Apparent mineralocorticoid excess and the long term treatment of genetic hypertension. Issue 165 (January 2017)

• Record Type: Journal Article
• Authors: Razzaghy-Azar, Maryam; Yau, Mabel; Khattab, Ahmed; New, Maria I.
• Is Part Of: Journal of steroid biochemistry and molecular biology. Issue 165:Part A(2017)
• Page Start: 145
• Page End: 150
• Publication Date: 2017-01
• Subjects: Low renin hypertension -- 11β-Hydroxysteroid dehydrogenase type 2 -- Spironolactone; Steroid hormones -- Periodicals; Biochemistry -- Periodicals; Hormones -- Periodicals; Molecular Biology -- Periodicals; Hormones stéroïdes -- Périodiques; Steroid hormones; Periodicals; 572.579
• DOI: 10.1016/j.jsbmb.2016.02.014
• Languages: English
• ISSNs: 0960-0760

Abstract

Highlights: AME is a hypertensive disorder owing to 11ßHSD2 deficiency. More than 40 mutations in the HSD11B2 gene causing AME have been identified. Chronic hypertension in AME leads to the early development of end organ damage. Spironolactone treatment of AME normalizes blood pressure and improves growth. Renal transplantation of patients with AME and renal failure led to cure of AME. 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 20 year 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.