MON-181 Clinical Features of Immune Checkpoint Inhibitor-Related Adrenal Insufficiency: A Retrospective Analysis

Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment over the past decade. Despite their increasing use in clinical practice, there are few established, evidence-based guidelines for the screening and management of immune-related adverse events (irAEs), particularly with regard to autoimmune endocrinopathies. Adrenal insufficiency is an irAE that is poorly characterized due to the nonspecific nature of its presentation and can be life-threatening if not promptly recognized and treated. Our aim is to better define the clinical, biochemical, and imaging features of ICI-related adrenal insufficiency (AI) to mediate earlier recognition and treatment. Methods: We identified a total of 54 patients treated with either nivolumab, pembrolizumab, or ipilimumab combination therapy between January 2010 and August 2018 found to have a random cortisol level less than 2 or morning cortisol less than 5 during or following therapy. Patients who had been on prednisone or dexamethasone at the time of cortisol testing, had a history of adrenalectomy or radiation to the adrenal glands, or had adrenal or pituitary metastasis were excluded. Results: 11 patients met criteria for new onset ICI-related AI based on clinical and biochemical findings. 78% were formally diagnosed with AI, 61% had subsequent workup with ACTH, 17% had dedicated MRI pituitary imaging, 22% had HPA axis testing, 50% were referred to Endocrinology, and 45% were appropriately treated with hydrocortisone. Mean time to onset was 137 days from initiation of ICI. Peripheral eosinophilia was observed in 55% of patients. No anti-21 hydroxylase antibodies were drawn, and no patients had known underlying autoimmune disease or auto-antibody positivity. Six patients (55%) were felt to have secondary AI from ICI-related hypophysitis and one patient (9%) was felt to have ICI-related adrenalitis. Conclusions: As ICIs are being used with increasing frequency, it is crucial for health care providers to recognize the characteristics of immune-mediated adrenal insufficiency and initiate the appropriate workup, treatment, and referrals. Cortisol levels are routinely ordered as part of screening of ICI infusion but often dismissed without proper workup or follow up when levels meet criteria for AI. Our findings suggest that ICI-related AI more frequently manifests as ACTH deficiency in the context of hypophysitis, though primary AI can occur as well. Ultimately, further investigation is necessary to develop a systematic approach to diagnosing and managing ICI-related AI. References: 1. Chang et al. Endocrine Toxicity of Cancer Immunotherapy Targeting Immune Checkpoints. Endocr Rev. 2019;40(1):17-65. 2. Castinetti et al. French Endocrine Society Guidance on endocrine side-effects of immunotherapy. Endocr Relat Cancer. 2018;26(2):G1-G8.