Endocrine Abstracts

Background

20–30% of patients with metastatic small intestine neuroendocrine tumours (SI-NETs) suffer from carcinoid syndrome (CS), i.e. diarrhea, flushing, and bronchospasm. Of these, 25–50% develop carcinoid heart disease (CHD) characterized by valve fibrosis and right heart failure. There are no early predictive markers of CHD, which typically is diagnosed in the advanced stage.

Aims of the study

To 1) detect possible early predictive alterations in endothelial and vascular function in carcinoid syndrome; 2) compare endothelial and vascular function in patients with and without increased S-5-HIAA; 3) study possible relationships between other biomarkers and clinical features with S-5-HIAA.

Subjects and methods

Sixty-six patients (50% men, mean age 64.2–8.8 years, duration of disease 75.7–57.6 months) with SI-NET treated at HUH. Biochemical and clinical features were assessed from electronic patient records and symptom questionnaire. Vascular and endothelial function was measured with pulse wave analysis (PWA), pulse wave velocity (PWV), and peripheral arterial tonometry (PAT). An expert abdominal radiologist assessed hepatic tumour load with a cutoff point of 10% for categorical statistical analysis. Patients were divided into two groups (high vs low) based on the upper limit of normal for the S-5-HIAA assay.

Results

fP-CgA (mean 164 vs. 3.0 nmol/l; P <0.001), weekly frequency of diarrhea (4.7 vs. 2.5 days; P = 0.011), use of somatostatin analogue (SSA; 97% vs. 81%; P = 0.034) and hepatic tumour load (P <0.001) differed significantly between the high vs low S-5-HIAA group. We found no differences in age, tumour Ki-67, S-proBNP (347 ng/l vs. 191 ng/l, P = 0.247), or prevalence of flush between the groups, neither in any vascular function measurements, including aortic systolic or diastolic pressure, systemic vascular resistance, aortic pulse wave velocity and rate controlled central augmentation index (C-AGPH HR75) between the groups. In the high S-5-HIAA group, S-5HIAA correlated inversely with C-AGPH HR75 (-0.363, P = 0.035). No such correlation was found in the low S-5-HIAA group (-0.303, P = 0.098).

Conclusions

Patients with increased S-5-HIAA concentrations are characterized by significantly higher fP-CgA, more frequent diarrhea and SSA use, and higher hepatic tumour load compared to those with normal S-5-HIAA. In patients with SI-NETs, S-5-HIAA did not predict endothelial dysfunction or increased arterial stiffness.