DOI: 10.1097/hjh.0000000000004367 ISSN: 0263-6352

Prevalence and cardiometabolic impact of mild autonomous cortisol secretion in primary aldosteronism: a systematic review and meta-analysis

Naseem Eisa, Mira Khoury
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Background:

Many primary aldosteronism (PA) patients harbor concomitant mild autonomous cortisol secretion (MACS), termed “Connshing syndrome.” The prevalence and cardiometabolic impact of this co-secretion have not been quantitatively synthesized.

Objective:

To determine the pooled prevalence of MACS in PA and evaluate its association with cardiovascular (CV) events, type 2 diabetes mellitus (T2DM), and obesity.

Data sources:

PubMed, Embase, Cochrane, Web of Science, and Scopus through January 2026.

Methods:

Following PRISMA 2020 and MOOSE guidelines (PROSPERO: CRD420261334965), studies reporting MACS prevalence [post-1 mg dexamethasone suppression test (DST) cortisol ≥1.8 μg/dl] in PA were included. Prevalence was pooled using random-effects models. Odds ratios (ORs) were calculated for cardiometabolic outcomes. Certainty was evaluated using GRADE.

Results:

Fourteen studies (2356 patients) were included. Pooled MACS prevalence was 26.2% [95% confidence interval (CI): 24.1–28.4; I 2 = 24.2%; prediction interval: 21.6–31.4%], consistent across European (27.0%) and East Asian (25.2%) cohorts ( P = 0.62). MACS + PA patients had higher odds of CV events (OR 1.60; 95% CI: 1.07–2.38; P = 0.021) and T2DM (OR 1.37; 95% CI: 1.00–1.86; P = 0.048), but not obesity (OR 1.10; P = 0.411). Sensitivity analyses confirmed robustness. GRADE certainty was moderate for prevalence and low for CV events.

Conclusions:

Approximately one in four PA patients has MACS, associated with a 60% higher CV event risk. These findings support routine DST screening in PA and have implications for perioperative management and cardiometabolic risk stratification.

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