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BML-ADR-008adrenal stressUSA

Cortisol (Serum) Test

The serum Cortisol test measures the principal glucocorticoid to assess hypothalamic-pituitary-adrenal axis function. Because cortisol follows a circadian rhythm, collection time is integral to interpretation, with morning sampling standard for adrenal insufficiency screening.

1

Biomarkers

Blood (serum)

Sample

1–3 business days

Turnaround

No

Fasting

What is the Cortisol test?

The Cortisol Test measures the principal glucocorticoid in serum, providing a direct assessment of hypothalamic-pituitary-adrenal axis output. Because cortisol governs the stress response, glucose metabolism, and immune regulation, its measurement underpins the investigation of both deficiency and excess states. In the diagnostic landscape, serum cortisol is the foundational analyte for adrenal assessment, but its value depends heavily on collection timing and on interpretation within dynamic protocols. A morning serum cortisol is the standard first step in screening for adrenal insufficiency, while suspected cortisol excess is investigated through low-dose dexamethasone suppression, late-night sampling, or urinary free cortisol. A single random value has limited utility; the test is most informative when timed to the circadian rhythm and paired with ACTH or interpreted as part of a stimulation or suppression study.

What does the Cortisol test measure?

1
Cortisol(Cortisol)
Range: AM (07:00–09:00): 6.2–19.4 µg/dL (171–536 nmol/L); PM (~16:00): 2.3–11.9 µg/dL (64–327 nmol/L) # REVIEWER FLAG: Time-of-day reference intervals are assay- and laboratory-specific — reviewer to confirm against LabCorp cortisol assay ranges before publication.Optimal: Functional medicine practitioners assess cortisol against the expected circadian curve rather than a single optimal value, often favouring diurnal salivary profiling # REVIEWER FLAG: Functional diurnal-curve framing is not standardised — reviewer to confirm whether the platform wishes to present one.µg/dL / nmol/L

Cortisol is the principal glucocorticoid, synthesised in the zona fasciculata of the adrenal cortex under hypothalamic-pituitary-adrenal (HPA) axis control via CRH and ACTH. It exhibits a pronounced circadian rhythm, peaking in the early morning and reaching a nadir near midnight, with superimposed pulsatile secretion. The majority circulates bound to corticosteroid-binding globulin (CBG) and albumin, with only the free fraction biologically active. It regulates gluconeogenesis, immune modulation, vascular tone, and the stress response.

Serum cortisol assesses HPA-axis function and is central to the evaluation of both adrenal insufficiency and cortisol excess (Cushing's syndrome). Because of the circadian rhythm, the time of collection is integral to interpretation, and morning measurement is standard for screening adrenal insufficiency. It is typically used within dynamic testing protocols — such as the ACTH stimulation test or dexamethasone suppression test — rather than as a single static value, and in integrative practice it anchors assessment of the stress axis.

Why is the Cortisol test ordered?

  • Screening for adrenal insufficiency — morning serum cortisol in patients with fatigue, hypotension, hyponatraemia, or unexplained weight loss
  • Investigation of suspected Cushing's syndrome, as part of dexamethasone suppression or late-night cortisol protocols
  • Baseline and stimulated measurement within an ACTH (Synacthen) stimulation test to assess adrenal reserve
  • Evaluation of suspected secondary adrenal insufficiency following prolonged exogenous glucocorticoid therapy
  • Assessment of HPA-axis recovery during glucocorticoid tapering
  • Investigation of adrenal crisis in acutely unwell patients with compatible electrolyte and haemodynamic findings
  • Integrative and functional medicine assessment of the stress axis, typically alongside DHEA-S and diurnal profiling
  • Evaluation of incidental adrenal masses where autonomous cortisol secretion is being excluded

Sample collection and turnaround

Sample type

Blood (serum)

Fasting required

No

Collection method

Venipuncture at patient service centre

Turnaround

1–3 business days

Collection notes

Collection time is integral to interpretation owing to the circadian rhythm — morning samples are typically drawn between 07:00 and 09:00, and the exact time must be recorded on the request. Document glucocorticoid and oestrogen use. Where part of a stimulation or suppression protocol, follow the specific timed-sampling instructions for that study.

Specimen requirements

Minimum 0.5 mL serum. Separate serum from cells within 2 hours of collection. Record the precise time of draw.

What can affect Cortisol results?

variableTime of day (circadian rhythm)

Cortisol peaks in the early morning and falls to a nadir near midnight, so results are uninterpretable without the collection time. Morning sampling is standard for adrenal insufficiency screening.

elevatesAcute physical or psychological stress

Stress, including illness, pain, surgery, and venepuncture anxiety, activates the HPA axis and raises cortisol, potentially masking insufficiency or mimicking excess.

elevatesOestrogen therapy and pregnancy

Oestrogen increases corticosteroid-binding globulin, raising total serum cortisol without a corresponding rise in free, active hormone. Free cortisol or alternative methods may be needed for clarification.

variableExogenous glucocorticoids

Synthetic glucocorticoids suppress endogenous cortisol via HPA feedback, while some cross-react with the assay; the effect depends on the agent and timing. # REVIEWER FLAG: Confirm assay cross-reactivity profile for common synthetic steroids with LabCorp.

elevatesCritical illness

Severe illness activates the HPA axis and alters binding-protein levels, complicating interpretation; dynamic assessment may be required rather than a single value.

variableShift work and disrupted sleep-wake cycle

Altered circadian entrainment shifts the cortisol rhythm, so reference intervals based on a conventional sleep-wake cycle may not apply to shift workers.

What do Cortisol results mean?

Elevated

Elevated cortisol, particularly loss of the normal circadian fall or failure to suppress with dexamethasone, raises concern for Cushing's syndrome and warrants confirmatory dynamic testing. Stress, illness, oestrogen therapy, and pregnancy can elevate total cortisol without true pathological excess.

Normal

A robust morning cortisol makes adrenal insufficiency unlikely but does not exclude milder or secondary forms; equivocal results require dynamic testing. Normal values are interpreted strictly in the context of collection time and clinical presentation.

Reduced

Low morning cortisol suggests adrenal insufficiency and should prompt ACTH measurement and a stimulation test to distinguish primary from secondary causes. A clearly low value in an acutely unwell patient may indicate adrenal crisis requiring urgent treatment.

Note: Serum cortisol must be interpreted with the collection time and, where relevant, within dynamic protocols rather than as a standalone random value. Total cortisol reflects binding-protein status, so oestrogen therapy and pregnancy can mislead; free cortisol or alternative sampling may be required. Acute stress at venepuncture can transiently raise the result.

Frequently asked questions

Cortisol follows a circadian rhythm, peaking in the early morning and falling to a nadir near midnight, so results are uninterpretable without the collection time. Morning sampling between 07:00 and 09:00 is standard for adrenal insufficiency screening.

How to access the Cortisol test

The Cortisol reference page is free and open to all practitioners. Create a free practitioner account to see pricing, save tests to your list, and generate requisition forms. Verification takes 1–2 business days.

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