Primary Adrenal Insufficiency from Immune Checkpoint Inhibitors
Objective: To describe a rare case of primary adrenal insufficiency (PAI) from immune checkpoint inhibitors (ICPIs). Methods: We describe the clinical presentation, supportive laboratory findings, long-term outcomes, and a review of the current available literature on PAI following administration of ipilimumab and nivolumab. Results: A 49-year-old Caucasian male with stage IIIB metastatic melanoma and failed standard chemotherapy and monotherapy with ipilimumab was started on nivolumab in addition to ipilimumab. Two months after starting the combination therapy, he presented with weakness, lethargy, nausea, and diarrhea for 1 to 2 weeks. Since there was a concern for treatment-associated endocrinopathy, an 8 AM cortisol and adrenocorticotrophic hormone (ACTH) were measured and noted to be 5.4 μg/dL (normal, 5 to 25 μg/dL) and 224 pg/mL (normal, 15 to 66 pg/mL), respectively. The cortisol was interpreted as normal, and follow-up was arranged in the endocrinology clinic. ACTH was drawn at the same time but reported after discharge. He presented again in 2 weeks with progressive symptoms, and a prestimulus cortisol was 1.6 μg/dL and 60 minutes after cosyntropin administration did not change, at 1.7 μg/dL. The patient was diagnosed with PAI based on additional data that included a plasma ACTH concentration of 827 pg/mL, elevated renin, and undetectable aldosterone with concurrent hyponatremia and hyperkalemia. He was treated with glucocorticoid and mineralocorticoid replacement and has since been in cancer remission. Conclusion: This case exemplifies how the diagnosis of a classic disease can be confounded in a complex patient and adds to the list of endocrinopathies from ICPI, where a high clinical suspicion should be maintained. Abbreviations: ACTH adrenocorticotrophic hormone anti-CTLA-4 Ab anti–cytotoxic T-cell antigen 4 antibody ICPI immune checkpoint inhibitor PAI primary adrenal insufficiency PD-1 programmed death 1 PDL-1 programmed death ligand 1