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SUN-172 Diabetic Ketoacidosis Precipitated by Treatment with PD-1 Inhibitor: A Rare Immune Related Adverse Event
Introduction: Programmed cell death protein 1 (PD-1) inhibitors stimulate the immune system to produce anti-tumor effects and are among a novel drug class of cancer immunotherapy. PD-1 inhibitors are associated with various immune related adverse events (IRAEs) owing to their indiscriminate activati...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Endocrine Society
2019
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6553092/ http://dx.doi.org/10.1210/js.2019-SUN-172 |
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author | Qureshi, Mohammed |
author_facet | Qureshi, Mohammed |
author_sort | Qureshi, Mohammed |
collection | PubMed |
description | Introduction: Programmed cell death protein 1 (PD-1) inhibitors stimulate the immune system to produce anti-tumor effects and are among a novel drug class of cancer immunotherapy. PD-1 inhibitors are associated with various immune related adverse events (IRAEs) owing to their indiscriminate activation of the immune system. IRAEs involving the endocrine system, particularly affecting the thyroid, pituitary and adrenal glands, are well-established. We however present a case of diabetic ketoacidosis (DKA), an exceedingly rare and life threatening immune-related endocrinopathy, precipitated by the PD-1 inhibitor Pembrolizumab. Clinical case: A 52-year-old female with PMH of T2DM (A1c 8.1%) and metastatic NSCLC (Non-Small Cell Lung Cancer) presented with 1-day history of nausea, vomiting, polyuria, and lethargy. She received an infusion of Pembrolizuab 5 days prior to onset of symptoms. On admission, she was found to have a BG of 617 mg/dL (reference range (RR): 65-99 mg/dL), ketonuria (3+; 80mg/dL; RR: negative), anion gap of 22 mEq/L (RR: 7-15 mEq/L), serum CO2 17 mEq/L (RR: 24-31 mEq/L), and arterial pH 7.29 (RR: 7.35-7.45). Infection work up was negative. She was treated for DKA with IV fluids and IV insulin. After resolution of acidosis, evaluation revealed normal adrenal and thyroid function but undetectable C-Peptide (< 0.9ng/mL; RR: 1.1-4.4 ng/mL) which was previously normal. Diabetes related antibodies were negative. The patient subsequently required insulin to maintain euglycemia, though she was previously treated with oral agents alone, and was discharged on basal bolus insulin. This series of events signifies the abrupt loss β cell function that resulted in profound insulinopenia and DKA. This is recognized to be a rare immune-related endocrinopathy secondary to Pembrolizumab, with DKA occurring in only 0.1% of patients in clinical trials. Pembrolizumab blocks PD-1 receptors on the surface of T cells in order to restore T cell anti-tumor function. This blockade can trigger T cell mediated destruction of various host cells. Pancreatic β cells express PD Ligand-1, which binds to PD-1 receptors as a mode to evade T cell immunity. PD-1 inhibition potentiates inflammation and destruction of pancreatic β cells resulting in worsening control of DM or in rare instances, fulminant β cell failure and DKA. There does not appear to be a dose dependent relationship or serum antibody markers predictive of this adverse event. Conclusion: The expanding use PD-1 inhibitors in cancer treatment has resulted in a host of IRAEs. This case highlights that clinicians and patients alike must be aware of the importance of recognizing DKA as a rare yet potentially lethal adverse event of PD-1 inhibitors. There is currently no clear method to predict which patients are at risk of developing DKA but early and regular screening for glucose intolerance should be standard of care when initiating anti-PD1 therapy. |
format | Online Article Text |
id | pubmed-6553092 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Endocrine Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-65530922019-06-13 SUN-172 Diabetic Ketoacidosis Precipitated by Treatment with PD-1 Inhibitor: A Rare Immune Related Adverse Event Qureshi, Mohammed J Endocr Soc Diabetes Mellitus and Glucose Metabolism Introduction: Programmed cell death protein 1 (PD-1) inhibitors stimulate the immune system to produce anti-tumor effects and are among a novel drug class of cancer immunotherapy. PD-1 inhibitors are associated with various immune related adverse events (IRAEs) owing to their indiscriminate activation of the immune system. IRAEs involving the endocrine system, particularly affecting the thyroid, pituitary and adrenal glands, are well-established. We however present a case of diabetic ketoacidosis (DKA), an exceedingly rare and life threatening immune-related endocrinopathy, precipitated by the PD-1 inhibitor Pembrolizumab. Clinical case: A 52-year-old female with PMH of T2DM (A1c 8.1%) and metastatic NSCLC (Non-Small Cell Lung Cancer) presented with 1-day history of nausea, vomiting, polyuria, and lethargy. She received an infusion of Pembrolizuab 5 days prior to onset of symptoms. On admission, she was found to have a BG of 617 mg/dL (reference range (RR): 65-99 mg/dL), ketonuria (3+; 80mg/dL; RR: negative), anion gap of 22 mEq/L (RR: 7-15 mEq/L), serum CO2 17 mEq/L (RR: 24-31 mEq/L), and arterial pH 7.29 (RR: 7.35-7.45). Infection work up was negative. She was treated for DKA with IV fluids and IV insulin. After resolution of acidosis, evaluation revealed normal adrenal and thyroid function but undetectable C-Peptide (< 0.9ng/mL; RR: 1.1-4.4 ng/mL) which was previously normal. Diabetes related antibodies were negative. The patient subsequently required insulin to maintain euglycemia, though she was previously treated with oral agents alone, and was discharged on basal bolus insulin. This series of events signifies the abrupt loss β cell function that resulted in profound insulinopenia and DKA. This is recognized to be a rare immune-related endocrinopathy secondary to Pembrolizumab, with DKA occurring in only 0.1% of patients in clinical trials. Pembrolizumab blocks PD-1 receptors on the surface of T cells in order to restore T cell anti-tumor function. This blockade can trigger T cell mediated destruction of various host cells. Pancreatic β cells express PD Ligand-1, which binds to PD-1 receptors as a mode to evade T cell immunity. PD-1 inhibition potentiates inflammation and destruction of pancreatic β cells resulting in worsening control of DM or in rare instances, fulminant β cell failure and DKA. There does not appear to be a dose dependent relationship or serum antibody markers predictive of this adverse event. Conclusion: The expanding use PD-1 inhibitors in cancer treatment has resulted in a host of IRAEs. This case highlights that clinicians and patients alike must be aware of the importance of recognizing DKA as a rare yet potentially lethal adverse event of PD-1 inhibitors. There is currently no clear method to predict which patients are at risk of developing DKA but early and regular screening for glucose intolerance should be standard of care when initiating anti-PD1 therapy. Endocrine Society 2019-04-30 /pmc/articles/PMC6553092/ http://dx.doi.org/10.1210/js.2019-SUN-172 Text en Copyright © 2019 Endocrine Society https://creativecommons.org/licenses/by-nc-nd/4.0/ This article has been published under the terms of the Creative Commons Attribution Non-Commercial, No-Derivatives License (CC BY-NC-ND; https://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Diabetes Mellitus and Glucose Metabolism Qureshi, Mohammed SUN-172 Diabetic Ketoacidosis Precipitated by Treatment with PD-1 Inhibitor: A Rare Immune Related Adverse Event |
title | SUN-172 Diabetic Ketoacidosis Precipitated by Treatment with PD-1 Inhibitor: A Rare Immune Related Adverse Event |
title_full | SUN-172 Diabetic Ketoacidosis Precipitated by Treatment with PD-1 Inhibitor: A Rare Immune Related Adverse Event |
title_fullStr | SUN-172 Diabetic Ketoacidosis Precipitated by Treatment with PD-1 Inhibitor: A Rare Immune Related Adverse Event |
title_full_unstemmed | SUN-172 Diabetic Ketoacidosis Precipitated by Treatment with PD-1 Inhibitor: A Rare Immune Related Adverse Event |
title_short | SUN-172 Diabetic Ketoacidosis Precipitated by Treatment with PD-1 Inhibitor: A Rare Immune Related Adverse Event |
title_sort | sun-172 diabetic ketoacidosis precipitated by treatment with pd-1 inhibitor: a rare immune related adverse event |
topic | Diabetes Mellitus and Glucose Metabolism |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6553092/ http://dx.doi.org/10.1210/js.2019-SUN-172 |
work_keys_str_mv | AT qureshimohammed sun172diabeticketoacidosisprecipitatedbytreatmentwithpd1inhibitorarareimmunerelatedadverseevent |