Certain Factors Linked With Future Carcinoid Syndrome Diagnosis

Patients with gastrointestinal neuroendocrine tumors (NETs) with carcinoid syndrome (CS) are more than twice as likely to have certain pre-existing diagnoses compared with patients without CS, according to the results of a study published in the World Journal of Gastroenterology.

CS occurs in between 8% to 35% of patients with NETs. According to the study, CS occurs when functional carcinoid tumors metastasize to the liver or outside the gastrointestinal tract, and “the vasoactive hormones secreted by metastases, such as serotonin, histamine, or tachykinins, are no longer metabolized and inactivated by the liver and reach the general circulation.”

In this analysis, Beilei Cai, PhD, of Novartis Pharmaceuticals, and colleagues sought to discover unknown factors associated with CS in order to help diagnosis the condition earlier. The retrospective study included patients aged 18 or older with newly diagnosed gastrointestinal NETs. These patients were matched 3:1 to patients with CS based on NET diagnosis date. There were 251 patients with gastrointestinal NETs and CS matched with 753 controls included in a development database. 

Excluding conditions already known to be associated with CS, the researchers identified 33 common diagnoses in the development database. Eight of these diagnoses remained significant in a forward step-wise logistic regression model and were further validated in a validation database that included 181 patients with gastrointestinal NETs and CS matched with 1,158 controls.

The final analysis showed three factors significantly associated with higher risk for CS including liver disorders (odds ratio [OR], 3.38; 95% CI, 2.07–5.51), enlargement of lymph nodes (OR, 2.13; 95% CI, 1.10–4.11), and abdominal mass (OR, 3.79; 95% CI, 1.87–7.69).

“Among patients with NETs, pre-existing enlarged lymph nodes, abdominal mass lesions, and a liver disorder seem to jointly indicate increasing tumor burden, which implies that tumor progression may be associated with a higher risk of developing CS,” the researchers wrote.

“Although there is no obvious clinical explanation for these findings, we propose the following two considerations: first, patients with CS have a larger systemic tumor bulk at diagnosis than patients who do not manifest CS, implying that increasing tumor burden correlates with increasing tumor products, which in turn led to the syndrome; and second, that patients with CS have more aggressive tumors than those without CS, which leads to more rapid growth of tumor and a larger burden of disease when diagnosed.”

According to the researchers the data from this study suggest that “in a patient with NET, even in the absence of typical symptoms, if one of these three findings is noted, consideration should be given to ordering a 5-HIAA or serotonin level.”