Clinical feature: 

Definition: Apparent mineralocorticoid excess (AME) is an autosomal recessive disorder that imitates all symptoms of elevated mineralocorticoid levels, including hypertension and hypokalemia, despite rather suppressed secretion of renin and aldosterone. Due to a deficiency in cortisol to cortisone conversion in the kidney, the mineralocorticoid receptor is unspecifically stimulated by cortisol.

Pathogenesis: The disease AME is caused by cortisol 11-beta-ketoreductase deficiency. This enzyme resides in epithelial cell of the distal convoluted tubule, the site where fine tuning of renal potassium secretion happens and other genes such as mineralocorticoid receptor and the sodium channel ENaC are expressed. Cortisol too can effectively stimulate the mineralocorticoid receptor, and because it is more abundant than aldosteron, it would almost replace aldosterone if there were not the enzyme in place which converts cortisol to cortisone. The latter is unable to stimulate the mineralocorticoid receptor and crosses the apical membran into the urine. If this enzyme is deficient, the mineralocoirticoid receptor action is no more regulated by aldosterone but cortisol. Hence every therapy that either blocks the mineralocorticoid receptor stimulation or cortisol production is highly effective.

Clinical picture: Apparent mineralocorticoid excess is characterized by all symptoms of hyperaldosteronism despite a rather decreased renin stimulated aldosterone secretion. The disease is marked by hypertension and hypokalemia that begin in childhood.
   Spironolactone and low sodium diet relief the symptoms. However pathognomonic is the response to dexamethasone. As this remedy suppresses cortisol secretion, it ceases unspecific stimulation of the renal mineralocorticoid receptor by cortisol.

Diagnostics: 

Diagnosis: The diagnosis of AME is made by increased urinary excretion of cortiol when related to plasma and cortisone

Differential: Liddle syndrome has a smilar clinical appearance (hypokalemia, hypertension, supressed renin and aldosterone) but shows no relief when treated with spironolactone or dexamethasone. Only amiloride is effective.  » » » 

Literature: 

Palermo M et al. (2004) Apparent mineralocorticoid excess syndrome: an overview.
Toka HR et al. () The molecular basis of hypertension.
White PC et al. (2001) 11beta-hydroxysteroid dehydrogenase and its role in the syndrome of apparent mineralocorticoid excess.
Ferrari P et al. (2001) Juvenile hypertension, the role of genetically altered steroid metabolism.
Wilson RC et al. (2001) Apparent mineralocorticoid excess.
Kamide K et al. (2006) Genetic variations of HSD11B2 in hypertensive patients and in the general population, six rare missense/frameshift mutations.