• Xuefeng Bai, Xiahong Lin, Kainan Zheng, Xiaoyu Chen, Xiaohong Wu, Yinqiong Huang, and Yong Zhuang.
• Department of Endocrinology, The Second Affiliated Hospital of Fujian Medical University, No. 950 Donghai Street, Fengze District, Quanzhou, Fujian Province, China.
• Endocrine. 2020 Sep 1; 69 (3): 670-681.

PurposeOur study aimed to map endocrine toxicity spectrum of immune checkpoint inhibitors (ICIs).MethodsWe obtained data from VigiBase, between January 1, 2011 and March 6, 2019. All endocrine adverse drug reactions (ADRs) were classified by group queries according to the Medical Dictionary for Regulatory Activities. Disproportionality analysis was performed with information component (IC) and reporting odds ratio (ROR). We used IC to identify meaningful endocrinopathies associated with ICIs and ROR to compare differences between ICI subgroups of ADRs. IC025 (lower end of the 95% confidence interval of IC) is considered significant if larger than 0.ResultsIn all, 6089 reports for endocrinopathies associated with ICIs were involved, with a male to female ratio of 1.5:1. The disproportionality analysis indicated significance of not only common endocrinopathies: thyroid dysfunction, hypophysitis/hypopituitarism, adrenal insufficiency, T1DM, fulminant T1DM (IC025: 4.12-6.62), but also rare endocrinopathies: hypoparathyroidism, diabetes insipidus, hypogonadism (IC025: 1.56-2.04). Increased risk of ADR reporting emerged in anti-CTLA-4 (e.g., hypophysitis/hypopituitarism, adrenal insufficiency) or in anti-PD-1/PD-L1 (e.g., thyroid dysfunction, T1DM, fulminant T1DM). In general, combination therapy (anti-CTLA-4 plus anti-PD-1/PD-L1) had a stronger association with endocrinopathies than monotherapy (ROR: 2.8, 95% CI: 2.5-3.1). Onset time of common endocrinopathies differed between different ICI therapies, typically within 12 weeks in anti-CTLA-4 monotherapy but diffusely ranging from 0 to 48 weeks in anti-PD-1 monotherapy.ConclusionsOur study shows rising reporting frequencies of endocrinopathies caused by ICIs, especially aggravated in combination therapy. Clinicians should be early aware of latent endocrine toxicity and different onset time of endocrinopathies when implementing ICI therapies.

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