SAT-433 - Central Adrenal Insufficiency Triggered by Ipilimumab-Nivolumab in Metastatic Renal Cell Carcinoma

Background: Immune checkpoint inhibitors (ICIs) have improved outcomes in advanced renal cell carcinoma but can trigger endocrine immune‑related adverse events (irAEs), including adrenal insufficiency (AI). Ipilimumab (anti‑CTLA‑4) enhances T‑cell priming in lymphoid tissues, while nivolumab (anti‑PD‑1) restores exhausted effector T‑cell function in peripheral tissues and the tumor microenvironment. Heightened immunity may inadvertently target endocrine organs, leading to primary adrenalitis or central (secondary) AI. Because AI presents with nonspecific symptoms (fatigue, nausea, weakness), early recognition and treatment are critical to prevent adrenal crisis.

Case Description: A 76‑year‑old female with metastatic clear‑cell RCC (high‑grade, rhabdoid features) underwent partial and radical nephrectomy with metastasectomy and later received combination ipilimumab + nivolumab. She presented with severe nausea, vomiting, fatigue, poor oral intake, and worsening lower‑back/right‑leg pain. Physical examination revealed dry mucous membranes, decreased skin turgor, and tachycardia. Laboratory evaluation showed AM cortisol 0.7 µg/dL, ACTH 6 pg/mL, sodium 135 mmol/L, TSH 1.8 mIU/L, and free T4 1.3 ng/dL, consistent with secondary (central) AI without overt thyroid dysfunction. Endocrinology was consulted due to concern for AI, with the differential including adrenalitis versus pituitary involvement. She received hydrocortisone 50 mg IV every 8 hours, with rapid symptom improvement, then transitioned to an oral taper and physiologic replacement (20 mg AM/10 mg PM). She returned to baseline function and remained hemodynamically stable. Education on stress‑dose principles and medical alert identification was provided. Immunotherapy was continued as nivolumab monotherapy once she was stable on glucocorticoid replacement. Planned outpatient evaluation included repeat ACTH, DHEA‑S, and abdominal imaging to assess adrenal morphology.

Learning Points:
• Combination CTLA‑4/PD‑1 blockade is a recognized risk for endocrine irAEs; maintain high suspicion for AI in patients with nonspecific constitutional or gastrointestinal symptoms.
• Low morning cortisol with low/normal ACTH indicates central AI; in symptomatic patients, do not delay treatment for dynamic testing.
• Long‑term glucocorticoid replacement, stress‑dose education, and coordinated endocrine–oncology follow‑up enable safe continuation of nivolumab in appropriately stabilized patients.

Conclusion: Early recognition and guideline‑based management of ICI‑associated adrenal insufficiency enable symptom resolution, prevent adrenal crisis, and support ongoing cancer immunotherapy through coordinated multidisciplinary care.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*