What is the next step in management for a 24-year-old female with normal Complete Blood Count (CBC) and thyroid studies, but elevated Total Iron-Binding Capacity (TIBC), low iron, and low ferritin levels, suggestive of iron deficiency anemia?

Management of Iron Deficiency Without Anemia in a 24-Year-Old Female

Direct Recommendation

Start oral iron supplementation immediately with ferrous sulfate 65 mg elemental iron daily (or alternate-day dosing) and screen for celiac disease with tissue transglutaminase antibodies; gastrointestinal investigation is not mandatory at this time unless red flags develop. 1, 2

Understanding the Laboratory Pattern

This patient has iron deficiency without anemia—a condition where iron stores are depleted but hemoglobin remains normal. 1

Key Laboratory Findings:

• Ferritin 37 μg/L: This is above the absolute deficiency threshold of <15 μg/L but below the optimal cutoff of 45 μg/L (specificity 0.92 for iron deficiency). 1 Values <30 μg/L generally indicate low body iron stores. 1, 2
• TIBC 430 mg/dL (elevated): Elevated TIBC reflects the body's attempt to capture more circulating iron when stores are low. 1
• Iron 92 μg/dL: While this appears "normal," calculate the transferrin saturation (TSAT): (92 ÷ 430) × 100 = 21%. 1 This is just above the traditional deficiency threshold of <20%, but in the context of low ferritin, confirms early iron deficiency. 1

This pattern represents Stage 1 iron deficiency—depleted iron stores with normal hemoglobin but insufficient iron availability for optimal erythropoiesis. 2

Immediate Management Steps

1. Initiate Iron Supplementation Without Delay

Do not wait for further investigation results before starting treatment. 2

• Dose: Ferrous sulfate 324 mg tablet (65 mg elemental iron) daily 3 OR 60 mg elemental iron every other day. 2
• Alternate-day dosing may improve absorption and reduce gastrointestinal side effects compared to daily dosing. 2
• Timing: Take on empty stomach for optimal absorption, or with meals if gastrointestinal symptoms (constipation, nausea, diarrhea) occur. 2
• Target: Ferritin >100 ng/mL to restore iron stores and prevent recurrence. 2

2. Screen for Celiac Disease

Celiac disease is present in 3-5% of iron deficiency cases and is easily missed without serologic screening. 1, 2

• Order tissue transglutaminase antibodies (tTG-IgA) with total IgA level. 1, 2
• This is a high-yield test that can identify a treatable cause of ongoing iron malabsorption. 1

3. Assess Menstrual Blood Loss

Menstrual blood loss is the most common cause of iron deficiency in premenopausal women. 2, 4

• Document menstrual history: frequency, duration, heaviness (number of pads/tampons per day, clots, flooding). 2
• If heavy menstrual bleeding is present, gynecologic evaluation may be warranted. 2

When to Pursue Gastrointestinal Investigation

GI investigation is NOT mandatory for this patient at this time. 1, 2 The British Society of Gastroenterology and American Gastroenterological Association recommend conditional rather than mandatory GI evaluation for premenopausal women with iron deficiency. 1, 2

Reserve Bidirectional Endoscopy For:

• Age ≥50 years (higher risk of GI malignancy) 2
• GI symptoms: abdominal pain, change in bowel habits, blood in stool 2
• Positive celiac or H. pylori testing requiring confirmation 2
• Failure to respond to adequate oral iron therapy after 8-10 weeks 1, 2
• Strong family history of colorectal cancer 2

The yield of extensive GI investigation in young, asymptomatic premenopausal women with heavy menses is extremely low (0-6.5%). 2

Follow-Up and Monitoring

At 8-10 Weeks:

• Repeat CBC and ferritin to assess response to treatment. 2
• Expected response: Hemoglobin rise ≥10 g/L within 2 weeks is highly suggestive of absolute iron deficiency. 1
• If no improvement, consider malabsorption (celiac disease, H. pylori, inflammatory bowel disease), non-compliance, ongoing blood loss, or need for IV iron. 2

Long-Term Management:

• For menstruating females: Screen ferritin every 6-12 months, as this is a high-risk population for recurrent iron deficiency. 2
• Do not continue daily iron supplementation once ferritin normalizes (>100 ng/mL), as this is potentially harmful. 2

Critical Pitfalls to Avoid

Pitfall #1: Assuming Normal Hemoglobin Excludes Iron Deficiency

Iron deficiency without anemia can still cause significant symptoms—fatigue, reduced exercise tolerance, hair loss, restless legs—even before anemia develops. 2, 4 Ferritin <45 μg/L warrants treatment regardless of hemoglobin level. 1, 2

Pitfall #2: Over-Investigating Young Premenopausal Women

Extensive GI investigation in asymptomatic young women with heavy menses has extremely low yield. 2 Start with iron supplementation and celiac screening first. 1, 2

Pitfall #3: Ignoring Celiac Disease

Celiac disease is present in 3-5% of iron deficiency cases and will cause treatment failure if not identified. 1, 2 Always screen serologically. 1

Pitfall #4: Misinterpreting "Normal" Serum Iron

Serum iron of 92 μg/L appears normal but must be interpreted in context. 1 The calculated TSAT of 21% combined with ferritin 37 μg/L confirms iron deficiency. 1, 2 Serum iron alone is unreliable due to diurnal variation. 2

Summary Algorithm

1. Start oral iron supplementation immediately (65 mg elemental iron daily or alternate-day). 2, 3
2. Screen for celiac disease with tTG-IgA. 1, 2
3. Assess menstrual blood loss history. 2
4. Recheck CBC and ferritin at 8-10 weeks. 2
5. Pursue GI investigation only if: age ≥50, GI symptoms, positive celiac/H. pylori testing, or failure to respond to iron therapy. 1, 2
6. Monitor ferritin every 6-12 months long-term in menstruating women. 2