Clinical Endocrinology (2008) 68, 640–645 doi: 10.1111/j.1365-2265.2007.03091.x © 2007 The Authors 640 Journal compilation © 2007 Blackwell Publishing Ltd ORIGINAL ARTICLE Blackwell Publishing Ltd Chronic unexplained anaemia in isolated autoimmune thyroid disease or associated with autoimmune related disorders Rosanna Sibilla, Maria Giulia Santaguida, Camilla Virili, Lucilla Gargano, Serena Nardo, Michele Della Guardia, Nicola Viceconti, Antonella Franchi and Marco Centanni Endocrinology Unit, Department of Experimental Medicine, University of Rome ‘Sapienza’, Polo Pontino, Latina, Italy Summary Objective The prevalence of chronic unexplained anaemia was analysed in patients with autoimmune thyroid disease (ATD). Design The presence of chronic unexplained anaemia, defined as anaemia not related to evident or occult bleeding and/or to eryth- ropoietic disorders, was retrospectively assessed and compared in patients with nonautoimmune thyroid disease (NATD) and in patients with ATD. Subjects and measurements Biochemical and morphological parameters of anaemia were investigated and characterized in 1643 consecutive Caucasian outpatients with thyroid disease. In 991 patients, thyroid disease had a nonautoimmune origin. ATD was diagnosed in 652 patients (71 had Graves’ disease and 581 had Hashimoto’s thyroiditis and its variants). In 145 patients ATD was associated with other autoimmune disorders. Results The presence of chronic unexplained anaemia was diagnosed in 123 patients (7·5%). Forty-eight had a thalassaemic trait, representing 2·9% of the whole sample. A true chronic un- explained anaemia was recorded in 75/1643 (4·6%). The occurrence of unexplained anaemia was similar in patients with NATD (1·9%) and in those with isolated ATD (2·96%; P = NS) but increased in patients with ATD and autoimmune related disorders (ARD) compared to patients with isolated ATD and/or with NATD (28·3%; both P < 0·0001; RR = 9·56 and 14·75, respectively). Chronic unexplained anaemia was virtually absent in hyperthyroid patients and was more prevalent in hypothyroid than in euthyroid patients with ATD (P = 0·0047; RR = 2·104). Conclusions These results indicate that the increased frequency of chronic anaemia in patients with ATD is essentially due to the presence of concomitant autoimmune gastrointestinal diseases. (Received 2 July 2007; returned for revision 17 August 2007; finally revised 20 September 2007; accepted 25 September 2007) Introduction Anaemia represents a public health concern, following evidence that even mild forms are associated with decline in physical performance and increased morbidity and mortality in the elderly. 1–4 However, although the pathogenesis of transient anaemia is often clinically evident, chronic forms of anaemia, refractory to treatment, are often unexplained. 4,5 Unexplained anaemia is anaemia not related to evident causes of blood loss (e.g. gastrointestinal, urogenital, epistaxis) or to defined haematological diseases. 3–5 Chronic unexplained anaemia may be responsible for several common symptoms such as fatigue, skin pallor, asthenia, arrhythmias, and dyspnoea. 1,6 The presence of anaemia is also associated with worse cardiac clinical status, more severe systolic and diastolic dysfunction and may play a significant role as a pathogenic cofactor in coronary disease and heart ischaemia. 1,2,6 The presence of different forms of anaemia in thyroid disease has been described. 7–10 Early studies suggested overt and mild hypothyroidism as a cause of anaemia, because of the lack of thyroid hormone stimuli on erythropoiesis. 8,11 An increased prevalence of pernicious anaemia in autoimmune thyroid disease has also been described since the early sixties. 8,12,13 More recently, some studies have focused on anaemia as a marker of an occult chronic atrophic gastritis (CAG), 5,14,15 a disease involved in multiple autoimmune processes, including Hashimoto’s thyroiditis. 10,16 Evidence for an immunomodulatory involvement of cytokines (IFNγ, TNFα, hepcidin) in iron metabolism has also been provided in the anaemia of chronic disease. 17 So far, it appears that the presence of active autoimmune processes plays a role in the pathogenesis of some forms of chronic anaemias. However, despite the detrimental effects on patients’ health and quality of life and the frequent association between anaemia and autoimmune thyroid disease, its presence is often under recognized and sometimes neglected. These findings prompted us to assess the presence of chronic unexplained anaemia in autoimmune thyroid diseases (ATD). Subjects and methods A total of 1643 consecutive adult patients with thyroid disease, whose red cell count and characteristics were available, were retrospectively analysed in a referral centre for thyroid disease at the University of Rome ‘La Sapienza’. Of these, 652 patients were affected by autoimmune thyroid disease (71 had Graves’ disease and 581 had Hashimoto’s Correspondence: Prof Marco Centanni, c/o Dipartimento di Medicina Sperimentale, Policlinico Umberto I, 00161 Rome, Italy. Tel. and Fax: +39 06 49972604; E-mail: marco.centanni@uniroma1.it