Free cortisol measurement in urine is a screening test for Cushing's syndrome.
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The diagnosis of Cushing syndrome (CS) requires evidence of cortisol hypersecretion. While serum cortisol levels fluctuate unpredictably and strongly depend on concurrent cortisol-binding globulin (CBG) levels, a 24-hour urine specimen integrates the cortisol production for an entire day and is unaffected by CBG. Urinary cortisol reflects the portion of serum-free cortisol filtered by the kidney and correlates well with the cortisol secretion rate.
The most common causes of Cushing syndrome are pituitary adenoma (65% to 70%), adrenal tumor (15% to 20%), and ectopic Cushing (10% to 15%).
Measurement of free cortisol in urine does not help evaluate adrenal insufficiency because results overlap with normal ranges. Increased excretion may be found with the pseudo-Cushing syndrome, trauma, infection, pregnancy, and oral contraceptives.