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Difficulty: MediumOrdering Laboratory Tests

A 2828-year-old woman comes to the clinic complaining of intermittent, crampy abdominal pain, bloating, and loose, foul-smelling stools for the past 44 months. She also reports progressive fatigue and an unintentional weight loss of 33 kg (6.66.6 lbs) during this time. Her past medical history is significant for autoimmune thyroiditis, for which she takes levothyroxine. Vital signs are within normal limits. Physical examination reveals mild abdominal distension without tenderness. Laboratory studies show a hemoglobin concentration of 10.210.2 g/dL and a mean corpuscular volume of 7474 fL.

Which of the following is the most appropriate next step in laboratory evaluation?

  1. A
    Measurement of deamidated gliadin peptide IgG antibodies
  2. B
    Fecal calprotectin assay
  3. Measurement of tissue transglutaminase IgA antibodies and total serum IgA levelsAnswer
  4. D
    HLA-DQ2 and HLA-DQ8 genotyping
  5. E
    Hemoglobin electrophoresis

Answer

Measurement of tissue transglutaminase IgA antibodies and total serum IgA levels is the most appropriate initial diagnostic laboratory test.
The correct answer is the measurement of tissue transglutaminase IgA antibodies and total serum IgA levels. This patient presents with chronic diarrhea, bloating, weight loss, and microcytic anemia, which forms a classic presentation of malabsorption. Given her history of autoimmune thyroiditis, celiac disease is the most likely diagnosis. The initial laboratory evaluation for suspected celiac disease is serologic screening with tissue transglutaminase (tTG) IgA antibodies. Because celiac disease is highly associated with selective IgA deficiency, a total serum IgA level must be measured concurrently. If the patient is IgA deficient, the tTG-IgA test could yield a false-negative result, and IgG-based testing would then be required.

Step-by-Step Solution

1
Analyze the clinical presentation.
The patient has chronic loose stools, bloating, weight loss, and microcytic anemia, alongside a personal history of an autoimmune disorder.
Identifying this constellation of symptoms helps formulate a differential diagnosis centered around malabsorption and autoimmune enteropathy.
2
Identify the most likely underlying condition.
Celiac disease emerges as the top differential diagnosis.
Celiac disease classically presents with malabsorption and iron deficiency anemia, and has a strong association with other autoimmune diseases such as Hashimoto thyroiditis.
3
Determine the optimal initial laboratory evaluation.
Serologic screening with tissue transglutaminase (tTG) IgA and total serum IgA is indicated.
tTG-IgA is a highly sensitive and specific first-line test. Total IgA must be checked simultaneously to rule out selective IgA deficiency, which could otherwise cause a false-negative tTG-IgA result.

Key Concept

The initial laboratory evaluation for suspected celiac disease involves measuring tissue transglutaminase (tTG) IgA antibodies alongside a total serum IgA level to account for the possibility of concurrent selective IgA deficiency.
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Ordering Laboratory Tests

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