Which syndrome features elevated cortisol to cortisone ratio in the urine despite normal serum cortisol levels?
The syndrome of apparent mineralocorticoid excess (AME) is characterized by autosomal recessive hypertension and hypokalemia associated with metabolic alkalosis. In some cases, nephrocalcinosis and renal cysts are observed. The syndrome is caused by bi-allelic loss-of-function mutations in the kidney-specific isoform of 11β-hydroxysteroid dehydrogenase (11β-HSD 2), which allow concentrations of cortisol to rise in distal tubular cells and subsequent activation of the mineralocorticoid receptor (MR). Usually the 11β-HSD 2 enzymes “protect” MR from cortisol by oxidizing it to its inactive metabolite cortisone. The function of 11β-HSD 2 is important, since cortisol has the same affinity for the MR as aldosterone and typically a 10-fold greater level than aldosterone. An elevated urine (tetrahydro)cortisol-to-(tetrahydro)cortisone ratio greater than 0.5 establishes the diagnosis. The mainstay of therapy hinges on MR blockade with spironolactone. Adjunctive therapy includes potassium supplementation and low sodium diet.
