The diagnosis of Cushing syndrome (CS) requires evidence of cortisol hypersecretion. While serum cortisol levels fluctuate unpredictably and are strongly dependent on concurrent cortisol-binding globulin (CBG) levels, a 24-hour urine specimen integrates the cortisol production for an entire day and is not affected by CBG. Urinary cortisol reflects the portion of serum-free cortisol filtered by the kidney, and correlates well with cortisol secretion rate.

The most common causes of CS are pituitary adenoma (65% to 70%), adrenal tumor (15% to 20%), and ectopic CS (10% to 15%).

Not useful in the evaluation of adrenal insufficiency (AI). Results in AI overlap with normal ranges. Increased in pregnancy and with oral contraceptives. Increased excretion may be found with pseudo-Cushing syndrome, trauma, or infection.² Tetracyclines may cause false elevation of results.

This test was developed and its performance characteristics determined by LabCorp. It has not been cleared or approved by the Food and Drug Administration.

This test is useful in the initial evaluation of patients with suspected Cushing syndrome (CS).^1,2 Patients with CS usually have urine free cortisol >100 μg/24 hours, but there is wide variation and no single cutoff can be used safely. If the 24-hour urine free cortisol is elevated, additional testing is indicated to differentiate among pituitary-dependent CS, pituitary-independent CS, and pseudo-Cushing syndrome.²

Some patients with an elevated 24-hour urine cortisol do not have Cushing syndrome and are often classified as pseudo-Cushing syndrome. Establishing this diagnosis requires additional testing which includes the low-dose dexamethasone suppression test, the CRH stimulation test, or a protocol that combines them both.³

The diagnosis of CS requires a meticulous history and physical examination,² and these should precede a biochemical evaluation.

1. Watts NB, Keffer JH. Adrenal cortex. Practical Endocrinology. 4th ed. Philadelphia, Pa: Lea & Febiger;1989.

2. Orth DN. Cushing's syndrome. N Engl J Med. 1995 Mar 23; 332(12):791-803. Erratum: 1995 Jun 1; 332(22):1527. PubMed 7862184

3. Yanovski JA, Cutler GB Jr, Chrousos GP, Nieman LK. Corticotropin-releasing hormone stimulation following low-dose dexamethasone administration, A new test to distinguish Cushing's syndrome from pseudo-Cushing's states. JAMA. 1993 May 5; 269(17):2232-2238. PubMed 8386285

Canalis E, Reardon GE, Caldarella AM. A more specific, liquid-chromatographic method for free cortisol in urine. Clin Chem. 1982 Dec; 28(12):2418-2420. PubMed 7139923