Combined Use of Cocaine-and-Amphetamine-Regulated-Transcript (CART) Peptide and Chromogranin A Improves Diagnostic Sensitivity in Neuroendocrine Tumours
Department of Endocrinology, Hammersmith and Charing Cross Hospitals, Imperial College Healthcare NHS Trust, Du Cane Road, London, W12 0HS
R Ramachandran, P Bech, KG Murphy, WS Dhillo, T Tan, K Meeran, MA Ghatei, SR Bloom, M Caplin, NM Martin
A 16 year old gentleman with MEN 1 was found to have multiple lesions (octreotide positive lymph node near the lesser curvature of the stomach, 13mm lesion in pancreatic head and 15mm lesion in the body of the pancreas), on routine surveillance. An ultrasound guided biopsy confirmed these lesions were neuroendocrine tumours (NETs) (Ki67 index 1%). A gut hormone profile including chromogranin A (Cg A) was within the reference range. Plasma Cocaine-and-amphetamine-regulated-transcript (CART), which has been proposed to be an effective NET marker, was elevated at123 pmol/L (diagnostic cut-off 80 pmol/L). On further questioning, the patient described episodes suggestive of hypoglycaemia. A three day fast confirmed a biochemical diagnosis of insulinoma and subsequent selective angiography and intra-arterial calcium injection confirmed that both pancreatic lesions were insulinomas. The patient underwent enucleation of the pancreatic lesions and a wedge resection of the lesser curvature of the stomach including the lymph node. Post-operatively, the patient remains asymptomatic and follow-up surveillance imaging does not reveal any recurrent disease. Consistent with this, plasma CART fell post-operatively to 46 pmol/L and has remained within normal limits during surveillance. This case highlights potential advantages of using CART in addition to CgA for the diagnosis and monitoring of NETs.
This interesting finding has led me to focus on the role of CART as a NET marker. I have measured plasma CART in 241 patients with a diagnosis of NET (103 midgut carcinoids, 80 gastro-pancreatic NETs, 29 NETs with unknown primary and 28 non-gastroenteropancreatic NETs) compared with181 healthy controls. Plasma CART was significantly higher in NET groups compared to controls: [controls] 51 ± 1.4 pmol/L; [midgut carcinoids] 121 ± 15.5 pmol/L (p<0.0001 vs. controls), [gastro-pancreatic NETs] 373 ± 42.5 pmol/L (p<0.0001 vs. controls), [non- gastroenteropancreatic NETs] 404.2 ± 78.3 pmol/L (p<0.0001 vs. controls) and [NETs with unknown primary] 376 ±74.1 pmol/L (p<0.0001 vs. controls). A diagnostic cut-off of 80pmol/L for plasma CART offers a sensitivity of 77% and a specificity of 95% for the diagnosis of NETs compared to a sensitivity of 77% and specificity of only 71% for Cg A. Combined use of CART and Cg A increases this sensitivity to 91%. These results support a role for CART as a novel, clinically useful NET marker.