Snapshot A 10-year-old boy with autism presents to his pediatrician’s office for muscle weakness. He has been refusing all food except licorice. His parents have been buying him bags of licorice in an effort to prevent starvation. Laboratory test reveals hypokalemia and metabolic alkalosis. His parents are counseled about eating excessive licorice and the family is referred to a specialist center for behavioral therapy. Introduction Clinical definition Syndrome of Apparent Mineralocorticoid Excess (SAME) is a hereditary defect in 11β-hydroxysteroid dehydrogenase causing hypertension hypokalemia metabolic alkalosis these findings are similar to those in primary aldosteronism Epidemiology Demographics early childhood onset Risk factors family history Etiology Hereditary deficiency Acquired disorder ingestion of glycyrrhetinic acid (licorice) Pathogenesis genetic loss-of-function mutation in 11β-hydroxysteroid dehydrogenase (kidney isoform) 11β-hydroxysteroid dehydrogenase usually converts cortisOL to cortisONE cortisOL can activate mineralocorticoid receptors (in fact, similar affinity with aldosterone) cortisone is inactive deficiency results in excess cortisol, which will increase activation of mineralocorticoid receptor glycyrrhetinic acid inhibits 11β-hydroxysteroid dehydrogenase and reduces gene expression Genetics inheritance pattern autosomal recessive mutations chromosome 16 11β-HSD2 gene Associated conditions nephrogenic diabetes inspidus induced by chronic hypokalemia Presentation Symptoms infants low birth weight failure to thrive Physical exam muscle weakness due to hypokalemia hypertension Studies Labs hypokalemia metabolic alkalosis ↓ aldolsterone level ↓ renin activity may have ↑ creatinine Urine hypercalciuria free cortisol to free cortisone ratio on 24-hour urine collection normal ratio is 0.3-0.5 in hereditary disorder, ratio is 5-18 in licorice ingestion, ratio is only modestly elevated Differential Liddle syndrome urine cortisol to cortisone ratio is normal Primary aldosteronism elevated aldosterone Treatment Conservative remove licorice from diet indications for those with acquired SAME from licorice ingestion Medical mineralocorticoid blockade indications for those with hereditary SAME drugs spironolactone eplerenone amiloride triamterene corticosteroids indications if mineralocorticoid blockade is not effective or tolerated thiazides indications hypercalciuria Complications Cardiac arrhythmia from hypokalemia