SAT-436 The Long Shadow of Immune Checkpoint inhibitors: Adrenal Insufficiency After Pembrolizumab

Abstract Disclosure: K. Zulqadar: None. S. Iftikhar: None. T. Jain: None. A. Khan: None. F. Wazin: None. Introduction: Pembrolizumab is an immune checkpoint inhibitor targeting programmed death receptor-1 (PD-1), widely used for advanced renal cell carcinoma. While generally well tolerated, it can cause immune-related adverse events (irAEs) affecting the thyroid, pituitary, adrenal glands, and pancreatic islet cells. Adrenal insufficiency (AI) is a rare but serious complication, often resulting from hypophysitis or direct adrenal dysfunction. We present a case of late-onset AI following pembrolizumab therapy. Case description: A 57-year-old male with a history of stage III right renal cell carcinoma was treated with pembrolizumab as adjuvant immunotherapy. His treatment was discontinued after he developed by cytokine release syndrome as an irAEs, requiring high-dose prednisone, which was gradually tapered over two months. Shortly after completing his steroid taper, he presented to the emergency department with profound fatigue, nausea, andgeneralized weakness. He denied fever, headache, chest pain, or shortness of breath. Initial laboratory evaluation revealed severe hyponatremia (serum sodium 108 mEq/L). Endocrine workup during admission demonstrated adrenal insufficiency, with early morning cortisol of 0.8 µg/dL. An ACTH stimulation test showed an inadequate cortisol response, and ACTH was 5 pg/mL, confirming secondary adrenal insufficiency as an irAE secondary to pembrolizumab. He was started on stress-dose steroids, which were gradually tapered to hydrocortisone 20 mg twice daily, leading to resolution of symptoms. Discussion: Pembrolizumab, a PD-1 receptor inhibitor, is widely used to treat various malignancies but can cause immune-related adverse events (irAEs), including adrenal insufficiency (AI). AI commonly presents with fatigue, nausea, hypotension, and electrolyte abnormalities, diagnosed with abnormal morning cortisol levels and ACTH stimulation tests. In cases of low ACTH levels, secondary AI due to hypophysitis should be suspected, while elevated ACTH indicates primary AI due to direct adrenal dysfunction. Hypophysitis is a rare but serious irAE that may require lifelong glucocorticoid therapy. While AI typically develops during treatment, delayed presentation post therapy is uncommon. Given the potential for delayed AI onset, routine post-treatment cortisol monitoring should be considered. Early recognition and prompt glucocorticoid replacement are crucial to preventing adrenal crisis, a life-threatening complication. Presentation: Saturday, July 12, 2025