Exacerbation of Pre-existing Hypothyroidism Following Enarodustat Administration in a Patient on Peritoneal Dialysis: A Case Report.

Hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitors are widely used to treat renal anemia in patients with chronic kidney disease (CKD). While roxadustat, an HIF-PH inhibitor, is known to induce central hypothyroidism via thyroid hormone receptor-beta agonism, thyroid dysfunction associated with other HIF-PH inhibitors, such as enarodustat, remains unrecognized. We report the case of a 32-year-old male on peritoneal dialysis (PD) with underlying subclinical mild primary hypothyroidism and erythropoiesis-stimulating agent (ESA)-resistant renal anemia secondary to primary hyperparathyroidism. Following a switch from ESAs to enarodustat and its subsequent dose escalation (up to 6 mg/day), the patient experienced severe exacerbation of hypothyroidism characterized by markedly elevated thyroid-stimulating hormone (TSH: 139 µIU/mL) and decreased free thyroxine (FT4: 0.42 ng/dL), culminating in acute decompensated heart failure that required emergency admission and temporary hemodialysis. Initial emergency management with blood purification therapy successfully stabilized his respiratory status, whereas treatment with levothyroxine alone had failed to control his TSH levels. Discontinuation of enarodustat, combined with levothyroxine titration, led to a gradual restoration of thyroid function and resolution of systemic symptoms, allowing the successful resumption of PD. Unlike the central hypothyroidism caused by roxadustat, enarodustat may have contributed to the exacerbation of pre-existing hypothyroidism, suggesting a distinct pathophysiological mechanism, such as impaired thyroid hormone synthesis or secretion. To our knowledge, this is the first report demonstrating that a non-roxadustat HIF-PH inhibitor, enarodustat, could cause severe exacerbation of hypothyroidism in a CKD patient. These findings highlight the critical need to closely monitor thyroid function when prescribing any HIF-PH inhibitor, particularly in patients with pre-existing thyroid disorders.