scholarly journals The influence of monoclonal antibodies for cancer treatment on the endocrine system

2021 ◽  
Vol 75 ◽  
pp. 317-327
Author(s):  
Kamil Dyrka ◽  
Daria Witasik ◽  
Agata Czarnywojtek ◽  
Katarzyna Łącka
Keyword(s):  
Monoclonal Antibodies ◽  
Adverse Effects ◽  
Cancer Treatment ◽  
Checkpoint Inhibitors ◽  
Endocrine System ◽  
New Methods ◽  
Threatening Condition ◽  
Life Threatening ◽  
Causes Of Mortality ◽  
Cessation Of Treatment

Cancer is one of the main causes of mortality worldwide. Thanks to scientific research, new methods of cancer treatment, including molecularly targeted therapy, are being developed. Monoclonal antibodies are used to treat many diseases, including some types of cancer, and affect various systems of the human body. The presented article aims to present the adverse effects of molecularly targeted cancer therapy on the endocrine system based on the current literature data. Immune checkpoint inhibitors, such as anti-CTLA-4 and anti-PD-1 or its ligand PD-L1, can cause a variety of autoimmune adverse effects, among others, thyroid dysfunction, hypophysitis, and diabetes mellitus. The authors also paid attention to monitoring selected diagnostic parameters to prevent endocrine adverse effects during a therapy with monoclonal antibodies. The development of adverse effects may sometimes progress atypically and rapidly, and may be a life-threatening condition. Clinicians should choose individual schemes of treatment for particular patients. The patient’s condition should also be monitored before, during and after the therapy. The decision about the continuation of treatment with monoclonal antibodies should be based especially on a risk connected with the cessation of treatment. Clinical trials should be continued to improve knowledge about the side effects of monoclonal antibodies.

scholarly journals Myxedema Coma: A Life-Threatening Condition in Patients Using Pembrolizumab

2020 ◽  
Vol 2020 ◽  
pp. 1-2
Author(s):  
Sangeetha Gummalla ◽  
Madhura Manjunath ◽  
Brian Phillips
Keyword(s):  
Adverse Effects ◽  
Checkpoint Inhibitors ◽  
Thyroid Stimulating Hormone ◽  
Diagnostic Challenge ◽  
Myxedema Coma ◽  
Advanced Malignancies ◽  
Threatening Condition ◽  
Life Threatening ◽  
Rapid Transition

The advent of immune checkpoint inhibitors has significantly improved the prognosis of patients with advanced malignancies. As we begin to understand these medications, multiple immune-related adverse effects (irAEs) have been found with these drugs, including endocrinopathies. Understanding the treatment-related adverse events of these medications is critical for clinical practice. Thyroid-related adverse effects usually occur within the first three months of treatment and rarely after eight months. It can manifest as an early onset of thyrotoxicosis, which is largely asymptomatic, followed by a rapid transition to hypothyroidism, requiring long-term levothyroxine substitution. We present a case in which our patient was found unresponsive, hypothermic, and with respiratory failure almost after completing a year of treatment with pembrolizumab. He had an initial mild elevation in thyroid-stimulating hormone (TSH) of 6.52, although with normal free thyroxine (T4) of 1.06, in his first three months of starting treatment which then rapidly progressed to a true myxedema coma. The infrequency with which this occurs makes it a diagnostic challenge.

Adverse reactions to medication

2019 ◽  
pp. 103-114
Author(s):  
Tomasz Bajorek ◽  
Jonathan Hafferty
Keyword(s):  
Adverse Effect ◽  
Adverse Effects ◽  
Adverse Reactions ◽  
Bleeding Risk ◽  
Inpatient Setting ◽  
Extrapyramidal Side Effects ◽  
Inpatient Psychiatry ◽  
Drug Induced ◽  
Threatening Condition ◽  
Life Threatening

Adverse reactions to medication represent a major issue in inpatient psychiatry. This chapter systematically explores the most relevant, concerning, and problematic adverse effects routinely encountered in an inpatient setting. It describes the typical presentation, pathophysiology, incidence, and practical management of these problems. Extrapyramidal side effects including acute dystonia, drug-induced parkinsonism, akathisia, and tardive dyskinesia are considered before the chapter explores the rare but potentially life-threatening condition of neuroleptic malignant syndrome. Other adverse effects common to antipsychotics that are described include hyperprolactinaemia and psychotropic-induced arrhythmias including QTc prolongation. Sexual dysfunction is an under-recognized and undertreated adverse effect common to several classes of psychotropic medication and is also considered. Focusing on antidepressants, the chapter reviews the frequently encountered issue of hyponatraemia as well as serotonin syndrome and selective serotonin reuptake inhibitor-induced bleeding risk. Finally, the chapter addresses perinatal considerations for psychotropic drugs.

Evaluation of tolerability and reactions of immune checkpoint inhibitors.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e14605-e14605 ◽  
Author(s):  
Ozlem Nuray Sever ◽  
Ozlem Sonmez ◽  
Osman Gokhan Demir
Keyword(s):  
Monoclonal Antibodies ◽  
Side Effects ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Treatment Interruption ◽  
Ease Of Use ◽  
Treatment Change ◽  
Function Test ◽  
Cessation Of Treatment

e14605 Background: Immunotherapies have revolutionized the treatment of cancer, especially in recent years. Today, there are anti-CTLA-4 antibodies and PD-L1 monoclonal antibodies which are active in use as checkpoint inhibitors. Side effects of these agents have a different spectrum in the form of immuno-related side effects. Methods: In this study, we aimed to evaluate the side effect and tolerability in patients treated with immune checkpoint inhibitors in our clinic. Results: 32 patients who were treated with PD-L1 monoclonal antibodies between August 2015 and January 2017 were screened retrospectively in our clinic. Six of the cases had immuno-related side effects (18.75%). 2 patients had a elevated liver function test. Both patients were diagnosed with NSCLC. In both of them, elevation was detected in the second course of nivolumab treatment, and the USG and hepatitis markers of the patients were normal. Enzymes returned to normal after treatment interruption. In a patient diagnosed with malignant melanoma that receiving pembrolizumab colitis was developed after 3th cycles of the therapy. The treatment of the patient who recovered after steroid administration and treatment interruption continued until the 8th cure. In the third cure of the patient with NSCLC, when nivolumab was used pneumonitis was diagnosed. Steroid treatment was applied for 2 weeks. Our patient continued to use nivolumab for up to 22 cycles. In our patient with malign melanoma that treated with pembrolizumab autoimmune thyroiditis developed. We started prednisolone treatment. After recovery our patient's treatment continued. In one of our patient who was diagnosed with malign melanoma, after the second cure of the treatment, diffuse edema and shortness of breath due to heart failure was detected. Echocardiography revealed a low ejection fraction. Methylprednisolone was started by cessation of treatment. Control ejection fractions normalized. Conclusions: İmmuno-related side effects were regarded as manageable side effects and no treatment change was needed. Immune Checkpoint inhibitors, which have been shown to be useful for survival every day, are proceeding to take a favorable position in the treatment of cancer with ease of use and lack of side effects.

scholarly journals Spontaneous massive duodenal perforation after ovarian cancer treatment with bevacizumab

2020 ◽  
Vol 2020 (6) ◽  
Author(s):  
Michael Karanikas ◽  
Konstantinia Kofina ◽  
Dimitrios Potolidis ◽  
Soultana Foutzitzi ◽  
Savas Deftereos ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Adverse Effects ◽  
Cancer Treatment ◽  
Bowel Perforation ◽  
Gastrointestinal Perforation ◽  
Duodenal Perforation ◽  
Life Threatening ◽  
Life Threatening Complication ◽  
Caucasian Female

Abstract Bevacizumab has been used as an effective drug for ovarian cancer. However, serious adverse effects, such as gastrointestinal perforation, can occur. Spontaneous gastrointestinal perforation is an uncommon, yet life-threatening complication related to bevacizumab administration. We present the case of a 65-year-old Caucasian female who presented with acute abdomen 10 days after the first administration of bevacizumab for ovarian cancer treatment, and she was diagnosed intraoperatively with a massive duodenal perforation. Bowel perforation after bevacizumab administration is a serious and potentially lethal complication. Careful follow-up of the patients is necessary in order to detect any signs of this condition in time.

scholarly journals SAT-492 Impending Thyroid Storm Induced by Checkpoint Inhibitors

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Ya Zhou ◽  
Kathryn Jobbins ◽  
Raju Panta
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Disease ◽  
Checkpoint Inhibitors ◽  
Early Recognition ◽  
Nodular Goiter ◽  
Thyroid Storm ◽  
Prior History ◽  
Free T4 ◽  
Threatening Condition ◽  
Life Threatening

Abstract Introduction: Thyroid storm is a rare but life threatening condition due to thyroid hormone excess and is usually caused by Graves disease, toxic nodular goiter or rarely due to thyroiditis. Immune checkpoint inhibitors (ICI) are a novel choice for treating cancers, and carry a risk for development of endocrinopathies. We report a case of impending thyroid storm 5 weeks after initiation of ICI. Case Presentation: 81-year-old Caucasian male with metastatic renal cell carcinoma presented with generalized weakness and fatigue 5 weeks after ipilimumab and nivolumab were started. He had no prior history of thyroid disease and had normal thyroid functions before the treatment. He complained of palpitations, heat intolerance and loose stools on admission. On examination he was disoriented, tachycardic (128bpm) with new onset atrial fibrillation, had moist skin and brisk reflexes. He had non-tender thyroid, no thyromegaly, and no nodules palpated. Burch-Wartofsky score was 35, suggesting impending thyroid storm. Laboratory investigation showed elevated free T4 (>7.77), elevated free T3 (8.6) with a suppressed TSH (< 0.02). He had positive anti-TPO but Thyrotropin receptor antibody was negative. He was treated with propranolol 40 mg three times daily, prednisone 40 daily, methimazole 30mg three times a day with significant improvement in free T4 (5.67) within first 48 hours. Discussion: Imipimumab and nivolumab are monoclonal antibodies against cytotoxic T-lymphocyte associated protein 4 (CTLA-4) and programmed death receptor-1 (PD-1) respectively. The reported incidence of thyroid dysfunction after combined imipimumab and nivolumab therapy can be as high as 22%1. Thyroiditis could present as early as 2-6 weeks 2 after treatment, and hypothyroidism tends to present between 5 months and 3 years3. According to a current consensus4, baseline TSH and FT4 should be drawn prior to initiating ICI. Thyroid storm is a clinical diagnosis and Burch-Wartofsky score can help in diagnosis. A high degree of suspicion and prompt diagnosis of thyroid storm and treatment is of utmost importance especially in this patient population. Rapid improvements in thyroid hormone levels suggest thyroiditis as a potential cause for thyrotoxicosis. Conclusion: ICI induced thyroid disease is not an uncommon condition. It could present as either thyrotoxicosis or hypothyroidism. Both patient and clinician should be aware of potential signs and symptoms of thyroid storm for early recognition and timely treatment of this life-threatening condition. [1] Byun DJ et al.Nat Rev Endocrinol. 2017 Apr;13(4):195-207 [2] Iyer PC et al. Thyroid. 2018 Oct;28(10):1243-1251 [3] Endocr Relat Cancer. 2014 Mar 7;21(2):371-81 [4] Puzanov et al. Journal for ImmunoTherapy of Cancer (2017) 5:95

scholarly journals Lack of an Association between the Functional Polymorphism TREM-1 rs2234237 and the Clinical Course of Sepsis among Critically Ill Caucasian Patients—A Monocentric Prospective Genetic Association Study

2019 ◽  
Vol 8 (3) ◽  
pp. 301
Author(s):  
Julius Runzheimer ◽  
Caspar Mewes ◽  
Benedikt Büttner ◽  
José Hinz ◽  
Aron-Frederik Popov ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Disease Severity ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Kaplan Meier ◽  
Threatening Condition ◽  
Life Threatening ◽  
Secondary Endpoints ◽  
Causes Of Mortality ◽  
Caucasian Patients

Sepsis is a life-threatening condition and a significant challenge for those working in intensive care, where it remains one of the leading causes of mortality. According to the sepsis-3 definition, sepsis is characterized by dysregulation of the host response to infection. The TREM-1 gene codes for the triggering receptor expressed on myeloid cells 1, which is part of the pro-inflammatory response of the immune system. This study aimed to determine whether the functional TREM-1 rs2234237 single nucleotide polymorphism was associated with mortality in a cohort of 649 Caucasian patients with sepsis. The 90-day mortality rate was the primary outcome, and disease severity and microbiological findings were analyzed as secondary endpoints. TREM-1 rs2234237 TT homozygous patients were compared to A-allele carriers for this purpose. Kaplan–Meier survival analysis revealed no association between the clinically relevant TREM-1 rs2234237 single nucleotide polymorphism and the 90-day or 28-day survival rate in this group of septic patients. In addition, the performed analyses of disease severity and the microbiological findings did not show significant differences between the TREM-1 rs2234237 genotypes. The TREM-1 rs2234237 genotype was not significantly associated with sepsis mortality and sepsis disease severity. Therefore, it was not a valuable prognostic marker for the survival of septic patients in the studied cohort.

scholarly journals Hyperglycemia During Childhood Cancer Therapy: Incidence, Implications, and Impact on Outcomes

2019 ◽  
Vol 2019 (54) ◽  
pp. 132-138 ◽  
Author(s):  
Allison Grimes ◽  
Ashraf Mohamed ◽  
Jenna Sopfe ◽  
Rachel Hill ◽  
Jane Lynch
Keyword(s):  
Risk Factors ◽  
Cancer Therapy ◽  
Adverse Effects ◽  
Cancer Treatment ◽  
Childhood Cancer ◽  
Pediatric Cancer ◽  
Immune Checkpoint Inhibitors ◽  
Systematic Approach ◽  
Checkpoint Inhibitors ◽  
Limited Data

Abstract Hyperglycemia is a known complication of therapies used in the treatment of childhood cancer, particularly glucocorticoids and asparaginase. It has been linked to increased infection and reduced survival. With more limited data on hyperglycemia during childhood cancer treatment compared with adult cancer, impact on outcomes is less clear in this population. As additional glycemic-altering cancer agents including immune checkpoint inhibitors and targeted therapies make their way into pediatric cancer treatment, there is a more pressing need to better understand the mechanisms, risk factors, and adverse effects of hyperglycemia on the child with cancer. Thus, we utilized a systematic approach to review the current understanding of the incidence, implications, and outcomes of hyperglycemia during childhood cancer therapy.

scholarly journals Osteoradionecrosis Rate in Patients Undergoing Radiotherapy for Head and Neck Cancer Treatment: A Six Months Follow-Up of a Perspective Clinical Study

Proceedings ◽  
2019 ◽  
Vol 35 (1) ◽  
pp. 35
Author(s):  
Rupe ◽  
Miccichè ◽  
Paludetti ◽  
Gallenzi ◽  
Lajolo
Keyword(s):  
Head And Neck Cancer ◽  
Clinical Study ◽  
Adverse Effects ◽  
Cancer Treatment ◽  
Head And Neck ◽  
Neck Cancer ◽  
High Dose ◽  
Life Threatening

High-dose radiotherapy (RT) for head and neck cancer has significant adverse effects on maxillofacial tissues, among which osteoradionecrosis (ORN) is the most severe and potentially life-threatening. [...]

scholarly journals Therapeutic and Systemic Adverse Events of Immune Checkpoint Inhibitors Targeting the PD-1/PD-L1 axis for Clinical Management of NSCLC

2021 ◽  
Vol 30 ◽  
pp. 096368972110415
Author(s):  
Jing Chen ◽  
Yaser Alduais ◽  
Baoan Chen
Keyword(s):  
Monoclonal Antibodies ◽  
Adverse Effects ◽  
Adverse Events ◽  
Immune Evasion ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Critical Parameters ◽  
Small Cell Lung ◽  
Randomized Controlled ◽  
Google Search

Non-small-cell lung cancer takes up the majority of lung carcinoma-caused deaths. It is reported that targeting PD-1/PD-L1, a well-known immune evasion checkpoint, can eradicate tumor. Checkpoint inhibitors, such as monoclonal antibodies, are actively employed in cancer treatment. Thus, this review aimed to assess the therapeutic and toxic effects of PD-1/PD-L1 inhibitors in treatment of NSCLC. So far, 6 monoclonal antibodies blocking PD-1/PD-L1 interaction are identified and used in clinical trials and randomized controlled trials for NSCLC therapy. These antibody-based therapies for NSCLC were collected by using search engine PubMed, and articles about the assessment of adverse events were collected by using Google search. Route of administration and dosage are critical parameters for efficient immunotherapy. Although antibodies can improve overall survival and are expected to be target-specific, they can cause systemic adverse effects in the host. Targeting certain biomarkers can limit the toxicity of adverse effects of the antibody-mediated therapy. Clinical experts with knowledge of adverse effects (AEs) of checkpoint inhibitors can help manage and reduce mortalities associated with antibody-based therapy of NSCLC.

scholarly journals Acute thrombocytopenia due to meropenem: a case report

2019 ◽  
Vol 8 (12) ◽  
pp. 2766
Author(s):  
Priti Dhande ◽  
Shreyas Deshmukh
Keyword(s):  
Case Report ◽  
Adverse Effects ◽  
Broad Spectrum ◽  
Antibacterial Drug ◽  
Immune Mechanism ◽  
Drug Induced ◽  
Threatening Condition ◽  
Life Threatening ◽  
Severe Infections ◽  
Abdominal Infections

Meropenem is a broad spectrum antibacterial drug from the carbapenem family. It is commonly used as an empirical antimicrobial in severe infections like pneumonia, intra-abdominal infections, septicaemia, meningitis etc. Severe adverse effects with meropenem are rare (<1 %) which include hypersensitivity and hematologic adverse effects. In the literature, few cases have been reported of meropenem induced thrombocytopenia that has shown the immune mechanism by which thrombocytopenia occurs. Drug induced thrombocytopenia (DITP) can be a life threatening condition if not diagnosed and managed properly. As meropenem is being widely used in hospitals nowadays, it is important to be aware of the rare but serious adverse effects it causes.

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