Cortisol, Cortisone, and 6-Hydroxycortisol, 24-Hour Urine (with Ratios)

Cortisol, Cortisone, and 6-Hydroxycortisol, 24-Hour Urine (with Ratios) supports evaluation of suspected hypercortisolism (Cushing syndrome) by measuring urinary free cortisol (hydrocortisone; Compound F). The panel also aids in assessing adrenocortical function and disorders of cortisol metabolism. The urinary cortisol/cortisone ratio is used to screen for altered 11-hydroxysteroid dehydrogenase activity, while the 6-hydroxycortisol/cortisol ratio offers a qualitative index of CYP3A4 activity. This testing assists in the differential diagnosis of adrenal disorders and in monitoring metabolic effects of exogenous agents that modulate glucocorticoid interconversion or CYP3A4-mediated biotransformation.

Cortisol (hydrocortisone) is produced in the adrenal zona fasciculata under hypothalamic–pituitary regulation and facilitates proteolysis and hepatic gluconeogenesis. Cortisol and cortisone are interconverted by 11-hydroxysteroid dehydrogenase isozymes: 11α-HSD converts cortisol to cortisone (inactivation), and 11β-HSD regenerates cortisol from cortisone. The relative amounts of cortisol, cortisone, and their tetrahydro-metabolites mirror overall 11HSD activity. Both steroids undergo further inactivation by 5β-reductase to form tetrahydrocortisol and tetrahydrocortisone, which are predominantly eliminated in urine as glucuronide and sulfate conjugates. 6-Hydroxycortisol arises from cortisol through CYP3A4, a major hepatic and intestinal cytochrome P450 isoenzyme influenced by numerous xenobiotics. The urinary 6-hydroxycortisol/cortisol ratio functions as a qualitative readout of CYP3A4 activity. Measuring cortisol, cortisone, and 6-hydroxycortisol in a timed 24-hour urine collection, together with their ratios, characterizes glucocorticoid excess and abnormalities of cortisol metabolism while avoiding confounding by diurnal variation.