MON-454 Pembrolizumab Induced Hypothyroidism in a Patient With Triple-Negative Breast Cancer

Abstract Disclosure: N. Seth: None. T. John: None. G. Patel: None. P. Lekprasert: None. K.K. Win: None. Introduction: Pembrolizumab, a humanized immunoglobulin G4 (IgG4) monoclonal antibody, is an immune checkpoint inhibitor (ICI) that functions by blocking the programmed cell death protein 1 (PD-1) receptors on lymphocytes. Many immune-related adverse events affecting the skin, gastrointestinal tract, liver, and endocrine system are associated with ICIs and occur in 20% of patients, with thyroid disorders (hypothyroidism, 8%, hyperthyroidism, 6%) being the most frequently occurring adverse events caused by pembrolizumab. The pathogenesis remains unclear; some studies suggest that ICIs may provoke autoimmune reactions in the thyroid gland or that ICIs may change thyroid-related gene expression, causing hypothyroidism. Here, we report a case of pembrolizumab-induced hypothyroidism. CASE PRESENTATION: The patient is a 76-year-old woman with a past medical history of hypertension who was diagnosed with synchronous bilateral stage IIb triple-negative breast cancer after abnormal findings were detected on a screening mammogram. She was started on neoadjuvant chemotherapy with four cycles of carboplatin, paclitaxel, and pembrolizumab, followed by four cycles of adriamycin, cyclophosphamide, and pembrolizumab. After her fifth cycle of chemotherapy, she developed severe fatigue that worsened throughout the remainder of her chemotherapy course. A thyroid stimulaiting hormone (TSH) was obtained after her 8th cycle and was noted to be elevated at 74.73 mIU/mL. She had no other symptoms of hypothyroidism, no history of prior radiation exposure, and her family history was significant only for a benign thyroid nodule in her sister. Her hypothyroidism was deemed likely to be immune-therapy mediated. She was started on levothyroxine 100mcg daily with subsequent improvement in fatigue. She was continued on chemotherapy with maintenance pembrolizumab every three weeks. A repeat TSH after 5 months of treatment with levothyroxine was 3.13 mIU/mL. The patient remained clinically euthyroid, allowing for the completion of pembrolizumab therapy as was initially planned. CONCLUSION: Our case report underscores the importance of early recognition of thyroid dysfunction in patients started on ICIs, particularly pembrolizumab. To allow for uninterrupted oncologic treatment, periodic evaluation and prompt treatment of thyroid dysfunction are indicated in patients undergoing immunotherapy with pembrolizumab. Presentation: Monday, July 14, 2025