{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T02:24:20Z","timestamp":1790821460795,"version":"4.1.0"},"reference-count":44,"publisher":"The Endocrine Society","issue":"11","license":[{"start":{"date-parts":[[2020,8,12]],"date-time":"2020-08-12T00:00:00Z","timestamp":1597190400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81800683"],"award-info":[{"award-number":["81800683"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shanghai Medical and Health Development Foundation","award":["805344"],"award-info":[{"award-number":["805344"]}]},{"name":"Shanghai Municipal Health System","award":["2017YQ005"],"award-info":[{"award-number":["2017YQ005"]}]},{"DOI":"10.13039\/100017950","name":"Shanghai Municipal Health Commission","doi-asserted-by":"crossref","award":["201740040"],"award-info":[{"award-number":["201740040"]}],"id":[{"id":"10.13039\/100017950","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100017950","name":"Shanghai Municipal Health Commission","doi-asserted-by":"crossref","award":["201840049"],"award-info":[{"award-number":["201840049"]}],"id":[{"id":"10.13039\/100017950","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004921","name":"Shanghai Jiao Tong University","doi-asserted-by":"publisher","award":["YG2019QNB26"],"award-info":[{"award-number":["YG2019QNB26"]}],"id":[{"id":"10.13039\/501100004921","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shanghai Ruijin Hospital","award":["KY20193701"],"award-info":[{"award-number":["KY20193701"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>Pancreatic neuroendocrine tumors (pNETs) causing ectopic adrenal corticotropic hormone (ACTH) syndrome (EAS) are rare and aggressive with little known information. We aimed to elucidate the clinical features and molecular mechanisms of pNETs with EAS by methylation analysis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Seven patients with ectopic ACTH-secreting pNETs who were diagnosed at Shanghai Clinical Endocrine and Metabolic Diseases Center and Pancreatic Disease Center in Ruijin Hospital between 2001 and 2019 were enrolled. Twenty patients with ectopic ACTH-secreting thymic neuroendocrine tumors (TNETs) and 7 with nonfunctional pNETs (nf-pNETs) were also enrolled as controls. We collected clinical data and measured POMC promoter CpG methylation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>All 7 patients had elevated ACTH and urinary free cortisol (UFC) levels with positive ACTH staining in the pancreas and were diagnosed with ectopic ACTH-secreting pNET. Of the 7 patients, 6 underwent surgery and 1 underwent transarterial embolization (TAE). Two patients were free of disease after surgery; 2 died within 90 days after surgery; and 3 had metastases and died within 1 year. Compared with ACTH-secreting TNETs, ACTH-secreting pNETs had similar clinical and biochemical features but a significantly poorer prognosis. POMC promoter CpG methylation was significantly lower in ACTH-secreting pNETs than in nf-pNETs and normal pancreas.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>ACTH-secreting pNETs are aggressive and fatal. Surgery is definitively curative for patients with resectable primary tumors without metastasis. Pro-opiomelanocortin (POMC) promoter hypomethylation caused pNETs to produce ACTH. This study further supplements the genetic features of ACTH-secreting NETs.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgaa507","type":"journal-article","created":{"date-parts":[[2020,9,12]],"date-time":"2020-09-12T15:54:05Z","timestamp":1599926045000},"page":"3449-3458","source":"Crossref","is-referenced-by-count":29,"title":["The Clinical Features and Molecular Mechanisms of ACTH-secreting Pancreatic Neuroendocrine Tumors"],"prefix":"10.1210","volume":"105","author":[{"given":"Cui","family":"Zhang","sequence":"first","affiliation":[{"name":"Shanghai Key Laboratory for Endocrine Tumors, Shanghai Clinical Center for Endocrine and Metabolic Diseases and Key Laboratory for Endocrine and Metabolic Diseases of Chinese Health Ministry, Ruijin Hospital, Ruijin Hospital Shanghai Jiaotong University School of Medicine, Shanghai, 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Jiaotong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingwei","family":"Su","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory for Endocrine Tumors, Shanghai Clinical Center for Endocrine and Metabolic Diseases and Key Laboratory for Endocrine and Metabolic Diseases of Chinese Health Ministry, Ruijin Hospital, Ruijin Hospital Shanghai Jiaotong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Jiang","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory for Endocrine Tumors, Shanghai Clinical Center for Endocrine and Metabolic Diseases and Key Laboratory for Endocrine and Metabolic Diseases of Chinese Health Ministry, Ruijin Hospital, Ruijin Hospital Shanghai Jiaotong University School of Medicine, Shanghai, 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Ruijin Hospital, Ruijin Hospital Shanghai Jiaotong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guang","family":"Ning","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory for Endocrine Tumors, Shanghai Clinical Center for Endocrine and Metabolic Diseases and Key Laboratory for Endocrine and Metabolic Diseases of Chinese Health Ministry, Ruijin Hospital, Ruijin Hospital Shanghai Jiaotong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baiyong","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Pancreatic Disease Center, Research Institute of Pancreatic Diseases, State Key Laboratory of Oncogenes and Related Genes (Shanghai), Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, 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