Long-term outcomes and survival predictors in patients with ectopic ACTH syndrome: data from a retrospective cohort study.

Background: Ectopic ACTH syndrome (EAS) is caused by non-pituitary neuroendocrine tumor (NET) that produces adrenocorticotropic hormone (ACTH).

Objective: To identify survival predictors and to analyze long-term outcomes in patients with EAS.

Methods: Medical records of patients with verified EAS between 1990 and 2024 were analyzed to obtain the initial clinical and biochemical data along with subsequent interventions and survival outcomes.

Results: The study included 173 patients (107 women and 66 men), with a median (Q25-Q75) age of 42 years (29; 55). The median follow-up period was 54 months (16; 99) with a maximum of 402 months. Over the observation period, death was registered in 50 (28.9%) cases. The overall 3- and 5-year survival rates were 77 and 70%, respectively. Multivariable analysis revealed the following negative predictive factors for survival: age at diagnosis ≥51 years (hazard ratio (HR) 3.53; 95% confidence interval (CI): 1.67-7.5; P = 0.001), presence of metastases (HR 2.93; 95% CI: 1.35-6.32; P = 0.006), and active hypercortisolism (HR 5.58; 95% CI 1.62-19.24; P = 0.006) along with late night salivary cortisol levels (LNSC) above 130 nmol/L (HR 2.81; 95% CI: 1.30-6.07; P = 0.009).

Conclusion: Active hypercortisolism, high LNSC, distant metastases and older age at diagnosis are factors associated with mortality in EAS. As severity of hypercortisolism is the main targetable factors, it should be the focus of intervention and further studies aimed at improving outcomes.