Nivolumab, a programmed death-1 (PD-1) immune checkpoint inhibitor (ICI), improves outcomes in advanced renal cell carcinoma (RCC) by enhancing antitumor T-cell activity. Immune activation may result in immune-related adverse events, including endocrine dysfunction. Thyroid abnormalities are commonly observed, whereas adrenal insufficiency is less frequent but clinically significant. We report a 59-year-old man with metastatic chromophobe RCC who developed autoimmune thyroiditis followed by secondary adrenal insufficiency after treatment with nivolumab. Thyroid dysfunction occurred approximately one month after therapy initiation, and adrenal insufficiency developed eight months later, presenting with orthostatic hypotension and severe hyponatremia. Laboratory evaluation demonstrated undetectable cortisol with inappropriately normal adrenocorticotropic hormone, consistent with ICI-related hypophysitis. The hyponatremia improved after fludrocortisone was added to glucocorticoid therapy due to clinical refractoriness. This case highlights the rare occurrence of concurrent endocrine immune-related adverse events during PD-1 inhibitor therapy and underscores the importance of vigilant longitudinal monitoring of endocrine function in patients receiving ICI. Early recognition and prompt multidisciplinary management are essential to prevent life-threatening complications while allowing continuation of effective oncologic therapy.
Dooley et al. (Sun,) studied this question.