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BackgroundThe COVID-19 pandemic profoundly impacted the delivery of care and timing of elective surgical procedures. Most endocrine-related operations were considered elective and safe to postpone, providing a unique opportunity to assess clinical outcomes under protracted treatment plans.MethodsAmerican Association of Endocrine Surgeon members were surveyed for participation. A Research Electronic Data Capture survey was developed and distributed to 27 institutions to assess the impact of COVID-19-related delays. The information collected included patient demographics, primary diagnosis, resumption of care, and assessment of disease progression by the surgeon.ResultsTwelve out of 27 institutions completed the survey (44.4%). Of 850 patients, 74.8% (636) were female; median age was 56 (interquartile range, 44-66) years. Forty percent (34) of patients had not been seen since their original surgical appointment was delayed; 86.2% (733) of patients had a delay in care with women more likely to have a delay (87.6% vs 82.2% of men, χ2 = 3.84, P = .05). Median duration of delay was 70 (interquartile range, 42-118) days. Among patients with a delay in care, primary disease site included thyroid (54.2%), parathyroid (37.2%), adrenal (6.5%), and pancreatic/gastrointestinal neuroendocrine tumors (1.3%). In addition, 4.0% (26) of patients experienced disease progression and 4.1% (24) had a change from the initial operative plan. The duration of delay was not associated with disease progression (P = .96) or a change in operative plan (P = .66).ConclusionAlthough some patients experienced disease progression during COVID-19 delays to endocrine disease-related care, most patients with follow-up did not. Our analysis indicated that temporary delay may be an acceptable course of action in extreme circumstances for most endocrine-related surgical disease.

Primary hyperparathyroidism is a common endocrine disorder. It is characterised by elevated parathyroid hormone (PTH) level causing hypercalcemia. 90-95% of cases have a spontaneous cause, with the remaining 5-10% having a genetic basis. On routine examination, a 47-year-old patient was found to have hypercalcemia, vitamin D deficiency, normal PTH levels and no hypercalciuria. Despite vitamin supplementation, calcemia remained unchanged. Single photon emission computed tomography (SPECT) examination detected possible adenomas in the lower parathyroids regions, and ultrasound revealed an adenoma of the lower left parathyroid gland and hypertrophy of the lower right parathyroid gland. The atypical clinical presentation - young age, inadequate normal PTH levels and the location of the lesions within the two parathyroid glands suggested genetic testing, which confirmed the presence of a genetic mutation - the GCM2 variant. Treatment included exploration of the parathyroid area using fluorescence. Both lower parathyroid glands were dissected. PTH monitoring showed a decrease in baseline levels of more than 50% after surgery. One month after surgery, PTH and calcium levels remained normal. Primary hyperparathyroidism is usually asymptomatic, detected when laboratory tests are performed for another cause. Symptoms include nephrolithiasis, bone and joint pain, osteoporosis, arrhythmias and fatigue. The typical patient has high PTH levels and hypercalcemia, but not every case will be schematic. High serum calcium levels do not always result in increased PTH levels and an in-depth diagnosis is required. The GCM2 mutation, detected in the patient presented here, may occur in familial isolated hyperparathyroidism. Correct diagnosis and treatment is crucial not only for the patient, as it significantly improves their quality of life, but also for their family members, who may also have a genetic mutation and be unaware of the disorder developing in their body.

ObjectiveRapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation and Autonomic Dysregulation (ROHHAD), is a severe pediatric disorder of uncertain etiology resulting in hypothalamic dysfunction and frequent sudden death. Frequent co-occurrence of neuroblastic tumors have fueled suspicion of an autoimmune paraneoplastic neurological syndrome (PNS); however, specific anti-neural autoantibodies, a hallmark of PNS, have not been identified. Our objective is to determine if an autoimmune paraneoplastic etiology underlies ROHHAD.MethodsImmunoglobulin G (IgG) from pediatric ROHHAD patients (n = 9), non-inflammatory individuals (n = 100) and relevant pediatric controls (n = 25) was screened using a programmable phage display of the human peptidome (PhIP-Seq). Putative ROHHAD-specific autoantibodies were orthogonally validated using radioactive ligand binding and cell-based assays. Expression of autoantibody targets in ROHHAD tumor and healthy brain tissue was assessed with immunohistochemistry and mass spectrometry, respectively.ResultsAutoantibodies to ZSCAN1 were detected in ROHHAD patients by PhIP-Seq and orthogonally validated in 7/9 ROHHAD patients and 0/125 controls using radioactive ligand binding and cell-based assays. Expression of ZSCAN1 in ROHHAD tumor and healthy human brain tissue was confirmed.InterpretationOur results support the notion that tumor-associated ROHHAD syndrome is a pediatric PNS, potentially initiated by an immune response to peripheral neuroblastic tumor. ZSCAN1 autoantibodies may aid in earlier, accurate diagnosis of ROHHAD syndrome, thus providing a means toward early detection and treatment. This work warrants follow-up studies to test sensitivity and specificity of a novel diagnostic test. Last, given the absence of the ZSCAN1 gene in rodents, our study highlights the value of human-based approaches for detecting novel PNS subtypes. ANN NEUROL 2022;92:279-291.

BackgroundUltrasonography has become an essential tool for the evaluation and management of thyroid and parathyroid diseases. Its applications extend beyond neck endocrine conditions to a multitude of pathologies within the head and neck region.ObjectivesOur study aimed to: (1) provide a broad review of neck ultrasonography and key findings in neck endocrine diseases; (2) support skilled performance office-based diagnostic ultrasonography and its varied applications.Materials and methodsA review of the current literature was supplemented with clinical examples of key ultrasonographic findings.ResultsCurrent applications and key findings of ultrasonography in the diagnosis and management of neck endocrine conditions are reviewed.ConclusionUltrasonography is a fundamental component in the evaluation and management of neck endocrine diseases. The reader is encouraged to use this review to enhance office-based performance and application of ultrasonography.

INTRODUCTION: Several endocrine manifestations have been described in patients with 22q11 deletion syndrome, including growth retardation, hypoparathyroidism, and thyroid disorders. This study aimed to characterize these abnormalities in a Colombian retrospective cohort of children with this condition. METHODS: A retrospective study comprising a cohort of children with 22q11 deletion syndrome in Medellín, Colombia followed up between 2011 and 2017 was conducted. RESULTS: Thirty-seven patients with a confirmed diagnosis of 22q11 deletion syndrome were included. 37.8% had some endocrinopathy, the most frequent being hypoparathyroidism (21.6%), followed by hypothyroidism (13.5%), hyperthyroidism (2.7%) and growth hormone deficiency (2.7%). There was wide heterogeneity in the clinical presentation, with late onset of severe hypocalcemia associated with seizure or precipitated in postoperative cardiac surgery, which highlights the importance of continuous follow-up as indicated by the guidelines. Short stature was mainly related to nutritional factors. Growth monitoring is required with the use of syndrome-specific charts and careful monitoring of the growth rate. DISCUSSION AND CONCLUSION: As previously reported, a significant proportion of patients with endocrine abnormalities were found in this cohort. This highlights that it is essential to carry out an adequate multidisciplinary follow-up, based on the specific clinical guidelines, in order to avoid serious complications such as convulsions due to hypocalcemia. It is important to track size with curves specific to the syndrome and analyze the growth rate.

The Korean National Health Information Database (NHID) contains big data combining information obtained from the National Health Insurance Service and health examinations. Data are provided in the form of a cohort, and the NHID can be used to conduct longitudinal studies and research on rare diseases. Moreover, data on the cause and date of death are provided by Statistics Korea. Research and publications based on the NHID have increased explosively in the field of endocrine disorders. However, because the data were not collected for research purposes, studies using the NHID have limitations, particularly the need for the operational definition of diseases. In this review, we describe the characteristics of the Korean NHID, operational definitions of endocrine diseases used for research, and an overview of recent studies in endocrinology using the Korean NHID.

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OBJECTIVE: Type 2 diabetes mellitus (T2DM) and polycystic ovary syndrome (PCOS) are highly prevalent endocrine system diseases. However, studies on the molecular mechanisms of T2DM and PCOS at the transcriptomic level are still few. Thus, we aimed to reveal the potential common genetic and molecular pathways between T2DM and PCOS via bioinformatics analyses. MATERIALS AND METHODS: We downloaded the GSE10946 and GSE18732 datasets for T2DM and PCOS, respectively, from the National Center for Biotechnology Information's Gene Expression Omnibus (GEO) database. These datasets were subjected to integrated differential and weighted gene co-expression network analyses (WGCNA) to screen common genes. Thereafter, functional enrichment and disease gene association analyses were performed, transcription factor (TF)-gene and TF-miRNA-gene regulatory networks were constructed, and finally, the relevant target drugs were identified. RESULTS: We identified common genes (BIRC3, DEPTOR, TNNL3, ADRA2A) in T2DM and PCOS. Pathway enrichment analysis depicted that the common genes were enriched in smooth muscle contraction, channel inhibitor activity, apoptosis, and tumor necrosis factor (TNF) signaling pathways. TFs such as SP7, KLF8, HCFC1, IRF1, and MLLT1 played key roles in TF regulatory networks. Orlistat was indicated to be an important gene-targeting drug. CONCLUSIONS: This study is the first study to explore four diagnostic biomarkers and gene regulatory networks for T2DM and PCOS. The findings of our study provide novel insights into the diagnosis and treatment of T2DM and PCOS. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective: To evaluate the association between the patients’ characteristics and the development of endocrine toxicity and to assess the association between endocrine-related adverse effects (ERAE) development and mortality. Subjects and methods: A retrospective observational study was conducted in 98 patients submitted to immunotherapy in our centre since its introduction in 2015 until March 2021. We excluded patients for which data regarding the corticotroph axis evaluation was missing. We used linear and logistic regression models to address our aims. Results: We observed a significant negative association between ERAE development and death (OR 0.32; p = 0.028). We detected no associations between ERAE and the following characteristics: age at immune checkpoint inhibitors (ICI) initiation, sex, diabetes mellitus, medical history, immunotherapy duration and ICI type. Conclusion: The development of an ERAE may be associated with a better overall survival rate in advanced oncologic disease, supporting the role of an unleashed immune system response to malignant cells.

Immune checkpoint inhibitors (ICIs) including an anti-cytotoxic T-lymphocyte-associated antigen 4 inhibitor, anti-programmed cell death protein 1 (PD-1) inhibitors, and anti-PD-ligand 1 inhibitors are representative therapeutics for various malignancies. In oncology, the application of ICIs is currently expanding to a wider range of malignancies due to their remarkable clinical outcomes. ICIs target immune checkpoints which suppress the activity of T-cells that are specific for tumor antigens, thereby allowing tumor cells to escape the immune response. However, immune checkpoints also play a crucial role in preventing autoimmune reactions. Therefore, ICIs targeting immune checkpoints can trigger various immune-related adverse events (irAEs), especially in endocrine organs. Considering the endocrine organs that are frequently involved, irAEs associated endocrinopathies are frequently life-threatening and have unfavorable clinical implications for patients. However, there are very limited data from large clinical trials that would inform the development of clinical guidelines for patients with irAEs associated endocrinopathies. Considering the current clinical situation, in which the scope and scale of the application of ICIs are increasing, position statements from clinical specialists play an essential role in providing the appropriate recommendations based on both medical evidence and clinical experience. As endocrinologists, we would like to present precautions and recommendations for the management of immune-related endocrine disorders, especially those involving the adrenal, thyroid, and pituitary glands caused by ICIs.

Little is known about the incidence of late effects following non-Hodgkin lymphoma (NHL) among adolescent and young adult (AYA, 15-39 years) survivors. Using data from the California Cancer Registry linked to hospital discharge, we estimated the cumulative incidence of late effects at 10 years among AYAs diagnosed with NHL during 1996-2012, who survived ≥2 years. Cox proportional-hazards models were used to investigate the influence of sociodemographic and clinical factors on the occurrence of late effects. Of 4392 HIV-uninfected patients, the highest incident diseases were: endocrine (18·5%), cardiovascular (11·7%), and respiratory (5·0%), followed by secondary primary malignancy (SPM, 2·6%), renal and neurologic (2·2%), liver/pancreatic (2·0%), and avascular necrosis (1·2%). Among the 425 HIV-infected survivors, incidence was higher for all late effects, especially over threefold increased risk of SPM, compared to HIV-uninfected patients (8·1% vs. 2·6%). In multivariable models for HIV-uninfected patients, public or no health insurance (vs. private), residence in lower socioeconomic neighbourhoods (vs. higher), and receipt of a haematopoietic stem cell transplant were associated with a greater risk of most late effects. Our findings of substantial incidence of late effects among NHL AYA survivors emphasise the need for longterm follow-up and appropriate survivorship care to reduce morbidity and mortality in this vulnerable population.

Objective: Several endocrine manifestations have been described in patients with 22q11 deletion syndrome, including growth retardation, hypoparathyroidism, and thyroid disorders. This study aimed to characterize these abnormalities in a Colombian retrospective cohort of children with this condition. Methods: A retrospective study comprising a cohort of children with 22q11 deletion syndrome in Medellín, Colombia followed up between 2011 and 2017 was conducted. Results: Thirty-seven patients with a confirmed diagnosis of 22q11 deletion syndrome were included. 37.8% had some endocrinopathy, the most frequent being hypoparathyroidism (21.6%), followed by hypothyroidism (13.5%), hyperthyroidism (2.7%) and growth hormone deficiency (2.7%). There was wide heterogeneity in the clinical presentation, with late onset of severe hypocalcemia associated with seizure or precipitated in postoperative cardiac surgery, which highlights the importance of continuous follow-up as indicated by the guidelines. Short stature was mainly related to nutritional factors. Growth monitoring is required with the use of syndrome-specific charts and careful monitoring of the growth rate. Conclusion: As previously reported, a significant proportion of patients with endocrine abnormalities were found in this cohort. This highlights that it is essential to carry out an adequate multidisciplinary follow-up, based on the specific clinical guidelines, in order to avoid serious complications such as convulsions due to hypocalcemia. It is important to track size with curves specific to the syndrome and analyze the growth rate. [ABSTRACT FROM AUTHOR]

Copyright of Saúde Coletiva is the property of MPM Comunicacao and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Saúde Coletiva is the property of MPM Comunicacao and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Context: Haematopoietic stem cell transplantation (HSCT) is a therapeutic option for numerous haematologic diseases and solid tumours. Increasing indications for HSCT and reduction in associated mortality have been raising the number of paediatric HSCT survivors and their long‐term toxicities. Objective: To characterize the endocrine disorders developed after HSCT. Design and Patients: Retrospective analysis of 152 patients submitted to HSCT in paediatric age with at least 24 months of follow‐up at our endocrine late‐effects clinics. Results: Patients were followed up for 9.9 (interquartile range [IQR]: 12.2) years. The median age at HSCT was 7.5 (IQR: 9) years. At least one endocrine complication was observed in 65.1% of the patients. Primary hypogonadism was detected in 34.2%. Female gender (p <.001), HSCT > 10 years old (p =.01) and chemotherapy before HSCT (p <.001) were identified as risk factors for developing gonadal dysfunction. Growth hormone deficiency (GHD) occurred in 23.0% with a mean stature Z‐score at diagnosis of −1.8 ± 1.4. GHD was associated with cranial (p <.001) and HSCT < 10 years old (p ≤ 0.001). Patients who were exposed to total body irradiation (TBI) were at higher risk for primary hypothyroidism (22.3%) (p =.01), thyroid nodules (17.1%) (p <.001), thyroid carcinoma (5.3%) (p <.001), dyslipidaemia (19.1%) (p <.001) and disturbance of carbohydrate metabolism (19.1%) (p <.001). Conclusion: At least one endocrine complication was diagnosed in 65.1% of patients, with gonadal dysfunction being the most prevalent. The conditioning regimen with TBI was a risk factor for the development of several endocrine disorders. This study is one of the largest series evaluating the endocrine disorders among survivors of paediatric HSCT and intends to reinforce the importance of routine follow‐up of these patients. [ABSTRACT FROM AUTHOR]

Introduction: the phlebotomy is a therapeutic blood extraction procedure, indicated in hematological alterations, and since last decades, they have been related with the compromise of organs that participate in metabolism. Objective: to describe a group of patients treated with phlebotomy in the National Blood Bank, identifying in they, the presence of diseases or clinical symptoms related to endocrinological or metabolic pathologies. Methodology: it is an observational, descriptive and retrospective study. Were reviewed 583 medical records of patients phlebotomized, between 2010 until 2017. The statistical analysis included measures of central tendency and dispersion, besides OR and chi square for correlation evaluation. Results: it was observed 42.36 % overweight, 27.62 % obesity, and presence of diseases as hypothyroidism, liver and kidney disorders, SAHOS and metabolic syndrome. in addition to classic hematological alterations, with a significant correlation between hematological and endocrine or metabolic disorders (Chi square 18.84). Conclusion: endocrinological alterations may be present in patients with hematological alterations and this could raise the use of phlebotomy as an adjuvant in their management or prevention. Additionally, it is necessary the standardization of management protocols in the use of phlebotomy. [ABSTRACT FROM AUTHOR]

BackgroundBreast cancer is the most prevalent cancer in females and disease recurrence remains a significant problem. To prevent recurrence, tamoxifen is prescribed for at least 5 years. However, among patients who receive tamoxifen, individual responses are highly variable. These responses are affected by the type, frequency, and severity of endocrine symptoms, as well as adherence rates. Polymorphisms in genes involved in the metabolism of tamoxifen (ie, CYP3A4, CYP2D6) may influence responses to tamoxifen. In this study, the inter-relationships among endocrine symptoms, drug adherence, and genetic polymorphisms in Chinese breast cancer patients receiving tamoxifen therapy will be examined. We hypothesize that patients with more severe endocrine symptoms will be less likely to adhere to tamoxifen treatment. In addition, we hypothesize that a relationship will exist between the severity of tamoxifen-induced symptoms and allelic variations in tamoxifen metabolism-related genes. Although many association studies have determined that select genotypes influence the efficacy of tamoxifen, very few studies have investigated for associations between tamoxifen-induced endocrine symptoms and these polymorphisms.ObjectivesThe aim of this study was to characterize genetic polymorphisms in tamoxifen metabolism-associated genes in Chinese women with breast cancer and to explore the inter-relationships between genetic polymorphisms, endocrine symptoms, and adherence to tamoxifen.MethodWe will conduct a prospective cohort study that follows 200 Chinese women over 18 months and assess treatment-related symptoms and genetic variations. Endocrine symptoms and drug adherence will be determined through interview-administered standardized questionnaires. Polymorphisms in drug metabolism genes will be determined using real-time polymerase chain reaction based genotyping method. Data will be analyzed to determine associations between allelic variations, endocrine symptoms, and adherence.DiscussionThe proposed study will evaluate for polymorphisms in gene(s) that are associated with tamoxifen-related endocrine symptoms and adherence with tamoxifen. We will explore the relationships between genotypes, endocrine symptoms, and drug adherence in Chinese breast cancer patients. Findings from this study may assist clinicians to identify patients at higher risk for a worse symptom experience and lower adherence rates and enable them to initiate appropriate interventions. In the long term, the findings from this study may be used to develop and test tailored symptom management interventions for these patients.

BACKGROUND:There are an estimated 1.4 million colorectal cancer (CRC) survivors in the United States. Research on endocrine and metabolic diseases over the long term in CRC survivors is limited. Obesity is a risk factor for CRC; thus it is of interest to investigate diseases that may share this risk factor, such as diabetes, for long-term health outcomes among CRC survivors. METHODS:A total of 7114 CRC patients were identified from the Utah Population Database and matched to a general population cohort of 25 979 individuals on birth year, sex, and birth state. Disease diagnoses (assessed over three time periods of 1-5 years, 5-10 years, and >10 years) were identified using electronic medical records and statewide ambulatory and inpatient discharge data. Cox proportional hazard models were used to estimate the risk of endocrine and metabolic disease. RESULTS:Across all three time periods, risks for endocrine and metabolic diseases were statistically significantly greater for CRC survivors compared with the general population cohort. At 1-5 years postdiagnosis, CRC survivors' risk for diabetes mellitus with complications was statistically significantly elevated (hazard ratio [HR] = 1.36, 99% confidence interval [CI] = 1.09 to 1.70). CRC survivors also experienced a 40% increased risk of obesity at 1-5 years postcancer diagnosis (HR= 1.40, 99% CI= 1.66 to 2.18) and a 50% increased risk at 5-10 years postdiagnosis (HR = 1.50, 99% CI= 1.16 to 1.95). CONCLUSIONS:Endocrine and metabolic diseases were statistically significantly higher in CRC survivors throughout the follow-up periods of 1-5 years, 5-10 years, and more than 10 years postdiagnosis. As the number of CRC survivors increases, understanding the long-term trajectory is critical for improved survivorship care.

Background: Medical comorbidity may influence treatment initiation and engagement for alcohol and other drug (AOD) use disorders. We examined the association between medical comorbidity and Healthcare Effectiveness Data and Information Set (HEDIS) treatment initiation and engagement measures.Methods: We used electronic health record and insurance claims data from 7 US health care systems to identify patients with AOD use disorders between October 1, 2014, and August 15, 2015 (N = 86,565). Among patients identified with AOD use disorders in outpatient and emergency department (ED) settings, we examined how Charlson/Deyo comorbidity index scores and medical complications of AOD use were associated with treatment initiation. Among those who initiated treatment in inpatient and outpatient/ED settings, we also examined how comorbidity and AOD use-related medical complications were associated with treatment engagement. Analyses were conducted using generalized estimating equation logistic regression modeling.Results: Among patients identified as having an AOD diagnosis in outpatient and ED settings (n = 69,965), Charlson/Deyo comorbidity index scores of 2 or more were independently associated with reduced likelihood of initiation (risk ratio [RR] = 0.80, 95% confidence interval [CI] = 0.74, 0.86; reference score = 0), whereas prior-year diagnoses of cirrhosis (RR = 1.25, 95% CI = 1.12, 1.35) and pancreatic disease (RR = 1.34, 95% CI = 1.15, 1.56) were associated with greater likelihood of initiation. Among those who were identified in outpatient/ED settings and initiated, higher comorbidity scores were associated with lower likelihood of engagement (score 1: RR = 0.85, 95% CI = 0.76, 0.94; score 2+: RR = 0.61, 95% CI = 0.53, 0.71).Conclusion: Medical comorbidity was associated with lower likelihood of initiating or engaging in AOD treatment, but cirrhosis and pancreatic disease were associated with greater likelihood of initiation. Interventions to improve AOD treatment initiation and engagement for patients with comorbidities are needed, such as integrating medical and AOD treatment.

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To evaluate incidence of stroke, myocardial infarction (MI), and peripheral artery disease (PAD) in patients with type 2 diabetes mellitus (T2DM) and assess associated health care resource utilization (HCRU) and costs in the United States. Patients ≥18 years of age with a T2DM diagnosis, with or without incident stroke/MI/PAD, were indexed between 1 January 2012 and 31 December 2020, from the deidentified Optum Clinformatics Data Mart claims database. Incidence of stroke, MI, and PAD was evaluated in the year following T2DM. HCRU and costs were measured in the 12 months following study entry in patients with T2DM + stroke, T2DM + MI, and T2DM + PAD (experimental cohorts) and compared to HCRU and costs in patients with T2DM alone (control cohorts). Incidence of stroke, MI, and PAD in patients with T2DM was 0.9% (n = 16,034), 0.7% (n = 13,681), and 4.1% (n = 68,479), respectively. Compared to matched patients with T2DM alone, patients with T2DM + stroke/MI/PAD had significantly higher total healthcare costs in the year post-index date (T2DM + stroke: +$5962 per patient per month [PPPM]; T2DM + MI: +$7932 PPPM; T2DM + PAD: +$2652 PPPM; p <.05). Patients with T2DM + stroke/MI/PAD had significantly higher mean HCRU than patients without stroke/MI/PAD in all categories measured. Having stroke, MI, or PAD was associated with increases in HCRU and costs in patients with T2DM. Although PAD was associated with smaller per patient increases in total healthcare costs than patients with T2DM + stroke/MI, the higher frequency of incident PAD may make it more costly than MI or stroke in a large population of patients with T2DM. Compared to patients without type 2 diabetes (T2D), patients with T2D have a greater chance of having a stroke, heart attack, and narrowing of blood vessels in the arms and legs (peripheral artery disease [PAD]). A stroke, heart attack, or PAD may lead to hospitalization or death. We sought to understand healthcare usage (hospital visits, emergency room visits, office visits, etc.) and costs associated with stroke, heart attack, and PAD in patients with T2D in the United States. Healthcare resource usage and costs were estimated by using data from health insurance claims to compare healthcare usage and costs among patients with T2D, some of whom had a stroke, heart attack, or PAD, and some who did not. Compared to patients with T2D without stroke/heart attack/PAD, patients with T2D and stroke/heart attack/PAD had more overnight hospital visits, doctors' office visits, and emergency room visits. Patients with T2D and stroke/heart attack/PAD also had longer hospital stays. Patients with T2D and stroke/heart attack/PAD all had higher total healthcare costs in the year following their diagnoses, compared to patients with T2D without stroke/heart attack/PAD. By highlighting the greater costs and use of healthcare associated with stroke, heart attack, and PAD in patients with T2D, we hope to encourage more preventative management of stroke, heart attack, and PAD in patients with T2D. [ABSTRACT FROM AUTHOR]

BACKGROUND: Chronic mucocutaneous candidiasis is a primary immunodeficiency characterized by chronic and recurrent non-invasive infections caused by Candida in skin, nails and mucous membranes, as well as associated autoimmune manifestations and endocrinopathies. CLINICAL CAS] A 42-year-old male patient, with chronic mucocutaneous candidiasis with multiple recurrences, so he has been treated with different azolic derivates. CONCLUSIONS: Chronic mucocutaneous candidiasis is part of the primary immunodeficiencies and has an important clinical diversity, it can cause complications due to chronic Candida infection, such as: keratoconjunctivitis, esophageal stenosis, squamous cell carcinoma of the mouth and esophagus. [ABSTRACT FROM AUTHOR]

Although air pollution is well known to be harmful to the lung and airways, it can also damage most other organ systems of the body. It is estimated that about 500,000 lung cancer deaths and 1.6 million COPD deaths can be attributed to air pollution, but air pollution may also account for 19% of all cardiovascular deaths and 21% of all stroke deaths. Air pollution has been linked to other malignancies, such as bladder cancer and childhood leukemia. Lung development in childhood is stymied with exposure to air pollutants, and poor lung development in children predicts lung impairment in adults. Air pollution is associated with reduced cognitive function and increased risk of dementia. Particulate matter in the air (particulate matter with an aerodynamic diameter < 2.5 μm) is associated with delayed psychomotor development and lower child intelligence. Studies link air pollution with diabetes mellitus prevalence, morbidity, and mortality. Pollution affects the immune system and is associated with allergic rhinitis, allergic sensitization, and autoimmunity. It is also associated with osteoporosis and bone fractures, conjunctivitis, dry eye disease, blepharitis, inflammatory bowel disease, increased intravascular coagulation, and decreased glomerular filtration rate. Atopic and urticarial skin disease, acne, and skin aging are linked to air pollution. Air pollution is controllable and, therefore, many of these adverse health effects can be prevented.

Background/Aim. Phthalates are recognized as endocrine-disrupting compounds and are extensively present in a variety of everyday products. Chronic exposure to phthalates is suspected to be associated with a range of health disorders. The aim of the study was to examine the abundance of phthalate metabolites in the urine samples among adults in the Autonomous Province of Vojvodina, Serbia, and to determine the prevalence of phthalate metabolites in healthy individuals and those with metabolic disorders such as obesity and newly diagnosed type 2 diabetes mellitus (T2DM). Methods. For the study purpose, the first morning urine sample of 308 participants was screened for the presence of 10 phthalate metabolites: mono-ethyl phthalate (MEP), mono-(2-ethylhexyl) phthalate (MEHP), mono-n-butyl phthalate (MBP), mono-iso-allyl phthalate (MiAP), mono-n-allyl phthalate (MnAP), mono-cyclohexyl phthalate (MCHP), mono-benzyl phthalate (MBzP), mono-n-octyl phthalate (MOP), mono-n-propyl phthalate (MPP) and mono-methyl phthalate (MMP). Results. At least one phthalate metabolite was detected in the first morning urine sample in 50.32% of the examined population. The most frequently detected phthalate metabolites were MEP and MEHP. Out of all phthalate-positive participants, 38.3% of them had one, 10.7% had two, while 1.3% of participants had three phthalate metabolites in the first morning urine sample. A significant difference (p < 0.05) between groups was observed on MEP and MMP frequency, while border-line significant difference (p < 0.1) between groups was observed on MEHP and MCHP frequency. Conclusion. In the Vojvodina region, both healthy adults and those with metabolic disorders such as obesity and newly diagnosed T2DM are predominantly exposed to di-ethyl phthalate and di-(2-ethylhexyl)phthalate since MEP and MEHP were the most frequently detected phthalate metabolites. Further re-search is required in order to provide more details of the phthalates influence on the adverse health effects.

ObjectivesPreprotein convertase 1/3 deficiency is a rare autosomal recessive disorder in which patients present with malabsorptive diarrhea and a series of symptoms of endocrine disorders such as polydipsia, reactive hypoglycemia, growth hormone deficiency, hypothyroidism, adrenal insufficiency, and early onset obesity. In its essence, pituitary hormone deficiency is caused by insufficient cleavage of pituitary prohormones. Here, we describe a female child with a rare double-site homozygous mutation in PCSK1 (Proprotein convertase subtilisin/kexin-type 1) gene, and thereby intend to investigate the relationship between these novel mutation sites and changes in protein synthesis and function.MethodsWe tested this patient's blood and urine fecal indicators of infection, blood electrolytes, and relevant endocrine hormone levels in the laboratory. Next Generation Sequencing was applied to screen the patient's DNA. Western Blot was performed to evaluate the mutant protein's expression. The enzymatic activity was measured as the rate of cleavage of a synthetic fluorogenic substrate in a specific solution.ResultsWe found that this patient presented shortly after birth with uncorrectable diarrhea and symptoms of metabolic acidosis with hypothyroidism. Next Generation Sequencing revealed that a rare double-site homozygous missense mutation, c.763G > A (p.G255R) and c.758C > T (p.S253L), were detected in exon 7 of PCSK1 (Proprotein convertase subtilisin/kexin-type 1) gene on chromosome 5 of the patient. Western blotting revealed that there was no significant decrease in protein synthesis levels in the mutant phenotype compared to the wild type. Compared with WT type, the proteins expressed by the mutations showed a significant decrease in the enzyme activity towards the fluorescent substrates. However, neither the single site mutation p.S253L or p.G255R, nor the double-site mutation of both, all showed no significant differences from each other.ConclusionsThese two missense mutations have not been reported before, and it is even rarer to find homozygous variation of two sites in one patient. This study identifies two novel mutations for the first time and further investigates the changes in protein synthesis and enzyme activity, providing a new pathway to continue to explore the pathogenesis of diseases associated with the function of PC1/3.

BackgroundImmunomodulatory therapies, including CTLA-4 and PD-1 inhibitors, provide a directed attack against cancer cells by preventing T cell deactivation. However, these drugs also prevent the downregulation of auto-reactive T cells, resulting in immune-related adverse events (IRAEs). Reports show a varied incidence of endocrine IRAEs, ranging from 0% to 63%.ObjectiveTo describe the frequency and clinical characteristics of endocrine IRAEs in patients taking cancer immunomodulatory therapies.DesignRetrospective cohort study.PatientsA total of 388 patients aged ≥18 years who were prescribed ipilimumab, nivolumab and/or pembrolizumab between 2009 and 2016 at our institution.MeasurementsBiochemical criteria were used to define endocrine IRAEs, including thyroid, pituitary, pancreas and adrenal dysfunction, following use of immunomodulatory therapies.ResultsFifty endocrine IRAEs occurred in our cohort, corresponding to a rate of 12.9%. The most common endocrine IRAEs were thyroid dysfunction (11.1%), with a lower incidence of pituitary dysfunction (1.8% of patients).ConclusionsOver 12% of patients receiving ipilimumab, nivolumab and/or pembrolizumab in our study sample developed an endocrine IRAE. Patients who undergo treatment with immunomodulatory therapies should be monitored for the development of endocrine IRAEs.

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The obstetrics-gynecology community has issued a call to action to prevent toxic environmental chemical exposures and their threats to healthy human reproduction. Recent committee opinions recognize that vulnerable and underserved women may be impacted disproportionately by environmental chemical exposures and recommend that reproductive health professionals champion policies that secure environmental justice. Beauty product use is an understudied source of environmental chemical exposures. Beauty products can include reproductive and developmental toxicants such as phthalates and heavy metals; however, disclosure requirements are limited and inconsistent. Compared with white women, women of color have higher levels of beauty product-related environmental chemicals in their bodies, independent of socioeconomic status. Even small exposures to toxic chemicals during critical periods of development (such as pregnancy) can trigger adverse health consequences (such as impacts on fertility and pregnancy, neurodevelopment, and cancer). In this commentary, we seek to highlight the connections between environmental justice and beauty product-related chemical exposures. We describe racial/ethnic differences in beauty product use (such as skin lighteners, hair straighteners, and feminine hygiene products) and the potential chemical exposures and health risks that are associated with these products. We also discuss how targeted advertising can take advantage of mainstream beauty norms to influence the use of these products. Reproductive health professionals can use this information to advance environmental justice by being prepared to counsel patients who have questions about toxic environmental exposures from beauty care products and other sources. Researchers and healthcare providers can also promote health-protective policies such as improved ingredient testing and disclosure for the beauty product industry. Future clinical and public health research should consider beauty product use as a factor that may shape health inequities in women's reproductive health across the life course.

Background: Cases of RNF216 -related disorder have been reported sporadically. However, the clinical and genetic spectrum of this disorder has not been fully studied., Methods: We identified an individual with a novel causative RNF216 variant in our institution and reviewed all individuals with causative RNF216 variants in previous reports. The clinical and genetic features of all the described individuals were analysed and summarised., Results: Twenty-four individuals from 17 families with causative RNF216 variants were identified. The mean age at the onset of neurological symptoms was 29.2 years (range 18-49 years). Ataxia (57%) was the most frequent initial symptoms in individuals under 30 years old, while chorea (63%) was the most frequent initial symptom in individuals over 30 years old. Over 90% of individuals presented with cognitive impairment and hypogonadotropic hypogonadism throughout the disease. White matter lesions (96%) and cerebellar atrophy (92%) were the most common imaging findings. Twenty pathogenic variants in RNF216 were detected. The variants in 12 (71%) families were inherited in a monogenic recessive pattern, whereas the variants in 5 (29%) were inherited in a digenic pattern by acting with variants in other genes. The majority of the RNF216 variants (85%) resulted in amino acid changes or the truncation of the 'RING between RING' (RBR) domain or C-terminal extension., Conclusion: RNF216 -related disorder is an inherited neuroendocrine disease characterised by cerebellar ataxia, chorea, cognitive impairment and hypogonadotropic hypogonadism. Most causative variants in patients with RNF216 -related disorder influence the RBR domain or C-terminal extension of RNF216., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: This study aims to explore the significant impact of environmental chemicals on disease development, focusing on their role in developing metabolic and endocrine diseases. The objective is to understand how these chemicals contribute to the increasing prevalence of precocious puberty, considering various factors, including epigenetic changes, lifestyle, and emotional disturbances., Methods: The study employs a comprehensive review of descriptive observational studies in both human and animal models to identify a degree of causality between exposure to environmental chemicals and disease development, specifically focusing on endocrine disruption. Due to ethical constraints, direct causation studies in human subjects are not feasible; therefore, the research relies on accumulated observational data., Results: Puberty is a crucial life period with marked physiological and psychological changes. The age at which sexual characteristics develop is changing in many regions. The findings indicate a correlation between exposure to endocrine-disrupting chemicals and the early onset of puberty. These chemicals have been shown to interfere with normal hormonal processes, particularly during critical developmental stages such as adolescence. The research also highlights the interaction of these chemical exposures with other factors, including nutritional history, social and lifestyle changes, and emotional stress, which together contribute to the prevalence of precocious puberty., Conclusion: Environmental chemicals significantly contribute to the development of certain metabolic and endocrine diseases, particularly in the rising incidence of precocious puberty. Although the evidence is mainly observational, it adequately justifies regulatory actions to reduce exposure risks. Furthermore, these findings highlight the urgent need for more research on the epigenetic effects of these chemicals and their wider impact on human health, especially during vital developmental periods., Competing Interests: Disclosure The authors have no multiplicity of interest to disclose., (Copyright © 2024 AACE. Published by Elsevier Inc. All rights reserved.)

Background: Colombia's health system allows workers to claim paid sick leave due to health conditions, some of this conditions are related to metabolic and cardiovascular disease. There has been an association between these diseases and depression. However, the effect of behavioral disorders such as depression on absence from work is unknown in the developing world. The objective of the research is to estimate whether low-wage workers suffering from depression, metabolic disease, and cardiovascular disease request more paid sick days than people with the same medical comorbidities, but without depression. Data and Methods: We conducted a retrospective study using data from an insurer in the southwestern region of Colombia in 2016. Depression was identified using an international algorithm that detects chronic conditions from diagnosis and pharmacy data. Outcome variables were the number of days on sick leave allowed by the insurer in one year, and the amount paid by the insurer. We used multivariate regression to estimate whether depression increases sick leave due to metabolic and cardiovascular disease after pre-processing the data using coarsened exact matching. Results: Individuals diagnosed with depressive disorders and absent from work due to metabolic and cardiovascular disease tend to have more paid sick days throughout the year than individuals with no depression suffering from these diseases. Additional absence days were statistically significant in nutritional and metabolic disease (10.6 days) and circulatory diseases (7.4 days). Conclusions: Depression comorbid with a physical disease increases the number of days and consequently the associated costs to the insurer. The incremental cost due to depression is higher compared to what insurers receive annually from the government to cover health services; consequently, additional research is warranted to identify prevention activities that can treat depression, thus lowering the healthcare system's financial burden. [ABSTRACT FROM AUTHOR]

Myxedema coma is the most serious complication of hypothyroidism. It usually occurs in the context of elderly women, with known hypothyroidism without proper management and in the presence of a triggering event. The diagnosis is challenging and must be made in a timely manner to prevent the development of adverse outcomes. Coma is one of the neurological manifestations of the entity, not being necessary for its diagnosis. This case report presents a constellation of unusual manifestations of a male patient with myxedema coma at the debut of severe hypothyroidism with predictors of poor prognosis during hospitalization, but due to the early approach and comprehensive management, this uncommon endocrinological emergency was satisfactorily resolved.

Erectile dysfunction is a multidimensional but common male sexual dysfunction that involves an alteration in any of the components of the erectile response, including organic, relational and psychological. Roles for nonendocrine (neurogenic, vasculogenic and iatrogenic) and endocrine pathways have been proposed. Owing to its strong association with metabolic syndrome and cardiovascular disease, cardiac assessment may be warranted in men with symptoms of erectile dysfunction. Minimally invasive interventions to relieve the symptoms of erectile dysfunction include lifestyle modifications, oral drugs, injected vasodilator agents and vacuum erection devices. Surgical therapies are reserved for the subset of patients who have contraindications to these nonsurgical interventions, those who experience adverse effects from (or are refractory to) medical therapy and those who also have penile fibrosis or penile vascular insufficiency. Erectile dysfunction can have deleterious effects on a mans quality of life; most patients have symptoms of depression and anxiety related to sexual performance. These symptoms, in turn, affect his partners sexual experience and the couples quality of life. This Primer highlights numerous aspects of erectile dysfunction, summarizes new treatment targets and ongoing preclinical studies that evaluate new pharmacotherapies, and covers the topic of regenerative medicine, which represents the future of sexual medicine.

Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver diseases worldwide and covers a series of pathological manifestations from hepatic steatosis to inflammation, fibrosis, and even liver cirrhosis. NAFLD is associated with a wide range of extrahepatic diseases, including metabolic syndrome, cardiovascular disease, chronic kidney disease, endocrine diseases, obstructive sleep apnea-hypopnea syndrome, psoriasis, and skeleton-muscle diseases. The major causes of death in patients with NAFLD include cardiovascular disease, malignancies, and liver-related complications, suggesting that extrahepatic diseases associated with NAFLD should be taken seriously by clinicians. This article reviews the research advances in extrahepatic diseases associated with NAFLD, so as to provide ideas for clinical assessment and treatment. [ABSTRACT FROM AUTHOR]

The world is entering an era of disaster and chaos due to coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2. Since its first emergence in December 2019 in Wuhan, China, COVID-19 has swept through Asia and propagated throughout the world to Europe and North America. As of April 13, 1,773,084 people were infected and 111,652 people had died from COVID-19 globally, and new record levels of infection are being reported every day. Based on the data that have been amassed so far, the primary risk factors for a severe disease course or even mortality from COVID-19 are underlying diseases such as diabetes and hypertension. As the global prevalence of diabetes continues to increase, patients with endocrine diseases such as diabetes mellitus and those who are on long-term corticosteroid therapy due to adrenal insufficiency or hypopituitarism are at risk for a poor prognosis of COVID-19. As endocrinologists, we would like to briefly review the current knowledge about the relationship between COVID-19 and endocrine diseases and to discuss what we can do for the safety and health of our patients with endocrine diseases in this globally threatening situation.

Endocrinopathies have a variety of orofacial presentations which span from dental malocclusion to facial disfigurement. These characteristics depend on the nature and severity of the condition. An orthodontist should understand the body’s physiological processes to be able to timely determine the optimum intervention and plan treatment stages accordingly in compromised individuals. Communication between the two specialties should be well coordinated and should help facilitate quality health care to the patient. This review was aimed to impart the basic knowledge and the pivotal guidelines for orthodontic management in these conditions. Systemic conditions require multidisciplinary management and the dental team should aim to provide quality oral health care to enhance the overall quality of life and the orthodontist plays a vital role in helping patients achieve physical and psychological health.

Endocrinopathies are relatively rare causes of erectile dysfunction. Cases of hyperprolactinemia and pituitary adenomas have been previously reported. We present a clinical case of a 27-year-old male with suspected infertility and recent symptoms of erectile dysfunction. Additional radiological and endocrinologic workup revealed underlying subependymoma, which was expanding in the sellar and suprasellar regions, causing pressure against the pituitary gland. The resulting endocrine disorder caused problems that were subjectively at first manifested mainly as erectile dysfunction. The case is an educative example pointing to the need of taking possible intracranial lesions in consideration when starting workup in a patient presenting with erectile dysfunction. It may be of broad clinical interest not only for endocrinologists but also for practitioners in various fields.

Coronavirus disease 2019 (COVID-19) due to a severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection can include various systemic organ disorders including endocrinopathies and neurological manifestations. We report the case of a 65-year-old Japanese man who developed isolated adrenocorticotropic hormone (ACTH) deficiency and encephalopathy following SARS-CoV-2 infection. Two weeks after his COVID-19 diagnosis, he was emergently admitted to our hospital because of subacute-onset delirium. On admission, he presented hyponatremia (128 mEq/L) and secondary adrenal insufficiency (ACTH <1.5 pg/mL, cortisol 0.53 μg/dL). Brain imaging and laboratory examinations including SARS-CoV-2 polymerase chain reaction testing in the cerebrospinal fluid revealed no abnormalities. His consciousness level worsened despite the amelioration of hyponatremia by intravenous hydrocortisone (100 mg/day), but his neurological presentations completely resolved after three consecutive days of high-dose (400 mg/day) hydrocortisone. His encephalopathy did not deteriorate during hydrocortisone tapering. He continued 15 mg/day hydrocortisone after discharge. His encephalopathy might have developed via a disturbance of the autoimmune system, or a metabolic effect associated with adrenal insufficiency, although the time lag between the hyponatremia's improvement and the patient's neurological response to the steroid was incompatible with common cases of delirium concurrent with adrenal insufficiency. At 13 months after his hospitalization, the patient's neurological symptoms have not recurred and he has no endocrinological dysfunctions other than the remaining ACTH deficiency. A thorough consideration of the immunological and metabolic characteristics of SARS-CoV-2 is advisable when clinicians treat patients during and even after their COVID-19 disease period.

Phaeochromocytomas and paragangliomas are rare catecholamine-producing neuroendocrine tumours which can potentially cause catastrophic crises with high morbidity and mortality. This best practice article considers the causes and presentation of such tumours, screening and diagnostic tests, management of these patients and consideration of family members at risk., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: Post-ovariectomy (OVX) changes in hormones induce obesity and white adipose tissue (WAT) inflammation. Increased energy expenditure via WAT browning is a novel therapeutic strategy for treating obesity. Naringenin (NAR) reduces inflammation and lipogenesis in obesity and attenuates estrogen deficiency-associated metabolic disorders; however, its role in WAT browning remains unclear., Materials and Methods: We investigated NAR ability to inhibit estrogen deficiency-associated obesity in vivo using a rat model and in vitro using 3T3-L1 adipocytes., Key Findings: NAR significantly decreased the body weight and WAT mass of rats. O 2 consumption, CO 2 production, and energy expenditure were significantly lower in the OVX group than in the sham group, but NAR treatment reversed these effects of OVX. NAR treatment markedly improved glucose intolerance and lipid profiles as well as leptin, adiponectin, and irisin levels. NAR upregulated markers of browning and mitochondrial biogenesis in inguinal WAT. Moreover, it enhanced markers of mitochondrial fusion and inhibited fission via activating the AMP-activated protein kinase pathway. Similar results were observed in 3T3-L1 adipocytes. Moreover, NAR-induced mitochondrial biogenesis and fusion were suppressed by dorsomorphin (an AMP-activated protein kinase inhibitor)., Significance: NAR alleviates obesity and metabolic dysfunction through the induction of WAT browning achieved via the modulation of AMP-activated protein kinase-regulated mitochondrial dynamics in WATs. NAR supplementation may therefore represent a potential intervention for preventing postmenopausal adipose tissue dysregulation., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Management of type 2 diabetes has now been simplified by the understanding that the condition is caused by excess fat in the liver together with suppression of beta cell function by the associated excess liver export of fat. These factors can be reversed by substantial weight loss leading to remission in the early years after diagnosis, or at least major decrease in cardiovascular risks and improvement in glucose control for all. Weight loss by any means is successful, but it is most easily achieved by rapid action using a low or very low calorie diet of around 800 kcal/day followed by sustained modest restraint of dietary habits. Oral hypoglycaemic agents and one antihypertensive drug can be withdrawn on day 1 of the weight loss diet, raising the importance of appropriate deprescribing., Competing Interests: Competing interests: None declared. Refer to the online supplementary files to view the ICMJE form(s)., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Nitrogen dioxide (NO 2 ) has been frequently linked to a range of diseases and associated with high rates of mortality and morbidity worldwide. However, there is limited evidence regarding the risk of NO 2 on a spectrum of causes of mortality. Moreover, adjustment for potential confounders in NO 2 analysis has been insufficient, and the spatial resolution of exposure assessment has been limited., Objective: This study aimed to quantitatively assess the relationship between short-term NO 2 exposure and death from a range of causes by adjusting for potential confounders in Guangzhou, China, and determine the modifying effect of gender and age., Methods: A time series study was conducted on 413,703 deaths that occurred in Guangzhou during the period of 2010 to 2018. The causes of death were classified into 10 categories and 26 subcategories. We utilized a generalized additive model with quasi-Poisson regression analysis using a natural cubic splines function with lag structure of 0 to 4 days to estimate the potential lag effect of NO 2 on cause-specific mortality. We estimated the percentage change in cause-specific mortality rates per 10 μg/m 3 increase in NO 2 levels. We stratified meteorological factors such as temperature, humidity, wind speed, and air pressure into high and low levels with the median as the critical value and analyzed the effects of NO 2 on various death-causing diseases at those high and low levels. To further identify potentially vulnerable subpopulations, we analyzed groups stratified by gender and age., Results: A significant association existed between NO 2 exposure and deaths from multiple causes. Each 10 μg/m 3 increment in NO 2 density at a lag of 0 to 4 days increased the risks of all-cause mortality by 1.73% (95% CI 1.36%-2.09%) and mortality due to nonaccidental causes, cardiovascular disease, respiratory disease, endocrine disease, and neoplasms by 1.75% (95% CI 1.38%-2.12%), 2.06% (95% CI 1.54%-2.59%), 2.32% (95% CI 1.51%-3.13%), 2.40% (95% CI 0.84%-3.98%), and 1.18% (95% CI 0.59%-1.78%), respectively. Among the 26 subcategories, mortality risk was associated with 16, including intentional self-harm, hypertensive disease, and ischemic stroke disease. Relatively higher effect estimates of NO 2 on mortality existed for low levels of temperature, relative humidity, wind speed, and air pressure than with high levels, except a relatively higher effect estimate was present for endocrine disease at a high air pressure level. Most of the differences between subgroups were not statistically significant. The effect estimates for NO 2 were similar by gender. There were significant differences between the age groups for mortality due to all causes, nonaccidental causes, and cardiovascular disease., Conclusions: Short-term NO 2 exposure may increase the risk of mortality due to a spectrum of causes, especially in potentially vulnerable populations. These findings may be important for predicting and modifying guidelines for NO 2 exposure in China., (©Jie Zeng, Guozhen Lin, Hang Dong, Mengmeng Li, Honglian Ruan, Jun Yang. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 05.02.2024.)