Novel Metabolomic Profile of Subjects with Non-classic Apparent Mineralocorticoid Excess

Abstract

Nonclassic apparent mineralocorticoid excess (NC-AME) is proposed as a novel clinical condition with a mild phenotypic spectrum that ranges from normotension to severe hypertension. This condition is mainly characterized by a high serum cortisol to cortisone ratio (F/E) and concomitant low cortisone (E), however further metabolic changes in NC-AME have not been studied. A cross-sectional study was performed in a primary-care cohort of 396 Chilean subjects, which were classified in two groups: NC-AME (n=28) and healthy controls (n=27). An untargeted metabolomics assay in serum samples from both groups was performed by UPLC-Q-TOF/MS. Global metabolic variations were assayed by principal component analysis (PCA) and further compared by orthogonal partial least-squares discriminant analysis (OPLS-DA). NC-AME subjects exhibited higher values of blood pressure, fractional excretion of potassium, and lower plasma renin activity and urinary sodium to potassium ratio. Metabolomic analyses showed 36 differentially regulated metabolites between NC-AME and control subjects. The ROC curve analyses identified eight metabolites with high discriminatory capacity between NC-AME and control subjects. Moreover, gamma-L-glutamyl-L-methionine sulfoxide and 5-sulfoxymethylfurfural (SMF), exhibited significant association with cortisone, which are potential biomarkers of NCAME, however further assays should elucidate its biological role in setup and progression of this phenotype.

A genome-wide association study identifies a novel association between SDC3 and apparent treatment-resistant hypertension

“…But our results do not correlate with previous hypertension researches. The reasons for this may be hypertension is mainly related to blood pressure regulation [20,[41][42][43][44], while resistant hypertension is closely related to metabolism [45][46][47][48][49], like fatty acid, lipid, amino acid, and purine metabolism. So, it is not surprising that there are no repeated results between our study and theirs.…”

Renin, Aldosterone, and Cortisol in Pregnancy-Induced Hypertension

“…The causes for the above-described phenomenon remain yet to be elucidated. It should be mentioned, however, that conditions associated with low renin hypertension, such as Liddle syndrome or apparent mineralocorticoid excess, have been excluded on clinical grounds as only healthy and previously normotensive women were recruited into the study, though non-classical forms of an apparent mineralocorticoid excess have been recently described 12 .…”

“…In the context of our study, we have to limit the interpretation of our findings to parameters that we have actually measured, though we suggest that assessment of a urinary steroid profile by the mass spectrometry method might provide more insight into the minutes of steroid metabolism in PIH. Indeed, the mass spectrometry method has already been employed to assess steroid metabolism in non-pregnant subjects 12 .…”