{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:20:14Z","timestamp":1784557214191,"version":"3.55.0"},"reference-count":0,"publisher":"Bioscientifica","issue":"5","content-domain":{"domain":["erc.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,5,1]]},"abstract":"\n Neuroendocrine neoplasms (NENs) are rare, usually slow-growing tumors, often presenting with extensive liver metastases. Hyperammonemia due to insufficient hepatic clearance has been described in NEN cases; however, no systematic evaluation of risk factors and outcomes of NEN-associated hyperammonemia exists so far. This case report and retrospective review of NEN patients developing hyperammonemia from the years 2000 to 2020 at the Erasmus Medical Center in Rotterdam, the Netherlands, aimed to describe these patients and determine prognostic factors to improve evaluation and treatment. Forty-four NEN patients with documented hyperammonemia were identified. All patients had liver metastases with 30% (\n n<\/jats:italic>\n \u2009= 13) showing signs of portal hypertension. Patients who developed encephalopathy had higher median ammonia levels, but there was no association between the severity of hyperammonemia and liver tumor burden or presence of liver insufficiency. Eighty-four percent (\n n<\/jats:italic>\n \u2009= 37) of patients died during follow-up. The median (IQR) time from diagnosis of hyperammonemia to death was 1.7 months (0.1\u201322.7). Hyperbilirubinemia, hypoalbuminemia, elevated international normalized ratio, presence of liver insufficiency, encephalopathy and ascites were associated with worse outcomes. Their role as independent risk factors for mortality was confirmed using the Child\u2013Pugh score as a summary factor (\n P<\/jats:italic>\n \u2009 < 0.001). No difference was seen concerning overall survival between our hyperammonemia patients and a propensity score-matched control stage IV NEN cohort. In conclusion, hyperammonemia comprises a relevant and potentially underdiagnosed complication of NEN liver metastases and is associated with worse outcomes. Assessment of signs of encephalopathy, risk factors and the Child\u2013Pugh score could be helpful in selecting patients in whom ammonia levels should be measured.\n <\/jats:p>","DOI":"10.1530\/erc-21-0346","type":"journal-article","created":{"date-parts":[[2022,2,16]],"date-time":"2022-02-16T09:56:03Z","timestamp":1645005363000},"page":"241-250","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-8","source":"Crossref","is-referenced-by-count":3,"title":["Prognostic significance of hyperammonemia in neuroendocrine neoplasm patients with liver metastases"],"prefix":"10.1530","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3040-4685","authenticated-orcid":true,"given":"Julie","family":"Refardt","sequence":"first","affiliation":[{"name":"1ENETS Center of Excellence, Department of Internal Medicine, Section of Endocrinology, Erasmus Medical Center and Erasmus Cancer Institute, Rotterdam, The Netherlands"},{"name":"2ENETS Center of Excellence, Department of Endocrinology, University Hospital Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline M","family":"den Hoed","sequence":"additional","affiliation":[{"name":"3Department of Gastroenterology and Hepatology, Erasmus MC Transplant Institute, Erasmus MC University Medical Center, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janneke","family":"Langendonk","sequence":"additional","affiliation":[{"name":"4Department of Internal Medicine, Center for Lysosomal and Metabolic Diseases, Erasmus Medical Center, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7979-6969","authenticated-orcid":true,"given":"Wouter T","family":"Zandee","sequence":"additional","affiliation":[{"name":"5Division of Endocrinology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8439-231X","authenticated-orcid":true,"given":"Ayoub","family":"Charehbili","sequence":"additional","affiliation":[{"name":"6ENETS Center of Excellence, Department of Radiology & Nuclear Medicine, Erasmus Medical Center, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A","family":"Feelders","sequence":"additional","affiliation":[{"name":"1ENETS Center of Excellence, Department of Internal Medicine, Section of Endocrinology, Erasmus Medical Center and Erasmus Cancer Institute, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1463-5165","authenticated-orcid":true,"given":"Wouter W","family":"de Herder","sequence":"additional","affiliation":[{"name":"1ENETS Center of Excellence, Department of Internal Medicine, Section of Endocrinology, Erasmus Medical Center and Erasmus Cancer Institute, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tessa","family":"Brabander","sequence":"additional","affiliation":[{"name":"6ENETS Center of Excellence, Department of Radiology & Nuclear Medicine, Erasmus Medical Center, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Hofland","sequence":"additional","affiliation":[{"name":"1ENETS Center of Excellence, Department of Internal Medicine, Section of Endocrinology, Erasmus Medical Center and Erasmus Cancer Institute, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","container-title":["Endocrine-Related Cancer"],"original-title":[],"link":[{"URL":"https:\/\/erc.bioscientifica.com\/view\/journals\/erc\/29\/5\/ERC-21-0346.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/erc.bioscientifica.com\/downloadpdf\/journals\/erc\/29\/5\/ERC-21-0346.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:56:11Z","timestamp":1784555771000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/erc\/article\/29\/5\/241-250\/25612"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,1]]},"references-count":0,"journal-issue":{"issue":"5"},"URL":"https:\/\/doi.org\/10.1530\/erc-21-0346","relation":{},"ISSN":["1351-0088","1479-6821"],"issn-type":[{"value":"1351-0088","type":"print"},{"value":"1479-6821","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,1]]}}}