CLINICAL STUDY High prevalence of autoimmune thyroiditis in patients with polycystic ovary syndrome Onno E Janssen, Nadine Mehlmauer 2 , Susanne Hahn, Alexandra H O ¨ ffner 1 and Roland Ga ¨rtner 2 Division of Endocrinology, Department of Medicine, University of Essen, Essen, Germany, 1 Division of Angiology, Department of Medicine, Hospital Schwabing, Munich, Germany and 2 Division of Endocrinology, Department of Medicine, Ludwig-Maximilians-University, Munich, Germany (Correspondence should be addressed to Roland Ga ¨rtner, Division of Endocrinology, Department of Medicine, Ludwig-Maximilians-University, Ziemssenstr. 1, 80336 Munich, Germany; Email: roland.gaertner@medinn.med.uni-muenchen.de) Abstract Objective: To investigate the prevalence of autoimmune thyroiditis (AIT) in patients with polycystic ovary syndrome (PCOS). Design: Over a period of 30 months, 175 patients with PCOS were recruited to a prospective multi- center study to evaluate thyroid function and morphology; 168 age-matched women without PCOS were studied as a control group. Methods: PCOS was defined as a- or oligomenorrhea, hyperandrogenism and exclusion of other dis- turbances of estrogen or androgen synthesis. All laboratory parameters were determined with auto- mated immunoassays. Thyroid morphology was assessed by ultrasound. Results: PCOS patients were characterized by an increased LH/FSH ratio, low progesterone, elevated testosterone and a high prevalence of hirsutism (PCOS 83%, control 3%; mean hirsutism score 12^5 and 3^2 respectively), but no differences in estrogen levels were found. Thyroid function and thyroid- specific antibody tests revealed elevated thyroperoxidase (TPO) or thyroglobulin (TG) antibodies in 14 of 168 controls (8.3%), and in 47 of 175 patients with PCOS (26.9%; P , 0.001). On thyroid ultra- sound, 42.3% of PCOS patients, but only 6.5% of the controls (P , 0.001) had a hypoechoic tissue typical of AIT; while thyroid hormone levels were normal in all subjects, PCOS patients had a higher mean TSH level (P , 0.001) and a higher incidence of TSH levels above the upper limit of normal (PCOS 10.9%, controls 1.8%; P , 0.001). Conclusion: This prospective study demonstrates a threefold higher prevalence of AIT in patients with PCOS, correlated in part with an increased estrogen-to-progesterone ratio and characterized by early manifestation of the disease. European Journal of Endocrinology 150 363–369 Introduction Chronic autoimmune thyroiditis (AIT, Hashimoto’s thy- roiditis) is a common disease and the most prevalent cause of hypothyroidism in areas with sufficient iodine intake. Its two major forms, goitrous and atropic AIT, are both characterized by gradual thyroid dysfunc- tion. Nearly all patients have high serum levels of anti- bodies against one or more thyroid antigens, lymphocytic infiltration of the thyroid, and a typical hypoechoic pattern on thyroid ultrasound (1). The cause of AIT is thought to be a combination of gen- etic susceptibility and environmental factors. AIT clus- ters in families, either alone or in combination with Graves’ disease, and these two autoimmune thyroid dis- orders may evolve into one another. Genetic susceptibility to AIT is also obvious from its increased fre- quency in patients with Down’s and Turner’s syndrome (2). The prevalence of AIT has been correlated with the HLA DR3 and DR5 genes (3) and certain alleles of CTLA-4, a T-cell surface molecule involved in T-cell acti- vation (4). However, the development of AIT cannot be predicted from susceptibility genes alone. Environmental factors contributing to the develop- ment of AIT are viral infections, stress and sex steroid hormones, of which the latter appear to be the most important (5). Compared with men, the five- to tenfold higher prevalence of AIT in women has been correlated to their high estrogen levels, which are implicated as enhancers of humoral immunity, while androgens and progesterone are thought to be protective as natu- ral immune suppressors (6). The striking preponder- ance of autoimmune diseases has also been shown in several animal models, in which estrogens promote, whereas androgens abrogate, B-cell-mediated auto- immune diseases (7, 8). Autoimmune responses are also controlled by complex interactions of cytokines, exemplified by the predisposition to autoimmunity European Journal of Endocrinology (2004) 150 363–369 ISSN 0804-4643 q 2004 Society of the European Journal of Endocrinology Online version via http://www.eje.org