approximately 6 times normal) and concerning 5
• However, morning samples have significant overlap between normal and Cushing's patients and are not diagnostically useful alone 2

Immediate Next Steps

Do not rely on a single measurement—obtain at least 2-3 additional late-night salivary cortisol samples on different nights before making definitive diagnostic decisions. 1, 3

Why Multiple Samples Are Essential:

• Cushing's syndrome can be cyclic, with periods of normal cortisol alternating with hypercortisolism 1
• Intra-patient variability is significant 1
• A single elevated value requires confirmation 3

Confirmatory Testing Algorithm:

1. Repeat late-night salivary cortisol 2-3 times (collect at usual bedtime, not strictly midnight) 1, 3
2. Add 24-hour urinary free cortisol (UFC) - at least 2-3 collections 1
3. Perform overnight 1-mg dexamethasone suppression test (cortisol <1.8 μg/dL at 0800h is normal) 1
4. If all tests confirm hypercortisolism, proceed to determine etiology (ACTH level, imaging) 1

Common Pitfalls to Avoid

False Positive Causes (That Don't Apply Here Given Magnitude):

• Topical hydrocortisone contamination - can falsely elevate results, though your value is too high to explain by contamination alone 1, 3
• Night shift work or disrupted sleep-wake cycle - invalidates the test 1
• Physiologic stress or acute illness - can activate the HPA axis 4
• Collection technique errors - blood contamination or insufficient saliva volume 3, 6

Critical Errors to Avoid:

• Do not dismiss this result without proper follow-up - even "mild" Cushing's has significant morbidity (hypertension, diabetes, osteoporosis, cardiovascular disease) 1
• Do not use salivary cortisol as the only diagnostic test - always confirm with additional testing modalities 3
• Do not delay endocrinology referral if repeat testing confirms hypercortisolism 1

Clinical Significance

Untreated Cushing's syndrome carries substantial mortality and morbidity risk:

• Increased cardiovascular mortality 1
• Severe metabolic complications (diabetes, hypertension, dyslipidemia) 1
• Osteoporosis with fracture risk 4
• Psychiatric manifestations 1
• Immunosuppression and infection risk 1

The combination of elevated late-night salivary cortisol AND elevated 24-hour UFC identifies 100% of Cushing's syndrome patients. 2

Assay Considerations

• Most labs use immunoassay (enzyme immunoassay) for salivary cortisol 3
• LC-MS/MS provides superior sensitivity and can differentiate cortisol from cortisone, avoiding topical hydrocortisone interference 1
• Confirm your lab's reference ranges and units (ng/mL vs nmol/L) 3