Apalutamide-induced severe hypothyroidism: case series and practice recommendations for thyroid management

The androgen receptor signaling inhibitor apalutamide is used successfully for the treatment of prostate cancer. An increased risk of hypothyroidism, mostly subclinical, has been reported in the SPARTAN and TITAN trials. We present three cases of subacute deterioration of previously known but well-controlled hypothyroidism treated with levothyroxine, occurring shortly after the initiation of treatment with apalutamide, resulting in severe hypothyroidism. These cases highlight the importance of awareness of thyroid dysfunction during treatment with apalutamide, particularly in patients with pre-existing thyroid disease, common in the general population. We provide practice recommendations for thyroid management prior to and during apalutamide treatment as well as after the interruption of this therapy.