Immunoreactive tachykinins in 24-h collections of urine from patients with carcinoid tumours: characterization and correlation with plasma concentrations

Abstract

Tachykinins are a family of peptides that may be present in and secreted from carcinoid tumours of mid-gut origin. They are likely to play a role in the pathogenesis of, e.g. the flush, dyspnoea and valvular heart disease seen in the carcinoid syndrome. Since tachykinins are secreted from the tumour into the circulation in bursts, coinciding with flushing attacks, and have short half-lives, we anticipated that analysis of 24-h urine excretion of immunoreactive tachykinin metabolites might prove to be a more sensitive and stable parameter for monitoring than tachykinin-like immunoreactivity in plasma. The study included 48 patients hospitalized for treatment of advanced carcinoid tumours and 32 healthy controls. The urine excretion of tachykinin-like immunoreactive metabolites in the carcinoid patients (median 27.5 pmol 24 h⁻¹, interquartile range (IQR) 8.5–51.0 pmol 24 h⁻¹) was significantly (p<0.001) higher than that in the 32 healthy subjects (median 3.0 pmol 24 h⁻¹, IQR 0.9–4.20 pmol 24 h⁻¹). Of the patients, 38 (79%) had elevated 24-h urine excretion of tachykinin-like immunoreactive metabolites while 31 (64%) had elevated plasma concentrations of tachykinin-like immunoreactive metabolites. Of the patients, 27 (56%) had elevated concentrations of tachykinin-like immunoreactive metabolites both in plasma and urine, 12 (25%) had elevated concentrations only in urine excretion, 3 (6%) had elevated concentrations of only plasma tachykinin-like immunoreactive metabolites and 7 (14%) had elevation of neither plasma nor urine concentrations. Analysis by means of different column chromatographic techniques indicated that the immunoreactive material was heterogeneous, with some components co-eluting with oxidized neurokinin A (NKA) and neuropeptide K (NPK). The urine tachykinin-like immunoreactivity correlates well with that of plasma, but is a slightly more sensitive indicator of elevated tachykinin-like immunoreactivity, probably since levels of urine tachykinin-like immunoreactive metabolites reflect the overall amount of the latter secreted into the circulation during 24 h.

Key Words:

• carcinoid tumours
• neurokinin A
• neuropeptide K
• radioimmunoassay
• tachykinin-like immunoreactivity (TKLI)