Which test result is most diagnostic for pernicious anemia when evaluating megaloblastic anemia?

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Understanding megaloblastic anemia often hinges on distinguishing true B12 deficiency from folate deficiency. Pernicious anemia is caused by autoimmune loss of intrinsic factor, so B12 cannot be absorbed properly. The Schilling test specifically tests this mechanism: you give radioactive B12 and check its urinary excretion, then repeat with intrinsic factor added. If B12 reappears in the urine after intrinsic factor is given, it shows that the gut could not absorb B12 because intrinsic factor was missing, and once intrinsic factor is provided, absorption proceeds. That pattern is the most diagnostic for pernicious anemia, because it links the deficiency to intrinsic factor lack rather than to other causes of B12 deficiency such as inadequate intake. Elevated ferritin, normal B12, or a low MCV are not specific for pernicious anemia and don’t pinpoint the intrinsic factor–dependent absorption defect.