Apparent mineralocorticoid excess.
In 1979, Ulick and New first coined the term Apparent Mineralocorticoid Excess (AME) for a syndrome of hypertension, hypokalaemia, suppressed renin-angiotensin-aldosterone axis and raised urinary ratio of 11 beta-hydroxy to 11-oxo metabolities of cortisol (suggesting a failure of conversion 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 intrinsically nonspecific kidney mineralocorticoid receptors by converting the active glucocorticoid cortisol to its inactive 11-oxo form (cortisone). Patients with AME have a deficiency of this enzyme which allows physiological 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 11beta-OHSD by virtue of its active ingredient glycyrrhetinic acid, resulting in an identical clinical picture. Renal 11beta-OHSD is the protagonist in AME but this enzyme is found in many other tissues including liver, placenta and vasculature, and one-third of essential hypertensives 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 placentas 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Benediktsson
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R
University Department of Medicine, Western General Hospital, Edinburgh, UK.
Edwards
C R
CR
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000450:Aldosterone / Q000097:blood*; D006035:Glycyrrhiza; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000378:metabolism / Q000502:physiology; D006973:Hypertension / Q000150:complications*; D007008:Hypokalemia / Q000150:complications*; D008901:Mineralocorticoids / Q000378:metabolism*; D010946:Plants, Medicinal; D012083:Renin / Q000097:blood*; D013577:Syndrome
D008901:Mineralocorticoids; D000450:Aldosterone; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D012083:Renin