{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T22:14:32Z","timestamp":1787004872277,"version":"build-2736575974"},"reference-count":15,"publisher":"Georg Thieme Verlag KG","issue":"02","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Exp Clin Endocrinol Diabetes"],"published-print":{"date-parts":[[2026,2]]},"abstract":"Abstract<\/jats:title>\n Ectopic Cushing\u2019s syndrome is a severe endocrine disorder with high morbidity\n and mortality, making timely diagnosis and effective cortisol control\n crucial. The aim of this study was to assess the 12-year experience at a\n tertiary centre.<\/jats:p>\n We retrospectively analyzed clinical, biochemical, imaging, treatment, and\n outcome data in this single-center, non-interventional cohort of patients\n treated from 2012 to 2024 at the University Hospital Centre Zagreb.<\/jats:p>\n Twelve patients were included (10\/12 female, 83.3%; median age 43.5 years,\n range 22\u201374). Primary tumors were predominantly neuroendocrine (8\/12,\n 66.7%), and 9\/12 (75.0%) had metastatic disease at diagnosis. Common\n features were fat redistribution in 10\/12 (83.3%), facial plethora in 8\/12\n (66.7%), hypertension in 8\/12 (66.7%), and peripheral edema in 7\/12 (58.3%).\n Frequent biochemical alterations were hypokalemia in 11\/12 (91.7%) and\n hyperglycemia or new-onset\/worsening diabetes in 10\/12 (83.3%). Median\n 24-hour urinary free cortisol was 5,594 nmol\/24 h (range: 196\u201372,954), and\n ACTH 52.4 pmol\/L (range: 8\u2013498). A urinary free cortisol level\u226550\u00d7the upper\n limit of normal identified a high-risk group with shorter survival (Spearman\n \u03c1=\u22120.50). Biochemical remission was achieved in 1\/12 (8.3%) patient through\n tumor resection, while the majority required bilateral adrenalectomy (8\/12,\n 66.7%) due to inadequate response to medical therapy or as first-line\n treatment. At the time of last follow-up, 8\/12 (66.7%) patients had died due\n to disease progression, with a median time to death of 12 months (range:\n 1\u201351). The median overall survival was 20 months (range: 1\u2013154).<\/jats:p>\n Most patients presented with metabolic disturbances and limited response to\n medical therapy, leading to bilateral adrenalectomy. Early mortality was\n driven by uncontrolled hypercortisolism rather than tumor burden, and higher\n urinary free cortisol was associated with shorter survival. These findings\n highlight the prognostic relevance of cortisol burden and the importance of\n prompt cortisol control.<\/jats:p>","DOI":"10.1055\/a-2799-7997","type":"journal-article","created":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T00:17:30Z","timestamp":1772756250000},"page":"43-51","source":"Crossref","is-referenced-by-count":1,"title":["The Clinical Spectrum and Management of Ectopic Cushing\u2019s Syndrome: A\n 12-Year Single-Center Experience"],"prefix":"10.1055","volume":"134","author":[{"given":"Ivana","family":"Kraljevic","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, University Hospital Centre\n Zagreb, Zagreb, Croatia"},{"name":"University of Zagreb School of Medicine, Zagreb,\n Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3034-5598","authenticated-orcid":false,"given":"Darko","family":"Kastelan","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, University Hospital Centre\n Zagreb, Zagreb, Croatia"},{"name":"University of Zagreb School of Medicine, Zagreb,\n Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gordan","family":"Vukman","sequence":"additional","affiliation":[{"name":"University of Zagreb School of Medicine, Zagreb,\n Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4379-2250","authenticated-orcid":false,"given":"Mirsala","family":"Solak","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, University Hospital Centre\n Zagreb, Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Skoric Polovina","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, University Hospital Centre\n Zagreb, Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemarie","family":"Balasko","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, University Hospital Centre\n Zagreb, Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marija","family":"Tripolski","sequence":"additional","affiliation":[{"name":"Polyclinic Borzan, Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anela","family":"Novak","sequence":"additional","affiliation":[{"name":"University Hospital Centre Split Kri\u017eine, Split,\n Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2026,3,5]]},"reference":[{"key":"ref1","first-page":"143","article-title":"Ectopic ACTH syndrome","volume":"35","author":"J Newell-Price","year":"2006","journal-title":"Front Horm Res"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1210\/jc.2005-1542","article-title":"The ectopic adrenocorticotropin syndrome: clinical features, diagnosis,\n management and long-term follow-up","volume":"91","author":"A M Isidori","year":"2006","journal-title":"J Clin Endocrinol Metab"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"4955","DOI":"10.1210\/jc.2004-2527","article-title":"Cushing's syndrome due to ectopic corticotropin secretion: twenty years at\n NIH","volume":"90","author":"I Ilias","year":"2005","journal-title":"J Clin Endocrinol Metab"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1016\/S0140-6736(14)61375-1","article-title":"Cushing\u2019s syndrome","volume":"386","author":"A Lacroix","year":"2015","journal-title":"Lancet"},{"key":"ref5","first-page":"451","article-title":"Prognostic factors in ectopic Cushing\u2019s syndrome due to NETs","volume":"176","author":"M V Davi","year":"2017","journal-title":"Eur J Endocrinol"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"S53","DOI":"10.1093\/ejendo\/lvaf114","article-title":"Survival probabilities in patients with ectopic Cushing\u2019s syndrome\u2014a systematic\n reeview and a single-arm meta-analysis","volume":"192","author":"M Piasecka","year":"2025","journal-title":"Eur J Endocrinol"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.tem.2023.12.003","article-title":"A clinical perspective on ectopic Cushing's syndrome","volume":"35","author":"O Ragnarsson","year":"2024","journal-title":"Trends Endocrinol Metab"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1007\/s11102-018-0894-2","article-title":"Two types of ectopic Cushing syndrome or a continuum?","volume":"21","author":"M Araujo Castro","year":"2018","journal-title":"Pituitary"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"R29","DOI":"10.1530\/EJE-19-0877","article-title":"Cushing's syndrome due to ectopic ACTH secretion: an expert operational\n opinion","volume":"182","author":"J Young","year":"2020","journal-title":"Eur J Endocrinol"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/s11154-010-9139-z","article-title":"The ectopic ACTH syndrome","volume":"11","author":"K I Alexandraki","year":"2010","journal-title":"Rev Endocr Metab Disord"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"bvae194","DOI":"10.1210\/jendso\/bvae194","article-title":"Recognition and Management of Ectopic ACTH Secreting Tumors","volume":"9","author":"H Elenius","year":"2025","journal-title":"Endocr Soc"},{"key":"ref12","first-page":"110","article-title":"The Mount Sinai Clinical Pathway for the Diagnosis and Management of\n Hypercortisolism due to Ectopic ACTH Syndrome","volume":"6","author":"E A Alba","year":"2022","journal-title":"Endocr Soc"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"P460","DOI":"10.1016\/j.amjsurg.2020.08.047","article-title":"Differences in outcomes of bilateral adrenalectomy in patients with ectopic ACTH\n producing tumor of known and unknown origin","volume":"221","author":"T S Yamashita","year":"2021","journal-title":"The American Journal of Surgery"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1007\/s00464-007-9478-3","article-title":"Laparoscopic bilateral adrenalectomy: results for 30 consecutive cases","volume":"22","author":"M C Takata","year":"2008","journal-title":"Surg Endosc"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"2481","DOI":"10.1007\/s00423-022-02568-8","article-title":"Differences in morbidity and mortality between unilateral adrenalectomy for\n adrenal Cushing\u2019s syndrome and bilateral adrenalectomy for therapy refractory\n extra-adrenal Cushing\u2019s syndrome","volume":"407","author":"J Reibetanz","year":"2022","journal-title":"Langenbecks Arch Surg"}],"container-title":["Experimental and Clinical Endocrinology & Diabetes"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2799-7997.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T00:17:37Z","timestamp":1772756257000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2799-7997"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2]]},"references-count":15,"journal-issue":{"issue":"02","published-online":{"date-parts":[[2026,3,5]]},"published-print":{"date-parts":[[2026,2]]}},"URL":"https:\/\/doi.org\/10.1055\/a-2799-7997","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0947-7349","1439-3646"],"issn-type":[{"value":"0947-7349","type":"print"},{"value":"1439-3646","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2]]}}}