{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T22:41:17Z","timestamp":1793400077274,"version":"4.5.0"},"reference-count":50,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2023,8,11]],"date-time":"2023-08-11T00:00:00Z","timestamp":1691712000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Carcinoid syndrome (CS), mostly associated with small intestinal neuroendocrine tumors (SI-NETs) or lung-related NETs, is characterized by symptoms related to hormonal secretion and long-term complications, including carcinoid heart disease (CHD), which is potentially life-threatening. In the early stages of the disease, symptoms are non-specific, which leads to delayed diagnoses. The availability of reliable tumor markers is crucial for a prompt diagnosis and proper management. This review summarizes available evidence on the role of 24 h urinary 5-hydroxyindolacetic acid (24u5HIAA), which is the urinary breakdown metabolite of serotonin, in the diagnosis\/follow-up of NET-related CS, with a focus on its potential prognostic role, while eventually attempting to suggest a timeline for its measurement during the follow-up of NET patients. The use of 24u5HIAA is an established biomarker for the diagnosis of NETs with CS since it shows a sensibility and specificity of 100% and 85\u201390%, respectively. The downside of 24u5-HIAA is represented by the need for 24 h urine collection and the risk of confounding factors (foods and medication), which might lead to false positive\/negative results. Moreover, 24u5HIAA is useful in the follow-up of NETs with CS since a shorter double time correlates to a higher risk of disease progression\/disease-specific mortality. Furthermore, an elevation in 24u5-HIAA is correlated with a dismal prognosis because it is associated with an increased likelihood of CHD development and disease progression\/mortality. Other potentially interesting biochemical markers have been proposed, including plasmatic 5HIAA, although further standardization and prospective studies are required to define their role in the management of NETs. Meanwhile, 24u5HIAA remains the most accurate CS biomarker.<\/jats:p>","DOI":"10.3390\/cancers15164065","type":"journal-article","created":{"date-parts":[[2023,8,11]],"date-time":"2023-08-11T10:33:23Z","timestamp":1691750003000},"page":"4065","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Urinary 5-Hydroxyindolacetic Acid Measurements in Patients with Neuroendocrine Tumor-Related Carcinoid Syndrome: State of the Art"],"prefix":"10.3390","volume":"15","author":[{"given":"Roberta Elisa","family":"Rossi","sequence":"first","affiliation":[{"name":"Gastroenterology and Endoscopy Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Lavezzi","sequence":"additional","affiliation":[{"name":"Endocrinology and Diabetology Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Jaafar","sequence":"additional","affiliation":[{"name":"Endocrinology and Diabetology Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo","family":"Cristofolini","sequence":"additional","affiliation":[{"name":"Endocrinology and Diabetology Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Laffi","sequence":"additional","affiliation":[{"name":"Hematology and Oncology, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gennaro","family":"Nappo","sequence":"additional","affiliation":[{"name":"Pancreatic Surgery Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy"},{"name":"Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Carrara","sequence":"additional","affiliation":[{"name":"Gastroenterology and Endoscopy Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexia Francesca","family":"Bertuzzi","sequence":"additional","affiliation":[{"name":"Hematology and Oncology, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Uccella","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072 Milan, Italy"},{"name":"Pathology Service, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Repici","sequence":"additional","affiliation":[{"name":"Gastroenterology and Endoscopy Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy"},{"name":"Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Zerbi","sequence":"additional","affiliation":[{"name":"Pancreatic Surgery Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy"},{"name":"Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea Gerardo Antonio","family":"Lania","sequence":"additional","affiliation":[{"name":"Endocrinology and Diabetology Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy"},{"name":"Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1111\/his.13975","article-title":"The 2019 WHO Classification of Tumours of the Digestive System","volume":"76","author":"Nagtegaal","year":"2020","journal-title":"Histopathology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e405","DOI":"10.1016\/j.amjmed.2018.05.026","article-title":"Diagnostic Dilemma: Carcinoid Syndrome","volume":"131","author":"Beri","year":"2018","journal-title":"Am. 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