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Introduction: Nivolumab is approved in Portugal for non-small cell metastatic lung cancer, as one of the indications, after progressing on chemotherapy. As an immune checkpoint inhibitor (ICI) immune-related adverse events (irAE) are possible reactions. Case report: A 64-year-old man with stage III lung adenocarcinoma who progressed after chemoradiotherapy and first line metastatic chemotherapy started nivolumab. Approximately 16 months after starting treatment he is admitted to the hospital with suspected brain metastasis due to vomiting, prostration and altered mental state. Brain-CT showed no abnormalities, but analyses showed decreased levels of ACTH and cortisol, which supported the diagnosis of hypophysitis. Nivolumab was stopped and high-dose hydrocortisone was initiated with good response. After discharge, patient showed disease stability and maintained vigilance. Discussion: Hypophysitis is an uncommon endocrine irAE of nivolumab. It appears on average 6 months after starting treatment and shows nonspecific symptoms often misjudged as disease progression. Only a high degree of suspicion can lead to appropriate investigation and treatment.