What is the diagnosis and treatment for a patient with hypoferritinemia, low transferrin saturation, normal Total Iron-Binding Capacity (TIBC), and normal transferrin levels?

Diagnosis and Management of Iron Deficiency Without Inflammation

This patient has iron deficiency without evidence of inflammation, diagnosed by low serum iron (4.2), low transferrin saturation, and normal TIBC/transferrin—the classic pattern requires iron supplementation and investigation of the underlying cause. 1

Diagnostic Interpretation

Your laboratory pattern indicates absolute iron deficiency in the absence of inflammation:

• Low serum iron (4.2) combined with low transferrin saturation (<16%) confirms depleted iron stores 1
• Normal TIBC and transferrin rules out anemia of chronic disease (ACD), which would show low TIBC 1
• In patients without biochemical or clinical inflammation, serum ferritin <30 μg/L or transferrin saturation <16% defines iron deficiency 1

The normal TIBC is particularly important—it excludes inflammatory conditions where TIBC would be suppressed. This distinguishes your case from ACD, where you would see ferritin >100 μg/L with transferrin saturation <16-20% in the presence of elevated inflammatory markers (CRP, ESR). 1

Mandatory Evaluation for Underlying Cause

You must identify and treat the source of iron deficiency, as it may indicate serious pathology including malignancy 2, 3:

• Gastrointestinal blood loss: Most common cause requiring gastroscopy and colonoscopy 2, 3
• Menstrual blood loss: In reproductive-age women (38% have iron deficiency without anemia) 3
• Malabsorption disorders: Celiac disease (check tissue transglutaminase antibodies), atrophic gastritis, H. pylori infection, post-bariatric surgery 3, 4
• Dietary insufficiency: Particularly in vegetarians/vegans 3
• Medications: NSAIDs causing occult GI bleeding 3

Do not simply treat with iron without investigating the cause—this is a critical pitfall that can delay diagnosis of serious conditions like colorectal cancer. 2

Treatment Approach

First-Line: Oral Iron Supplementation

Start with ferrous sulfate 325 mg daily or on alternate days 5, 3:

• Each 325 mg tablet contains 65 mg elemental iron 5
• Alternate-day dosing (every other day) may improve absorption and reduce side effects compared to daily dosing 1
• Take on empty stomach for optimal absorption, though may take with food if GI side effects occur 3
• Common side effects include constipation, diarrhea, nausea (occur frequently) 1

Reassess iron studies after 8-10 weeks—not earlier, as ferritin levels can be falsely elevated immediately after treatment 1

Indications for Intravenous Iron

Switch to IV iron if 3, 6, 4:

• Intolerance to oral iron (GI side effects preventing adherence)
• Malabsorption conditions (celiac disease, post-bariatric surgery, inflammatory bowel disease)
• Ongoing blood loss exceeding oral replacement capacity
• Need for rapid repletion (severe symptomatic anemia, preoperative optimization)
• Pregnancy (second/third trimester) 3
• Chronic inflammatory conditions (though you don't have inflammation currently) 1, 3

Available IV formulations include ferric carboxymaltose, iron sucrose, and ferumoxytol, which allow rapid administration of large doses with very low rates of serious adverse events (<1:250,000) 1

Key Clinical Pitfalls to Avoid

• Don't skip the diagnostic workup: Iron deficiency always requires investigation unless the cause is obvious (e.g., documented heavy menstrual bleeding, known malabsorption) 2, 3
• Don't check ferritin too early after starting treatment: Wait 8-10 weeks for accurate reassessment 1
• Don't assume normal hemoglobin excludes iron deficiency: Iron deficiency without anemia is common and causes symptoms (fatigue, restless legs, pica, exercise intolerance) 3
• Don't continue oral iron indefinitely without response: If no improvement after 8-10 weeks, consider malabsorption, ongoing blood loss, or incorrect diagnosis 1, 6

Monitoring Symptoms

Iron deficiency, even without anemia, commonly causes 3:

• Fatigue and difficulty concentrating
• Restless legs syndrome (32-40% of cases)
• Pica (40-50% of cases)
• Exercise intolerance
• Depression and irritability

These symptoms should improve with adequate iron repletion, providing additional confirmation of the diagnosis and treatment efficacy.