Low Thyroid Function and Anemia in Old Age: The Leiden 85‐Plus Study

Abstract

To the Editor: Anemia and low thyroid function are common, especially in older individuals.1-3 Thyroid function measurements are often included in the clinical examination of anemia. The symptoms of (subclinical) hypothyroidism and anemia are similar, which not only frequently presents a challenging diagnostic problem, but may also point to a causal relationship between low thyroid function and anemia.4 Several experimental and animal studies support a causal association between low thyroid function and anemia. Thyroid hormone stimulates the production of hemoglobin5 and enhances red blood cell formation.4 Already in 1885, a decrease in red blood cells was reported in monkeys after removal of the thyroid.6 Low hematocrit levels have been observed in mice deficient in the thyroid hormone receptor,7 and administration of thyroid hormones to hypophysectomized rats has been shown to correct anemia.8 Data in humans also indicate a causal association between (subclinical) hypothyroidism and anemia. In several studies, lower hemoglobin9-11 and a higher prevalence of anemia12, 13 were observed in persons with (subclinical) hypothyroidism than in euthyroid persons. In addition, in a number of small intervention studies, treatment of (subclinical) hypothyroidism with thyroid hormone resulted in a significant increase in hemoglobin13-15 or erythropoietin level.16 Because effects of common risk factors in the general population, including the effect of low thyroid hormone levels on mortality,17 are often absent or even reversed in the oldest old, the aim of the present study was to investigate the association between low thyroid function and anemia in 85-year-olds in the general population. The present cross-sectional study is embedded in the Leiden 85-plus Study, a population-based prospective follow-up study of 85-year-old inhabitants of Leiden, the Netherlands. Plasma levels of thyroid-stimulating hormone (TSH) and free thyroxine (fT4) were measured in one batch (Elecsys 2010 system, Hitachi, Tokyo, Japan) in a completely automated laboratory robot using an electrochemiluminescence technique (Boehringer, Mannheim, Germany). Plasma levels of free triiodothyronine (fT3) were determined using a microparticle enzyme immunoassay (Abbott Diagnostics, Abbott Park, IL). Thyroid hormone groups were created based on serum TSH and fT4 levels as widely clinically accepted:18 euthyroidism (TSH 0.5–4.5 mIU/L; n = 451), overt hypothyroidism (TSH >4.5 mIU/L, fT4 <13 pmol/L; n = 40), subclinical hypothyroidism (TSH >4.5 mIU/L, fT4 13–23 pmol/L; n = 35). Hemoglobin was measured on the day the blood sample was drawn using a fully automated system (Sysmex XE-2100, TOA Medical Electronics, Kobe, Japan). Anemia was defined according to the World Health Organization criteria (hemoglobin <13 g/dL for men, <12 g/dL for women).19 Of 526 participants, 177 (33.7%) were male, and 136 (25.9%) had anemia. Median TSH was 1.9 mU/L (interquartile range (IQR) 1.3–3.0), and median fT4 was 14.3 pmol/L (IQR 12.8–15.7). The prevalence of anemia was 25% in participants with euthyroidism (reference group), 26% in those with subclinical hypothyroidism (sex-adjusted odds ratio (OR) = 1.16, 95% confidence interval (CI) = 0.52–2.57), and 35% in those with hypothyroidism (sex-adjusted OR = 1.76, 95% CI=0.89–3.51). No differences were observed in sex-adjusted mean hemoglobin levels between thyroid function groups (euthyroidism, 13.0 (standard error (SE) 0.1) g/dL; subclinical hypothyroidism, 13.1 (0.2) g/dL, P = .68; overt hypothyroidism, 12.8 (SE 0.2) g/dL, P = .37). In a linear regression analysis (adjusted for sex), no association was found between TSH and hemoglobin or between fT4 and hemoglobin in the total population (Table 1). Similar results were observed when the analyses were stratified according to sex, except for fT4 in men. In men, for each unit increase in fT4, hemoglobin levels increased 0.12 g/dL (95% CI = 0.01–0.23). In the total population, a unit increase in free