Pembrolizumab-Induced Hypophysitis: A Rare Immune-Related Adverse Event in a Patient With Metastatic Non-small Cell...

Immune checkpoint inhibitors (ICIs), such as pembrolizumab, have revolutionized cancer treatment but are associated with immune-related adverse events (irAEs). Hypophysitis, though rare, is a serious endocrine complication that can lead to life-threatening adrenal insufficiency if not promptly recognized and treated. A 62-year-old man with metastatic non-small cell lung cancer presented with fatigue, headache, and hyponatremia after four cycles of pembrolizumab. Laboratory evaluation revealed secondary adrenal insufficiency (low cortisol and adrenocorticotropic hormone) and central hypothyroidism (low free thyroxine, T4, with inappropriately normal thyroid-stimulating hormone). Magnetic resonance imaging of the brain showed a normal pituitary gland. A diagnosis of pembrolizumab-induced hypophysitis was made based on clinical and biochemical findings. Pembrolizumab was temporarily withheld, and the patient was started on hydrocortisone and levothyroxine replacement. Symptoms improved within one week, and pembrolizumab was resumed without complications. This case highlights the importance of monitoring for endocrine irAEs in patients receiving ICIs, even without radiographic abnormalities. Early recognition and treatment are critical to reduce morbidity. Clinicians should suspect hypophysitis in patients presenting with nonspecific symptoms such as fatigue, headache, or hyponatremia during ICI therapy.