An adult patient has ferritin 20 ng/mL, serum iron 47 µg/dL, total iron‑binding capacity 302 µg/dL, transferrin saturation 16% and chronic fatigue; what is the diagnosis and how should the iron deficiency be evaluated and managed?

Iron Deficiency Without Anemia: Diagnosis and Management

This patient has absolute iron deficiency confirmed by ferritin 20 ng/mL and transferrin saturation 16%, and requires immediate oral iron supplementation plus investigation for the source of iron loss, particularly gastrointestinal pathology if male or postmenopausal female. 1, 2

Diagnostic Confirmation

Your laboratory values definitively confirm absolute iron deficiency:

• Ferritin 20 ng/mL is below the 30 ng/mL threshold that indicates depleted body iron stores in patients without inflammation 1, 2, 3
• Transferrin saturation 16% falls below the critical 16–20% threshold, confirming iron-deficient erythropoiesis—meaning insufficient iron is available for red blood cell production 1, 2
• Serum iron 47 µg/dL (low) combined with TIBC 302 µg/dL (normal-to-high) reflects the body's attempt to capture more circulating iron when stores are depleted 1
• The absence of anemia (hemoglobin presumably normal) indicates Stage 1 iron deficiency—iron stores are exhausted but anemia has not yet developed 1, 2

Critical point: Chronic fatigue is a cardinal symptom of iron deficiency even without anemia, affecting exercise tolerance, cognitive function, and quality of life. 2, 3

Investigation for Underlying Cause

Iron deficiency in adults always requires investigation because recurrent blood loss accounts for 94% of cases. 3

For Men and Postmenopausal Women

Bidirectional endoscopy (colonoscopy and upper endoscopy) is mandatory to exclude gastrointestinal malignancy, which is found in 9% of patients over 65 years with iron deficiency. 4, 5, 3

For Premenopausal Women

• Assess menstrual blood loss history first—heavy menstrual bleeding is the most common cause in this population 1, 2
• Screen for celiac disease with tissue transglutaminase antibodies (present in 3–5% of iron deficiency cases) 4, 1, 3
• Test for Helicobacter pylori non-invasively (stool antigen or urea breath test) 4, 1, 3
• Reserve bidirectional endoscopy for: age ≥50 years, gastrointestinal symptoms (abdominal pain, change in bowel habits, blood in stool), positive celiac or H. pylori testing, or failure to respond to adequate oral iron after 8–10 weeks 4, 1

Additional Screening (All Patients)

• Check inflammatory markers (CRP, ESR) to rule out chronic inflammatory conditions that can cause functional iron deficiency 1, 6
• Assess for chronic kidney disease (serum creatinine, eGFR) if not already done 4
• Consider thyroid function testing if fatigue is prominent 4

Treatment Protocol

Immediate Oral Iron Supplementation

Start oral iron immediately—do not wait for completion of diagnostic workup. 1, 2, 3

• Ferrous sulfate 325 mg daily (65 mg elemental iron) OR ferrous bisglycinate 30–60 mg elemental iron daily 1, 2, 3
• Alternate-day dosing (60 mg elemental iron every other day) improves absorption and reduces gastrointestinal side effects compared to daily dosing 1, 2, 3
• Take on empty stomach for optimal absorption; if gastrointestinal symptoms occur (constipation, nausea, diarrhea), take with meals or switch to alternate-day dosing 1, 3

Expected Response and Monitoring

• Hemoglobin should rise by 1–2 g/dL within 4 weeks of starting therapy 1, 5, 3
• Repeat CBC and ferritin at 8–10 weeks to assess response 1, 3
• Target ferritin >100 ng/mL to fully restore iron stores and prevent recurrence 1

When to Consider Intravenous Iron

IV iron is indicated if: 4, 2, 3

• Oral iron intolerance (gastrointestinal side effects)
• Malabsorption (celiac disease, post-bariatric surgery, inflammatory bowel disease)
• Ongoing blood loss that cannot be controlled
• Failure to respond to adequate oral iron after 8–10 weeks (suggests malabsorption, non-compliance, or ongoing blood loss)
• Chronic inflammatory conditions (chronic kidney disease, heart failure, inflammatory bowel disease, cancer)

Ferric carboxymaltose is the preferred IV formulation, delivering up to 750 mg iron per infusion with hypersensitivity rates <1%. 7, 3

Common Pitfalls to Avoid

• Do not assume normal hemoglobin excludes clinically significant iron deficiency—ferritin 20 ng/mL with transferrin saturation 16% confirms depleted stores requiring treatment 1, 2
• Do not overlook celiac disease—it is present in 3–5% of iron deficiency cases and causes treatment failure if undiagnosed 4, 1, 3
• Do not continue daily oral iron indefinitely once ferritin normalizes—this is potentially harmful and unnecessary 1
• Do not skip gastrointestinal investigation in men or postmenopausal women—malignancy must be excluded 4, 5, 3

Long-Term Management

• For high-risk groups (menstruating females, vegetarians, athletes, regular blood donors), screen ferritin every 6–12 months 1
• Address the underlying cause of iron loss to prevent recurrence 2, 3
• Re-evaluate iron parameters 3–6 months after correction of the underlying cause 1