Clinical, Biochemical, and Kidney Abnormalities in McKittrick–Wheelock Syndrome: An Individual-Patient Systematic Review of Published Cases

Background/Objectives: McKittrick–Wheelock syndrome is a rare entity secondary to colorectal tumors, characterized by chronic diarrhea, electrolyte and acid–base disturbances, and impaired kidney function; its pathophysiology and biochemical spectrum remain incompletely defined. Methods: We conducted an individual-patient systematic review of published cases (PROSPERO CRD420251233022). Eligible patients had a colorectal tumor, chronic diarrhea, and at least one otherwise unexplained electrolyte or acid–base disturbance. Data on demographics, presentation, tumor characteristics, electrolyte and acid–base abnormalities, creatinine levels, and mechanisms of diarrhea were extracted and analyzed. Results: Among 195 reports including 231 patients, median age was 68 years and symptoms usually persisted >12 months. Tumors were predominantly large distal colorectal adenomas: 97% were within 29 cm and 68% within 10 cm of the anal verge; none measured ≤50 mm and 78% measured ≥100 mm. Hypokalemia occurred in 90%, hyponatremia in 91%, metabolic acidosis in 50%, metabolic alkalosis in 28%, and elevated creatinine in 91%. Stool osmotic-gap data in eight patients and reduced stool losses with non-steroidal anti-inflammatory drugs in seven cases were compatible with secretory, partly prostaglandin-mediated diarrhea. No statistically significant, biochemical differences were detected by tumor size. Conclusions: McKittrick–Wheelock syndrome is a recognizable, potentially treatable syndrome associated with chronic diarrhea and major metabolic and kidney abnormalities, requiring early recognition.