Fulminant type 1 diabetes associated with Isolated ACTH deficiency induced by anti-programmed cell death 1 antibody—insight into the pathogenesis of autoimmune endocrinopathy—
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- Okahata Sumie
- Division of Diabetes and Metabolism, Toho University Ohashi Medical Center, Tokyo 153-8515, Japan
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- Sakamoto Kentaro
- Division of Diabetes and Metabolism, Toho University Ohashi Medical Center, Tokyo 153-8515, Japan
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- Mitsumatsu Takako
- Division of Diabetes and Metabolism, Toho University Ohashi Medical Center, Tokyo 153-8515, Japan
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- Kondo Yuko
- Division of Diabetes and Metabolism, Toho University Ohashi Medical Center, Tokyo 153-8515, Japan
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- Noso Shinsuke
- Department of Endocrinology, Metabolism and Diabetes, Kindai University Faculty of Medicine, Osaka 589-8511, Japan
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- Ikegami Hiroshi
- Department of Endocrinology, Metabolism and Diabetes, Kindai University Faculty of Medicine, Osaka 589-8511, Japan
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- Shiba Teruo
- Division of Diabetes and Metabolism, Toho University Ohashi Medical Center, Tokyo 153-8515, Japan
Bibliographic Information
- Other Title
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- Fuluminant type 1 diabetes associated with isolated ACTH deficiency induced by anti-programmed cell death 1 antibody-insight into the pathogenesis of autoimmune endocrinopathy
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Description
<p>Therapeutic blocking antibodies against programmed death 1 (PD1) and cytotoxic T-lymphocyte antigen 4 (CTLA4) are applied for advanced cancer therapy, but induce a wide range of immune-related adverse events. In our recent case of a 52-year-old female doctor suffering from breast cancer having metastasized to the lung and liver, it was decided to use nivolumab to prevent the disease progressing after excisional surgeries and multiple chemotherapies. One month after completing the nivolumab course, fatigue, hypoglycemia and hypotension developed and isolated ACTH deficiency (IAD) was diagnosed. A further month later, under steroid supplementation, hyperglycemia emerged alongside thirst and polydipsia, prompting a diagnosis of fulminant type 1 diabetes (FT1D). Her susceptibility to type 1 diabetes was examined by HLA haplotype and CTLA4 gene polymorphism analyses. Polymorphisms CT60G>A and +49G>A in CTLA4 both generated a GG genotype. Our patient manifested one of the rarest combinations of autoimmune disease induced by nivolumab. Whereas the HLA haplotype was unsusceptible to autoimmune type 1 diabetes, polymorphisms of CTLA4, the antibody of which frequently causes hypophysitis, were susceptible to FT1D. Peripheral modulation of activated T cells, mainly by PD-1 antibodies, induced FT1D associated with IAD in patients with CTLA4 polymorphism. This case reveals hints of the T-cell etiology in T1D and evidence of CTLA4 involvement in IAD.</p>
Journal
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- Endocrine Journal
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Endocrine Journal 66 (4), 295-300, 2019
The Japan Endocrine Society