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Commentary on a Case of Unexpected Hyperglycemia

Commentary on a Case of Unexpected Hyperglycemia Fatica and colleagues describe a patient with a history of undifferentiated pleomorphic sarcoma presenting with new onset symptoms concerning for hyperglycemia. Initial investigation revealed both an increased blood glucose concentration and ketone production, key findings in the diagnosis of diabetic ketoacidosis. However, this case was complicated by bicarbonate and pH within reference limits, and an unusually low pO2. Furthermore, although the patient had complaints of polydipsia, polyuria, and weight loss over several days, there were no signs or symptoms of acidosis or the respiratory changes that would be associated with compensation. Anti-PD-1 therapies and other immune checkpoint inhibitors generally function to dampen the suppression of antitumor response by blocking the natural immune system brakes. For instance, PD-1 is expressed during lymphocyte activation and functions as a negative feedback for further lymphocytic activity. As agents that activate the immune system against cancer, these immunotherapies can lead to “immune activation gone astray,” and target normal cells. Side effects, including colitis, hepatitis, pancreatitis, nephritis, and skin pathologies are seen in up to a third of patients on anti-PD-1 therapies (1). Retrospective cohorts have also reported autoimmune endocrinopathies including: diabetes mellitus, both hyper- and hypothyroidism, adrenal insufficiency, and hypophysitis in 6%–10% of patients receiving anti-PD-1 therapy (1, 2). As endocrinopathies can present with nonspecific symptoms, such as the case presented, these incidences are likely underestimated. With immune checkpoint blockers now a mainstay of clinical management for many malignancies, more iatrogenic endocrinopathies can be expected. These complications do not have clear timelines and, as in the case presented, patients receive these therapies over the course of years. Thus, possible new-onset endocrinopathy is an important differential when working up a patient on immune checkpoint blockade. Author Contributions All authors confirmed they have contributed to the intellectual content of this paper and have met the following 4 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; (c) final approval of the published article; and (d) agreement to be accountable for all aspects of the article thus ensuring that questions related to the accuracy or integrity of any part of the article are appropriately investigated and resolved. Authors' Disclosures or Potential Conflicts of Interest No authors declared any potential conflicts of interest. References 1 Hofmann L , Forschner A, Loquai C, Goldinger SM, Zimmer L, Ugurel S, et al. Cutaneous, gastrointestinal, hepatic, endocrine, and renal side-effects of anti-PD-1 therapy . Eur J Cancer 2016 ; 60 : 190 – 209 . Google Scholar Crossref Search ADS PubMed WorldCat 2 Chan KK , Bass AR. Autoimmune complications of immunotherapy: pathophysiology and management . BMJ 2020 ; 369 : m736 . Google Scholar PubMed OpenURL Placeholder Text WorldCat © American Association for Clinical Chemistry 2021. All rights reserved. For permissions, please email: [email protected]. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Clinical Chemistry Oxford University Press

Commentary on a Case of Unexpected Hyperglycemia

Borcherding, Nicholas; Gronowski, Ann M
Clinical Chemistry , Volume 67 (8): 2 – Aug 3, 2021
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References (2)

Publisher
Oxford University Press
Copyright
© American Association for Clinical Chemistry 2021. All rights reserved. For permissions, please email: [email protected].
ISSN
0009-9147
eISSN
1530-8561
DOI
10.1093/clinchem/hvab085
Publisher site
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Abstract

Fatica and colleagues describe a patient with a history of undifferentiated pleomorphic sarcoma presenting with new onset symptoms concerning for hyperglycemia. Initial investigation revealed both an increased blood glucose concentration and ketone production, key findings in the diagnosis of diabetic ketoacidosis. However, this case was complicated by bicarbonate and pH within reference limits, and an unusually low pO2. Furthermore, although the patient had complaints of polydipsia, polyuria, and weight loss over several days, there were no signs or symptoms of acidosis or the respiratory changes that would be associated with compensation. Anti-PD-1 therapies and other immune checkpoint inhibitors generally function to dampen the suppression of antitumor response by blocking the natural immune system brakes. For instance, PD-1 is expressed during lymphocyte activation and functions as a negative feedback for further lymphocytic activity. As agents that activate the immune system against cancer, these immunotherapies can lead to “immune activation gone astray,” and target normal cells. Side effects, including colitis, hepatitis, pancreatitis, nephritis, and skin pathologies are seen in up to a third of patients on anti-PD-1 therapies (1). Retrospective cohorts have also reported autoimmune endocrinopathies including: diabetes mellitus, both hyper- and hypothyroidism, adrenal insufficiency, and hypophysitis in 6%–10% of patients receiving anti-PD-1 therapy (1, 2). As endocrinopathies can present with nonspecific symptoms, such as the case presented, these incidences are likely underestimated. With immune checkpoint blockers now a mainstay of clinical management for many malignancies, more iatrogenic endocrinopathies can be expected. These complications do not have clear timelines and, as in the case presented, patients receive these therapies over the course of years. Thus, possible new-onset endocrinopathy is an important differential when working up a patient on immune checkpoint blockade. Author Contributions All authors confirmed they have contributed to the intellectual content of this paper and have met the following 4 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; (c) final approval of the published article; and (d) agreement to be accountable for all aspects of the article thus ensuring that questions related to the accuracy or integrity of any part of the article are appropriately investigated and resolved. Authors' Disclosures or Potential Conflicts of Interest No authors declared any potential conflicts of interest. References 1 Hofmann L , Forschner A, Loquai C, Goldinger SM, Zimmer L, Ugurel S, et al. Cutaneous, gastrointestinal, hepatic, endocrine, and renal side-effects of anti-PD-1 therapy . Eur J Cancer 2016 ; 60 : 190 – 209 . Google Scholar Crossref Search ADS PubMed WorldCat 2 Chan KK , Bass AR. Autoimmune complications of immunotherapy: pathophysiology and management . BMJ 2020 ; 369 : m736 . Google Scholar PubMed OpenURL Placeholder Text WorldCat © American Association for Clinical Chemistry 2021. All rights reserved. For permissions, please email: [email protected]. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Journal

Clinical Chemistry – Oxford University Press

Published: Aug 3, 2021

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