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Difficulty: MediumOrdering Laboratory Tests

A 3232-year-old woman comes to the primary care clinic reporting a 66-month history of chronic diarrhea, abdominal bloating, and an unintentional weight loss of 55 kg (1111 lbs). She describes her bowel movements as bulky, foul-smelling, and difficult to flush. Her medical history is significant for type 11 diabetes mellitus, which is managed with an insulin pump. Vital signs are within normal limits. Physical examination reveals a mildly distended abdomen with hyperactive bowel sounds but no tenderness, guarding, or organomegaly. Initial laboratory studies show a hemoglobin of 10.510.5 g/dL with a mean corpuscular volume of 7474 fL. Which of the following is the most appropriate next step in diagnostic evaluation?

  1. Serum tissue transglutaminase (tTG) IgA antibody and total IgA levelsAnswer
  2. B
    Computed tomography (CT) of the abdomen and pelvis with intravenous contrast
  3. C
    HLA-DQ2 and HLA-DQ8 genetic testing
  4. D
    Fecal elastase-1 concentration
  5. E
    Quantitative 7272-hour fecal fat measurement

Answer

Serum tissue transglutaminase (tTG) IgA antibody and total IgA levels
The correct answer is to order tissue transglutaminase (tTG) IgA antibody and total serum IgA levels. The patient's presentation of chronic diarrhea, steatorrhea (indicated by bulky, foul-smelling stools that are difficult to flush), unintentional weight loss, and microcytic anemia strongly suggests a malabsorptive process. Given her history of type 1 diabetes mellitus, she is at exceptionally high risk for other autoimmune conditions, particularly celiac disease. The most appropriate, cost-effective, and highly sensitive initial laboratory evaluation for celiac disease is testing for tissue transglutaminase (tTG) IgA antibodies. Because selective IgA deficiency is more common in patients with celiac disease (occurring in about 2-3% of these patients) and can lead to false-negative tTG IgA results, a total serum IgA level must be measured simultaneously to validate the serologic screening.

Step-by-Step Solution

1
Analyze the patient's clinical presentation and laboratory findings.
The patient exhibits chronic diarrhea, steatorrhea, weight loss, and microcytic anemia, which are classic signs of malabsorption. Her history of type 1 diabetes strongly increases the risk for other autoimmune disorders.
Establishing a syndromic diagnosis of malabsorption with an autoimmune predisposition narrows the differential diagnosis significantly toward celiac disease.
2
Determine the most appropriate initial screening test for the suspected etiology.
The preferred initial test is tissue transglutaminase (tTG) IgA antibody combined with a total serum IgA level.
tTG-IgA is highly sensitive and specific. Total IgA must be measured concurrently because selective IgA deficiency is common in celiac patients and would cause a false-negative tTG-IgA result.

Key Concept

The initial laboratory evaluation for suspected celiac disease includes tissue transglutaminase (tTG) IgA antibody testing accompanied by a total serum IgA level to prevent false-negative results in patients with concurrent selective IgA deficiency.
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Ordering Laboratory Tests

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