High prevalence of autoimmune thyroid disease in subjects with sicca symptoms without Sjogren's syndrome

Sir, Autoimmune thyroid diseases (ATDs) are the most common autoimmune diseases associated with SS. Thyroid autoimmunity causes several forms of thyroiditis and may lead to hypothyroidism (Hashimoto’s thyroiditis) as well as Graves’ disease [1]. Sometimes, an onset of ATD precedes the diagnosis of SS. The aim of our study was to evaluate the prevalence of ATD in subjects with suspected SS and healthy volunteers as well as to compare the features of sicca syndrome in SS patients with ATD versus sicca subjects with ATD. The cross-sectional study included 305 subjects with sicca symptoms referred to the Institute of Rheumatology, Belgrade, from 2007 to 2011 and 54 asymptomatic healthy subjects. Informed consent was obtained and approval was given by the ethics committee of the Institute of Rheumatology, Belgrade. Symptoms of dry mouth and/or eyes were confirmed by the questionnaire, proposed by American–European Criteria (AEC) for SS [2]. These subjects were further examined by Schirmer-I test, sialoscintigraphy and biopsy of the minor salivary glands. Anti-SSA and anti-SSB antibodies were tested by ELISA. All subjects were screened for ATD. The diagnosis of Hashimoto’s thyroiditis and Graves’ disease was based on the presence of anti-thyroid peroxidase (TPO) antibody and thyroid stimulating hormone (TSH) receptor antibody. Additionally, serum thyrotropin (TSH) and thyroxine (T4) were measured. Of 305 subjects, 159 patients fulfilled the AEC for SS. Fifty-nine subjects with sicca symptoms without confirmed SS were classified as sicca subjects. Eighty-seven subjects were excluded due to exclusion criteria for SS (hepatitis C, lymphoma, other autoimmune diseases, etc.) according to AEC [2]. Asymptomatic healthy volunteers were labelled as HS. Statistical analysis was performed using SPSS, version 16.0. Groups were comparable regarding age and gender. Twenty-one (13.2%) out of 159 patients with SS had ATD. Twenty of them had Hashimoto’s thyroiditis, while one patient had Graves’ disease. Seventeen subjects (28.8%) among 59 sicca subjects had ATD. Fifteen of them had Hashimoto’s thyroiditis, while two subjects had Graves’ disease. The occurrence of ATD in SS patients and HS was similar (P = 0.33). The frequency of ATD was significantly higher in sicca subjects than in SS patients and HS (χ2, P = 0.007). Despite discrepancy in the ATD rate, the frequency of thyroid functional disturbance (hypothyreosis) was similar in the symptomatic groups: 7/20 patients in the SS group and 5/15 sicca subjects. All four (7.4%) subjects out of 54 HS with ATD had subclinical Hashimoto’s thyroiditis. The prevalence of clinical features of sicca syndrome in SS patients with ATD as well as in sicca subjects with ATD is shown in Table 1. There were no statistically significant differences in the frequencies of clinical features (P > 0.05). The prevalence of clinical features of sicca syndrome in the examined groups *P < 0.05: statistically significant. The prevalence of clinical features of sicca syndrome in the examined groups *P < 0.05: statistically significant. ATDs can develop either before or after the diagnosis of SS. In our study, ATD precedes SS in 13.2% of patients. This finding is consistent with previous research results that showed that 10–30% of SS patients suffer from ATD [3, 4]. However, most of these results had been published before the AEC for SS were established. Two of the largest studies used European Classification Criteria (ECC) for SS. In one of the studies, the prevalence of ATD in SS patients was 20% [5]. Another follow-up study found ATD to be more frequent in the SS patients than in the controls (30% vs 4%) [6]. AEC were used to diagnose SS in the present study. Our finding of 13.2% ATD among SS patients is comparable to the results of Biro et al. [7], who also used AEC for diagnosing SS. They found that the prevalence of ATD was 10%. We found a significantly higher prevalence of ATD in sicca subjects than in SS patients and HS (P < 0.01). Although ATD is a common diagnosis in clinical practice, the prevalence of ATD is not known in our country. On the other hand, we found no difference in the frequency of clinical features of sicca syndrome between SS patients with ATD and sicca subjects with ATD (P > 0.05). Based on similar clinical findings, ATD could be misdiagnosed as SS, and vice versa. Therefore the symptoms of dryness should always be given serious consideration as possible signs of either SS or ATD (sometimes both). High prevalence of ATD in sicca subjects suggests that all subjects with sicca symptoms should be screened for ATD. All authors included in the manuscript fulfil the criteria of authorship. V.D.M. is responsible for the design of the study, coordinated and participated in data management and prepared the manuscript for publication as well as drafted the manuscript. G.R. participated in the design of the study and data management, performed statistical analyses and drafted the manuscript. Biopsy specimens of minor salivary glands were evaluated by I.B. and diagnosis autoimmune thyroid disease was confirmed by S.O. R.P. participated in analysis and interpretation of data. M.R.-P. and N.V.-S. participated in data management. N.D. participated in the design of the study, interpretation of data and approved the final version of the manuscript. Disclosure statement: The authors have declared no conflicts of interest.