Cardiometabolic Complications of Cushing's Syndrome: Mechanism and Management – A Systematic review

ABSTRACT: Background: Cushing’s syndrome (CS), caused by chronic endogenous or exogenous glucocorticoid excess, is associated with a severe cardiometabolic phenotype and increased cardiovascular morbidity and mortality. Many complications persist even after biochemical remission, highlighting the need for comprehensive long-term management. Objective: To systematically review the epidemiology, pathophysiological mechanisms, clinical assessment, and management strategies for cardiometabolic complications in CS, and to identify gaps in current evidence. Methods: A systematic literature search was conducted in PubMed, Embase, Scopus, and Google Scholar for studies published up to 2025, in accordance with PRISMA guidelines. Eligible articles included observational studies, interventional trials, systematic reviews, and guidelines addressing cardiovascular and metabolic outcomes in CS. Data were extracted and synthesized qualitatively across predefined domains. Results: CS is characterized by resistant hypertension, visceral obesity, insulin resistance and diabetes, dyslipidemia, nonalcoholic fatty liver disease, a prothrombotic state, and accelerated atherosclerosis. These abnormalities result from multifactorial glucocorticoid effects on metabolism, vasculature, and inflammation. Although definitive control of cortisol improves outcomes, residual cardiometabolic risk frequently persists after remission. Targeted management of blood pressure, glycaemia, lipids, and thrombotic risk, along with perioperative thromboprophylaxis and rehabilitation, is essential for risk reduction. Conclusions: Cardiometabolic complications are major determinants of morbidity and mortality in CS. Normalization of cortisol alone is often insufficient; an integrated, long-term strategy addressing persistent metabolic and vascular dysfunction is required. Further high-quality prospective studies are needed to define optimal post-remission management and long-term outcomes. Top of Form Bottom of Form Keywords: Cushing’s syndrome, hypercortisolism, hypertension, insulin resistance, dyslipidemia, venous thromboembolism, cardiovascular risk, management