Context: Cocaine-and amphetamine-regulated transcript (CART) codes for a peptide widely distributed in nervous and endocrine tissues. CART-immunoreactivity (CART-LI) has been detected in human insulinomas.

Objective: To investigate the measurement of plasma CART-(LI) as a tumour marker of neuroendocrine malignancy.

Design and subjects: Plasma CART-LI levels were measured in 401 patients with a range of diagnoses; neuroendocrine malignancy (n=131), following removal of neuroendocrine malignancy (n=27), without any form of tumour or renal impairment (n=192), with renal impairment (n=17) and with non-neuroendocrine tumours (n=34). Chromatography methods were used to investigate CART-LI circulating in human plasma.

Results: The upper limit of normal calculated for CART-LI was 150 pmol/ L. Mean circulating plasma CART-LI amongst neuroendocrine tumour patients was 440pmol/L, 56% of subjects having levels greater than 150pmol/L. Measuring CART-LI in addition to CgA improved the sensitivity for neuroendocrine malignancy from 85% to 91% whereas combined use of CgA and CgB had a joint sensitivity of 89%. Of 38 patients with pancreatic neuroendocrine tumours, 71% had plasma CART-LI levels >150 pmol/L, increasing to 95% in those classified with progressive disease (n=20, mean CART-LI 625pmol/L) compared with 80% for CgA. Chromatographic analysis suggests that circulating CART-LI is present as one major form, which may correspond to CART (62–102) or another unknown form.

Conclusions: We demonstrate CART-LI as a specific tumour marker in patients with a range of neuroendocrine tumours. Used in combination with CgA, CART-LI measurement has the potential to improve sensitivity in diagnosis and follow up of neuroendocrine tumours, in particular progressive pancreatic neuroendocrine tumours.