What is the diagnosis and management for an adult patient with elevated Total Iron-Binding Capacity (TIBC), transferrin, and low iron levels, potentially indicating iron deficiency anemia?

Iron Deficiency Without Anemia

Your laboratory values (TIBC 519 mg/dL, transferrin 371 mg/dL, iron 90 µg/dL) indicate iron deficiency without anemia, requiring both iron supplementation and investigation for underlying causes, particularly gastrointestinal pathology if you are male or postmenopausal female. 1, 2

Laboratory Interpretation

Your transferrin saturation is approximately 17% (calculated as serum iron 90 ÷ TIBC 519 × 100), which is just above the diagnostic threshold of <16% used to confirm iron deficiency in adults. 1 However, your elevated TIBC of 519 mg/dL (normal range typically 250-450 mg/dL) strongly indicates depleted iron stores, as TIBC increases when serum iron concentration and stored iron are low. 1, 2

• The elevated transferrin (371 mg/dL) and TIBC (519 mg/dL) are characteristic findings of iron deficiency, reflecting increased availability of iron-binding sites on transferrin as the body attempts to capture more iron from the circulation. 1
• Your serum iron of 90 µg/dL may appear normal but must be interpreted in context with the elevated TIBC, which reveals relative iron deficiency. 1
• Serum ferritin should be measured immediately as it is the single most useful marker of iron deficiency, though other tests like transferrin saturation help when false-normal ferritin is suspected due to inflammation. 1

Immediate Management

Start oral iron supplementation without delay while pursuing diagnostic workup. 2

• Ferrous sulfate 324 mg daily (containing 65 mg elemental iron) is the recommended first-line choice. 2, 3
• Alternative dosing of 100-200 mg elemental iron daily can be used depending on tolerance and severity. 2
• Reassess hemoglobin and iron studies after 2-4 weeks, expecting a hemoglobin rise ≥10 g/L within 2 weeks if true iron deficiency exists. 1, 2

Investigation for Underlying Cause

The approach to investigation depends critically on your demographic profile:

For Men and Postmenopausal Women:

• Bidirectional endoscopy (gastroscopy and colonoscopy) should be first-line investigation, as approximately one-third have underlying gastrointestinal pathology including malignancy. 1, 2
• Do not delay investigation pending response to iron therapy, as this may miss gastrointestinal cancer. 2
• Screen for celiac disease serologically or via small bowel biopsy at gastroscopy, as it is present in 3-5% of iron deficiency anemia cases. 1, 2
• Perform urinalysis or urine microscopy to exclude urinary tract blood loss. 1

For Premenopausal Women:

• Evaluate menstrual history thoroughly, as heavy menstrual bleeding is the most common cause, but severe anemia should not preclude further gastrointestinal evaluation. 2
• Perform dietary assessment to evaluate for inadequate iron intake, particularly in vegetarians or those with restrictive eating patterns. 2
• Consider stool guaiac testing for occult blood to evaluate for gastrointestinal bleeding. 2

Differential Diagnosis Considerations

Your laboratory pattern must be distinguished from anemia of chronic disease (ACD):

• In ACD, both serum iron AND TIBC are typically low (not elevated like your TIBC of 519), with normal or elevated ferritin due to inflammation. 1, 4, 5
• Serum transferrin receptor (sTfR) testing can definitively differentiate iron deficiency from ACD when results are equivocal, as sTfR is elevated in iron deficiency but normal in ACD and is not affected by inflammation. 1, 4
• Your elevated TIBC strongly argues against ACD and supports true iron deficiency. 1, 4

Follow-Up Strategy

If initial investigations are negative:

• Capsule endoscopy is the preferred test for small bowel examination if iron deficiency persists or recurs after negative bidirectional endoscopy. 1
• Long-term iron replacement therapy may be appropriate when the cause is unknown or irreversible after thorough investigation. 1
• Consider intravenous iron if oral iron is not tolerated, malabsorption is documented, or ongoing blood loss continues. 2

Critical Pitfalls to Avoid

• Do not assume dietary deficiency alone without excluding pathologic causes, especially in men and postmenopausal women where gastrointestinal malignancy must be ruled out. 2
• Do not rely solely on serum iron levels, as they have significant diurnal variation (rising in morning, falling at night) and day-to-day fluctuation. 1
• Do not overlook inflammation as a confounding factor that can falsely elevate ferritin levels, masking true iron deficiency. 1