Probable Hypophysitis Recognized More Than Two Years After Pembrolizumab Discontinuation

Immune checkpoint inhibitor-associated hypophysitis is an uncommon but clinically important endocrine immune-related adverse event. We report a 70-year-old man with a history of non-small cell lung cancer previously treated with approximately two years of pembrolizumab, with his last dose administered approximately 28 months before presentation. He developed progressive fatigue, anorexia, hypotension, functional decline, and confusion and was subsequently hospitalized with multifocal pneumonia and septic shock. Although the infection and hemodynamic instability improved, encephalopathy, weakness, poor oral intake, and dysphagia persisted. Brain magnetic resonance imaging demonstrated new pituitary enlargement compared with imaging obtained approximately three months earlier. Dedicated pituitary imaging showed enlargement measuring approximately 1.5 × 2.0 cm without definite differential enhancement to suggest a pituitary adenoma. Endocrine testing demonstrated a cortisol level of 3.3 µg/dL with an inappropriately low adrenocorticotropic hormone level of 6.5 pg/mL, free thyroxine of 0.36 ng/dL with thyroid-stimulating hormone of 2.0 µIU/mL, suppressed gonadotropins, and testosterone <10 ng/dL, supporting central adrenal insufficiency and central hypothyroidism with marked gonadal-axis suppression. Cerebrospinal fluid cytology and paraneoplastic studies were unrevealing. The patient was treated with hydrocortisone before thyroid hormone replacement and subsequently showed progressive improvement in mental status, oral intake, and participation in rehabilitation. This case highlights that pituitary immune-related adverse events may be recognized long after pembrolizumab discontinuation and emphasizes the importance of considering prior immune checkpoint inhibitor exposure in patients with unexplained endocrine and constitutional decline.