Challenges in the Management of Atrial Fibrillation With Subclinical Hyperthyroidism

Subclinical thyroid disorders have a high prevalence among older individuals and women. Subclinical hypothyroidism is diagnosed by elevated serum levels of thyroid-stimulating hormone (TSH) with thyroxine levels within the reference range, and subclinical hyperthyroidism is diagnosed by low TSH in conjunction with thyroxine and triiodothyronine levels within reference ranges. Atrial fibrillation is the most commonly diagnosed cardiac arrhythmia and has been associated with an increased risk of mortality, heart failure, stroke, and depression. Mechanistic data from animal and human physiology studies as well as observational data in humans support an association of subclinical hyperthyroidism with atrial fibrillation. Guidelines recommend the measurement of TSH in the evaluation of new-onset atrial fibrillation. All patients with overt hyperthyroidism should be treated, and treatment of subclinical hyperthyroidism should be considered in patients older than 65 years with TSH < 0.4 mlU/L, or in younger patients with TSH < 0.1 mlU/L. Guidelines also recommend screening for AF in patients with known hyperthyroidism. Wearable devices that measure the heart electrical activity continuously may be a novel strategy to detect atrial fibrillation in patients at risk. In this review, we explore the interplay between thyroid hormones and atrial fibrillation, management controversies in subclinical hyperthyroidism, and potential strategies to improve the management of atrial fibrillation in patients with subclinical hyperthyroidism.

Download Full-text

Approach to Subclinical Thyroid Diseas

Journal of Bangladesh College of Physicians and Surgeons ◽

10.3329/jbcps.v26i2.4187 ◽

1970 ◽

Vol 26 (2) ◽

pp. 91-96

Author(s):

Satya Ranjan Sutradhar

Keyword(s):

Subclinical Hypothyroidism ◽

Thyroid Dysfunction ◽

Hormone Level ◽

Elevated Serum ◽

Thyroid Stimulating Hormone ◽

Good Evidence ◽

Reference Ranges ◽

Mineral Density ◽

Asymptomatic Patients ◽

Stimulating Hormone

Subclinical thyroid dysfunction is defined as an abnormal serum thyroid-stimulating hormone level and free thyroxine and triiodothyronine levels within their reference ranges. The prevalence of subclinical hyperthyroidism is about 2 percent. Subclinical hypothyroidism is found in approximately 4 to 8.5 percent of the population. Most national organizations recommend against routine screening of asymptomatic patients, but screening is recommended for high risk populations. The management of subclinical thyroid dysfunction is controversial. There is good evidence that subclinical hypothyroidism is associated with progression to overt disease. Patients with a serum thyroid-stimulating hormone level greater than 10 mIU/L have a higher incidence of elevated serum low density lipoprotein cholesterol concentrations; however, evidence is lacking for other associations. There is insufficient evidence that treatment of subclinical hypothyroidism is beneficial. A serum thyroid stimulating hormone level of less than 0.1 mIU/L is associated with progression to overt hyperthyroidism, atrial fibrillation, reduced bone mineral density, and cardiac dysfunction. There is little evidence that early treatment alters the clinical course. DOI: 10.3329/jbcps.v26i2.4187 J Bangladesh Coll Phys Surg 2008; 26: 91-96

Download Full-text

Thyroid Hormone Therapy and Incident Stroke

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgab444 ◽

2021 ◽

Author(s):

Maria Papaleontiou ◽

Deborah A Levine ◽

David Reyes-Gastelum ◽

Sarah T Hawley ◽

Mousumi Banerjee ◽

...

Keyword(s):

Atrial Fibrillation ◽

Thyroid Hormone ◽

Hormone Treatment ◽

Population Based ◽

Thyroid Stimulating Hormone ◽

Prior History ◽

Veterans Health ◽

Health Administration ◽

Free T4 ◽

Increased Risk

Abstract Context Stroke is a leading cause of death and disability and there is a need to identify modifiable risk factors. Objective Determine the relationship between thyroid hormone treatment intensity and incidence of atrial fibrillation and stroke. Design Retrospective cohort study using data from the Veterans Health Administration between 2004 and 2017, with a median follow-up of 59 months. Setting Population-based. Participants 733,208 thyroid hormone users aged ≥18 years with at least two thyroid stimulating hormone (TSH) measurements between thyroid hormone initiation and incident event or study conclusion (406,030 thyroid hormone users with at least two free T4 measurements). Main Outcome Measures Incident atrial fibrillation and stroke. Results Overall, 71,333/643,687 (11.08%) participants developed incident atrial fibrillation and 41,931/663,809 (6.32%) stroke. In multivariable analyses controlling for pertinent factors such as age, sex and prior history of atrial fibrillation, low TSH or high free T4 levels (i.e., exogenous hyperthyroidism; e.g., TSH<0.1 mIU/L, OR 1.33, 95% CI 1.24-1.43) and high TSH or low free T4 levels (i.e., exogenous hypothyroidism; e.g., TSH>5.5 mIU/L, OR 1.29, 95% CI 1.26-1.33; free T4<0.7 ng/dL, OR 1.29, 95% CI 1.22-1.35) were associated with higher incidence of stroke compared to euthyroidism (TSH >0.5-5.5 mIU/L and free T4 0.7-1.9 ng/dL). Risk of developing atrial fibrillation and stroke was cumulative over time for both patients with exogenous hyperthyroidism and hypothyroidism. Conclusions Both exogenous hyper- and hypothyroidism were associated with increased risk of stroke, highlighting the importance of patient medication safety.

Download Full-text

Th1, Th2, and Th17 Cytokine Involvement in Thyroid Associated Ophthalmopathy

Disease Markers ◽

10.1155/2015/609593 ◽

2015 ◽

Vol 2015 ◽

pp. 1-6 ◽

Cited By ~ 34

Author(s):

Jie Shen ◽

Zhangfang Li ◽

Wenting Li ◽

Ying Ge ◽

Min Xie ◽

...

Keyword(s):

Interleukin 1 ◽

Elevated Serum ◽

Serum Levels ◽

Thyroid Stimulating Hormone ◽

Enzyme Linked Immunosorbent Assay ◽

Healthy Controls ◽

Necrosis Factor Alpha ◽

Thyroid Associated Ophthalmopathy ◽

Th17 Cytokines ◽

Th17 Cytokine

To determine serum cytokine profiles in Graves’ disease (GD) patients with or without active and inactive thyroid associated ophthalmopathy (TAO), we recruited 65 subjects: 10 GD only (without TAO), 25 GD + active TAO, 20 GD + TAO, and 10 healthy controls. Liquid chip assay was used to measure serum Th1/Th2/Th17 cytokines including IFN-γ(interferon-gamma), TNF-α(tumor necrosis factor-alpha), IL-1α(interleukin-1 alpha), IL-1Ra (IL-1 receptor antagonist), IL-2, IL-4, IL-6, and IL-17 and two chemokines: RANTES (regulated upon activation, normal T cell expressed and secreted) and IP-10 (IFN-γ-induced protein 10). Serum levels of TSH (thyroid stimulating hormone) receptor autoantibodies (TRAb) were measured using an enzyme linked immunosorbent assay. Compared with healthy controls, TAO patients showed significantly elevated serum levels of IFN-γ, TNF-α, IL-1α, IL-4, IL-6, IL-17, and IP-10. Comparing active and inactive TAO, serum Th1 cytokines IFN-γand TNF-αwere elevated in active TAO, while serum Th2 cytokine IL-4 was elevated in inactive TAO. Serum Th17 cytokine IL-17 was elevated in GD but reduced in both active and inactive TAO. A positive correlation was found between TRAb and IFN-γ, TNF-α, IL-1α, IL-2, IL-4, and IL-6. Taken together, serum Th1/Th2/Th17 cytokines and chemokines reflect TAO disease activity and may be implicated in TAO pathogenesis.

Download Full-text

Analysis of serum levels of organochlorine pesticides and related factors in Parkinson’s disease

10.21203/rs.3.rs-64368/v2 ◽

2020 ◽

Author(s):

Shaoqing Xu ◽

Xiaodong Yang ◽

Yiwei Qian ◽

Dayong Wan ◽

Fenghua Sun ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Organochlorine Pesticides ◽

Genetic Variants ◽

Cell Model ◽

Elevated Serum ◽

Depression Scale ◽

Serum Levels ◽

Hamilton Depression Scale ◽

Increased Risk

Abstract Background: There is evidence that genetic and environmental factors contribute to the onset and progression of Parkinson’s disease (PD). Pesticides are a class of environmental toxins that are linked to increased risk of PD. However, few studies have investigated the interaction between specific pesticides and genetic variants related to PD in the Chinese population.Methods: In this cross-sectional study, 19 serum levels of pesticides were measured. In addition, we also analyzed the interaction between specific pesticides and candidate genetic variants for PD. Finally, we investigated the mechanistic basis for the association between pesticides and increased risk of PD.Results: Serum levels of organochlorine pesticides including α-hexachlorocyclohexane (α-HCH), β-HCH, γ-HCH, δ-HCH, propanil, heptachlor, dieldrin, hexachlorobenzene, p,p’-dichlorodiphenyltrichloroethane (p,p’-DDE) and o,p’-dichloro-diphenyl-trichloroethane (o,p’-DDT) were higher in PD patients than in controls. α-HCH and propanil levels were associated with increased PD risk. Serum levels of dieldrin were associated with Hamilton Depression Scale and Montreal Cognitive Assessment scores in PD patients. Interactions between high pesticide levels and polymorphisms in rs11931074 and rs16940758 (α-HCH or β-HCH interacted with TT genotype in rs11931074 and δ-HCH interacted with TT genotype in rs16940758) were associated with the risk of PD. In cell model, α-HCH and propanil increased the level of reactive oxygen species and decreased the mitochondrial membrane potential. Propanil but not α-HCH induced the aggregation of α-synuclein.Conclusions: Elevated serum levels of α-HCH and propanil are associated with increased risk of PD. Serum levels of dieldrin were associated with depression and cognitive function in PD patients. The interaction between genetic variants and pesticides also increased the risk of PD. Effects of genetic variants and pesticides on the risk of PD should be studied in more detail with a larger sample size to further understand the mechanisms involved.

Download Full-text

Subclinical Hypothyroidism In Childhood, Treatment Or Only Follow-Up?

10.21203/rs.3.rs-16945/v1 ◽

2020 ◽

Author(s):

Marta Murillo-Vallés ◽

Santiago Martinez ◽

Cristina Aguilar-Riera ◽

Miguel Angel Garcia-Martin ◽

Joan Comós Bel ◽

...

Keyword(s):

Subclinical Hypothyroidism ◽

Therapy Group ◽

Roc Curves ◽

Serum Levels ◽

Thyroid Stimulating Hormone ◽

Free T4 ◽

Laboratory Findings ◽

Increased Risk ◽

Group 3 ◽

Group 1

Abstract Background: Subclinical hypothyroidism is defined as serum levels of thyroid-stimulating hormone (TSH) above the upper limit with normal concentrations of free T4 (fT4). Its management remains challenging. The aim of the study was to evaluate clinical and laboratory findings as well as clinical course of children with SH followed in a third level hospital. 65 patients aged between 2 and 18 years were retrospectively studied. Methods: The patients were followed for a median period of 9 months (range 6 months to 24 months). Those who normalized TSH levels were discharged (Group 1). If TSH persisted mild elevated (5-10µUI/mL) with normal fT4 and negative TPOAb/TgAb were classified as Group 2 and followed semiannually without treatment. In those patients who’s TSH raised ≥10µUI/mL or maintained TSH 5-10µUI/mL and positive TPOAb/TgAb were considered suitable for thyroxin therapy (Group 3, G3). Results: By ROC curves analysis we tested which initial TSH concentration best discriminated between patients who reverted to normality (Group 1) from those who finally required treatment (Group 3), the best cut-off being a TSH concentration >8.1µUI/mL (93.18% E, 57.14% S, AUC 0.765±0.107, p= 0.01). In 89% of our patients, TSH concentrations spontaneously reverted to normality or remained stable without treatment, whereas less than 11% progressed to clinical hypothyroidism. Conclusion: patients with initial TSH concentrations above 8.1µUI/mL have an increased risk of progression to hypothyroidism.

Download Full-text

The risk of atrial fibrillation associated with hyperuricemia

Ukrainian Therapeutical Journal ◽

10.30978/utj2021-1-78 ◽

2021 ◽

Author(s):

V. A. Chernyshov

Keyword(s):

Oxidative Stress ◽

Atrial Fibrillation ◽

Elevated Serum ◽

Renin Angiotensin System ◽

Oxidase Inhibitor ◽

Important Place ◽

Xanthine Oxidase Inhibitor ◽

Increased Risk ◽

The Relationship

The article summarizes mechanisms, linking hyperuricemia, the elevated serum levels of uric acid (UA), and atrial fibrillation (AF), the most frequent cardiac arrhythmia. The actuality of the problem is explained by the fact that UA is considered as an independent risk marker of AF closely associated with the onset and subsequent persistence of AF as well as by the AF increased risk in males and females with hyperuricemia. It has been shown how hyperuricemia, combined with other AF risk factors, contributeы to the development of arrhythmia, as well as the role of hyperuricemia, oxidative stress and renin‑angiotensin system (RAS) activation in the AF pathogenesis. The consideration have been given to the hyperuricemia association with a prevalence of AF among the patients with carbohydrate exchange disorders such as metabolic syndrome and type 2 diabetes mellitus as well as to the relationship between hyperuricemia and endothelial vascular dysfunction, oxidative stress, high blood concentration of systemic inflammatory markers and insulin resistance (IR). Some mechanisms of hyperuricemia participation in cardiac remodeling as a risk factor of AF are adduced. In particular, the relationship between hyperuricemia and left atrial (LA) size that could be mediated through systemic inflammation and IR is discussed. A significance of a direct impaired action of UA on LA cardiomyocytes resulted in their structural and ionic remodeling is shown. The role of xanthinoxidase (XO) activation in initiation of oxidative stress and inflammation in cardiomyocytes and endothelial cells is discussed. All these mechanisms are emphasized to be able to shorten a potential of action of atrial cardiomyocytes as well as to reduce a threshold of re‑entry mechanism initiation and to promote an appearance of the first and the following AF episodes. An important place in the review is taken for an intracellular UA and its cellular transporters in the context of their participation in pathogenesis of AF. The possibilities of drug hyperuricemia correction have been described in regards the reduction of AF risk, in particular, the role of reducing of the oxidative stress intensity with the use of xanthine oxidase inhibitor allopurinol, the inhibitor of NADPH oxidase apocynin, the antioxidant N‑acetylcysteine in the reduction of the risk of onset and subsequent recurrences of AF episodes, and transition of arrhythmia in the persistent form. Some perspectives of probenecid (an inhibitor of UA intracellular transporter activity) usage in the reduction of AF risk due to such of its mechanisms as a reduction of intracellular UA accumulation and antiapoptotic action as well as an ability of this agent to inhibit a locally activated oxidative stress and locally activated tissue RAS are discussed. A significance of the further detailed study of pathophysiological mechanisms of AF in hyperuricemia is emphasized for elaboration of the most effective practical recommendations in prevention of this arrhythmia in persons with UA exchange disorders.

Download Full-text

Elevated serum microRNA 483-5p levels may predict patients at risk of post-operative atrial fibrillation

European Journal of Cardio-Thoracic Surgery ◽

10.1093/ejcts/ezw245 ◽

2016 ◽

Vol 51 (1) ◽

pp. 73-78 ◽

Cited By ~ 29

Author(s):

Leanne Harling ◽

Jonathan Lambert ◽

Hutan Ashrafian ◽

Ara Darzi ◽

Nigel J. Gooderham ◽

...

Keyword(s):

Atrial Fibrillation ◽

At Risk ◽

Elevated Serum ◽

Serum Microrna ◽

Post Operative Atrial Fibrillation ◽

Patients At Risk

Download Full-text

Investigating the prevalence of primary thyroid dysfunction in obese and overweight individuals: Tehran thyroid study

BMC Endocrine Disorders ◽

10.1186/s12902-021-00743-4 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Mahdi Mahdavi ◽

Atieh Amouzegar ◽

Ladan Mehran ◽

Elham Madreseh ◽

Maryam Tohidi ◽

...

Keyword(s):

Serum Levels ◽

Thyroid Stimulating Hormone ◽

Normal Weight ◽

Control Group ◽

Overt Hypothyroidism ◽

Thyroid Peroxidase ◽

Cross Sectional ◽

Increased Risk ◽

Prevalence Of Obesity ◽

Thyroid Dysfunctions

Abstract Background Due to the increasing worldwide prevalence of obesity, it is essential to determine the prevalence of obesity-related thyroid dysfunctions. The purpose of this study was to investigate the prevalence of thyroid dysfunctions, namely hypothyroidism and hyperthyroidism, and their association with BMI among adult Iranian overweight and obese individuals. Method This cross-sectional study was carried out within the framework of the Tehran Thyroid Study (TTS); 5353 participants (57.5% female) entered our study. Anthropometric measurements were performed. Serum levels of thyroid-stimulating hormone (TSH), free thyroxine (FT4), and thyroid peroxidase antibody (TPOAb) were assayed. We categorized individuals into 3 BMI groups (normal-weight, overweight and obese), then calculated prevalence rate, odds ratio (OR), and 95% confidence interval (CI) for outcomes in overweight and obese groups. The normal-weight group was used as the control group. Results We found a higher prevalence of hypothyroidism (11.6% vs 8.2% Total, 4.0% vs 1.1% overt and 7.6% vs 7.1% subclinical, P < 0.001) and TPOAb positivity (17.3% vs 11.6%, P < 0.001) in obese participants compared with normal-weight participants. Hyperthyroidism’s overall prevalence was 4.2, 5.7, and 4.9% in obese, overweight, and normal-weight groups, respectively. Obesity was associated with higher odds of overt hypothyroidism (OR: 2.0, 95% CI: 1.15–3.49, P < 0.05) and TPOAb positivity (OR: 1.29, 95% CI: 1.04–1.60, P < 0.05) after adjusting for confounding variables. In contrast, no association was observed between the overweight group and the odds of hypothyroidism and TPOAb positivity in the adjusted results. Conclusions Obesity was associated with an increased risk of overt hypothyroidism and TPOAb positivity.

Download Full-text

Genetic variants of interferon-gamma and its mRNA expression and inflammatory parameters in the pathogenesis of vitiligo

Biochemistry and Cell Biology ◽

10.1139/bcb-2016-0228 ◽

2017 ◽

Vol 95 (4) ◽

pp. 474-481 ◽

Cited By ~ 7

Author(s):

Rehab A. Karam ◽

Haidy E. Zidan ◽

Mohamed H. Khater

Keyword(s):

Elevated Serum ◽

Serum Levels ◽

Intercellular Adhesion Molecule ◽

Control Group ◽

Intercellular Adhesion Molecule 1 ◽

Inflammatory Parameters ◽

Increased Risk ◽

Tnf Α ◽

Ifn Γ

Although genetics plays an essential role in the pathogenesis of vitiligo, vitiligo pathogenesis is still unclear. Our aim was to investigate the role of IFN-γ expression and polymorphism in vitiligo susceptibility and whether intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor (TNF)-α, and TNF-β play a role in vitiligo pathogenesis as important inflammatory parameters. Eighty-five patients with vitiligo and 90 controls were investigated for IFN-γ gene expression by quantitative real-time PCR and genotyped for IFN-γ +874T/A (rs2430561) and IFN-γ +2109A/G (rs1861494) gene polymorphisms by sequence-specific primer (SSP)-PCR and PCR-restriction fragment length polymorphism (RFLP), respectively. Serum levels of inflammatory parameters were measured using ELISA. Frequencies of the +874 TT genotype and T allele were significantly higher in patients with active vitiligo than in stable patients (P = 0.01 and 0.03, respectively). Calculation of odds ratio suggested a 1.7-fold increased risk of vitiligo in individuals having the TA haplotype. We observed overexpression of IFN-γ mRNA with elevated serum levels of IFN-γ, ICAM-1, TNF-α, and TNF-β in patients with vitiligo when compared with the control group (P = 0.001, for all). In addition, these levels were elevated in patients with active vitiligo compared with stable patients with vitiligo (P = 0.008, 0.006, 0.01, 0.01, and 0.03, respectively), which suggests the involvement of these cytokines in disease activity. In conclusion, IFN-γ is a promising immunological marker in vitiligo pathogenesis.

Download Full-text

Spectrum of thyroid dysfunction and dementia: a dose–response meta-analysis of 344,248 individuals from cohort studies

Endocrine Connections ◽

10.1530/ec-21-0047 ◽

2021 ◽

Vol 10 (4) ◽

pp. 410-421

Author(s):

Xingyao Tang ◽

Zhi-Hui Song ◽

Dawei Wang ◽

Jinkui Yang ◽

Marly Augusto Cardoso ◽

...

Keyword(s):

Dose Response ◽

Thyroid Dysfunction ◽

Disease Risk ◽

Meta Analysis ◽

Functional Relation ◽

Thyroid Stimulating Hormone ◽

Subclinical Hyperthyroidism ◽

Hormone Concentration ◽

Increased Risk ◽

Stimulating Hormone

Thyroid hormone, as a modifiable risk factor for dementia, promotes neurocognitive function and regulates metabolic processes. Various studies have defined different thyroid-stimulating hormone cutoffs, but the safest thyroid-stimulating hormone concentration was absent. A dose–response meta-analysis describing the overall functional relation and identifying exposure intervals associated with a higher or lower disease risk is thus desirable. Therefore, our current analysis was conducted to understand the influence of thyroid dysfunction on dementia risk. We searched PubMed, Embase, and Web of Science before May 1, 2020 for human studies published in English. Studies were considered for inclusion if they used a cohort study design to measure the risk of dementia in different thyroid function status groups, diagnosed thyroid functional status and all-cause dementia, included participants aged >18 years, and provided quantitative measures of data. The analysis contained 17 articles with 344,248 individuals with a 7.8-year mean follow-up. Ten studies with 329,287 participants indicated that only subclinical hyperthyroidism was associated with an increased risk of dementia. In contrast, subclinical hypothyroidism, clinical hyperthyroidism, and clinical hypothyroidism did not affect dementia. In the dose–response meta-analysis with 46,417 samples from 11 studies, the association of thyroid-stimulating hormone with the risk of dementia exhibited a U-shaped curve. Our study indicated that subclinical hyperthyroidism was associated with the risk of dementia and the thyroid-stimulating hormone concentration at around 1.55–1.60 mU/L as the optimum range for the risk of dementia.

Download Full-text