Should a patient with iron deficiency anemia (IDA) without anemia undergo bidirectional endoscopy?

From the Guidelines

Bidirectional endoscopy is not generally recommended for patients with iron deficiency without anemia, as the cancer risk in this population is low. According to the British Society of Gastroenterology guidelines for the management of iron deficiency anaemia in adults 1, age, sex, Hb concentration, and mean cell volume are all independent predictors of risk of GI cancer in IDA, and the cancer risk in iron deficiency without anaemia is low. However, in certain cases, such as men and postmenopausal women with newly diagnosed iron deficiency without anemia, gastroscopy and colonoscopy should be considered as first-line GI investigations if there are risk factors or symptoms suggesting gastrointestinal pathology 1.

For premenopausal women, endoscopy may be considered if they have gastrointestinal symptoms, family history of colorectal cancer, or if iron deficiency persists despite iron supplementation. The rationale for this approach is that iron deficiency, even without anemia, can be an early indicator of gastrointestinal bleeding from conditions such as peptic ulcers, gastritis, inflammatory bowel disease, celiac disease, or gastrointestinal malignancies. These conditions may cause chronic, low-grade blood loss that depletes iron stores before hemoglobin levels fall below normal. Early detection through endoscopy can lead to timely intervention for potentially serious conditions. Before proceeding with endoscopy, other causes of iron deficiency should be considered, including dietary insufficiency, malabsorption, or increased physiological demands.

Key considerations for bidirectional endoscopy in patients with iron deficiency without anemia include:

• Patient population: men and postmenopausal women with newly diagnosed iron deficiency without anemia, and premenopausal women with risk factors or symptoms suggesting gastrointestinal pathology
• Treatment recommendations: gastroscopy and colonoscopy as first-line GI investigations
• Strength of recommendation: strong for men and postmenopausal women, conditional for premenopausal women
• Quality of evidence: moderate to high
• Comments: other causes of iron deficiency should be considered before proceeding with endoscopy, and the cancer risk in iron deficiency without anaemia is low 1.

From the Research

Diagnosis and Treatment of Iron Deficiency

• Iron deficiency without anaemia is a common condition that can have significant health implications if left untreated 2.
• The causes of iron deficiency may sometimes be obvious, but many tend to be overlooked, and diagnosing iron deficiency without anaemia relies on a combination of tests, including haemoglobin and ferritin levels, as well as transferrin saturation 2.
• Bidirectional endoscopy (gastroscopy and colonoscopy) is recommended for unexplained anaemia with iron deficiency, but not required in premenopausal women < 40 years of age 3.

Risk of Gastrointestinal Malignancy

• Men and postmenopausal women with iron deficiency anaemia have the highest overall prevalence of gastrointestinal malignancy (∼11%), while premenopausal women with iron deficiency anaemia (<1.5%) and those with iron deficiency without anaemia (<0.5%) have a very low risk 4.
• The risk of malignant disease of the gastrointestinal tract is associated with iron deficiency without overt GI bleeding, with upper gastrointestinal cancer being 1/7 as common as colon cancer 3.

Diagnostic Strategy

• A diagnostic strategy for unexplained iron deficiency without anaemia should include serological celiac disease screening with transglutaminase antibody (IgA type) and IgA testing 3.
• Bidirectional endoscopy may be considered in patients with iron deficiency without anaemia, especially if there are red flags indicating malignant or inflammatory small bowel disease (e.g., involuntary weight loss, abdominal pain or increased CRP) 3.
• Noninvasive investigation with fecal immunochemical test and fecal calprotectin may hold promise to guide further investigations in lower risk groups 4.

Treatment of Iron Deficiency

• Oral iron therapy is the first-line treatment for managing iron deficiency without anaemia, but intravenous supplementation should be used in chronic inflammatory conditions and when oral therapy is poorly tolerated or ineffective 2, 5.
• Counselling and oral iron therapy are usually combined as a first step in treatment, and integrating haem and free iron regularly into the diet, looking for enhancers and avoiding inhibitors of iron uptake is beneficial 5.