SAT-439 Atezolizumab-Induced Hypophysitis: A Case of Endocrine Dysfunction in Cancer Therapy

Abstract Disclosure: M. Shah: None. R. Devbhandari: None. C. Bhimineni: None. R.M. Jhingan: None. Background: Atezolizumab, a PD-L1 inhibitor, enhances T-cell activity to improve anti-cancer responses by preventing tumor immune evasion. While effective in treating various cancers, atezolizumab can cause immune-related adverse events (irAEs), including endocrine dysfunctions such as hypophysitis. This case report describes atezolizumab-induced hypophysitis, resulting in secondary adrenal insufficiency and central hypothyroidism, which are rare but potentially severe complications. It emphasizes the importance of early recognition and management of these life-threatening endocrine abnormalities. Case Presentation A 67-year-old male with stage II squamous cell lung carcinoma underwent resection, adjuvant chemotherapy, and atezolizumab therapy. Six months later, he presented with altered mental status, weakness, and severe hyponatremia. Differential diagnoses included SIADH, paraneoplastic syndrome, and adrenal insufficiency. Diagnostic evaluation revealed secondary adrenal insufficiency and central hypothyroidism. Morning serum cortisol was <0.1 mcg/dL (normal 5-25 mcg/dL), with low ACTH, confirming secondary adrenal insufficiency. Free T4 was low, with normal TSH, confirming central hypothyroidism. MRI revealed pituitary enlargement and homogeneous contrast enhancement, consistent with hypophysitis. The patient was started on hormone replacement therapy with hydrocortisone and levothyroxine, resulting in significant improvement in his symptoms and clinical status. The patient’s quality of life improved as his energy levels and cognition returned to baseline, and he was able to continue cancer treatment without further complications. Conclusion: Atezolizumab-induced hypophysitis, although rare, can lead to severe and life-threatening endocrine dysfunctions. Symptoms such as fatigue, altered mental status, and hyponatremia can complicate diagnosis, and MRI findings vary from early stages with pituitary enlargement and enhancement, to later stages with atrophy or an empty sella. Early initiation of glucocorticoid and thyroid hormone replacement is critical for preventing morbidity and enabling continued cancer treatment. Adrenal insufficiency is often permanent, while central hypothyroidism may be transient. Long-term endocrine follow-up is necessary for managing hormone replacement therapy and adjusting dosages. This case underscores the importance of recognizing atezolizumab-induced hypophysitis as a serious irAE and highlights the need for early diagnosis and prompt intervention. By addressing these complications in a timely manner, clinicians can minimize complications and help ensure that patients can continue their cancer therapy without interruptions. Long-term follow-up care is essential for proper hormone replacement and improving the patient’s health and quality of life during and after treatment. Presentation: Saturday, July 12, 2025