Endocrine Abstracts

Introduction and Aim: Obesity is associated with an increased risk of hypothyroidism and chronic autoimmune thyroiditis (AIT). However, little is known about the underlying pathogenic mechanisms. Recently it has been evaluated the role played by sex hormones in the onset of AIT and, analysing the data from a large cohort of normal/overweight males, a positive correlation between an increased ratio of estradiol/testosterone levels (E2/T) and AIT was found. Since obese males are more likely to have decreased testosterone and increased circulating estradiol levels, we investigated whether there was a causal relationship between an imbalance of the E2/T ratio and AIT in obese male patients.

Patients and Methods: We retrospectively evaluated anthropometric data (weight, height, BMI), thyroid assessment (thyroid ultrasonography and TSH, FT3, FT4, TgAb, TPOAb levels) and gonadal hormones [total testosterone (T), estradiol (E2), gonadotropins] of 337 obese male patients (age: 50±11.5 years, BMI: 46±7.6 Kg/m2). AIT was defined in different ways: the serum TPOAb and/or TgAb positivity (>100 IU/mL) and/or characteristic US features (diffuse parenchymal hypoechogenicity and/or heterogeneous echogenic pattern of the thyroid gland) and/or hypothyroidism.

Results: AIT prevalence in our cohort was 6.5%. The prevalence of AIT did not correlate with age (P = 0.9), BMI (P = 0.9), hypogonadism (P = 0.7), E2 (P = 0.1) and T (P = 0.4) levels, while an increased E2/T ratio was observed in subjects with AIT, although this difference was not statistically significant (P = 0.07). By ROC curve analysis (AUC 0.614; CI 95%:0.51-0.73, P = 0.045) we identified a E2/T ratio cut-off value significantly associated with AIT: 63.6% of subjects with E2/T ≥18.8 had AIT while this was observed only in 36.4% of subjects with a E2/T ratio <18.8 (P = 0.035). This cut-off also predicted the absence of AIT with an excellent diagnostic accuracy (96% NPV). Then we carried out a multivariate statistical analysis and the E2/T ratio ≥18.8 was confirmed as a parameter independently associated with AIT (OR 2.80; CI 95%:1.17-7.21, P = 0.024).

Conclusions: Our results suggest that higher E2/T ratios were significantly associated with AIT among obese male patients. Since estrogens and androgens play an important role in autoimmunity due to their capacity of modulating the immune response via estrogen and androgen receptors, such mechanisms could provide a possible explanation for the correlation between the imbalance of the physiological E2/T ratio and the higher prevalence of AIT observed in obese male patients.