Polyendocrinopathy resulting from pembrolizumab in a patient with a malignant melanoma
Open accessAbstract
INTRODUCTION: Checkpoint inhibitors have significantly improved the prognosis of patients with advanced melanoma. These cancer immunotherapy drugs have specific endocrine autoimmune toxicity. We describe a case of an adrenal insufficiency secondary to pembrolizumab, an anti-programmed cell death-1 monoclonal antibody. Moreover, this case of polyendocrinopathy resulting from a pembrolizumab as the adrenal insufficiency occurred after a thyroiditis. PARTICIPANT: A 55-year-old female was started on pembrolizumab immunotherapy for a metastatic choroidal melanoma. Five months after initiation, she suffered from thyrotoxicosis. A thyroiditis was diagnosed by iodine-123 thyroid scintigraphy and ultrasonography. Pembrolizumab therapy was maintained. Two weeks later, without any other treatment given, she patient developed hypothyroidism and levothyroxine substitution was started. Pembrolizumab proved to be ineffective and was stopped 9 months after initiation. One month following its discontinuation, the patient was hospitalized in the intensive care unit. Severe hyponatremia (115 mmol/L) associated with hyperkalemia (5.7 mmol/L) led to the early recognition and treatment of an acute adrenal insufficiency. Positive results for adrenal cortex and 21-hydroxylase antibodies were in favor of autoimmune toxicity. CONCLUSION: This case highlights the diversity of potential endocrine toxicity of checkpoint inhibitors. Because acute adrenal crisis may be associated with substantial morbidity and mortality, physicians must be aware of these rare adverse events to allow an early diagnosis.
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Primary adrenal insufficiency is related to immune destruction of the adrenal glands consequent to hyperstimulation of the immune system due to the mechanism of action of immune checkpoint inhibitors.
“Primary AI is related to an immune destruction of the adrenal glands consequent to a hyperstimulation of the immune system due to ICIs mechanism of action.”
From The Changing Face of Drug-induced Adrenal Insufficiency in the Food and Drug Administration Adverse Event Reporting System (2022) · cites this paper as [33]
The Discussion reports pembrolizumab-associated primary adrenal failure and says positive antiadrenal antibodies confirmed an autoimmune cause in the patient. The paper also says checkpoint inhibitors restore T-cell activity and can cause autoimmune toxicity, but it does not establish immune-system hyperstimulation as the mechanism of adrenal destruction; it says the mechanisms of endocrine toxicity remain unclear. No page numbers are available in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredPrimary adrenal insufficiency has been linked to antiadrenal antibodies and adrenal gland atrophy.
“It has been linked to antiadrenal antibodies (32, 33), while atrophy of the glands has been reported as well (33).”
From The Changing Face of Drug-induced Adrenal Insufficiency in the Food and Drug Administration Adverse Event Reporting System (2022) · cites this paper as [33]
The plausible mechanisms underlying immune checkpoint inhibitor-induced adrenal insufficiency are adrenal hypofunction (primary adrenal insufficiency) or pituitary ACTH deficiency (secondary adrenal insufficiency).
“The plausible mechanisms underlying the development of AI by ICIs are adrenal hypofunction (primary AI) or pituitary ACTH deficiency (secondary AI).”
From The Changing Face of Drug-induced Adrenal Insufficiency in the Food and Drug Administration Adverse Event Reporting System (2022) · cites this paper as [33]
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Cites
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- Authors
- Paepegaey, A.-C., Lheure, C., Ratour, C., Lethielleux, G., Clerc, J., Bertherat, J., Kramkimel, N., & Groussin, L.
- Affiliations
- Hôpital Cochin (FR)
- Department of Endocrinology, Cochin Hospital, Assistance Publique Hôpitaux de Paris, Paris Descartes University, 75014 Paris, France
- Department of Nuclear Medicine, Cochin Hospital, Assistance Publique Hôpitaux de Paris, Paris Descartes University, 75014 Paris, France
- Corresponding author
- Paepegaey, Anne-Cécile
- Venue
- Journal of the Endocrine Society
- Publisher
- The Endocrine Society
- Published
- 2017-04-28
- Volume
- 1
- Issue
- 6
- Pages
- 646-649
- ISSN
- 2472-1972 (ISSN-L)
- PMC
- PMC5686573
- OpenAlex
- W2607950543
- Cited by
- 102
- References
- 11
- Citations by year
- 2026: 4 · 2025: 12 · 2024: 10 · 2023: 17 · 2022: 9 · 2021: 13 · 2020: 17 · 2019: 10 · 2018: 10
- FWCI
- 8.00
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of the Endocrine Society (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
- Keywords
- pembrolizumab, polyendocrinopathy, adrenal insufficiency, autoimmune adrenal insufficiency, choroidal melanoma, immune checkpoint inhibitors, thyrotoxicosis, thyroiditis, hyponatremia, hyperkalemia, 21-hydroxylase antibodies, adverse drug reactions, immunotherapy toxicity
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