Nivolumab-induced Adrenal Insufficiency in Patients With Renal Cell Carcinoma

Adrenal insufficiency is an extremely rare event in patients treated nivolumab, an anti-programmed death-1 (PD-1) monoclonal antibody, and its detailed clinical characteristics remain unclear. The objective was to elucidate the clinical features of adrenal insufficiency related to nivolumab in patients with metastatic renal cell carcinoma (mRCC). A total of 49 consecutive patients with mRCC or unresectable renal cell carcinoma were treated with nivolumab at Kobe University Hospital between December 2016 and August 2018. Adrenal insufficiency occurred in 5 (10.2%) of these patients. We retrospectively collected the data of these 5 patients, including their clinical characteristics, clinical and laboratory findings of adrenal insufficiency, and the clinical outcome of nivolumab treatment. All cases were diagnosed with secondary adrenal insufficiency due to isolated hyposecretion of adrenocorticotropic hormone. Eosinophilia at the onset of symptoms was observed in 4 patients. No patients showed signs of hypophysitis on brain magnetic resonance imaging and the secretion of other pituitary hormones were normal in all cases. The conditions of all patients were improved by hydrocortisone replacement therapy at a physiological dose. Notably, all 5 patients showed a partial response to nivolumab and remained stable after the cessation of nivolumab. In conclusion, we described, for the first time, a case series of nivolumab-induced adrenal insufficiency in patients with mRCC. Our findings may be useful for the accurate diagnosis and the prompt treatment of this condition. In addition, there is a possibility that adrenal insufficiency may be associated with a favorable response to nivolumab in patients with mRCC.