Endocrine dynamic function tests - urinary free cortisol / salivary cortisol

Role

24-hour urinary free cortisol measures integrated cortisol production over a full day, used as one of the confirmatory tests for Cushing syndrome (alongside dexamethasone suppression testing and late-night salivary cortisol) - each test exploits a different aspect of cortisol physiology, and using more than one improves overall diagnostic confidence
Used as part of the confirmatory work-up once initial Cushing syndrome screening has raised suspicion, given its complementary strengths and limitations relative to the other standard confirmatory tests

Urinary free cortisol reflects the portion of circulating cortisol not bound to cortisol-binding globulin (the biologically active fraction) filtered and excreted renally - this integrates cortisol production across the full 24-hour cycle, in contrast to a single time-point serum measurement, making it less susceptible to the diurnal cortisol variation that can complicate interpretation of isolated measurements

Requires an accurately collected complete 24-hour urine sample - incomplete collection is a common, significant source of error, and creatinine measurement on the same sample helps verify collection adequacy
Reduced renal function lowers urinary free cortisol excretion independent of true cortisol production, potentially causing false-negative results in patients with significant renal impairment - a specific interpretive limitation relevant to result interpretation in this population

An elevated result, particularly when concordant with other confirmatory tests (dexamethasone suppression, late-night salivary cortisol), strengthens confidence in a Cushing syndrome diagnosis and supports proceeding to localisation testing
Discordant results between different confirmatory tests should prompt repeat testing or specialist endocrinology input rather than relying on a single test result to make the diagnosis

Collection completeness verification (creatinine co-measurement), renal impairment falsely lowering results, use alongside (not instead of) other Cushing syndrome confirmatory tests, cyclical Cushing syndrome (a recognised pattern that can cause intermittently normal results)

Using more than one confirmatory test (urinary free cortisol alongside dexamethasone suppression and/or late-night salivary cortisol) improves diagnostic confidence in suspected Cushing syndrome, since each test has different limitations and false-positive/negative causes - concordant results across multiple tests provide more reliable confirmation than any single test alone

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