Background Nivolumab is an anti-programmed cell death protein 1 antibody, typically used as cancer immunotherapy agent. Despite multiple clinical benefits it might cause autoimmune-related side-effects, often involving the endocrine system. To our knowledge, this is the first case of nivolumab-induced hypophysitis manifesting several months after treatment discontinuation. Case presentation We, herein, report a 53-year-old patient with hypophysitis and isolated adrenocorticotropic hormone deficiency, who presented with recurring syncopal episodes and persistent mild hyponatremia. The performed challenged tests were consistent with secondary adrenal insufficiency, while responses of other anterior pituitary hormones were preserved. Magnetic resonance imaging revealed thickened pituitary stalk, consistent with hypophysitis. The patient’s condition gradually improved after administration of hydrocortisone, with normalization of sodium and glucose-levels. The related literature is discussed. Conclusions We conclude that even after discontinuation of nivolumab, isolated adrenal insufficiency can occur. Therefore, in case of administration of such agents, clinical assessment, and routine monitoring of blood pressure, sodium-, glucose-levels, pituitary hormones as well as magnetic resonance imaging are needed to identify such conditions and prevent an adrenal crisis.