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.

Hyperthyroidism-driven bone loss depends on BMP receptor Bmpr1a expression in osteoblasts.

Hyperthyroidism is a well-known trigger of high bone turnover that can lead to the development of secondary osteoporosis. Previously, we have shown that blocking bone morphogenetic protein (BMP) signaling systemically with BMPR1A-Fc can prevent bone loss in hyperthyroid mice. To distinguish between bone cell type-specific effects, conditional knockout mice lacking Bmpr1a in either osteoclast precursors (LysM-Cre) or osteoprogenitors (Osx-Cre) were rendered hyperthyroid and their bone microarchitecture, strength and turnover were analyzed. While hyperthyroidism in osteoclast precursor-specific Bmpr1a knockout mice accelerated bone resorption leading to bone loss just as in wildtype mice, osteoprogenitor-specific Bmpr1a deletion prevented an increase of bone resorption and thus osteoporosis with hyperthyroidism. In vitro, wildtype but not Bmpr1a-deficient osteoblasts responded to thyroid hormone (TH) treatment with increased differentiation and activity. Furthermore, we found an elevated Rankl/Opg ratio with TH excess in osteoblasts and bone tissue from wildtype mice, but not in Bmpr1a knockouts. In line, expression of osteoclast marker genes increased when osteoclasts were treated with supernatants from TH-stimulated wildtype osteoblasts, in contrast to Bmpr1a-deficient cells. In conclusion, we identified the osteoblastic BMP receptor BMPR1A as a main driver of osteoporosis in hyperthyroid mice promoting TH-induced osteoblast activity and potentially its coupling to high osteoclastic resorption.

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.

[Patient needs at the heart of the national hyperthyroidism guideline]. / Patientens behov i fokus i vårdprogram för hypertyreos.

Hyperthyroidism is a common disease that primarily affects women of all ages, and in addition to physical symptoms, mental symptoms are common, such as mental fatigue, anxiety, difficulty concentrating and mood changes. A common opinion is that the patient is recovered once the thyroid disorder is treated. However, many patients will experience persistent brain fatigue and mental problems, even after normal thyroid function is restored. Patients want to live as good a life as possible despite their illness, and in healthcare, they request interventions for rehabilitation. A new guideline for hyperthyroidism was launched in January 2023 that highlights many of these aspects, including the mental symptoms and the patient's perspective on hyperthyroidism. In this article, we want to address the patient's needs and how we can meet them in healthcare to increase their participation, confidence and quality of life, with continuity throughout the entire care process.

[Hyperthyroidism - a classic disease]. / Hypertyreos är inte bara endokrinologens angelägenhet.

Hyperthyroidism presents with various forms of generalized symptoms. Primary care physicians as well as other specialists should have this in mind when meeting patients with symptoms such as palpitations, sweating, fatigue and weight loss. Thyroid-stimulating hormone (TSH) is a highly specific test and useful in ruling out hyperthyroidism. The severity of the disease determines the pace of management. Primary care is often involved in detection of hyperthyroidism but also takes part in the work of rehabilitation and the lifelong hormonal substitution that is necessary for 2/3 of all patients. Subclinical hyperthyroidism, characterized by low TSH levels but normal levels of T4 and T3, is associated with increased mortality by 24 percent and risks of cardiovascular disease, atrial fibrillation and osteoporosis. Treatment depends on age, presence of comorbidity and TSH-levels. In addition to specific endocrinological treatment, person-centered care is crucial during active disease and rehabilitation. The first Swedish care program for hyperthyroidism aims to enhance care efficiency and equity.

[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.

Associations of TSH, free T3, free T4, and conversion ratio with incident hypertension: results from the prospective Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

Objective: To evaluate the association of TSH, free T3 (FT3), free T4 (FT4), and conversion (FT3:FT4) ratio values with incident hypertension. Materials and methods: The study included data from participants of the ELSA-Brasil study without baseline hypertension. Serum TSH, FT4 and FT3 levels, and FT3:FT4 ratio values were assessed at baseline, and incident hypertension (defined by blood pressure levels ≥ 140/90 mmHg) was estimated over a median of 8.2 years of follow-up. The risk of incident hypertension was evaluated considering a 1-unit increase in TSH, FT4, FT3, and conversion ratio values and after dividing these variables into quintiles for further analysis using Poisson regression with robust variance. The results are presented as relative risks (RR) and 95% confidence intervals (CIs) before and after adjustment for multiple variables. Results: The primary analysis incorporated data from 5,915 euthyroid individuals, and the secondary analysis combined data from all euthyroid individuals, 587 individuals with subclinical hypothyroidism, and 31 individuals with subclinical hyperthyroidism. The rate of incident hypertension was 28% (95% CI: 27%-29.3%). The FT4 levels in the first quintile (0.18-1.06 ng/dL) were significantly associated with incident hypertension (RR: 1.03, 95% CI: 1.01-1.06) at follow-up. The association between FT4 levels in the first quintile and incident hypertension was also observed in the analysis of combined data from euthyroid individuals and participants with subclinical thyroid dysfunction (RR: 1.04, 95% CI: 1.01-1.07). The associations were predominantly observed with systolic blood pressure levels in euthyroid individuals. However, in the combined analysis incorporating euthyroid participants and individuals with subclinical thyroid dysfunction, the associations were more pronounced with diastolic blood pressure levels. Conclusion: Low FT4 levels may be a mild risk factor for incident hypertension in euthyroid individuals and persons with subclinical thyroid dysfunction.

Cardiac evaluation in amiodarone-induced thyroid dysfunction with suspected cardiac ischemia?: a case report and review of the literature.

BACKGROUND: Amiodarone-induced thyroid dysfunction (AIT) is a side-effect associated with the use of Amiodarone for the treatment of refractory arrythmias. Resulting hyperthyroidism can precipitate cardiac complications, including cardiac ischemia and myocardial infarction, although this has only been described in a few case reports. CASE PRESENTATION: We present here a clinical scenario involving a 66-year-old male Caucasian patient under Amiodarone for atrial fibrillation, who developed AIT. In the presence of dyspnea, multiple cardiovascular risk factors and ECG abnormalities, a transthoracic echocardiogram was performed, showing inferobasal hypokinesia. This led to further investigations through a cardiac PET-CT, where cardiac ischemia was suspected. Ultimately, the coronary angiography revealed no abnormalities. Nonetheless, these extensive cardiologic investigations led to a delay in initiating an emergency endovascular revascularization for acute-on-chronic left limb ischemia. Although initial treatment using Carbimazole was not successful after three weeks, the patient reached euthyroidism after completion of the treatment with Prednisone so that eventually thyroidectomy was not performed. Endovascular revascularization was finally performed after more than one month. CONCLUSIONS: We discuss here cardiac abnormalities in patients with AIT, which may be due to relative ischemia secondary to increased metabolic demand during hyperthyroidism. Improvement of cardiac complications is expected through an optimal AIT therapy including medical therapy as the primary approach and, when necessary, thyroidectomy. Cardiac investigations in the context of AIT should be carefully considered and may not justify delaying other crucial interventions. If considered mandatory, diagnostic procedures such as coronary angiography should be preferred to functional testing.

A Novel TSHR Gene Mutation in a Family with Non-autoimmune Hyperthyroidism.

Background: Familial non-autoimmune hyperthyroidism is a rare disorder characterized by the absence of thyroid autoimmunity, particularly TSH receptor antibody [TRAb]. Objective: The aim of this study was to describe a novel TSHR mutation identified in a family of two siblings and their father. Methods: Two siblings presented for endocrine assessment at ages 7 and 14 years with mild T3 toxicosis, and the father presented at 30 years of age with non-autoimmune thyrotoxicosis. Both siblings were treated with oral antithyroid therapy to achieve reasonable symptom control and thyroid function normalization. The father was treated with oral antithyroid therapy, radioactive iodine, thyroidectomy, and thyroid replacement therapy. Peripheral blood DNA was extracted from both affected siblings and father. Mutation analysis of TSHR was carried out by PCR and Sanger sequencing of both strands of the extracted DNA. Results: Both siblings and their father were heterozygous for the missense TSHR variant c.1855G>C, p.[Asp619His], in exon 10. Conclusions: This novel TSHR variant is associated with T3 toxicosis during childhood. Therefore, early identification and treatment may improve patient outcomes.

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).

Diagnoses of obstetric and postpartum thyroid disease: a Danish validation study.

Different diagnoses of thyroid disease are available in the 10th International Classification of Diseases (ICD-10), but the validity of diagnoses related to obstetric and postpartum thyroid disease is unknown. This was a retrospective cohort study of all patients in the North Denmark Region with a diagnosis of postpartum thyroiditis (PPT) (ICD-10: O905) from 2016 to 2019 or obstetric thyroid disease in 2019 (ICD-10: O992B (hypothyroidism) or O992C (hyperthyroidism)) registered in the Danish National Hospital Register. Information from nationwide registers and medical records were used to assess the validity. Among patients with an O905-diagnosis (n = 40), abnormal thyroid function test results were seen in all cases. A total of eight patients (20.0%) were positive for thyrotropin receptor antibodies postpartum, however, in low titers, and PPT was verified in 39 of 40 cases (97.5%). Altogether 45 of 50 patients with an O992B-diagnosis (90.0%) correctly had hypothyroidism, whereas hyperthyroidism was found in 25 of 39 patients with an O992C-diagnosis (64.1%). This is the first study to validate ICD-10 diagnoses of obstetric and postpartum thyroid disease. A high validity was seen for PPT (O905) and obstetric hypothyroidism (O992B), whereas for obstetric hyperthyroidism (O992C), the diagnosis could not be verified in one third of the cases.

The Danish investigation on iodine intake and thyroid disease (DanThyr): history and implications.

Due to mild-to-moderate iodine deficiency in Denmark, health authorities initiated a voluntary iodine fortification (IF) program in 1998, which became mandatory in 2000. In line with recommendations from the World Health Organization, the Danish investigation on iodine intake and thyroid disease (DanThyr) was established to monitor the effect on thyroid health and disease. The program involved different study designs and followed two Danish sub-populations in the years before IF and up till 20 years after. Results showed that the IF was successfully implemented and increased the level of iodine intake from mild-moderate iodine deficiency to low adequacy. The level of thyroglobulin and thyroid volume decreased following IF, and there was an indication of fewer thyroid nodules. The incidence of hyperthyroidism increased transiently following IF but subsequently decreased below the pre-fortification level. Conversely, thyroid-stimulating hormone levels and the prevalence of thyroid autoimmunity increased along with an increase in the incidence of hypothyroidism. These trends were mirrored in the trends in treatments for thyroid disease. Most differences in thyroid health and disease between regions with different iodine intake levels before IF attenuated. This review illustrates the importance of a monitoring program to detect both beneficial and adverse effects and exemplifies how a monitoring program can be conducted when a nationwide health promotion program - as IF - is initiated.

Frequency and characteristics of immune-related thyroid adverse events in patients with resected stage III/IV melanoma treated with adjuvant PD-1 inhibitors: a national cohort study.

PURPOSE: Immune-related thyroid adverse events (irTAEs) occur frequently following immune checkpoint inhibitor (ICI) therapy. The purpose of this study is to provide knowledge about the incidence, clinical timeline characteristics, associated factors of irTAEs, and potential impact on treatment efficacy in patients with melanoma receiving adjuvant ICI therapy. METHODS: A national multicenter retrospective cohort study of patients with resected stage III/IV melanoma treated with adjuvant PD-1 inhibitors between November 2018 and December 2020. Data were extracted from the Danish Metastatic Melanoma Database. The irTAEs were defined as two consecutive abnormal TSH values and subdivided into transient or persistent. RESULTS: Of 454 patients, 99 developed an irTAE (21.8%), of these were 46 transient (46.5%) and 53 persistent (53.5%). Median time to transient and persistent irTAE was 55 and 44 days, respectively (p = 0.57). A hyperthyroid phase followed by hypothyroidism was seen in 73.6% of persistent irTAEs, whereas 87% of transient irTAEs developed an isolated hypo- or hyperthyroid phase. Multiple variable analysis demonstrated an association between irTAE and female sex (HR 2.45; 95% CI 1.63-3.70; p < 0.001), but no association with recurrence-free survival (HR 0.86; 95% CI 0.50-1.48; p = 0.587) or overall survival (HR 1.05; 95% CI 0.52-2.12, p = 0.891). CONCLUSIONS: IrTAE is a common side effect to PD-1 inhibitors primarily occurring within the first 3 months, with a high risk of persistency. Female sex is a strong predictive factor. IrTAE was not associated with improved clinical outcome.

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 function and polycystic ovary syndrome: a Mendelian randomization study.

Background: Multiple evidence suggests that thyroid function is associated with polycystic ovary syndrome (PCOS), but whether thyroid function is causally related to PCOS is unclear. To investigate whether the association reflect causality, a Mendelian randomization (MR) analysis was conducted. Methods: Single nucleotide polymorphisms (SNPs) involved in this study were acquired from The ThyroidOmics Consortium and the IEU Open Genome-wide association study (GWAS) database, respectively. In forward MR analysis, we included normal free thyroxine (FT4, n=49,269), normal thyroid-stimulating hormone (TSH, n=54,288), hypothyroidism (n=53,423) and hyperthyroidism (n=51,823) as exposure. The outcome was defined as PCOS in a sample size of 16,380,318 individuals. The exposure in the reverse MR analyses was chosen as PCOS, while the outcome consisted of the four phenotypes of thyroid function. The inverse-variance weighted (IVW) method was performed as the major analysis, supplemented by sensitivity analyses. Results: The occurrence of PCOS was associated with increased risk of hyperthyroidism (IVW, OR=1.08, 95%CI=1.02-1.13, P=0.004). No evidence suggested that other phenotypes of thyroid function were related to PCOS. Conclusions: Our findings demonstrate a cause-and-effect connection between PCOS and hyperthyroidism. The study established foundation for further investigation for interaction between thyroid function and PCOS.

Causal association between thyroid dysfunction and sepsis: a two-sample mendelian randomization study.

Background: The causal association between thyroid dysfunction (including hyperthyroidism and hypothyroidism) and sepsis is controversial in previous studies. Therefore, we used Mendelian randomization (MR) to explore the causal association between hyperthyroidism or hypothyroidism and the susceptibility to four distinct subtypes of sepsis (streptococcal sepsis, puerperal sepsis, asthma-associated pneumonia or sepsis, and other sepsis). Methods: In our research, we conducted two-sample Mendelian randomization (MR) analyses utilizing publicly available genome-wide association studies (GWAS) data from Sakaue et al. and the Finnish database to investigate the potential causal associations between hyperthyroidism, hypothyroidism, and each of the four distinct subtypes of sepsis, in addition to reverse MR analyses of the positive results to examine the existence of reverse causality. Results: Genetic hypothyroidism was causally related to the development of asthma-associated pneumonia or sepsis (ORIVW: 1.097, 95% CI: 1.024 to 1.174, P = 0.008); hypothyroidism was significantly associated with the development of other sepsis (ORIVW: 1.070, 95% CI: 1.028 to 1.115, P < 0.001). In addition, sensitivity analysis substantiated the robustness of these two MR findings, with no evidence of horizontal pleiotropy observed (P > 0.05). MR Egger regression analysis demonstrated no heterogeneity between instrumental variables (IVs). Inverse MR results confirmed no reverse causality between hypothyroidism and asthma-associated pneumonia or sepsis, or between hypothyroidism and other sepsis. The findings of this study also unveiled that there is no evidence of a causal link between hypothyroidism and the development of streptococcal sepsis or puerperal sepsis. Additionally, the research provided evidence indicating the absence of a causal relationship between hyperthyroidism and streptococcal sepsis, puerperal sepsis, asthma-associated pneumonia or sepsis, and other sepsis. Conclusions: This study identified a causal link between hypothyroidism and the occurrence of asthma-associated pneumonia or sepsis, and other sepsis, but not with the development of streptococcal sepsis and puerperal sepsis. Moreover, our findings did not reveal any causal association between hyperthyroidism and streptococcal sepsis, puerperal sepsis, asthma-associated pneumonia or sepsis, and other sepsis.

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.

High prevalence of erectile dysfunction in men with hyperthyroidism: a meta-analysis.

OBJECTIVE: The objective of this study was to evaluate the association between hyperthyroidism and the risk of developing erectile dysfunction (ED). METHODS: A comprehensive search of multiple databases, including PubMed, Embase, Cochrane, and Web of Science, was conducted to identify relevant studies investigating the relationship between hyperthyroidism and ED in men. The quality of the included studies was assessed using the Newcastle‒Ottawa Quality Rating Scale, and a meta-analysis was performed using Stata 16.0 and RevMan 5.3 software. RESULTS: A total of four papers encompassing 25,519 study subjects were included in the analysis. Among these, 6,429 individuals had hyperthyroidism, while 19,090 served as controls. The overall prevalence of ED in patients with hyperthyroidism was determined to be 31.1% (95% CI 0.06-0.56). In patients with uncomplicated hyperthyroidism, the incidence of ED was 21.9% (95% CI 0.05-0.38). The combined odds ratio (OR) for the four studies was 1.73 (OR: 1.73; 95% CI [1.46-2.04]; p < .00001). CONCLUSION: Our findings demonstrate a higher incidence of ED in patients with hyperthyroidism. These results provide valuable information for healthcare professionals and can facilitate discussions surrounding appropriate treatment options for ED in patients with hyperthyroidism.

The genetic association between hyperthyroidism and heart failure: a Mendelian randomization study.

Background and aims: Hyperthyroidism is an endocrine disease with multiple etiologies and manifestations. Heart failure (HF) is a common, costly, and deadly medical condition in clinical practice. Numerous studies have suggested that abnormal thyroid function can induce or aggravate the development of heart disease. However, no study has demonstrated a causal relationship between hyperthyroidism and heart failure. Therefore, the purpose of this study was to explore the causal link between hyperthyroidism and HF. Methods: Summary data for genetically predicted hyperthyroidism were obtained from a genetic association study. The data examined for genetically determined all-cause heart failure came from 218,208 individuals from the FinnGen Consortium. Two-sample Mendelian randomization (MR) analysis was used to estimate the causal link between hyperthyroidism and heart failure. Statistical analyses were conducted using the inverse variance-weighted, weighted median, simple median, weighted mode, MR-PRESSO (number of distribution = 5000), MR-Egger, and leave-one-out. Results: The results of the inverse-variance weighted analysis indicated a causal association between hyperthyroidism and an increased risk of all-cause heart failure (IVW: ß=0.048, OR=1.049, 95%CI: [1.013 to 1.087], P=0.007). Similarly, the weighted median approach demonstrated a positive correlation between hyperthyroidism and all-cause heart failure (OR=1.049, [95% CI, 1.001-1.100]; P=0.044). Additionally, no horizontal pleiotropy or heterogeneity was observed. The leave-one-out analysis revealed that the majority of the SNP-driven associations were not influenced by a single genetic marker. Conclusion: Our study observed a causal relationship between hyperthyroidism and all-cause heart failure. Hyperthyroidism may associate with heart failure genetically.