The cortisol-cortisone shuttle and hypertension.
11 beta-OHSD is an enzyme complex consisting of 11 beta-DH, converting cortisol to cortisone in man and an 11-keto-reductase performing the reverse reaction. Congenital deficiency of 11 beta-DH should be considered in any child presenting with mineralocorticoid hypertension and suppression of the renin-angiotensin-aldosterone axis. The keystone to diagnosis is the demonstration of a reduced daily production rate of cortisol and an increase in its plasma half-life. In the majority of cases diagnosis can be made from a urinary steroid metabolite profile indicating a high excretion of cortisol relative to cortisone metabolites. Cortisol is the responsible mineralocorticoid, and as such treatment with the pure glucocorticoid dexamethasone will prevent life-threatening hypokalemia, although additional anti-hypertensive drugs are usually required to control blood pressure. Liquorice and carbenoxolone, for years thought to be direct "agonists" of the mineralocorticoid receptor, in fact cause sodium retention through inhibition of 11 beta-DH. The demonstration of 11 beta-DH activity in the vasculature raises the possibility that it locally modules access of glucocorticoids to mineralocorticoid and possibly glucocorticoid receptors in the vessel wall. It remains possible that subtle alterations of this cortisol-cortisone shuttle are responsible for other forms of hypertension which are currently classified under the umbrella diagnosis of essential hypertension.
Stewart
P M
PM
Department of Medicine, Queen Elizabeth Medical Centre, Edgbaston, Birmingham, U.K.
Edwards
C R
CR
D000818:Animals; D002229:Carbenoxolone / Q000494:pharmacology; D003348:Cortisone / Q000378:metabolism*; D006035:Glycyrrhiza; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D006913:Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006973:Hypertension / Q000503:physiopathology*; D007668:Kidney / Q000378:metabolism; D008901:Mineralocorticoids / Q000378:metabolism; D010946:Plants, Medicinal; D014882:Water-Electrolyte Balance
D008901:Mineralocorticoids; D006913:Hydroxysteroid Dehydrogenases; D002229:Carbenoxolone; D003348:Cortisone; D006854:Hydrocortisone