The Differential Effect of Excess Aldosterone on Skeletal Muscle Mass by Sex.

Seung Hun Lee,Seung-Eun Lee,Mi Kyung Kwak,Jung-Min Koh,Sunghwan Suh,Kee-Ho Song,Yoon Young Cho,Jae Hyeon Kim,Beom-Jun Kim

doi:10.3389/fendo.2019.00195

Abstract

The effects of excess aldosterone on skeletal muscle in individuals with primary aldosteronism (PA) are unknown. To examine the effects of aldosterone on skeletal muscle mass in patients with PA, by sex, 309 consecutive patients were enrolled. Skeletal muscle and fat mass of 62 patients with PA were compared with those of 247 controls with non-functioning adrenal incidentaloma (NFAI). Body composition parameters were measured using bioelectrical impedance analysis, and plasma aldosterone concentration (PAC) was measured using radioimmunoassay. The PAC in all women, but not in men, showed an inverse association with both appendicular skeletal muscle mass (ASM) (β = −0.197, P = 0.016) and height-adjusted ASM (HA-ASM) (β = −0.207, P = 0.009). HA-ASM in women (but not in men) with PA was 5.0% lower than that in women with NFAI (P = 0.036). Furthermore, women with PA had a lower HA-ASM than 1:1 age- and sex-matched controls with NFAI by 5.7% (P = 0.049) and tended to have a lower HA-ASM than 1:3 age-, sex-, and menopausal status-matched controls without adrenal incidentaloma (AI) by 7.3% (P = 0.053). The odds ratio (OR), per quartile increase in PAC, of low HA-ASM in women was 1.18 [95% confidence interval (CI), 1.01–1.39; P = 0.035]. The odds of HA-ASM in subjects with PA were 10.63-fold (95% CI: 0.83–135.50) higher, with marginal significance (P = 0.069) than in those with NFAI. Skeletal muscle mass in women with PA was lower than that in women with NFAI; suggesting that excess aldosterone has adverse effects on skeletal muscle metabolism.

Highlights

Aging is associated with sarcopenia, which is characterized by loss of skeletal muscle mass and strength, and/or decline in physical performance [1]
The majority of studies examining the detrimental effects of aldosterone on skeletal muscle have been conducted in animals, in patients with congestive heart failure (CHF), or patients with alcoholic liver cirrhosis (LC), in whom muscle wasting may be caused by cachexia with impaired cardiac function or the toxic effects of alcohol
There was no significant difference in age, menopausal status of women, and in height, weight, and Glomerular filtration rate (GFR) in both sexes, between the primary aldosteronism (PA) group and the non-functioning adrenal incidentaloma (NFAI) group

Summary

Introduction

Aging is associated with sarcopenia, which is characterized by loss of skeletal muscle mass and strength, and/or decline in physical performance [1]. Blocking the mineralocorticoid receptor (MR) for aldosterone with spironolactone prevents the loss of skeletal myocytes [12], improves vascular endothelial function and muscle blood flow [13], and improves muscle contractile performance by increasing the magnesium levels and up-regulating Na+/K+ pumps [8]. Sarcopenia is caused by failure of satellite cell activation or by the promotion of proinflammatory cytokines [16] It is unclear whether excess aldosterone contributes to the development of sarcopenia in the general population

Methods

Results

Conclusion