How should malabsorption be diagnosed?

How to Diagnose Malabsorption

Begin with antiendomysium antibody testing (or tissue transglutaminase IgA) as the first-line serological test for celiac disease, followed by upper endoscopy with distal duodenal biopsies if positive or if small bowel malabsorption is suspected despite negative serology. 1

Initial Screening Blood Tests

Start with a comprehensive panel to identify nutritional deficiencies and guide further testing:

• Complete blood count to detect anemia from iron, folate, or B12 malabsorption 1, 2
• Iron studies, vitamin B12, and folate to assess for micronutrient deficiencies 1, 3
• Erythrocyte sedimentation rate and C-reactive protein for inflammatory markers 1
• Liver function tests, calcium, and thyroid function as part of baseline screening 1
• Fat-soluble vitamins (A, D, E, K) if malabsorption is suspected, as these can be reduced even in mild-to-moderate cases 4, 2
• Serum albumin to exclude protein malabsorption or protein-losing enteropathy 2

Important caveat: These screening tests have high specificity but low sensitivity for organic disease, so normal results do not exclude malabsorption. 1

Serological Testing for Celiac Disease

• Antiendomysium antibody testing is the preferred first-line test for celiac disease 1
• Alternatively, use tissue transglutaminase IgA with total IgA level, as IgA deficiency causes false-negative celiac serology 2
• This must be checked immediately in patients with chronic abdominal symptoms, as celiac disease can present with subtle or no gastrointestinal symptoms 3, 2

Non-Invasive Tests for Fat Malabsorption

Fecal Elastase-1 (Preferred)

• Fecal elastase-1 is the most commonly used and preferred first-line test for pancreatic exocrine insufficiency, requiring only a single 100 mg stool sample 4, 2
• Interpretation: FE-1 <200 μg/g is abnormal, <100 μg/g indicates moderate-to-severe pancreatic insufficiency, and <50 μg/g is most reliable for severe disease 4, 2
• Sensitivity is 73-100% and specificity is 80-100% for moderate to severe pancreatic insufficiency, but poor sensitivity (<60%) for mild disease 4
• Must be performed on semi-solid stool, as results can be falsely low in watery diarrhea due to dilution 4, 2
• The test is unaffected by enzyme therapy or diet 2

Stool Fat Collection (Traditional but Limited)

• Three-day stool collection for fecal fat has been the standard test for decades but has significant limitations 1
• Requires a diet of known fat content over 5 days with stool collection during the final 3 days 4
• Fecal fat >7% of ingested fat or >13 g/day (47 mmol/day) indicates severe steatorrhea, typically from pancreatic exocrine insufficiency 4
• Limitations include difficulty collecting complete samples, lack of quality control, and lack of standardization between laboratories 1

Breath Tests (Alternative)

• Breath tests using C-triolein or 13C-substrates offer an attractive alternative to stool tests, with sensitivities of 85-100% and specificity >90% 1
• However, test procedures are not well standardized and inappropriate in patients with diabetes, liver disease, or obesity 1

Endoscopic Evaluation

Upper Endoscopy with Duodenal Biopsies

• Perform upper endoscopy with distal duodenal biopsies if celiac serology is positive or if small bowel malabsorption is suspected despite negative serology 1, 2
• This assesses for celiac disease and other small bowel enteropathies 1
• Duodenal biopsy remains the gold standard for diagnosing celiac disease 5

Colonoscopy vs. Flexible Sigmoidoscopy

• In patients <45 years with chronic diarrhea and/or atypical symptoms, flexible sigmoidoscopy is the first-line investigation, as diagnostic yield differs little from colonoscopy in this age group 1
• In patients >45 years with chronic diarrhea, colonoscopy with ileoscopy is preferred, yielding abnormalities in up to 30% of cases 1
• Colonoscopy is mandatory when age >45 years for colorectal cancer screening or when weight loss and microcytic anemia are present 2

Small Bowel Imaging

• Reserve small bowel imaging (barium follow-through or enteroclysis) for cases where small bowel malabsorption is suspected and distal duodenal histology is normal 1
• Technetium-HMPAO labeled white cell scanning is a non-invasive technique with equivalent sensitivity to small bowel follow-through for assessing terminal ileal Crohn's disease 1

Additional Specialized Testing

Bile Acid Malabsorption

• SeHCAT testing (where available) is sensitive for bile acid malabsorption 4
• If unavailable, consider a therapeutic trial of cholestyramine 4

Imaging for Pancreatic Disease

• CT or MRI to evaluate for chronic pancreatitis or pancreatic carcinoma if fecal elastase suggests pancreatic insufficiency or clinical suspicion is high 4

Diagnostic Algorithm Based on Clinical Context

When malabsorption is suspected:

1. Start with screening blood tests (CBC, iron studies, B12, folate, vitamin D, calcium, liver function, albumin) and celiac serology 1, 3, 2

2. If celiac serology is positive → proceed to upper endoscopy with duodenal biopsies 1, 2

3. If steatorrhea is suspected → check fecal elastase-1 on semi-solid stool 4, 2

4. If fecal elastase <100 μg/g → consider CT/MRI for pancreatic disease 4

5. If fecal elastase is normal but malabsorption persists → proceed to upper endoscopy with duodenal biopsies to assess for mucosal disease 4, 2

6. If duodenal biopsies are normal → consider small bowel imaging 1

7. Age-appropriate colonoscopy based on patient age and symptoms 1, 2

Critical Clinical Pearls

• Do not wait for overt steatorrhea, as milder forms of malabsorption may not result in any reported stool abnormality 3, 2
• Clinical assessment of steatorrhea by stool inspection alone is unreliable 4
• Maintain a high index of suspicion, as many malabsorptive disorders manifest through subtle, non-gastrointestinal findings rather than classic symptoms 3, 6
• Screen high-risk populations proactively, including patients with chronic pancreatitis, inflammatory bowel disease, post-surgical patients, and first-degree relatives of celiac patients 3
• Perform appropriate testing before initiating pancreatic enzyme replacement therapy to avoid masking other disorders such as celiac disease 4
• Multiple causes of malabsorption may coexist, particularly in patients with complex medical histories 4