Delayed-onset central adrenal insufficiency following adjuvant pembrolizumab therapy for renal cell carcinoma

This report describes a woman in her early 70s who developed severe central adrenal insufficiency 11 months after completing 1 year of adjuvant pembrolizumab for resected clear cell renal cell carcinoma. She presented with debilitating fatigue, profound weakness, unintentional weight loss and hypotension. Because these symptoms were non-specific and emerged long after immunotherapy discontinuation, the diagnosis was delayed for several months. Laboratory testing showed a markedly suppressed morning cortisol with an inappropriately low adrenocorticotropic hormone (ACTH) level and no response to cosyntropin, confirming central adrenal insufficiency. Other pituitary hormone axes remained intact, consistent with isolated ACTH deficiency. Imaging demonstrated adrenal atrophy, supporting chronic central adrenal insufficiency. The patient improved rapidly after starting hydrocortisone replacement. This case highlights a prolonged interval between checkpoint inhibitor cessation and endocrine toxicity, emphasising the importance of continued surveillance for late-onset immune-related endocrinopathies even after therapy completion.