Malabsorption

Primary Authors: Couturier, Marc Roger, PhD, D(ABMM). Grenache, David G., PhD.

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 Inflammatory bowel disease (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	Do not use to diagnose IBD or irritable bowel syndrome (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		Specimen – fecal, single random Method – ELISA
Calprotectin, Fecal 0092303	Inflammation assessment (indirect) Aid in differentiation of IBD from IBS and other functional disorders of the GI system 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
Disaccharidase, Tissue 2002247	Use to evaluate malabsorption due to disaccharidase deficiency		Specimen – tissue biopsy of small bowel Method – quantitative spectrophotometry
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 – 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 enzyme-linked immunosorbent assay/semiquantitative indirect fluorescent antibody Multiple methods for cascade
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	Specimen – 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	Measurement of fecal fats can be useful in establishing a diagnosis of pancreatic disease	High sensitivity/ specificity when fat malabsorption >10 g/24 hr	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 hr 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-hour 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
* 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 by ELISA 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
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
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: 15 Things Physicians and Patients Should Question, 2016; 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
- Refer to Key Points section

Imaging Studies

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

Differential Diagnosis

Refer to causes of malabsorption in Clinical Background section

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

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

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

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

Recommended Use

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

Aid in monitoring of IBD and prediction of relapse

Clinical sensitivity for diagnosis of IBD – 95%

Clinical specificity for diagnosis of IBD – 91%

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, C. parvum
Cyclospora cayetanensis
Dientamoeba fragilis
Entamoeba histolytica
Giardia lamblia/intestinalis/duodenalis

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

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

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

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

Disaccharidase, Tissue 2002247
Method: Quantitative Spectrophotometry

Recommended Use

Use to evaluate carbohydrate malabsorption due to disaccharidase deficiency

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

Preferred reflex screening test for celiac disease

May aid in monitoring adherence to gluten-free diet

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

Fat, Fecal Qualitative 0020385
Method: Qualitative Microscopy/Stain

Recommended Use

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

Use for random stool collection

Limitations

Results cannot be used if patient on low-fat diet

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

Recommended Use

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

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

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

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

Recommended Use

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

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

Recommended Use

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

Pancreatic Elastase, Fecal by ELISA 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

Choosing Wisely. An initiative of the ABIM Foundation. [Accessed: Sep 2017]

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

References from the ARUP Institute for Clinical and Experimental Pathology®

Beal SG, Couturier MR, Gander RM, Doern CD. Diagnostic Algorithm for the Diagnosis of Pediatric Parasitic Gastroenteritis. J Clin Lab Anal. 2016; 30(2): 155-60. PubMed

Erickson A, Aldeen WE, Grenache DG, Ashwood ER. Evaluation of a fecal pancreatic elastase-1 enzyme-linked immunosorbent assay: Assessment versus an established assay and implication in classifying pancreatic function. Clin Chim Acta. 2008; 397(1-2): 87-91. PubMed

Hackenmueller SA, Grenache DG. Reference Intervals for Intestinal Disaccharidase Activities Determined from a Non-Reference Population. American Association for Clinical Chemistry. [Published Sep 2016; Accessed: Apr 2017]

Lu J, Pulsipher BS, Grenache DG. An automated method for the measurement of total protein in homogenates of intestinal mucosa. Clin Chim Acta. 2013; 421: 59. PubMed

Medical Reviewers

Couturier, Marc Roger, PhD, D(ABMM), Medical Director, Microbial Immunology, Parasitology and Fecal Testing, and Infectious Disease Rapid Testing at ARUP Laboratories; Assistant Professor of Clinical Pathology, University of Utah

Delgado, Julio, MD, MS, Chief Medical Officer; Director of Laboratories; Co-Chief, Clinical Pathology Division at ARUP Laboratories; Associate Professor of Clinical Pathology, University of Utah

Grenache, David G., PhD, Medical Director, Special Chemistry; Co-Director, Electrophoresis and Manual Endocrinology; Chief Medical Director, Clinical Chemistry at ARUP Laboratories; Associate Professor of Clinical Pathology, University of Utah

Anemia