Hypophysitis induced by anti-programmed cell death protein 1 immunotherapy in non-small cell lung cancer: Three case reports

BACKGROUND: Hypophysitis induced by programmed cell death 1 protein (PD-1) immune checkpoint inhibitors is rare and poorly described. We report three patients with non-small cell lung cancer who developed hypophysitis after anti-PD-1 immunotherapy. CASE SUMMARY: Both case 1 and case 2 presented with common symptoms of fatigue, nausea, and vomiting. However, case 3 showed rare acute severe symptoms such as hoarse voice, bucking, and difficulty in breathing even when sitting. Following two cycles of immunotherapy in case 3, the above severe symptoms and pituitary gland enlargement were found on magnetic resonance imaging at the onset of hypophysitis. These symptoms were relieved after 10 d of steroid treatment. Case 3 was the first patient with these specific symptoms, which provided a new insight into the diagnosis of hypophysitis. In addition, we found that the clinical prognosis of patients with hypophysitis was related to the dose of steroid therapy. Case 3 was treated with high-dose hormone therapy and her pituitary-corticotropic axis dysfunction returned to normal after more than 6 mo of steroid treatment. Cases 1 and 2 were treated with the low-dose hormone, and dysfunction of the pituitary-corticotropic axis was still present after up to 7 mo of steroid treatment. CONCLUSION: The clinical symptoms described in this study provide a valuable reference for the diagnosis and treatment of immune-related hypophysitis.