apparent mineralocorticoid excess syndrome

Etiology

• licorice ingestion
• - genetic defect (see Genetics below)

Pathology

• glycyrrhetinic acid found in licorice or triazole antifungals inhibits 11 beta-hydroxysteroid dehydrogenase thus biosynthesis of aldosterone
• cortisol binds to the mineralocorticoid receptor with a similar affinity to aldosterone
• 11 beta-hydroxysteroid dehydrogenase converts cortisol to cortisone, which does not bind the mineralocorticoid receptor
• activation of the mineralocorticoid receptor by cortisol
• because cortisol levels are 100-fold greater than aldosterone, inhibition of 11 beta-hydroxysteroid dehydrogenase will produce a syndrome similar to primary hyperaldosteronism*

Genetics

• congenital genetic mutation in the 11 beta-hydroxysteroid dehydrogenase gene HSD11B2
• ingestion of an agent that can inhibit this enzyme

Clinical manifestations

• new-onset hypokalemia, metabolic alkalosis, & hypertension

Laboratory

• plasma renin: low
• plasma aldosterone: low
• serum potassium is low
• serum bicarbonate is high
• 24-hour urine cortisol/cortisone ratio > 1.0 for diagnostic confirmation
  • normally < 0.5

Complications

• nephrocalcinosis
• potentially fatal

Differential diagnosis

• Liddle syndrome
  • autosomal dominant disease, family history
  • most frequently presents at a young age
  • not be associated with sudden onset

Management

• avoid liquorice
• thiazide diuretics
• aldosterone antagonist, potassium-sparing diuretic
  • spironolactone
  • triamterene
  • amiloride

More general terms

• genetic disease of the endocrine system
• syndrome

Database

• OMIM: https://mirror.omim.org/entry/218030