Primary aldosteronism (PA) patients frequently exhibit metabolic syndrome and obesity, with excess aldosterone causing cardiac remodeling and metabolic issues like visceral obesity, insulin resistance, and impaired glucose homeostasis. Autonomous cortisol secretion (ACS), often underdiagnosed in PA, increases obesity, diabetes, and cardiovascular events. Studies show that ACS (without PA) links to higher visceral adipose tissue and reduced muscle quantity. However, ACS's effect on body composition in PA patients is unclear; some studies show no difference in fat volumes between ACS and non-ACS groups in PA patients, while others show lower skeletal muscle area in APA patients with ACS. Myosteatosis, excessive fat in skeletal muscle, is a negative prognostic factor in various diseases and is associated with poor outcomes. While Cushing's syndrome shows visceral obesity and muscle wasting, research on ACS cohorts in PA is limited. This study aims to clarify the relationship between muscle fat content, especially myosteatosis, and ACS in APA patients.

The existing literature presents conflicting evidence regarding the relationship between autonomous cortisol secretion (ACS) and body composition in patients with primary aldosteronism (PA). Some studies report no significant difference in fat distribution between ACS and non-ACS groups within the PA population, while others demonstrate a clear association between ACS and reduced skeletal muscle mass in aldosterone-producing adenoma (APA) patients. The impact of ACS on myosteatosis, specifically, remains unexplored. The association of myosteatosis with poor prognosis in various conditions, including cardiovascular disease and cancer, highlights the need for further investigation into its connection with endocrine disorders such as ACS. Prior research has extensively documented the link between hypercortisolism and disruptions in muscle metabolism, but the specifics of these effects in the context of APA and ACS remain largely unknown.

This retrospective study analyzed data from the Taiwan Primary Aldosteronism Investigators (TAIPAI) database, focusing on 228 adult APA patients (≥18 years) who underwent unilateral adrenalectomy between January 2009 and April 2024. PA diagnosis was based on an aldosterone-renin ratio >35 ng/mL/h, plasma aldosterone concentration >16 ng/dL, or PAC/plasma renin activity >35 ng/dL. APA diagnosis required evidence of PA, lateralized aldosterone secretion confirmed by adrenal vein sampling, histopathological evidence of adenoma, and PA correction post-adrenalectomy. ACS was defined by an overnight 1 mg dexamethasone suppression test (DST) with serum cortisol ≥5 µg/dL. Body composition was assessed via computed tomography (CT) scans at the L3 vertebral level, measuring intermuscular adipose tissue (IMAT), skeletal muscle area (SMA), skeletal muscle density (SMD), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT). A blinded researcher, guided by radiologists, analyzed the CT images using sliceOmatic software. Statistical analysis included t-tests, chi-square tests, multivariable linear regression (adjusting for age, sex, BMI, systolic BP, diabetes, triglycerides, and cholesterol), Pearson's correlation, and the Wilcoxon signed-rank test. A subset of 44 patients had 1-year post-adrenalectomy follow-up CT scans.

Of the 228 APA patients, 76 (33.3%) had ACS. ACS patients were older (P=0.002), had higher serum potassium (P=0.012), higher post-DST cortisol (P<0.001), lower baseline ACTH (P<0.001), and lower dehydroepiandrosterone sulfate (P<0.001) compared to non-ACS patients. ACS patients showed significantly higher IMAT area (P=0.042), lower IMAT density (P=0.006), lower SMD (P<0.001), and lower SMA (P=0.002) than non-ACS patients. Multivariable regression confirmed that ACS was independently associated with higher IMAT area and lower SMA and SMD (all P<0.05). Post-DST serum cortisol levels positively correlated with IMAT area (R²=0.027, P=0.012) and negatively correlated with SMA (R²=0.060, P<0.001) and SMD (R²=0.123, P<0.001). In the 44 patients with 1-year follow-up, the ACS group showed a significant decrease in IMAT area (P=0.001) and an increase in SMA (P=0.031) post-adrenalectomy. The non-ACS group showed no IMAT changes but significant increases in VAT and SAT areas (P<0.001 and P=0.008, respectively).

This study reveals a novel association between ACS and myosteatosis in APA patients, independent of sarcopenia. The findings demonstrate that ACS is linked to increased intramuscular fat deposition and reduced skeletal muscle mass and density. The improvement in IMAT and SMA following adrenalectomy in ACS patients strongly suggests a causal relationship between ACS and these muscle alterations. The lack of change in IMAT in the non-ACS group post-adrenalectomy further supports this conclusion. These results highlight the importance of considering ACS in assessing cardiovascular risk and muscle health in APA patients. The observed changes in body composition could contribute to the increased cardiovascular morbidity associated with ACS.

This study demonstrates a clear link between autonomous cortisol secretion (ACS) and both myosteatosis and sarcopenia in patients with aldosterone-producing adenomas (APA). The significant improvements in muscle parameters after adrenalectomy underscore the detrimental effects of ACS on muscle health. Further research should explore the underlying mechanisms of this association and investigate whether targeted interventions to mitigate the effects of ACS could improve muscle health and cardiovascular outcomes in these patients.

The retrospective nature of the study and the relatively small sample size of the follow-up group are limitations. The use of a single-slice CT scan at the L3 vertebral level for body composition analysis may not fully represent whole-body muscle composition. The cross-sectional design prevents determination of causality. Further prospective studies with larger sample sizes and more comprehensive assessments of body composition are needed to validate these findings.