AUTHOR=Ren Yuqian , Liu Zhenchao , Wang Meng , Wang Yanzhi , Wang Yun TITLE=Acute immunometabolic changes in first-presentation Graves’ hyperthyroidism patients undergoing strenuous physical activity JOURNAL=Frontiers in Endocrinology VOLUME=Volume 16 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2025.1685496 DOI=10.3389/fendo.2025.1685496 ISSN=1664-2392 ABSTRACT=ObjectiveThis study systematically evaluated immunometabolic responses in newly diagnosed female Graves’ hyperthyroidism patients versus healthy controls following repeated high-intensity intermittent exercise (HIIE, Wingate test). It also preliminarily explored the associations of thyroid hormone levels and muscle mass with these responses.MethodsWe enrolled 25 newly diagnosed female Graves’ hyperthyroidism patients (observation group) and 25 healthy women (control group). All participants underwent three HIIE. Blood samples, collected before and immediately after the third test, were analyzed for glucose, lactate, leptin, irisin, creatine kinase (CK), interleukin-6 (IL-6), interleukin-15 (IL-15), and tumor necrosis factor-alpha (TNF-α) levels. Baseline skeletal muscle index (SMI) and thyroid hormone levels were also measured. Data were analyzed using repeated measures ANOVA, Bayesian repeated measures ANOVA, and Bayesian network analysis.ResultsBaseline data indicated that the observation group exhibited significant higher free triiodothyronine (FT3) and free thyroxine (FT4), and lower thyroid-stimulating hormone (TSH) (P < 0.001). Additionally, this group demonstrated a markedly reduced SMI. (P = 0.005). Both peak and mean HIIE power significant decreased with increasing repetitions in both groups (P < 0.001). While peak power decline showed no significant group difference, mean power decline revealed a significant “Times x Group interaction” (P < 0.001), indicating distinct fatigue patterns. Metabolically, lactate and glucose significant increased post-HIIE in both groups (P < 0.001), with no significant group differences in their trends. Leptin significant increase in both groups (P < 0.001), and Bayesian analysis indicated significant inter-group differences. CK and irisin significant increased post-HIIE (P < 0.001) with no significant group differences in levels or trends. Inflammatory markers showed that IL-6 had a significant average level difference between groups (P < 0.001) and increased significant post-HIIE (P < 0.001), with a significant interaction in its increase trend (P = 0.017). IL-15 and TNF-α exhibited significant average level differences (P < 0.05) but no significant post-HIIE changes or group differences in trends. Bayesian network analysis in the hyperthyroidism group revealed complex interrelationships among FT3, FT4, TSH, IL-15, leptin, IL-6, and TNF-α, with TSH significant regulating inflammatory responses and SMI potentially influencing pre- and post-exercise glucose levels. The control group network was simpler.ConclusionThis study, for the first time, systematically evaluated immunometabolic responses in female Graves’ hyperthyroidism patients following HIIE. While muscle loss in newly diagnosed hyperthyroidism patients did not significant impair short-term explosive power, it may reduce endurance during sustained high-intensity exercise. The hyperthyroid state markedly altered exercise-induced immunometabolic dynamics, underscoring the need for comprehensive consideration of hyperthyroidism’s complex physiological impact when designing personalized exercise regimens.