Should an adult with ferritin 7 ng/mL and hemoglobin 130 g/L be treated for iron deficiency?

Should Iron Deficiency with Ferritin 7 ng/mL Be Treated?

Yes, a ferritin of 7 ng/mL should be treated with iron supplementation, even though the hemoglobin of 130 g/L is not anemic, because this represents severe iron deficiency that can cause symptoms and will inevitably progress to anemia if left untreated.

Understanding the Clinical Situation

Your patient has non-anemic iron deficiency (NAID), defined as depleted iron stores (ferritin <15 μg/L) with hemoglobin still in the normal range 1. A ferritin of 7 ng/mL indicates virtually absent iron stores and is highly specific for absolute iron deficiency (specificity 0.99) 1, 2.

Why Treatment Is Necessary

Iron Deficiency Causes Symptoms Even Without Anemia

• Iron deficiency without anemia commonly causes fatigue, exercise intolerance, difficulty concentrating, irritability, depression, restless legs syndrome (32-40% of cases), and pica (40-50% of cases) 3
• In athletes, iron deficiency even without anemia negatively impacts aerobic performance because iron is essential for hemoglobin, myoglobin, and oxidative ATP production 1
• These symptoms can significantly impair quality of life and warrant treatment regardless of hemoglobin level

Progressive Nature of Iron Deficiency

• Iron deficiency progresses through stages: first depleting iron stores (your patient's current state), then causing iron-deficient erythropoiesis, and finally resulting in iron deficiency anemia 3
• Treating at the NAID stage prevents progression to anemia and maintains optimal tissue iron levels 1

Investigation Before Treatment

The threshold for investigating the cause should be determined by patient demographics:

High Priority for Investigation

• Men of any age with ferritin 7 ng/mL require gastrointestinal investigation to exclude malignancy, as menstrual loss is not a factor 1
• Postmenopausal women similarly require investigation for occult GI bleeding or malignancy 1
• Anyone with GI symptoms (abdominal pain, change in bowel habits, weight loss) or family history of GI pathology 1

Lower Priority for Investigation

• Premenopausal women without GI symptoms generally do not require endoscopic investigation, as menstrual blood loss and/or recent pregnancy are the likely causes 1
• However, even in this group, consider celiac disease screening (tissue transglutaminase antibody) as it is found in 3-5% of iron deficiency cases 1

Mandatory Initial Workup

• Urinalysis or urine microscopy to exclude renal tract blood loss 1, 2
• Celiac disease screening 1, 2
• Consider checking for other causes: dietary history (vegetarian/vegan diet has lower iron bioavailability), NSAID use, inflammatory bowel disease 3

Treatment Approach

First-Line: Oral Iron Therapy

Oral iron is the appropriate initial treatment for most patients with NAID:

• Ferrous sulfate 325 mg daily OR alternate-day dosing (which may improve absorption by avoiding hepcidin upregulation) 3, 1
• Co-ingest with vitamin C to enhance absorption of non-heme iron 1
• Avoid tea and coffee around meal times as they impair iron absorption 1
• Common side effects include constipation, nausea, and dyspepsia 1

When to Use Intravenous Iron

Consider IV iron if:

• Oral iron intolerance or gastrointestinal side effects 3
• Malabsorption conditions (celiac disease, post-bariatric surgery, inflammatory bowel disease) 3
• Chronic inflammatory conditions where hepcidin is upregulated (chronic kidney disease, heart failure, inflammatory bowel disease, cancer) 3, 1
• Ongoing blood loss 3
• Pregnancy (second and third trimesters) 3

Monitoring Response

• Recheck hemoglobin in 2 weeks: A rise of ≥10 g/L confirms the diagnosis of iron deficiency even if initial iron studies were equivocal 1, 2
• Recheck ferritin after completing treatment course: Target ferritin >30 μg/L at minimum, though some evidence suggests targeting 50-100 ng/mL for optimal tissue iron stores 4, 5, 6
• If no response to oral iron after 4 weeks, consider trial of IV iron as absorption may be impaired 1

Common Pitfalls to Avoid

• Don't dismiss iron deficiency just because hemoglobin is normal – symptoms and progression to anemia are real concerns 1, 3
• Don't assume ferritin >15 μg/L excludes iron deficiency – in inflammatory states, ferritin up to 45-50 μg/L may still represent iron deficiency 1, 4, 5
• Don't forget to investigate the underlying cause, especially in men and postmenopausal women where GI malignancy risk is significant 1
• Don't use parenteral iron as first-line unless specific indications exist (malabsorption, intolerance, chronic inflammation) 1, 3