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European Journal of Endocrinology Sep 2019To better define the rare adverse event (AE) of diabetes mellitus associated with immune checkpoint inhibitors (ICIs).
OBJECTIVE
To better define the rare adverse event (AE) of diabetes mellitus associated with immune checkpoint inhibitors (ICIs).
DESIGN AND METHODS
We report the case of a lung cancer patient with diabetic ketoacidosis (DKA) and autoimmune thyroiditis during pembrolizumab treatment. We provide a systematic review of all published cases (PubMed/Web of Science/Cochrane, through November 2018) of autoimmune diabetes mellitus related to blockade of the cytotoxic T-lymphocyte antigen 4 (CTLA-4)-, programmed cell death 1 (PD-1) receptor or its ligand (PD-L1) or combination (ICI) therapy.
RESULTS
Our literature search identified 90 patient cases (our case excluded). Most patients were treated with anti-PD-1 or anti-PD-L1 as monotherapy (79%) or in combination with CTLA-4 blockade (15%). On average, diabetes mellitus was diagnosed after 4.5 cycles; earlier for combination ICI at 2.7 cycles. Early-onset diabetes mellitus (after one or two cycles) was observed during all treatment regimens. Diabetic ketoacidosis was present in 71%, while elevated lipase levels were detected in 52% (13/25). Islet autoantibodies were positive in 53% of patients with a predominance of glutamic acid decarboxylase antibodies. Susceptible HLA genotypes were present in 65% (mostly DR4). Thyroid dysfunction was the most frequent other endocrine AE at 24% incidence in this patient population.
CONCLUSION
ICI-related diabetes mellitus is a rare but often life-threatening metabolic urgency of which health-care professionals and patients should be aware. Close monitoring of blood glucose and prompt endocrine investigation in case of hyperglycemia is advisable. Predisposing factors such as HLA genotype might explain why some individuals are at risk.
Topics: Antineoplastic Agents, Immunological; Carcinoma, Non-Small-Cell Lung; Diabetes Mellitus, Type 1; Humans; Immunologic Factors; Lung Neoplasms; Male; Middle Aged
PubMed: 31330498
DOI: 10.1530/EJE-19-0291 -
Frontiers in Endocrinology 2020To explore the risk factors that may predict the lymph node metastasis potential of these lesions and new prevention strategies in papillary thyroid carcinoma patients.... (Meta-Analysis)
Meta-Analysis
To explore the risk factors that may predict the lymph node metastasis potential of these lesions and new prevention strategies in papillary thyroid carcinoma patients. In total, 9,369 papillary thyroid carcinoma patients with 37.17% lymph node metastasis were analyzed (Revman 5.3 software) in this study. The PubMed and Embase databases were used for searching works systematically that were published through to January 22, 2020. Several factors were related to the increased risk of lymph node metastasis in patients with papillary thyroid carcinoma: age <45 years (pooled OR = 1.52, 95% CI = 1.14-2.01, <0.00001); gender = male (pooled OR = 1.68, 95% CI = 1.51-1.87, <0.00001); multifocality (pooled OR = 2.05, 95% CI = 1.45-2.89, <0.0001); tumor size ≥1.0 cm (pooled OR = 3.53, 95% CI = 2.62-4.76, <0.00001); tumor location at the upper pole 1/3 (pooled OR =1.46, 95% CI = 1.04-2.04, = 0.03); capsular invasion + (pooled OR = 3.48, 95% CI = 1.69-7.54, = 0.002); and extrathyroidal extension + (pooled OR = 2.03, 95% CI= 1.78-2.31, <0.00001). However, tumor bilaterality (pooled OR = 0.85, 95% CI = 0.54-1.34, = 0.49) and Hashimoto's thyroditis (pooled OR = 1.08, 95% CI = 0.79-1.49, = 0.62) showed no correlation with lymph node metastasis in papillary thyroid carcinoma patients. The systematic review and meta-analysis defined several significant risk factors of lymph node metastasis in papillary thyroid cancer patients: age (<45 years), gender (male), multifocality, tumor size (>1 cm), tumor location (1/3 upper), capsular invasion, and extra thyroidal extension. Bilateral tumors and Hashimoto's thyroiditis were unrelated to lymph node metastasis in patients with papillary thyroid cancer.
Topics: Humans; Lymphatic Metastasis; Prognosis; Risk Factors; Thyroid Cancer, Papillary; Thyroid Neoplasms
PubMed: 32477264
DOI: 10.3389/fendo.2020.00265 -
Frontiers in Immunology 2022Some degree of platelet index abnormality has been found clinically in the autoimmune thyroid disease (AITD), but the findings are not uniform. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Some degree of platelet index abnormality has been found clinically in the autoimmune thyroid disease (AITD), but the findings are not uniform.
METHODS
The PubMed, Web of Science, Cochrane Library, and Embase databases were searched for relevant articles published up to August 16th, 2022, with no restrictions on the language of the articles. Reference lists of eligible articles were also searched. A random effect model was used to pool the standardized mean difference (SMD) and 95% confidence interval (95% CI) of platelet count (PLT), mean platelet volume (MPV), and platelet distribution width (PDW) between AITD patients and healthy controls, and subgroup analyses were performed.
RESULTS
A total of 19 articles with 6173 people (3824 AITD patients and 2349 healthy people) were included in the meta-analysis. The results showed that PLT and MPV values were significantly increased in AITD patients when compared with healthy people (SMD: 0.164, 95% CI: 0.044 to 0.285; SMD: 0.256, 95% CI: 0.013 to 0.500), while no significant difference was found in PDW between the AITD group and the control group (SMD: 0.060, 95% CI: -0.164 to 0.284). Subgroup analysis according to disease type and thyroid function revealed that for PLT, this difference was only found in the Hashimoto's thyroiditis (HT) and hypothyroid groups, but not in the Graves' disease (GD) and hyperthyroid groups. For MPV, the results were the opposite of those for PLT: MPV was significantly higher in the GD, hyperthyroid, and euthyroid groups than in the control group, but not in the HT and hypothyroid groups. Sensitivity analysis showed that the stability of the pooled MPV was not good. No publication bias was found.
CONCLUSIONS
PLT and MPV are significantly elevated in patients with AITD, with PLT being more significantly elevated in HT and hypothyroidism, and MPV being more significantly increased in GD and hyperthyroidism. Appropriate clinical attention can be paid to the thyroid function of patients when abnormal platelet indices are found, and conversely, the consequences of abnormal platelet parameters such as elevated MPV lead to an increased occurrence of cardiovascular events, which should also be addressed in the AITD population.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022341823.
Topics: Humans; Hashimoto Disease; Mean Platelet Volume; Platelet Count; Graves Disease; Hyperthyroidism; Hypothyroidism
PubMed: 36618418
DOI: 10.3389/fimmu.2022.1089469 -
Seizure Oct 2021Diverse neuronal antibodies are related to autoimmune encephalitis (AE) and AE-related epilepsy. However, the epidemiological characteristics of AE, AE-associated... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Diverse neuronal antibodies are related to autoimmune encephalitis (AE) and AE-related epilepsy. However, the epidemiological characteristics of AE, AE-associated antibodies, and AE-related seizures are still unclear.
AIMS
This research evaluated the relationship between AE, AE-related seizures, and neuronal antibodies, as well as the morbidity of AE with early incidence.
METHODS
The PubMed, Embase, Cochrane, and Web of Science databases were searched. Pooled estimates and 95% confidence intervals (CIs) were calculated using a random-effects model.
RESULTS
Of the 4,869 citations identified, 100 articles were reviewed in full, and 42 subgroups were analyzed. The overall incidence of AE patients with seizures was 42% (95% CI: 0.40-0.44), and among them, the incidence of epilepsy in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis patients was 73% (95% CI: 0.70-0.77). Subsequently, we found that the prevalence of AE as the cause of epilepsy within the pooled period was 1% (95% CI: 0.01-0.02), while the overall positive rate of neuronal antibodies in epilepsy patients was 4% (95% CI: 0.03-0.05). Additionally, the detection rates of different antibodies among epilepsy patients were as follows: anti-NMDAR, 1%; anti-leucine-rich glioma inactivated 1 (LGI1), 1%; anti-contactin-associated protein-like 2 (CASPR2), 2%.
CONCLUSION
Based on our findings, neuronal antibodies may serve as a bridge to study AE and immune-related epilepsy. To further understand the differences in outcomes following different treatment measures, and to provide more information for public health policy and prevention, more research is needed to improve the accuracy of estimations.
Topics: Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Autoantibodies; Encephalitis; Epilepsy; Hashimoto Disease; Humans
PubMed: 34284303
DOI: 10.1016/j.seizure.2021.07.005 -
Frontiers in Endocrinology 2022A growing body of research suggests that patients with polycystic ovary syndrome (PCOS) may be at increased risk of developing Hashimoto's thyroiditis (HT), and having... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
A growing body of research suggests that patients with polycystic ovary syndrome (PCOS) may be at increased risk of developing Hashimoto's thyroiditis (HT), and having both conditions can make the condition worse. However, current research views are not uniform. Therefore, to explore the link between PCOS and HT, we conducted this study.
METHODS
From the establishment of the database to August 2022, we searched 2 databases to study the correlation between Hashimoto's and polycystic ovary syndrome. Two authors independently screened the articles for eligibility, and three authors extracted relevant data. Statistical analysis was performed using STATA16.0 software.
RESULTS
A total of 20 studies were included, including 7 case-control studies and 13 cross-sectional studies. A total of 13 countries and 7857 participants were embraced. Studies have demonstrated that both PCOS patients have an increased risk of HT, and meanwhile, HT patients also have an increased risk of PCOS compared with controls. The study also incorporated that the prevalence of HT in PCOS patients in India and Turkey was higher than in other countries, and the prevalence of HT in PCOS patients in South America was higher than in Asia and Europe.
CONCLUSIONS
In conclusion, our study illustrates that there is a correlation between PCOS and HT, and it is necessary to further study the underlying mechanism between PCOS and HT. At the same time, it is of great significance to regularly screen PCOS patients for HT risk and HT patients for PCOS risk.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD 42022351168.
Topics: Female; Humans; Polycystic Ovary Syndrome; Cross-Sectional Studies; Hashimoto Disease; Prevalence; India
PubMed: 36387911
DOI: 10.3389/fendo.2022.1025267 -
European Review For Medical and... Jan 2017Thyroid disorders, especially Hashimoto's thyroiditis (HT), are observed significantly more often in patients with polycystic ovary syndrome (PCOS) than in the general... (Review)
Review
OBJECTIVE
Thyroid disorders, especially Hashimoto's thyroiditis (HT), are observed significantly more often in patients with polycystic ovary syndrome (PCOS) than in the general population - approximately 27% and 8%, respectively. This is extremely important in young women, because both disorders are connected with fertility problems. As HT and PCOS occur together, fertility problems may become a serious clinical issue in these patients.
MATERIALS AND METHODS
A systematic literature review in PubMed of PCOS- and HT-related articles in English, published until December 2015 was conducted.
RESULTS
The reasons for joint prevalence still remain unclear. Genetic and autoimmune backgrounds are recognized to be possible common etiological factors. Three genetic polymorphisms have been described to play a role in PCOS as well as in HT. They are polymorphism of the gene for fibrillin 3 (FBN3) regulating the activity of transforming growth factor-b (TGF-b) and regulatory T cell levels, gonadotropin-releasing hormone receptor (GnRHR) polymorphism and CYP1B1 polymorphism standing for estradiol hydroxylation. High estrogen-to-progesterone ratios owing to anovulatory cycles, as well as high estrogen levels during prenatal life, disrupt development of the thymus and its function in maintaining immune tolerance, and are suspected to enhance autoimmune response in PCOS. Vitamin D deficiency could be also involved in the pathogenesis of HT and PCOS.
CONCLUSIONS
The above-mentioned common etiological factors associated with fertility problems in HT and PCOS require further research.
Topics: Cytochrome P-450 CYP1B1; Female; Fibrillins; Hashimoto Disease; Humans; Polycystic Ovary Syndrome; Receptors, LHRH; Transforming Growth Factor beta
PubMed: 28165551
DOI: No ID Found -
Frontiers in Endocrinology 2022Hashimoto's thyroiditis (HT) is the most common type of thyroid disease and can cause many different manifestations. The local symptoms of HT are an under-studied area... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Hashimoto's thyroiditis (HT) is the most common type of thyroid disease and can cause many different manifestations. The local symptoms of HT are an under-studied area of research. Therefore, the purpose of this study was to investigate the local symptoms of HT and their prevalence.
METHODS
A systematic review was performed to find articles in PubMed that discuss the local symptoms of HT. Relevant vocabulary terms and key terms included: autoimmune thyroid disease (AITD), hyperthyroidism, hypothyroidism, neck, throat, pharynx, airway, esophagus, breathe, swallow, globus, sleep apnea, symptoms, and quality of life. Two investigators independently screened the eligible studies.
RESULTS
A total of 54 articles fulfilled the inclusion criteria. Of these, 25 were clinical studies, 24 were case reports, and five were reviews. These clinical studies and case reports included a total of 2660 HT patients. There were eight local symptoms related to HT: neck pain (0.02%~16%), voice changes (7%~30%), throat discomfort (20%~43.7%), shortness of breath (28%~50%), dysphagia (29%), goiter-related symptoms (69.44%), sleep apnea, and generally defined compressive symptoms. Due to the use of different outcome measures among all the studies, a meta-analysis of the data could not be performed.
CONCLUSION
Goiter symptoms, which are an item on the ThyPRO scales, are the most frequent local symptoms in HT patients, and include neck pain, voice changes, throat discomfort, and dysphagia. These local symptoms should be identified in the clinic and included in the early diagnosis and management of HT, as well as evaluated further to understand their relevance in the pathogenesis of HT.
Topics: Humans; Deglutition Disorders; Goiter; Hashimoto Disease; Neck Pain; Quality of Life
PubMed: 36743914
DOI: 10.3389/fendo.2022.1076793 -
Cureus Jun 2022Despite recent evidence that low serum 25-hydroxyvitamin D (25(OH)D) levels and deflects may influence the emergence of autoimmune thyroid disorders (AITD), the... (Review)
Review
Despite recent evidence that low serum 25-hydroxyvitamin D (25(OH)D) levels and deflects may influence the emergence of autoimmune thyroid disorders (AITD), the relationship between vitamin D deficiency and Graves' disease (GD) and Hashimoto's thyroiditis (HT), which comprise AITD, remains unclear. We retrieved studies that described vitamin D association with HT and GD from PubMed/Medline, Google Scholar, and the Cochrane Library. We included research studies that compared vitamin D levels and deficiency or sufficiency between AITD cases such as HT and GD cases and control subjects. The final assessment comprised 11 studies that recruited 1952 AITD cases (HT and GD) that were published between 2011 and 2021; these were included in the final review. All the included studies were observational, and more precisely, case-control studies that recruited healthy subjects as well as controls. The majority of the studies reviewed indicated that HT and GD patients have a greater prevalence of vitamin D deficiency or low serum 25 (OH)-D levels. Two studies failed to establish an association between vitamin D deficiency and HT and GD disease. In conclusion, vitamin D deficiency or insufficiency can increase the rate of autoimmune diseases such as HT and GD. Randomized controlled trials with a longer follow-up period are needed to confirm the causal relationship between autoimmune thyroid disorder and vitamin D and to provide more reliable insights into the relevance of treatment effects of vitamin D therapy or supplementation.
PubMed: 35836431
DOI: 10.7759/cureus.25869 -
International Journal of Environmental... Mar 2023Autoimmune thyroid disease (AITD) is a dysregulation of the immune system that causes an attack on the thyroid gland. Two major clinical manifestations are Hashimoto's... (Review)
Review
Autoimmune thyroid disease (AITD) is a dysregulation of the immune system that causes an attack on the thyroid gland. Two major clinical manifestations are Hashimoto's thyroiditis and Graves' disease. Saliva performs many functions and, importantly, has the potential for easy, non-invasive diagnostics of several systemic disorders. This systematic review was designed to answer the question whether salivary alterations are reliable for the diagnosis of autoimmune thyroid diseases. Following the inclusion and exclusion criteria, fifteen studies were included. Due to their heterogeneity, saliva analysis was divided into two subgroups: quantitative assessment analysing salivation and qualitative assessment concerning potential salivary biomarkers for AITD. In addition to detecting altered levels of thyroid hormones and antibodies, salivary changes were also observed in the concentrations of total protein, cytokines and chemokines, as well as markers of oxidative status. According to the saliva flow rate values, significantly reduced saliva secretion was observed in patients with HT. In conclusion, it is not possible to unequivocally state if salivary biomarkers can potentially be used in autoimmune thyroid disease diagnosis. Therefore, further investigations, including salivation disorders, are necessary to validate these findings.
Topics: Humans; Thyroiditis, Autoimmune; Hashimoto Disease; Graves Disease; Thyroid Hormones; Autoimmune Diseases; Thyroid Diseases
PubMed: 36981758
DOI: 10.3390/ijerph20064849 -
International Journal of Environmental... May 2023(1) Background: Immunological laboratory testing is known to be complex, and it is usually performed in tertiary referral centers. Many criticalities affect diagnostic... (Review)
Review
(1) Background: Immunological laboratory testing is known to be complex, and it is usually performed in tertiary referral centers. Many criticalities affect diagnostic immunological testing, such as limited availability, the need for specifically trained laboratory staff, and potential difficulties in collecting blood samples, especially in the most vulnerable patients, i.e., the elderly and children. For this reason, the identification of a new feasible and reliable methodology for autoantibody detection is urgently needed. (2) Methods: We designed a systematic review to investigate the available literature on the utilization of saliva samples for immunological testing. (3) Results: A total of 170 articles were identified. Eighteen studies met the inclusion criteria, accounting for 1059 patients and 671 controls. The saliva collection method was mostly represented by passive drooling (11/18, 61%), and the most frequently described methodology for antibody detection was ELISA (12/18, 67%). The analysis included 392 patients with rheumatoid arthritis, 161 with systemic lupus erythematosus, 131 with type 1 diabetes mellitus, 116 with primary biliary cholangitis, 100 with pemphigus vulgaris, 50 with bullous pemphigoids, 49 with Sjogren syndrome, 39 with celiac disease, 10 with primary antiphospholipid syndromes, 8 with undifferentiated connective tissue disease, 2 with systemic sclerosis, and 1 with autoimmune thyroiditis. The majority of the reviewed studies involved adequate controls, and saliva testing allowed for a clear distinction of patients (10/12 studies, 83%). More than half of the papers showed a correlation between saliva and serum results (10/18, 55%) for autoantibody detection, with varying rates of correlation, sensitivity, and specificity. Interestingly, many papers showed a correlation between saliva antibody results and clinical manifestations. (4) Conclusions: Saliva testing might represent an appealing alternative to serum-based testing for autoantibody detection, considering the correspondence with serum testing results and the correlation with clinical manifestations. Nonetheless, standardization of sample collection processing, maintenance, and detection methodology has yet to be fully addressed.
Topics: Child; Humans; Aged; Saliva; Lupus Erythematosus, Systemic; Sjogren's Syndrome; Autoantibodies; Arthritis, Rheumatoid
PubMed: 37239511
DOI: 10.3390/ijerph20105782