Reduced Circulating MOTS-c Levels in Hashimoto's Thyroiditis Reflect Integrated Autoimmune and Metabolic Dysregulation: A Cross-Sectional Study.

This cross-sectional study investigated circulating levels of MOTS-c — a mitochondria-derived peptide involved in metabolic and immune regulation — in patients with Hashimoto's thyroiditis (HT) compared to healthy controls. A total of 180 participants (90 HT patients and 90 age- and sex-matched healthy controls) were enrolled. The study found that circulating MOTS-c levels were significantly lower in HT patients than in controls. Lower MOTS-c levels were independently associated with insulin resistance and markers of autoimmune burden (such as thyroid autoantibodies). The authors propose that impaired mitochondrial signaling, as reflected by reduced MOTS-c, may contribute to the pathophysiology of thyroid autoimmunity and metabolic dysregulation seen in HT. The study's cross-sectional design limits causal inference — it is unclear whether reduced MOTS-c is a cause or consequence of HT. Additional limitations include the single-timepoint measurement, potential confounders not fully addressed, and the absence of longitudinal follow-up. The findings position MOTS-c as a candidate biomarker linking metabolic dysfunction and immune dysregulation in thyroid autoimmunity, though further prospective and mechanistic research is needed to confirm this relationship.

Why this grade: Cross-sectional design in a modest sample (n=180) establishes association but cannot determine causality, and single-timepoint measurement limits conclusions about MOTS-c's role in HT pathophysiology.