Impatto cardiometabolico delle patologie surrenaliche: evidenze da studi clinici

Introduction and Aim: Adrenal hormone excess, whether involving aldosterone, cortisol or adrenal androgen, has systemic cardiometabolic consequences that extend beyond classical endocrine manifestations. The specific aims of this thesis were: 1) to evaluate the diagnostic value of postural stimulation test (PST) in distinguishing primary aldosteronism (PA) from low-renin hypertension (LRH) and to investigate the prevalence of MASLD in patients with PA, compared to benign adrenal adenomas: 2) to investigate the persistence of cardiometabolic alterations and long-term cardiovascular risk in patients with Cushing’s disease following remission: 3) to assess the impact of dual-release hydrocortisone therapy on disease control and metabolic outcomes in patients with congenital adrenal hyperplasia, with a focus on improving treatment personalization and reducing long-term cardiometabolic complications. These aims were pursued through retrospective and longitudinal analyses, dynamic hormonal testing, quantitative liver imaging and statistical approaches for clinical phenotyping. Materials and methods: We conducted a series of clinical investigations including a retrospective study of patients referred for suspected PA, a computed tomography (CT)-based sub analysis of hepatic steatosis in PA, a longitudinal study of 60 patients with Cushing’s disease with up to five years of follow-up, and a cohort study of patients with congenital adrenal hyperplasia evaluated before and after switching to dual-release hydrocortisone. Diagnostic phenotyping employed the postural stimulation test (PST) with dynamic assessment of renin and aldosterone, and statistical approaches included clustering analyses and longitudinal outcome comparisons. Results: Renin response during PST distinguished autonomous aldosterone secretion from low-renin hypertension: persistence of renin suppression in orthostatism strongly predicted PA, while renin de-suppression detected low-renin hypertension. Cluster analyses identified discrete phenotypic groups and suggested early, subclinical stages of aldosterone autonomy. Metabolic dysfunction-associated steatotic liver disease (MASLD) was highly prevalent in patients with PA, more frequent in unilateral than bilateral disease, and occurred at rates comparable to overt Cushing’s syndrome; hepatic steatosis improved after both surgical and medical treatment of aldosterone excess. In Cushing’s disease, biochemical remission did not uniformly normalize cardiometabolic risk: persistent disruption of circadian cortisol rhythmicity, particularly impaired late-night suppression, was more closely associated with adverse metabolic outcomes and surgical remission more effectively restored physiological rhythms than medical therapy. In congenital adrenal hyperplasia, dual-release hydrocortisone improved metabolic indices but was associated with inadequate overnight cortisol coverage and worsening androgen markers, indicating a trade-off between metabolic benefit and androgen control. Conclusions: These studies support a continuum model of adrenal disorders with substantial, partly reversible cardiometabolic and hepatic consequences. The PST, interpreted through renin response, showed its role in differentiating PA from low renin HTN. Routine hepatometabolic assessment should be integrated into adrenal disease care, and therapeutic strategies should prioritize restoration of physiological hormonal rhythmicity and individualized glucocorticoid regimens to balance metabolic protection with endocrine control. Future prospective and interventional studies are warranted to determine whether early identification and targeted correction of subclinical adrenal autonomy translate into durable reductions in cardiometabolic morbidity.