APPARENT MINERALOCORTICOID EXCESS

In 1979, Ulick and New first coined the term Apparent Mineralocorticoi d Excess (AME) for a syndrome of hypertension, hypokalaemia, suppresse d renin-angiotensin-aldosterone axis and raised urinary ratio of 11bet a-hydroxy to 11-oxo metabolites of cortisol (suggesting a failure of c onversion of cortisol to cortisone). In retrospect, the first case was described in 1974 and since then over 20 children have been reported worldwide but only one adult patient. The enzyme 11beta-hydroxysteroid dehydrogenase (11beta-OHSD) confers aldosterone specificity on intrin sically nonspecific kidney mineralocorticoid receptors by converting t he active glucocorticoid cortisol to its inactive 11-oxo form (cortiso ne). Patients with AME have a deficiency of this enzyme which allows p hysiological levels of cortisol to flood mineralocorticoid receptors. Dexamethasone, by suppressing adrenal cortisol production, reverts the biochemistry but not usually the BP to normal. Liquorice inhibits 11b eta-OHSD by virtue of its active ingredient glycyrrhetinic acid, resul ting in an identical clinical picture. Renal 11beta-OHSD is the protag onist in AME but this enzyme is found in many other tissues including liver, placenta and vasculature, and one-third of essential hypertensi ves have deficient 11beta-OHSD. The placental isoform is thought to be the main barrier to maternal glucocorticoids reaching the fetus. The lowest rat placental 11beta-OHSD activity is found in the largest plac entas corresponding to the smallest fetuses (presumably exposed to the highest glucocorticoid levels). This is the group which in humans are most at risk of developing hypertension. In support of the hypothesis that glucocorticoid excess in utero imprints patterns leading to hype rtension in adults is our observation that treatment of pregnant rats with dexamethasone leads to the development of hypertension in adult o ffspring.