What is the appropriate diagnosis and treatment for an adult patient with a ferritin level indicating iron deficiency and no significant medical history?

Interpreting Iron Studies and Ferritin in Adults

For an adult patient with ferritin indicating iron deficiency and no significant medical history, diagnose iron deficiency anemia if hemoglobin is <13 g/dL in men or <12 g/dL in women AND ferritin is <45 ng/mL, then initiate oral ferrous sulfate 325 mg daily (or alternate days) while simultaneously investigating for gastrointestinal blood loss with bidirectional endoscopy in men and postmenopausal women. 1, 2

Diagnostic Thresholds for Iron Deficiency

Ferritin interpretation depends critically on inflammatory status:

• Without inflammation: Ferritin <30 ng/mL is diagnostic of iron deficiency 1, 2, 3
• With inflammation or chronic disease: Use ferritin <45 ng/mL as the diagnostic threshold, as ferritin is an acute-phase reactant that can be falsely elevated 1
• Ferritin >100 ng/mL: Iron deficiency is almost certainly not present, even with inflammation 1

Key caveat: The traditional laboratory reference range lower limit of 12-15 ng/mL has very poor sensitivity for detecting iron deficiency. Studies demonstrate that 30-50% of healthy women have no bone marrow iron stores despite "normal" ferritin by conventional ranges 4. A ferritin cutoff of 30-45 ng/mL provides significantly higher sensitivity with minimal loss of specificity 1, 5.

Additional Iron Studies to Confirm Diagnosis

When ferritin is borderline (30-100 ng/mL) or inflammation is present:

• Transferrin saturation (TSAT) <20% confirms iron deficiency 1, 2, 3
• Elevated TIBC indicates the body is compensating for low iron stores by producing more transferrin 2
• Transferrin saturation = (serum iron/TIBC) × 100 3

In inflammatory conditions (IBD, CKD, heart failure, cancer): Ferritin can be falsely elevated, so TSAT <20% becomes critical for confirming true iron deficiency even when ferritin is 30-100 ng/mL 1, 2

Identifying the Underlying Cause

The investigation algorithm differs by patient demographics:

For Men and Postmenopausal Women:

• Bidirectional endoscopy is strongly recommended as gastrointestinal blood loss accounts for 94% of cases 1, 2, 6
• Before endoscopy: Perform non-invasive testing for H. pylori and celiac disease serologies 1, 2
• Small bowel biopsies should be obtained during upper endoscopy, as 2-3% of patients have celiac disease 1

For Premenopausal Women:

• Conditional recommendation for endoscopy unless heavy menstrual bleeding clearly explains the deficiency 1, 2
• Younger premenopausal women with obvious menstrual losses may reasonably choose empiric iron supplementation with hemoglobin monitoring at one month 1, 7
• However, if hemoglobin does not increase by 1-2 g/dL within one month, proceed to endoscopic evaluation 7

Common pitfall: Do not assume dietary insufficiency or menstrual bleeding is the sole cause without excluding gastrointestinal pathology, especially in patients over age 50 where 9% have gastrointestinal cancer 7.

Treatment Approach

First-Line: Oral Iron

• Ferrous sulfate 325 mg daily or on alternate days (provides 65 mg elemental iron per dose) 2, 8, 3
• Alternate-day dosing improves absorption and reduces adverse effects, which cause decreased adherence in approximately 50% of patients 6, 3
• Expected response: Hemoglobin should increase by 1-2 g/dL within one month 2, 6, 7

Indications for Intravenous Iron:

IV iron is indicated as first-line or alternative therapy in: 2, 3

• Intolerance to oral iron
• Malabsorption conditions (celiac disease, post-bariatric surgery, atrophic gastritis)
• Ongoing significant blood loss
• Chronic inflammatory conditions (IBD, CKD, heart failure, cancer)
• Pregnancy (second and third trimesters)
• Need for rapid iron repletion
• Heart failure patients (to increase exercise capacity) 6, 3

For inflammatory bowel disease specifically: IV iron should be considered first-line in clinically active disease, previous oral iron intolerance, hemoglobin <100 g/L, or when erythropoiesis-stimulating agents are needed 1

Monitoring Treatment Response

Evaluate response at 2-4 weeks: 6, 3

• Check hemoglobin for expected 1-2 g/dL increase
• If no response, consider malabsorption, continued bleeding, or unknown lesion 7

At 8-10 weeks: 2

• Hemoglobin should normalize
• Ferritin should rise above 30 ng/mL (ideally >100 ng/mL for complete iron store restoration) 1

If inadequate response to oral iron: Switch to intravenous iron rather than continuing ineffective oral therapy 6, 3

Long-term monitoring: Once iron stores are restored, continue hemoglobin monitoring every 6-12 months, particularly in patients with ongoing risk factors 1, 2

Special Considerations for Interpretation

Ferritin as an acute-phase reactant: 1

• Elevated in chronic kidney disease, inflammatory states, malignancy, and hepatic disease
• Always interpret ferritin in context of C-reactive protein (CRP) or clinical inflammatory markers
• A cancer patient with ferritin 60 ng/mL may actually have absolute iron deficiency due to inflammation falsely elevating ferritin 1

Non-anemic iron deficiency (ferritin low but hemoglobin normal): 1

• GI investigation generally not warranted in premenopausal women (likely menstrual losses)
• Low threshold for investigation in men, postmenopausal women, those with GI symptoms, or family history of GI pathology 1