What diagnosis and management are indicated for a patient with normal transferrin (~260 mg/dL), low serum iron (~25 µg/dL), and low transferrin saturation (~8 %)?

Absolute Iron Deficiency Requiring Immediate Treatment and Investigation

This patient has absolute iron deficiency confirmed by a transferrin saturation of 8% (well below the 16–20% diagnostic threshold) and low serum iron of 25 µg/dL, despite normal transferrin levels. 1

Understanding the Laboratory Pattern

Your patient's iron studies reveal:

• Transferrin saturation of 8% is severely below the diagnostic cutoff of <16% for absolute iron deficiency in adults without inflammation, confirming that iron delivery to the bone marrow for hemoglobin synthesis is critically impaired. 1
• Low serum iron (25 µg/dL) reflects insufficient circulating iron available for red blood cell production. 1
• Normal transferrin (~260 mg/dL) indicates the body has not yet mounted a compensatory increase in iron-binding proteins, suggesting either very early iron deficiency or co-existing inflammation that suppresses transferrin synthesis. 1

The combination of low iron, low TSAT, and normal (rather than elevated) transferrin is atypical for pure iron deficiency and warrants immediate measurement of inflammatory markers (CRP, ESR) to exclude anemia of chronic disease or functional iron deficiency. 1

Immediate Diagnostic Work-Up

1. Complete Iron Panel and Inflammatory Assessment

• Measure serum ferritin immediately to distinguish absolute iron deficiency (ferritin <30 ng/mL without inflammation, or <100 ng/mL with inflammation) from functional iron deficiency (ferritin 100–300 ng/mL with TSAT <20%). 1
• Check CRP and ESR to identify chronic inflammation that may suppress the expected TIBC rise and alter ferritin interpretation. 1
• Obtain complete blood count (hemoglobin, MCV, MCH, reticulocyte count) to assess anemia severity and red-cell indices. 1
• Measure renal function (creatinine, eGFR) because chronic kidney disease alters iron metabolism and influences treatment choice. 1

2. Investigate Sources of Iron Loss

In adult men and postmenopausal women:

• Bidirectional endoscopy (upper GI gastroscopy + colonoscopy) is mandatory to exclude gastrointestinal malignancy, which may present solely with iron deficiency. 1
• Screen for celiac disease with tissue transglutaminase IgA antibodies; celiac disease accounts for 3–5% of iron-deficiency cases and causes treatment failure when missed. 1
• Test for Helicobacter pylori (stool antigen or urea-breath test) because the organism impairs iron absorption. 1

In premenopausal women:

• Assess menstrual blood loss patterns to identify gynecologic sources of iron depletion. 1
• Screen for celiac disease and H. pylori as above. 1
• Reserve bidirectional endoscopy for women ≥50 years, those with gastrointestinal symptoms (abdominal pain, altered bowel habits, visible blood), positive celiac or H. pylori tests, lack of response to oral iron after 8–10 weeks, or strong family history of colorectal cancer. 1

Treatment Algorithm

Step 1: Initiate Oral Iron Immediately

• Start oral ferrous sulfate 65 mg elemental iron daily (or 60–65 mg every other day); alternate-day dosing improves absorption by 30–50% and reduces gastrointestinal side effects (constipation, nausea, diarrhea). 1
• Do not delay iron therapy while awaiting diagnostic work-up results. 1
• Expected response: Hemoglobin should rise by ≥10 g/L within 2 weeks; absence of this rise suggests malabsorption, non-compliance, or ongoing blood loss. 1

Step 2: Determine Iron Deficiency Type Based on Ferritin and Inflammatory Markers

CRP/ESR Status	Ferritin Level	TSAT	Diagnosis	Next Step
Normal	<30 ng/mL	<16%	Absolute iron deficiency	Continue oral iron; investigate source of loss [1]
Elevated	<100 ng/mL	<20%	Absolute iron deficiency with inflammation	Consider IV iron if chronic disease present [1]
Elevated	100–300 ng/mL	<20%	Functional iron deficiency	Switch to IV iron [1]
Elevated	>300 ng/mL	<20%	Anemia of chronic disease	Treat underlying inflammatory condition; consider IV iron [1]

Step 3: Switch to Intravenous Iron When Indicated

Indications for IV ferric carboxymaltose (15 mg/kg, maximum 1000 mg per dose): 1, 2

• 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 with eGFR <30 mL/min/1.73m², heart failure NYHA class II–III, active IBD, cancer)
• Lack of hemoglobin response after 8–10 weeks of adequate oral iron

IV iron efficacy: Ferric carboxymaltose produces reticulocytosis within 3–5 days and yields a mean hemoglobin increase of ≈8 g/L over 8 days, demonstrating superior efficacy compared to oral iron in the indicated populations. 1

Monitoring and Follow-Up

• Re-check CBC and ferritin at 8–10 weeks after initiating oral iron to assess therapeutic response. 1
• Do not measure iron parameters within 4 weeks of IV iron infusion because circulating iron interferes with assay accuracy and ferritin may be falsely elevated. 1
• Continue oral iron for 3 months after hemoglobin normalizes to achieve target ferritin >100 ng/mL and fully restore iron reserves. 1
• For high-risk groups (menstruating females, vegetarians, athletes), schedule ferritin screening every 6–12 months to detect early depletion before anemia develops. 1

Critical Pitfalls to Avoid

• Normal transferrin does not exclude iron deficiency; TSAT <16–20% is the definitive marker of iron-deficient erythropoiesis regardless of transferrin level. 1, 3
• Do not assume dietary iron alone will correct deficiency; oral supplementation is required for clinically acceptable repletion. 1
• Do not overlook celiac disease screening (3–5% prevalence in iron deficiency); missing this diagnosis leads to treatment failure. 1
• Do not delay endoscopic evaluation in high-risk patients (age ≥50, alarm symptoms, treatment failure), as gastrointestinal malignancy can present solely with iron deficiency. 1
• In patients with chronic inflammation, oral iron is ineffective because hepcidin blocks intestinal absorption; IV iron is required. 1