In 2 unrelated patients, Ulick et al. (1979) described a disorder in the peripheral metabolism of cortisol, manifested by hypertension, hypokalemia, low plasma renin activity, and responsiveness to spironolactone. Aldosterone levels were subnormal. Although the features suggested primary mineralocorticoid excess, no overproduction of mineralocorticoid could be demonstrated. One of the patients, who had been reported by New et al. (1977), was a 3-year-old Zuni Indian girl with hypertension, hypokalemia, and decreased secretion of all known sodium-retaining corticosteroids. The second patient was a boy of Middle Eastern parentage who had a stroke with residual left hemiparesis at age 7, and was first found to be hypertensive at age 9 (blood pressure as high as 250/180 mm Hg). Other findings included growth retardation, grade III retinopathy, hypokalemia, and hyposthenuria. Biochemical studies indicated a decreased rate of conversion of active cortisol to cortisone, and the authors postulated a defect in 11-beta-hydroxy oxidation of cortisol. Ulick et al. (1979) suggested the term 'apparent mineralocorticoid excess.'
"The whole body 11bHSD1 activity reflects mainly hepatic expression. Initial studies that relied on measurements of cortisol-to-cortisone metabolites in urine (23,36) should be taken with caution as indicative of 11bHSD1 activity, because several other cortisol and cortisone metabolizing enzymes are deregulated in obesity (36). Of greater importance is the finding of reduced hepatic 11bHSD1 activity measured by the conversion of orally administered cortisone to cortisol (23,37). Thus, 11bHSD1 upregulation in obesity seems not to be a generalized process. In both the whole body and the splanchnic circulation there are no differences between obese and lean subjects regarding cortisol regeneration rates (as measured by [2H4]-cortisol tracer), presumably because an upregulation in adipose tissue is counterbalanced by a downregulation in the liver (15).
11 beta-hydroxysteroid dehydrogenase (11 beta HSD) has both dehydrogenase (11 beta DH) and reductase (11 beta R) activities, which catalyse the interconversion of cortisol and cortisone, and prednisolone and prednisone. This enzyme confers specificity on the mineralocorticoid receptor by local oxidation of cortisol to cortisone. Using radiolabelled cortisol 11 beta HSD activity has been shown to be lower in some cases of essential hypertension. This study investigated a novel approach to estimating 11 beta HSD activity in vivo. Plasma steroid kinetics were investigated following oral hydrocortisone (a substrate for 11 beta DH) and prednisone (a substrate for 11 beta R) in five normotensive volunteers after dexamethasone suppression of endogenous steroid production. This approach was evaluated by inducing partial deficiency of 11 beta HSD in the volunteers who took liquorice (to inhibit 11 beta DH) and then carbenoxolone (to inhibit both 11 beta DH and 11 beta R). The ratio of cortisol to prednisolone (formed from prednisone) provided a measure of the activity of both 11 beta DH and 11 beta R. At 75 min after the steroid bolus the ratio increased from (-) (median, range) under control conditions to (-) after liquorice (P = , n = 5), and (-) after carbenoxolone (P = , n = 5). It may therefore be applied to the measurement of 11 beta HSD activity in vivo in large numbers of hypertensive patients without the use of radioisotopes.