Anemia and thyroid hormones

Anemia is a fascinating and nuanced clinical challenge, and especially significant because anemia of any type diminishes the capacity of every cell in the body to do its work. Are you vexed by the slippery task of tracking down contributing causes to a patient's normocytic anemia? A study just published in the European Journal of Internal Medicine sheds light on the impact of diminished free T4 (thyroxin; fT4) on erythrocyte production and anemia. The authors state:

"Hypothyroidism is associated with normocytic anaemia. Indeed, a limited number of studies have shown significant associations between free thyroxin (T4) and erythrocyte indices. These studies did not include vitamin B12, folic acid, iron and renal function in the analyses. We therefore studied the association between thyroid hormones and erythrocyte indices in a population-based cohort of older euthyroid subjects, with adjustment for major confounding parameters."

They applied multivariable linear regression analyses data accumulated as part of the Longitudinal Aging Study Amsterdam to discern the associations between free T4, thyroid stimulating hormone (TSH) and erythrocyte indices that included hemoglobin, haematocrit, mean cell volume (MCV) and RBC count) in a sub-sample of subjects with (relatively) normal thyroid values. Importantly, they adjusted their models for vitamin B12, folic acid, iron levels and renal function. The data showed an association between fT4 and key anemia indices:

"In 708 euthyroid older subjects, an increase of 5pmol/L free T4 was associated with a mean increase of 0.12mmol/L or 0.19g/dL of haemoglobin, 0.068 1012/L erythrocytes and 0.006L/L haematocrit. Free T4 was not significantly associated with MCV. TSH appeared not to be associated with any of the erythrocyte indices."

When surveying possible contributing causes for anemia clinicians should be attentive to small shifts in free thyroxin. The authors elaborate on their findings in relation to an earlier study, and the obvious question of an association between free T3 and anemia:

"In the present study, free T4 was significantly associated with parameters of erythropoiesis, including haemoglobin concentration, haematocrit and erythrocyte count, whereas TSH was not significantly associated with any of these parameters. Our study is, to the best of our knowledge, the second study assessing the relation of thyroid hormones and haematological parameters in a larger population based cohort study. The results of the present study are in line with the study of Bremner and co-workers, who showed that free T4 was significantly associated to haemoglobin concentration, erythrocyte count and haematocrit. However, in contrast to the study of Bremner et al., we found no association between free T4 and MCV. In the study of Bremner et al., the regression coefficient of the association of free T4 and haemoglobin converted to change of haemoglobin in mmol/L per 5 pmol/L equalled 0.084 and is comparable to the results in the present study (i.e. 0.12 mmol/L or 0.19 g/dL haemoglobin per 5 pmol/L free T4). Bremner and co-workers also demonstrated significant associations of T3 with the studied erythrocyte indices. Unfortunately, T3 was not determined in the baseline measurements of LASA. Furthermore, TSH was not associated with any of the erythrocyte parameters which is in line with the findings of Bremner and co-workers."

It's tempting to speculate about the mechanism by which suboptimal T4 and T3 could cause diminished RBC indices: Stimulation of erythropoietin (EPO) production? Iron metabolism? RBC receptors? An obvious question regards the possible link between thryroid dysregulation, anemia and autoimmunity.

"In conclusion, in the present study significant associations between free T4 and erythrocyte indices, including haemoglobin concentration, haematocrit and erythrocyte count were demonstrated. These results may be relevant for the further understanding of the role of thyroid hormones in the regulation of erythropoiesis."