What is the likely diagnosis and treatment for an elderly patient with elevated Total Iron Binding Capacity (TIBC) and Unsaturated Iron Binding Capacity (UIBC), normal other lab results, and suspected iron deficiency or abnormal iron metabolism?

Iron Overload, Not Iron Deficiency

This elderly patient has iron overload, not iron deficiency, and requires investigation for hemochromatosis and other causes of elevated iron stores.

Understanding the Laboratory Values

The key to interpreting these results is calculating the transferrin saturation (TSAT):

• Serum Iron = TIBC - UIBC = 217 - 101 = 116 μg/dL
• TSAT = (Serum Iron / TIBC) × 100 = (116 / 217) × 100 = 53.5%

This TSAT of >45% indicates iron overload, not iron deficiency 1.

Why This Is Not Iron Deficiency

• Iron deficiency is characterized by:

  • Low serum iron
  • High TIBC (typically >350 μg/dL) 2
  • Low TSAT (<16%) 1
  • High UIBC

• This patient has:

  • Normal/low TIBC (217 μg/dL, which is below normal range of 250-400 μg/dL)
  • Elevated TSAT (53.5%)
  • This pattern indicates iron overload 1

Diagnostic Approach

Immediate Next Steps

1. Measure serum ferritin to assess total body iron stores 1

   • If ferritin >200 μg/L (female) or >300 μg/L (male) with TSAT >45%, proceed with hemochromatosis workup 1

2. Complete blood count to assess for:

   • Anemia or polycythemia
   • Red cell indices (MCV, MCH) 1

3. Liver function tests given the association of iron overload with hepatic disease 1

Genetic Testing for Hemochromatosis

For patients of European origin with TSAT >45% and elevated ferritin:

• HFE gene testing for C282Y and H63D mutations is first-line 1
• C282Y homozygosity is the most common cause of hereditary hemochromatosis 1

For patients of non-European origin:

• Consider direct sequencing of HFE and non-HFE genes (HJV, TFR2, CP, SLC40A1) without initial HFE genotyping, as C282Y prevalence is very low 1

Additional Evaluation

Screen for secondary causes of iron overload 1:

• Chronic liver disease (hepatitis B/C, alcoholic liver disease, non-alcoholic fatty liver disease)
• Dysmetabolic iron overload syndrome (metabolic syndrome)
• Repeated blood transfusions
• Excessive oral iron supplementation
• Hemolytic anemias with ineffective erythropoiesis

Assess for end-organ damage if significant iron overload confirmed 1:

• Liver: Hepatic MRI for iron quantification, consider liver biopsy if cirrhosis suspected
• Heart: ECG and echocardiography if ferritin markedly elevated
• Pancreas: Fasting glucose and HbA1c (diabetes screening)
• Joints: Assess for arthropathy, particularly metacarpophalangeal joints 1

Common Pitfalls to Avoid

1. Do not assume iron deficiency based on "low" TIBC alone - A low TIBC with normal/elevated serum iron indicates iron overload, not deficiency 1, 2

2. Do not start iron supplementation - This would be harmful and exacerbate iron overload 1

3. Do not dismiss findings in elderly patients - While hemochromatosis typically presents earlier, secondary iron overload and late presentations occur 1

4. Calculate TSAT before making diagnostic decisions - TSAT is more informative than individual iron parameters alone 1

Treatment Considerations (Once Diagnosis Confirmed)

If hereditary hemochromatosis confirmed:

• Therapeutic phlebotomy is first-line treatment 1
• Target ferritin <50 μg/L during induction, then maintain 50-100 μg/L 1
• Monitor for anemia development during phlebotomy, particularly in elderly patients 1

If secondary iron overload:

• Address underlying cause
• Consider phlebotomy or iron chelation depending on etiology and severity 1