In a patient with borderline‑normal hemoglobin (~13–14 g/dL) on serial measurements, low ferritin (20.5 ng/mL) and gastrointestinal irritation (galling), what is the most likely diagnosis and what initial work‑up and treatment should be pursued?

Iron Deficiency Without Anemia Requiring Gastrointestinal Evaluation

This patient has iron deficiency without anemia and should undergo bidirectional endoscopy (upper endoscopy plus colonoscopy) to exclude gastrointestinal malignancy, along with non-invasive testing for Helicobacter pylori and celiac disease, followed by oral iron supplementation. 1

Diagnostic Interpretation

Hemoglobin Status

• The serial hemoglobin measurements (13.1–14.1 g/dL) remain above the WHO anemia threshold of 12 g/dL for non-pregnant women, confirming the absence of anemia. 1
• However, borderline-normal hemoglobin does not exclude clinically significant iron deficiency or underlying gastrointestinal pathology. 1, 2

Iron Deficiency Confirmation

• A ferritin of 20.5 ng/mL falls well below the 30 µg/L threshold that indicates depleted iron stores in the absence of inflammation. 1, 3
• This ferritin level (20.5 ng/mL) has high specificity for absolute iron deficiency and warrants full diagnostic evaluation regardless of hemoglobin level. 3, 4
• The presence of gastrointestinal symptoms ("galling"—presumably gastric irritation or dyspepsia) makes this a symptomatic patient with iron deficiency, mandating endoscopic evaluation. 1

Recommended Diagnostic Work-Up

Non-Invasive Testing First

• Perform non-invasive testing for H. pylori (stool antigen or urea breath test) and celiac disease (tissue transglutaminase IgA with total IgA) before proceeding to endoscopy. 1
• If either test is positive, treat the underlying condition and reassess iron status after therapy. 1

Bidirectional Endoscopy

• If non-invasive testing is negative, proceed with bidirectional endoscopy (upper endoscopy and colonoscopy) to evaluate for occult gastrointestinal bleeding sources, including malignancy. 1
• The 2020 Gastroenterology guideline provides a strong recommendation with moderate-quality evidence for bidirectional endoscopy in post-menopausal women with iron deficiency anemia. 1
• Although this patient does not meet strict anemia criteria, the combination of documented iron deficiency (ferritin 20.5 ng/mL) plus gastrointestinal symptoms mandates the same evaluation pathway. 1
• Gastrointestinal malignancy remains the most important diagnosis to exclude in adults with iron deficiency, even when hemoglobin is preserved. 2, 5

Endoscopic Biopsy Strategy

• Avoid routine biopsies for celiac disease and H. pylori unless serologies are positive or endoscopic abnormalities are visualized. 1
• Reserve celiac biopsies for patients with positive serologies requiring pathologic confirmation or those with continued high suspicion despite negative serologies. 1
• Reserve H. pylori biopsies for patients with endoscopic abnormalities in the setting of negative non-invasive testing. 1

Iron Supplementation

Initiation of Therapy

• Start oral elemental iron 100–200 mg daily immediately while the diagnostic work-up proceeds. 3
• A typical regimen is ferrous sulfate 325 mg (65 mg elemental iron) two to three times daily. 2, 6

Duration and Monitoring

• Continue iron supplementation for at least 3–6 months after hemoglobin normalization to fully replenish iron stores, targeting a ferritin > 50–100 µg/L. 1, 3
• Recheck complete blood count and ferritin at one month to confirm hemoglobin response (expected rise of 1–2 g/dL). 2
• If hemoglobin fails to rise appropriately, consider malabsorption, continued occult bleeding, or non-adherence. 2

Critical Pitfalls to Avoid

Do Not Delay Endoscopy Based on Hemoglobin Level

• Borderline-normal hemoglobin (13–14 g/dL) does not reduce the urgency of gastrointestinal evaluation when iron deficiency is documented. 1, 2
• Approximately 9% of patients older than 65 years with iron deficiency anemia have gastrointestinal cancer; this risk applies equally to patients with iron deficiency before overt anemia develops. 2
• Many US primary care physicians inappropriately defer bidirectional endoscopy in patients with new-onset iron deficiency, contributing to delayed cancer diagnosis. 5

Do Not Attribute Iron Deficiency to Gastrointestinal Irritation Alone

• While gastric irritation may contribute to poor iron absorption or minor mucosal blood loss, it does not explain ferritin depletion to 20.5 ng/mL without excluding structural lesions. 1, 2
• The presence of gastrointestinal symptoms makes this a symptomatic patient who requires tailored endoscopic evaluation according to symptom localization. 1

Do Not Stop Iron Prematurely

• Iron supplementation must continue for 3–6 months after hemoglobin normalization to restore tissue iron stores (ferritin > 50–100 µg/L). 1, 3
• Premature discontinuation leads to rapid recurrence of iron deficiency. 3

Do Not Misinterpret Ferritin in the 20–45 ng/mL Range

• A ferritin of 20.5 ng/mL is often misinterpreted as "borderline" or "low-normal," but it represents true iron depletion. 3, 4, 5
• The traditional cutoff of ferritin < 15 ng/mL has 99% specificity but very low sensitivity, missing the majority of iron deficiency cases. 3, 4
• The optimal diagnostic threshold is ferritin < 30–45 ng/mL, which balances sensitivity and specificity. 1, 3, 4

Additional Laboratory Studies

Complete Initial Panel

• Obtain a complete blood count with red-cell distribution width (RDW) and mean corpuscular volume (MCV), transferrin saturation (TSAT), and C-reactive protein (CRP) to assess for concurrent inflammation. 1, 3
• An elevated RDW is an early and sensitive marker of iron deficiency, even when MCV remains normal. 1, 3
• A TSAT < 20% confirms iron-restricted erythropoiesis. 1, 3

Assess for Inflammation

• Measure CRP to determine whether ferritin reflects true iron stores or an acute-phase response. 1, 3
• In the absence of elevated CRP, a ferritin of 20.5 ng/mL reliably indicates depleted iron stores. 1, 3