Exploring the high prevalence, comorbidities, and indicators of mild autonomous cortisol secretion in primary aldosteronism: a cohort study and systematic review.

Emerging evidence has suggested a significant prevalence of mild autonomous cortisol secretion (MACS) among patients diagnosed with primary aldosteronism (PA). However, MACS's clinical characteristics and implications in PA patients remain largely unexplored. To investigate the prevalence, comorbidities, and indicators of MACS in PA patients, we conducted a retrospective cohort study including 874 PA patients with dexamethasone suppression test results in the Taiwan Primary Aldosteronism Investigators (TAIPAI) cohort between February 2011 and February 2024. Additionally, we performed a systematic review and meta-analysis of 11 studies, encompassing a total of 2882 PA patients (CRD42023486755). After including the TAIPAI cohort data in the meta-analysis, the prevalence of MACS among PA patients was 21.9% (95% confidence interval [C.I.]: 18.1, 26.2), with a negative correlation with estimated glomerular filtration rate (eGFR) (r = -0.028, P < 0.01). The characteristics associated with MACS in PA patients included older age (mean difference [MD] = 5.51 year, P < 0.01), higher plasma aldosterone concentration (MD = 5.36 ng/dL, P < 0.01), lower plasma renin activity (MD = -0.15 ng/mL/h, P < 0.01), lower eGFR (MD = -4.91 mL/min/1.73 m, P = 0.01), and larger adrenal tumor size (MD = 0.41 cm, P < 0.01). MACS was significantly associated with chronic kidney disease (odds ratio [OR] = 1.96, P < 0.01), diabetes mellitus (OR = 1.60, P = 0.04), and cardiovascular diseases (OR = 1.37, P = 0.02) among PA patients. The high prevalence and strong association of MACS with comorbidities underscore the importance of identifying it in PA patients. Clinical features such as advanced age, significant aldosterone-renin dysregulation, impaired kidney function, diabetes, cardiovascular disease, and large adrenal tumors are indicators for MACS screening in PA patients.