Original article Thyroid hormones and erythrocyte indices in a cohort of euthyroid older subjects ☆ Roger K. Schindhelm a, b, ⁎, Edwin ten Boekel a, b , Nathalie E. Heima c , Natasja M. van Schoor d , Suat Simsek c, e a Department of Clinical Chemistry, Haematology & Immunology, Medical Centre Alkmaar, Alkmaar, The Netherlands b Department of Clinical Chemistry & Haematology, Gemini Hospital, Den Helder, The Netherlands c Department of Internal Medicine, VU University Medical Centre, Amsterdam, The Netherlands d Department of Epidemiology and Biostatistics, EMGO Institute for Health and Care Research, Amsterdam, The Netherlands e Department of Internal Medicine, Medical Centre Alkmaar, Alkmaar, The Netherlands abstract article info Article history: Received 31 October 2012 Received in revised form 3 December 2012 Accepted 5 December 2012 Available online 28 December 2012 Keywords: Thyroid hormones Haemoglobin Older subjects Cohort Objectives: 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 in- clude vitamin B12, folic acid, iron and renal function in the analyses. We therefore studied the association be- tween thyroid hormones and erythrocyte indices in a population-based cohort of older euthyroid subjects, with adjustment for major confounding parameters. Design: Data, including thyroid hormones and erythrocyte indices, are from the Longitudinal Aging Study Amsterdam (LASA), an ongoing cohort study on predictors and consequences of changes in health in the ageing population in the Netherlands. Multivariable linear regression analyses were applied to study the cross-sectional associations between free T4, thyroid stimulating hormone (TSH) and erythrocyte indices (haemoglobin con- tent, haematocrit, mean cell volume (MCV) and erythrocyte count) in a euthyroid sub-sample. The final models were adjusted for vitamin B12, folic acid, iron levels and renal function. Results: In 708 euthyroid older subjects, an increase of 5 pmol/L free T4 was associated with a mean increase of 0.12 mmol/L or 0.19 g/dL of haemoglobin, 0.068 10 12 /L erythrocytes and 0.006 L/L haematocrit (P =0.007, P = 0.005, P =0.001, respectively). Free T4 was not significantly associated with MCV (P >0.05). TSH appeared not to be associated with any of the erythrocyte indices (all P >0.05). Conclusions: In a cohort of older subjects, free T4, but not TSH, was associated with erythrocyte indices, confirming the role of thyroid hormones in the regulation of erythropoiesis. © 2012 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved. 1. Introduction Thyroid hormones have regulatory functions in erythropoiesis [1–8]; however, the mechanisms by which thyroid hormones regulate erythro- poiesis are not yet fully elucidated but seem to be multiple in nature. In humans, a limited number of studies have addressed the association of thyroid function with haematological parameters [9–12]. In a case– control study, iron and ferritin levels were lower in 57 women with sub-clinical hypothyroidism than in the 61 euthyroid controls [9], and in a clinical trial, thyroxin treatment was shown to increase erythropoie- tin levels in 63 women with sub-clinical hypothyroidism, but no significant effects on haemoglobin concentration or haematocrit were observed [10]. In euthyroid subjects, the association between thyroid hormones and erythrocyte indices has been studied recently [11,12]. In the Haemochromatosis and Iron Overload Screening study, the associa- tion of free thyroxin (T4) with haemoglobin and red cell distribution width (RDW) was studied in 141 patients with haemochromatosis and 243 healthy controls. In the controls subjects, but not in the patients, free T4 was positively correlated with haemoglobin concentration and negatively correlated with RDW [11]. In that study, no multivariable regression analyses were performed with adjustments for potential confounders. In a population-based cohort of 1011 euthyroid older sub- jects, significant associations between free T4 and haemoglobin concen- tration, erythrocyte count and haematocrit were found [12]. In that particular study, no adjustments for other potential confounding factors including nutritional parameters (vitamin B12, folic acid and iron) and renal function were applied in the multivariable linear regression analy- ses. Indeed, a number of studies have shown that renal function, either expressed as estimated glomerular filtration rate (eGFR) or serum creat- inine level, is significantly associated to both thyroid function (TSH) [13–15] and haemoglobin concentration [16]. In addition, some [17,18], but not all studies [19,20], have found a higher prevalence of vitamin B12 and/or folic acid deficiency in patients with hypothyroidism. None- theless, additional adjustments for vitamin B12, folic and iron seem ap- propriate to minimize residual confounding. European Journal of Internal Medicine 24 (2013) 241–244 ☆ Grant support: The Longitudinal Aging Study Amsterdam (LASA) is largely supported by a grant from the Netherlands Ministry of Health, Welfare and Sports, Directorate of Nursing Care and Older Persons. ⁎ Corresponding author at: Medical Centre Alkmaar, Juliana van Stolberglaan 13, 1814 HB Alkmaar, The Netherlands. Tel.: +31 223 696969. E-mail address: roger@schindhelm.nl (R.K. Schindhelm). 0953-6205/$ – see front matter © 2012 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.ejim.2012.12.004 Contents lists available at SciVerse ScienceDirect European Journal of Internal Medicine journal homepage: www.elsevier.com/locate/ejim