Carcinoid heart disease: the role of urinary 5-hydroxyindoleacetic acid excretion and plasma levels of atrial natriuretic peptide, transforming growth factor-beta 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-beta (TGF-beta), 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 micromol/24 hours versus 233 micromol/24 hours (P = 0.02). No difference in TGF-beta 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-beta or FGF was been found.