Central diabetes insipidus related to anti-programmed cell-death 1 protein active immunotherapy

Cancer immunotherapy is a breakthrough strategy entwined with toxicity. Immune-related hypophysitis is conventionally considered distinctive of cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitors. Immune-related central diabetes insipidus (CDI) is exceptional. CDI rarely manifests as hypernatremia, which is almost always euvolemic. We report a 71-years-old male patient with advanced lung cancer who experienced severe chronic hypernatremia presented as alterations in mental status five months after initiation of treatment with the anti-PD-1 checkpoint inhibitor nivolumab. Combination of persistent hypernatremia, polyuria, high plasma osmolality and hyposthenuria raised suspicion of diabetes insipidus, prompting measurement of serum concentration of arginine vasopressin (AVP). The inappropriately undetectable serum levels of AVP confirmed central diabetes insipidus (CDI). Nivolumab-related hypophysitis was recognized as possible cause of CDI. Further hormonal assessment excluded any endocrinopathy indicating disorder of posterior pituitary. Pituitary MRI was normal with persistence of hyperintensity of posterior pituitary on T1-weighted images (bright spot). The patient was scheduled to receive 1-deamino-8-D-arginine vasopressin (DDAVP), but he died suddenly due to cardiac arrest before initiation of treatment. Our report describes the first case of nivolumab related CDI, building on existing literature through: (I) underscoring hypovolemic hypernatremia as CDI manifestation; (ii) bringing into spotlight the rare anti-PD-1 treatment related hypophysitis; (iii) enriching the limited evidence on immune-related CDI. Increased awareness of nivolumab related CDI will enable prompt recognition and therapeutic intervention.