# Apalutamide‐Induced Hypothyroidism Associated With Increased Thyroid Hormone Clearance in Metastatic Prostate Cancer Patient: A Case Report

## TL;DR

A prostate cancer patient with a history of thyroidectomy experienced severe hypothyroidism after starting apalutamide treatment, highlighting the need for close thyroid monitoring.

## Contribution

This case report highlights apalutamide's rare but significant effect of increasing thyroid hormone clearance in patients with prior thyroidectomy.

## Key findings

- The patient's TSH levels rose despite increased levothyroxine dosage after apalutamide initiation.
- TSH improved rapidly after apalutamide withdrawal, suggesting a direct drug effect.
- The case underscores the need for close endocrine monitoring during apalutamide treatment in thyroid-compromised patients.

## Abstract

Apalutamide (APA) is an androgen receptor signaling inhibitor widely used for metastatic hormone‐sensitive prostate cancer (mHSPC), though it can induce hypothyroidism. We report a severe case of APA‐induced hypothyroidism in a patient with a history of total thyroidectomy.

A 65‐year‐old man receiving levothyroxine (175 μg/day) after thyroidectomy was diagnosed with mHSPC (Gleason score 4 + 4; PSA 13 904 ng/mL) with findings suggestive of cancer‐associated disseminated intravascular coagulation. Following APA initiation (240 mg/day), PSA decreased rapidly to 0.01 ng/mL. However, TSH levels rose progressively despite increasing levothyroxine to 275 μg/day. After a 4‐month follow‐up interruption, TSH reached 187.9 mIU/L. APA withdrawal led to rapid TSH improvement.

Careful TSH monitoring is essential during APA treatment, especially in patients with pre‐existing thyroid dysfunction or prior thyroidectomy. Appropriate levothyroxine titration and multidisciplinary collaboration are essential for the continuation of oncological therapy with APA.

We report a case of hypothyroidism, a rare adverse effect of apalutamide. In patients with pre‐existing thyroid disease, apalutamide treatment has been associated with increased thyroid hormone clearance, resulting in decreased serum thyroxine levels and elevated TSH. These findings underscore the importance of careful endocrine monitoring, such as during apalutamide treatment.