McKittrick–Wheelock syndrome

Overview

McKittrick–Wheelock syndrome is a rare but potentially life-threatening condition characterized by severe fluid and electrolyte depletion caused by secretory diarrhea from a large colorectal villous adenoma or adenocarcinoma. The syndrome was first described in 1954 by Drs. McKittrick and Wheelock, who identified a connection between large rectosigmoid tumors and profound metabolic derangements.

The hallmark of the syndrome is chronic, watery diarrhea leading to significant losses of sodium, potassium, and chloride, resulting in hyponatremia, hypokalemia, hypochloremia, and metabolic acidosis. Without timely diagnosis and treatment, patients may progress to volume depletion, renal dysfunction, or cardiac arrhythmias. Definitive treatment typically involves surgical resection of the tumor.

Causes

McKittrick–Wheelock syndrome is caused by a large, secretory colorectal tumor, most commonly a:

• Villous adenoma – a type of benign colorectal polyp with a high mucin-producing capability

• Villous adenocarcinoma – a malignant tumor that retains secretory properties

These tumors are usually located in the distal colon or rectum. Their mucinous secretion is rich in electrolytes, especially potassium and sodium, leading to chronic diarrhea and systemic fluid loss.

The continuous loss of water and electrolytes overwhelms the body's compensatory mechanisms, especially when the tumor is large (often >4 cm in diameter) and left untreated.

Symptoms

The clinical presentation of McKittrick–Wheelock syndrome is often dramatic, especially as electrolyte abnormalities progress. Common symptoms include:

• Chronic, profuse watery diarrhea: Often persistent and unresponsive to standard treatments; can occur multiple times daily

• Severe dehydration: Due to ongoing fluid losses

• Electrolyte imbalances:

  • Hyponatremia (low sodium)

  • Hypokalemia (low potassium)

  • Hypochloremia (low chloride)

• Generalized weakness and fatigue

• Muscle cramps

• Dizziness and orthostatic hypotension

• Weight loss

• Renal dysfunction: Due to volume depletion and electrolyte disturbances

• Cardiac arrhythmias: Particularly from severe hypokalemia

In some cases, symptoms may be misattributed to chronic gastrointestinal disorders such as irritable bowel syndrome or inflammatory bowel disease, leading to delayed diagnosis.

Diagnosis

The diagnosis of McKittrick–Wheelock syndrome involves a combination of clinical suspicion, biochemical analysis, and imaging studies. Diagnostic steps include:

• Laboratory tests:

  • Serum electrolytes showing hyponatremia, hypokalemia, hypochloremia

  • Metabolic acidosis (often a non-anion gap acidosis)

  • Elevated blood urea nitrogen (BUN) and creatinine due to volume depletion

• Stool analysis:

  • Watery, mucinous stool with high sodium and potassium content

• Colonoscopy:

  • Essential for identifying the underlying lesion

  • Reveals a large, often sessile villous adenoma or mucinous adenocarcinoma in the rectosigmoid region

  • Biopsy is necessary to determine histology and assess for malignancy

• Abdominal imaging (CT/MRI):

  • May show a mass in the rectum or distal colon

  • Useful for preoperative planning and evaluating tumor extent

The syndrome should be suspected in patients with unexplained, refractory diarrhea and marked electrolyte abnormalities, particularly when associated with a pelvic mass.

Treatment

The definitive treatment of McKittrick–Wheelock syndrome involves complete surgical resection of the tumor. Management can be divided into two phases:

1. Initial Medical Stabilization

• Correction of fluid and electrolyte imbalance:

  • Intravenous fluids to restore intravascular volume

  • Electrolyte replacement, especially potassium and sodium

• Monitoring: Cardiac monitoring and renal function assessment are important due to the risk of arrhythmia and acute kidney injury.

2. Definitive Surgical Management

• Local excision: For benign tumors that are small and well-demarcated

• Segmental colectomy or low anterior resection: For large or invasive lesions, especially those with signs of malignancy

• Oncologic follow-up: If malignancy is confirmed, further management with chemotherapy may be considered

Surgery not only removes the source of fluid loss but also eliminates the potential for malignant progression in adenomas. After tumor removal, diarrhea typically resolves rapidly, and electrolyte balance is restored.

Prognosis

The prognosis of McKittrick–Wheelock syndrome is generally excellent with early diagnosis and surgical intervention. Key factors that influence prognosis include:

• Timeliness of treatment: Early surgical removal of the tumor can reverse symptoms and prevent permanent renal or cardiac complications.

• Tumor pathology: Villous adenomas have low malignant potential if removed early, whereas adenocarcinomas require additional oncologic treatment.

• Reversibility of organ dysfunction: Acute kidney injury due to prolonged dehydration may be reversible with rehydration, but chronic damage may persist if diagnosis is delayed.

With proper care, most patients recover fully after surgery, and recurrence is rare if complete resection is achieved. Regular follow-up and colonoscopic surveillance are advised to monitor for new polyps or tumors, especially in patients with a history of villous adenomas.