Thyroid Function Within the Normal Range, Subclinical Hypothyroidism, and the Risk of Atrial Fibrillation

Context: Hyperthyroidism is an established risk factor for atrial fibrillation (AF), but information concerning the association with variations within the normal range of thyroid function and subgroups at risk is lacking. Objective: This study aimed to investigate the association between normal thyroid function and AF prospectively and explore potential differential risk patterns. Design, Setting, and Participants: From the Rotterdam Study we included 9166 participants ≥ 45 y with TSH and/or free T4 (FT4) measurements and AF assessment (1997–2012 median followup, 6.8 y), with 399 prevalent and 403 incident AF cases. Main Outcome Measures: Outcome measures were 3-fold: 1) hazard ratios (HRs) for the risk of incident AF by Cox proportional-hazards models, 2) 10-year absolute risks taking competing risk of death into account, and 3) discrimination ability of adding FT4 to the CHARGE-AF simple model, an established prediction model for AF. Results: Higher FT4 levels were associated with higher risks of AF (HR 1.63, 95% confidence interval, 1.19–2.22), when comparing those in the highest quartile to those in lowest quartile. Absolute 10-year risks increased with higher FT4 in participants ≤65 y from 1–9% and from 6–12% in subjects ≥ 65 y. Discrimination of the prediction model improved when adding FT4 to the simple model (c-statistic, 0.722 vs 0.729; P = .039). TSH levels were not associated with AF. Conclusions: There is an increased risk of AF with higher FT4 levels within the normal range, especially in younger subjects. Adding FT4 to the simple model slightly improved discrimination of risk prediction.

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Thyroid Function in 3000 Cases of Patients With Atrial Fibrillation Treated With Catheter Ablation

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.2003 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A979-A980

Author(s):

Sayaka Yamada ◽

Yasuyo Nakajima ◽

Ayaka Nishikido ◽

Masako Akuzawa ◽

Koji Sakamaki ◽

...

Keyword(s):

Atrial Fibrillation ◽

Catheter Ablation ◽

Thyroid Hormones ◽

Thyroid Function ◽

Subclinical Hypothyroidism ◽

Treated Group ◽

Control Group ◽

Subclinical Hyperthyroidism ◽

Treated Male ◽

Overt Hyperthyroidism

Abstract Objective: Thyroid hormones have various effects on cardiac and circulatory systems, leading to arrhythmias and heart failure. In Europe and the United States, it has been reported that elevated thyroid hormones within the normal range have been reported to be associated with a risk of atrial fibrillation, however, there was no report on Japanese cases, a country that differs in iodine intake and ethnicity from the West. Therefore, we evaluated the abnormality of thyroid function in a large number of cases of atrial fibrillation (AF) who received catheter ablation (RFCA) in Japan. Methods: We evaluated 2,937 cases of atrial fibrillation (2,084 males, mean age 64.1±10.7 years and 853 females, 69.0±8.5 years) who underwent RFCA at the Gunma Prefectural Cardiovascular Center between 2012 and 2018. As a control we used a total of 15,660 participants for health check-up (9,176 males, mean age 49.7±9.8 years and 6,484 females, 48.9±10.3 years) from 2006 to 2013, and we evaluated thyroid function after adjusting for gender-specific age. Results: The prevalence of overt hyperthyroidism was significantly higher in the RFCA-treated male group (0.43%) than in the control group (0.07%), even after adjusting for age (p<0.01). Similarly, the prevalence of subclinical hyperthyroidism was also significantly higher in the RFCA-treated male group (3.12%) than in the control group (0.94%) after adjusting for age (p<0.01). On the other hand, subclinical hypothyroidism was significantly lower in the RFCA-treated group after adjusting for age (2.97% in the RFCA-treated group and 3.93% in the control group, p<0.01). Females showed the same results as males. Conclusions: In an iodine rich country Japan, not only overt hyperthyroidism but also subclinical hyperthyroidism is an obvious risk factor for severe atrial fibrillation in Japan. Intriguingly, subclinical hypothyroidism might contribute to the prevention of atrial fibrillation, suggesting that slightly higher serum TSH levels might be better for elderlies.

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Mendelian Randomization analyses reveal a causal effect of thyroid function on stroke via atrial fibrillation

10.1101/718429 ◽

2019 ◽

Author(s):

Eirini Marouli ◽

Aleksander Kus ◽

M. Fabiola Del Greco ◽

Layal Chaker ◽

Robin Peeters ◽

...

Keyword(s):

Risk Factors ◽

Atrial Fibrillation ◽

Thyroid Function ◽

Mendelian Randomization ◽

Normal Range ◽

Standard Deviation Increase ◽

Hashimoto’S Disease ◽

Increased Risk ◽

Hashimoto's Disease ◽

Cad Risk

AbstractBackgroundSeveral observational studies suggest that variations in thyroid function, even within the normal range, are a risk factor for cardiovascular diseases, but it remains to be determined if these associations are causal or not. This study investigates whether the relationship between variation in normal range thyroid function, as well as hypothyroidism and hyperthyroidism, and the risk of stroke and Coronary Artery Disease (CAD) are causal and via which pathways these relations are mediated.Methods and FindingsWe performed Mendelian Randomization (MR) analyses for stroke and CAD using genetic instruments associated with TSH and FT4 levels respectively within either the normal range, hypothyroidism or hyperthyroidism. In detected associations, the potential mediatory role of known stroke and CAD risk factors was also examined. A one standard deviation increase in TSH was associated with a 5% decrease in the risk of stroke (OR=0.95, 95% CI= 0.91 to 0.99). Multivariable MR analyses indicated that this effect is mediated through atrial fibrillation (AF). Hashimoto’s Disease (HD) was associated with a 7% increased risk of CAD (OR=1.07, 95% CI= 1.01 to 1.13). The effect of Hashimoto’s Disease (HD) on CAD risk appears to be mediated via body mass index (BMI).ConclusionsThese results provide important new insights into the causal relationships and mediating pathways between thyroid function, stroke and CAD. Specifically, we identify normal range TSH levels and HD as potential modifiable risk factors for stroke and CAD, respectively.

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Genetic Determination of Normal-Range Thyroid Function Affects Risk of Atrial Fibrillation

Clinical Thyroidology ◽

10.1089/ct.2019;31.165-168 ◽

2019 ◽

Vol 31 (4) ◽

pp. 165-168

Author(s):

Tim I.M. Korevaar

Keyword(s):

Atrial Fibrillation ◽

Thyroid Function ◽

Normal Range ◽

Genetic Determination

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SUN-409 Subclinical Hypothyroidism in Hospitalized Patients with Chronic Heart-Failure or Chronic Renal-Failure Is Most Probably Not Due to Thyroid Disease

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.373 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Amir Bashkin ◽

Wagde Abu Saleh ◽

Ohad Ronen

Keyword(s):

Heart Failure ◽

Renal Failure ◽

Chronic Renal Failure ◽

Chronic Heart Failure ◽

Thyroid Function ◽

Subclinical Hypothyroidism ◽

Thyroid Disease ◽

Final Analysis ◽

Hospitalized Patients ◽

Normal Range

Abstract Introduction: Subclinical hypothyroidism is common in chronic diseases such as heart failure and advanced chronic renal failure. It is unclear whether this is a thyroid disease or an isolated TSH elevation. The goal of this study was to investigate the prevalence of worsening thyroid function in these patients with recurrent admissions. Methods: We performed a retrospective review of medical records of hospitalized patients in non-surgical wards from 2013–2016. First, all patients with TSH levels above the normal range (4.95 mIU/L) and up to 12 mIU/L with FT4 levels in the normal range were identified. We then investigated which of these patients were re-hospitalized at least once within at least six months. According to data from the re-hospitalization, an increase in TSH level above 12 mIU/L or initiation of levothyroxine treatment was defined as worsening of thyroid function. Patients treated with a drug affecting thyroid function or with a known thyroid disease prior to first hospitalization were excluded from the study. Chronic heart failure and chronic renal failure were determined according to reported diagnosis and drug treatment. Chronic renal failure patients were included if the glomerular filtration rate (GFR) in the first hospitalization was below 30 ml/min/1.72 square meter. Results: Overall, 90,199 TSH tests were sent from the non-surgical wards, most of them as part of the admissions profile. Of these, 2,116 hospitalizations met the inclusion criteria of the first hospitalization. In the final analysis, 126 inpatients with at least one re-hospitalization were included, of whom 43 (34.1%) had chronic heart failure and 22 (17.5%) had chronic renal failure. According to the most recent re-hospitalization, thyroid function was worse in 11(8.7%), 4 (9.3%) and 2 (9.1%) patients of the total, heart failure and renal failure groups respectively. The TSH level was found to be normal in re-hospitalization in 81.4% of those with heart failure and 86.4% of those with renal-failure. No association between heart failure or renal-failure and thyroid function worsening was found (p = 1.00 for both). Of 34 patients with chronic heart failure re-hospitalized after 1/2-1 year, in 29 (85.3%) the repeated TSH was normal, in 3 (8.8%) it was unchanged and in 2 (5.9%) it was worse. In most re-hospitalization the worsening was due to initiation of Levothyroxin treatment and because of the retrospective nature of the study we cannot be sure whether the initiation was justified; therefore, it is likely that the worsening percentage is even lower. Conclusions: An isolated TSH elevation in hospitalized patients with past medical history of chronic heart-failure or chronic renal failure does not indicate thyroid disease, in most cases.

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Thyroid Function Affects the Risk of Stroke via Atrial Fibrillation: A Mendelian Randomization Study

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa239 ◽

2020 ◽

Vol 105 (8) ◽

pp. 2634-2641 ◽

Cited By ~ 2

Author(s):

Eirini Marouli ◽

Aleksander Kus ◽

Fabiola Del Greco M ◽

Layal Chaker ◽

Robin Peeters ◽

...

Keyword(s):

Risk Factors ◽

Atrial Fibrillation ◽

Thyroid Function ◽

Hashimoto’S Thyroiditis ◽

Mendelian Randomization ◽

Hashimoto's Thyroiditis ◽

Normal Range ◽

Standard Deviation Increase ◽

Increased Risk ◽

Cad Risk

Abstract Context Observational studies suggest that variations in normal range thyroid function are associated with cardiovascular diseases. However, it remains to be determined whether these associations are causal or not. Objective To test whether genetically determined variation in normal range thyroid function is causally associated with the risk of stroke and coronary artery disease (CAD) and investigate via which pathways these relations may be mediated. Design, Setting, and Participants Mendelian randomization analyses for stroke and CAD using genetic instruments associated with normal range thyrotropin (TSH) and free thyroxine levels or Hashimoto’s thyroiditis and Graves’ disease. The potential mediating role of known stroke and CAD risk factors was examined. Publicly available summary statistics data were used. Main Outcome Measures Stroke or CAD risk per genetically predicted increase in TSH or FT4 levels. Results A 1 standard deviation increase in TSH was associated with a 5% decrease in the risk of stroke (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.91-0.99; P = 0.008). Multivariable MR analyses indicated that this effect is mainly mediated via atrial fibrillation. MR analyses did not show a causal association between normal range thyroid function and CAD. Secondary analyses showed a causal relationship between Hashimoto’s thyroiditis and a 7% increased risk of CAD (OR, 1.07; 95% CI, 1.01-1.13; P = 0.026), which was mainly mediated via body mass index. Conclusion These results provide important new insights into the causal relationships and mediating pathways between thyroid function, stroke, and CAD. We identify variation in normal range thyroid function and Hashimoto’s thyroiditis as risk factors for stroke and CAD, respectively.

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Longitudinal Study of Thyroid Function in Children with Mild Hyperthyrotropinemia at Neonatal Screening for Congenital Hypothyroidism

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2007-2612 ◽

2008 ◽

Vol 93 (7) ◽

pp. 2679-2685 ◽

Cited By ~ 50

Author(s):

Daniela Leonardi ◽

Nunziella Polizzotti ◽

Anna Carta ◽

Rossella Gelsomino ◽

Lidia Sava ◽

...

Keyword(s):

Early Childhood ◽

Longitudinal Study ◽

Thyroid Function ◽

Subclinical Hypothyroidism ◽

False Positive ◽

Neonatal Screening ◽

Late Childhood ◽

Normal Range ◽

Free T3 ◽

Prospective Longitudinal

Abstract Objective: Long-term outcome of thyroid function in children with very short-lasting neonatal hyperthyrotropinemia (“false positive” at neonatal screening) was studied in an observational, prospective study. Thyroid function and morphology were evaluated in 44 “false positive” children up to advanced childhood (8.0 ± 0.7 yr of age). In these children a high prevalence (50%) of subclinical hypothyroidism in early childhood (2.8 ± 0.5 yr) had already been described. Results: At an average of 5.3 yr, subclinical hypothyroidism persisted in 19 of 44 (43.2%) children and, more specifically, in two of three of those who had increased TSH in early childhood. Euthyroidism was present in all cases that were euthyroid in early childhood, although they had TSH and free T3 values significantly higher than control children with a normal TSH at birth (TSH = 2.6 ± 0.7 vs. 1.5 ± 0.6 mU/liter, P < 0.001; free T3 = 4.9 ± 0.8 vs. 3.9 ± 0.9 pmol/liter, P < 0.01). Thyroid morphology alterations were frequent in the group of children with subclinical hypothyroidism. At an average of 8.0 yr, subclinical hypothyroidism persisted in 14 of 44 (31.8%) children. In all other children, TSH and thyroid hormones were confirmed within the normal range. Conclusions: This prospective longitudinal study confirms that newborns “false positive” at neonatal screening have a high risk to develop persistent subclinical hypothyroidism. The prevalence of hypothyroidism decreases with increasing age, but it is still high (>30%) in late childhood. Even those “false positive” children that maintain euthyroidism in late childhood have an average TSH value that, although within the normal range, is higher than in normal controls, a possible marker of minor congenital thyroid function abnormalities.

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