How to effectively recognize adrenocorticotropic hormone deficiency as an immune-related adverse event associated with immune checkpoint blockade

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  • 免疫チェックポイント阻害薬の免疫関連有害事象として発生するACTH 分泌低下症に如何にして気づくか

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<p>Aim: To evaluate the predictive values of hyponatremia, eosinophilia, and hypoglycemia as biomarkers for the diagnosis of adrenocorticotropic hormone (ACTH) deficiency, which is referred to as an immune-related adverse event associated with immune checkpoint blockade. Methods: We examined 7 patients who developed secondary adrenal insufficiency caused by ACTH deficiency during immune checkpoint inhibitor treatment, and were referred to our department between December 2017 and November 2018. Their clinical symptoms, routine laboratory test results, endocrine data, and radiological findings at diagnosis of ACTH deficiency were collected. Results: The mean age was 69 years. All patients received anti-programmed death 1 (PD-1) antibodies. The median period between the date of the first dose of immune checkpoint inhibitors and the date of diagnosis of adrenal insufficiency was 154 days. Three patients presented with chronic fatigue and 4 with acute fatigue at diagnosis. Cortisol levels were lower than 4 µg/dL in 6 patients and lower than 10 µg/dL in the remaining 1. The levels of plasma ACTH in all patients were close to or below the lower limit of the normal range, suggesting secondary adrenal insufficiency caused by the insufficient secretion of ACTH. Secretion of anterior pituitary hormones other than ACTH was not affected. No inflammatory condition or apoplexy of the pituitary gland was identified by magnetic resonance imaging studies. Four patients exhibited new hyponatremia, eosinophilia, or hypoglycemia, whereas the remaining 3 lacked abnormalities. Conclusion: Routine laboratory test results do not effectively predict ACTH deficiency leading to secondary adrenal insufficiency caused by immune checkpoint blockade.</p>

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  • Tenri Medical Bulletin

    Tenri Medical Bulletin 22 (2), 94-100, 2019-12-25

    Tenri Foundation, Tenri Institute of Medical Research

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