What is the best course of treatment for an adult patient with low iron saturation and no significant medical history?

Management of Low Iron Saturation in Adults

For an adult with low iron saturation and no significant medical history, initiate oral iron therapy with ferrous sulfate 325 mg daily (or on alternate days to improve tolerability) while simultaneously investigating for underlying causes, as gastrointestinal pathology—including malignancy—commonly presents with iron deficiency even in asymptomatic patients. 1, 2

Diagnostic Confirmation

Confirm true iron deficiency before proceeding:

• Transferrin saturation <20-30% supports iron deficiency diagnosis 1
• Measure serum ferritin—the most powerful single test for iron deficiency, with levels <30 ng/mL diagnostic in the absence of inflammation 1, 2
• If ferritin is 30-45 ng/mL, iron deficiency remains likely and warrants treatment consideration, particularly with low transferrin saturation 3
• Check C-reactive protein to exclude inflammation, as ferritin may be falsely elevated in inflammatory states despite true iron deficiency 4
• A therapeutic trial showing hemoglobin rise ≥10 g/L within 2-3 weeks confirms true iron deficiency 1, 4

Mandatory Investigation for Underlying Causes

Do not assume dietary deficiency alone—full gastrointestinal investigation is required even with poor dietary intake, as GI malignancies commonly present with iron deficiency: 1

• Perform bidirectional endoscopy (gastroscopy and colonoscopy) in all men and postmenopausal women with confirmed iron deficiency 1
• Upper endoscopy reveals a cause in 30-50% of patients and should include small bowel biopsies to detect celiac disease 1
• Complete colonoscopy even if upper endoscopy is positive, as dual pathology occurs in 10-15% of cases 1
• Screen for celiac disease with tissue transglutaminase antibody, as 3-5% of iron deficiency cases are due to celiac disease 1
• Perform urinalysis to exclude urinary blood loss 1

For premenopausal women:

• Detailed menstrual history is essential 1
• GI investigation may be deferred if heavy menstrual bleeding is clearly the cause and there are no alarm symptoms 3
• However, maintain low threshold for endoscopy if iron deficiency persists despite treatment 3

Key history elements to elicit:

• NSAID/aspirin use (stop if clinically appropriate) 3, 1
• Dietary iron intake patterns 3, 1
• Family history of bleeding disorders, celiac disease, or colorectal cancer 3, 1
• Previous GI surgery or bariatric procedures 3

Iron Replacement Therapy

Oral iron is first-line for most patients:

• Ferrous sulfate 325 mg daily (containing 65 mg elemental iron) 5, 2
• Alternate-day dosing may improve tolerability with similar efficacy 2
• Preparations with 28-50 mg elemental iron content minimize gastrointestinal side effects while maintaining effectiveness 4
• Expect hemoglobin rise ≥10 g/L within 2 weeks if true iron deficiency 1
• Recheck hemoglobin, ferritin, and transferrin saturation after 8-10 weeks 4

Dietary counseling should accompany supplementation:

• Integrate heme iron sources (meat, poultry, fish) regularly 4
• Avoid iron absorption inhibitors (tea, coffee, calcium supplements) near iron intake 4
• Consider vitamin C to enhance absorption 4

Indications for Intravenous Iron

Switch to intravenous iron for: 1, 2, 6

• Oral iron intolerance or significant gastrointestinal side effects
• Malabsorption conditions (celiac disease, inflammatory bowel disease, post-bariatric surgery)
• Chronic inflammatory conditions (chronic kidney disease, heart failure, inflammatory bowel disease, cancer)
• Ongoing blood loss exceeding intestinal absorption capacity
• Second and third trimesters of pregnancy
• Failure to respond to adequate oral iron therapy

Further Investigation if Initial Workup Negative

If bidirectional endoscopy is negative and iron deficiency persists or recurs despite adequate replacement: 1

• Capsule endoscopy is the preferred test for small bowel examination 1
• CT/MR enterography may be considered as complementary investigation for inflammatory or neoplastic small bowel disease 1

Critical Pitfalls to Avoid

• Never stop investigation after finding minor upper GI lesions (gastritis, esophagitis)—always complete lower GI evaluation 1
• Do not assume dietary deficiency explains iron deficiency without completing appropriate investigation 1
• In inflammatory states, ferritin may be falsely normal—use transferrin saturation <20% to diagnose iron deficiency 1
• Monitor hemoglobin after iron replacement—failure to respond or recurrence warrants further small bowel investigation 1
• Avoid long-term daily iron supplementation once ferritin normalizes, as this is potentially harmful 4

Long-Term Monitoring

For patients with recurrent iron deficiency: 4

• Intermittent oral supplementation preserves iron stores
• Repeat basic blood tests every 6-12 months to monitor iron stores
• Consider underlying conditions requiring ongoing surveillance (heavy menstrual bleeding, inflammatory bowel disease)