Causal relationship between thyroid dysfunction and gastric cancer: a two-sample Mendelian randomization study.

Backgroud: Gastric cancer is one of the most common cancers worldwide, and its development is associated with a variety of factors. Previous observational studies have reported that thyroid dysfunction is associated with the development of gastric cancer. However, the exact relationship between the two is currently unclear. We used a two-sample Mendelian randomization (MR) study to reveal the causal relationship between thyroid dysfunction and gastric cancer for future clinical work. Materials and methods: This study is based on a two-sample Mendelian randomization design, and all data are from public GWAS databases. We selected hyperthyroidism, hypothyroidism, free thyroxine (FT4), and thyroid-stimulating hormone (TSH) as exposures, with gastric cancer as the outcome. We used three statistical methods, namely Inverse-variance weighted (IVW), MR-Egger, and weighted median, to assess the causal relationship between thyroid dysfunction and gastric cancer. The Cochran's Q test was used to assess the heterogeneity among SNPs in the IVW analysis results, and MR-PRESSO was employed to identify and remove IVs with heterogeneity from the analysis results. MR-Egger is a weighted linear regression model, and the magnitude of its intercept can be used to assess the horizontal pleiotropy among IVs. Finally, the data were visualized through the leave-one-out sensitivity test to evaluate the influence of individual SNPs on the overall causal effect. Funnel plots were used to assess the symmetry of the selected SNPs, forest plots were used to evaluate the confidence and heterogeneity of the incidental estimates, and scatter plots were used to assess the exposure-outcome relationship. All results were expressed as odds ratios (OR) and 95% confidence intervals (95% CI). P<0.05 represents statistical significance. Results: According to IVW analysis, there was a causal relationship between hypothyroidism and gastric cancer, and hypothyroidism could reduce the risk of gastric cancer (OR=0.936 (95% CI:0.893-0.980), P=0.006).This means that having hypothyroidism is a protective factor against stomach cancer. This finding suggests that hypothyroidism may be associated with a reduced risk of gastric cancer.Meanwhile, there was no causal relationship between hyperthyroidism, FT4, and TSH and gastric cancer. Conclusions: In this study, we found a causal relationship between hypothyroidism and gastric cancer with the help of a two-sample Mendelian randomisation study, and hypothyroidism may be associated with a reduced risk of gastric cancer, however, the exact mechanism is still unclear. This finding provides a new idea for the study of the etiology and pathogenesis of gastric cancer, and our results need to be further confirmed by more basic experiments in the future.

Association between physical activity and thyroid function in American adults: a survey from the NHANES database.

OBJECTIVE: Physical activity (PA) is closely related to our lives, and the effects of PA on thyroid function have not been elucidated. METHODS: Using data from the National Health and Nutrition Examination Survey (NHANES) 2007-2012, we included 5877 participants and analyzed the associations of thyroid function with weekly physical activity (PAM, expressed in metabolic equivalents of task) and physical activity time (PAT) in American adults. Univariate and multivariate logistic analyses were used to demonstrate the associations of PAM and PAT with the primary outcome. Linear regression analysis was performed to determine the associations between thyroid biochemical indicators/diseases and PAM/PAT. RESULTS: Our study revealed noticeable sex differences in daily PA among the participants. The odds ratio of the fourth versus the first quartile of PAM was 3.07 (confidence interval, CI [1.24, 7.58], p = 0.02) for overt hypothyroidism, 3.25 (CI [1.12, 9.45], p = 0.03) for subclinical hyperthyroidism in adult men. PAT in the range of 633-1520 min/week was found to be associated with the occurrence of subclinical hyperthyroidism [p < 0.001, OR (95% CI) = 5.89 (1.85, 18.80)], PAT of the range of > 1520 min/week was found to be associated with the occurrence of overt hypothyroidism [p < 0.001, OR (95% CI) = 8.70 (2.80, 27.07)] and autoimmune thyroiditis (AIT) [p = 0.03, OR (95% CI) = 1.42 (1.03, 1.97)] in adult men. When PAM < 5000 MET*minutes/week or PAT < 1000 min/week, RCS showed an L-shaped curve for TSH and an inverted U-shaped curve for FT4. The changes in FT3 and TT3 in men were linearly positively correlated with PAM and PAT, while TT4 is linearly negatively correlated. CONCLUSION: The amount of daily physical activity of American adults is strongly associated with changes in thyroid function, including thyroid hormone levels and thyroid diseases. Thyroid hormone levels were varied to a certain extent with changes in PAM and PAT.

[Perioperative management of non-thyroid surgery in patients with thyroid dysfunction].

Thyroid diseases are relatively common in clinical practice. Surgery and use of related drugs may exacerbate the underlying thyroid diseases, increasing the difficulty of perioperative management. However, there is a lack of guidelines and consensus for non-thyroid surgery in patients with thyroid dysfunction. This review mainly summaries the perioperative management of non-thyroid surgery in patients with hypothyroidism and hyperthyroidism to provide clinical treatment suggestions and reduce the risk of perioperative complications.

Prevalence of hyperthyroidism and hypothyroidism in liver transplant recipients and associated risk factors.

The prevalence of hyperthyroidism and hypothyroidism and associated risk factors are unknown in liver transplant recipients. We aimed to determine the prevalence of hyperthyroidism and hypothyroidism and associated risk factors in liver transplant recipients and to compare it with controls from the general population. As part of the Danish Comorbidity in Liver Transplant Recipients (DACOLT) Study, all Danish liver transplant recipients over the age of 20 were invited for measurements of concentrations of thyrotropin and thyroid hormones. The prevalence of hyperthyroidism and hypothyroidism was compared to age- and sex-matched controls from the Copenhagen General Population Study. Using logistic regression adjusted for age, sex, smoking, and body-mass index, we investigated potential risk factors. We recruited 489 liver transplant recipients and 1808 controls. Among liver transplant recipients, 14 (2.9%) had hyperthyroidism compared with 21 (1.2%) of controls (adjusted odds ratio [aOR] 2.24, 95% confidence interval [CI] 1.05-4.75, P = 0.04), while 42 (5.7%) had hypothyroidism compared with 139 (7.7%) of controls (aOR 0.68, 95% CI 0.43-1.08, P = 0.10). Female sex, and autoimmune hepatitis and primary sclerosing cholangitis as causes of transplantation were associated with hyperthyroidism after adjustments. Age, female sex, and autoimmune liver diseases as cause of transplantation were associated with hypothyroidism after adjustments. DACOLT is registered in ClinicalTrials.gov (NCT04777032).

Immune Checkpoint Inhibitor Use During Pregnancy and Outcomes in Pregnant Individuals and Newborns.

Importance: With the widespread use of immune checkpoint inhibitors (ICIs), concerns about their pregnancy outcomes through maternal exposure have emerged, and clinical comparative data are lacking. Objective: To assess the risk of pregnancy-, fetal-, and/or newborn-related adverse outcomes associated with exposure to ICIs compared with exposure to other anticancer agents. Design, Setting, and Participants: In this cohort study, all reports mentioning a pregnancy-related condition and an antineoplastic agent (Anatomical Therapeutic Chemical classification group L01) used for a cancer indication registered in the World Health Organization international pharmacovigilance database VigiBase up to June 26, 2022, were extracted. Exposure: Anticancer agents, including ICIs, used during pregnancy for a cancer indication. Immune checkpoint inhibitors included blockers of programmed cell death 1 (PD1) or its ligand (PD-L1) or cytotoxic T-lymphocyte-associated protein 4 (CTLA4). Main Outcomes and Measures: The main outcome was the reporting odds ratio (ROR) for maternal, fetal, or newborn complications in patients treated with ICIs vs any other anticancer drug. Adverse events, categorized into 45 individual maternofetal adverse outcomes, were directly mapped to Medical Dictionary for Regulatory Activities preferred terms in VigiBase. Results: A total of 3558 reports (ICI: 91 [2.6%]; other anticancer drugs: 3467 [97.4%]) were included in the analysis. In the ICI group, most reports were from the US (60 [65.9%]), and the mean (SD) patient age was 28.9 (10.2) years; in 24 of 55 reports with data on cancer type (43.6%), patients were treated for melanoma. The molecules involved in the ICI group were anti-PD1 (58 reports [63.7%]), anti-PD1 plus anti-CTLA4 (15 [16.5%]), anti-CTLA4 (13 [14.3%]), anti-PD-L1 (4 [4.4%]), and anti-PD1 plus anti-lymphocyte activation gene 3 (1 [1.1%]). An ICI was used in combination with a non-ICI anticancer agent in 10 participants (11.0%). Compared with other anticancer drugs, none of the 45 adverse outcomes identified were overreported in the group exposed to ICIs. However, preterm birth was significantly overreported for the anti-PD1 plus anti-CTLA4 combination compared with other anticancer drugs (12 of 15 [80.0%] vs 793 of 3452 [23.0%]; ROR, 13.87; 95% CI, 3.90-49.28; P < .001) but not for anti-PD-L1 or anti-CTLA4 monotherapy. Three reports of possibly immune-related maternofetal events were identified: 1 case of maternal antiphospholipid syndrome leading to spontaneous abortion, 1 case of pneumonitis leading to neonatal respiratory distress syndrome and death, and 1 case of transient congenital hypothyroidism. Conclusions and Relevance: In this cohort study of 91 individuals exposed to ICIs during pregnancy, ICI exposure was not associated with overreporting of specific adverse pregnancy, fetal, and/or newborn outcomes compared with other anticancer treatments. However, due to possible rare immune-related neonatal adverse events, ICI use in pregnant women should be avoided when possible, especially the anti-PD1 plus anti-CTLA4 combination.

A machine learning approach for predicting radiation-induced hypothyroidism in patients with nasopharyngeal carcinoma undergoing tomotherapy.

The purpose of this study was to establish an integrated predictive model that combines clinical features, DVH, radiomics, and dosiomics features to predict RIHT in patients receiving tomotherapy for nasopharyngeal carcinoma. Data from 219 patients with nasopharyngeal carcinoma were randomly divided into a training cohort (n = 175) and a test cohort (n = 44) in an 8:2 ratio. RIHT is defined as serum thyroid-stimulating hormone (TSH) greater than 5.6 µU/mL, with or without a decrease in free thyroxine (FT4). Clinical features, 27 DVH features, 107 radiomics features and 107 dosiomics features were extracted for each case and included in the model construction. The least absolute shrinkage and selection operator (LASSO) regression method was used to select the most relevant features. The eXtreme Gradient Boosting (XGBoost) was then employed to train separate models using the selected features from clinical, DVH, radiomics and dosiomics data. Finally, a combined model incorporating all features was developed. The models were evaluated using receiver operating characteristic (ROC) curves and decision curve analysis. In the test cohort, the area under the receiver operating characteristic curve (AUC) for the clinical, DVH, radiomics, dosiomics and combined models were 0.798 (95% confidence interval [CI], 0.656-0.941), 0.673 (0.512-0.834), 0.714 (0.555-0.873), 0.698 (0.530-0.848) and 0.842 (0.724-0.960), respectively. The combined model exhibited higher AUC values compared to other models. The decision curve analysis demonstrated that the combined model had superior clinical utility within the threshold probability range of 1% to 79% when compared to the other models. This study has successfully developed a predictive model that combines multiple features. The performance of the combined model is superior to that of single-feature models, allowing for early prediction of RIHT in patients with nasopharyngeal carcinoma after tomotherapy.

Incidence of thyroid dysfunction caused by immune checkpoint inhibitors combined with chemotherapy: A systematic review and meta-analysis.

BACKGROUND: The combination of immune checkpoint inhibitors (ICIs) and chemotherapy as a first-line treatment for triple-negative breast cancer (TNBC) has been associated with many adverse reactions. Thyroid dysfunction, the most common adverse reaction of the endocrine system, has also attracted significant attention. This study aimed to analyse the effect of ICIs combined with chemotherapy on thyroid function in patients with TNBC. METHODS: As of November 4, 2023, we searched the PubMed, Web of Science, and Cochrane Library databases for clinical trials of ICIs combined with chemotherapy for the treatment of TNBC. The incidence of hypothyroidism and hyperthyroidism was calculated using a random-effects model. RESULTS: In the final analysis, 3,226 patients from 19 studies were included. The total incidence of all-grade hypothyroidism induced by the combination of ICIs and chemotherapy in treating TNBC (12% (95% confidence intervals(CI): 0.10-0.15)) was higher than that of hyperthyroidism (5% (95% CI: 0.04-0.06)). Pembrolizumab combined with chemotherapy caused the highest incidence of all grades of hypothyroidism for 13% (95% CI: 0.05-0.06). Durvalumab combined with chemotherapy caused the highest incidence of all grades of hyperthyroidism, at 7% (95% CI: 0.03-0.11). ICIs combined with chemotherapy caused a higher incidence of all grades of hypothyroidism in advanced TNBC (15% (95% CI: 0.13-0.17)) than in early stage TNBC (10% (95% CI: 0.07-0.13)). CONCLUSION: In TNBC, the incidence of hypothyroidism caused by the combination of ICIs and chemotherapy was significantly higher than that caused by hyperthyroidism. Pembrolizumab combined with chemotherapy resulted in the highest incidence of hypothyroidism. The incidence of hypothyroidism in patients with advanced TNBC was significantly higher than that in patients with early stage TNBC. In addition, ICIs combined with chemotherapy resulted in 16 out of 3,226 patients experiencing grade ≥ 3 thyroid dysfunction. Although the incidence of severe thyroid dysfunction is low, it requires attention. PROSPERO: CRD42023477933.

Thyroid abnormalities in patients with Hodgkin lymphoma: The importance of close surveillance.

INTRODUCTION: Survival in paediatric patients with Hodgkin lymphoma (HL) has increased over the last decades. However, these patients are at increased risk of developing late thyroid sequelae due to the treatment with irradiation and alkylating agents. METHODS: We conducted an observational and retrospective study in patients with a diagnosis of HL between 2007 and 2022, in a hospital that is a paediatric oncology reference centre, through the review of electronic health records. We collected data on demographic (age, sex), clinical, radiological and histopathological variables, the dosage of alkylating agents and radiotherapy (RT) and on thyroid disorders using Microsoft Excel. The data analysis was conducted with SPSS version 17, using the Fisher exact test for qualitative data, a nonparametric test for quantitative data and Kaplan-Meier curves. RESULTS: Sixty patients received a diagnosis of HL from 2007 to 2022. The median duration of follow-up was 78.5 months. There were 4 detected cases of hypothyroidism, 5 of thyroid nodules and 1 of subclinical hyperthyroidism. Treatment with RT was significantly associated with the development of hypothyroidism (P= .026), thyroid nodules (P= .01) and thyroid disease overall (P= .003). We estimated that the risk of thyroid disease increased 8-fold with each additional Grey received (hazard ratio, 1.081; 95% CI, 1.014-1.152; P= .017). CONCLUSION: Hodgkin lymphoma patients treated with RT are at increased risk of late thyroid disorders, mainly hypothyroidism and malignancy. This risk is greater the higher the RT dosage and the longer the follow-up. We did not find evidence of an association between the use of alkylating agents and an increase in the risk of thyroid disease.

Prevalence of thyroid dysfunction and associated factors among adult type 2 diabetes mellitus patients, 2000-2022: a systematic review and meta-analysis.

BACKGROUND: Thyroid dysfunction (TD) and type 2 diabetes mellitus (T2DM) frequently co-occur and have overlapping pathologies, and their risk increases with age. Thyroid dysfunction along with T2DM will worsen macro- and microvascular complications, morbidity, and mortality. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement guideline was followed. The databases used were Embase, ScienceDirect, PubMed, and Google Scholar. The Joana Briggs Institute (JBI) scale was used to assess the quality of the included studies. The data was extracted by Microsoft Excel and analyzed through STATA version 14 software. The overall pooled prevalence of TD and its main components were estimated using the random-effects model. The consistency of studies was assessed by I2 test statistics. Pooled meta-logistic regression was used to present the pooled prevalence with a 95% confidence interval (CI). Besides, subgroup and sensitivity analyses were employed. RESULT: Thirty-eight studies were included. The pooled prevalence of TD was 20.24% (95% CI: 17.85, 22.64). The pooled prevalence of subclinical hypothyroidism, hypothyroidism, subclinical hyperthyroidism, and hyperthyroidism was found to be 11.87% (95% CI: 6.90, 16.84), 7.75% (95% CI: 5.71, 9.79), 2.49% (95% CI: 0.73, 4.25), and 2.51% (95% CI: 1.89, 3.13), respectively. Subgroup analysis based on continent revealed a higher prevalence of TD in Asia and Africa. Factors like being female, HbA1c ≥ 7%, DM duration > 5 years, family history of TD, central obesity, smoking, the presence of retinopathy, and neuropathy were found associated with TD. CONCLUSION: The current systematic review and meta-analysis showed that the TD's pooled prevalence was relatively higher than the general population. Therefore, regular screening of TD should be done for T2DM patients.

Preoperative comorbidities as a predictor of EBWL after bariatric surgery: a retrospective cohort study.

INTRODUCTION: The purpose of this study is to investigate the impact of preoperative comorbidities, including depression, anxiety, type 2 diabetes mellitus, obstructive sleep apnea, hypothyroidism, and the type of surgery on %EBWL (percent estimated body weight loss) in patients 1 year after bariatric surgery. Patients who choose to undergo bariatric surgery often have other comorbidities that can affect both the outcomes of their procedures and the postoperative period. We predict that patients who have depression, anxiety, diabetes mellitus, obstructive sleep apnea, or hypothyroidism will have a smaller change in %EBWL when compared to patients without any of these comorbidities. METHODS AND PROCEDURES: Data points were retrospectively collected from the charts of 440 patients from March 2012-December 2019 who underwent a sleeve gastrectomy or gastric bypass surgery. Data collected included patient demographics, select comorbidities, including diabetes mellitus, obstructive sleep apnea, hypothyroidism, depression, and anxiety, and body weight at baseline and 1 year postoperatively. Ideal body weight was calculated using the formula 50 + (2.3 × height in inches over 5 feet) for males and 45.5 + (2.3 × height in inches over 5 feet) for females. Excess body weight was then calculated by subtracting ideal body weight from actual weight at the above forementioned time points. Finally, %EBWL was calculated using the formula (change in weight over 1 year/excess weight) × 100. RESULTS: Patients who had a higher baseline BMI (p < 0.001), diabetes mellitus (p = 0.026), hypothyroidism (p = 0.046), and who had a laparoscopic sleeve gastrectomy rather than Roux-en-Y gastric bypass (p < 0.001) had a smaller %EBWL in the first year after bariatric surgery as compared to patients without these comorbidities at the time of surgery. Controversially, patients with anxiety or depression (p = 0.73) or obstructive sleep apnea (p = 0.075) did not have a statistically significant difference in %EBWL. CONCLUSION: A higher baseline BMI, diabetes mellitus, hypothyroidism, and undergoing laparoscopic sleeve gastrectomy may lead to lower %EBWL in the postoperative period after bariatric surgery. At the same time, patients' mental health status and sleep apnea status were not related to %EBWL. This study provides new insight into which comorbidities may need tighter control in order to optimize weight loss outcomes after bariatric surgery.

Factors affecting timing of hypothyroidism following radioactive iodine therapy (RAIT) for patients with Graves' disease: A 12-month observational study.

BACKGROUND: This retrospective study analyzed factors influencing hypothyroidism development after radioactive iodine therapy for Graves' disease. PATIENTS AND METHODS: Three hundred and three patients with Graves' disease treated with radioactive iodine (RAI) from 2013 to 2022 at two Egyptian hospitals were included. Data collected included demographics, lab values, thyroid imaging, RAI doses, and outcomes. Patients were followed for ≥1 year to assess hypothyroidism onset. RESULTS: At the end of 1 year, around 79.5% of the individuals developed hypothyroidism while 12.5% continued to experience hyperthyroidism. The onset of hypothyroidism occurred earlier in those with thyroid volume (≤75.5 cm 3 ), lower thyroid weight (≤84.7 g), thyroid uptake (≤18.8%), and higher RAI dose/volume (≥0.1022 mCi/ml) ( P  < 0.001). Additionally, there was a correlation between anti-thyroid peroxidase (anti-TPO) antibodies and faster development of hypothyroidism compared to those who were negative for antibodies (2.9 vs 8.9 months, P  = 0.001). When considering factors in analysis it was found that anti-TPO antibodies were the only independent predictor, for developing hypothyroidism (hazard risk 30.47, P  < 0.001). Additionally, thyroid volume and uptake independently predicted successful treatment outcomes ( P  < 0.05). CONCLUSION: Positive anti-TPO antibodies strongly predict hypothyroidism risk after RAI therapy for Graves' disease. Smaller thyroid size, lower uptake, and higher RAI dose/volume correlate with earlier hypothyroidism onset but are less significant predictors than anti-TPO status. Findings can guide RAI therapy personalization to optimize outcomes.

Protective effect of higher free thyroxine levels within the reference range on biliary tract cancer risk: a multivariable mendelian randomization and mediation analysis.

Background: Hepatobiliary cancer (HBC), including hepatocellular carcinoma (HCC) and biliary tract cancer (BTC), is currently one of the malignant tumors that mainly cause human death. Many HBCs are diagnosed in the late stage, which increases the disease burden, indicating that effective prevention strategies and identification of risk factors are urgent. Many studies have reported the role of thyroid hormones on HBC. Our research aims to assess the causal effects and investigate the mediation effects between thyroid function and HBC. Methods: Utilizing the Mendelian randomization (MR) approach, the study employs single nucleotide polymorphisms (SNPs) as instrumental variables (IVs) to explore causal links between thyroid function [free thyroxine (FT4), thyroid stimulating hormone (TSH), hyperthyroidism and hypothyroidism] and HBC. Data were sourced from the ThyroidOmic consortium and FinnGen consortium. The analysis included univariable and multivariable MR analysis, followed by mediation analysis. Results: The study found a significant causal association between high FT4 levels and the reduced risk of BTC, but not HCC. However, TSH, hyperthyroidism and hypothyroidism had no causal associations with the risk of HBC. Notably, we also demonstrated that only higher FT4 levels with the reference range (FT4-RR) could reduce the risk of BTC because this protective effect no longer existed under the conditions of hyperthyroidism or hypothyroidism. Finally, we found that the protective effect of FT4-RR on BTC was mediated partially by decreasing the risk of metabolic syndrome (MetS) and reducing the waist circumference (WC). Conclusion: The findings suggest that higher FT4-RR may have a protective effect against BTC, which is partially mediated by decreased risk of MetS and a reduction in WC. This study highlights the potential role of FT4 in the pathogenesis of BTC and underscores that MetS and WC may play mediation effects as two mediators in this process.

Thyroid dysfunction after immune checkpoint inhibitors in a single-centre UK pan-cancer cohort: A retrospective study.

PURPOSE: This study investigated thyroid dysfunction with immune checkpoint inhibitors (ICIs) in terms of proportions affected, risk factors, thyroid sequelae, and overall survival (OS). METHODS: Among patients with normal baseline free T4 (fT4) and thyroid stimulating hormone (TSH) receiving ICIs at a large cancer centre, proportions of hyperthyroidism/hypothyroidism were determined (any, subclinical [normal fT4, abnormal TSH], overt [abnormal fT4, abnormal TSH], isolated hyperthyroxinaemia/hypothyroxinaemia and secondary) with onset times and subsequent thyroid statuses. Associations of overt dysfunction with OS were estimated using Cox regression and methods robust to immortal time bias (time-dependent Cox regression and 3- and 6-month landmark analyses). Associations of baseline variables with overt hyperthyroidism and hypothyroidism were estimated using Fine and Gray regression. RESULTS: Of 1349 patients, 34.2% developed hyperthyroidism (10.3% overt), including 54.9% receiving combination ICIs, while 28.2% developed hypothyroidism (overt 9.3%, secondary 0.5%). A third of overt hypothyroidism cases occurred without preceding hyperthyroidism. Subclinical thyroid dysfunction returned directly to normal in up to half. Overt hyperthyroidism progressed to overt hypothyroidism in 55.4% (median 1.6 months). Melanoma treatment in the adjuvant vs. advanced setting caused more overt hyperthyroidism (12.1% vs. 7.5%) and overt hypothyroidism (14.5% vs. 9.7%). Baseline eGFR < 60 mL/min/1.73 m2 (HR=1.68, 1.07-2.63) was associated with overt hyperthyroidism and sex (HR=0.60, 0.42-0.87) and TSH (4th vs. 1st quartile HR=1.87, 1.10-3.19) with overt hypothyroidism. Overt dysfunction was associated with OS in the Cox analysis (HR=0.65, 0.50-0.85, median follow-up 22.2 months) but not in the time-dependent Cox (HR=0.79, 0.60-1.03) or landmark analyses (3-month HR=0.74, 0.51-1.07; 6-month HR=0.91, 0.66-1.24). CONCLUSION: Thyroid dysfunction affects up to half of patients receiving ICIs. The association with OS is unclear after considering immortal time bias. The clinical courses include recovery, thyrotoxicosis and de novo overt hypothyroidism. Adjuvant treatment for melanoma, where longer-term harms are of concern, causes more frequent/aggressive dysfunction.

Impact of subclinical hypothyroidism on outcomes after coronary artery bypass grafting: a systematic review and meta-analysis.

INTRODUCTION: Coronary artery bypass grafting (CABG) is a surgical procedure that restores blood flow to heart muscle by bypassing the blocked or narrowed coronary arteries. On the other hand, subclinical hypothyroidism (SCH) is characterized by an elevated serum concentration of thyroid stimulating hormone with normal levels of serum free thyroxine. With limited research into the impact of SCH on postoperative CABG outcomes, this systematic review and meta-analysis was performed. EVIDENCE ACQUISITION: An electronic search of PubMed, Cochrane Library, and Scopus was performed from inception to April 2023. After the inclusion of five studies, a total of 2,786 patients were pooled in this quantitative synthesis. EVIDENCE SYNTHESIS: It was observed that SCH significantly increased cardiovascular mortality (OR: 2.80; 95% CI: 1.37, 5.72; P=0.005), and all-cause mortality (OR: 2.62; 95% CI: 1.80, 3.80; P<0.00001). However, no significant differences were observed for secondary outcomes, including major adverse cardiac events, incidence of postoperative stroke, and incidence of postoperative myocardial infarction. CONCLUSIONS: To the best of our knowledge, this is the first meta-analysis conducted that evaluates the impact of SCH on outcomes after CABG. The preoperative assessment of thyroid function may be considered prior to cardiovascular procedures, particularly within CABG. However, future comprehensive studies, with individual participant-level data, are necessary in order to arrive at a valid conclusion and recommendation.

Aversion of surgical exploration in patients with complex ovarian cysts secondary to overt hypothyroidism: A series of three cases.

Long-standing, overt hypothyroidism-induced bilateral multiloculated ovarian cysts represent an infrequent occurrence. Our first case, presented with bilateral complex ovarian masses, exhibited overt hypothyroidism symptoms, including lethargy, weight gain and subfertility, prompting consideration for surgical intervention. Similarly, in the second case, a girl aged 11 years with stunting, delayed bone age and academic challenges was referred for surgical exploration due to bilateral complex ovarian masses. Both cases revealed elevated thyroid-stimulating hormone levels during preoperative workup. Commencing levothyroxine replacement therapy resulted in complete regression of ovarian cysts and substantial symptom improvement within an 8-week timeframe. The third case, a previously diagnosed patient with Hashimoto's thyroiditis, benefited from the lessons gleaned in managing the initial cases, responding well to levothyroxine therapy, thereby averting the necessity for surgery in all three instances. These cases underscore the significance of considering thyroid function in the evaluation of ovarian masses and highlight the efficacy of levothyroxine replacement therapy in resolving both hypothyroidism and associated ovarian cysts, thereby obviating the need for surgical intervention.

Thyroid hormone deprival and TSH/TSHR signaling deficiency lead to central hypothyroidism-associated intestinal dysplasia.

BACKGROUND: Central hypothyroidism (CH) is characterized by low T4 levels and reduced levels or bioactivity of circulating TSH. However, there is a lack of studies on CH-related intestinal maldevelopment. In particular, the roles of TH and TSH/TSHR signaling in CH-related intestinal maldevelopment are poorly understood. Herein, we utilized Tshr-/- mice as a congenital hypothyroidism model with TH deprival and absence of TSHR signaling. METHODS: The morphological characteristics of intestines were determined by HE staining, periodic acid-shiff staining, and immunohistochemical staining. T4 was administrated into the offspring of homozygous mice from the fourth postnatal day through weaning or administrated after weaning. RT-PCR was used to evaluate the expression of markers of goblet cells and intestinal digestive enzymes. Single-cell RNA-sequencing analysis was used to explore the cell types and gene profiles of metabolic alternations in early-T4-injected Tshr-/- mice. KEY FINDINGS: Tshr deletion caused significant growth retardation and intestinal maldevelopment, manifested as smaller and more slender small intestines due to reduced numbers of stem cells and differentiated epithelial cells. Thyroxin supplementation from the fourth postnatal day, but not from weaning, significantly rescued the abnormal intestinal structure and restored the decreased number of proliferating intestinal cells in crypts of Tshr-/- mice. Tshr-/- mice with early-life T4 injections had more early goblet cells and impaired metabolism compared to Tshr+/+ mice. SIGNIFICANCE: TH deprival leads to major defects of CH-associated intestinal dysplasia while TSH/TSHR signaling deficiency promotes the differentiation of goblet cells and impairs nutrition metabolism.

Immune-related adverse events associated with first-line immune checkpoint inhibitors for metastatic renal cell carcinoma: A systematic review and network meta-analysis.

BACKGROUND: In the realm of metastatic renal cell carcinoma (mRCC), the introduction of immune checkpoint inhibitors (ICIs) has revolutionized treatment paradigms. Despite their effectiveness, the comprehensive safety profile of these therapies remains inadequately explored. This network meta-analysis aims to comparing the safety profiles of ICI-based treatments in mRCC, offering vital insights that could lead to the optimization of treatment strategies and improvement of patient care. METHODS: We conducted a comprehensive search of PubMed, Cochrane Library, Embase, Web of Science, ClinicalTrials.gov, Google Schola, OpenGrey and Scopus through November 1, 2023. The risk of bias assessment was performed using the Risk of Bias version 2 tool. RESULTS: Seven randomized controlled trials (RCTs) with a total of 5976 patients were included for data analysis. The risk of bias results showed that all RCTs were considered "some concerns". The probability of hypothyroidism (surface under the cumulative ranking curve (SUCRA) = 0.981), hyperthyroidism (SUCRA = 0.983) and dermatologic immune-related adverse events (irAEs) (SUCRA = 0.955) in the Nivolumab + Cabozantinib ranked the first. The Avelumab + Axitinib had the highest incidence of adrenal insufficiency (AI) (SUCRA = 0.976), hepatitis (SUCRA = 0.937) and colitis (SUCRA = 0.864). The Nivolumab + Ipilimumab exhibited the highest incidence of pneumonitis (SUCRA = 0.755). Pembrolizumab + Lenvatinib had the highest incidence of nephritic irAEs (SUCRA = 0.788). The ICI-based group showed a higher incidence of hypothyroidism, hyperthyroidism, dermatologic irAEs, hepatitis and nephritic irAEs than sunitinib. However, the confidence in the evidence regarding the impact of ICI-based treatments on AI, pneumonia, and colitis remains limited. CONCLUSION: The analysis focused on the probability of irAEs occurrence in each system when mRCC patients were treated with different ICI-based therapies, potentially offering significant value for guiding clinical prevention, early diagnosis, and management of irAEs. The limitations of the study included the potential heterogeneity and low certainty of part of the evidence.

Development of hypothyroidism following hemithyroidectomy: A population-based study.

PURPOSE: Hypothyroidism is a known possibility after hemithyroidectomy, with a highly variable incidence in the literature ranging from 8 to 60 %. Incidence of hypothyroidism after hemithyroidectomy was evaluated with a secondary aim to assess incidence in patients with Hashimoto's disease. MATERIALS & METHODS: A retrospective study using the TriNetX global federated research network was performed. We included patients within the last 15 years that were ≥18 years of age and had Current Procedural Terminology codes for hemithyroidectomy. Patients were excluded if they had a total or completion thyroidectomy at any time, a history of thyroid cancer, were preoperatively either on levothyroxine, diagnosed with hypothyroidism, or had a Thyroid Stimulating Hormone ≥ 4 m[IU]/L. We assessed the 3 month incidence of hypothyroidism postoperatively based on the International Classification of Diseases code, TSH ≥ 4 m[IU]/L, or taking levothyroxine after surgery. RESULTS: 6845 patients met the inclusion criteria. Most of the cohort was female (67 %) and white (63 %). The mean age at surgery for this population was 54 ± 14.8 years. During the 15 years of data, we found the 3-month incidence of hypothyroidism following hemithyroidectomy to be 23.58 %. The median time to develop the disease was 41.8 months. A subgroup analysis of those with Hashimoto's revealed a 3-month incidence of 31.1 % of patients developing hypothyroidism after surgery. CONCLUSIONS: This population-based study gives additional insight into the incidence of hypothyroidism after hemithyroidectomy. This will help improve perioperative patient counseling and management.

Relationship Between Urinary Iodine Concentration and the Prevalence of Thyroid Nodules and Subclinical Hypothyroidism.

The aim of the study was to investigate the iodine intake in the resident population in Xi'an and analyze the relationship between iodine nutritional status and the prevalence of subclinical hypothyroidism and thyroid nodules (TNs). A total of 2507 people were enrolled in Xi'an. Venous serum thyroid stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb), urinary iodine concentration (UIC), and thyroid ultrasonography were collected. Patients with abnormal TSH were checked for free thyroxine (FT4) and triiodothyronine (FT3). Adults in Xi'an had median UICs of 220.80 µg/L and 178.56 µg/l, respectively. A sum of 16.78% of people had subclinical hypothyroidism. Both iodine excess and iodine deficit increased the frequency of subclinical hypothyroidism. The lowest was around 15.09% in females with urine iodine levels between 200 and 299 µg/l. With a rate of 10.69%, the lowest prevalence range for males was 100-199 µg/l. In Xi'an, 11.37% of people have TNs. In comparison to other UIC categories, TN occurrences were higher in females (18.5%) and males (12%) when UIC were below 100 µg/l. In conclusion, iodine intake was sufficient in the Xi'an area, while the adults' UIC remains slightly higher than the criteria. Iodine excess or deficiency can lead to an increase in the prevalence of subclinical hypothyroidism. Patients with iodine deficiency are more likely to develop TNs.