A physician-validated, board-style question from the Active Transport QBank. Try it, then check the reasoning for every option.
A 55-year-old woman presents with fatigue. She says her symptoms are present throughout the day and gradually started 4 months ago. Her past medical history is significant for rheumatoid arthritis–treated with methotrexate, and diabetes mellitus type 2–treated with metformin. The patient is afebrile, and her vital signs are within normal limits. A physical examination reveals pallor of the mucous membranes. Initial laboratory tests show hemoglobin of 7.9 g/dL, hematocrit of 22%, and mean corpuscular volume of 79 fL. Which of the following is the best next diagnostic step in this patient?
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A
Serum ferritin levelIncorrect. Ferritin alone is unreliable in inflammatory states (RA) because it rises as an acute-phase reactant and may appear normal even with concurrent iron deficiency.
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B
Serum ferritin and serum iron levelsIncorrect. Serum iron is too non-specific (varies diurnally, drops in any acute illness) and adds little to ferritin alone — neither test distinguishes ACD from ACD + IDA.
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C
Serum ferritin and soluble transferrin receptor levelsCorrect. Combining ferritin with sTfR (which is unaffected by inflammation) is the recommended way to detect iron deficiency superimposed on anemia of chronic disease in patients with RA.
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D
Serum iron levelIncorrect. Serum iron alone is the weakest single marker for evaluating iron status, given its high variability and lack of specificity.
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E
Bone marrow biopsyIncorrect. Bone marrow biopsy is invasive and reserved for unexplained cytopenias or suspected primary marrow disorder; in a patient with RA, combined ferritin and sTfR levels are the appropriate next step to distinguish ACD from concurrent iron deficiency.
↑ Tap an answer to reveal the reasoning
Answer: C. This 55-year-old woman has rheumatoid arthritis (a chronic inflammatory disease) plus a normocytic anemia (Hb 7.9, MCV 79 is at the low end of normal). The differential for anemia in chronic inflammation centers on anemia of chronic disease (ACD) versus iron deficiency anemia (IDA), and importantly, the two can coexist — which dramatically complicates iron studies.
In pure ACD, hepcidin is elevated, sequestering iron in macrophages: ferritin is normal-to-high, serum iron is low, and soluble transferrin receptor (sTfR) is normal. In pure IDA, ferritin is low and sTfR is high (because iron-starved erythroid precursors upregulate transferrin receptors). When both coexist, ferritin can be falsely "normal" because it is an acute-phase reactant elevated by inflammation — masking the iron deficiency. sTfR is NOT an acute-phase reactant and remains a reliable marker of true iron deficiency even in inflammation, so the sTfR/log(ferritin) index (or simply combining both tests) is the recommended approach to distinguish ACD alone from ACD + IDA.
Key pearl: in any patient with chronic inflammation and anemia, ferritin alone is insufficient — pair it with sTfR.
**Why each option:**
**A.** Ferritin alone is unreliable in inflammatory states (RA) because it rises as an acute-phase reactant and may appear normal even with concurrent iron deficiency.
**B.** Serum iron is too non-specific (varies diurnally, drops in any acute illness) and adds little to ferritin alone — neither test distinguishes ACD from ACD + IDA.
**C.** Correct. Combining ferritin with sTfR (which is unaffected by inflammation) is the recommended way to detect iron deficiency superimposed on anemia of chronic disease in patients with RA.
**D.** Serum iron alone is the weakest single marker for evaluating iron status, given its high variability and lack of specificity.