Patient with iron‑deficiency anemia, elevated erythrocyte sedimentation rate and C‑reactive protein, borderline diabetes (HbA1c 6.0 %), urinary candidiasis and a thyroid‑stimulating hormone level of 6.5 µIU/mL—what is the appropriate evaluation and management plan?

Management of Iron-Deficiency Anemia with Elevated Inflammatory Markers and Subclinical Hypothyroidism

Immediate Priority: Comprehensive Iron Status Assessment

This patient requires urgent evaluation for functional iron deficiency given the combination of anemia, elevated inflammatory markers (ESR/CRP), and borderline diabetes—all conditions that sequester iron and render ferritin unreliable as a sole diagnostic marker. 1

Complete the Iron Panel Immediately

• Obtain transferrin saturation (TSAT), serum iron, total iron-binding capacity (TIBC), and ferritin to distinguish absolute from functional iron deficiency 1
• TSAT <20% with ferritin 100-300 ng/mL defines functional iron deficiency in inflammatory states, where hepcidin traps iron in storage sites making it unavailable for erythropoiesis 1
• Elevated TIBC combined with low serum iron indicates the body is attempting to capture more iron but cannot access stored iron 1
• Do not rely on ferritin alone—in chronic inflammatory conditions, ferritin up to 100-300 ng/mL may still reflect true iron deficiency because ferritin is an acute-phase reactant 2, 1

Interpret Results Based on Inflammatory Status

CRP Status	Ferritin Threshold	TSAT Threshold	Diagnosis
Elevated	<100 ng/mL	<20%	Absolute iron deficiency [1]
Elevated	100-300 ng/mL	<20%	Functional iron deficiency [1]

Mandatory Evaluation for Blood Loss Sources

Gastrointestinal Investigation

• Upper and lower endoscopy are mandatory to exclude malignancy as a source of chronic blood loss in any patient with iron-deficiency anemia and elevated inflammatory markers 2
• Screen for celiac disease serologically (tissue transglutaminase antibody) or via small bowel biopsy at gastroscopy—celiac disease is found in 3-5% of iron-deficiency anemia cases 2
• Urinalysis or urine microscopy to exclude urinary blood loss 2

Additional Workup

• Renal function (serum creatinine, eGFR) to evaluate for chronic kidney disease, which influences iron metabolism and treatment choice 1
• Hemoglobin A1c is already borderline at 6.0%, indicating prediabetes—this chronic inflammatory state contributes to functional iron deficiency 1
• Treat the urinary candidiasis promptly, as infection elevates inflammatory markers and worsens iron sequestration 2

Iron Replacement Strategy

Route Selection Algorithm

If TSAT <20% with ferritin 100-300 ng/mL (functional iron deficiency):

• Intravenous iron is first-line because it bypasses hepcidin-mediated blockade of intestinal iron absorption that occurs in inflammatory states 2, 1
• Oral iron is ineffective when inflammation and elevated hepcidin trap iron—absorption declines dramatically when ferritin exceeds 200 ng/mL 1
• IV formulations include ferric carboxymaltose, iron sucrose, or low-molecular-weight iron dextran 2, 1

If TSAT <16-20% with ferritin <30-100 ng/mL (absolute iron deficiency without severe inflammation):

• Trial of oral iron 100-200 mg elemental iron daily in divided doses 1
• Alternate-day dosing improves absorption and reduces gastrointestinal adverse effects compared with daily dosing 1
• Switch to IV iron if no hemoglobin increase of 1-2 g/dL within 4-8 weeks, or if gastrointestinal intolerance occurs 1

Monitoring Iron Therapy

• Do not recheck iron parameters within 4 weeks of IV iron infusion—circulating iron interferes with assay accuracy and ferritin may be falsely elevated 1
• Optimal timing for reassessment is 4-8 weeks after the last IV iron dose 1
• Target TSAT ≥20% after iron repletion to ensure adequate iron availability for erythropoiesis 1
• Expect hemoglobin to rise by 1-2 g/dL within 4-8 weeks of adequate treatment 1

Thyroid Management

TSH 6.5 µIU/mL Interpretation

This TSH level represents mild subclinical hypothyroidism and warrants levothyroxine initiation, especially given the patient's borderline diabetes and anemia—both conditions worsened by hypothyroidism. 3

• TSH >5 µIU/mL with symptoms (fatigue, anemia) or metabolic complications (prediabetes) is an indication to treat 3
• Thyroid dysfunction should be part of routine assessment in patients with anemia and chronic inflammatory conditions 2

Levothyroxine Dosing

• Starting dose: 1.6 mcg/kg/day for new-onset hypothyroidism in adults 3
• In patients at risk for cardiac complications or elderly patients, start at 25-50 mcg daily and titrate upward 3
• Monitor TSH at 6-8 weeks after initiation or any dose change 3
• Target TSH within normal range (generally 0.5-4.5 µIU/mL) 3

Thyroid-Iron Interaction

• Hypothyroidism impairs erythropoiesis independently of iron status 2
• Correcting hypothyroidism may improve anemia response to iron therapy 2
• Do not delay iron replacement while awaiting thyroid normalization—treat both conditions simultaneously 2

Prediabetes Management

• HbA1c 6.0% represents prediabetes and contributes to chronic low-grade inflammation 1
• Lifestyle modification (diet, exercise) to prevent progression to diabetes 1
• Improved glycemic control may reduce inflammatory markers and improve iron utilization 1

Common Pitfalls to Avoid

• Do not assume normal ferritin excludes iron deficiency in the setting of elevated CRP/ESR—ferritin is an acute-phase reactant and may be falsely elevated 2, 1
• Do not prescribe oral iron for functional iron deficiency—it provides no benefit and causes unnecessary gastrointestinal adverse effects 1
• Do not measure iron parameters too early after IV iron (within 4 weeks)—results will be falsely elevated 1
• Do not overlook gastrointestinal malignancy—endoscopic evaluation is mandatory in iron-deficiency anemia with elevated inflammatory markers 2
• Do not treat anemia without addressing the underlying cause—identify and correct the source of blood loss 2

Follow-Up Timeline

1. Week 0: Complete iron panel (TSAT, ferritin, iron, TIBC), initiate levothyroxine, treat candidiasis, refer for GI endoscopy
2. Week 4-8: Reassess hemoglobin, iron parameters (if IV iron given), TSH
3. Week 12: Confirm hemoglobin normalization, adjust levothyroxine if needed, repeat HbA1c
4. Ongoing: Monitor TSH every 6-12 months once stable, repeat iron studies if anemia recurs 3