Causes of Secretory Acute Diarrhea in Adults
In acute secretory diarrhea, the primary causes are infectious agents (bacterial enterotoxins and viruses), followed by medications, laxatives, and rarely, acute presentations of hormone-secreting tumors or bile acid malabsorption.
Infectious Causes (Most Common in Acute Settings)
- Bacterial enterotoxins are the predominant cause of acute secretory diarrhea, producing toxins that activate chloride channels and cyclic nucleotide pathways in enterocytes 1, 2
- Viral pathogens breach cell barriers and disrupt fluid secretion across the epithelium by altering ion transport mechanisms 2
- These pathogens specifically fault the cystic fibrosis transmembrane conductance regulator (CFTR) and calcium-activated chloride channels, leading to massive fluid secretion 1, 2
Medication and Exogenous Causes
- Laxative abuse can present acutely and should be suspected when initial workup is negative; factitious diarrhea accounts for 4% of cases in general gastroenterology clinics but increases to 20% at tertiary centers 3
- Medications including magnesium products, NSAIDs, antibiotics, antihypertensives, and theophyllines can trigger acute secretory diarrhea 4
- Secretagogues and endogenous detergents (such as bile acids) can cause acute onset of large-volume watery diarrhea 5, 6
Neuroendocrine Tumors (Rare but Important)
- VIPomas produce profuse secretory diarrhea exceeding 1 liter per day with severe dehydration and hypokalemia in 100% of cases, though the incidence is fewer than 1 in 10 million per year 3, 7
- Gastrinomas (Zollinger-Ellison syndrome) cause diarrhea in 50-65% of cases through gastric acid hypersecretion, with an incidence of approximately 1 in 1 million per year 3, 7
- Carcinoid syndrome causes diarrhea in 50% of cases, typically occurring with hepatic metastases that allow vasoactive compounds like serotonin to bypass hepatic metabolism 3, 7
Bile Acid Malabsorption
- Cholecystoenteric fistulae to the colon can cause acute bile acid diarrhea 3
- Bile acids acting as luminal secretagogues produce watery diarrhea that typically worsens after meals 8, 6
Clinical Characteristics to Identify Secretory Diarrhea
- Large-volume watery diarrhea (usually >1 liter per day) that persists with fasting 5
- Stool osmolality gap less than 40 mOsm/kg, distinguishing it from osmotic diarrhea 5, 9
- Painless diarrhea with minimal abdominal cramping in most cases 5
- Dehydration and electrolyte abnormalities, particularly hypokalemia in severe cases 3
Critical Diagnostic Pitfalls
- Do not assume all acute diarrhea is infectious—medication review is mandatory as up to 4% of chronic cases (and likely more acute cases) are medication-induced 4
- Screen for laxative abuse when initial infectious workup is negative, using urine testing for anthraquinones, bisacodyl, and phenolphthalein, and stool testing for magnesium and phosphate 3
- Consider neuroendocrine tumors only after excluding common causes, as hormone-secreting tumors are rare (prevalence of 10 per million population) and testing should be reserved for cases with characteristic features like massive volume (>1 L/day), severe hypokalemia, or flushing 3