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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.The objective of the study was to investigate the measurement of plasma CART-LI as a tumor marker of neuroendocrine malignancy.Plasma CART-LI levels were measured in 401 patients with a range of diagnoses: neuroendocrine malignancy (n = 131), after removal of neuroendocrine malignancy (n = 27), without any form of tumor or renal impairment (n = 192), with renal impairment (n = 17) and with nonneuroendocrine tumors (n = 34). Chromatography methods were used to investigate CART-LI circulating in human plasma.The upper limit of normal calculated for CART-LI was 150 pmol/liter. Mean circulating plasma CART-LI among neuroendocrine tumor patients was 440 pmol/liter, 56% of subjects having levels greater than 150 pmol/liter. Measuring CART-LI in addition to chromogranin (Cg)-A 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 tumors, 71% had plasma CART-LI levels greater than 150 pmol/liter, increasing to 95% in those classified with progressive disease (n = 20, mean CART-LI 625 pmol/liter), 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.We demonstrate CART-LI as a specific tumor marker in patients with a range of neuroendocrine tumors. Used in combination with CgA, CART-LI measurement has the potential to improve sensitivity in diagnosis and follow-up of neuroendocrine tumors, in particular progressive pancreatic neuroendocrine tumors.

The McKittrick-Wheelock syndrome is characterized by severe electrolyte and fluid depletion as a result of rectal tumor hypersecretion. Typically, a metabolic acidosis ensues. We report the case of a 58-year-old man who presented with a mixed metabolic acidosis and alkalosis. He was hyponatremic, hypokalemic, and hypochloremic, with acute renal failure on blood testing. Following fluid resuscitation, a predominant alkalemia was observed. The patient was found to be passing 1.5 L of mucous per rectum per day, containing high concentrations of sodium and potassium, similar to that observed in cholera stool. A large rectal villous adenoma was discovered on sigmoidoscopy, and definitive management was achieved by removal of the tumor. This case provides a demonstration of the ranging metabolic disturbance associated with secretory diarrhea. Other endogenous and infective causes are discussed, and mechanisms compared with the case described.