Low Cortisone as a Novel Predictor of the Low-Renin Phenotype

Abstract

A large proportion of low-renin hypertensive (LRH) patients correspond to primary aldosteronism. However, some of these subjects have low to normal aldosterone. Since low-renin is driven by excessive mineralocorticoids or glucocorticoids acting on mineralocorticoid receptor (MR), we hypothesize that a low-cortisone condition, associated classically to 11BHSD2 deficiency, is a proxy of chronic MR activation by cortisol, which also can lead to low-renin, elevated blood pressure, renal and vascular alterations. Objective To evaluate low cortisone as a predictor of low-renin activity and its association with parameters of kidney and vascular damage. Design A cross-sectional study was carried out in 206 adult subjects. The subjects were classified according to low renin activity (<1 ng/ml*h) and low-cortisone (<p25th). Results Renin activity was associated with aldosterone (r = 0.36; p < 0.001) and cortisone (r = 0.22; p = 0.001). A binary logistic regression analysis showed that serum cortisone per ug/dl increase predicted the LR phenotype (OR = 0.4 [95% CI, 0.21–0.78]). The ROC curves for cortisone showed an AUC of 0.6 to discriminate subjects with low-renin activity from controls. The low-cortisone subjects showed higher albuminuria and PAI-1 and lower sodium excretion. The association study also showed that urinary cortisone was correlated with blood pressure and serum potassium (p < 0.05). Conclusion This is the first study showing that low-cortisone is a predictor of a low-renin condition. Low-cortisone predicted also surrogate markers of vascular and renal damage. Since the aldosterone to renin ratio is used in the screening of PA, low cortisone values should be considered additionally to avoid false positives in the ARR calculation.