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Hematologic Effects of Levothyroxine in Iron-Deficient Subclinical Hypothyroid Patients: A Randomized, Double-Blind, Controlled Study

Departments of Internal Medicine (H.C., C.B., F.G.) and Public Health and Biostatistics (T.B.), Duzce University School of Medicine, Duzce 81620, Turkey

Address all correspondence and requests for reprints to: Hakan Cinemre, M.D., Department of Internal Medicine, Duzce University School of Medicine, Duzce 81620, Turkey. E-mail: cinemre_h{at}ibu.edu.tr.

Context: In patients with coexisting iron-deficiency anemia and subclinical hypothyroidism, anemia does not adequately respond to oral iron therapy.

Objective: We studied whether iron-deficiency anemia might indicate treatment of subclinical hypothyroidism.

Design: Patients were assigned to a control or experimental group: 240 mg/d oral iron alone (iron group) or 240 mg/d oral iron plus 75 µg/d levothyroxine (iron/levothyroxine group). Levels of hemoglobin, hematocrit, red blood cell count, serum iron levels, ferritin, total iron-binding capacity, TSH, and free T₄ were measured before and after treatment.

Setting: The study was conducted at a university hospital outpatient clinic.

Patients: Fifty-one patients with coexisting iron-deficiency anemia and subclinical hypothyroidism participated in the study.

Intervention: Patients were treated as described above in either the iron group or the iron/levothyroxine group.

Main Outcome Measure: A clinically satisfactory increase in hemoglobin was regarded as successful.

Results: Mean hemoglobin levels increased by 0.4 g/dl in the iron group [95% confidence interval (CI) 0.2–0.7, P = 0.001], whereas it increased by a mean of 1.9 g/dl in the iron/levothyroxine group (95% CI 1.5–2.3, P < 0.0001). The increase in serum iron was greater in the iron/levothyroxine group by a mean of 47.6 µg/dl (95% CI 34.5–60.6, P < 0.0001). Increases in hemoglobin, red blood cells, hematocrit, and serum ferritin levels after treatment were statistically significantly greater in the iron/levothyroxine group (P < 0.0001). Starting hemoglobin and increase in hemoglobin were negatively correlated in the iron/levothyroxine group (r = –0.531, P = 0.006).

Conclusions: Subclinical hypothyroidism should be treated in iron-deficiency anemia patients when both conditions coexist. This would provide a desired therapeutic response to oral iron replacement and prevent ineffective iron therapy.