Arterial function, biomarkers, carcinoid syndrome and carcinoid heart disease in patients with small intestinal neuroendocrine tumours

Purpose Carcinoid heart disease (CHD) is a life-threatening complication of carcinoid syndrome (CS) characterised by tricuspid regurgitation (TR). However, there is an unmet need for earlier diagnosis of CHD. We cross-sectionally assessed the prevalence and potential predictive or diagnostic markers for CS and CHD in a contemporary cohort of patients with small intestinal neuroendocrine tumours (SI-NETs). Methods Biochemical characteristics, hepatic tumour load, measures of arterial and endothelial function, atherosclerosis, and transthoracic echocardiography were analysed in a prospective cross-sectional setting. Results Among the 65 patients studied, 29 (45%) had CS (CS+), and 3 (5%) CHD. CS+ was characterised by significantly higher hepatic tumour load, S-5-HIAA and fP-CgA, higher frequency of diarrhoea and flushing, and more frequent PRRT compared to CS- (for all, P < 0.05). Central systolic, central mean, and central end-systolic blood pressures were significantly higher in CS+ than in CS- (for all, P < 0.05). Subjects with grades 2-4 TR had higher hepatic tumour burden, fP-CgA, and S-5-HIAA compared to those with grades 0-1 TR, but measures of vascular function did not differ. fP-CgA (P = 0.017) and S-5-HIAA (P = 0.019) but not proBNP increased significantly according to the severity of TR. Conclusion Although CS is common, the prevalence of CHD was found to be lower in a contemporary cohort of SI-NET patients than previously anticipated. Measures of arterial or endothelial function or carotid atherosclerosis do not identify subjects with mild TR. Echocardiography remains the most sensitive means to diagnose CHD in CS patients with high tumour burden and elevated CgA and 5-HIAA.

Automated summary

This cross-sectional study investigated the prevalence and potential markers for predicting or diagnosing carcinoid syndrome (CS) and carcinoid heart disease (CHD) in patients with small intestinal neuroendocrine tumors (SI-NETs). The results showed that CS+ patients had higher hepatic tumor load, S-5-HIAA, and fP-CgA levels, as well as a higher frequency of diarrhea, flushing, and PRRT compared to CS- patients. Central systolic, central mean, and central end-systolic blood pressures were significantly higher in CS+ patients. Patients with grades 2-4 tricuspid regurgitation (TR) had higher hepatic tumor burden, fP-CgA, and S-5-HIAA levels compared to those with grades 0-1 TR. Measures of vascular function did not differ between the two groups.