The Clinical Spectrum and Management of Ectopic Cushing's Syndrome: A 12-Year Single-Center Experience

Ectopic Cushing's syndrome is a severe endocrine disorder with high morbidity and mortality, making timely diagnosis and effective cortisol control crucial. The aim of this study was to assess the 12-year experience at a tertiary centre.We retrospectively analyzed clinical, biochemical, imaging, treatment, and outcome data in this single-center, non-interventional cohort of patients treated from 2012 to 2024 at the University Hospital Centre Zagreb.Twelve patients were included (10/12 female, 83.3%; median age 43.5 years, range 22-74). Primary tumors were predominantly neuroendocrine (8/12, 66.7%), and 9/12 (75.0%) had metastatic disease at diagnosis. Common features were fat redistribution in 10/12 (83.3%), facial plethora in 8/12 (66.7%), hypertension in 8/12 (66.7%), and peripheral edema in 7/12 (58.3%). Frequent biochemical alterations were hypokalemia in 11/12 (91.7%) and hyperglycemia or new-onset/worsening diabetes in 10/12 (83.3%). Median 24-hour urinary free cortisol was 5,594 nmol/24 h (range: 196-72,954), and ACTH 52.4 pmol/L (range: 8-498). A urinary free cortisol level≥50×the upper limit of normal identified a high-risk group with shorter survival (Spearman ρ=-0.50). Biochemical remission was achieved in 1/12 (8.3%) patient through tumor resection, while the majority required bilateral adrenalectomy (8/12, 66.7%) due to inadequate response to medical therapy or as first-line treatment. At the time of last follow-up, 8/12 (66.7%) patients had died due to disease progression, with a median time to death of 12 months (range: 1-51). The median overall survival was 20 months (range: 1-154).Most patients presented with metabolic disturbances and limited response to medical therapy, leading to bilateral adrenalectomy. Early mortality was driven by uncontrolled hypercortisolism rather than tumor burden, and higher urinary free cortisol was associated with shorter survival. These findings highlight the prognostic relevance of cortisol burden and the importance of prompt cortisol control.