BACKGROUND: Thyroid hormone (TH) sensitivity at type 1 diabetes mellitus (T1DM) onset and its connection with acute kidney injury (AKI) has not been investigated. We aimed to evaluate changes in TH sensitivity in children with and without AKI at T1DM onset and to assess the role of euthyroid sick syndrome (ESS) in this relationship. METHODS: We included 161 children with new-onset T1DM and followed them until renal function normalized. The free triiodothyronine (FT3)/free thyroxine (FT4) ratio was used to assess peripheral TH sensitivity, while the TSH index (TSHI), thyrotroph T4 resistance index (TT4RI), thyrotroph T3 resistance index (TT3RI), Thyroid Feedback Quantile-based Index (TFQI), and parametric TFQI (PTFQI) were used for central sensitivity. RESULTS: Patients with AKI exhibited greater weight loss, higher serum ketones, creatinine, corrected sodium, and glycated hemoglobin, but lower bicarbonate and estimated glomerular filtration rate compared to those without AKI. Logistic regression showed that the odds of AKI increased by 11.5-fold for each unit decrease in TFQI, 4.0-fold per unit decrease in PTFQI, and 1.7-fold per unit decrease in TSHI, adjusting for age and gender. After adjusting for age, gender, and ESS, the odds for AKI significantly increased (4.8-fold for each 1-unit decrease) only for TFQI. CONCLUSIONS: AKI at the onset of T1DM has a dual effect on TH. It reduces peripheral sensitivity while increasing central sensitivity. This effect appears to be largely driven by ESS, with the exception of the association between AKI and TFQI, which remains independent of ESS.