Apparent mineralocorticoid excess

Synonyms

1

Overview

Apparent mineralocorticoid excess (AME/AME1) is a form of inherited high blood pressure/ hypokalemia (abnormally low levels of potassium)or an autosomal recessive disorder that starts during early childhood. The condition results from a genetic defect which causes impaired metabolism of cortisol. The condition responds to glucocorticoid treatment.

Other conditions such as Liddle's Syndrome can mimic the clinical features of AME, so diagnosis can be made by calculating the ratio of free urinary cortisol to free urinary cortisone. Since AME patients create less cortisone, the ratio will much be higher than non-affected patients. Alternatively, one could differentiate between the two syndromes by administering a potassium-sparing diuretic. Patients with Liddle's syndrome will only respond to a diuretic that binds the ENaC channel, whereas those with AME will respond to a diuretic that binds to ENaC or the mineralcorticoid receptor.

AME is exceedingly rare, with less than 100 cases recorded worldwide. Liquorice consumption may also cause a temporary form of AME due to its ability to block 11β-hydroxysteroid dehydrogenase type 2, in turn causing increased levels of cortisol. Cessation of licorice consumption will reverse this form of AME.

Symptoms

  • Hypertension
  • Failure to thrive
  • Hypercalciuria
  • Nephrocalcinosis
  • Hypokalemia
  • Metabolic alkalosis
  • Low birth weight
  • Excessive urination
  • Excessive thirst
  • High levels of calcium in urine
  • Low rennin levels
  • Metabolic acidosis
  • Hyperaldosteronism
  • Low levels of aldosterone
  • 11beta-hydroxy dehydrogenase deficiency
  • Increased kidney cortisol level
  • Poor growth
  • Increased risk of stroke during childhood or adolescence

Causes

It results from mutations in the HSD11B2gene, which encodes the kidney isozyme of 11β-hydroxysteroid dehydrogenase type 2. In an unaffected individual, this isozyme inactivates circulating cortisol to the less-active metabolite cortisone. The inactivating mutation leads to elevated local concentrations of cortisol in the kidney. Cortisol at high concentrations can cross-react and activate the mineralocorticoid receptor, leading to aldosterone-like effects in the kidney. This is what causes the hypokalemia, hypertension, and hypernatremia associated with the syndrome.

Resources

  • NIH