In a 63-year-old woman with type 1 diabetes who has serum iron 32 µg/dL, total iron‑binding capacity 303 µg/dL, unsaturated iron‑binding capacity 271 µg/dL, and transferrin saturation 11 %, what is the most likely cause of her anemia and what is the appropriate next diagnostic step?

Iron Deficiency Anemia with Depleted Iron Stores

This patient has classic iron deficiency anemia with depleted iron stores, confirmed by transferrin saturation of 11% (well below the 16% diagnostic threshold) and elevated TIBC of 303 µg/dL. 1

Diagnostic Interpretation

The iron panel unequivocally demonstrates iron deficiency:

• Transferrin saturation of 11% is markedly below the diagnostic cutoff of <16% for iron deficiency in adults, confirming true deficiency 2, 1
• Elevated TIBC (303 µg/dL) indicates the body is attempting to maximize iron-binding capacity in response to depleted iron stores 1
• Elevated UIBC (271 µg/dL) is a highly accurate marker for empty iron stores, with diagnostic accuracy of 0.80-0.97, and is more reliable than serum iron or transferrin saturation alone 1
• Low serum iron (32 µg/dL) further supports the diagnosis, though this parameter has high day-to-day variability and should not be used in isolation 1

Essential Next Diagnostic Step

Measure serum ferritin immediately to quantify iron stores and assess for inflammation. 1

• In the absence of inflammation (normal CRP), ferritin <30 µg/L definitively confirms iron deficiency 2, 1
• If inflammation is present, ferritin up to 100 µg/L may still be consistent with iron deficiency 2
• Obtain C-reactive protein (CRP) simultaneously to identify concurrent inflammation, because inflammation can falsely elevate ferritin and mask true iron deficiency 1

Mandatory Workup for Underlying Cause

Iron deficiency rarely occurs without an identifiable source of loss or inadequate intake: 1

• Screen for gastrointestinal blood loss with fecal occult blood testing, as GI bleeding is a common cause requiring endoscopic evaluation if positive 1
• Assess for malabsorption disorders including celiac disease and inflammatory bowel disease, particularly given the patient's autoimmune history (type 1 diabetes) 1, 3
• Evaluate for dietary insufficiency and restrictive eating patterns 1
• Consider NSAID use, which can cause occult GI bleeding 1

Type 1 Diabetes-Specific Considerations

• Screen for parietal cell antibodies (PCAs) and consider gastric autoimmunity, as 15-20% of type 1 diabetic patients have PCAs and are at increased risk for iron deficiency anemia and atrophic gastritis 3
• Soluble transferrin receptor (sTfR) levels are higher in PCA-positive type 1 diabetic patients and can help diagnose iron deficiency anemia independent of inflammation 3
• Iron deficiency anemia is 3-fold more prevalent in PCA-positive versus PCA-negative type 1 diabetic patients 3

Additional Laboratory Testing

• Complete blood count with MCV and RDW to assess for microcytic anemia and red cell distribution width 2
• Calculate estimated glomerular filtration rate (eGFR) to assess for chronic kidney disease, as CKD can complicate iron deficiency diagnosis and treatment 1
• Urinalysis to screen for proteinuria or hematuria if renal dysfunction is suspected 1

Critical Diagnostic Pitfalls to Avoid

• Do not dismiss iron deficiency based on "normal" serum iron alone, as serum iron exhibits high day-to-day variability and is influenced by recent meals, diurnal changes, and inflammation 1
• Normal ferritin does not exclude iron deficiency, especially if inflammation is present or if the patient has early/functional iron deficiency 1
• In the presence of inflammation, the ferritin threshold for diagnosing iron deficiency should be raised to ≥100 µg/L rather than the standard lower cutoff 1

Treatment Considerations After Diagnosis Confirmation

Once ferritin confirms iron deficiency: 1

• Therapeutic goal: Achieve ferritin ≥100 ng/mL and transferrin saturation ≥20% 1
• Consider intravenous iron if oral iron is not tolerated due to GI side effects, if eGFR <30 mL/min/1.73 m², or if there is lack of hematologic response after 4-8 weeks of adequate oral iron therapy 1