How should I evaluate and manage an adult with low ferritin indicating iron deficiency?

Evaluation and Management of Low Ferritin in Adults

Begin oral iron supplementation immediately with ferrous sulfate 65 mg elemental iron daily (or alternate-day dosing) while simultaneously investigating the underlying cause, because low ferritin confirms depleted iron stores that require treatment regardless of hemoglobin level. 1

Diagnostic Interpretation of Low Ferritin

Ferritin Thresholds for Iron Deficiency

• Ferritin <15 μg/L has 99% specificity for absolute iron deficiency, providing definitive confirmation without need for additional testing 1, 2
• Ferritin 15-30 μg/L indicates depleted body iron stores and warrants treatment 1
• Ferritin <45 μg/L provides optimal sensitivity-specificity balance (92% specificity) for clinical decision-making, according to the American Gastroenterological Association 1, 2
• In patients with chronic inflammation (inflammatory bowel disease, chronic kidney disease, heart failure, malignancy), the threshold shifts upward to <100 μg/L because ferritin is an acute-phase reactant that rises during inflammation and can mask true iron deficiency 1, 2

Essential Complementary Testing

You must calculate transferrin saturation (TSAT) to assess iron availability for erythropoiesis, because ferritin alone provides an incomplete picture 1:

• TSAT = (serum iron × 100) ÷ total iron-binding capacity (TIBC) 1
• TSAT <16-20% confirms iron deficiency (absolute or functional) regardless of ferritin level 1, 2
• When ferritin is 30-100 μg/L with elevated CRP/ESR, check inflammatory markers (CRP, ESR) to determine if ferritin is falsely elevated by inflammation 1

Mandatory Investigation for Underlying Causes

All Adults: Universal Screening

Screen every patient with iron deficiency for celiac disease and Helicobacter pylori infection, because these are common, treatable causes that lead to treatment failure if missed 1:

• Tissue transglutaminase IgA antibodies for celiac disease (present in 3-5% of iron deficiency cases) 1
• Non-invasive H. pylori testing (stool antigen or urea breath test) 1

Men and Postmenopausal Women: Urgent GI Evaluation

Bidirectional endoscopy (upper endoscopy + colonoscopy) is mandatory because iron deficiency may be the sole manifestation of gastrointestinal malignancy 1:

• Recurrent blood loss accounts for 94% of iron deficiency cases in this population 3
• Do not delay endoscopy while awaiting response to iron therapy 1

Premenopausal Women: Conditional GI Evaluation

GI investigation is conditional rather than mandatory in premenopausal women, because menstrual blood loss is the most common cause 1, 2:

Reserve bidirectional endoscopy for women with any of the following 1:

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

For young women <50 years with heavy menstrual bleeding and no GI symptoms, empiric oral iron supplementation without immediate endoscopy is appropriate after celiac/H. pylori screening 1

Oral Iron Supplementation Protocol

First-Line Treatment

Initiate ferrous sulfate 65 mg elemental iron daily or 60-65 mg every other day 1, 3:

• Alternate-day dosing improves absorption by 30-50% and reduces GI side effects compared to daily dosing 1, 3
• Take on empty stomach for optimal absorption, or with meals if GI symptoms occur 1
• Expected side effects include constipation, nausea, or diarrhea 1

Expected Response and Monitoring

Hemoglobin should rise by ≥10 g/L within 2 weeks of starting therapy 1, 3:

• Repeat CBC and ferritin at 8-10 weeks to assess response 1
• Target ferritin >100 ng/mL to fully restore iron stores and prevent recurrence 1
• Continue oral iron for 3 months after hemoglobin normalizes to replenish ferritin, because absorbed iron is preferentially used for red cell production before refilling storage compartments 1

Indications for Intravenous Iron

Switch to intravenous ferric carboxymaltose (15 mg/kg, maximum 1000 mg per dose) when any of the following are present 1:

• Oral iron intolerance (marked nausea, constipation, diarrhea)
• Confirmed malabsorption (celiac disease, inflammatory bowel disease, post-bariatric surgery)
• Ongoing blood loss exceeding oral replacement capacity
• Chronic inflammatory conditions (chronic kidney disease, heart failure, cancer)
• Pregnancy in second/third trimester
• Lack of hemoglobin response after 8-10 weeks of adequate oral iron

IV iron produces reticulocytosis within 3-5 days and yields a mean hemoglobin increase of ≈8 g/L over 8 days, demonstrating superior efficacy in these populations 1

Long-Term Monitoring for High-Risk Groups

For patients at risk of recurrent iron depletion (menstruating females, vegetarians, athletes, regular blood donors), screen ferritin every 6-12 months to detect early depletion before anemia develops 1:

• Menstruating females require twice-yearly screening 1
• Males and non-menstruating females require annual screening 1

Critical Pitfalls to Avoid

Do not assume normal ferritin excludes iron deficiency in patients with inflammation—ferritin is an acute-phase reactant that rises during infection, inflammation, or tissue damage, potentially masking depleted iron stores 1, 2

Do not overlook celiac disease screening—its 3-5% prevalence in iron deficiency cases can lead to treatment failure if not identified 1

Do not discontinue iron therapy once hemoglobin normalizes—an additional 3 months of supplementation is required for ferritin to reach >100 ng/mL 1

Do not continue daily iron supplementation once ferritin normalizes—this is potentially harmful 1

Do not delay endoscopic evaluation in high-risk patients (men, postmenopausal women, age ≥50, alarm symptoms, treatment failure), as GI malignancy can present solely with iron deficiency 1