From the Guidelines
For a 44-year-old male with worsening iron deficiency anemia, pre-diabetes, and obesity, despite a negative colonoscopy, I recommend upper gastrointestinal endoscopy (EGD) as the next diagnostic step. This procedure would evaluate the esophagus, stomach, and duodenum for potential bleeding sources such as peptic ulcers, gastritis, esophageal varices, or malignancies that could explain the ongoing iron loss 1. Additionally, celiac disease testing with tissue transglutaminase antibodies should be performed, as this condition can cause iron deficiency without visible bleeding, and is found in 3%–5% of cases of IDA 1. A complete blood count with peripheral smear would help characterize the anemia further. Helicobacter pylori testing is warranted since infection can cause occult bleeding and gastritis. For patients with persistent unexplained iron deficiency, video capsule endoscopy may be necessary to evaluate the small bowel, which is not accessible via standard endoscopy.
While addressing the anemia, management should include oral iron supplementation, typically ferrous sulfate 325mg daily between meals, along with vitamin C to enhance absorption. The patient should also be counseled on dietary modifications to increase iron intake. The connection between the patient's conditions is important to recognize, as obesity and pre-diabetes can contribute to chronic inflammation, potentially worsening iron absorption, while the metabolic conditions themselves require separate management strategies. According to the British Society of Gastroenterology guidelines, IDA may be the first presenting manifestation of colonic or oesophago-gastric carcinoma, highlighting the importance of swift and complete investigation 1.
Key considerations in the workup of this patient include:
- Detailed history to provide clues as to the cause of IDA
- Initial investigation including urinalysis, screening for coeliac disease, and endoscopic examination of the upper and lower GI tract
- Age, sex, Hb concentration, and mean cell volume as independent predictors of risk of GI cancer in IDA
- Consideration of dual pathology, particularly in older patients
- The potential role of faecal immunochemical testing for risk stratification, although current evidence is evolving and not yet recommended for routine use 1.
From the Research
Further Testing for Iron Deficiency Anemia
Given the patient's worsening iron deficiency anemia, pre-diabetes, and obesity, with a recent colonoscopy showing no evidence of gastrointestinal bleeding except for a few internal hemorrhoids and a comprehensive metabolic panel (CMP) with no significant abnormalities, further testing is recommended to identify the underlying cause of the anemia.
- The patient has already undergone colonoscopy, which is a crucial step in evaluating the lower gastrointestinal tract for sources of bleeding 2.
- Since the colonoscopy did not reveal a significant source of bleeding, evaluation of the upper gastrointestinal tract is necessary 2.
- Bidirectional endoscopy (gastroscopy and colonoscopy) is recommended for diagnostic work-up of unexplained anemia with iron deficiency without overt bleeding 3.
- Serological celiac disease screening with transglutaminase antibody (IgA type) and IgA testing should be conducted to rule out celiac disease as a cause of iron malabsorption 3.
- Small intestine investigation (capsule endoscopy, CT, or MRI enterography) may not be necessary unless there are red flags indicating malignant or inflammatory small bowel disease 3.
- Checking for Helicobacter pylori infection and atrophic gastritis may also be relevant, as these conditions can lead to iron deficiency anemia without overt bleeding 4, 5.
Laboratory Tests
- Serum ferritin levels should be checked to confirm iron deficiency, and C-reactive protein (CRP) analysis should accompany serum ferritin measurement to account for potential inflammation 6.
- Complete blood count (CBC) and iron studies, including transferrin saturation and total iron-binding capacity, can help assess the severity of iron deficiency anemia.