Refractory Iron Deficiency Anemia in a Young Adult: Diagnostic Challenges

Abstract

Iron deficiency anemia (IDA) is the most common cause of anemia worldwide and is usually responsive to oral iron therapy. However, refractory IDA warrants further evaluation to identify underlying causes such as occult blood loss or malabsorption. We report the case of a 29-year-old male who presented with chronic fatigue and exertional dyspnea and was found to have persistent iron deficiency anemia unresponsive to oral iron supplementation. Despite initial management, hemoglobin levels failed to improve, prompting an extensive diagnostic workup. Subsequent investigations revealed occult gastrointestinal blood loss secondary to a small bowel vascular lesion. Targeted intervention led to hematologic recovery. This case highlights the importance of systematic evaluation of refractory iron deficiency anemia and the role of early investigation for occult gastrointestinal pathology.

Introduction

Iron deficiency anemia (IDA) is a common hematological condition resulting from inadequate iron intake, impaired absorption, or chronic blood loss. In young adults, IDA is frequently attributed to nutritional deficiency, dietary habits, or—in females—menstrual blood loss. However, in males and non-menstruating individuals, the presence of IDA warrants careful evaluation for underlying pathology, particularly chronic gastrointestinal blood loss, even in the absence of overt symptoms [1,2]. Failure to investigate appropriately may result in missed diagnoses of clinically significant conditions.

Refractory iron deficiency anemia, defined as a suboptimal or absent hematologic response to adequate oral iron therapy, represents a distinct clinical challenge. Poor response may result from nonadherence, incorrect dosing, or inadequate duration of therapy, but true refractoriness should prompt further investigation [3]. Important etiologies include malabsorption syndromes such as celiac disease, Helicobacter pylori–associated gastritis, inflammatory bowel disease, autoimmune gastritis, and ongoing occult blood loss from gastrointestinal lesions, including polyps, angiodysplasia, or malignancy [4,5].

Young adults with refractory IDA often present with nonspecific symptoms such as fatigue, reduced exercise tolerance, dyspnea on exertion, and cognitive impairment, which may be mistakenly attributed to lifestyle factors or stress. As a result, diagnosis is frequently delayed, leading to prolonged morbidity and impaired quality of life. A structured, stepwise diagnostic approach incorporating laboratory evaluation, assessment of iron indices, and targeted gastrointestinal investigations is therefore essential.

This case highlights the diagnostic complexity of refractory IDA in a young adult and underscores the importance of maintaining a high index of suspicion for occult gastrointestinal blood loss. Early recognition of refractory disease and timely identification of the underlying cause are critical to instituting definitive management, preventing recurrence, and avoiding long-term complications associated with chronic iron deficiency.

Patient Information

• Age / Gender: 29-year-old male
• Occupation: Marketing executive
• Medical History: No known chronic illnesses
• Surgical History: None
• Family History: No hematological disorders or gastrointestinal malignancy
• Social History: Non-smoker, occasional alcohol use
• Dietary History: Mixed diet, adequate iron intake reported
• Medications: Oral ferrous sulfate (self-initiated, 3 months)
• Chief Complaints: Progressive fatigue, exertional dyspnea, reduced exercise tolerance

Clinical Findings

• General Examination: Pallor present, no icterus or lymphadenopathy

• Vital Signs: Stable
• Cardiovascular Examination: Flow murmur consistent with anemia
• Abdominal Examination: Soft, non-tender, no organomegaly
• Rectal Examination: No overt bleeding

Initial Impression: Chronic anemia, likely iron deficiency, with poor response to oral therapy.

Timeline

• Month 0: Onset of fatigue and weakness
• Month 2: Initial evaluation revealed microcytic anemia
• Month 3: Oral iron therapy initiated
• Month 5: No improvement in hemoglobin levels
• Month 6: Referral to hematology
• Month 7: Gastrointestinal evaluation initiated
• Month 8: Occult bleeding source identified
• Month 9: Definitive treatment performed
• Month 10: Hematologic recovery documented

Diagnostic Assessment

Laboratory Investigations:

• Hemoglobin: 8.6 g/dL
• Mean corpuscular volume (MCV): 68 fL
• Serum ferritin: 6 ng/mL
• Serum iron: Low
• Total iron-binding capacity: Elevated
• Reticulocyte count: Low-normal

Additional Tests:

• Vitamin B12 and folate: Normal
• Celiac serology: Negative
• Stool occult blood test: Positive on repeated testing

Imaging and Endoscopy:

• Upper GI endoscopy: Normal
• Colonoscopy: Normal
• Capsule endoscopy: Revealed small bowel angiodysplasia

Diagnosis: Refractory iron deficiency anemia due to occult gastrointestinal blood loss.

Differential Diagnosis

• Poor compliance or intolerance to iron therapy

• Iron malabsorption (celiac disease)
• Anemia of chronic disease
• Hemoglobinopathy
• Occult gastrointestinal malignancy

These were excluded based on laboratory findings, serology, and imaging.

Therapeutic Intervention

Step 1 – Optimization of Iron Therapy

• Discontinuation of ineffective oral iron
• Initiation of intravenous iron sucrose

Step 2 – Definitive Management

• Endoscopic treatment of small bowel vascular lesion

Step 3 – Supportive Care

• Nutritional counseling
• Monitoring for recurrent blood loss

Challenges Faced

• Delayed suspicion of gastrointestinal bleeding due to young age

• Initial attribution of anemia to nutritional causes
• Limited availability of small bowel imaging

Follow-Up and Outcomes

• Month 1 Post-Treatment: Hemoglobin increased to 11.2 g/dL
• Month 3: Hemoglobin normalized to 13.6 g/dL
• Month 6: Ferritin levels restored, no recurrence of symptoms
• Functional Outcome: Resolution of fatigue and return to normal activity

Discussion

Refractory iron deficiency anemia necessitates a high index of suspicion for ongoing blood loss or malabsorption, particularly in young male patients where nutritional deficiency alone is unlikely [2,4]. Failure to respond to oral iron therapy is a key clinical clue and should prompt early re-evaluation rather than prolonged empirical treatment.

Occult gastrointestinal bleeding remains one of the most important and potentially serious causes of refractory IDA. While upper and lower endoscopy are first-line investigations, lesions within the small bowel may be missed without advanced diagnostic modalities such as capsule endoscopy [5]. Early identification of the bleeding source allows targeted intervention and prevents long-term complications, including repeated transfusions and reduced quality of life.

This case underscores the importance of guideline-driven evaluation and a multidisciplinary approach involving hematology and gastroenterology to achieve optimal outcomes.

Multidisciplinary Approach

• Hematologist: Anemia evaluation and iron therapy
• Gastroenterologist: Endoscopic assessment and intervention
• Dietitian: Nutritional optimization
• Primary Care Physician: Long-term monitoring

Key Takeaways

• Refractory iron deficiency anemia requires systematic evaluation

• Young male patients warrant early investigation for occult blood loss
• Failure of oral iron therapy is a critical diagnostic clue
• Capsule endoscopy is valuable in unexplained cases
• Treating the underlying cause is essential for sustained recovery

Patient’s Perspective

“I was taking iron tablets for months with no improvement. Once the real cause was found and treated, my energy returned completely.”

Conclusion

This case highlights the diagnostic challenges associated with refractory iron deficiency anemia (IDA) in young adults, particularly in populations where nutritional deficiency is often presumed to be the primary cause. Persistent anemia despite adequate oral iron therapy should raise immediate concern and prompt a systematic evaluation for secondary etiologies, including occult blood loss, malabsorption disorders, and chronic inflammatory conditions. In males and non-menstruating individuals, gastrointestinal sources of blood loss must be carefully excluded, even in the absence of gastrointestinal symptoms or overt bleeding.

Delayed recognition of refractory IDA can result in prolonged morbidity, functional impairment, and reduced quality of life. Chronic iron deficiency is associated not only with fatigue and reduced exercise capacity but also with impaired cognitive function, decreased work productivity, and, in severe cases, cardiovascular strain. Furthermore, failure to identify the underlying cause may allow potentially serious conditions—such as inflammatory bowel disease, peptic ulcer disease, or gastrointestinal malignancy—to progress unchecked. This underscores the importance of moving beyond empirical iron supplementation when treatment response is inadequate.

Early identification and targeted treatment of the underlying pathology are essential to achieving sustained hematologic recovery and preventing recurrence. A structured diagnostic algorithm incorporating detailed history taking, adherence assessment, laboratory evaluation of iron indices, and appropriate endoscopic or radiologic investigations can significantly reduce diagnostic delay. In cases of confirmed malabsorption or ongoing blood loss, timely escalation to parenteral iron therapy and disease-specific management is often required.

A multidisciplinary approach involving primary care physicians, hematologists, gastroenterologists, and dietitians plays a critical role in optimizing outcomes. Such collaboration ensures comprehensive evaluation, individualized treatment planning, and long-term follow-up. Ultimately, increased clinician awareness and adherence to evidence-based diagnostic pathways are key to improving care for young adults with refractory iron deficiency anemia.

References

1. World Health Organization. Iron deficiency anaemia: assessment, prevention, and control. WHO; 2001.
2. Short MW, Domagalski JE. Iron deficiency anemia: evaluation and management. Am Fam Physician. 2013;87(2):98–104.
3. Cappellini MD, Musallam KM, Taher AT. Iron deficiency anemia revisited. J Intern Med. 2020;287(2):153–170.
4. Goddard AF, James MW, McIntyre AS, Scott BB. Guidelines for the management of iron deficiency anaemia. Gut. 2011;60(10):1309–1316.
5. Gerson LB, Fidler JL, Cave DR, Leighton JA. ACG clinical guideline: diagnosis and management of small bowel bleeding. Am J Gastroenterol. 2015;110(9):1265–1287.
6. Camaschella C. Iron-deficiency anemia. N Engl J Med. 2015;372(19):1832–1843.
7. DeLoughery TG. Microcytic anemia. N Engl J Med. 2014;371(14):1324–1331.

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