scholarly journals Isolated Adrenocorticotropic Hormone Deficiency Caused by Camrelizumab in a Patient with Lung Sarcoma: A Case Report and Literature Review

Author(s):  
Wen Huang ◽  
Saran Feng

Abstract Background Immune checkpoint inhibitors significantly increase survival in some malignant tumors, but they also lead to a variety of immune-related adverse events that affect multiple organs, including the liver, lung and endocrine system. Isolated adrenocorticotropic hormone (ACTH) deficiency (IAD) is a rare pituitary disorder characterized by secondary adrenal insufficiency with low or absent cortisol production but the normal secretion of pituitary hormones other than ACTH. IAD caused by atezolizumab, pembrolizumab and nivolumab therapy had been reported, but none is reported in camrelizumab, a new immune checkpoint inhibitor (ICI). Clinicians may not be aware of this unusual side effect. Case presentation: Here, we describe a 70-year-old male patient who had lung sarcoma and was treated with camrelizumab. After nine months of treatment, he developed immune-related pneumonia and hepatitis associated with camrelizumab. The patient discontinued the drug and recovered soon after administration of glucocorticoids. But he subsequently appeared severe hyponatremia, and was diagnosed with late-onset IAD induced by camrelizumab. His symptoms alleviated after glucocorticoid replacement therapy. Conclusion Regular monitoring serum sodium levels and testing endocrine function should be beneficial for cancer patients not only during the treatment of camrelizumab but also after discontinuation of the ICI. Clinicians should consider IAD induced by ICIs when hyponatremia occurs in the patients.

Biology ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 561
Author(s):  
Anca Bobircă ◽  
Florin Bobircă ◽  
Ioan Ancuta ◽  
Alesandra Florescu ◽  
Vlad Pădureanu ◽  
...  

The advent of immunotherapy has changed the management and therapeutic methods for a variety of malignant tumors in the last decade. Unlike traditional cytotoxic chemotherapy, which works by interfering with cancer cell growth via various pathways and stages of the cell cycle, cancer immunotherapy uses the immune system to reduce malignant cells’ ability to escape the immune system and combat cell proliferation. The widespread use of immune checkpoint inhibitors (ICIs) over the past 10 years has presented valuable information on the profiles of toxic adverse effects. The attenuation of T-lymphocyte inhibitory mechanisms by ICIs results in immune system hyperactivation, which, as expected, is associated with various adverse events defined by inflammation. These adverse events, known as immune-related adverse events (ir-AEs), may affect any type of tissue throughout the human body, which includes the digestive tract, endocrine glands, liver and skin, with reports of cardiovascular, pulmonary and rheumatic ir-AEs as well. The adverse events that arise from ICI therapy are both novel and unique compared to those of the conventional treatment options. Thus, they require a multidisciplinary approach and continuous updates on the diagnostic approach and management.


Author(s):  
Jie Zhang ◽  
Zhujiang Dai ◽  
Cheng Yan ◽  
Wenjie Zhang ◽  
Daorong Wang ◽  
...  

AbstractCancer immunotherapy has revolutionized the treatment of many malignant tumors. Although immune checkpoint inhibitors (ICIs) can reactivate the anti-tumor activity of immune cells, sensitivity to immune checkpoint inhibitor therapy depends on the complex tumor immune processes. In recent years, numerous researches have demonstrated the role of intestinal microbiota in immunity and metabolism of the tumor microenvironment, as well as the efficacy of immunotherapy. Epidemiological studies have further demonstrated the efficacy of antibiotic therapy on the probability of patients' response to ICIs and predictability of the short-term survival of cancer patients. Disturbance to the intestinal microbiota significantly affects ICIs-mediated immune reconstitution and is considered a possible mechanism underlying the development of adverse effects during antibiotic-based ICIs treatment. Intestinal microbiota, antibiotics, and ICIs have gradually become important considerations for the titer of immunotherapy. In the case of immunotherapy, the rational use of antibiotics and intestinal microbiota is expected to yield a better prognosis for patients with malignant tumors.


2021 ◽  
Vol 20 ◽  
pp. 153303382110399
Author(s):  
Fan-li Zeng ◽  
Jing-fang Chen

Cholangiocarcinoma is a general term for intrahepatic and extrahepatic malignant tumors deriving in the biliary system. According to the location, it is divided into intrahepatic cholangiocarcinoma, hilar cholangiocarcinoma, and distal cholangiocarcinoma. Progressive cholangiocarcinoma yields poor outcomes with radiotherapy; therefore, there is an urgent need for new therapeutic breakthroughs. Immune checkpoint inhibitor (ICI) therapy brings the treatment for cancer into a new field, with the use of drugs targeting PD-1/PD-L1 and CTLA-4 considerably extending the survival of patients with melanoma, lung cancer, and other solid tumors. The FDA has approved the application of pembrolizumab for solid tumors with high microsatellite instability and defective mismatch repair, including cholangiocarcinoma. Moreover, the combination of ICIs with chemotherapy and radiation therapy showed good promise. The aim of the present study was to review the application of ICIs in the treatment of cholangiocarcinoma and to summarize the reported individualized immunotherapy-based protocols and ongoing clinical trials for clinical reference.


Digestion ◽  
2021 ◽  
pp. 1-9
Author(s):  
Shunichi Yanai ◽  
Yosuke Toya ◽  
Tamotsu Sugai ◽  
Takayuki Matsumoto

<b><i>Background:</i></b> As immune-checkpoint inhibitors (ICI) are becoming standard therapies for malignant tumors, increasing attention has been paid to their associated immune-related adverse events (irAEs). The gastrointestinal tract is the major site of irAEs, and it has recently become evident that the large bowel is the most frequently affected region. The aim of this narrative review was to clarify the endoscopic and histopathologic findings of and treatments for ICI-induced colitis. <b><i>Summary:</i></b> Endoscopic findings of ICI-induced colitis include a reddish, edematous mucosa with increased mucous exudate, loss of normal vascularity, and a granular mucosa with or without mucosal breaks. Histopathologic findings of ICI-induced colitis are expansion of the lamina propria, intraepithelial infiltration of neutrophils, crypt architectural distortion, neutrophilic crypt abscess, and prominent apoptosis. The clinical, endoscopic, and histopathologic severity of ICI-induced colitis is diverse, but colonoscopy together with biopsy is necessary for diagnosis. While a certain proportion of patients with ICI-induced colitis have an intractable clinical course, management guidelines are based on retrospective analyses. Prospective studies are needed to assess the efficacy of various medications, including immunosuppressive regimens. <b><i>Key Messages:</i></b> Colonoscopy with biopsy is the gold standard for the diagnosis of ICI-induced colitis. Endoscopists should be aware of the clinical features and pathophysiology of ICI-induced colitis for prompt diagnosis and treatment planning.


Author(s):  
Margit G. Proescholdt ◽  
Marc Walter

Alcohol has widespread effects on multiple organs, including the endocrine organs, potentially impairing endocrine function and affecting the entire endocrine milieu. Endocrine impairment may be observed with acute alcohol ingestion, excessive chronic alcohol consumption, and during alcohol withdrawal. Whereas many effects of alcohol on the endocrine organs are reversible following cessation of alcohol consumption, some changes may extend into abstinence. Importantly, endocrine dysfunction observed in alcoholism, is no longer considered to simply result from hepatic failure or chronic malnutrition, but, at least partially, from direct, toxic actions of alcohol on the endocrine organs themselves. In addition, there is increasing evidence that the endocrine system itself may play a crucial role in the pathogenesis of addictive behaviour. Ethanol and its metabolite acetaldehyde directly affect cell membranes and influences intracellular metabolism. Indirect effects include stress, nausea, and vomiting during acute intoxication and withdrawal. Whereas the list of alcohol-induced endocrine dysfunction is long, scientific and epidemiological evidence is frequently controversial. Controversies may result from the highly heterogenic group of alcohol-dependent individuals regarding dose and duration of alcohol consumption, periods of abstinence, age, gender, nutritional status, cigarette smoking, use of other drugs, presence of other diseases, particularly liver disease, and the complexity of endocrine regulation in general.


2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Ayumu Takeno ◽  
Masahiro Yamamoto ◽  
Miwa Morita ◽  
Sayuri Tanaka ◽  
Ippei Kanazawa ◽  
...  

2019 ◽  
Vol 12 (8) ◽  
pp. e230848 ◽  
Author(s):  
Julien Pierrard ◽  
Bénédicte Petit ◽  
Sarah Lejeune ◽  
Emmanuel Seront

The increased use of immune checkpoint inhibitors (ICIs) has led to the observation of a variety of immune-related adverse events (irAEs). These irAEs occur usually within the first months after ICIs onset and can involve theorically all organs. We describe two rare irAEs occurring in a 70-year-old caucasian man who was treated with nivolumab for an advanced urothelial cancer of the left kidney. He developed an isolated adrenocorticotropic hormone deficiency that was diagnosed at week 19 and a neurological complication that appeared at week 79 and initially confounded with a lumbar spinal stenosis. Diagnosis of Guillain-Barré syndrome was finally confirmed with the complete resolution of symptoms after 5 days of intravenous immunoglobulin and corticosteroids. We highlight the importance of quickly recognising these potential life-threatening irAEs such as cortisol insufficiency and neurologic adverse events whose initially presentation could be non-specific.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Wenwen Yang ◽  
Caining Lei ◽  
Shaoming Song ◽  
Wutang Jing ◽  
Chuanwei Jin ◽  
...  

AbstractAfter being stagnant for decades, there has finally been a paradigm shift in the treatment of cancer with the emergence and application of immune checkpoint inhibitors (ICIs). The most extensively utilized ICIs are targeting the pathways involving programmed death-1 (PD-1) and cytotoxic T-lymphocyte associated protein 4 (CTLA-4). PD-1, as an crucial immune inhibitory molecule, by and large reasons the immune checkpoint response of T cells, making tumor cells get away from immune surveillance. Programmed cell death ligand-1 (PD-L1) is exceptionally expressed in most cancers cells and approves non-stop activation of the PD-1 pathway in the tumor microenvironment. PD-1/PD-L1 inhibitors can block the combination of PD-1 and PD-L1, inhibit hostile to regulatory signals, and restore the activity of T cells, thereby bettering immune response. The current researchers assume that the efficacy of these drugs is related to PD-L1 expression in tumor tissue, tumor mutation burden (TMB), and other emerging biomarkers. Although malignant tumors can benefit from the immunotherapy of PD-1/PD-L1 inhibitors, formulating a customized medication model and discovering biomarkers that can predict efficacy are the new trend in the new era of malignant tumor immunotherapy. This review summarizes the mechanism of action of PD-1/PD-L1 inhibitors, their clinical outcomes on various malignant tumors, their efficacy biomarkers, as well as predictive markers of irAEs.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sofia Antoniou ◽  
Georgios Bazazo ◽  
Ludwig Röckl ◽  
Marios Papadakis ◽  
Christian Berg

Abstract Background Nivolumab is an anti-programmed cell death protein 1 antibody, typically used as cancer immunotherapy agent. Despite multiple clinical benefits it might cause autoimmune-related side-effects, often involving the endocrine system. To our knowledge, this is the first case of nivolumab-induced hypophysitis manifesting several months after treatment discontinuation. Case presentation We, herein, report a 53-year-old patient with hypophysitis and isolated adrenocorticotropic hormone deficiency, who presented with recurring syncopal episodes and persistent mild hyponatremia. The performed challenged tests were consistent with secondary adrenal insufficiency, while responses of other anterior pituitary hormones were preserved. Magnetic resonance imaging revealed thickened pituitary stalk, consistent with hypophysitis. The patient’s condition gradually improved after administration of hydrocortisone, with normalization of sodium and glucose-levels. The related literature is discussed. Conclusions We conclude that even after discontinuation of nivolumab, isolated adrenal insufficiency can occur. Therefore, in case of administration of such agents, clinical assessment, and routine monitoring of blood pressure, sodium-, glucose-levels, pituitary hormones as well as magnetic resonance imaging are needed to identify such conditions and prevent an adrenal crisis.


2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Yetao Wang ◽  
Suying Qian ◽  
Kesang Li

Targeted immune checkpoint-based immunotherapy has achieved remarkable success in the treatment of malignant tumors. Immune checkpoint inhibitor-programmed cell death protein 1 (PD-1) antibody opens a new era of immunotherapy for platinum-refractory recurrent/metastatic oral squamous cell carcinoma (OSCC). The overall survival of patients treated with immunological checkpoint inhibitors was significantly prolonged, and the overall incidence of grade 3-4 drug-related adverse events (AEs) occurred was lower. This article briefly describes the development of PD-1 inhibitors in the treatment of OSCC. The purpose of this review is to briefly highlight the clinical development of PD-1 inhibitors in OSCC therapy to date.


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