2022 Volume 11 Issue 2 Pages 179-183
We present a case in which serum thyroid-stimulating hormone (TSH) level is decreased by treatment with roxadustat but not with daprodustat, both of which are hypoxia-inducible factor-prolyl hydroxylase (HIF-PH) inhibitors.
The patient was a woman in her 90s with chronic kidney disease G5 and no previous indication of thyroid function abnormalities. She was sequentially treated with daprodustat, darbepoetin alfa, and then roxadustat for renal anemia. During treatment with daprodustat, TSH and free thyroxine (FT4) levels were 5.950 μIU/mL and 0.77 ng/dL, respectively. After initiating hemodialysis therapy, daprodustat was switched to darbepoetin alfa. During this phase of treatment, TSH and FT4 levels were 2.830 μIU/mL and 1.14 ng/dL, respectively. Hemoglobin remained low (7.9-9.8 g/dL), so darbepoetin alfa was replaced with roxadustat. Approximately 4 days after initiating roxadustat, fatigue appeared. On day 15 of roxadustat therapy, the patient experienced depressive symptoms such as suicidal ideation and hemodialysis refusal. Based on these symptoms and previous reports, roxadustat-related hypothyroidism was suspected. On day 16 after roxadustat initiation, TSH and FT4 levels were 0.051 μIU/mL and 0.77 ng/dL, respectively, revealing a marked decrease in TSH level. On day 21, roxadustat treatment was terminated. Approximately 7 days later, fatigue was reduced. By day 19 following roxadustat discontinuation, TSH level returned to within normal range.
Roxadustat has a chemical structure similar to tri-iodothyronine, potentially acts on thyroid hormone receptors in the hypothalamus and pituitary gland, and suppresses TSH secretion. This case revealed that the TSH-lowering effect may not be a common phenomenon among all HIF-PH inhibitors. After initiation of roxadustat, we recommend that thyroid related testing be performed and symptoms associated with abnormal thyroid function monitored.
