TOPLINE

Ectopic Cushing syndrome (ECS) was associated with significantly reduced overall survival and an increased burden of morbidity in patients with neuroendocrine neoplasms. Reduced survival seemed to be driven primarily by hypercortisolism rather than tumour progression.

METHODOLOGY

• Researchers conducted a retrospective cohort study using data from the TriNetX Global Collaborative Network to evaluate the association of ECS with overall survival and clinical outcomes in patients with neuroendocrine neoplasms.
• They included 264 patients with neuroendocrine neoplasms and concomitant ECS, identified using standardised diagnostic codes, who were propensity score matched 1:1 to those without concomitant ECS.
• The primary outcome was overall survival; secondary outcomes included all-cause hospitalisations, severe infections, venous thromboembolism, metabolic complications, organ dysfunction, and the development of metastatic events.
• Survival was assessed at 2, 4, 6, and 8 years, and the other outcomes were evaluated at 4 and 8 years.

TAKEAWAY

• Among patients with neuroendocrine neoplasms, those with ECS showed significantly shorter overall survival than those without ECS across all time periods, with an estimated 8-year survival of 55.3% vs 71.2% (hazard ratio, 1.848; P <.001).
• At both 4 and 8 years, patients with ECS had significantly higher risks for hospitalisation than those without ECS. They also experienced higher risks for venous thromboembolism, severe infections such as pneumonia and sepsis, and metabolic complications including hypertension, diabetes, and hypokalaemia.
• Organ dysfunction such as liver and kidney failure occurred more frequently in patients with ECS than in those without ECS at 4 and 8 years.
• The occurrence of new metastatic events including liver, bone, or any metastases did not differ significantly between patients with and without ECS.

IN PRACTICE

"[The study] findings suggest that the higher mortality in ECS NEN [neuroendocrine neoplasm] patients may predominantly be driven by direct Cushing-related complications rather than higher tumor aggressiveness," the authors wrote.

"The early survival divergence underscores the importance of prompt diagnosis and aggressive management of hypercortisolism," they added.

SOURCE

This study was led by Max Kappenstein, Department of Nuclear Medicine, Clinic for Radiology and Nuclear Medicine, Goethe University Frankfurt, University Hospital, Frankfurt, Germany. It was published online on July 23, 2026, in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS

The reliance on standardised diagnostic codes may have introduced the risk for coding inaccuracies, misclassification, and underreporting. The study might not have captured all cases of ectopic adrenocorticotropic hormone secretion. The possibility of unmeasured confounding cannot be entirely ruled out.

DISCLOSURES

This study did not receive any funding. The authors declared having no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.