Malabsorption

Primary Author: Couturier, Marc Roger, PhD, D(ABMM).

Diarrhea is a common complaint in malabsorptive disorders. Multiple tests are available for evaluating malabsorption; some are more sensitive than others. Test choice depends on the clinician’s suspicion regarding the etiology of the malabsorption (eg, carbohydrate malabsorption versus fat malabsorption). “Shotgun” approaches to malabsorption evaluations are not recommended.

Inflammation/infection testing

Inflammation/Infection Testing*
Test	Purpose of Test	Sensitivity/Specificity False Positives/Negatives	Test Characteristics/Requirements
Fecal leukocytes	Inflammation assessment IBD Infectious etiologies	Sensitive for inflammation Not specific	Specimen – fecal, single random Method – trichrome stain with microscopic evaluation
Occult Blood, Fecal by Immunoassay 2007190	Fecal blood assessment IBD Malignancy Infectious etiologies	Sensitive Not specific	Specimen – fecal, single random Method – quantitative immunoassay
Lactoferrin, Fecal by ELISA 0061164 OR Calprotectin, Fecal 0092303	Inflammation assessment (indirect) Differentiate IBD from IBS and other functional disorders of the intestinal tract Positive result less indicative of IBS Monitor IBD		Specimen – fecal, single random Method – ELISA
Gastrointestinal Parasite Panel by PCR 2011150	Infectious assessment	High sensitivity/specificity	Specimen – fecal, single random Method – PCR
Gastrointestinal Bacterial Panel by PCR 2012678	Infectious assessment	High sensitivity/specificity	Specimen – fecal, single random Method – PCR
* All linked tests are offered by ARUP Laboratories

Carbohydrate malabsorption testing

Carbohydrate Malabsorption Testing*
Test	Purpose of Test	Sensitivity/Specificity False Positives/Negatives	Test Characteristics/Requirements
Reducing Substances, Fecal 0020373	Carbohydrate malabsorption assessment (indirect) Presence of reducing substances suggests carbohydrate malabsorption Most useful in children who are unable to undergo lactose tolerance or hydrogen breath tests	Poor sensitivity for oligosaccharide malabsorption False positives – other compounds can reduce cupric ions to cuprous ions	Specimen – fecal, single random Method – semiquantitative colorimetry
pH, Fecal 0020518	Carbohydrate malabsorption assessment (indirect) Acidic pH (<5.5) suggests carbohydrate (lactose) malabsorption	Moderate sensitivity Increasing age of stool will increase rate of false positives	Specimen – fecal, single random Discontinue antibiotics 1-2 wks prior to test Method – Nitrazine paper using quantitative pH meter
Celiac Disease Reflexive Cascade 2008114	Celiac disease assessment High antibody titers very suggestive of celiac disease Gold standard for diagnosis is tissue biopsy	High sensitivity/ specificity	Specimen – serum Method – quantitative nephelometry/semiquantitative enzyme-linked immunosorbent assay/semiquantitative indirect fluorescent antibody Multiple methods for cascade
Xylose Absorption Test (Adult - 25g dose) 0020609 Xylose Absorption Test (Adult - 5g dose) 0020615 Xylose Absorption Test (Child) 0020612	Distinguishes mucosal malabsorption (usually secondary to bacterial overgrowth) from pancreatic disease Low post-dose levels suggest mucosal malabsorption	Variable High rate of false positives and negatives (at least 20%)	Fasting serum, followed by 5 hr urine, 2 hr serum post-xylose ingestion 5-25 g oral dose of xylose Serum or urine sample obtained post oral dose No ingestion of foods high in pentose sugar for 24 hr pretest Method – quantitative spectrophotometry
Hydrogen breath test	Carbohydrate (lactose or fructose) malabsorption or bacterial overgrowth assessment Late peak (2-4 hr) of >10-20 ppm of exhaled H2 is suggestive of malabsorption ~2 hr peak >10-20 ppm of exhaled H2 is suggestive of bacterial overgrowth	Sensitivity Greater than lactose tolerance test Approximates small bowel culture for bacterial overgrowth evaluation False negatives Carbohydrate malabsorption (eg, chronic pancreatitis, celiac disease, delayed gastric emptying) False positives Gastric motility disorders	Basal breath test, interval testing Follow up hydrogen breath levels at 30 minute intervals for 4-5 hours post dose Oral glucose/lactose – bacterial overgrowth Oral fructose/sucrose – fructose malabsorption Overnight fast required Reduced carbohydrate diet for 24 hr pretest
Lactose Tolerance 0020407	Carbohydrate (lactose) malabsorption assessment Not recommended – has been replaced by hydrogen breath test	Variable	Fasting serum, interval sampling post-dose Reduced carbohydrate diet for 24 hr pretest Method – quantitative enzymatic
* All linked tests are offered by ARUP Laboratories

Carbohydrate Malabsorption Testing*

Test

Purpose of Test

Sensitivity/Specificity
False Positives/Negatives

Test Characteristics/Requirements

Reducing Substances, Fecal 0020373

Carbohydrate malabsorption assessment (indirect)

Presence of reducing substances suggests carbohydrate malabsorption

Most useful in children who are unable to undergo lactose tolerance or hydrogen breath tests

Poor sensitivity for oligosaccharide malabsorption

False positives – other compounds can reduce cupric ions to cuprous ions

Specimen – fecal, single random

Method – semiquantitative colorimetry

pH, Fecal 0020518

Carbohydrate malabsorption assessment (indirect)

Acidic pH (<5.5) suggests carbohydrate (lactose) malabsorption

Moderate sensitivity

Increasing age of stool will increase rate of false positives

Specimen – fecal, single random

Discontinue antibiotics 1-2 wks prior to test

Method – Nitrazine paper using quantitative pH meter

Celiac Disease Reflexive Cascade 2008114

Celiac disease assessment

High antibody titers very suggestive of celiac disease

Gold standard for diagnosis is tissue biopsy

High sensitivity/ specificity

Specimen – serum

Method – quantitative nephelometry/semiquantitative enzyme-linked immunosorbent assay/semiquantitative indirect fluorescent antibody

Multiple methods for cascade

Xylose Absorption Test (Adult - 25g dose) 0020609

Xylose Absorption Test (Adult - 5g dose) 0020615

Xylose Absorption Test (Child) 0020612

Distinguishes mucosal malabsorption (usually secondary to bacterial overgrowth) from pancreatic disease

Low post-dose levels suggest mucosal malabsorption

Variable

High rate of false positives and negatives (at least 20%)

Fasting serum, followed by 5 hr urine, 2 hr serum post-xylose ingestion

5-25 g oral dose of xylose

Serum or urine sample obtained post oral dose

No ingestion of foods high in pentose sugar for 24 hr pretest

Method – quantitative spectrophotometry

Hydrogen breath test

Carbohydrate (lactose or fructose) malabsorption or bacterial overgrowth assessment

Late peak (2-4 hr) of >10-20 ppm of exhaled H2 is suggestive of malabsorption
~2 hr peak >10-20 ppm of exhaled H2 is suggestive of bacterial overgrowth

Sensitivity

Greater than lactose tolerance test
Approximates small bowel culture for bacterial overgrowth evaluation

False negatives

Carbohydrate malabsorption (eg, chronic pancreatitis, celiac disease, delayed gastric emptying)

False positives

Gastric motility disorders

Basal breath test, interval testing

Follow up hydrogen breath levels at 30 minute intervals for 4-5 hours post dose
Oral glucose/lactose – bacterial overgrowth
Oral fructose/sucrose – fructose malabsorption
Overnight fast required
Reduced carbohydrate diet for 24 hr pretest

Lactose Tolerance 0020407

Carbohydrate (lactose) malabsorption assessment

Not recommended – has been replaced by hydrogen breath test

Variable

Fasting serum, interval sampling post-dose

Reduced carbohydrate diet for 24 hr pretest

Method – quantitative enzymatic

* All linked tests are offered by ARUP Laboratories

Fat malabsorption testing

Fat Malabsorption Testing*
Test	Purpose of Test	Sensitivity/ Specificity False Positives/Negatives	Test Characteristics/Requirements
Fat, Fecal Qualitative 0020385	Fat malabsorption assessment	High sensitivity/ specificity when fat malabsorption >10 g/24 hr	Specimen – fecal, 24 hr required Daily intake 70-100 g/day fat 2-5 days prior to testing Method – Sudan stain of stool
Fat, Fecal Quantitative, Homogenized Aliquot 2002350 Fat, Fecal Quantitative 24-Hour Collection (Includes Homogenization) 2002354 Fat, Fecal Quantitative 48-Hour Collection (Includes Homogenization) 2002355 Fat, Fecal Quantitative 72-Hour Collection (Includes Homogenization) 2002356	Fat malabsorption assessment >7 g/24 hr is suggestive of fat malabsorption Gold standard No longer required for pancreatic disease	High sensitivity/lacks specificity False negatives – incomplete collection, uncontrolled fat intake	Specimen – fecal, 72-hr collection Daily intake 70-100 g/day fat 2-5 days prior to testing Method – NMR spectroscopy
* All linked tests are offered by ARUP Laboratories

Pancreatic exocrine function testing

Pancreatic Exocrine Function Testing*
Test	Purpose of Test	Sensitivity/Specificity False Positives/Negatives	Test Characteristics/Requirements
Pancreatic Elastase, Fecal 0080526	Pancreatic exocrine function assessment Low concentrations suggest pancreatic exocrine dysfunction	Sensitive, specific Good correlation with invasive tests of exocrine function results	Specimen – fecal, single random Pancreatic enzyme supplementation must be discontinued prior to testing Method – ELISA using monoclonal antibody to elastase-1
Chmyotrypsin, Fecal 2005160	Pancreatic exocrine function assessment Low concentrations suggest pancreatic exocrine dysfunction Not recommended – elastase measures are better	Fecal elastase testing is superior in sensitivity and specificity	Specimen – fecal, single random Pancreatic enzyme supplementation must be discontinued prior to testing Method – enzymatic detection
Secretin stimulation test	Pancreatic exocrine function assessment Gold standard test	High sensitivity for pancreatic function	Overnight fast required Discontinuation of H2 blockers 24 hrs prior to test Discontinuation of proton-pump inhibitors 7 days prior to test Method – collection of duodenal fluids for 2 hrs after stimulation with IV secretin
* All linked tests are offered by ARUP Laboratories

Indications for Testing

Chronic diarrhea, steatorrhea, or preexisting condition that may predispose to malabsorption

Laboratory Testing

Initial nonspecific screening tests
- CBC
  - Mild anemia frequent; leukocytosis in IBD or infectious etiology
  - Eosinophilia – consider parasitic evaluation
- Electrolyte panel
- C-reactive protein (CRP)
  - Preferred test to detect inflammatory processes (Choosing Wisely: 5 Things Physicians and Patients Should Question, 2015; American Society for Clinical Pathology)
  - If CRP not available, order erythrocyte sedimentation rate (ESR)
- Liver enzymes, including albumin – low albumin suggests chronic processes
Specific tests
- TSH – rule out thyroid disease
- Cystic fibrosis testing (sweat chloride)
- Initial fecal tests – perform in parallel with serum tests
- Consider celiac testing (tTG antibody testing with IgA level)
- Stool culture, ova and parasite – evaluation using GI panels; C. difficile testing if risk factors present
  - Fecal leukocytes – present in IBD, infectious diarrhea
  - Fecal occult blood
  - Fecal fat, qualitative/quantitative
Secondary testing
- Based on clinical history and above test results
- See Key Points section

Imaging Studies

If initial test results are normal, consider abdominal CT or ultrasound, endoscopy

Differential Diagnosis

See causes of malabsorption in Clinical Background

Anemia Testing Algorithm

Read more about Anemia Testing Algorithm

Celiac Disease Testing for Symptomatic Individuals Algorithm

Read more about Celiac Disease Testing for Symptomatic Individuals Algorithm

Immunodeficiency Evaluation for Chronic Infections in Adults and Older Children Testing Algorithm

Read more about Immunodeficiency Evaluation for Chronic Infections in Adults and Older Children Testing Algorithm

Immunodeficiency Evaluation for Chronic Infections in Infants and Children Testing Algorithm

Read more about Immunodeficiency Evaluation for Chronic Infections in Infants and Children Testing Algorithm

Zollinger-Ellison Syndrome Testing Algorithm

Read more about Zollinger-Ellison Syndrome Testing Algorithm

Malabsorption is characterized by the inability to digest or absorb nutrients from the small intestine into the bloodstream and is related to diseases of the pancreas, liver, and intestine.

Causes of Malabsorption

Inadequate digestion of nutrients
- Deficiencies of pancreatic enzymes (eg, chronic pancreatitis, pancreatic carcinoma, cystic fibrosis)
- Impaired synthesis or secretion of bile (eg, biliary obstruction, cirrhosis)
- Deconjugation of bile salts (eg, blind-loop syndrome)
Inadequate absorption of nutrients
- Shortened bowel or loss of absorptive surface (eg, inflammatory bowel disease [IBD], including ulcerative colitis, Crohn disease, gluten-sensitive enteropathy [Celiac sprue], tropical sprue, lymphoma, surgical loss of functional bowel, blind-loop syndrome, hormonal disorders)
- Impaired nutrient metabolism (eg, deficiency of intestinal disaccharidases, lactase deficiency)
- Nutrient-specific transport deficiencies (eg, Hartnup disease)
- Decreased availability of specific nutrients (eg, vitamin B₁₂ deficiency due to decreased intrinsic factor)
- Alterations of circulation (eg, mesenteric ischemia, heart failure, portal hypertension, lymphatic obstruction
Miscellaneous
- Amyloidosis, systemic sclerosis (scleroderma), hyperthyroidism, Zollinger-Ellison syndrome, atrophic gastritis, medication-induced malabsorption, neurofibromatosis

Pathophysiology

Nutrient digestion and absorption occur in three phases
- Luminal phase – breakdown and solubilization of proteins, carbohydrates, and fats by digestive enzymes and bile
- Mucosal phase – transport of digested nutrients into gastrointestinal epithelial cells
- Transport phase – transport of nutrients via lymphatics and portal circulation from small intestine to other parts of the body
Any process that disrupts one or more of these phases can cause malabsorption

Clinical Presentation

Prominent symptom – chronic diarrhea
Constitutional – weight loss, fatigue
Gastrointestinal – steatorrhea, abdominal bloating, abdominal pain, somatostatinoma
Extraintestinal – anemia, skin rashes, stomatitis, glossitis, peripheral edema, ascites

Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

Occult Blood, Fecal by Immunoassay 2007190
Method: Quantitative Immunoassay

Recommended Use

Assess for fecal blood

Lactoferrin, Fecal by ELISA 0061164
Method: Qualitative Enzyme-Linked Immunosorbent Assay

Recommended Use

Assess bowel inflammation

Do not use to diagnose inflammatory bowel disease (IBD) or irritable bowel syndrome (IBS); may be used for monitoring IBD activity

Determine presence of fecal leukocytes

Calprotectin, Fecal 0092303
Method: Quantitative Enzyme-Linked Immunosorbent Assay

Recommended Use

May be used to differentiate IBD from IBS and other functional disorders of the intestinal tract; also may be used for monitoring IBD activity

Gastrointestinal Parasite Panel by PCR 2011150
Method: Qualitative Polymerase Chain Reaction

Recommended Use

Aid in the diagnosis of GI infections caused by common protozoal pathogens

Do not order for patients with diarrhea developed during prolonged hospitalization

Use as a sensitive alternative to traditional, insensitive ova and parasite examinations of stool specimens for the evaluation of GI infections

Detects the following

Cryptosporidium hominis and parvum
Cyclospora cayetanensis
Dientamoeba fragilis
Entamoeba histolytica
Giardia lamblia/intestinalis/duodenalis

Analytical sensitivity

C. cayetanensis – 80 copies/reaction
Cryptosporidium parvum/hominis – 216 copies/reaction
D. fragilis – 200 copies/reaction
E. bieneusi – 1,600 copies/100 μL stool
E. histolytica – 100 copies/reaction
Encephalitozoon spp (E. intestinalis) – 440 copies/100 μL stool
Giardia – 960 copies/reaction

Analytical specificity – no cross-reactivity observed for 48 organisms tested

Limitations

Due to periodic shedding of some parasites, a result of “not detected” cannot completely rule out infection with these parasites

If clinical signs and symptoms persist, an additional specimen for testing may be indicated

Viral and bacterial gastroenteritis are more common than parasite gastroenteritis and should be considered as alternative diagnoses

Asymptomatic infections are known to occur, and therefore correlation of test results with clinical signs and symptoms is imperative

Panel does not detect

Helminths (flatworms, roundworms, and flukes)
Nonpathogenic protozoa
Cystoisospora
Microsporidia

Gastrointestinal Bacterial Panel by PCR 2012678
Method: Qualitative Polymerase Chain Reaction

Recommended Use

Aid in the diagnosis of GI infections caused by pathogenic bacteria

Use as a sensitive alternative to traditional stool culture to detect the most common GI bacterial pathogens, including

Salmonella
Shigella/enteroinvasive E. coli
Campylobacter jejuni/coli
Shiga-toxigenic E. coli
Can also detect Campylobacter upsaliensis, which cannot be readily cultured

Analytical sensitivity – limit of detection

Shigella – 36,200 copies/mL
Salmonella – 1,520 copies/mL
Campylobacter jejuni/coli – 3,780 copies/mL
Campylobacter upsaliensis – 1,510 copies/mL
Shiga-like toxin 1 – 5,180 copies/mL
Shiga-like toxin 2 – 4,080 copies/mL

Analytical specificity

No cross-reactivity seen for 43 organisms (bacteria, viruses, and parasites) tested

Limitations

Negative result does not rule out presence of PCR inhibitors in the patient specimen, test-specific nucleic acid in concentrations below the level of detection

Molecular assays will not detect rare or unusual enteric bacterial pathogens that are not specifically targeted by the test (eg, Aeromonas, Plesiomonas, Yersinia, Vibrio, and enterotoxigenic E. coli)

A bacterial isolate is not obtained if antimicrobial susceptibility testing is indicated

Reducing Substances, Fecal 0020373
Method: Semi-quantitative Colorimetry

Recommended Use

Carbohydrate malabsorption assessment (indirect)

Presence of reducing substance suggests carbohydrate malabsorption

Most useful in children who are unable to undergo lactose tolerance or hydrogen breath tests

pH, Fecal 0020518
Method: Quantitative pH Indicator Strips/Quantitative pH Meter

Recommended Use

Carbohydrate malabsorption assessment (indirect)

Acidic pH (<5.5) suggests carbohydrate (lactose) malabsorption

Celiac Disease Reflexive Cascade 2008114
Method: Quantitative Nephelometry/Semi-Quantitative Enzyme-Linked Immunosorbent Assay//Semi-Quantitative Indirect Fluorescent Antibody

Recommended Use

Evaluates serum IgA levels to determine immune status

Reflex pattern – test begins with Immunoglobulin A; depending on findings, one or more reflexive tests may be required in order to provide a clinical interpretation

Tests added may include Tissue Transglutaminase Antibody, IgA; Tissue Transglutaminase Antibody, IgG; Endomysial Antibody, IgA by IFA; Deamidated Gliadin Peptide (DGP) Antibody, IgA; Deamidated Gliadin Peptide (DGP) Antibody, IgG; and/or Celiac Disease Dual Antigen Screen

Xylose Absorption Test (Adult - 25g dose) 0020609
Method: Quantitative Spectrophotometry

Recommended Use

Evaluate carbohydrate absorption by the mucosa of the proximal small intestine

Decreased absorption of D-xylose is due to impaired intestinal absorption

Xylose Absorption Test (Adult - 5g dose) 0020615
Method: Quantitative Spectrophotometry

Recommended Use

Evaluate carbohydrate absorption by the mucosa of the proximal small intestine

5g dose is preferred in patients who do not tolerate the 25g dose

Xylose Absorption Test (Child) 0020612
Method: Quantitative Spectrophotometry

Recommended Use

Nonstandard test for determining cause of malabsorption

Test evaluates carbohydrate absorption of the proximal small intestine

Fat, Fecal Qualitative 0020385
Method: Qualitative Microscopy/Stain

Recommended Use

Fat malabsorption assessment

Limitations

Results cannot be used if patient on low-fat diet

Fat, Fecal Quantitative, Homogenized Aliquot 2002350
Method: Nuclear Magnetic Resonance Spectroscopy

Recommended Use

Fat malabsorption assessment

Gold standard

Limitations

Results cannot be used if patient on low-fat diet

Fat, Fecal Quantitative 24-Hour Collection (Includes Homogenization) 2002354
Method: Nuclear Magnetic Resonance Spectroscopy

Recommended Use

Fat malabsorption assessment

Gold standard

No longer required for pancreatic disease

Fat, Fecal Quantitative 48-Hour Collection (Includes Homogenization) 2002355
Method: Nuclear Magnetic Resonance Spectroscopy

Recommended Use

Fat malabsorption assessment

Gold standard

No longer required for pancreatic disease

Fat, Fecal Quantitative 72-Hour Collection (Includes Homogenization) 2002356
Method: Nuclear Magnetic Resonance Spectroscopy

Recommended Use

Fat malabsorption assessment of >7 g/24 hr suggestive of fat malabsorption

Gold standard

No longer required for pancreatic disease

Pancreatic Elastase, Fecal 0080526
Method: Quantitative Enzyme-Linked Immunosorbent Assay

Recommended Use

Screen for exocrine pancreatic function

Limitations

If pancreatic insufficiency is present, consider cystic fibrosis testing

Guidelines

American Society for Clinical Pathology. Choosing Wisely - Five Things Physicians and Patients Should Question. An initiative of the ABIM Foundation. [Last revision Feb 2015; Accessed: Jan 2016]

Holbrook I, British society of Gastroenterology. The British Society of Gastroenterology guidelines for the investigation of chronic diarrhoea, 2nd edition. Ann Clin Biochem. 2005; 42(Pt 3): 170-4. PubMed

General References

Abenavoli L, Proietti I, Vonghia L, Leggio L, Ferrulli A, Capizzi R, Mirijello A, Cardone S, Malandrino N, Leso V, Rotoli M, Amerio PL, Gasbarrini G, Addolorato G. Intestinal malabsorption and skin diseases. Dig Dis. 2008; 26(2): 167-74. PubMed

Ammoury RF, Croffie JM. Malabsorptive disorders of childhood. Pediatr Rev. 2010; 31(10): 407-15; quiz 415-6. PubMed

Chapman TP, Chen LY, Leaver L. Investigating young adults with chronic diarrhoea in primary care. BMJ. 2015; 350: h573. PubMed

Holt PR. Intestinal malabsorption in the elderly. Dig Dis. 2007; 25(2): 144-50. PubMed

Juckett G, Trivedi R. Evaluation of chronic diarrhea. Am Fam Physician. 2011; 84(10): 1119-26. PubMed

Montalto M, Santoro L, D'Onofrio F, Curigliano V, Visca D, Gallo A, Cammarota G, Gasbarrini A, Gasbarrini G. Classification of malabsorption syndromes. Dig Dis. 2008; 26(2): 104-11. PubMed

Schiller LR. Diarrhea and malabsorption in the elderly. Gastroenterol Clin North Am. 2009; 38(3): 481-502. PubMed

Schiller LR. Management of diarrhea in clinical practice: strategies for primary care physicians. Rev Gastroenterol Disord. 2007; 7 Suppl 3: S27-38. PubMed