Cortisol/Cortisone – Free, 24 hr Urine

Most patients with Cushing syndrome have increased 24-hour urinary excretion of cortisol and/or cortisone. Further studies, including suppression or stimulation tests, measurement of serum corticotropin (adrenocorticotropic hormone) concentrations, and imaging are usually necessary to confirm the diagnosis and determine the etiology.
Values in the normal range may occur in patients with mild Cushing syndrome or with periodic hormonogenesis. In these cases, continuing follow-up and repeat testing are necessary to confirm the diagnosis.
Patients with Cushing syndrome due to intake of synthetic glucocorticoids should have both suppressed cortisol and cortisone. In these circumstances a synthetic glucocorticoid screen might be ordered.
Suppressed cortisol and cortisone values may also be observed in primary adrenal insufficiency and hypopituitarism. However, random urine specimens are not useful for evaluation of hypocorticalism. Further, many normal individuals also may exhibit a very low 24-hour urinary cortisol excretion with considerable overlap with the values observed in pathological hypocorticalism. Therefore, without other tests, 24-hour urinary cortisol measurements cannot be relied upon for the diagnosis of hypocorticalism.
Patients with 11-beta hydroxy steroid dehydrogenase deficiency may have cortisone to cortisol ratios <1, whereas a ratio of 2:1 to 3:1 is seen in normal patients. Excessive licorice consumption and use of carbenoxolone, a synthetic derivative of glycyrrhizinic acid used to treat gastroesophageal reflux disease, also may suppress the ratio to <1.
Acute stress (including hospitalization and surgery), alcoholism, depression, and many drugs (eg, exogenous cortisone, anticonvulsants) can obliterate normal diurnal variation, affect response to suppression/stimulation tests, and increase baseline levels.
This methodology (liquid chromatography tandem mass spectrometry) eliminates analytical interferences including carbamazepine (Tegretol) and synthetic corticosteroids.
This test has limited usefulness in the evaluation of adrenal insufficiency.
Improper collection may alter results. For example, a missed morning collection may result in false-negative tests; an extra morning collection (ie, >24 hours) may give false-positive results.
Renal disease (decreased clearance) may cause falsely low values.
Values may be elevated to twice normal in pregnancy.
Patients with exogenous Cushing syndrome caused by ingestion of hydrocortisone will not have suppressed cortisol and cortisone values.