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Review
. 2023 Aug 11;15(16):4065.
doi: 10.3390/cancers15164065.

Urinary 5-Hydroxyindolacetic Acid Measurements in Patients with Neuroendocrine Tumor-Related Carcinoid Syndrome: State of the Art

Roberta Elisa Rossi  1 , Elisabetta Lavezzi  2 , Simona Jaafar  2 , Giacomo Cristofolini  2 , Alice Laffi  3 , Gennaro Nappo  4   5 , Silvia Carrara  1 , Alexia Francesca Bertuzzi  3 , Silvia Uccella  5   6 , Alessandro Repici  1   5 , Alessandro Zerbi  4   5 , Andrea Gerardo Antonio Lania  2   5
Affiliations
Review

Urinary 5-Hydroxyindolacetic Acid Measurements in Patients with Neuroendocrine Tumor-Related Carcinoid Syndrome: State of the Art

Roberta Elisa Rossi et al. Cancers (Basel). .

Abstract

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 85-90%, 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.

Keywords: 5-hydroxyindolacetic acid; biomarkers; carcinoid syndrome; diagnosis; follow-up; neuroendocrine tumors; prognosis; small intestinal neuroendocrine tumors.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Serotonin pathway in small intestinal enterochromaffin-like cells. ECL cell: enterochromaffin-like cell; MAO: monoamine oxidase; 5HIAA: 5-hydroxyindolacetic acid. Created using BioRender.com.
Figure 2
Figure 2
The biochemical pathway for serotonin synthesis and metabolism. Created using BioRender.com.
See this image and copyright information in PMC

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