Apparent mineralocorticoid excess type II

The syndrome of apparent mineralocorticoid excess (AME) is currently understood to reflect impaired peripheral metabolism of cortisol, which is then able to activate the non-selective mineralocorticoid (MC) receptor. The failure of glucocorticoid inactivation at the MC target tissue level in AME involves abnormal activity of 11β-hydroxysteroid dehydrogenase, with impaired conversion of cortisol to cortisone, and also of 5β-reductase. We have discovered a new form of AME (Type II) in four patietns with the same clinical picture of hypertension, hypokalemia, and suppressed renin-angiotensin-aldosterone system, but in whom this conversion seems either to be normal (since cortisol to cortisone metabolite ratio is normal) or to be impaired in both directions, leaving the ratio unchanged. Both types are characterized by a profound decrease in cortisol turnover quotient and Ring A reduction constant. Short-term dexamethasone treatment is effective in correcting the MC-derived abnormalities, while in the long term the addition of other antihypertensive drugs may be required to control the severity of hypertension.