Background <p>Destructive thyroiditis is among the most frequent endocrine adverse events of immune checkpoint inhibitors (ICIs). Most reports focus on thyroid dysfunction; less is known about how ICI-induced destructive thyroiditis may remodel thyroid architecture and alter pre-existing nodular disease.</p> Patient findings <p>A 56-year-old woman with a previously documented high-risk thyroid nodule (13 mm, EU-TIRADS 5) was diagnosed with triple-negative breast cancer and started on neoadjuvant therapy including pembrolizumab. Several months into therapy, pre-operative routine testing revealed de novo asymptomatic overt primary hypothyroidism (TSH 123 mIU/L, fT4 0.14 ng/dL), leading to postponement of breast surgery. Levothyroxine was initiated (100 µg/day), normalizing fT4 within 2 weeks and allowing surgery to proceed, while TSH remained markedly elevated. Thyroid autoantibodies were negative; ICI-induced destructive thyroiditis was presumed. Follow-up ultrasound, performed for planned fine-needle aspiration of the EU-TIRADS 5 nodule, showed a markedly atrophic thyroid gland with no residual suspicious nodules, with the previously documented high-risk nodule no longer detectable. These changes were interpreted as sequelae of destructive thyroiditis. The patient remains asymptomatic on stable levothyroxine replacement, with controlled hypothyroidism, and no breast cancer recurrence at last follow-up.</p> Conclusions <p>This case highlights that ICI-induced destructive thyroiditis can not only cause severe hypothyroidism but also dramatically remodel thyroid morphology, including regression of an EU-TIRADS 5 nodule. It also illustrates a real-world perioperative dilemma, namely, whether normal fT4, despite very high TSH, is sufficient to proceed with major surgery. Finally, it raises questions about optimal follow-up when a suspicious nodule vanishes following ICI-related thyroiditis.</p>