Investigating the causal relationship between thyroid dysfunction diseases and osteoporosis: a two-sample Mendelian randomization analysis.

The prevalence of thyroid dysfunction diseases (TDFDs) and osteoporosis (OP) is high. Previous studies have indicated a potential association between TDFDs and OP, yet the causal direction remains unclear. This study aimed to investigate the potential causal relationship between TDFDs and the risk of developing OP and related fractures. We obtained pooled data from genome-wide association studies (GWASs) conducted on TDFDs and OP in European populations and identified single-nucleotide polymorphisms (SNPs) with genome-wide significance levels associated with exposure to TDFDs as instrumental variables. Inverse variance weighted (IVW) was employed as the primary method for Mendelian randomization (MR) analysis, supplemented by MR‒Egger, weighted median, simple mode and weighted mode methods. Sensitivity analyses were conducted to evaluate the robustness of the findings. The IVW method demonstrated an increased risk of OP in patients with TDFDs, including hyperthyroidism and hypothyroidism (TDFDs: OR = 1.11; 95% CI 1.09, 1.13; hypothyroidism: OR = 1.14; 95% CI 1.10, 1.17; hyperthyroidism: OR = 1.09; 95% CI 1.06, 1.12). These findings were supported by supplementary analysis, which revealed a positive correlation between TDFDs and the risk of OP. Multiple sensitivity analyses confirmed the absence of horizontal pleiotropy in the study, thus indicating the robustness of our results. The causal relationship between TDFDs and increased risk of OP implies the need for early bone mineral density (BMD) screening and proactive prevention and treatment strategies for individuals with TDFDs.

Control rate of hyperthyroidism and its associated factors after prolonged use of anti-thyroid drugs in a hospital setting, Northwest Ethiopia.

Hyperthyroidism is increased synthesis and secretion of thyroid hormones by the thyroid gland resulting in thyrotoxicosis. The modality of therapy for hyperthyroidism includes anti-thyroid drugs, radioiodine and surgery. Anti-thyroid drugs are the only available therapy for hyperthyroid patients in developing world as radioiodine is inaccessible and surgical set up does not exist as required. The aim of this study was to determine the magnitude and predictors of uncontrolled hyperthyroidism among hyperthyroid patients after prolonged anti-thyroid drug use. An institutional-based cross sectional study was conducted at the University of Gondar hospital, Northwest Ethiopia, between April 1, 2022 and October 31, 2022. A consecutive sampling method was used to recruit 317 study subjects. Data were collected through a pre-designed questionnaire. Patients were interviewed to obtain socio-demographic data and relevant medical information. Laboratory analyses were done based on the follow up protocol. Data were entered into EPI Info version 4.6.0.0 (EPI Info, Atlanta) and analyzed in STATA version 14 (Stata Corp LP, Texas, USA). Binary logistic regression model was used to identify variables associated with uncontrolled hyperthyroidism among hyperthyroid patients. P value < .05 was used to declare significant association. A total of 317 patients with hyperthyroidism were included in the study. The median age of the study subjects was 45 years (IQR 36-55 years). Most (95%) of the study participants were females. Toxic multi-nodular goiter was the most common cause of hyperthyroidism (92%), followed by toxic adenoma (5%) and Graves' disease (2%). On multivariate binary logistic regression, large goiter size (AOR: 3.163, 95% CI [1.333-7.506]), severe disease (AOR: 2.275, 95% CI [1.060-4.880]), infrequent iodinated salt intake (AOR: 3.668, 95% CI [1.245-10.802]), and poor adherence to anti-thyroid drug (AOR:15.724, 95% CI [5.542-44.610]) were statistically significant with uncontrolled hyperthyroidism at 12 months of anti-thyroid drug intake. A quarter of patients with hyperthyroidism didn't achieve euthyroid state after 12 months of anti-thyroid drug use. The identified predictors for non-euthyroid state were large goiter size, severe disease, infrequent iodinated salt intake, and poor adherence to anti-thyroid drug.

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.

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.

[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.

[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.

The association between three prevalent autoimmune disorders and the likelihood of developing prostate cancer: a Mendelian randomization study.

Numerous studies establish a significant correlation between autoimmune disorders (AIDs) and prostate cancer (PCa). Our Mendelian randomization (MR) analysis investigates the potential connection between rheumatoid arthritis (RA) and PCa, aiming to confirm causal links between systemic lupus erythematosus (SLE), hyperthyroidism, and PCa. Summary statistics from genome-wide association studies provided data on PCa and three AIDs. MR analysis, using IVW as the main approach, assessed causal relationships, validated by sensitivity analysis. IVW revealed a correlation between genetically anticipated RA and PCa, notably in Europeans (OR = 1.03; 95% CI 1.01-1.04, p = 2*10-5). Evidence supported a lower PCa risk in individuals with SLE (OR = 0.94; 95% CI 0.91-0.97, p = 2*10-4) and hyperthyroidism (OR = 0.02; 95% CI 0.001-0.2, p = 2*10-3). Weighted mode and median confirmed these findings. No pleiotropic effects were observed, and MR heterogeneity tests indicated dataset homogeneity. Our study establishes a causal link between RA, SLE, hyperthyroidism, and PCa.

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

PURPOSE: Observational studies and clinical validation have suggested a link between thyroid dysfunction and an elevated ovarian cancer (OC) risk. However, whether this association indicates a cause-and-effect relationship remains uncertain. We aimed to investigate the plausible causal impact of thyroid dysfunction on OC through a Mendelian randomization (MR) study. METHODS: Genome-wide association study (GWAS) data for thyrotropin (TSH), free thyroxine (FT4), hypothyroidism, and hyperthyroidism were obtained as exposures and those for OC (N = 199,741) were selected as outcomes. Inverse variance-weighted method was used as the main estimation method. A series of sensitivity analyses, including Cochran's Q test, MR-Egger intercept analysis, forest plot scatter plot, and leave-one-out test, was conducted to assess the robustness of the estimates. RESULTS: Genetic prediction of hyperthyroidism was associated with a potential increase in OC risk (odds ratio = 1.094, 95% confidence interval: 1.029-1.164, p = 0.004). However, no evidence of causal effects of hypothyroidism, TSH, and FT4 on OC or reverse causality was detected. Sensitivity analyses demonstrated consistent and reliable results, with no significant estimates of heterogeneity or pleiotropy. CONCLUSIONS: This study employed MR to establish a correlation between hyperthyroidism and OC risk. By genetically predicting OC risk in patients with hyperthyroidism, our research suggests new insights for early prevention and intervention of OC.

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.

[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.

Air pollution exposure, accelerated biological aging, and increased thyroid dysfunction risk: Evidence from a nationwide prospective study.

BACKGROUND: Long-term air pollution exposure is a major health concern, yet its associations with thyroid dysfunction (hyperthyroidism and hypothyroidism) and biological aging remain unclear. We aimed to determine the association of long-term air pollution exposure with thyroid dysfunction and to investigate the potential roles of biological aging. METHODS: A prospective cohort study was conducted on 432,340 participants with available data on air pollutants including particulate matter (PM2.5, PM10, and PM2.5-10), nitrogen dioxide (NO2), and nitric oxide (NO) from the UK Biobank. An air pollution score was calculated using principal component analysis to reflect joint exposure to these pollutants. Biological aging was assessed using the Klemera-Doubal method biological age and the phenotypic age algorithms. The associations of individual and joint air pollutants with thyroid dysfunction were estimated using the Cox proportional hazards regression model. The roles of biological aging were explored using interaction and mediation analyses. RESULTS: During a median follow-up of 12.41 years, 1,721 (0.40 %) and 9,296 (2.15 %) participants developed hyperthyroidism and hypothyroidism, respectively. All air pollutants were observed to be significantly associated with an increased risk of incident hypothyroidism, while PM2.5, PM10, and NO2 were observed to be significantly associated with an increased risk of incident hyperthyroidism. The hazard ratios (HRs) for hyperthyroidism and hypothyroidism were 1.15 (95 % confidence interval: 1.00-1.32) and 1.15 (1.08-1.22) for individuals in the highest quartile compared with those in the lowest quartile of air pollution score, respectively. Additionally, we noticed that individuals with higher pollutant levels and biologically older generally had a higher risk of incident thyroid dysfunction. Moreover, accelerated biological aging partially mediated 1.9 %-9.4 % of air pollution-associated thyroid dysfunction. CONCLUSIONS: Despite the possible underestimation of incident thyroid dysfunction, long-term air pollution exposure may increase the risk of incident thyroid dysfunction, particularly in biologically older participants, with biological aging potentially involved in the mechanisms.

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.

Minor hyperthyroidism with normal levels of thyroid-stimulating hormone receptor antibodies: a case report.

The present report describes for the first time a case of diffuse hyperthyroidism in a 30-year-old female patient who had normal levels of thyroid-stimulating hormone receptor antibodies (TSHR-Ab), slightly elevated plasma levels of thyroid hormones, and slightly increased thyroid blood flow. Seven years before, after severe stress, she had Graves' disease with elevated plasma levels of TSHR-Ab. The patient's recent medical history included mental stress and autonomic dysfunction. This report describes a mild form of hyperthyroidism in terms of elevated plasma levels of thyroid hormones and Doppler ultrasonography data; this condition was first defined as 'minor hyperthyroidism'. The examination data suggest a probable secondary role of the immune system and primary role of the autonomic nervous system in the pathogenesis of Graves' disease.

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.

Endocrine Fever.

Fever is usually thought to be of an infectious or inflammatory etiology. In this brief communication, we explore the multifaceted connections between fever and endocrine dysfunction. Impaired resistance to infection often leads to fever in conditions like diabetes and Cushing's syndrome. Additionally, several endocrine disorders, including hyperthyroidism, subacute thyroiditis, carcinoid syndrome, and pheochromocytoma, can manifest as fever. Furthermore, fever can be an adverse effect of various endocrine treatments, such as bisphosphonates and antithyroid drugs. We refer to these scenarios as 'endocrine fever.' Increased awareness of these clinical associations can aid in prompt diagnosis and management of these conditions.

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.

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).