Apparent Mineralocorticoid Excess

Apparent mineralocorticoid excess (AME) is an autosomal recessive disorder from loss of function of 11-beta hydroxysteroid dehydrogenase type 2 (HSD11B2), which normally inactivates cortisol to cortisone in mineralocorticoid-sensitive tissues.

• Cortisol therefore activates the mineralocorticoid receptor, causing sodium retention, hypertension, hypokalaemia, metabolic alkalosis, low renin and low aldosterone.
• Severe form presents in infancy or childhood with failure to thrive, polyuria, polydipsia, severe hypertension, nephrocalcinosis, low birth weight; mild type 2 AME presents in adulthood.
• Acquired forms: liquorice and glycyrrhetinic acid ingestion (confectionery, herbal medicines, chewing tobacco, carbenoxolone), ectopic ACTH syndrome and Cushing syndrome (saturation of enzyme), grapefruit, steroid analogues, fludrocortisone.
• Complications: stroke, cardiac hypertrophy, hypokalaemic nephropathy, nephrocalcinosis, growth failure, death.

• Early severe hypertension, headaches, polyuria, muscle weakness, cramps, periodic paralysis, failure to thrive.
• Low birth weight and short stature, hypokalaemic alkalosis, hypercalciuria with nephrocalcinosis.
• Adult mild variant: resistant hypertension with hypokalaemia in the 3rd to 4th decade.
• Liquorice-induced: hypertension, oedema, hypokalaemia, myopathy, rhabdomyolysis.

• Hypertension, hypokalaemia, metabolic alkalosis, suppressed plasma renin activity and low or undetectable aldosterone.
• Elevated urinary ratio of free cortisol to free cortisone (urinary tetrahydrocortisol plus allo-tetrahydrocortisol to tetrahydrocortisone, THF+alloTHF/THE over 1 to 2 versus normal about 1), and prolonged cortisol half-life.
• Genetic testing for HSD11B2.
• Exclude Liddle syndrome (normal cortisol metabolism, amiloride-responsive), primary aldosteronism (high aldosterone), glucocorticoid-remediable aldosteronism, congenital adrenal hyperplasia (11-beta-hydroxylase, 17-alpha-hydroxylase), Cushing syndrome (24-hour urinary cortisol, dexamethasone suppression), and liquorice ingestion (history; urine glycyrrhetinic acid).
• Renal ultrasound for nephrocalcinosis; echocardiography; ECG.

• Stop liquorice or other acquired causes; treat ectopic ACTH or Cushing syndrome.
• Low sodium diet (under 2 g/day) and high potassium intake.
• Mineralocorticoid receptor blockade: spironolactone 1 to 3 mg/kg/day in children (adults 50 to 400 mg daily) or eplerenone 50 to 100 mg twice daily; effective in AME (unlike Liddle syndrome).
• Amiloride 5 to 20 mg daily or triamterene as ENaC blockers; thiazide diuretics (hydrochlorothiazide 12.5 to 25 mg) reduce calcium excretion and nephrocalcinosis (with potassium monitoring).
• Dexamethasone 0.25 to 1 mg daily (suppresses cortisol production, which is not metabolised by the defective enzyme) can improve control in some patients; monitor for growth suppression in children.
• Potassium supplementation (KCl 40 to 120 mmol/day) as needed.
• Additional antihypertensives (calcium channel blockers) as necessary.
• Monitor blood pressure, electrolytes, renal function, growth and nephrocalcinosis; renal transplantation for ESKD (not curative as the enzyme is also expressed elsewhere, but improves hypertension).
• Genetic counselling.