Outcomes and Prognostic Factors in Ectopic Cushing Syndrome: The Experience of Two Tertiary Referral Centers

Objective Ectopic Cushing syndrome (ECS) is an uncommon cause of adrenocorticotropic hormone (ACTH)-dependent Cushing syndrome associated with high morbidity and mortality. The aim of this study was to characterize patients with ECS and to identify potential prognostic factors associated with outcomes, including the clinical utility of serum inflammation-based scores (SIBS). Design A retrospective observational study of 30 patients with ECS managed at two tertiary endocrinology referral centers. Methods Demographic, tumor-related, clinical, and biochemical variables at diagnosis were analyzed. SIBS (neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio [PLR], lymphocyte-to-monocyte ratio, and systemic immune-inflammation index) were calculated from baseline laboratory parameters. Results Primary tumor sites were the lung (60%), pancreas (10%), thymus (3%), bladder (3%), adrenal gland (3%), and occult origin (20%). Metastatic disease was present in 65% of patients. Survival was markedly heterogeneous, with a median survival of 50.61 days. Tumor resection was associated with improved survival (HR = 0.225), whereas male sex (HR = 2.808), metastatic disease (HR = 15.82), ACTH (HR = 1.002), morning cortisol (HR = 1.023), and late-night cortisol concentrations (HR = 1.027) were associated with increased mortality risk. NLR positively correlated with ACTH (r = 0.575) and morning cortisol (r = 0.658), but none of the evaluated SIBS predicted survival. Conclusions ECS is characterized by a heterogeneous clinical course and poor early survival. Male sex, metastatic disease, and severe hypercortisolism are adverse prognostic factors for overall survival, whereas surgical resection is associated with better outcomes. Hormonal status correlates with inflammatory indices, but the prognostic value of SIBS requires further investigation.