Carcinoid heart disease: The role of urinary 5-hydroxyindoleacetic acid excretion and plasma levels of atrial natriuretic peptide, transforming growth factor-β and fibroblast growth factor

BACKGROUND. Serotonin excretion plays a role in the development of carcinoid heart disease (CHD), but the exact pathogenesis is not known. In the current study, the authors evaluated 24-hour urinary 5-hydroxyindoleacetic acid (5-HIAA) excretion, as well as plasma levels of transforming growth factor-β (TGF-β), fibroblast growth factor (FGF), and atrial natriuretic peptide (ANP) in patients with and without CHD determined by ultrasound examination. METHODS. Urine and plasma samples were obtained for 37 patients and cardiac ultrasound was performed during follow-up in 1999 and 2000. Median 5-HIAA excretion was calculated for the period between diagnosis and ultrasound examination. CHD was defined as the thickening of the tricuspid valve with additional III-IV/IV tricuspid valve regurgitation. RESULTS. CHD was found in 9 of 37 patients (24%). No significant differences were found for age, gender, presence, and duration of liver metastases. All CHD patients had symptoms of the carcinoid syndrome compared with 71% of the non-CHD patients (P = 0.159). Median 5-HIAA excretion was significantly higher in the CHD group compared with the non-CHD group: 576 μmol/24 hours versus 233 μmol/24 hours (P = 0.02). No difference in TGF-β and FGF plasma levels was observed between both groups (P = 0.139 and P = 0.985, respectively), nor was there a correlation with morphology of the tricuspid valve or degree of dilatation of the right atrium/ventricle. However, the CHD group had higher median ANP levels than the non-CHD group: 48 ng/L and 25 ng/L, respectively (P = 0.026). CONCLUSIONS. High levels of 5-HIAA excretion and plasma ANP were found to be associated with CHD. No significant relation with TGF-β or FGF was been found.