title: Mineralocorticoid hypertension and congenital deficiency of 11 beta-hydroxysteroid dehydrogenase in a family with the syndrome of 'apparent' mineralocorticoid excess.
abstract: The so-called syndrome of 'apparent mineralocorticoid excess' (AME) is a rare cause of endocrine hypertension thought to result from a defect 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 case is a 4-year-old boy with mineralocorticoid hypertension, short stature, failure to thrive, hypokalaemic nephropathy and osteopenia. The ratio of the urinary excretion of tetrahydrocortisone/tetrahydrocortisols was reduced at 0.05 (reference range 1.77-2.11), and the plasma half-life of 3H-11 alpha-cortisol elevated at 152 minutes (reference range 30-50) indicative of severe 11 beta-hydroxysteroid dehydrogenase deficiency. Plasma cortisol concentrations were normal and daily secretion rate reduced. Dexamethasone administration induced a natriuresis in keeping with the observation that cortisol itself is the implicated mineralocorticoid. Treatment with amiloride lowered blood pressure, increased 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 trivial diarrhoeal illness and was almost certainly affected. AME was also diagnosed in a younger brother (age 17 months), but both parents are normal. Congenital deficiency of 11 beta-hydroxysteroid dehydrogenase should be considered in any child with mineralocorticoid hypertension and failure to thrive. As cortisol is the 'offending' mineralocorticoid in this condition, the term 'apparent' mineralocorticoid excess is perhaps obsolete.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Paediatric Nephrology, Children's Hospital, Ladywood, Birmingham, UK.
authors.forename: D V
authors.initials: DV
authors.lastname: Milford
authors.forename: C H
authors.initials: CH
authors.lastname: Shackleton
authors.forename: P M
authors.initials: PM
authors.lastname: Stewart
mesh_terms: D042842:11-beta-Hydroxysteroid Dehydrogenases; D002675:Child, Preschool; D003241:Consanguinity; D004200:Diseases in Twins; D005190:Family; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D006913:Hydroxysteroid Dehydrogenases / Q000172:deficiency*; D006973:Hypertension / Q000097:blood*; D007223:Infant; D008297:Male; D013577:Syndrome
chemical_list: D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D006854:Hydrocortisone