Subclinical hypothyroidism – defined as an elevated serum thyroid stimulating hormone level in the presence of normal total or free T4 and T3 levels – is a common clinical problem that occurs in 4-10% of general patient populations. Anemia is frequently associated with overt hypothyroidism, and treatments such as T4 replacement have shown to be beneficial in normalizing anemia. However, limited studies have analyzed whether similar treatment benefits are attainable in terms of subclinical hypothyroidism and anemia. Recent clinical observations demonstrated that subclinical hypothyroidism was a common feature among iron-deficiency anemia patients who did not respond to oral iron therapy. Based on these observations, a study by Cinemre et al was designed to assess this association, as well as to explore whether thyroid replacement would reverse unresponsiveness to treatment in these patients.

In the study, 51 patients meeting inclusion criteria – newly diagnosed anemia and coexisting subclinical hypothyroidism – were selected from a study population of 2,421 patients at an internal medicine outpatient clinic. These patients were separated into two study groups: one that was instructed to take 80 mg capsules of ferrous sulfate three times daily, and the other 80 mg capsules of ferrous sulfate plus 25 μg of levothyroxine three times daily. After 12 weeks, the study was terminated. Upon completion of the study, patients receiving ferrous sulfate and levothyroxine had an average hemoglobin increase of 1.9 g/dL, compared to 0.4 g/dL in the group receiving ferrous sulfate alone. In addition, δ iron was significantly higher in the ferrous sulfate/levothyroxine group, as were red blood cell, hematocrit, transferrin saturation, ferritin, and T4 levels, compared to ferrous sulfate treatment alone. Also, no adverse reactions to the medications were reported in either group.

The authors concluded that patients with anemia and subclinical hypothyroidism can significantly benefit from treatment with ferrous sulfate and levothyroxine. The results also stress the need for testing thyroid function in patients with resistance to oral iron treatment. Although some research has shown that thyroid hormones can help initiate erythropoiesis, the parallel hematological improvements shown in this study suggest that erythropoiesis stimulation by thyroid hormones is not the sole mechanism of action. Further studies will be needed to elucidate other mechanisms so that these therapies can be optimized in clinical settings.

Cinemre H, Bilir C, Gokosmanoglu F, Bahcebasi T. Hematologic Effects of Levothyroxine in Iron-Deficient Subclinical Hypothyroid Patients: A Randomized, Double-Blind, Controlled Study. J Clin Endocrinol Metab. 2009 Jan;94(1):151-6.

NAAC Expert Commentary:
The co-existence of iron deficiency and thyroid disease is a common clinical observation, but one that has lacked full explanation or definitive study. Cinemre and colleagues from Duzce University School of Medicine in Turkey approached the problem with a randomized clinical trial of iron supplementation alone versus iron plus 75 mcg of levothyroxine in patients who were both anemic from iron deficiency and had subclinical hypothyroidism.

As they point out in a thoughtful discussion, Duzce is located on the coast of the Black Sea of Turkey, which is an endemic goiter region. There is a high likelihood that the goiters are caused by iodine deficiency, which is the most common cause of thyroid dysfunction worldwide and is still seen in developed countries. About 30% of their patients had anti-thyroid antibodies present, but iodine stores were not measured. After 12 weeks of treatment, iron stores and hematologic indices improved significantly more in the dual treatment group than the group who received only iron.

They discuss the possible mechanisms for this result, including increased iron absorption, the stimulatory effect of thyroid hormones on iron incorporation into erythrocytes, and the effect of thyroxine on erythroid progenitors. Animal studies have shown that iodine alone and inactive isomers of thyroxine have some of the same effects. Whether the marked improvement noted by the addition of levothyroxine is due to the effect of the hormone or simply the addition of iodine to iodine-deficient patients is not known, but could perhaps be studied in the same population by these clinical investigators.

Last Updated: March 4, 2009