Endocrine immune-related adverse events: Adrenal, parathyroid, diabetes insipidus, and lipoatrophy

Atkinson, Mark A.; Lansdown, Andrew

doi:10.1016/j.beem.2022.101635

Cited by 18 publications

(10 citation statements)

References 67 publications

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“…There are reports of rarer endocrinopathies associated with ICI treatment, including diabetes insipidus, hypoparathyroidism and autoimmune polyglandular syndromes (9,49). However, we focussed on endocrine irAEs most likely to be encountered in clinical practice (8,9).…”

Section: Discussionmentioning

confidence: 99%

Effects of immune checkpoint inhibitor associated endocrinopathies on cancer survival

Yang,

Murthy,

Cortellini

et al. 2024

Front. Endocrinol.

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ObjectivesImmune checkpoint inhibitors (ICIs) are associated with immune-related adverse events (irAEs), of which endocrinopathies are common. We characterized endocrine and non-endocrine irAEs in cancer patients receiving ICIs, identified risk factors for their development and established whether endocrine and non-endocrine irAEs were differentially associated with improved cancer prognosis.Design and methodsSingle-center, retrospective cohort study of patients with advanced or metastatic solid tumors receiving at least one ICI treatment cycle (242 men, 151 women, median age 65 years). Main outcome measures were incidence of any irAE during the study period, overall survival and time to treatment failure.ResultsNon-endocrine irAEs occurred in 32% and endocrine irAEs in 12% of patients. Primary thyroid dysfunction was the most common endocrine irAE (9.5%) and the majority of endocrinopathies required permanent hormone replacement. Women had an increased risk of developing endocrine irAEs (p = 0.017). The biggest survival advantage occurred in patients who developed both endocrine and non-endocrine irAEs (overall survival: HR 0.16, CI 0.09-0.28). Time to treatment failure was also significantly improved in patients who developed endocrine irAEs (HR 0.49, CI 0.34 – 0.71) or both (HR 0.41, CI 0.25 – 0.64) but not in those who only developed non-endocrine irAEs.ConclusionsWomen may have increased risk of endocrine irAEs secondary to ICI treatment. This is the first study to compare the effects of endocrine irAEs with non-endocrine irAEs on survival. Development of endocrine irAEs may confer survival benefit in ICI treatment and future, prospective studies are needed to elucidate this.

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Section: Discussionmentioning

confidence: 99%

Effects of immune checkpoint inhibitor associated endocrinopathies on cancer survival

Yang,

Murthy,

Cortellini

et al. 2024

Front. Endocrinol.

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“…Comorbidities and complications often negatively impact the therapeutic efficacy of immune checkpoint blockade therapy [31]. Some studies have shown that diabetic patients also face a higher risk of autoimmune diabetes and immune-related adverse effects such as immune inflammatory response and immune-related thyroid disease when receiving immune checkpoint blockade therapy, and these immune disorders may lead to decreased responsiveness to immune checkpoint blockade therapies and diminish the effectiveness of the anti-tumor immune response [32][33][34][35]. Also, these side effects may further exacerbate a patient›s pre-existing diabetic condition, leading to a variety of cytokines releasing, some of which may affect insulin secretion and use.…”

Section: Discussionmentioning

confidence: 99%

"Negative Association between Diabetes Mellitus and the Efficacy of Cancer Immunotherapy"

Sun

2024

BJSTR

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Diabetes mellitus (DM) is one of the risk factors for poor prognosis and outcomes in cancer patients. This study aimed to explore the efficacy of tumor immunotherapy for cancer patients with comorbid diabetes. A systematic electronic search on keywords including immunotherapy and tumor patients with diabetes was performed through electronic databases including PubMed, Embase and Web of Science. The primary outcome was the overall survival (OS). The secondary outcomes were the progression-free survival (PFS). Four retrospective cohort studies were included for analysis: A total of 3065 cancer patients were enrolled, including 1509 patients with comorbid diabetes. Compared to patients without diabetes, cancer patients with comorbid diabetes had a significantly lower overall survival (HR = 1.54, 95% CI: 1.27 to 1.87, P < 0.0001) and a similarly significantly shorter PFS (HR = 1.48, 95% CI: 1.24 to 1.78, P < 0.0001) after treatment with immunotherapy. This study suggested that DM might confer a shorter OS and PFS for advanced cancer patients with immunotherapy. Further prospective research is needed to confirm these findings.

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“…A small number of patients also have multiple pituitary hormone de ciencies. Damage to the posterior lobe can cause low-frequency symptoms such as diabetes insipidus and visual impairment [7][8]. Hypophysitis has no speci c clinical manifestations, usually presenting as headache, fatigue, and decreased appetite.…”

Section: Restart Immunotherapy and Follow-upmentioning

confidence: 99%

PD-1/PD-L1 Inhibitors-Induced Hypophysitis : A real-world retrospective cohort study

Zhu,

Zhang,

Luo

et al. 2023

Preprint

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Purpose:The main purposes and research question was to describe the clinical,laboratory, imageology and morphological characteristics of hypophysitis induced by PD-1/PD-L1 inhibitors,and its long-time course. Methods: This study was conducted at our hospital between January 2020 and October 2023,with longitudinal follow-up of patients 22 cases were included. Results: The onset time ranged from 13 days to 802 days,The main symptom of the patients were fatigue and poor appetite :about 16 cases complained of fatigue and 13 of poor appetite,other symptom have:nausea,vomiting,fever,chest and so on.All patients presented adrenocorticotropic hormone (ACTH) and Serum cortisol (COR) deficiency. Two patients showed Supersellae cistern herniation underwent pituitary MRI.All patients' symptoms improved after treatment with glucocorticoids. At last follow-up, None of patients serum cortisol and ACTH were recovered . Conclusion: Manifestations of PD-1/PD-L1 inhibitor-induced hypophysitis were nonspecific, serum hormone should be closely monitored in routine work.

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Endocrine immune-related adverse events: Adrenal, parathyroid, diabetes insipidus, and lipoatrophy

Cited by 18 publications

References 67 publications

Effects of immune checkpoint inhibitor associated endocrinopathies on cancer survival

Effects of immune checkpoint inhibitor associated endocrinopathies on cancer survival

"Negative Association between Diabetes Mellitus and the Efficacy of Cancer Immunotherapy"

PD-1/PD-L1 Inhibitors-Induced Hypophysitis : A real-world retrospective cohort study

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