Nivolumab-Induced Isolated Adrenal Insufficiency: A Case Report

ABSTRACT Objective: Novel autoimmune therapies such as nivolumab, an antibody that blocks the programmed death-1 receptor (PD-1), have revolutionized management of patients with cancer. Autoimmune therapies, however, can be associated with immune-related adverse effects. Cases of pituitary and thyroid dysfunction have been previously reported. We describe a case of isolated adrenocorticotropic hormone (ACTH) deficiency associated with the immune checkpoint inhibitor nivolumab in a patient with non-small cell adenocarcinoma. Methods: The clinical presentation, laboratory data, and imaging studies for the acute episode of adrenal insufficiency are described, as well as literature review. Results: An 84-year-old male with stage IV non-small cell lung cancer (NSCLC) was hospitalized for hypotension, malaise, and confusion while undergoing chemotherapy with nivolumab. Endocrine evaluation showed a morning serum cortisol level of 1.1 μg/dL (reference range, 5 to 25 μg/dL), with an ACTH level of 9 pg/mL (reference range, 6 to 50 pg/mL). A 6-hour ACTH stimulation test showed a basal serum cortisol of 0.7 μg/dL that increased to 14.7 μg/dL. Further evaluation revealed normal anterior pituitary function and normal contrast-enhanced magnetic resonance imaging. Treatment with steroid hormone replacement showed clinical improvement. Conclusion: This case highlights a unique presentation of isolated ACTH deficiency in a patient with NSCLC treated with the PD-1 inhibitor nivolumab. It is critical to recognize side effects that immunotherapy may have in the endocrine system and treat appropriately. Abbreviations: ACTH = adrenocorticotropic hormone CTLA-4 = cytotoxic T-lymphocyte-associated protein 4 IRAEs = immune-related adverse effects PD-1 = programmed death-1 receptor TSH = thyroid-stimulating hormone