Late-night salivary cortisol (single sample)

Pick Ordered or Not ordered to see the note.

Indicated when

• —Suspected Cushing's syndrome with discriminating features (easy bruising, facial plethora, proximal myopathy, wide violaceous striae, features unusual for age) or an adrenal incidentaloma: one of three recommended first-line tests [1]

Not indicated when

• —Obesity, metabolic syndrome, hypertension or diabetes alone, without discriminating Cushing's features [1]
• —Investigating fatigue, stress or 'adrenal fatigue' [3, 4]
• —Shift workers or others with a disrupted sleep-wake cycle, in whom the normal late-night fall in cortisol can't be assumed; interpret with care or choose another first-line test (unsourced in this batch; see evidence_notes)

Why not

Used without discriminating features, even a validated test produces false positives, because Cushing's syndrome is rare and common conditions share its non-specific features. A positive screen then leads to repeat testing, imaging and anxiety. A single abnormal result is not diagnostic: the Endocrine Society recommends a second, concordant test and endocrinology referral [1].

Better first step

Look for discriminating features first: easy bruising, facial plethora, proximal muscle weakness, wide purple striae, features unusual for age, or an adrenal incidentaloma. If present, this is a reasonable first-line test, alongside or instead of 24-hour urine free cortisol or a 1 mg overnight dexamethasone suppression test [1].

Typical ND rationale

An ND may include a bedtime saliva sample, often as the last point of a diurnal panel, reasoning that cortisol should be at its lowest at night and a high value suggests the stress response isn't switching off.

Ontario coverage & CONO orderability

OHIP status

unverified

The 2026 Schedule lists one 'Cortisol' line (L303) with no specimen qualifier, so whether a physician-ordered salivary cortisol is billable under it is unverified. The salivary panels seen in the Ontario ND landscape are sold directly to patients. ND-ordered testing is patient-paid regardless (Reg. 552 s. 22).

CONO orderable

Yes — CONO list #173

CONO list item 173, saliva: 'Cortisol – bound and unbound, no differentiation.' The CONO list authorizes the assay, not a specific collection protocol; NDs use it for both a single late-night sample and multi-point diurnal panels.

Linked conditions

• Cushing's syndrome ↗

Counselling script

“A bedtime saliva cortisol is a proven test for Cushing's syndrome, but only when there are specific signs like easy bruising, wide purple stretch marks, or weak thigh muscles. I don't see those today, so a result would be more likely to mislead than help. If those signs appear, I'll order it, usually on two nights.”

Revisit if

• —New bruising, facial plethora, or wide violaceous striae
• —Proximal muscle weakness
• —Adrenal mass found incidentally on imaging
• —Rapid weight gain together with these features

References

1. [1]Endocrine Society (2008). The Diagnosis of Cushing's Syndrome: An Endocrine Society Clinical Practice Guideline. linkolder guidelineA single late-night salivary cortisol is one of three first-line tests for Cushing's syndrome, used only in patients with discriminating features
2. [2]Pituitary Society (2021). Consensus on diagnosis and management of Cushing's disease: a guideline update. link2021 Pituitary Society consensus update on screening and diagnosis of Cushing's disease
3. [3]BMC Endocrine Disorders (2016). Adrenal fatigue does not exist: a systematic review. linkolder guidelineCortisol awakening response and salivary cortisol rhythm were the most-studied but never validated markers used to investigate 'adrenal fatigue'
4. [4]Endocrine Society (patient education) (2026). Adrenal Fatigue. linkThere is no test, including salivary cortisol patterns, that can detect 'adrenal fatigue'