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October 1, 2024Journal of the Endocrine Society1 citationsOpen Access

6399 Unmasking A Silent Threat

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KJKaren M St. JeanJUJagriti UpadhyayPAPolina Aron

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Abstract

Abstract Disclosure: K.M. St. Jean: None. J. Upadhyay: None. P. Aron: None. L. Tchong: None. G. Toraldo: None. Introduction: Checkpoint inhibitor-associated autoimmune diabetes mellitus (CIADM) is a rare illness, with an incidence of 0.2-1.4%. However, its clinical implications are significant due to the high incidence of DKA at presentation, the lifelong persistent insulin deficiency, and the associated risk factors of diabetes complications and decreased life expectancy. This substantially impacts the patient's quality of life, healthcare costs, and treatment adherence. Case Description: A 63-year-old man with a history of type 2 DM well controlled with GLP-1A once a week presented to the hospital for persistent hyperglycemia in the 400s associated with nausea and vomiting. Upon admission, the patient had DKA with a pH of 7.3, bicarbonate 9 mmol/L, AG 29 mmol/L, elevated beta-hydroxybutyrate 10.42 mmol/L, and glucose of 655 mg/dL. The patient had a significant past medical history of stage IIA lung adenocarcinoma in 2019, s/p surgery and adjuvant chemoradiotherapy and was on surveillance till he got metastatic recurrence in 2023. Four weeks before his admission, patient was started on immunotherapy with pembrolizumab for recurrent disease.A complete workup in the hospital showed a positive GAD-65 and a low C-peptide 0.10 ng/dL consistent with diagnosis of insulin deficiency likely causing DKA. The patient was started on insulin, and blood sugars are now well controlled on insulin regimen. Discussion: Our case had a unique presentation, given the acute onset within four weeks of starting immunotherapy and the severity of his presentations by developing DKA. The median onset described in the literature for insulin deficiency from immunotherapy is typically between 12-25 weeks in different reports. DKA is a life-threatening illness with a 2-5% mortality rate in the United States. Hence, early identification of at-risk patients is vital to prevent hospitalizations and mortality.Limited data is available about CIADM, and the presence of autoantibodies appears to be associated with a more rapid and severe onset of CIADM. This highlights the need for identifying biomarkers or predictive factors to help identify patients at higher risk and potentially intervene earlier in their treatment.Finally, CIADM is characterized by sudden permanent b-cell failure occurring after immuno-therapy. Therefore, it is essential to be familiarized with CIADM and its unique characteristics to provide timely and appropriate care to affected individuals. Moreover, as immunotherapy becomes increasingly common in cancer treatment, awareness of CIADM becomes even more critical for managing potential complications and optimizing patient outcomes. Presentation: 6/2/2024

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Jean et al. (2024) studied this question.

synapsesocial.com/papers/68e5611fe2b3180350efe2aahttps://doi.org/10.1210/jendso/bvae163.991
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Checkpoint Inhibitor–Associated Autoimmune Diabetes Following PD-1 Blockade: Severe Diabetic Ketoacidosis After Pembrolizumab2026
  2. 2201: FULMINANT DKA FROM NIVOLUMAB-INDUCED DIABETES IN A PATIENT WITH UROTHELIAL CARCINOMA2026
  3. 3Pembrolizumab-Associated Insulinopenic Diabetes Mellitus Presenting without Ketoacidosis and Mimicking Type 2 Diabetes Mellitus2026
  4. 4The clinical spectrum and causal relationship assessment of checkpoint inhibitor‐associated autoimmune diabetes mellitus (CIADM): A retrospective observational study2026 · 1 citations
  5. 56779 The Diversity of Immune Checkpoint Inhibitor Associated Diabetes2024