What does the Cortisol, Serum (Total — Bound and Free Fractions) test measure?

Why is Cortisol, Serum (Total — Bound and Free Fractions) measured?

Serum cortisol is the cornerstone test of adrenal cortical function assessment in mainstream endocrinology and is ordered across several distinct clinical contexts that require different timing, interpretive frameworks, and reference standards. As a morning cortisol screen, it is the first-line test for suspected adrenal insufficiency — a random morning cortisol below 3 µg/dL strongly suggests adrenal insufficiency in a patient who is not acutely stressed, while a morning cortisol above 18–20 µg/dL effectively excludes it; values between these thresholds require dynamic stimulation testing (Short Synacthen/ACTH stimulation test). As a Cushing's syndrome screen, late-night serum cortisol — while not the primary recommended method (late-night salivary cortisol and 24-hour urinary free cortisol are preferred) — can identify failure of normal diurnal suppression. In the context of critical illness, acute stress, surgery, and major trauma, cortisol rises dramatically as part of the stress response; a cortisol below 18–20 µg/dL in a critically ill patient may indicate relative adrenal insufficiency. In functional and integrative medicine, serum cortisol is used to assess HPA axis status alongside DHEA-S and the cortisol:DHEA-S ratio, characterising the adrenal hormonal landscape for stress adaptation assessment and adrenal support protocol guidance.

Reference ranges

Standard reference

AM (07:00–09:00): 6.2–19.4 µg/dL (171–535 nmol/L); PM (15:00–17:00): 2.3–11.9 µg/dL (63–327 nmol/L) # REVIEWER FLAG: Confirm Access Medical Laboratories reference ranges for morning and afternoon serum cortisol — values are time-of-collection-dependent and platforms vary. Some laboratories apply a single AM reference range only; others provide diurnal time-banded ranges. Confirm whether Access Medical Laboratories provides a single reference range or multiple time-specific ranges, and whether they require the collection time to be documented on the requisition form to apply the correct reference interval. Confirm assay methodology — most platforms use electrochemiluminescence immunoassay (ECLIA) or chemiluminescent microparticle immunoassay (CMIA); confirm whether Access Medical Laboratories uses one of these or an alternative platform, as this affects reference range calibration.

Functional medicine optimal

Morning (08:00–09:00): 10–18 µg/dL (functional medicine optimal — mid-to-upper reference range reflecting robust but not excessive morning HPA axis activation); afternoon (15:00–17:00): 3–8 µg/dL (reflecting adequate but declining cortisol for afternoon biological function without evening excess). # REVIEWER FLAG: Functional medicine optimal ranges for serum cortisol are not standardised in mainstream endocrine guidelines — reviewer to confirm appropriate framing distinguishing the functional optimal from the adrenal insufficiency diagnostic threshold.

Units

µg/dL, nmol/L

Reference ranges vary by laboratory and assay platform. Interpret in context of the issuing laboratory's stated range.