Tachykinins in endocrine tumors and the carcinoid syndrome

Abstract

Objective: A new antibody, active against the common tachykinin (TK) C-terminal, was used to study TK expression in patients with endocrine tumors and a possible association between plasma-TK levels and symptoms of diarrhea and flush in patients with metastasizing ileocecal serotonin-producing carcinoid tumors (MSPCs). Method: TK, serotonin and chromogranin A (CgA) immunoreactivity (IR) was studied by immunohistochemistry in tissue samples from 33 midgut carcinoids and 72 other endocrine tumors. Circulating TK (P-TK) and urinary-5 hydroxyindoleacetic acid (U-5HIAA) concentrations were measured in 42 patients with MSPCs before treatment and related to symptoms in patients with the carcinoid syndrome. Circulating CgA concentrations were also measured in 39 out of the 42 patients. Results: All MSPCs displayed serotonin and strong TK expression. TK-IR was also seen in all serotoninproducing lung and appendix carcinoids. None of the other tumors examined contained TK-IR cells. Concentrations of P-TK, P-CgA, and U-5HIAA were elevated in patients experiencing daily episodes of either flush or diarrhea, when compared with patients experiencing occasional or none of these symptoms. In a Spearman partial rank test, the correlation of P-TK with daily diarrhea was independent of both U-5HIAA and CgA levels. Conclusion: We found that TK synthesis occurs in serotonin-IR tumors and that P-TK levels are significantly correlated with symptoms of flush and diarrhea in patients with MSPCs. This is, to our knowledge, the first report demonstrating an independent correlation of P-TKs with carcinoid diarrhea, a symptom that is customarily regarded as serotonin mediated. Further investigations may present opportunities for new therapeutic possibilities.European Journal of Endocrinology 159 275-282

Carcinoid Heart Disease: From Pathophysiology to Treatment - ‘Something in the Way It Moves'

“…1 ). Despite the growing body of evidence showing the major involvement of serotonin in the development of CHD, more than 50% of patients with elevated circulating serotonin levels do not develop CHD [9] , implying therefore that other biochemical mediators are also significant; activin A [13] and connective tissue growth factor (CTGF) [71] have been associated with the development of the disease in these patients. Activin A, a cytokine member of the TGF-β superfamily with fibrogenic properties, was found to be expressed in the fibrotic plaques of CHD le-sions [72] .…”

“…These tumour products are usually inactivated by the liver [5][6][7][8][9] . In approximately 30-40% of NET patients, when hepatic spread from a primary gastrointestinal NET results in hormonally active tumour products exceeding the hepatic capacity for degradation, the classical carcinoid syndrome (CS) ensues [10][11][12] .…”

Cocaine- and Amphetamine-Regulated Transcript in Neuroendocrine Tumors

“…in a single tumor several biologically active peptides and amines may be expressed in addition to the one giving rise to the main symptoms [11,12,13,14]. For instance, ileal carcinoids arising from EC cells invariably produce the monoamine serotonin, but in addition often tachykinins, notably substance P and the related neuropeptide K (NPK) [12,15]. …”

Circulating Tumor Markers in Patients with Neuroendocrine Tumors – a Clinical Perspective

“…NKA can be reliably measured in plasma and may have a role in the prognostication of patients with NETs [66][67][68]. NKA is frequently elevated in patients with NETs and elevated levels have been shown to correlate with symptoms such as flushing and diarrhea in patients with the carcinoid syndrome [68,69]. No study has evaluated the sensitivity and specificity of the test and it can therefore not be recommended for diagnosis.…”