What laboratory tests should be run for chronic diarrhea?

Laboratory Evaluation for Chronic Diarrhea

All patients with chronic diarrhea require a standardized initial laboratory panel including complete blood count, inflammatory markers (ESR and CRP), comprehensive metabolic panel, liver function tests, iron studies, vitamin B12, folate, calcium, thyroid function tests, IgA tissue transglutaminase antibody with total IgA level, and stool testing for Giardia and fecal calprotectin. 1, 2

Initial Blood Work

The following blood tests should be ordered simultaneously as your first-line screening panel:

• Complete blood count (CBC): Anemia has high specificity for organic disease and is a sensitive indicator of small bowel enteropathy, particularly celiac disease 1, 2
• Inflammatory markers: ESR and CRP have high specificity (though lower sensitivity) for organic disease; abnormal results essentially rule out functional disorders 1, 2
• Comprehensive metabolic panel: Including electrolytes, renal function, and liver function tests 1
• Iron studies (ferritin): Iron deficiency is a sensitive indicator of small bowel enteropathy 1
• Vitamin B12 and folate: Screen for malabsorption 1
• Calcium: May be low in malabsorptive states 1
• Thyroid function tests: TSH is the best predictor for hyperthyroidism, which causes diarrhea through accelerated gut transit 1

Celiac Disease Screening (Mandatory)

IgA tissue transglutaminase (tTG) antibody with total IgA level must be ordered in all patients with chronic diarrhea. 1, 2

• Celiac disease is the most common small bowel enteropathy in Western populations, with prevalence of 3-10% in patients with chronic diarrhea 1
• Critical pitfall: Always check total IgA levels simultaneously—IgA deficiency occurs in approximately 2-3% of celiac patients and will cause false-negative tTG results 2
• If IgA deficient, order IgG-based tests (IgG-tTG or IgG deaminated gliadin peptides) instead 2

Stool Studies

Order these stool tests as part of your initial workup:

• Fecal calprotectin or fecal lactoferrin: Use threshold of 50 mg/g for calprotectin or 4.0-7.25 mg/g for lactoferrin to screen for inflammatory bowel disease with >90% sensitivity 2, 1
• Giardia antigen testing or PCR: Strongly recommended due to high prevalence and excellent test performance 2, 1
• Stool culture and microscopy: Though infectious causes are uncommon in immunocompetent patients with chronic symptoms, this should still be performed 1

Additional Testing Based on Clinical Context

If Malabsorption Suspected (bulky, pale, malodorous stools):

• Fecal elastase: Preferred non-invasive test for pancreatic insufficiency due to ease of use, though requires at least moderate pancreatic impairment for adequate sensitivity 1
• Avoid 3-day fecal fat: This test is unreliable in clinical practice and no longer recommended 1

If Factitious Diarrhea Suspected (especially in specialist referral settings):

• Laxative screen: Should include detection of anthraquinones, bisacodyl, and phenolphthalein in urine, and magnesium and phosphate in stool 1
• Stool magnesium >45 mmol/L strongly suggests magnesium-induced diarrhea 1
• Avoid alkalinization assays—insufficient sensitivity 1

If High-Volume Watery Diarrhea Persists After Negative Workup:

• Hormone testing (VIP, gastrin, glucagon): Only order when other causes excluded—these tumors are extremely rare and screening has more false-positives than true-positives 1, 3

Key Clinical Pitfalls to Avoid

• Do not rely solely on ESR/CRP to screen for IBD: Fecal calprotectin and lactoferrin are more sensitive markers 2
• Never order celiac testing without checking total IgA: This is the most common reason for missed celiac disease diagnosis 2
• Do not order hormone panels as screening tests: Reserve for high-volume secretory diarrhea after excluding common causes 1, 3
• Avoid empiric trials without documentation: While therapeutic trials of cholestyramine (for bile acid malabsorption) or antibiotics (for bacterial overgrowth) are sometimes used, their diagnostic validity has not been rigorously studied 1

Age-Stratified Approach to Further Investigation

After initial laboratory testing, the next step depends on results and patient age:

• Age >45 years or alarm features present (weight loss, nocturnal diarrhea, blood in stool, family history of colorectal cancer): Proceed directly to colonoscopy with biopsies 1
• Age <45 years without alarm features: Flexible sigmoidoscopy with biopsies may be sufficient if initial labs are reassuring 1
• Elevated fecal calprotectin: Mandates colonoscopy regardless of age 2