Endocrine Abstracts

Introduction: In small intestinal neuroendocrine tumors (SI-NET), unphysiological exposure to serotonin is considered as a major pathogenic factor predisposing to the development carcinoid heart disease (CHD), a complication of carcinoid syndrome associated with poor prognosis. The ability of biomarkers to predict the development of CHD is limited. The aim of our prospective study was to assess risk factors of CHD development and mortality in SI-NET.

Methods: We performed baseline transthoracic echocardiography (TTE), biochemical and radiological evaluation, and vascular function measurements for 65 patients with SI-NET. 42 (65%) of patients had liver metastases. 54 patients had follow-up TTE at median of 61 months. Vital status of patients was assessed at median follow-up of 72 months. Clinical data, including demographics, treatments, radiological and laboratory data was collected from electronic patient records. Hepatic tumor load was assessed at the time of TTE. Cumulative upper limit of normal (ULN) exceeding serum-5-HIAA exposure at the time of TTE was calculated. Westberg score of ≥3 in TTE was considered diagnostic for CHD.

Results: At the end of the follow-up, 22 (34%) patients had died. In 89%, death was due to SI-NET. Three patients had CHD at initial assessment, two patients (4%) were diagnosed with CHD during the 61-month median follow-up. At the follow-up TTE, 54% of the patients had received peptide receptor radionuclide therapy (PRRT) and 46% non-systemic treatments for metastases. Cumulative ULN exceeding serum-5-HIAA and proBNP had correlation with Westberg score (Spearman’s ρ 0.32, 0.31, respectively). Cumulative ULN exceeding serum-5-HIAA had good diagnostic capability in ROC analysis with AUC at 0.98 (95% CI 0.94-1.00), surpassing performance of proBNP and individual serum-5-HIAA measurements (AUC 0.75, 0.91, respectively). In TTE, minor alterations in regurgitation were frequent, with increase or decrease noted in 29% of tricuspid and 30% of pulmonic valves. CHD, hepatic tumor load, serum-5-HIAA, and elevated aortic pulse wave velocity were found to be associated with increased mortality in patients with SI-NET.

Conclusions: Exposure to serotonin measured as cumulative ULN exceeding serum-5-HIAA improves case detection and appears as a promising biomarker for assessing the risk of CHD. Aortic pulse wave velocity was found to be a novel prognostic marker in SI-NET. The incidence of CHD was small when compared to previous literature, possibly reflecting the frequent use of PRRT and other tumor burden reducing treatments.