{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T21:45:56Z","timestamp":1782855956409,"version":"3.54.5"},"reference-count":8,"publisher":"Walter de Gruyter GmbH","issue":"1","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,1]]},"abstract":"Abstract<\/jats:title>\n \n Objective.<\/jats:bold>\n Ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) is a rare, but potentially life-threatening cause of Cushing\u2019s syndrome. Its clinical recognition may be delayed, especially when classical features of hypercortisolism are absent. We present two cases, in which hypokalemic metabolic alkalosis was the initial and main clinical clue leading to the diagnosis of neuroendocrine carcinoma with ectopic ACTH production.\n <\/jats:p>\n \n Case 1.<\/jats:bold>\n The first case was a 71-year-old woman admitted with progressive weakness, gait disturbance, and uncontrolled hypertension. Laboratory tests revealed severe hypokalemia and metabolic alkalosis. Endocrine evaluation showed markedly elevated urinary free cortisol and plasma ACTH, with absent suppression on low-dose dexamethasone testing. Colonoscopy for anemia revealed a rectal mass and histopathology confirmed poorly differentiated neuroendocrine carcinoma. Imaging demonstrated widespread metastases. Despite supportive treatment, she died of multi-organ failure during hospitalization.\n <\/jats:p>\n \n Case 2.<\/jats:bold>\n The second case was a 67-year-old woman presenting with fatigue, weakness, and weight loss. Laboratory findings included hypokalemia, metabolic alkalosis, renal dysfunction, and elevated liver enzymes. Hormonal studies again confirmed ACTH-dependent Cushing\u2019s syndrome without suppression on dexamethasone testing. Imaging revealed a right hilar lung mass and bronchoscopy with biopsy confirmed small-cell neuroendocrine carcinoma. PET-CT showed disseminated metastases. Although chemotherapy was initiated, she developed rapid progression and died shortly thereafter.\n <\/jats:p>\n \n Conclusion.<\/jats:bold>\n These cases highlight that severe hypokalemic metabolic alkalosis may represent the primary manifestation of ectopic ACTH syndrome even in the absence of overt Cushingoid features. Recognition of this biochemical pattern should prompt consideration of neuroendocrine tumors allowing earlier diagnosis and timely therapeutic intervention in this aggressive condition.\n <\/jats:p>","DOI":"10.2478\/enr-2025-0031","type":"journal-article","created":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T05:58:10Z","timestamp":1767247090000},"page":"265-270","source":"Crossref","is-referenced-by-count":1,"title":["Hypokalemic metabolic alkalosis as a clinical clue to ectopic ACTH syndrome: two cases of neuroendocrine carcinoma"],"prefix":"10.2478","volume":"59","author":[{"given":"Cundullah","family":"Torun","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Goztepe Training and Research Hospital , Istanbul Medeniyet University, Kadikoy \/ Istanbul , Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erhan","family":"Eken","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Goztepe Training and Research Hospital , Istanbul Medeniyet University, Kadikoy \/ Istanbul , Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bahar","family":"Cak\u0131r","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Goztepe Training and Research Hospital , Istanbul Medeniyet University, Kadikoy \/ Istanbul , Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehmet","family":"Uzunlulu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Goztepe Training and Research Hospital , Istanbul Medeniyet University, Kadikoy \/ Istanbul , Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2025,12,31]]},"reference":[{"key":"2026063014594076179_j_enr-2025-0031_ref_001","doi-asserted-by":"crossref","unstructured":"Dasari A, Shen C, Halperin D, Zhao B, Zhou S, Xu Y, Shih T, Yao JC. Trends in the incidence, prevalence, and survival outcomes in patients with neuroendocrine tumors in the United States. JAMA Oncol 1, 1335\u20131342, 2017.","DOI":"10.1001\/jamaoncol.2017.0589"},{"key":"2026063014594076179_j_enr-2025-0031_ref_002","doi-asserted-by":"crossref","unstructured":"Do C, Vasquez PC, Soleimani M. Metabolic alkalosis pathogenesis, diagnosis, and treatment: Core curriculum 2022. Am J Kidney Dis 80, 536\u2013551, 2022.","DOI":"10.1053\/j.ajkd.2021.12.016"},{"key":"2026063014594076179_j_enr-2025-0031_ref_003","doi-asserted-by":"crossref","unstructured":"Gadelha M, Gatto F, Wildemberg LE, Fleseriu M. Cushing\u2019s syndrome. Lancet 402, 2237\u20132252, 2023.","DOI":"10.1016\/S0140-6736(23)01961-X"},{"key":"2026063014594076179_j_enr-2025-0031_ref_004","doi-asserted-by":"crossref","unstructured":"Kamp K, Alwani RA, Korpershoek E, Franssen GJ, de Herder WW, Feelders RA. Prevalence and clinical features of the ectopic ACTH syndrome in patients with gastroenteropancreatic and thoracic neuroendocrine tumors. Eur J Endocrinol 174, 271\u2013280, 2016.","DOI":"10.1530\/EJE-15-0968"},{"key":"2026063014594076179_j_enr-2025-0031_ref_005","doi-asserted-by":"crossref","unstructured":"Rindi G, Mete O, Uccella S, Basturk O, La Rosa S, Brosens LAA, Ezzat S, de Herder WW, Klimstra DS, Papotti M, Asa SL. Overview of the 2022 WHO classification of neuroendocrine neoplasms. Endocr Pathol 33, 115\u2013154, 2022.","DOI":"10.1007\/s12022-022-09708-2"},{"key":"2026063014594076179_j_enr-2025-0031_ref_006","doi-asserted-by":"crossref","unstructured":"Rizen EN, Phan AT. Neuroendocrine tumors: a relevant clinical update. Curr Oncol Rep 24, 703\u2013714, 2022.","DOI":"10.1007\/s11912-022-01217-z"},{"key":"2026063014594076179_j_enr-2025-0031_ref_007","doi-asserted-by":"crossref","unstructured":"White BE, Rous B, Chandrakumaran K, Wong K, Bouvier C, Van Hemelrijck M, George G, Russell B, Srirajaskanthan R, Ramage JK. Incidence and survival of neuroendocrine neoplasia in England 1995\u20132018: A retrospective, population-based study. Lancet Reg Health Eur 23, 100510, 2022.","DOI":"10.1016\/j.lanepe.2022.100510"},{"key":"2026063014594076179_j_enr-2025-0031_ref_008","doi-asserted-by":"crossref","unstructured":"Yan L, Xu Y, Pan J, Bai J, Long Q, He N, Hu P, Liu M, Ji H, Li X, Tang Q. Prognostic evaluation of patients with rectal neuroendocrine neoplasms and hepatic metastases: A SEER database Analysis. J Oncol 2022, 2451282, 2022.","DOI":"10.1155\/2022\/2451282"}],"container-title":["Endocrine Regulations"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/reference-global.com\/pdf\/10.2478\/enr-2025-0031","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T20:37:56Z","timestamp":1782851876000},"score":1,"resource":{"primary":{"URL":"https:\/\/reference-global.com\/article\/10.2478\/enr-2025-0031"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,1]]},"references-count":8,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12,31]]},"published-print":{"date-parts":[[2025,1,1]]}},"alternative-id":["10.2478\/enr-2025-0031"],"URL":"https:\/\/doi.org\/10.2478\/enr-2025-0031","relation":{},"ISSN":["1336-0329"],"issn-type":[{"value":"1336-0329","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,1]]}}}