Apparent mineralocorticoid excess syndrome: an overview.
Apparent mineralocorticoid excess (AME) syndrome results from defective 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2). This enzyme is co-expressed with the mineralocorticoid receptor (MR) in the kidney and converts cortisol (F) to its inactive metabolite cortisone (E). Its deficiency allows the unmetabolized cortisol to bind to the MR inducing sodium retention, hypokalemia, suppression of PRA and hypertension. Mutations in the gene encoding 11beta-HSD2 account for the inherited form, but a similar clinical picture to AME occurs following the ingestion of bioflavonoids, licorice and carbenoxolone, which are competitive inhibitors of 11beta-HSD2. Reduced 11beta-HSD2 activity may explain the increased sodium retention in preeclampsia, renal disease and liver cirrhosis. Relative deficiency of 11beta-HSD2 activity can occur in Cushing's syndrome due to saturation of the enzyme and explains the mineralocorticoid excess state that characterizes ectopic ACTH syndrome. Reduced placental 11beta-HSD2 expression might explain the link between reduced birth weight and adult hypertension. Polymorphic variability in the HSD11B2 gene in part determines salt sensitivity, a forerunner for adult hypertension onset. AME represents a spectrum of mineralocorticoid hypertension with severity reflecting the underlying genetic defect in the 11beta-HSD2; although AME is a genetic disorder, several exogenous compounds can bring about the symptoms by inhibiting 11beta-HSD2 enzyme. Substrate excess as seen in Cushing's syndrome and ACTH ectopic production can overwhelm the capacity of 11beta-HSD2 to convert F to E, leading up to an acquired form of AME.
Palermo
Mario
M
Institute of Endocrinology, University of Sassari, Sassari, Italy. mariocp@tin.it
Quinkler
Marcus
M
Stewart
Paul M
PM
D000471:Alkalosis / Q000235:genetics / Q000503:physiopathology; D003663:Decision Trees; D006801:Humans; D006973:Hypertension / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D007008:Hypokalemia / Q000235:genetics / Q000503:physiopathology; D043204:Mineralocorticoid Excess Syndrome, Apparent / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D010953:Plasma Volume; D012084:Renin-Angiotensin System; D013577:Syndrome