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Eleonora P. M. Corssmit - One of the best experts on this subject based on the ideXlab platform.
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autonomic nervous system function in chronic exogenous Subclinical thyrotoxicosis and the effect of restoring euthyroidism
The Journal of Clinical Endocrinology and Metabolism, 2008Co-Authors: C F A Eustatiarutten, Karen A Heemstra, Eleonora P. M. Corssmit, Johannes W A Smit, Rik C. Schoemaker, Johannes A. Romijn, Jacobus BurggraafAbstract:Context: Knowledge on the relationship between the autonomic nervous system and Subclinical Hyperthyroidism is mainly based upon cross-sectional studies in heterogeneous patient populations, and the effect of restoration to euthyroidism in Subclinical Hyperthyroidism has not been studied. Objective:We investigated the long-term effects of exogenous Subclinical Hyperthyroidism on the autonomic nervous system and the potential effects of restoration of euthyroidism. Design: This was a prospective single-blinded, placebo-controlled, randomized trial. Setting: The study was performed at a university hospital. Patients: A total of 25 patients who were on more than 10-yr TSH suppressive therapy after thyroidectomy was examined. Intervention:Patientswerestudiedatbaselineandsubsequentlyrandomizedtoa6-monththyroid hormone substitution regimen to obtain either euthyroidism or maintenance of the Subclinical hyperthyroid state. Main Outcome Measures: Urinary excretion of catecholamines and heart rate variability were measured. Baseline data of the Subclinical Hyperthyroidism patients were compared with data obtained in patients with Hyperthyroidism and controls. Results:UrinaryexcretionofnorepinephrineandvanillylmandelicacidwashigherintheSubclinical Hyperthyroidism patients compared with controls and lower compared with patients with overt Hyperthyroidism. Heart rate variability was lower in patients with Hyperthyroidism, intermediate in Subclinical Hyperthyroidism patients, and highest in the healthy controls. No differences were observed after restoration of euthyroidism.
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glucose tolerance and lipid profile in longterm exogenous Subclinical Hyperthyroidism and the effects of restoration of euthyroidism a randomised controlled trial
Clinical Endocrinology, 2006Co-Authors: Karen A Heemstra, J W A Smit, C F A Eustatiarutten, Annemieke C Heijboer, Marijke Frolich, Johannes A. Romijn, Eleonora P. M. CorssmitAbstract:Summary Objective The impact of prolonged Subclinical Hyperthyroidism on glucose and lipid metabolism is unclear. Therefore, we evaluated glucose and lipid metabolism in patients with differentiated thyroid carcinoma (DTC) on TSH suppressive thyroxine therapy as a model for Subclinical Hyperthyroidism and investigated whether restoration to euthyroidism affects metabolism. Design We performed a prospective, single-blinded, placebo-controlled, randomised trial of 6 months duration with 2 parallel groups. Patients Twenty-five subjects with a history of differentiated thyroid carcinoma with > 10 years TSH-suppressive therapy with l-thyroxine completed the study. l-thyroxine dose was replaced by study medication containing l-thyroxine or l-thyroxine plus placebo. Medication was titrated to establish continuation of TSH suppression (low-TSH group, 13 patients) and euthyroidism (euthyroidism group, 12 patients). Measurements We evaluated glucose metabolism by glucose tolerance test and HOMA (IR) and lipid metabolism by lipid profile. In addition, we measured plasma concentrations of glucoregulatory hormones. Results At baseline, glucose tolerance, HOMA (IR), lipid profile and plasma concentrations of glucoregulatory hormones were within the normal range. No significant differences between the low TSH and euthyroidism group were observed. After 6 months, neither glucose nor lipid metabolism in the low TSH group were different from baseline values. Conclusion In summary, glucose and lipid metabolism in patients with DTC and long-term Subclinical Hyperthyroidism in general are not affected. Restoration of euthyroidism in general does not affect glucose and lipid metabolism.
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quality of life in longterm exogenous Subclinical Hyperthyroidism and the effects of restoration of euthyroidism a randomized controlled trial
Clinical Endocrinology, 2006Co-Authors: C F A Eustatiarutten, Eleonora P. M. Corssmit, Marijke Frolich, Alberto M Pereira, Johannes A. Romijn, J W A SmitAbstract:Summary Objective The impact of prolonged Subclinical Hyperthyroidism on quality of life is unclear. Therefore, we evaluated quality of life in patients with differentiated thyroid carcinoma (DTC) on TSH-suppressive thyroxine therapy as a model for Subclinical Hyperthyroidism and we investigated whether restoration to euthyroidism affects quality of life. Design We performed a prospective, single-blinded, placebo-controlled, randomized trial of 6 months’ duration with two parallel groups. Patients and methods Twenty-four subjects with a history of differentiated thyroid carcinoma with > 10 years TSH-suppressive therapy with L-thyroxine completed the study. L-thyroxine dose was replaced by study medication containing L-thyroxine or L-thyroxine plus placebo. Medication was titrated to establish continuation of TSH suppression (low-TSH group) and euthyroidism (euthyroid group). Both groups consisted of 12 patients. We evaluated quality of life using five validated questionnaires. Results At baseline, the somatic disorder questionnaire (SDQ) indicated more somatic dysfunction in patients as compared with reference values, whereas the depression score (HADS) revealed a better score than the reference group. All other quality of life parameters were normal. At baseline, no significant differences between the low-TSH and the euthyroidism groups were observed. After 6 months, none of the quality of life parameters in the low-TSH group was different from baseline values. In the euthyroid group, motivation was significantly improved (Multidimensional Fatigue Index-20, P = 0·003), although this parameter did not differ from the reference group at baseline. A probable worsening in role limitations as a result of physical problems (Short Form-36; P = 0·050) was observed. No improvement in the SDQ score was observed. Conclusion In summary, quality of life in patients with DTC and long-term Subclinical Hyperthyroidism in general is preserved. Restoration of euthyroidism in general does not affect quality of life.
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reversible diastolic dysfunction after long term exogenous Subclinical Hyperthyroidism a randomized placebo controlled study
The Journal of Clinical Endocrinology and Metabolism, 2005Co-Authors: J W A Smit, C F A Eustatiarutten, Eleonora P. M. Corssmit, Marijke Frolich, Alberto M Pereira, Gabe B Bleeker, Eduard R Holman, E E Van Der Wall, Johannes A. RomijnAbstract:Background: Subclinical Hyperthyroidism has been reported to affect systolic and diastolic cardiac function. However, the reversibility of these effects is not well established. Objective: Our objective was to investigate the presence and reversibility of cardiac abnormalities in patients with long-term exogenous Subclinical Hyperthyroidism. Design: We conducted a prospective, single-blinded, placebo-controlled randomized trial of 6 months duration with two parallel groups. Setting: The study occurred at the Leiden University Medical Center, a tertiary referral center for thyroid carcinoma. Patients: As a model for Subclinical Hyperthyroidism, 25 patients with a history of differentiated thyroid carcinoma with more than 10 yr of TSH suppressive therapy with l-T4 were studied. Interventions: l-T4 dose was replaced by study medication containing l-T4 or placebo. Medication was titrated in a single-blinded fashion to establish continuation of TSH suppression (low-TSH group) or euthyroidism (euthyroid group)....
Anne R Cappola - One of the best experts on this subject based on the ideXlab platform.
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the relation between thyroid function and anemia a pooled analysis of individual participant data
The Journal of Clinical Endocrinology and Metabolism, 2018Co-Authors: Daisy M Wopereis, Douglas C Bauer, Anne R Cappola, Robert S Du Puy, Diana Van Heemst, John P Walsh, Alexandra Bremner, Stephan J L Bakker, Graziano CeresiniAbstract:Context Anemia and thyroid dysfunction often co-occur and both increase with age. Human data on the relationship between thyroid disease and anemia are scarce. Objective To investigate the cross-sectional and longitudinal associations between clinical thyroid status and anemia. Design Individual participant data meta-analysis. Setting Sixteen cohorts participating in the Thyroid Studies Collaboration (n=42 162). Main outcome measures Primary outcome measure was anemia (hemoglobin <130 g/L in men and <120 g/L in women). Results Cross-sectionally, participants with abnormal thyroid status had an increased risk of having anemia compared with euthyroid participants (overt hypothyroidism, pooled odds ratio 1.84 [95% CI: 1.35-2.50], Subclinical hypothyroidism 1.21 [1.02-1.43], Subclinical Hyperthyroidism 1.27 [1.03-1.57], overt Hyperthyroidism 1.69 [1.00-2.87]). Hemoglobin levels were lower in all groups compared to participants with euthyroidism. In the longitudinal analyses (n=25,466 from 14 cohorts), the pooled hazard ratio for the risk of development of anemia was 1.38 [95% CI: 0.86-2.20] for overt hypothyroidism, 1.18 [1.00-1.38] for Subclinical hypothyroidism, 1.15 [0.94-1.42] for Subclinical Hyperthyroidism and 1.47 [0.91-2.38] for overt Hyperthyroidism. Sensitivity analyses excluding thyroid medication or high levels of C-reactive protein yielded similar results. No differences in mean annual change in hemoglobin levels were observed between the thyroid hormone status groups. Conclusion Higher odds of having anemia were observed in both participants with hypothyroid function and hyperthyroid function. In addition, reduced thyroid function at baseline showed a trend of increased risk of developing anemia during follow-up. It remains to be assessed in a randomized controlled trial whether treatment is effective in reducing anemia.
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Subclinical thyroid dysfunction and fracture risk a meta analysis
JAMA, 2015Co-Authors: Manuel R Blum, Tinhhai Collet, Douglas C Bauer, Anne R Cappola, Howard A Fink, Bruno R Da Costa, Christina Doris Wirth, Robin P Peeters, Bjorn Olav AsvoldAbstract:Importance Associations between Subclinical thyroid dysfunction and fractures are unclear and clinical trials are lacking. Objective To assess the association of Subclinical thyroid dysfunction with hip, nonspine, spine, or any fractures. Data Sources and Study Selection The databases of MEDLINE and EMBASE (inception to March 26, 2015) were searched without language restrictions for prospective cohort studies with thyroid function data and subsequent fractures. Data Extraction Individual participant data were obtained from 13 prospective cohorts in the United States, Europe, Australia, and Japan. Levels of thyroid function were defined as euthyroidism (thyroid-stimulating hormone [TSH], 0.45-4.49 mIU/L), Subclinical Hyperthyroidism (TSH Main Outcome and Measures The primary outcome was hip fracture. Any fractures, nonspine fractures, and clinical spine fractures were secondary outcomes. Results Among 70 298 participants, 4092 (5.8%) had Subclinical hypothyroidism and 2219 (3.2%) had Subclinical Hyperthyroidism. During 762 401 person-years of follow-up, hip fracture occurred in 2975 participants (4.6%; 12 studies), any fracture in 2528 participants (9.0%; 8 studies), nonspine fracture in 2018 participants (8.4%; 8 studies), and spine fracture in 296 participants (1.3%; 6 studies). In age- and sex-adjusted analyses, the hazard ratio (HR) for Subclinical Hyperthyroidism vs euthyroidism was 1.36 for hip fracture (95% CI, 1.13-1.64; 146 events in 2082 participants vs 2534 in 56 471); for any fracture, HR was 1.28 (95% CI, 1.06-1.53; 121 events in 888 participants vs 2203 in 25 901); for nonspine fracture, HR was 1.16 (95% CI, 0.95-1.41; 107 events in 946 participants vs 1745 in 21 722); and for spine fracture, HR was 1.51 (95% CI, 0.93-2.45; 17 events in 732 participants vs 255 in 20 328). Lower TSH was associated with higher fracture rates: for TSH of less than 0.10 mIU/L, HR was 1.61 for hip fracture (95% CI, 1.21-2.15; 47 events in 510 participants); for any fracture, HR was 1.98 (95% CI, 1.41-2.78; 44 events in 212 participants); for nonspine fracture, HR was 1.61 (95% CI, 0.96-2.71; 32 events in 185 participants); and for spine fracture, HR was 3.57 (95% CI, 1.88-6.78; 8 events in 162 participants). Risks were similar after adjustment for other fracture risk factors. Endogenous Subclinical Hyperthyroidism (excluding thyroid medication users) was associated with HRs of 1.52 (95% CI, 1.19-1.93) for hip fracture, 1.42 (95% CI, 1.16-1.74) for any fracture, and 1.74 (95% CI, 1.01-2.99) for spine fracture. No association was found between Subclinical hypothyroidism and fracture risk. Conclusions and Relevance Subclinical Hyperthyroidism was associated with an increased risk of hip and other fractures, particularly among those with TSH levels of less than 0.10 mIU/L and those with endogenous Subclinical Hyperthyroidism. Further study is needed to determine whether treating Subclinical Hyperthyroidism can prevent fractures.
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Subclinical thyroid dysfunction and the risk of heart failure events an individual participant data analysis from 6 prospective cohorts
Circulation, 2012Co-Authors: Baris Gencer, Tinhhai Collet, Jacobijn Gussekloo, Douglas C Bauer, Wendy Den P J Elzen, Anne R Cappola, Philippe Balmer, Vanessa Virgini, David Nanchen, Robert LubenAbstract:Background —ACC/AHA Guidelines for the Diagnosis and Management of Heart Failure (HF) recommend investigating exacerbating conditions, such as thyroid dysfunction, but without specifying impact of different TSH levels. Limited prospective data exist regarding the association between Subclinical thyroid dysfunction and HF events. Methods and Results —We performed a pooled analysis of individual participant data using all available prospective cohorts with thyroid function tests and subsequent follow-up of HF events. Individual data on 25,390 participants with 216,248 person-years of follow-up were supplied from 6 prospective cohorts in the United States and Europe. Euthyroidism was defined as TSH 0.45-4.49 mIU/L, Subclinical hypothyroidism as TSH 4.5-19.9 mIU/L and Subclinical Hyperthyroidism as TSH <0.45 mIU/L, both with normal free thyroxine levels. Among 25,390 participants, 2068 had Subclinical hypothyroidism (8.1%) and 648 Subclinical Hyperthyroidism (2.6%). In age- and gender-adjusted analyses, risks of HF events were increased with both higher and lower TSH levels (P for quadratic pattern <0.01): hazard ratio (HR) was 1.01 (95% confidence interval [CI] 0.81-1.26) for TSH 4.5-6.9 mIU/L, 1.65 (CI 0.84-3.23) for TSH 7.0-9.9 mIU/L, 1.86 (CI 1.27-2.72) for TSH 10.0-19.9 mIUL/L (P for trend <0.01), and was 1.31 (CI 0.88-1.95) for TSH 0.10-0.44 mIU/L and 1.94 (CI 1.01-3.72) for TSH <0.10 mIU/L (P for trend = 0.047). Risks remained similar after adjustment for cardiovascular risk factors. Conclusions —Risks of HF events were increased with both higher and lower TSH levels, particularly for TSH ≥10 mIU/L and for TSH
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Subclinical thyroid dysfunction and the risk of heart failure events an individual participant data analysis from 6 prospective cohorts
Circulation, 2012Co-Authors: Baris Gencer, Tinhhai Collet, Jacobijn Gussekloo, Douglas C Bauer, Wendy Den P J Elzen, Anne R Cappola, Philippe Balmer, Vanessa Virgini, David Nanchen, Robert LubenAbstract:Background—American College of Cardiology/American Heart Association guidelines for the diagnosis and management of heart failure recommend investigating exacerbating conditions such as thyroid dysfunction, but without specifying the impact of different thyroid-stimulation hormone (TSH) levels. Limited prospective data exist on the association between Subclinical thyroid dysfunction and heart failure events. Methods and Results—We performed a pooled analysis of individual participant data using all available prospective cohorts with thyroid function tests and subsequent follow-up of heart failure events. Individual data on 25 390 participants with 216 248 person-years of follow-up were supplied from 6 prospective cohorts in the United States and Europe. Euthyroidism was defined as TSH of 0.45 to 4.49 mIU/L, Subclinical hypothyroidism as TSH of 4.5 to 19.9 mIU/L, and Subclinical Hyperthyroidism as TSH <0.45 mIU/L, the last two with normal free thyroxine levels. Among 25 390 participants, 2068 (8.1%) had su...
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Subclinical Hyperthyroidism and the risk of coronary heart disease and mortality
JAMA Internal Medicine, 2012Co-Authors: Tinhhai Collet, Jose A Sgarbi, Jacobijn Gussekloo, Douglas C Bauer, Wendy Den P J Elzen, Anne R Cappola, Philippe Balmer, Giorgio Iervasi, Bjorn Olav Asvold, Henry VolzkeAbstract:Background Data from prospective cohort studies regarding the association between Subclinical Hyperthyroidism and cardiovascular outcomes are conflicting. We aimed to assess the risks of total and coronary heart disease (CHD) mortality, CHD events, and atrial fibrillation (AF) associated with endogenous Subclinical Hyperthyroidism among all available large prospective cohorts. Methods Individual data on 52 674 participants were pooled from 10 cohorts. Coronary heart disease events were analyzed in 22 437 participants from 6 cohorts with available data, and incident AF was analyzed in 8711 participants from 5 cohorts. Euthyroidism was defined as thyrotropin level between 0.45 and 4.49 mIU/L and endogenous Subclinical Hyperthyroidism as thyrotropin level lower than 0.45 mIU/L with normal free thyroxine levels, after excluding those receiving thyroid-altering medications. Results Of 52 674 participants, 2188 (4.2%) had Subclinical Hyperthyroidism. During follow-up, 8527 participants died (including 1896 from CHD), 3653 of 22 437 had CHD events, and 785 of 8711 developed AF. In age- and sex-adjusted analyses, Subclinical Hyperthyroidism was associated with increased total mortality (hazard ratio [HR], 1.24, 95% CI, 1.06-1.46), CHD mortality (HR, 1.29; 95% CI, 1.02-1.62), CHD events (HR, 1.21; 95% CI, 0.99-1.46), and AF (HR, 1.68; 95% CI, 1.16-2.43). Risks did not differ significantly by age, sex, or preexisting cardiovascular disease and were similar after further adjustment for cardiovascular risk factors, with attributable risk of 14.5% for total mortality to 41.5% for AF in those with Subclinical Hyperthyroidism. Risks for CHD mortality and AF (but not other outcomes) were higher for thyrotropin level lower than 0.10 mIU/L compared with thyrotropin level between 0.10 and 0.44 mIU/L (for both, P value for trend, ≤.03). Conclusion Endogenous Subclinical Hyperthyroidism is associated with increased risks of total, CHD mortality, and incident AF, with highest risks of CHD mortality and AF when thyrotropin level is lower than 0.10 mIU/L.
Douglas C Bauer - One of the best experts on this subject based on the ideXlab platform.
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the relation between thyroid function and anemia a pooled analysis of individual participant data
The Journal of Clinical Endocrinology and Metabolism, 2018Co-Authors: Daisy M Wopereis, Douglas C Bauer, Anne R Cappola, Robert S Du Puy, Diana Van Heemst, John P Walsh, Alexandra Bremner, Stephan J L Bakker, Graziano CeresiniAbstract:Context Anemia and thyroid dysfunction often co-occur and both increase with age. Human data on the relationship between thyroid disease and anemia are scarce. Objective To investigate the cross-sectional and longitudinal associations between clinical thyroid status and anemia. Design Individual participant data meta-analysis. Setting Sixteen cohorts participating in the Thyroid Studies Collaboration (n=42 162). Main outcome measures Primary outcome measure was anemia (hemoglobin <130 g/L in men and <120 g/L in women). Results Cross-sectionally, participants with abnormal thyroid status had an increased risk of having anemia compared with euthyroid participants (overt hypothyroidism, pooled odds ratio 1.84 [95% CI: 1.35-2.50], Subclinical hypothyroidism 1.21 [1.02-1.43], Subclinical Hyperthyroidism 1.27 [1.03-1.57], overt Hyperthyroidism 1.69 [1.00-2.87]). Hemoglobin levels were lower in all groups compared to participants with euthyroidism. In the longitudinal analyses (n=25,466 from 14 cohorts), the pooled hazard ratio for the risk of development of anemia was 1.38 [95% CI: 0.86-2.20] for overt hypothyroidism, 1.18 [1.00-1.38] for Subclinical hypothyroidism, 1.15 [0.94-1.42] for Subclinical Hyperthyroidism and 1.47 [0.91-2.38] for overt Hyperthyroidism. Sensitivity analyses excluding thyroid medication or high levels of C-reactive protein yielded similar results. No differences in mean annual change in hemoglobin levels were observed between the thyroid hormone status groups. Conclusion Higher odds of having anemia were observed in both participants with hypothyroid function and hyperthyroid function. In addition, reduced thyroid function at baseline showed a trend of increased risk of developing anemia during follow-up. It remains to be assessed in a randomized controlled trial whether treatment is effective in reducing anemia.
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Subclinical thyroid dysfunction and fracture risk a meta analysis
JAMA, 2015Co-Authors: Manuel R Blum, Tinhhai Collet, Douglas C Bauer, Anne R Cappola, Howard A Fink, Bruno R Da Costa, Christina Doris Wirth, Robin P Peeters, Bjorn Olav AsvoldAbstract:Importance Associations between Subclinical thyroid dysfunction and fractures are unclear and clinical trials are lacking. Objective To assess the association of Subclinical thyroid dysfunction with hip, nonspine, spine, or any fractures. Data Sources and Study Selection The databases of MEDLINE and EMBASE (inception to March 26, 2015) were searched without language restrictions for prospective cohort studies with thyroid function data and subsequent fractures. Data Extraction Individual participant data were obtained from 13 prospective cohorts in the United States, Europe, Australia, and Japan. Levels of thyroid function were defined as euthyroidism (thyroid-stimulating hormone [TSH], 0.45-4.49 mIU/L), Subclinical Hyperthyroidism (TSH Main Outcome and Measures The primary outcome was hip fracture. Any fractures, nonspine fractures, and clinical spine fractures were secondary outcomes. Results Among 70 298 participants, 4092 (5.8%) had Subclinical hypothyroidism and 2219 (3.2%) had Subclinical Hyperthyroidism. During 762 401 person-years of follow-up, hip fracture occurred in 2975 participants (4.6%; 12 studies), any fracture in 2528 participants (9.0%; 8 studies), nonspine fracture in 2018 participants (8.4%; 8 studies), and spine fracture in 296 participants (1.3%; 6 studies). In age- and sex-adjusted analyses, the hazard ratio (HR) for Subclinical Hyperthyroidism vs euthyroidism was 1.36 for hip fracture (95% CI, 1.13-1.64; 146 events in 2082 participants vs 2534 in 56 471); for any fracture, HR was 1.28 (95% CI, 1.06-1.53; 121 events in 888 participants vs 2203 in 25 901); for nonspine fracture, HR was 1.16 (95% CI, 0.95-1.41; 107 events in 946 participants vs 1745 in 21 722); and for spine fracture, HR was 1.51 (95% CI, 0.93-2.45; 17 events in 732 participants vs 255 in 20 328). Lower TSH was associated with higher fracture rates: for TSH of less than 0.10 mIU/L, HR was 1.61 for hip fracture (95% CI, 1.21-2.15; 47 events in 510 participants); for any fracture, HR was 1.98 (95% CI, 1.41-2.78; 44 events in 212 participants); for nonspine fracture, HR was 1.61 (95% CI, 0.96-2.71; 32 events in 185 participants); and for spine fracture, HR was 3.57 (95% CI, 1.88-6.78; 8 events in 162 participants). Risks were similar after adjustment for other fracture risk factors. Endogenous Subclinical Hyperthyroidism (excluding thyroid medication users) was associated with HRs of 1.52 (95% CI, 1.19-1.93) for hip fracture, 1.42 (95% CI, 1.16-1.74) for any fracture, and 1.74 (95% CI, 1.01-2.99) for spine fracture. No association was found between Subclinical hypothyroidism and fracture risk. Conclusions and Relevance Subclinical Hyperthyroidism was associated with an increased risk of hip and other fractures, particularly among those with TSH levels of less than 0.10 mIU/L and those with endogenous Subclinical Hyperthyroidism. Further study is needed to determine whether treating Subclinical Hyperthyroidism can prevent fractures.
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Subclinical thyroid dysfunction and the risk of heart failure events an individual participant data analysis from 6 prospective cohorts
Circulation, 2012Co-Authors: Baris Gencer, Tinhhai Collet, Jacobijn Gussekloo, Douglas C Bauer, Wendy Den P J Elzen, Anne R Cappola, Philippe Balmer, Vanessa Virgini, David Nanchen, Robert LubenAbstract:Background —ACC/AHA Guidelines for the Diagnosis and Management of Heart Failure (HF) recommend investigating exacerbating conditions, such as thyroid dysfunction, but without specifying impact of different TSH levels. Limited prospective data exist regarding the association between Subclinical thyroid dysfunction and HF events. Methods and Results —We performed a pooled analysis of individual participant data using all available prospective cohorts with thyroid function tests and subsequent follow-up of HF events. Individual data on 25,390 participants with 216,248 person-years of follow-up were supplied from 6 prospective cohorts in the United States and Europe. Euthyroidism was defined as TSH 0.45-4.49 mIU/L, Subclinical hypothyroidism as TSH 4.5-19.9 mIU/L and Subclinical Hyperthyroidism as TSH <0.45 mIU/L, both with normal free thyroxine levels. Among 25,390 participants, 2068 had Subclinical hypothyroidism (8.1%) and 648 Subclinical Hyperthyroidism (2.6%). In age- and gender-adjusted analyses, risks of HF events were increased with both higher and lower TSH levels (P for quadratic pattern <0.01): hazard ratio (HR) was 1.01 (95% confidence interval [CI] 0.81-1.26) for TSH 4.5-6.9 mIU/L, 1.65 (CI 0.84-3.23) for TSH 7.0-9.9 mIU/L, 1.86 (CI 1.27-2.72) for TSH 10.0-19.9 mIUL/L (P for trend <0.01), and was 1.31 (CI 0.88-1.95) for TSH 0.10-0.44 mIU/L and 1.94 (CI 1.01-3.72) for TSH <0.10 mIU/L (P for trend = 0.047). Risks remained similar after adjustment for cardiovascular risk factors. Conclusions —Risks of HF events were increased with both higher and lower TSH levels, particularly for TSH ≥10 mIU/L and for TSH
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Subclinical thyroid dysfunction and the risk of heart failure events an individual participant data analysis from 6 prospective cohorts
Circulation, 2012Co-Authors: Baris Gencer, Tinhhai Collet, Jacobijn Gussekloo, Douglas C Bauer, Wendy Den P J Elzen, Anne R Cappola, Philippe Balmer, Vanessa Virgini, David Nanchen, Robert LubenAbstract:Background—American College of Cardiology/American Heart Association guidelines for the diagnosis and management of heart failure recommend investigating exacerbating conditions such as thyroid dysfunction, but without specifying the impact of different thyroid-stimulation hormone (TSH) levels. Limited prospective data exist on the association between Subclinical thyroid dysfunction and heart failure events. Methods and Results—We performed a pooled analysis of individual participant data using all available prospective cohorts with thyroid function tests and subsequent follow-up of heart failure events. Individual data on 25 390 participants with 216 248 person-years of follow-up were supplied from 6 prospective cohorts in the United States and Europe. Euthyroidism was defined as TSH of 0.45 to 4.49 mIU/L, Subclinical hypothyroidism as TSH of 4.5 to 19.9 mIU/L, and Subclinical Hyperthyroidism as TSH <0.45 mIU/L, the last two with normal free thyroxine levels. Among 25 390 participants, 2068 (8.1%) had su...
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Subclinical Hyperthyroidism and the risk of coronary heart disease and mortality
JAMA Internal Medicine, 2012Co-Authors: Tinhhai Collet, Jose A Sgarbi, Jacobijn Gussekloo, Douglas C Bauer, Wendy Den P J Elzen, Anne R Cappola, Philippe Balmer, Giorgio Iervasi, Bjorn Olav Asvold, Henry VolzkeAbstract:Background Data from prospective cohort studies regarding the association between Subclinical Hyperthyroidism and cardiovascular outcomes are conflicting. We aimed to assess the risks of total and coronary heart disease (CHD) mortality, CHD events, and atrial fibrillation (AF) associated with endogenous Subclinical Hyperthyroidism among all available large prospective cohorts. Methods Individual data on 52 674 participants were pooled from 10 cohorts. Coronary heart disease events were analyzed in 22 437 participants from 6 cohorts with available data, and incident AF was analyzed in 8711 participants from 5 cohorts. Euthyroidism was defined as thyrotropin level between 0.45 and 4.49 mIU/L and endogenous Subclinical Hyperthyroidism as thyrotropin level lower than 0.45 mIU/L with normal free thyroxine levels, after excluding those receiving thyroid-altering medications. Results Of 52 674 participants, 2188 (4.2%) had Subclinical Hyperthyroidism. During follow-up, 8527 participants died (including 1896 from CHD), 3653 of 22 437 had CHD events, and 785 of 8711 developed AF. In age- and sex-adjusted analyses, Subclinical Hyperthyroidism was associated with increased total mortality (hazard ratio [HR], 1.24, 95% CI, 1.06-1.46), CHD mortality (HR, 1.29; 95% CI, 1.02-1.62), CHD events (HR, 1.21; 95% CI, 0.99-1.46), and AF (HR, 1.68; 95% CI, 1.16-2.43). Risks did not differ significantly by age, sex, or preexisting cardiovascular disease and were similar after further adjustment for cardiovascular risk factors, with attributable risk of 14.5% for total mortality to 41.5% for AF in those with Subclinical Hyperthyroidism. Risks for CHD mortality and AF (but not other outcomes) were higher for thyrotropin level lower than 0.10 mIU/L compared with thyrotropin level between 0.10 and 0.44 mIU/L (for both, P value for trend, ≤.03). Conclusion Endogenous Subclinical Hyperthyroidism is associated with increased risks of total, CHD mortality, and incident AF, with highest risks of CHD mortality and AF when thyrotropin level is lower than 0.10 mIU/L.
C F A Eustatiarutten - One of the best experts on this subject based on the ideXlab platform.
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autonomic nervous system function in chronic exogenous Subclinical thyrotoxicosis and the effect of restoring euthyroidism
The Journal of Clinical Endocrinology and Metabolism, 2008Co-Authors: C F A Eustatiarutten, Karen A Heemstra, Eleonora P. M. Corssmit, Johannes W A Smit, Rik C. Schoemaker, Johannes A. Romijn, Jacobus BurggraafAbstract:Context: Knowledge on the relationship between the autonomic nervous system and Subclinical Hyperthyroidism is mainly based upon cross-sectional studies in heterogeneous patient populations, and the effect of restoration to euthyroidism in Subclinical Hyperthyroidism has not been studied. Objective:We investigated the long-term effects of exogenous Subclinical Hyperthyroidism on the autonomic nervous system and the potential effects of restoration of euthyroidism. Design: This was a prospective single-blinded, placebo-controlled, randomized trial. Setting: The study was performed at a university hospital. Patients: A total of 25 patients who were on more than 10-yr TSH suppressive therapy after thyroidectomy was examined. Intervention:Patientswerestudiedatbaselineandsubsequentlyrandomizedtoa6-monththyroid hormone substitution regimen to obtain either euthyroidism or maintenance of the Subclinical hyperthyroid state. Main Outcome Measures: Urinary excretion of catecholamines and heart rate variability were measured. Baseline data of the Subclinical Hyperthyroidism patients were compared with data obtained in patients with Hyperthyroidism and controls. Results:UrinaryexcretionofnorepinephrineandvanillylmandelicacidwashigherintheSubclinical Hyperthyroidism patients compared with controls and lower compared with patients with overt Hyperthyroidism. Heart rate variability was lower in patients with Hyperthyroidism, intermediate in Subclinical Hyperthyroidism patients, and highest in the healthy controls. No differences were observed after restoration of euthyroidism.
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glucose tolerance and lipid profile in longterm exogenous Subclinical Hyperthyroidism and the effects of restoration of euthyroidism a randomised controlled trial
Clinical Endocrinology, 2006Co-Authors: Karen A Heemstra, J W A Smit, C F A Eustatiarutten, Annemieke C Heijboer, Marijke Frolich, Johannes A. Romijn, Eleonora P. M. CorssmitAbstract:Summary Objective The impact of prolonged Subclinical Hyperthyroidism on glucose and lipid metabolism is unclear. Therefore, we evaluated glucose and lipid metabolism in patients with differentiated thyroid carcinoma (DTC) on TSH suppressive thyroxine therapy as a model for Subclinical Hyperthyroidism and investigated whether restoration to euthyroidism affects metabolism. Design We performed a prospective, single-blinded, placebo-controlled, randomised trial of 6 months duration with 2 parallel groups. Patients Twenty-five subjects with a history of differentiated thyroid carcinoma with > 10 years TSH-suppressive therapy with l-thyroxine completed the study. l-thyroxine dose was replaced by study medication containing l-thyroxine or l-thyroxine plus placebo. Medication was titrated to establish continuation of TSH suppression (low-TSH group, 13 patients) and euthyroidism (euthyroidism group, 12 patients). Measurements We evaluated glucose metabolism by glucose tolerance test and HOMA (IR) and lipid metabolism by lipid profile. In addition, we measured plasma concentrations of glucoregulatory hormones. Results At baseline, glucose tolerance, HOMA (IR), lipid profile and plasma concentrations of glucoregulatory hormones were within the normal range. No significant differences between the low TSH and euthyroidism group were observed. After 6 months, neither glucose nor lipid metabolism in the low TSH group were different from baseline values. Conclusion In summary, glucose and lipid metabolism in patients with DTC and long-term Subclinical Hyperthyroidism in general are not affected. Restoration of euthyroidism in general does not affect glucose and lipid metabolism.
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quality of life in longterm exogenous Subclinical Hyperthyroidism and the effects of restoration of euthyroidism a randomized controlled trial
Clinical Endocrinology, 2006Co-Authors: C F A Eustatiarutten, Eleonora P. M. Corssmit, Marijke Frolich, Alberto M Pereira, Johannes A. Romijn, J W A SmitAbstract:Summary Objective The impact of prolonged Subclinical Hyperthyroidism on quality of life is unclear. Therefore, we evaluated quality of life in patients with differentiated thyroid carcinoma (DTC) on TSH-suppressive thyroxine therapy as a model for Subclinical Hyperthyroidism and we investigated whether restoration to euthyroidism affects quality of life. Design We performed a prospective, single-blinded, placebo-controlled, randomized trial of 6 months’ duration with two parallel groups. Patients and methods Twenty-four subjects with a history of differentiated thyroid carcinoma with > 10 years TSH-suppressive therapy with L-thyroxine completed the study. L-thyroxine dose was replaced by study medication containing L-thyroxine or L-thyroxine plus placebo. Medication was titrated to establish continuation of TSH suppression (low-TSH group) and euthyroidism (euthyroid group). Both groups consisted of 12 patients. We evaluated quality of life using five validated questionnaires. Results At baseline, the somatic disorder questionnaire (SDQ) indicated more somatic dysfunction in patients as compared with reference values, whereas the depression score (HADS) revealed a better score than the reference group. All other quality of life parameters were normal. At baseline, no significant differences between the low-TSH and the euthyroidism groups were observed. After 6 months, none of the quality of life parameters in the low-TSH group was different from baseline values. In the euthyroid group, motivation was significantly improved (Multidimensional Fatigue Index-20, P = 0·003), although this parameter did not differ from the reference group at baseline. A probable worsening in role limitations as a result of physical problems (Short Form-36; P = 0·050) was observed. No improvement in the SDQ score was observed. Conclusion In summary, quality of life in patients with DTC and long-term Subclinical Hyperthyroidism in general is preserved. Restoration of euthyroidism in general does not affect quality of life.
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reversible diastolic dysfunction after long term exogenous Subclinical Hyperthyroidism a randomized placebo controlled study
The Journal of Clinical Endocrinology and Metabolism, 2005Co-Authors: J W A Smit, C F A Eustatiarutten, Eleonora P. M. Corssmit, Marijke Frolich, Alberto M Pereira, Gabe B Bleeker, Eduard R Holman, E E Van Der Wall, Johannes A. RomijnAbstract:Background: Subclinical Hyperthyroidism has been reported to affect systolic and diastolic cardiac function. However, the reversibility of these effects is not well established. Objective: Our objective was to investigate the presence and reversibility of cardiac abnormalities in patients with long-term exogenous Subclinical Hyperthyroidism. Design: We conducted a prospective, single-blinded, placebo-controlled randomized trial of 6 months duration with two parallel groups. Setting: The study occurred at the Leiden University Medical Center, a tertiary referral center for thyroid carcinoma. Patients: As a model for Subclinical Hyperthyroidism, 25 patients with a history of differentiated thyroid carcinoma with more than 10 yr of TSH suppressive therapy with l-T4 were studied. Interventions: l-T4 dose was replaced by study medication containing l-T4 or placebo. Medication was titrated in a single-blinded fashion to establish continuation of TSH suppression (low-TSH group) or euthyroidism (euthyroid group)....
Johannes A. Romijn - One of the best experts on this subject based on the ideXlab platform.
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autonomic nervous system function in chronic exogenous Subclinical thyrotoxicosis and the effect of restoring euthyroidism
The Journal of Clinical Endocrinology and Metabolism, 2008Co-Authors: C F A Eustatiarutten, Karen A Heemstra, Eleonora P. M. Corssmit, Johannes W A Smit, Rik C. Schoemaker, Johannes A. Romijn, Jacobus BurggraafAbstract:Context: Knowledge on the relationship between the autonomic nervous system and Subclinical Hyperthyroidism is mainly based upon cross-sectional studies in heterogeneous patient populations, and the effect of restoration to euthyroidism in Subclinical Hyperthyroidism has not been studied. Objective:We investigated the long-term effects of exogenous Subclinical Hyperthyroidism on the autonomic nervous system and the potential effects of restoration of euthyroidism. Design: This was a prospective single-blinded, placebo-controlled, randomized trial. Setting: The study was performed at a university hospital. Patients: A total of 25 patients who were on more than 10-yr TSH suppressive therapy after thyroidectomy was examined. Intervention:Patientswerestudiedatbaselineandsubsequentlyrandomizedtoa6-monththyroid hormone substitution regimen to obtain either euthyroidism or maintenance of the Subclinical hyperthyroid state. Main Outcome Measures: Urinary excretion of catecholamines and heart rate variability were measured. Baseline data of the Subclinical Hyperthyroidism patients were compared with data obtained in patients with Hyperthyroidism and controls. Results:UrinaryexcretionofnorepinephrineandvanillylmandelicacidwashigherintheSubclinical Hyperthyroidism patients compared with controls and lower compared with patients with overt Hyperthyroidism. Heart rate variability was lower in patients with Hyperthyroidism, intermediate in Subclinical Hyperthyroidism patients, and highest in the healthy controls. No differences were observed after restoration of euthyroidism.
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glucose tolerance and lipid profile in longterm exogenous Subclinical Hyperthyroidism and the effects of restoration of euthyroidism a randomised controlled trial
Clinical Endocrinology, 2006Co-Authors: Karen A Heemstra, J W A Smit, C F A Eustatiarutten, Annemieke C Heijboer, Marijke Frolich, Johannes A. Romijn, Eleonora P. M. CorssmitAbstract:Summary Objective The impact of prolonged Subclinical Hyperthyroidism on glucose and lipid metabolism is unclear. Therefore, we evaluated glucose and lipid metabolism in patients with differentiated thyroid carcinoma (DTC) on TSH suppressive thyroxine therapy as a model for Subclinical Hyperthyroidism and investigated whether restoration to euthyroidism affects metabolism. Design We performed a prospective, single-blinded, placebo-controlled, randomised trial of 6 months duration with 2 parallel groups. Patients Twenty-five subjects with a history of differentiated thyroid carcinoma with > 10 years TSH-suppressive therapy with l-thyroxine completed the study. l-thyroxine dose was replaced by study medication containing l-thyroxine or l-thyroxine plus placebo. Medication was titrated to establish continuation of TSH suppression (low-TSH group, 13 patients) and euthyroidism (euthyroidism group, 12 patients). Measurements We evaluated glucose metabolism by glucose tolerance test and HOMA (IR) and lipid metabolism by lipid profile. In addition, we measured plasma concentrations of glucoregulatory hormones. Results At baseline, glucose tolerance, HOMA (IR), lipid profile and plasma concentrations of glucoregulatory hormones were within the normal range. No significant differences between the low TSH and euthyroidism group were observed. After 6 months, neither glucose nor lipid metabolism in the low TSH group were different from baseline values. Conclusion In summary, glucose and lipid metabolism in patients with DTC and long-term Subclinical Hyperthyroidism in general are not affected. Restoration of euthyroidism in general does not affect glucose and lipid metabolism.
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quality of life in longterm exogenous Subclinical Hyperthyroidism and the effects of restoration of euthyroidism a randomized controlled trial
Clinical Endocrinology, 2006Co-Authors: C F A Eustatiarutten, Eleonora P. M. Corssmit, Marijke Frolich, Alberto M Pereira, Johannes A. Romijn, J W A SmitAbstract:Summary Objective The impact of prolonged Subclinical Hyperthyroidism on quality of life is unclear. Therefore, we evaluated quality of life in patients with differentiated thyroid carcinoma (DTC) on TSH-suppressive thyroxine therapy as a model for Subclinical Hyperthyroidism and we investigated whether restoration to euthyroidism affects quality of life. Design We performed a prospective, single-blinded, placebo-controlled, randomized trial of 6 months’ duration with two parallel groups. Patients and methods Twenty-four subjects with a history of differentiated thyroid carcinoma with > 10 years TSH-suppressive therapy with L-thyroxine completed the study. L-thyroxine dose was replaced by study medication containing L-thyroxine or L-thyroxine plus placebo. Medication was titrated to establish continuation of TSH suppression (low-TSH group) and euthyroidism (euthyroid group). Both groups consisted of 12 patients. We evaluated quality of life using five validated questionnaires. Results At baseline, the somatic disorder questionnaire (SDQ) indicated more somatic dysfunction in patients as compared with reference values, whereas the depression score (HADS) revealed a better score than the reference group. All other quality of life parameters were normal. At baseline, no significant differences between the low-TSH and the euthyroidism groups were observed. After 6 months, none of the quality of life parameters in the low-TSH group was different from baseline values. In the euthyroid group, motivation was significantly improved (Multidimensional Fatigue Index-20, P = 0·003), although this parameter did not differ from the reference group at baseline. A probable worsening in role limitations as a result of physical problems (Short Form-36; P = 0·050) was observed. No improvement in the SDQ score was observed. Conclusion In summary, quality of life in patients with DTC and long-term Subclinical Hyperthyroidism in general is preserved. Restoration of euthyroidism in general does not affect quality of life.
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reversible diastolic dysfunction after long term exogenous Subclinical Hyperthyroidism a randomized placebo controlled study
The Journal of Clinical Endocrinology and Metabolism, 2005Co-Authors: J W A Smit, C F A Eustatiarutten, Eleonora P. M. Corssmit, Marijke Frolich, Alberto M Pereira, Gabe B Bleeker, Eduard R Holman, E E Van Der Wall, Johannes A. RomijnAbstract:Background: Subclinical Hyperthyroidism has been reported to affect systolic and diastolic cardiac function. However, the reversibility of these effects is not well established. Objective: Our objective was to investigate the presence and reversibility of cardiac abnormalities in patients with long-term exogenous Subclinical Hyperthyroidism. Design: We conducted a prospective, single-blinded, placebo-controlled randomized trial of 6 months duration with two parallel groups. Setting: The study occurred at the Leiden University Medical Center, a tertiary referral center for thyroid carcinoma. Patients: As a model for Subclinical Hyperthyroidism, 25 patients with a history of differentiated thyroid carcinoma with more than 10 yr of TSH suppressive therapy with l-T4 were studied. Interventions: l-T4 dose was replaced by study medication containing l-T4 or placebo. Medication was titrated in a single-blinded fashion to establish continuation of TSH suppression (low-TSH group) or euthyroidism (euthyroid group)....
