Inflammatory Signaling and Emotional Symptoms in Hashimoto's Thyroiditis beyond Thyroid Function Status

Patients with Hashimoto's thyroiditis (HT) frequently report persistent emotional and cognitive symptoms even when thyroid hormone levels are within the reference range. The mechanisms underlying these symptoms beyond thyroid function status remain incompletely understood. This study aimed to characterize the symptom profile of HT patients with thyroid hormone levels within the reference ranges and to investigate whether peripheral inflammatory signaling is associated with emotional symptoms independent of thyroid-related factors.

Clinical data were analyzed from 80 patients with HT whose free triiodothyronine and free thyroxine levels were within the reference ranges and who did not have suppressed thyroid-stimulating hormone (TSH). Thyroid-related quality of life was assessed using the Thyroid Patient-Reported Outcome-39 (ThyPRO-39). Serum interleukin-6 (IL-6) and interleukin-17 (IL-17) levels were measured by enzyme-linked immunosorbent assay. Associations between symptom dimensions, thyroid-related factors, and inflammatory markers were evaluated using multivariable linear regression models with log-transformed cytokine levels, adjusting for age, sex, elevated TSH, current levothyroxine sodium use, and thyroid autoantibodies.

Symptom profiling revealed that fatigue and emotional dimensions, including emotional susceptibility, anxiety, and depressivity, were the most prominently affected domains, whereas thyroid-related somatic and social functioning domains were relatively preserved. Neither elevated TSH, current levothyroxine sodium use, nor thyroid autoantibody levels showed significant independent associations with emotional symptom scores. In contrast, higher peripheral IL-6 levels were independently associated with increased emotional susceptibility, anxiety, and depressivity after adjustment for thyroid-related parameters. No consistent independent associations were observed between IL-17 levels and emotional symptom dimensions.

In patients with HT whose thyroid hormone levels are within the reference ranges, emotional symptoms are common and cannot be fully explained by TSH status, levothyroxine sodium use, or thyroid autoantibody levels. Peripheral inflammatory signaling, particularly IL-6, may be associated with emotional symptom burden beyond classical thyroid-related mechanisms, highlighting a potential neuroimmune pathway underlying persistent symptoms in HT.