Can iron deficiency anemia be a sign of cancer?

Iron Studies Interpretation and Cancer Risk Assessment

Your iron studies show iron deficiency (ferritin 12 ng/mL) despite elevated iron saturation (57%), which is an unusual pattern that warrants investigation for underlying pathology, including potential gastrointestinal malignancy, particularly if you are over 50 years old or male.

Understanding Your Laboratory Results

Your iron panel reveals a contradictory pattern that requires careful interpretation:

• Ferritin 12 ng/mL: This confirms absolute iron deficiency, as levels <15-30 μg/L indicate depleted iron stores 1
• Iron saturation 57%: This is paradoxically elevated (normal is typically 20-45%)
• Serum iron 216 and TIBC 376: These values suggest adequate circulating iron despite depleted stores

This discordant pattern (low ferritin with high saturation) is atypical and may indicate:

• Recent iron supplementation or transfusion
• Laboratory error requiring repeat testing
• Hemolysis or other red cell disorders
• Early stages of investigation before full iron depletion manifests in saturation

Cancer Risk in Iron Deficiency Anemia

Iron deficiency anemia (IDA) can indeed be a presenting sign of cancer, particularly gastrointestinal malignancies. 1

Key Statistics and Risk Factors

• Approximately one-third of adults over age 50 with IDA have an underlying bleeding abnormality in the stomach or lower bowel 1
• Of those with bleeding abnormalities, about one-third prove to have cancer 1
• Gastrointestinal blood loss is the most common cause of IDA in adult men and postmenopausal women 1
• Asymptomatic colonic and gastric carcinoma may present with IDA as the only manifestation 1

Who Requires Investigation

Investigation for gastrointestinal cancer is strongly recommended if you are: 1

• Male with any degree of anemia and iron deficiency
• Postmenopausal woman with any degree of anemia and iron deficiency
• Have hemoglobin <110 g/L (11 g/dL) in men or <100 g/L (10 g/dL) in non-menstruating women (these warrant urgent fast-track referral) 1

The case for investigation is stronger with more severe anemia, as lower hemoglobin levels correlate with higher likelihood of serious underlying GI pathology 1

Recommended Diagnostic Approach

Immediate Steps

1. Confirm iron deficiency with repeat testing to verify the unusual pattern of low ferritin with high saturation 1

2. Check hemoglobin level if not already done, as this determines urgency of investigation 1

3. Obtain complete blood count including mean cell volume (MCV) and mean cell hemoglobin (MCH) to assess for microcytosis and hypochromia 1

Gastrointestinal Investigation

Both upper and lower GI tract evaluation is recommended because: 1

• Dual pathology (bleeding sources in both upper and lower GI tract) occurs in 1-10% or more of patients 1
• This risk increases with age 1

Standard investigation includes: 1

• Upper endoscopy (OGD) with duodenal biopsies to evaluate for:

  • Gastric or esophageal cancer
  • Peptic ulcer disease
  • Celiac disease (even if celiac serology is negative, biopsies should be taken if other features suggest it) 1

• Colonoscopy or CT colonography to evaluate for:

  • Colorectal cancer
  • Polyps
  • Inflammatory bowel disease
  • Angiodysplasia

Additional Testing

• Celiac serology (tissue transglutaminase antibody) should be performed, as celiac disease has approximately 5% pretest probability in IDA patients 1
• Hemoglobin electrophoresis if microcytosis is present with normal iron studies, particularly in appropriate ethnic backgrounds, to exclude thalassemia 1

Important Caveats

Common Pitfalls to Avoid

• Do not assume menstruation explains IDA in premenopausal women without investigation if anemia is significant or other risk factors are present 1
• Do not delay investigation while treating with iron supplementation - the underlying cause must be identified 1
• Do not rely solely on ferritin if inflammation is suspected, as ferritin is an acute phase protein and can be falsely normal in inflammatory conditions; transferrin saturation <20% with ferritin up to 45-100 μg/L may still indicate iron deficiency in inflammatory states 1
• NSAID use is a common cause of GI bleeding and IDA - document medication history including over-the-counter drugs 1

Response to Iron Therapy

A good response to iron therapy (hemoglobin rise ≥10 g/L within 2 weeks) is highly suggestive of absolute iron deficiency, even if iron study results are equivocal 1. However, response to iron does not exclude underlying malignancy and investigation should still proceed 1.

Clinical Significance Beyond Cancer

While cancer is a critical concern, other serious conditions that present with IDA include: 1, 2

• Celiac disease (most common malabsorption cause in UK)
• Peptic ulcer disease
• Inflammatory bowel disease
• Angiodysplasia
• Chronic NSAID-induced gastropathy

The discovery of underlying cancer occurs in approximately 6 cases per typical case series of IDA patients 2, making thorough investigation essential for optimal outcomes.

Bottom Line

Your ferritin of 12 ng/mL confirms iron deficiency that requires both treatment and investigation for the underlying cause. Given that gastrointestinal malignancy presents with IDA in a substantial proportion of cases, particularly in men and postmenopausal women, endoscopic evaluation of both upper and lower GI tracts is strongly recommended unless you are a premenopausal woman with clear menstrual blood loss explaining the deficiency 1.