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Marked Hypoleptinemia Precedes Overt Fat Loss in Immune Checkpoint Inhibitor-induced Acquired Generalized Lipodystrophy

Immune checkpoint inhibitors (ICIs) targeting cancer cells that evade immune T-cell regulation have revolutionized the treatment of metastatic carcinomas. Unfortunately, secondary endocrinopathies associated with ICI, including adrenal insufficiency, primary hypothyroidism, autoimmune diabetes, and...

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Autores principales: Dhanasekaran, Maheswaran, Sandooja, Rashi, Higgins, Alexandra S, Simha, Vinaya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10580409/
https://www.ncbi.nlm.nih.gov/pubmed/37908472
http://dx.doi.org/10.1210/jcemcr/luad025
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author Dhanasekaran, Maheswaran
Sandooja, Rashi
Higgins, Alexandra S
Simha, Vinaya
author_facet Dhanasekaran, Maheswaran
Sandooja, Rashi
Higgins, Alexandra S
Simha, Vinaya
author_sort Dhanasekaran, Maheswaran
collection PubMed
description Immune checkpoint inhibitors (ICIs) targeting cancer cells that evade immune T-cell regulation have revolutionized the treatment of metastatic carcinomas. Unfortunately, secondary endocrinopathies associated with ICI, including adrenal insufficiency, primary hypothyroidism, autoimmune diabetes, and rarely hypoparathyroidism, are increasing. Lipodystrophy, presumably due to the autoimmune destruction of adipocytes, leading to metabolic complications, is a less recognized adverse effect of ICI therapy. We present a case of a 66-year-old Caucasian woman treated with pembrolizumab, an anti-programmed death 1 inhibitor, for metastatic lung adenocarcinoma. Fifteen months after the treatment initiation, she was found to have hyperglycemia, hyperlipidemia, and hepatic steatosis but without any evidence of autoimmune diabetes. She was also noted to have isolated buccal fat pad loss, raising suspicion of acquired lipodystrophy. Despite well-preserved subcutaneous fat over the trunk and limbs, she had undetectable serum leptin levels. Whole-body fluorodeoxyglucose (FDG)-positron emission tomography scan showed diffuse mild FDG activity throughout the subcutaneous tissue, suggesting underlying inflammation. Over the next 3 months, she developed progressive fat loss leading to generalized lipodystrophy. Adipose tissue dysfunction, secondary to ICI-induced subclinical panniculitis, precedes overt fat loss and is characterized by hypoleptinemia and metabolic abnormalities.
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spelling pubmed-105804092023-10-31 Marked Hypoleptinemia Precedes Overt Fat Loss in Immune Checkpoint Inhibitor-induced Acquired Generalized Lipodystrophy Dhanasekaran, Maheswaran Sandooja, Rashi Higgins, Alexandra S Simha, Vinaya JCEM Case Rep Case Report Immune checkpoint inhibitors (ICIs) targeting cancer cells that evade immune T-cell regulation have revolutionized the treatment of metastatic carcinomas. Unfortunately, secondary endocrinopathies associated with ICI, including adrenal insufficiency, primary hypothyroidism, autoimmune diabetes, and rarely hypoparathyroidism, are increasing. Lipodystrophy, presumably due to the autoimmune destruction of adipocytes, leading to metabolic complications, is a less recognized adverse effect of ICI therapy. We present a case of a 66-year-old Caucasian woman treated with pembrolizumab, an anti-programmed death 1 inhibitor, for metastatic lung adenocarcinoma. Fifteen months after the treatment initiation, she was found to have hyperglycemia, hyperlipidemia, and hepatic steatosis but without any evidence of autoimmune diabetes. She was also noted to have isolated buccal fat pad loss, raising suspicion of acquired lipodystrophy. Despite well-preserved subcutaneous fat over the trunk and limbs, she had undetectable serum leptin levels. Whole-body fluorodeoxyglucose (FDG)-positron emission tomography scan showed diffuse mild FDG activity throughout the subcutaneous tissue, suggesting underlying inflammation. Over the next 3 months, she developed progressive fat loss leading to generalized lipodystrophy. Adipose tissue dysfunction, secondary to ICI-induced subclinical panniculitis, precedes overt fat loss and is characterized by hypoleptinemia and metabolic abnormalities. Oxford University Press 2023-03-09 /pmc/articles/PMC10580409/ /pubmed/37908472 http://dx.doi.org/10.1210/jcemcr/luad025 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Case Report
Dhanasekaran, Maheswaran
Sandooja, Rashi
Higgins, Alexandra S
Simha, Vinaya
Marked Hypoleptinemia Precedes Overt Fat Loss in Immune Checkpoint Inhibitor-induced Acquired Generalized Lipodystrophy
title Marked Hypoleptinemia Precedes Overt Fat Loss in Immune Checkpoint Inhibitor-induced Acquired Generalized Lipodystrophy
title_full Marked Hypoleptinemia Precedes Overt Fat Loss in Immune Checkpoint Inhibitor-induced Acquired Generalized Lipodystrophy
title_fullStr Marked Hypoleptinemia Precedes Overt Fat Loss in Immune Checkpoint Inhibitor-induced Acquired Generalized Lipodystrophy
title_full_unstemmed Marked Hypoleptinemia Precedes Overt Fat Loss in Immune Checkpoint Inhibitor-induced Acquired Generalized Lipodystrophy
title_short Marked Hypoleptinemia Precedes Overt Fat Loss in Immune Checkpoint Inhibitor-induced Acquired Generalized Lipodystrophy
title_sort marked hypoleptinemia precedes overt fat loss in immune checkpoint inhibitor-induced acquired generalized lipodystrophy
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10580409/
https://www.ncbi.nlm.nih.gov/pubmed/37908472
http://dx.doi.org/10.1210/jcemcr/luad025
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