Interleukin-1 receptor antagonist and heat shock protein 90alfa are independently associated with fatigue and general health in euthyroid Hashimoto's thyroiditis.

BACKGROUND: Patients with Hashimoto's thyroiditis frequently experience fatigue and impaired health-related quality of life (HRQOL) despite biochemical euthyroidism, suggesting that immune-mediated mechanisms beyond thyroid hormone deficiency contribute to symptom generation. The role of specific inflammatory mediators - including interleukin-1 receptor antagonist (IL-1Ra), heat shock protein 90α (HSP90α), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and anti-TPO antibodies - in relation to patient-reported outcomes (PROMs) has not been systematically examined.

METHODS: In a cross-sectional study of 36 euthyroid patients with confirmed Hashimoto's thyroiditis, serum/plasma levels of IL-1Ra, HSP90α, IL-6, and TNF-α were measured alongside anti-TPO. PROMs included the SF-36 General Health subscale (inverted; iGH), the Fatigue Visual Analog Scale (fVAS), and the Fatigue Severity Scale (FSS). Spearman correlations, univariable and multivariable linear regression, and principal component analysis (PCA) were applied.

RESULTS: The cohort displayed severe fatigue at baseline (median fVAS 85, FSS 6.7, SF-36 GH 16). IL-1Ra was the most consistent biomarker correlate of symptom burden, independently associated with poorer general health and more fatigue across all regression models. HSP90α showed an inverse and independent association with fatigue in multivariable models, suggesting a potentially protective role. IL-6 contributed in correlation analysis only, while TNF-α and anti-TPO were not significantly associated with any PROM in any analytical approach.

CONCLUSION: IL-1Ra and HSP90α, but not anti-TPO, are independently associated with fatigue and general health in euthyroid Hashimoto's thyroiditis, pointing to IL-1 pathway activity as associated with symptom burden and potentially playing a key role in this condition.