Nrf2, gp91phox and IL-17 are associated with severity and clinical outcomes of patients with subclinical hypothyroidism: a comparative study

Abstract

The mechanisms underlying subclinical hypothyroidism (SCH) remain unclear, making timely and accurate differentiation between hypothyroidism and SCH, as well as severity assessment, challenging. This study aimed to investigate the role of NFE2 like bZIP transcription factor 2 (Nrf2), gp91phox, and interleukin-17 (IL-17) in the pathogenesis of SCH. In this prospective comparative study, 105 SCH patients, 105 hypothyroidism patients, and 105 healthy individuals were enrolled from January 2022 to August 2023. SCH patients were categorized into mild-moderate and severe groups based on thyroid-stimulating hormone (TSH) levels. Levels of TSH, free T4 (FT4), free T3 (FT3), thyroglobulin antibodies (TG-Ab), thyroid peroxidase antibodies (TPO-Ab), cholesterol (TC), triglycerides (TG), high-density lipoprotein-cholesterol (HDL-ch), and low-density lipoprotein-cholesterol (LDL-ch) were measured. Nrf2, IL-1β, IL-6, IL-17, and gp91phox levels were tested using ELISA. Nrf2, IL-17 and gp91phox were significantly higher in SCH and hypothyroidism patients compared to the healthy controls, with hypothyroidism patients showing the highest levels. Nrf2 levels were negatively correlated with TSH, TG-Ab and IL-17, but not gp91phox. Nrf2, IL-17 and gp91phox could be used for diagnosis of SCH and severe SCH. Only TG-Ab, IL-17 and gp91phox were independent risk factors for severe SCH. This study demonstrates a negative correlation between serum Nrf2 levels and SCH severity. TG-Ab, IL-17, and gp91phox are independent risk factors, and their associations with SCH pathology suggest their potential roles in the disease mechanism. These findings provide insights into SCH pathogenesis and highlight the need for further research to elucidate their diagnostic or prognostic significance.