What is the diagnosis and treatment for a patient with fatigue, depression, cold intolerance, low hemoglobin, and an MCV of 70?

Diagnosis: Iron Deficiency Anemia with Possible Hypothyroidism

This patient has iron deficiency anemia (IDA) evidenced by microcytic anemia (MCV 70) with low hemoglobin, and the constellation of fatigue, depression, and cold intolerance strongly suggests concurrent hypothyroidism that must be evaluated immediately. 1, 2

Immediate Diagnostic Workup

Complete the anemia evaluation with:

• Serum ferritin (diagnostic if <30 ng/mL without inflammation) 1, 2
• Transferrin saturation (diagnostic if <20%) 3, 1
• C-reactive protein to assess for inflammation/chronic disease 3, 1
• Reticulocyte count to evaluate bone marrow response 3

Evaluate for hypothyroidism immediately:

• TSH and free T4 are mandatory given the triad of fatigue, depression, and cold intolerance 3
• Hypothyroidism can cause macrocytosis, but when combined with iron deficiency, the MCV may normalize or become microcytic 3

Screen for celiac disease before endoscopy:

• Tissue transglutaminase antibody (IgA) with total IgA level, as celiac disease is found in 3-5% of IDA cases 1

Identify the Source of Iron Loss

In premenopausal women, menstrual blood loss (especially menometrorrhagia) is the most common cause of IDA. 3, 4, 2 However, pictorial blood loss assessment charts should be used as history alone is unreliable for quantifying menstrual loss. 3

In men and postmenopausal women, gastrointestinal blood loss must be assumed until proven otherwise:

• Bidirectional endoscopy (upper endoscopy and colonoscopy) is mandatory 1
• Consider gastrointestinal malignancy, particularly colon cancer, especially with family history 1
• Angiodysplasia is common in elderly patients 1

Additional causes to evaluate:

• NSAID use (common cause of GI bleeding) 2
• Atrophic gastritis or prior bariatric surgery (impaired absorption) 2
• Inflammatory bowel disease (13-90% have iron deficiency) 2

Treatment Protocol

Initiate oral iron replacement immediately:

• Ferrous sulfate 325 mg daily (containing 65 mg elemental iron) 5, 2
• Alternative: ferrous sulfate 325 mg on alternate days if daily dosing not tolerated 2
• Ascorbic acid enhances absorption and should be added if response is poor 3
• Continue for 3 months after hemoglobin normalization to replenish stores (target ferritin >100 μg/L) 3, 1

Use intravenous iron if:

• Oral iron is not tolerated or ineffective 3, 1, 2
• Severe anemia is present 3, 1
• Malabsorption exists (celiac disease, post-bariatric surgery) 2
• Inflammatory bowel disease or chronic inflammatory conditions are present 2
• The patient is in second or third trimester of pregnancy 2

Intravenous iron dosing:

• Total dose of 1 gram empirically, or calculate using Ganzoni formula 3
• Regularly scheduled infusions may be needed if chronic bleeding continues 3

Address Hypothyroidism if Confirmed

If TSH is elevated, initiate levothyroxine replacement therapy. Hypothyroidism itself can contribute to anemia and will not resolve without thyroid hormone replacement. 3

Monitoring and Follow-Up

At 1 month:

• Assess hemoglobin rise (should increase ≥1.0 g/dL) 3
• Check ferritin and transferrin saturation normalization 3
• If inadequate response, increase oral iron dose or switch to intravenous iron 3

After anemia correction:

• Monitor hemoglobin and MCV every 3 months for 1 year, then annually 3
• Additional oral iron if hemoglobin or MCV falls below normal 3
• Further investigation only if hemoglobin cannot be maintained with iron supplementation 3

Critical Pitfalls to Avoid

Do not assume menstrual bleeding is the sole cause without investigation. Even in premenopausal women, if anemia is severe or refractory to iron replacement, gastrointestinal evaluation is warranted. 3, 1

Do not miss concurrent hypothyroidism. The combination of cold intolerance, depression, and fatigue is highly suggestive and requires thyroid function testing. 3

Do not use faecal occult blood testing as it is insensitive and non-specific for evaluating IDA. 3

Do not perform bone marrow biopsy initially unless there is failure to respond to appropriate iron replacement or concern for myelodysplastic syndrome. 1