Hypothyroidism caused by apalutamide

Apalutamide is an oral, nonsteroidal anti-androgen drug that delays disease progression and improves metastases-free and overall survival when added to androgen deprivation therapy in patients with nonmetastatic castration-resistant and metastatic castration-sensitive prostate cancer. Apalutamide is commonly dosed at 240 mg/d and continued for a median duration of 3.5 years. Hypothyroidism occurs in 5.7%-8% of patients taking apalutamide. Patients with pre-existing hypothyroidism are more susceptible to the drug's thyroid effects; worsening hypothyroidism was observed in 30% of these patients. The development of hypothyroidism does not necessitate a dose decrease of apalutamide. Most patients' TSH levels rise at a median time of 113 days. Baseline TSH should be checked before apalutamide is initiated. In clinical trials, TSH levels were monitored every 4 months. Repeating a TSH level sooner is appropriate if signs or symptoms of hypothyroidism develop. Apalutamide induces uridine diphosphate--glucuronyltransferases, catalyzing the attachment of glucuronic acid to levothyroxine and promoting biliary excretion of thyroid hormones, which increases TSH levels through negative feedback. Small case series have shown that a 2- to 3-fold increase in levothyroxine may be needed to achieve a euthyroid state in patients with pre-existing hypothyroidism.