What is the best treatment for a 55-year-old man with microcytic anemia, potential hypothyroidism, and symptoms of fatigue, depression, and cold intolerance?

Treatment of Microcytic Anemia with Concurrent Hypothyroidism

Immediate Treatment Priority

Start oral iron supplementation with ferrous sulfate 200 mg three times daily immediately, and address the hypothyroidism only after correcting the anemia to avoid intolerance to thyroid hormone replacement. 1, 2

Critical Clinical Reasoning

This patient presents with clear iron deficiency anemia (ferritin 13 μg/L, MCV 70 fL, hemoglobin 10 g/dL) and likely hypothyroidism based on symptoms of fatigue, depression, and cold intolerance. The TSH value appears incomplete in the presentation, but the constellation of symptoms strongly suggests thyroid dysfunction. The key clinical pitfall here is attempting to treat hypothyroidism before correcting the anemia—this can precipitate a hyperadrenergic state with palpitations, nervousness, and intolerance to levothyroxine. 2

Step-by-Step Treatment Algorithm

Phase 1: Iron Repletion (Weeks 0-4)

• Initiate ferrous sulfate 200 mg orally three times daily for at least three months after hemoglobin correction to fully replenish iron stores. 1, 3

• Add ascorbic acid (vitamin C) to enhance iron absorption. 1, 3

• If ferrous sulfate is not tolerated due to gastrointestinal side effects, switch to ferrous gluconate or ferrous fumarate as alternative formulations. 1, 3

• Monitor hemoglobin at 2 weeks—expect a rise of ≥10 g/L (≥1 g/dL), which confirms iron deficiency as the diagnosis. 1, 3

• Defer levothyroxine initiation during this period, even if TSH is elevated, to prevent thyroid hormone intolerance. 2

Phase 2: Thyroid Hormone Initiation (Week 4-7)

• Once hemoglobin improves by at least 2 g/dL after 4 weeks of iron therapy, initiate levothyroxine if TSH confirms hypothyroidism. 4, 2

• Start levothyroxine at a conservative dose (typically 1.6 mcg/kg/day for overt hypothyroidism with TSH ≥10 mIU/L, or 1.0 mcg/kg/day for TSH <10 mIU/L). 4

• In this 55-year-old man with anemia, consider starting at an even lower dose (25-50 mcg daily) and titrating up gradually to avoid cardiovascular stress or symptoms of intolerance. 4, 2

Phase 3: Monitoring and Adjustment (Months 2-6)

• Monitor hemoglobin and red cell indices at three-monthly intervals for one year, then annually thereafter. 1, 3

• Continue oral iron supplementation for at least three months after anemia correction to replenish tissue iron stores. 1, 3

• Monitor TSH at 6-8 weeks after initiating or changing levothyroxine dosage, then every 6-12 months once stable. 4

• Provide additional oral iron if hemoglobin or MCV falls below normal during follow-up. 1, 3

Investigation of Underlying Cause

In a 55-year-old man, iron deficiency anemia is most commonly caused by gastrointestinal blood loss or malabsorption—this requires investigation. 3, 5

• Obtain a detailed history for melena, hematochezia, NSAID use, or occult bleeding. 1

• Consider upper and lower gastrointestinal endoscopy to identify bleeding sources, particularly given the patient's age and sex. 3

• Screen for celiac disease if malabsorption is suspected, as this can impair both iron and levothyroxine absorption. 1

• Evaluate for Helicobacter pylori-associated atrophic gastritis, which can contribute to iron deficiency. 5

Critical Drug Interactions and Monitoring

• Iron supplements can decrease levothyroxine absorption—separate administration by at least 4 hours. 4

• Certain foods (soybean flour, walnuts, dietary fiber, grapefruit juice) can impair levothyroxine absorption and may require dosage adjustments. 4

• If the patient is on antidepressants for depression, be aware that levothyroxine may increase therapeutic and toxic effects of tricyclic antidepressants, and sertraline may increase levothyroxine requirements. 4

Common Pitfalls to Avoid

• Do not start levothyroxine before treating severe anemia—this creates a hyperadrenergic state with palpitations and intolerance. 2

• Do not assume all microcytic anemia is simple iron deficiency—if the patient fails to respond to oral iron therapy within 2-4 weeks, consider intravenous iron for malabsorption, or investigate for genetic disorders of iron metabolism (TMPRSS6 mutations causing iron-refractory iron deficiency anemia), thalassemia, or anemia of chronic disease. 1, 3, 5

• Do not overlook combined deficiencies—hypothyroidism can coexist with vitamin B12 or folate deficiency, which may cause macrocytic changes that mask the microcytosis from iron deficiency. 3, 6

• Do not stop iron supplementation once hemoglobin normalizes—continue for at least three months to replenish tissue stores. 1, 3

When to Consider Alternative Therapies

• If the patient fails to respond to oral iron after 4 weeks (hemoglobin increase <2 g/dL), consider intravenous iron if malabsorption is present. 1, 3

• For genetic disorders such as TMPRSS6 mutations (iron-refractory iron deficiency anemia), repeated intravenous iron (iron sucrose or ferric gluconate) may be necessary, though complete normalization is rarely achieved. 1, 5

• Monitor serum ferritin during IV iron therapy and do not exceed 500 μg/L to avoid iron overload risk. 1