MINERALOCORTICOID HYPERTENSION AND CONGENITAL DEFICIENCY OF 11-BETA-HYDROXYSTEROID DEHYDROGENASE IN A FAMILY WITH THE SYNDROME OF APPARENT MINERALOCORTICOID EXCESS

The so-called syndrome of 'apparent mineralocorticoid excess' (AME) is a rare cause of endocrine hypertension thought to result from a defec t in the peripheral conversion of cortisol to cortisone. Less than 30 cases have been described. From a consanguineous marriage we present a family comprising 2 and probably 3 affected cases of AME, The index c ase is a 4-year-old boy with mineralocorticoid hypertension, short sta ture, failure to thrive, hypokalaemic nephropathy and osteopenia, The ratio of the urinary excretion of tetrahydrocortisone/tetrahydrocortis ols was reduced at 0.05 (reference range 1.77-2.11), and the plasma ha lf-life of H-3-11 alpha-cortisol elevated at 152 minutes (reference ra nge 30-50) indicative of severe 11 beta-hydroxysteroid dehydrogenase d eficiency, Plasma cortisol concentrations were normal and daily secret ion rate reduced. Dexamethasone administration induced a natriuresis i n keeping with the observation that cortisol itself is the implicated mineralocorticoid, Treatment with amiloride lowered blood pressure, in creased potassium levels, and resulted in an increase in growth rate. The boy's twin brother died at the age of 3.5 years following a trivia l diarrhoeal illness and was almost certainly affected, AME was also d iagnosed in a younger brother (age 17 months), but both parents are no rmal. Congenital deficiency of 11 beta-hydroxysteroid dehydrogenase sh ould be considered in any child with mineralocorticoid hypertension an d failure to thrive, As cortisol is the 'offending' mineralocorticoid in this condition, the term 'apparent' mineralocorticoid excess is per haps obsolete. The cloning of renal isoforms of 11 beta-HSD should fac ilitate the description of the molecular basis of this condition.