What is the appropriate workup for a patient with suspected malabsorption syndrome?

Malabsorption Syndrome Workup

Initial Laboratory Screening

Begin with a focused laboratory panel to confirm malabsorption and identify the underlying cause: complete blood count, iron studies (ferritin, transferrin saturation), vitamin B12, folate, vitamin D (25-hydroxyvitamin D), calcium, albumin, and celiac serology (IgA anti-tissue transglutaminase with total IgA level). 1, 2, 3

Core Blood Tests

• Complete blood count to detect anemia, which is present in the majority of symptomatic malabsorption patients 1
• Ferritin and transferrin saturation (ferritin up to 100 μg/L may still indicate iron deficiency if transferrin saturation <20% in active disease) 1
• Vitamin B12 and folate every 3-6 months in patients with small bowel disease or previous resection 1, 2
• 25-hydroxyvitamin D (target ≥75 nmol/L), as deficiency occurs in 16-95% of patients with malabsorption 1
• Calcium and parathyroid hormone to exclude secondary hyperparathyroidism 1

Celiac Disease Screening

• IgA anti-tissue transglutaminase (TG2-IgA) is the primary screening test with highest accuracy 1, 3
• Total IgA level must be checked simultaneously, as IgA deficiency occurs in 2-3% of celiac patients 1
• IgA endomysial antibody (EMA) serves as confirmatory testing due to high specificity 1
• Do not restrict gluten intake before testing, as this reduces test sensitivity 4

Stool Studies

Obtain fecal elastase-1 and consider quantitative fecal fat measurement to distinguish pancreatic insufficiency from mucosal disease. 3, 5

• Fecal elastase-1 <100 μg/g indicates pancreatic exocrine insufficiency 3
• Quantitative fecal fat (72-hour collection) remains the gold standard for confirming fat malabsorption, though newer spot tests are available 3, 6
• Stool culture and ova/parasites if infectious etiology suspected (Giardia) 3

Endoscopic Evaluation

Proceed to upper endoscopy with duodenal biopsies if celiac serology is positive or if initial workup is negative but clinical suspicion remains high. 1, 3, 5

• Duodenal biopsies (at least 4-6 samples from second/third portion of duodenum) are the gold standard for diagnosing celiac disease and other mucosal disorders 1, 3
• Small bowel aspirate for bacterial culture if small intestinal bacterial overgrowth (SIBO) is suspected 5
• Visual inspection for scalloping, fissuring, or mosaic pattern suggesting villous atrophy 1

Additional Testing Based on Initial Results

If Pancreatic Insufficiency Suspected

• CT or MRI of pancreas to evaluate for chronic pancreatitis, pancreatic cancer, or structural abnormalities 3
• Consider secretin-stimulated pancreatic function testing in equivocal cases, though rarely performed in routine practice 1

If Bile Acid Malabsorption Suspected

• SeHCAT nuclear medicine scan (where available) or serum C4 and FGF19 measurements 3
• Bile acid malabsorption is present in approximately 28% of patients with diarrhea-predominant IBS 3

Fat-Soluble Vitamin Assessment

• Vitamin A if steatorrhea, night blindness, or protein malnutrition present 1, 2
• Vitamin E if unexplained anemia or neuropathy 1
• Vitamin K1 and PIVKA-II especially after malabsorptive procedures 1
• These deficiencies can occur even without overt steatorrhea 1, 2

Trace Elements

• Zinc if unexplained anemia, hair loss, or taste changes 1
• Copper if unexplained anemia or poor wound healing 1
• Selenium if chronic diarrhea, metabolic bone disease, unexplained anemia, or cardiomyopathy 1
• Magnesium as low levels indicate malabsorption 1

Imaging Studies

Order small bowel imaging if endoscopy is normal but malabsorption persists. 5

• Small bowel follow-through or CT/MR enterography to identify anatomical abnormalities, strictures, fistulas, or masses 1, 5
• Abdominal CT scan to evaluate pancreatic structure and rule out masses 6

Critical Pitfalls to Avoid

• Do not wait for steatorrhea to diagnose malabsorption, as milder forms may not cause obvious stool abnormalities 2
• Do not rely on albumin as a marker of malabsorption, as it is an acute phase reactant and does not correlate with nutritional status in otherwise healthy individuals 1
• Do not use BMI alone to assess nutritional status, as it fails to detect sarcopenia in obese patients with malabsorption 2
• Do not delay thiamine replacement if rapid weight loss, vomiting, or neuropathy present—treat immediately without waiting for laboratory confirmation 1
• Do not interpret normal ferritin as excluding iron deficiency in active disease, as ferritin up to 100 μg/L may still represent deficiency 1

High-Risk Populations Requiring Proactive Screening

• First-degree relatives of celiac patients (7.5% prevalence) 1, 2
• Type 1 diabetes (5-10% have celiac disease) 1
• Autoimmune thyroid disease, autoimmune liver disease 1
• Chronic pancreatitis patients (screen for micronutrient deficiencies at least annually) 1, 2
• Post-bariatric surgery patients (monitor at 3,6,12 months, then annually) 1
• Inflammatory bowel disease with small bowel involvement or resection 1, 2