Cargando…

THU353 Late Onset Of Immune Checkpoint Inhibitor-Related Diabetes After 3 Years

Disclosure: S. Avula: None. A. Ahmed: None. M. Salim: None. Z.J. Anderson: None. A. Kumar: None. A. Estrada: None. Background: Immune checkpoint inhibitor-induced diabetes mellitus (ICI-DM) is characterized by acute onset of dramatic hyperglycaemia with severe insulin deficiency following exposure t...

Descripción completa

Detalles Bibliográficos
Autores principales: Avula, Sreekant, Ahmed, Ammar, Salim, Michael, Anderson, Zachary J, Kumar, Ameya, Estrada, Allison
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10554210/
http://dx.doi.org/10.1210/jendso/bvad114.786
_version_ 1785116357933662208
author Avula, Sreekant
Ahmed, Ammar
Salim, Michael
Anderson, Zachary J
Kumar, Ameya
Estrada, Allison
author_facet Avula, Sreekant
Ahmed, Ammar
Salim, Michael
Anderson, Zachary J
Kumar, Ameya
Estrada, Allison
author_sort Avula, Sreekant
collection PubMed
description Disclosure: S. Avula: None. A. Ahmed: None. M. Salim: None. Z.J. Anderson: None. A. Kumar: None. A. Estrada: None. Background: Immune checkpoint inhibitor-induced diabetes mellitus (ICI-DM) is characterized by acute onset of dramatic hyperglycaemia with severe insulin deficiency following exposure to PD-1/PD-L1 inhibitors. The frequency of type 1 diabetes related to ICIs is estimated to be ∼3.5%. Endogenous insulin secretion is depleted within a few weeks of the clinical onset of diabetes. Moreover, the positive rate for islet-related autoantibodies varies from 5% to 50%. Case:  51-year-old male with a PMH of stage 4 adenocarcinoma of the lung with metastasis to brain, bone, and kidneys was sent to the ED for a POC BG above 700 mg/dl. He was diagnosed with stage 4 lung adenocarcinoma three years prior to the current presentation. He received stereotactic radiotherapy for the brain metastases, Carboplatin/pemetrexed/pembrolizumab x4 cycles, then continued maintenance therapy of pemetrexed/pembrolizumab with the last dose given 3 weeks prior. He had recent evidence of progression, so chemotherapy adjustment was planned, and he started dexamethasone 4mg on the day prior to presentation. Upon ED presentation, he reported new onset polyuria and polydipsia for 1 week accompanied by 10% weight loss over the last 3 months. His vitals were stable. Physical examination was unremarkable. Serum glucose level was found to be 726 mg/dl, Bicarbonate level 28 mEq/L (22-30), creatinine 1.99 mg/dl (baseline 1.2), venous blood PH was 7.29, Bicarbonate 24 mEq/L (24-28), anion gap 15 mEq/L (8-16), B-hydroxybutyrate 2.91 mmol/L (0.02-0.27), sodium 127 mEq/L(135-148) and HbA1c 6.3%. He received normal saline boluses and NPH insulin 15 units SQ, after which his repeat BG level was 426 mg/dl. Given prediabetic Hba1c with recent dexamethasone therapy he was thought to have steroid-induced hyperglycaemia. He was discharged on NPH 15 units daily with Novolog sliding scale. Upon clinic follow-up 1 week later, his BGs did not improve significantly despite stopping steroids. His C-peptide level was low at 0.22 ng/ml (1.10-4.40) with BG 443mg/dl, and GAD -65 antibodies were negative. He continued to have hyperglycaemia while on NPH /Novolog regimen, thus he was switched to Lantus and Novolog regimen with better glycaemic control. He continues to have significant insulin requirements 3 months later. Conclusion: Although the mean interval between the first ICI administration and T1DM development was found to be 201 ± 187 days, the development of type 1 DM may occur with longer intervals from initiating the ICI therapy. In our case, the patient developed new-onset diabetes with low C-peptide after 1,095 days from receiving the first dose of pembrolizumab. On the previous case reports, the presence of GAD-65 antibodies is typically associated with shortened intervals between receiving the ICI therapy and the development of DM. Presentation: Thursday, June 15, 2023
format Online
Article
Text
id pubmed-10554210
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Oxford University Press
record_format MEDLINE/PubMed
spelling pubmed-105542102023-10-06 THU353 Late Onset Of Immune Checkpoint Inhibitor-Related Diabetes After 3 Years Avula, Sreekant Ahmed, Ammar Salim, Michael Anderson, Zachary J Kumar, Ameya Estrada, Allison J Endocr Soc Diabetes And Glucose Metabolism Disclosure: S. Avula: None. A. Ahmed: None. M. Salim: None. Z.J. Anderson: None. A. Kumar: None. A. Estrada: None. Background: Immune checkpoint inhibitor-induced diabetes mellitus (ICI-DM) is characterized by acute onset of dramatic hyperglycaemia with severe insulin deficiency following exposure to PD-1/PD-L1 inhibitors. The frequency of type 1 diabetes related to ICIs is estimated to be ∼3.5%. Endogenous insulin secretion is depleted within a few weeks of the clinical onset of diabetes. Moreover, the positive rate for islet-related autoantibodies varies from 5% to 50%. Case:  51-year-old male with a PMH of stage 4 adenocarcinoma of the lung with metastasis to brain, bone, and kidneys was sent to the ED for a POC BG above 700 mg/dl. He was diagnosed with stage 4 lung adenocarcinoma three years prior to the current presentation. He received stereotactic radiotherapy for the brain metastases, Carboplatin/pemetrexed/pembrolizumab x4 cycles, then continued maintenance therapy of pemetrexed/pembrolizumab with the last dose given 3 weeks prior. He had recent evidence of progression, so chemotherapy adjustment was planned, and he started dexamethasone 4mg on the day prior to presentation. Upon ED presentation, he reported new onset polyuria and polydipsia for 1 week accompanied by 10% weight loss over the last 3 months. His vitals were stable. Physical examination was unremarkable. Serum glucose level was found to be 726 mg/dl, Bicarbonate level 28 mEq/L (22-30), creatinine 1.99 mg/dl (baseline 1.2), venous blood PH was 7.29, Bicarbonate 24 mEq/L (24-28), anion gap 15 mEq/L (8-16), B-hydroxybutyrate 2.91 mmol/L (0.02-0.27), sodium 127 mEq/L(135-148) and HbA1c 6.3%. He received normal saline boluses and NPH insulin 15 units SQ, after which his repeat BG level was 426 mg/dl. Given prediabetic Hba1c with recent dexamethasone therapy he was thought to have steroid-induced hyperglycaemia. He was discharged on NPH 15 units daily with Novolog sliding scale. Upon clinic follow-up 1 week later, his BGs did not improve significantly despite stopping steroids. His C-peptide level was low at 0.22 ng/ml (1.10-4.40) with BG 443mg/dl, and GAD -65 antibodies were negative. He continued to have hyperglycaemia while on NPH /Novolog regimen, thus he was switched to Lantus and Novolog regimen with better glycaemic control. He continues to have significant insulin requirements 3 months later. Conclusion: Although the mean interval between the first ICI administration and T1DM development was found to be 201 ± 187 days, the development of type 1 DM may occur with longer intervals from initiating the ICI therapy. In our case, the patient developed new-onset diabetes with low C-peptide after 1,095 days from receiving the first dose of pembrolizumab. On the previous case reports, the presence of GAD-65 antibodies is typically associated with shortened intervals between receiving the ICI therapy and the development of DM. Presentation: Thursday, June 15, 2023 Oxford University Press 2023-10-05 /pmc/articles/PMC10554210/ http://dx.doi.org/10.1210/jendso/bvad114.786 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Diabetes And Glucose Metabolism
Avula, Sreekant
Ahmed, Ammar
Salim, Michael
Anderson, Zachary J
Kumar, Ameya
Estrada, Allison
THU353 Late Onset Of Immune Checkpoint Inhibitor-Related Diabetes After 3 Years
title THU353 Late Onset Of Immune Checkpoint Inhibitor-Related Diabetes After 3 Years
title_full THU353 Late Onset Of Immune Checkpoint Inhibitor-Related Diabetes After 3 Years
title_fullStr THU353 Late Onset Of Immune Checkpoint Inhibitor-Related Diabetes After 3 Years
title_full_unstemmed THU353 Late Onset Of Immune Checkpoint Inhibitor-Related Diabetes After 3 Years
title_short THU353 Late Onset Of Immune Checkpoint Inhibitor-Related Diabetes After 3 Years
title_sort thu353 late onset of immune checkpoint inhibitor-related diabetes after 3 years
topic Diabetes And Glucose Metabolism
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10554210/
http://dx.doi.org/10.1210/jendso/bvad114.786
work_keys_str_mv AT avulasreekant thu353lateonsetofimmunecheckpointinhibitorrelateddiabetesafter3years
AT ahmedammar thu353lateonsetofimmunecheckpointinhibitorrelateddiabetesafter3years
AT salimmichael thu353lateonsetofimmunecheckpointinhibitorrelateddiabetesafter3years
AT andersonzacharyj thu353lateonsetofimmunecheckpointinhibitorrelateddiabetesafter3years
AT kumarameya thu353lateonsetofimmunecheckpointinhibitorrelateddiabetesafter3years
AT estradaallison thu353lateonsetofimmunecheckpointinhibitorrelateddiabetesafter3years