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10.03.2020 | Ausgabe 4/2020

Reviews in Endocrine and Metabolic Disorders 4/2020

Serotonin pathway in carcinoid syndrome: Clinical, diagnostic, prognostic and therapeutic implications

Zeitschrift:
Reviews in Endocrine and Metabolic Disorders > Ausgabe 4/2020
Autoren:
Giuseppe Fanciulli, Rosaria M. Ruggeri, Erika Grossrubatscher, Fabio Lo Calzo, Troy D. Wood, Antongiulio Faggiano, Andrea Isidori, Annamaria Colao, on behalf of NIKE
Wichtige Hinweise
Giuseppe Fanciulli and Rosaria M. Ruggeri contributed equally to this work.

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Abstract

Carcinoid syndrome represents the most common functional syndrome that affects patients with neuroendocrine neoplasms. Its clinical presentation is really heterogeneous, ranging from mild and often misdiagnosed symptoms to severe manifestations, that significantly worsen the patient’s quality of life, such as difficult-to-control diarrhoea and fibrotic complications. Serotonin pathway alteration plays a central role in the pathophysiology of carcinoid syndrome, accounting for most clinical manifestations and providing diagnostic tools. Serotonin pathway is complex, resulting in production of biologically active molecules such as serotonin and melatonin, as well as of different intermediate molecules and final metabolites. These activities require site- and tissue-specific catalytic enzymes. Variable expression and activities of these enzymes result in different clinical pictures, according to primary site of origin of the tumour. At the same time, the biochemical diagnosis of carcinoid syndrome could be difficult even in case of typical symptoms. Therefore, the accuracy of the diagnostic methods of assessment should be improved, also attenuating the impact of confounding factors and maybe considering new serotonin precursors or metabolites as diagnostic markers. Finally, the prognostic role of serotonin markers has been only evaluated for its metabolite 5-hydroxyindole acetic acid but, due to heterogeneous and biased study designs, no definitive conclusions have been achieved. The most recent progress is represented by the new therapeutic agent telotristat, an inhibitor of the enzyme tryptophan hydroxylase, which blocks the conversion of tryptophan in 5-hydroxy-tryptophan. The present review investigates the clinical significance of serotonin pathway in carcinoid syndrome, considering its role in the pathogenesis, diagnosis, prognosis and therapy.

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