#4846 roxadustat-induced hypothyroidism: the effect of roxadustat on suppression of thyroid function

Abstract Background and Aims There have been only two case reports of hypothyroidism in patients treated with roxadustat, a HIF-PH inhibitor as new renal anemia drug. However, there has yet been no studies to examine the effect of roxadustat on thyroid function. Method In this study, we retrospectively examined the effects of roxadustat on thyroid-stimulating hormone (TSH) in hemodialysis patients by two blood examinations, before and during treatment with roxadustat. We included patients who had TSH levels measured after at least two consecutive weeks of roxadustat treatment and before. We excluded patients with a history of taking other HIF-PH inhibitors before roxadustat. The period was from September 2021 to November 2022 in this interim analysis. A p value of<0.05 was considered statistically significant. Analyses were performed using SPSS. Results 93 patients were included in this analysis. TSH levels significantly decreased after treatment with roxadustat. A total of 58.1% of patients had decreased TSH levels (2.23 ± 1.18 v.s. 1.81 ± 1.35, μIU/mL, p value = 0.040, Wilcoxon signed-rank test), and 18.3% of patients had a significant decrease below the normal range. Additionally, patients treated with thyroid hormone replacement therapy in primary hypothyroidism had a higher frequency (81.0%) of TSH decrease compared to patients without (p value = 0.013, Pearson's chi-square test). Conclusion This is the first study to examine that roxadustat has a suppressive effect on TSH secretion in hemodialysis patients. We also found that roxadustat-induced hypothyroidism is prevalent in the high frequency of TSH suppression, especially in primary hypothyroidism patients treated with thyroid hormone replacement therapy. Thyroid hormone receptor beta (THRβ), which is expressed in the hypothalamus and pituitary gland, plays an important role in regulating thyroid hormone through feedback mechanisms. Yao et al. have reported that roxadustat has a similar structure to T3 and acts as a THRβ-selective ligand, particularly activating THRβ. Therefore, it is possible that roxadustat suppresses TSH secretion through negative feedback via THRβ. It is important to monitor thyroid function in patients receiving roxadustat. Roxadustat should be avoided in patients with primary hypothyroidism, since it is inferred that roxadustat-induced hypothyroidism cannot be improved by enhancement of thyroid hormone replacement therapy.