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    Programmed cell death-1 (PD-1) blockade therapy, an immune checkpoint treatment, can induce hypophysitis or hypopituitarism as an immune-related adverse event (pituitary irAE). We aimed to clarify the clinical features of pituitary irAEs during PD-1 blockade therapy. This retrospective study investigated consecutive patients treated with nivolumab, an anti-PD-1 antibody, at Kyoto University Hospital between 1 September 2014 and 31 August 2019. We examined patients' baseline characteristics and analysed the clinical data of those who developed pituitary irAEs. Of the 374 recruited patients, 7 (1.9%) developed pituitary irAEs, and each presented with isolated secondary adrenal insufficiency. In 4 patients, changes in ACTH were delayed relative to those in cortisol: when serum cortisol levels fell below the reference range, plasma ACTH levels were still normal. Pituitary irAEs were accompanied by elevated serum-free T3 (fT3) levels, which resolved with glucocorticoid replacement. Serum TSH levels were not suppressed despite elevated serum fT3 levels and 1 patient even presented with high fT3 level above the reference range (fT3, 7.1 pmol/L; free T4 (fT4), 13.9 pmol/L; and TSH, 5.1 mIU/L). Isolated secondary adrenal insufficiency was a common pituitary irAE during PD-1 blockade therapy. This condition was accompanied by thyroid dysfunction, including elevation of fT3 without TSH suppression. © 2020 John Wiley & Sons Ltd.


    Ichiro Yamauchi, Daisuke Taura, Takuro Hakata, Haruka Fujita, Kentaro Okamoto, Yohei Ueda, Toshihito Fujii, Nobuya Inagaki. Clinical features and thyroid dysfunction in adverse events involving the pituitary gland during PD-1 blockade therapy. Clinical endocrinology. 2021 Feb;94(2):258-268

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    PMID: 33037658

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