title: Apparent mineralocorticoid excess and the long term treatment of genetic hypertension.
abstract: Apparent mineralocorticoid excess (AME) is a genetic disorder causing severe hypertension, hypokalemia, and hyporeninemic hypoaldosteronism owing to deficient 11 beta-hydroxysteroid dehydrogenase type-2 (11βHSD2) enzyme activity. The 11βHSD2 enzyme confers mineralocorticoid receptor specificity for aldosterone by converting cortisol to its inactive metabolite, cortisone and inactivating the cortisol-mineralocorticoid receptor complex. The 20year follow-up of a consanguineous Iranian family with three sibs affected with AME shows the successes and pitfalls of medical therapy with spironolactone. The three sibs, (female, male, female) were diagnosed at the ages of 14, 11, and 4 years, respectively. At diagnosis, hypertensive retinopathy and left ventricular hypertrophy were present in the eldest female and retinopathy was noted in the male sib. Spironolactone treatment resulted in decreased blood pressure and rise in serum potassium levels. The older female, age 36, developed reduced left ventricular function with mitral and tricuspid regurgitation and renal failure after her second pregnancy. She was treated with renal transplantation resulting in cure of AME with decreased blood pressure and weaning from antihypertensives. Her younger sibs, age 34 and 26, do not have end organ damage. Early and vigilant treatment improves morbidity in patients with AME. Mineralocorticoid receptor antagonists normalize blood pressure, correct hypokalemia and reduce hypertensive end-organ damage in patients with AME. Low dose dexamethasone can be considered, though the response may be variable. Future directions of therapy include selective mineralocorticoid antagonists.
authors.affiliation: Metabolic Disorders Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Iran; H. Aliasghar Hospital, Iran University of Medical Sciences, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Razzaghy-Azar
authors.affiliation: Adrenal Steroid Disorder Group, Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, United States. Electronic address: mabel.yau@mssm.edu.
authors.forename: Mabel
authors.initials: M
authors.lastname: Yau
authors.affiliation: Adrenal Steroid Disorder Group, Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Khattab
authors.affiliation: Adrenal Steroid Disorder Group, Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
authors.forename: Maria I
authors.initials: MI
authors.lastname: New
mesh_terms: D042842:11-beta-Hydroxysteroid Dehydrogenases / Q000172:deficiency* / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D001794:Blood Pressure; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005091:Exons; D005192:Family Health; D005260:Female; D006801:Humans; D006973:Hypertension / Q000235:genetics* / Q000378:metabolism / Q000628:therapy*; D007492:Iran; D016030:Kidney Transplantation; D008297:Male; D043204:Mineralocorticoid Excess Syndrome, Apparent / Q000235:genetics* / Q000378:metabolism / Q000628:therapy*; D008901:Mineralocorticoids / Q000378:metabolism; D009154:Mutation; D010375:Pedigree; D011110:Polymorphism, Genetic; D011247:Pregnancy; D051437:Renal Insufficiency / Q000235:genetics / Q000628:therapy; D012083:Renin / Q000378:metabolism; D013148:Spironolactone / Q000737:chemistry / Q000627:therapeutic use
chemical_list: D008901:Mineralocorticoids; D013148:Spironolactone; D042842:11-beta-Hydroxysteroid Dehydrogenases; D012083:Renin
keywords: 11β-Hydroxysteroid dehydrogenase type 2; Low renin hypertension; Spironolactone