Endocrine Abstracts

Background: Apalutamide is known to cause hypothyroidism in 5-8% of people. Worsening of overt hypothyroidism is reported in 30% patients with pre-existing hypothyroidism. We report a case of worsening pre-existing hypothyroidism in a patient treated with Apalutamide.

Case Report: A 79-year-old male patient was referred to endocrine clinic for refractory hypothyroidism. He was diagnosed with prostate cancer in 2019 and had a long standing history of primary hypothyroidism treated with levothyroxine100micrograms daily. In March 2023, after being detected with metastatic prostate cancer, he was started on lifelong treatment with apalutamide. Preceding March 2023, he was biochemically euthyroid with normal TSH of 4.1 mU/l. However, his TSH elevated to 57 mU/L in April 2023 indicating worsening hypothyroidism. In response, levothyroxine dose was increased to 125 micrograms daily, but TSH remain elevated at 11.8mU/l despite his good compliance. Further increase in levothyroxine to 150 micrograms finally achieved biochemical euthyroidism with TSH level of 3.4mU/L

Conclusions: Apalutamide is non-steroidal, oral antiandrogen drug used in prostate cancer. Patients with pre-existing thyroid disorders are more prone to developing worsening hypothyroidism whilst on this therapy. Apalutamide increases the metabolism of levothyroxine by inducing uridine diphosphate-glucanosyltransferases which enhances the conjugation of levothyroxine with glucuronic acid, thereby promoting biliary excretion of thyroid hormones. This process reduces circulating thyroxine levels, leading to an elevation of TSH through a negative feedback mechanism. Hypothyroid patients on apalutamide may require a significant increase in their levothyroxine dosage to achieve biochemical euthyroidism, with some needing 2- to 3-fold increases. The impact of apalutamide on thyroid function is often underestimated, and regular monitoring of thyroid function tests is essential to adjust levothyroxine doses accordingly to maintain a euthyroid state.

Reference: 1. Daviduck Q, North S, Swaleh R. Hypothyroidism caused by apalutamide. CMAJ. 2023 Oct 30;195(42):E1443. doi: 10.1503