Autoimmune Diabetes and Thyroiditis Complicating Treatment with Nivolumab

Li, Li; Masood, Awais; Bari, Shahla; Yavuz, Sahzene; Grosbach, Alan

doi:10.1159/000456540

Cited by 37 publications

(18 citation statements)

References 14 publications

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“…In contrast, twelve cases of anti-PD-1 therapy-induced type 1 diabetes mellitus with positive islet-related autoantibodies (type 1A) have been reported in the literatures (Table 4) (Hughes et al 2015;Martin-Liberal et al 2015;Mellati et al 2015;Hansen et al 2016;Hofmann et al 2016;Lowe et al 2016;Li et al 2017;Araujo et al 2017;Chae et al 2017). Thyroid dysfunction accompanied by positive thyroid autoantibodies occurred in at least three out of these twelve cases of type 1 diabetes mellitus with positive isletrelated autoantibodies.…”

Section: Discussionmentioning

confidence: 98%

Painless Thyroiditis and Fulminant Type 1 Diabetes Mellitus in a Patient Treated with an Immune Checkpoint Inhibitor, Nivolumab

Sakurai

Niitsuma

Sato

et al. 2018

Tohoku J. Exp. Med.

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The programmed cell death-1 (PD-1) pathway is a novel therapeutic target in immune checkpoint therapy for cancer. Nivolumab, an anti-PD-1 monoclonal antibody, blocks PD-1 and can restore anti-cancer immune responses by disrupting the signal that inhibits T-cell activation. Nivolumab may induce endocrinerelated adverse events, including hypophysitis, autoimmune thyroiditis, and type 1 diabetes mellitus. Here we report a 68-year-old female patient with advanced renal cell carcinoma who was treated with nivolumab. She had positive anti-thyroglobulin antibodies and anti-thyroid peroxidase antibodies with slightly elevated thyroid-stimulating hormone (9.048 μU/mL), and was diagnosed as chronic thyroiditis with subclinical hypothyroidism before nivolumab therapy. She developed painless thyroiditis after the first cycle of the therapy (Day 14). At the 7th cycle of nivolumab therapy (Day 98), hyperglycemia (473 mg/dL) was noted, whereas glycated hemoglobin level was 6.9%. Islet-related autoantibodies were all negative. The glucagon tolerance test showed complete depletion of insulin. Human leukocyte antigen typing showed haplotype DRB1*09:01-DQB1*03:03, which was reported to be closely associated with type 1 diabetes mellitus in Japan. Fulminant type 1 diabetes mellitus was diagnosed, and she was immediately treated with multiple daily injections of insulin. Fulminant type 1 diabetes mellitus is characterized by rapid-onset diabetic ketoacidosis, and negative islet-related autoantibodies, and was proposed as a novel subtype of non-autoimmune diabetes. Preceding painless thyroiditis with positive thyroid autoantibodies observed in the present case, however, raises the possibility that autoimmune mechanisms are involved in the pathogenesis of nivolumab-induced fulminant type 1 diabetes mellitus.

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Section: Discussionmentioning

confidence: 98%

Painless Thyroiditis and Fulminant Type 1 Diabetes Mellitus in a Patient Treated with an Immune Checkpoint Inhibitor, Nivolumab

Sakurai

Niitsuma

Sato

et al. 2018

Tohoku J. Exp. Med.

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“…Only cases that involved nivolumab and had developed DKA were included in this study. A total of 20 patients were included in this study, and their patient data is presented in table 1 1 16–31…”

Section: Discussionmentioning

confidence: 99%

Rapid onset type-1 diabetes and diabetic ketoacidosis secondary to nivolumab immunotherapy: a review of existing literature

Abdullah¹,

Elnair

Khan

et al. 2019

BMJ Case Rep

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Nivolumab is a programmed cell death receptor (PD-1) inhibitor that is increasingly used for various malignancies, both as a first line agent and as salvage therapy. Being a PD-1/PD-1 ligand checkpoint inhibitor, it is known to cause autoimmune inflammation of various organs and has been associated with thyroiditis, insulitis, colitis, hepatitis and encephalitis to name a few. There are increasing reports of nivolumab leading to acute onset fulminant type 1 diabetes and diabetic ketoacidosis (DKA). We present a case of a 68-year-old man who developed DKA after 2 doses of nivolumab for metastatic melanoma. He was found to have type 1 diabetes, but no diabetes related antibodies were positive. He recovered from diabetes and continues to use insulin 1 year after his diagnosis. This case and associated review illustrates the importance of educating and monitoring patients who start nivolumab therapy regarding this potentially life threatening complication.

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“…The interaction of PD-1 and PD-L1 leads to the phosphorylation of the PD-1 intracellular tyrosine domain, which in turn leads to glucose metabolism quenching, a decrease in protein synthesis and the production of interleukin-10, which is a key factor inducing the anergy of CD4 + and CD8 + T lymphocytes [3]. In the case of other immune cells, stimulation of the PD-1 molecule results in inhibition of antibody production in B lymphocytes and lytic activity of NK cells [3,4,7]. As a result, immune response is suppressed.…”

Section: Inhibitory Molecules and Their Use In Oncologymentioning

confidence: 99%

Endocrine Adverse Events of Nivolumab in Non-Small Cell Lung Cancer Patients—Literature Review

Dudzińska

Szczyrek

Wojas‐Krawczyk

et al. 2020

Cancers

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In recent years, we have observed significant progress in cancer treatment associated with the development of immunotherapy. A programmed cell death 1 molecule (PD-1) on the surface of T lymphocytes may be stimulated via a specific PD-ligand 1 (PD-L1), which inhibits lymphocyte activation and leads to apoptosis. Some malignant cells are characterized by high PD-L1 expression. Nivolumab, an anti-PD-1 antibody, blocks the interaction between PD-1 and its ligands and inhibits the signaling pathway by preventing the tumor-derived PD-L1 from blocking T lymphocytes. In patients with non-small cell lung cancer (NSCLC), it is used either in monotherapy or in combination with other drugs. Immunotherapy is associated with the possibility of immune-related adverse effects (irAE) including endocrinopathies (3–23%). Thyroid disorders are the most common, with severity rarely exceeding grade 2. Hypophysitis, adrenal insufficiency and diabetes are possible complications which require immediate treatment. Individuals with autoimmune diseases diagnosed prior to immunotherapy are at risk of its exacerbation. In the management of patients receiving immunotherapy, evaluation of history of autoimmune diseases, awareness and early diagnosis of irAE are crucial and may affect treatment outcomes.

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Autoimmune Diabetes and Thyroiditis Complicating Treatment with Nivolumab

Cited by 37 publications

References 14 publications

Painless Thyroiditis and Fulminant Type 1 Diabetes Mellitus in a Patient Treated with an Immune Checkpoint Inhibitor, Nivolumab

Painless Thyroiditis and Fulminant Type 1 Diabetes Mellitus in a Patient Treated with an Immune Checkpoint Inhibitor, Nivolumab

Rapid onset type-1 diabetes and diabetic ketoacidosis secondary to nivolumab immunotherapy: a review of existing literature

Endocrine Adverse Events of Nivolumab in Non-Small Cell Lung Cancer Patients—Literature Review

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