Discriminating Capacity of Indole Markers in the Diagnosis of Carcinoid Tumors

Abstract

Background: We evaluated the discriminating capacity of the indole markers urinary 5-hydroxyindoleacetic acid (5-HIAA), urinary serotonin, and platelet serotonin in the diagnosis of carcinoid tumors. Methods: Indole markers were measured in 688 patients with suspected carcinoid disease. The initial values of indole markers from patients in whom a carcinoid tumor was confirmed during follow-up (n = 98) were used for ROC analysis. Two groups served as reference populations. The first consisted of 45 healthy individuals (“healthy controls”). The second was a random sample of 40 patients, drawn from the 590 (688 minus 98) patients with carcinoid-like symptoms but without a carcinoid tumor (“clinically suspected patients”). Results: ROC curve analysis showed platelet serotonin to have the highest discriminating capacity, especially in foregut carcinoids. Cutoff values for platelet serotonin obtained from ROC analysis with healthy controls as reference group (5.4 nmol/109 platelets) gave a sensitivity of 74%, specificity of 91%, positive predictive value of 63%, and negative predictive value of 95% when applied to the initial 688 patients. Using the cutoff value with the clinically suspected patients as the reference group (9.3 nmol/109 platelets) gave a sensitivity of 63%, specificity of 99%, positive predictive value of 89%, and negative predictive value of 93%. Indole markers were increased in 169 (25%) of 688 patients. In 76 (45%) of these 169 patients, a carcinoid tumor was present. Slight increases of markers were associated with non-carcinoid neuroendocrine tumors, non-neuroendocrine tumors, and disturbed bowel motility. Conclusions: ROC curve analysis shows that platelet serotonin is the most discriminating indole marker for the diagnosis of carcinoid tumors. Platelet serotonin especially improves the diagnosis of carcinoids producing small amounts of serotonin.

Serotonin (5‐HT) Transporter Ligands Affect Plasma 5‐HT in Rats

“…In a later study, the same group reported that patients with midgut carcinoid tumors had median platelet 5‐HT levels of 23.8 (nmol/10 9 platelets) as compared to 3.4 in normal controls (7.0‐fold increase) 70 . A similar 8.6‐fold increase in platelet 5‐HT was reported by others 71 . Robiolio et al 67 reported that patients with carcinoid syndrome and VHD had higher serum and platelet 5‐HT levels than carcinoid patients without VHD.…”

S2k-Leitlinie Neuroendokrine Tumore

“…Darüber hinaus werden für das Karzinoid-Syndrom neben Serotonin auch die Sekretion weiterer Tachykinine wie Substanz P und Neurokinin A verantwortlich gemacht, sodass in seltenen Fällen die 5-HIES-Ausscheidung auch beim Vorhandensein eines Karzinoid-Syndroms unauffällig sein kann, insbesondere wenn keine Durchfälle bestehen [68]. Durch Absenken des Grenzwerts auf 2,8 mmol/mol Kreatinin kann die Sensitivität auf 68 % angehoben werden (bei 89 % Spezifität), während bei einem hohen Grenzwert von 6,7 mmol/mol Kreatinin die Sensitivität bei nur 52 % liegt, aber die Spezifität bei 98 % [70]. Es besteht keine gute Korrelation zwischen der Höhe der 5-HIES-Spiegel und dem Schweregrad der Symptome, was wahrscheinlich auf eine fluktuierende Serotoninsekretion durch den Tumor und zusätzliche Mediatoren des Karzinoid-Syndroms zurückzuführen ist.…”

Incidence and prognostic value of serotonin secretion in pancreatic neuroendocrine tumours

“…Sometimes serotonin‐secreting PNETs are classified with use of tissue samples (serotonin staining); however, this does not always reflect clinical functionality of the tumour as assessed by determining the 24‐hours urinary 5‐hydroxyindoleacetic acid (5‐HIAA) excretion . In gastrointestinal NETs, 24‐hours urinary 5‐HIAA excretion has a high sensitivity and specificity for detecting metastatic midgut NETs, but it is less useful for predicting survival during follow‐up . In PNETs, the incidence and the effect of elevated 24‐hours urinary 5‐HIAA excretion on survival is unknown.…”