Cortisol:Cortisone Ratio Profile, LC/MS-MS

The mineralocorticoid receptor binds cortisol as an active ligand, yet in normal people cortisol levels are not related to sodium retention. While in vitro the mineralocorticoid receptor has a similar affinity as aldosterone and cortisol, and in vivo cortisol is found in concentrations 100 to 1000 times higher than those of aldosterone, 11β-hydroxysteroid dehydrogenase 2 protects the mineralocorticoid receptor by reducing cortisol to cortisone, which is not an active ligand. This enzyme occurs in cells that contain the receptor. A similar enzyme is present in other tissues but works more slowly and backwards, converting cortisone to cortisol. Defects in this system can cause hypertension and can be diagnosed from the cortisol to cortisone ratio.^1-6

Apparent mineralocorticoid excess (AME) is a rare recessive genetic disease that is characterized by childhood onset of hypertension, hypokalemic alkalosis, and low plasma renin and aldosterone levels.^7-8 Hypertension is due to impaired conversion of cortisol to cortisone due to an inactive 11β-hydroxysteroid dehydrogenase (11βHSD). This condition may be diagnosed with elevated cortisol metabolite to cortisone metabolite ratios in urine or more recently with an elevated cortisol to cortisone ratio in serum.¹ It is recommended that cortisol:cortisone ratios (F/E) be tested in hypokalemic hypertension cases in which aldosterone, deoxycorticosterone, and renin are all low.

Elevated cortisol:cortisone ratios may be found in chronic renal failure, excessive ingestion of glycyrrhetinic acid or derivatives, or in liver or bile-acid abnormalities.⁷ Even in these circumstances, however, determination of the cortisol:cortisone ratio is recommended to help shed light on the source of hypertension.