Watery diarrhea-hypokalemia-achlorhydria syndrome and carcinoma of the esophagus.

The watery diarrhea-hypokalemia-achlorhydria syndrome associated with ectopic secretion of vasoactive intestinal peptide has only been conclusively documented with tumors originating in the pancreas or sympathetic chain. We report here the case of a 50-yr-old woman who developed this syndrome 3 wk after an apparently effective course of radiotherapy for an obstructing, mixed-cell carcinoma of the esophagus. High concentrations of vasoactive intestinal peptide were found in plasma (100-200 pmol/L; normal less than 20 pmol/L) and in the metastatic skin nodules (750 pmol/g) that later developed and that contained one of the two cell types from the original tumor. Stool volumes reached a plateau of 15-20 L/day, and potassium requirements were greater than 1000 mmol/day. Symptoms failed to respond to any of the regimens previously described as effective in this syndrome. After 14 wk of massive fecal fluid and electrolyte losses, symptoms resolved dramatically with the first dose of 5-fluorouracil. Plasma vasoactive intestinal peptide concentration returned to normal, where it remained despite subsequent evidence of renewed tumor spread. This case illustrates the unpredictability of the response of this syndrome to medical treatment, and suggests that vasoactive intestinal peptide secretion may occur in a wider range of tumors than has so far been described.