In a 72‑year‑old man whose ferritin has fallen from 119.7 ng/mL to 20.5 ng/mL despite 65 mg elemental iron daily and who now has a positive fecal immunochemical test (FIT) for occult blood, what is the most likely diagnosis and what is the appropriate next diagnostic step?

Likely Diagnosis and Next Diagnostic Step in a 72-Year-Old Man with Falling Ferritin and Positive FIT

This patient requires urgent bidirectional endoscopy (upper endoscopy and colonoscopy) because the combination of progressive iron deficiency despite oral supplementation and a positive FIT test strongly suggests occult gastrointestinal blood loss, with colorectal cancer being the most concerning diagnosis in this age group. 1

Most Likely Diagnosis

Occult gastrointestinal malignancy—particularly colorectal cancer—is the primary concern in a 72-year-old man with:

• Progressive ferritin decline from 119.7 to 20.5 ng/mL despite 65 mg daily elemental iron 1
• Positive fecal immunochemical test indicating active gastrointestinal bleeding 2
• Male gender and age >65 years, which are high-risk factors for GI malignancy 1

The ferritin level of 20.5 ng/mL confirms absolute iron deficiency (threshold <30 ng/mL indicates depleted stores), and the failure to adequately respond to oral iron supplementation combined with a positive FIT test indicates ongoing blood loss that exceeds replacement capacity. 1

Immediate Diagnostic Algorithm

Step 1: Urgent Bidirectional Endoscopy (Within 2-4 Weeks)

Both upper endoscopy (EGD) and colonoscopy must be performed because: 1

• Colonoscopy is the priority given the positive FIT test and high pretest probability of colorectal neoplasia in this demographic 1, 3
• Upper endoscopy will detect gastric cancer, angiodysplasia, and other upper GI sources that account for 30-50% of cases 1, 4
• During upper endoscopy, obtain duodenal biopsies to screen for celiac disease, which accounts for 2-3% of iron deficiency cases and can cause treatment failure 1

Step 2: Concurrent Non-Invasive Testing

While awaiting endoscopy, order: 1

• Tissue transglutaminase IgA antibodies for celiac disease screening (present in 3-5% of iron deficiency cases) 1, 4
• Non-invasive Helicobacter pylori testing (stool antigen or urea breath test), as the organism impairs iron absorption 1
• Complete blood count to assess for microcytic anemia and calculate mean corpuscular volume 1

Step 3: Calculate Transferrin Saturation

Using the formula: (serum iron × 100) ÷ total iron-binding capacity 1

• TSAT <16-20% confirms iron deficiency and indicates insufficient iron delivery to bone marrow for erythropoiesis 1
• This parameter helps distinguish absolute iron deficiency from anemia of chronic disease 1

Common Gastrointestinal Causes in This Population

The most likely lesions in a 72-year-old man include: 1

Common Causes	Uncommon but Important
Colorectal cancer/polyps	Gastric cancer
Angiodysplasia	Small bowel tumors
NSAID-induced lesions	Crohn's disease

Colorectal cancer is the most critical diagnosis to exclude because it frequently presents with iron deficiency as the sole manifestation, and all four patients with colonic cancer in one study showed active bleeding on gut lavage testing. 1, 5

Why the Rising Ferritin Trend Does Not Exclude Malignancy

The recent rising trend in ferritin (likely from oral iron supplementation) does not rule out ongoing blood loss. 1

• Iron absorption from supplementation may temporarily stabilize ferritin while occult bleeding continues 1
• The positive FIT test indicates active bleeding at the time of testing, overriding any reassurance from improving ferritin 2
• Ferritin can rise with inflammation (an acute-phase reactant), potentially masking continued iron depletion 1

Critical Pitfalls to Avoid

Do not delay endoscopy based on the rising ferritin trend or assume NSAID use alone explains the findings. 1

• While NSAIDs cause erosions/ulcerations in 36% of users, this does not exclude coexisting malignancy 4
• Do not perform colonoscopy alone—upper endoscopy is mandatory in iron deficiency anemia because upper GI lesions are found in 30-50% of cases 1, 4
• Do not skip duodenal biopsies during upper endoscopy—celiac disease is easily missed without routine sampling and causes treatment failure 1
• Do not assume a negative initial endoscopy is definitive—if both upper and lower endoscopy are normal but anemia persists or worsens, small bowel investigation with capsule endoscopy must be considered 1, 6

If Initial Endoscopy is Negative

Should both upper and lower endoscopy reveal no source: 1, 6

• Repeat endoscopic examinations using cap-fitted endoscopy to examine blind areas (high lesser curve, posterior duodenal bulb) 1
• Consider capsule endoscopy to evaluate the small bowel, as angiodysplasias account for up to 80% of obscure bleeding causes in older patients 1
• Continue oral iron supplementation and monitor response; lack of hemoglobin rise ≥10 g/L within 2 weeks suggests ongoing blood loss or malabsorption 1

Treatment During Diagnostic Workup

Continue oral iron supplementation (65 mg elemental iron daily or alternate-day dosing) while investigations proceed. 1

• Expected response: hemoglobin should rise ≥10 g/L within 2 weeks if bleeding has stopped 1
• Failure to respond indicates ongoing blood loss exceeding replacement capacity or malabsorption 1
• Switch to intravenous ferric carboxymaltose (15 mg/kg, max 1000 mg per dose) if oral iron fails after 8-10 weeks, severe intolerance develops, or ongoing blood loss is confirmed 1