Objective: To summarize the clinical characteristics, treatment strategies, and prognosis of ectopic ACTH syndrome (EAS) caused by pancreatic neuroendocrine tumors (pNETs).

Methods: The clinical data, diagnosis, treatment, and follow-up outcomes of 11 patients with pNET-induced EAS diagnosed at Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from 2001 to 2024 were retrospectively analyzed.

Results: Among the 11 patients, 5 were male, and 6 were female, with a median age of 44.0 (32.5, 54.5) years. All patients presented with hypokalemia and significantly elevated levels of serum/urinary cortisol and ACTH. Imaging examinations revealed pancreatic masses (uncinate process: 4 cases, head: 3 cases, body: 1 case, tail: 2 cases, multiple: 1 case) in all patients, with 4 cases having distant metastases at initial diagnosis. Of the 11 patients, 9 underwent surgical resection, 1 received transarterial embolization (TAE), and 1 received medical therapy. The median follow-up time was 30.0 (6.0, 96.0) months. Until the last follow-up, 2 patients were disease-free, 4 died from severe postoperative infections, 1 died from pulmonary embolism, 3 were alive with disease, and 1 was still on medical therapy.

Conclusion: EAS caused by pNETs is characterized by an acute onset and poor prognosis. The core of management is rapid control of hypercortisolism and its complications. For patients with localized and resectable tumors, surgical resection is the curative treatment. For those with metastatic or unresectable diseases, multimodal comprehensive therapy, including bilateral adrenalectomy, steroidogenesis inhibitors, TAE, targeted therapy, and chemotherapy, is required. A multidisciplinary team (MDT) approach is crucial.

Cui Zhang is an endocrinologist and clinical researcher affiliated with the Shanghai Clinical Center for Endocrine and Metabolic Diseases and the Shanghai Key Laboratory for Endocrine Tumors at Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, China. Her research focuses on endocrine tumors, neuroendocrine neoplasms, Cushing's syndrome, pituitary disorders, and adrenal diseases. She has made significant contributions to the understanding of ectopic adrenocorticotropic hormone (ACTH) syndrome caused by pancreatic neuroendocrine tumors, with particular emphasis on their clinical characteristics, molecular mechanisms, diagnosis, and treatment strategies.

Zhang has authored and co-authored numerous peer-reviewed publications in leading endocrinology journals, including studies published in The Journal of Clinical Endocrinology & Metabolism. Her work integrates clinical research with translational medicine to improve the diagnosis and management of rare endocrine disorders and neuroendocrine tumors. Through her research on pancreatic neuroendocrine tumors and ectopic ACTH syndrome, she continues to advance evidence-based endocrine care and contributes to improving outcomes for patients with complex endocrine and metabolic diseases.