Classic and Nonclassic Apparent Mineralocorticoid Excess Syndrome.

Abstract

CONTEXT\nArterial hypertension (AHT) is one of the most frequent pathologies in the general population. Subtypes of essential hypertension characterized by low-renin levels allowed the identification of two different clinical entities: aldosterone-mediated mineralocorticoid receptor (MR) activation and cortisol-mediated MR activation.\n\n\nEVIDENCE ACQUISITION\nThis review is based upon a search of Pubmed and Google Scholar databases, up to August 2019, for all publications relating to endocrine hypertension, apparent mineralocorticoid excess (AME) and cortisol (F) to cortisone (E) metabolism.\n\n\nEVIDENCE SYNTHESIS\nThe spectrum of cortisol-mediated MR activation includes the classic AME to milder (nonclassic) forms of AME, the latter with a much higher prevalence (7.1%) than classic AME but different phenotype and genotype. NC-AME is mainly related to partial 11βHSD2 deficiency associated with genetic variations and epigenetic modifications (first hit) and potential additive actions of endogenous or exogenous inhibitors (i.e., glycyrrhetinic acid-like factors (GALFS)) and other factors (i.e. age, high sodium intake) (second hit). Subjects with NC-AME are characterized by high F/E ratio and low E levels, normal and elevated blood pressure, low-renin and increased urinary potassium excretion. NC-AME condition should benefits from low-sodium and potassium diet recommendations and monotherapy with MR antagonists.\n\n\nCONCLUSIONS\nNC-AME has higher prevalence and a milder phenotypical spectrum than AME. NC-AME etiology is associated to a first hit (gene & epigene level) and an additive second hit. NC-AME subjects are candidates to be treated with MR antagonists aimed to improve blood pressure, end-organ damage and modulate the renin levels.