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Malabsorption. ARUP Consult®. Retrieved October 20, 2020, https://arupconsult.com/content/malabsorption

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Malabsorption

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. 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.

Quick Answers for Clinicians

Which testing algorithms are related to this topic?
Anemia Testing Algorithm
Celiac Disease Testing for Symptomatic Individuals Algorithm
Immunodeficiency Evaluation for Chronic Infections in Adults and Older Children Testing Algorithm
Immunodeficiency Evaluation for Chronic Infections in Infants and Children Testing Algorithm

Key Points

Diarrhea is a common complaint in malabsorptive disorders. Multiple tests are available for evaluating malabsorption; some are more sensitive than others.

Inflammation/Infection Testinga
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 – qualitative immunoassay

Lactoferrin, Fecal by ELISA 0061164
  • Do not use to diagnose IBD or IBS
  • Positive result – indicative of the presence of lactoferrin, a marker for fecal leukocytes
  • Negative result – does not exclude the presence of intestinal inflammation
  • Monitor IBD

n/a

Specimen – fecal, single random

Method – ELISA
Calprotectin, Fecal  by Immunoassay 3002859

Inflammation assessment (indirect)

  • Aid in differentiation of IBD from IBS and other functional disorders of the GI system
  • Monitor IBD
 n/a

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

aAll linked tests are offered by ARUP Laboratories

ELISA, enzyme-linked immunosorbent assay; GI, gastrointestinal; IBD, inflammatory bowel disease; IBS, irritable bowel syndrome; n/a, not available; PCR, polymerase chain reaction
Carbohydrate Malabsorption Testinga
Test Purpose of Test Sensitivity/Specificity

False Positives/Negatives

 Test Characteristics/Requirements
Disaccharidase in Tissue 3002037 Use to evaluate malabsorption due to disaccharidase deficiency n/a

Specimen – tissue biopsy of small bowel

Method – quantitative spectrophotometry

Reducing Substances - Fecal 3002514

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 – quantitative pH indicator strips/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 ELISA/semiquantitative IFA

Multiple methods for cascade

Hydrogen breath test

Carbohydrate (lactose or fructose) malabsorption or bacterial overgrowth assessment

  • Late peak (2-4 hrs) of >10-20 ppm of exhaled H2 – suggestive of malabsorption
  • ~2 hr peak >10-20 ppm of exhaled H2 – 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 min intervals for 4-5 hrs 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 – replaced by hydrogen breath test

Variable

Specimen – fasting serum, interval sampling post dose

  • Reduced carbohydrate diet for 24 hr pretest

Method – quantitative enzymatic

aAll linked tests are offered by ARUP Laboratories

ELISA, enzyme-linked immunosorbent assay; IFA, indirect fluorescent antibody; n/a, not available
Fat Malabsorption Testinga
Test Purpose of Test Sensitivity/ Specificity

False Positives/Negatives

 Test Characteristics/Requirements

Fat, Fecal Qualitative 0020385

Measurement of fecal fats can be useful in establishing a diagnosis of pancreatic disease

High sensitivity/specificity when fat malabsorption >10 g/24 hrs

Specimen – fecal, random

  • Daily intake 50-150 g/day fat 3 days prior to testing

Method – qualitative microscopy/stain

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 hrs is suggestive of fat malabsorption

High sensitivity/lacks specificity

False negatives – incomplete collection, uncontrolled fat intake

Specimen – fecal, random (for quantitative test); 24-, 48-, and 72-hr tests are available (refer to list of tests in first column)

  • Daily intake 50-150 g/day fat 3 days prior to testing

Method – NMR spectroscopy

aAll linked tests are offered by ARUP Laboratories

NMR, nuclear magnetic resonance
Pancreatic Exocrine Function Testinga
Test Purpose of Test Sensitivity/ Specificity

False Positives/Negatives

 Test Characteristics/Requirements

Pancreatic Elastase, Fecal by Immunoassay 3002858

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

Chymotrypsin, 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 – quantitative enzymatic/spectometry

Secretinstimulation 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

aAll linked tests are offered by ARUP Laboratories

ELISA, enzyme-linked immunosorbent assay; IV, intravenous

Diagnosis

Indications for Testing

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

Laboratory Testing

  • Initial nonspecific screening tests
  • Specific tests
    • Thyroid stimulating hormone (TSH) – rule out thyroid disease
    • Cystic fibrosis testing (sweat chloride)
    • Initial fecal tests – perform in parallel with serum tests
    • Consider celiac testing (tissue transglutaminase [tTG] antibody testing with IgA level)
    • Stool culture, ova and parasite – evaluation using gastrointestinal panels; Clostridium 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
    • Refer to Key Points

Imaging Studies

If initial test results are normal, consider abdominal computed tomography (CT) or ultrasound, endoscopy.

Differential Diagnosis

Refer to causes of malabsorption in Background.

Background

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], 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

Pathophysiology

  • Nutrient digestion and absorption occur in 3 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

ARUP Laboratory Tests

Assess for fecal blood

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

Aid in differentiation of IBD from IBS and other functional disorders of the gastrointestinal (GI) system

Aid in monitoring of IBD and prediction of relapse

Not specific for IBD

Not diagnostic for IBD

Does not distinguish celiac disease (CD) from ulcerative colitis

Results may fluctuate as disease activity fluctuates

False negatives are more common in children than adults

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

Detect Cryptosporidium hominis, C. parvum, Cyclospora cayetanensis, Dientamoeba fragilis, Entamoeba histolytica, and Giardia lamblia/intestinalis/duodenalis

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, or microsporidia

​Negative result does not rule out presence of polymerase chain reaction (PCR) inhibitors in specimen or assay-specific nucleic acid in concentrations below the level of detection

Important informationThis test has been temporarily inactivated due to reagent shortages; refer to the Stool Culture and E. coli Shiga-like Toxin by EIA test (0060134)

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, and Shiga-toxigenic E. coli

Can also detect Campylobacter upsaliensis, which cannot be readily cultured

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

Evaluate carbohydrate malabsorption due to disaccharidase deficiency

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

Carbohydrate malabsorption assessment (indirect)

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

Preferred reflex screening test for CD

May aid in monitoring adherence to gluten-free diet (GFD)

Correlation between CD serologic tests may be variable at low antibody titers, early disease, or treatment with GFD; strong clinical correlation is recommended

At screening dilution, endomysial antibody (EMA) may show prozone phenomenon; if suspicion for disease is strong, consider testing for tissue transglutaminase (tTg) and/or deamidated gliadin peptide (DGP) antibodies

Sera containing antismooth muscle antibodies (ASMA) will interfere with the detection of EMA IgG; sera should be further tested at higher dilutions

False-negative results possible in early disease, in individuals on GFD, and with use of immunosuppression

With false-positive results, consider early disease and/or specific risk for CD

Small bowel biopsy and/or HLA DQ typing may be important in establishing a diagnosis of CD based on patient’s age, clinical symptoms, and/or risk for disease

Reflex pattern: test begins with immunoglobulin A; depending on findings, one or more of the following tests may be added for clinical interpretation

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
Celiac Disease Dual Antigen Screen

Measurement of fecal fats can be useful in establishing a diagnosis of pancreatic disease

Use for random stool collection

Measurement of fecal fats can be useful in establishing a diagnosis of pancreatic disease

Testing requires submission of an aliquot from a 24-, 48-, or 72-hour stool collection

For random stool collection, refer to qualitative fecal fat test

For complete 24-hour stool collections, order 24-hour quantitative fecal fat test

For complete 48-hour stool collections, order 48-hour quantitative fecal fat test

For complete 72-hour stool collections, order 72-hour quantitative fecal fat test

Measurement of fecal fats can be useful in establishing a diagnosis of pancreatic disease

Testing requires submission of an entire 24-hour stool collection

For random stool collection, refer to qualitative fecal fat test

For testing of an aliquot from a 24-, 48-, or 72-hour stool collection, order the quantitative fecal fat test

For complete 48-hour stool collections, order 48-hour quantitative fecal fat test

For complete 72-hour stool collections, order 72-hour quantitative fecal fat test

Measurement of fecal fats can be useful in establishing a diagnosis of pancreatic disease

Testing requires submission of an entire 48-hour stool collection

For random stool collection, refer to qualitative fecal fat test

For testing of an aliquot from a 24-, 48-, or 72-hour stool collection, order the quantitative fecal fat test

For complete 24-hour stool collections, order 24-hour quantitative fecal fat test

For complete 72-hour stool collections, order 72-hour quantitative fecal fat test

Measurement of fecal fats can be useful in establishing a diagnosis of pancreatic disease

Testing requires submission of an entire 72-hour stool collection

For random stool collection, refer to qualitative fecal fat test

For testing of an aliquot from a 24-, 48-, or 72-hour stool collection, order the quantitative fecal fat test

For complete 24-hour stool collections, order 24-hour quantitative fecal fat test

For complete 48-hour stool collections, order 48-hour quantitative fecal fat test

Screen for exocrine pancreatic function

Related Tests

Assess for presence of anemia and leukocytosis

Assess for inflammatory processes

Panel includes anion gap, carbon dioxide, chloride, potassium, and sodium 

Preferred test to detect acute phase inflammation (eg, autoimmune diseases, connective tissue disease, rheumatoid arthritis, infection, or sepsis)

Nonspecific test used to detect inflammation associated with infections, cancers, and autoimmune diseases

Initial screening test for hepatobiliary inflammation

Panel includes albumin; alkaline phosphatase (ALP); aspartate aminotransferase (AST); alanine aminotransferase (ALT); bilirubin, direct; protein, total; and bilirubin, total

Screen for other causes of malabsorption

May assist in assessing nutritional status or indicating a possible chronic process

Assess thyroid function

Identify risk in patients with palpable thyroid nodules

Reflex pattern: if thyroid stimulating hormone (TSH) is outside the reference interval, then free T4 testing will be added

Preferred test for screening and monitoring of thyroid function

Determine whether to use IgA or IgG tissue transglutaminase (tTG) and deamidated gliadin peptide (DGP) assays

Recommended single screening test for IgA-deficient individuals with suspected celiac disease (CD)

IgA testing recommended to identify IgA deficiency prior to choosing tTG test

May aid in monitoring adherence to gluten-free diet (GFD) in CD-confirmed patients

Recommended rapid, stand-alone diagnostic test for Clostridium difficile-associated diarrhea

Assess fat malabsorption

Use for nutritional assessment of vitamin A (retinol and retinyl palmitate) in serum or plasma

Preferred test to diagnose vitamin D insufficiency and monitor response to therapy

Testing is recommended only for patients at risk for vitamin D insufficiency

Use for nutritional assessment of vitamin E (alpha- and gamma-tocopherols)

Aid in detection of vitamin B12 deficiency in individuals with macrocytic or unexplained anemia, or unexplained neurologic disease

Carbohydrate (lactose) malabsorption assessment

Not recommended: replaced by hydrogen breath test

Pancreatic exocrine function assessment

Not recommended; elastase measures are better

Medical Experts

Contributor

Couturier

Marc Roger Couturier, PhD, D(ABMM)
Marc Roger Couturier, PhD, D(ABMM)
Associate Professor of Clinical Pathology, University of Utah
Medical Director, Parasitology/Fecal Testing, Infectious Disease Antigen Testing, Bacteriology, and Molecular Amplified Detection, ARUP Laboratories
Contributor

Genzen

Jonathan R. Genzen, MD, PhD
Jonathan R. Genzen, MD, PhD
Associate Professor of Clinical Pathology, University of Utah
Chief Operations Officer: Medical Director, Automated Core Laboratory, ARUP Laboratories
Contributor

References

Additional Resources
Resources from the ARUP Institute for Clinical and Experimental Pathology®

Related Information