Is Thyroid Hormone Suppression Therapy Prothrombotic?

Horne, McDonald K.; Singh, Kulvinder K.; Rosenfeld, Kathryn G; Wesley, Robert; Skarulis, Monica C.; Merryman, Paula K.; Cullinane, Ann M.; Costello, Rene; Patterson, Amy P.; Eggerman, Thomas L.; Bernstein, Donna M.; Pucino, Frank; Csákó, György

doi:10.1210/jc.2004-0536

Cited by 58 publications

(54 citation statements)

References 28 publications

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“…While Siegert et al proposed a pathogenetic mechanism based on local venous compression by large goiter [7], our case with normal thyroid size does not corroborate this finding. Another clinical study demonstrated that the postulated association between hyperthyroidism and prothrombotic state/hypercoagulability can be supported by measurable blood parameters [8]. In particular, the reported dependency of protein C levels on thyroid hormones levels is in line with the present case, where a decreased level of functional protein C was measured during phases of high T 3 /T 4 levels.…”

Section: Discussionsupporting

confidence: 89%

Cerebral Venous Sinus Thrombosis in a Patient With Graves’ Disease

Hieber

Lambeck

2016

J Endocrinol Metab

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Cerebral venous sinus thrombosis (CVST) constitutes a small proportion of stroke. Its risk factors include hypercoagulability of various causes. We report the case of a 54-year-old woman in whom thrombosis of the left transverse and sigmoid sinus was diagnosed. The extended etiological workup revealed hyperthyroidism, and further analysis showed clinical results consistent with Graves' disease and decreased levels of protein C. A small number of similar cases -of both the general association of hyperthyroidism and CVST and the additional finding of low protein C -have been described in the literature, so that our case further supports the likely association of hyperthyroidism and hypercoagulability.

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Section: Discussionsupporting

confidence: 89%

Cerebral Venous Sinus Thrombosis in a Patient With Graves’ Disease

Hieber

Lambeck

2016

J Endocrinol Metab

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“…A number of long-term safety issues surround THST, particularly in growing patients who are likely to receive the modality for a very long time (Muller et al 1995, Shapiro et al 1997, Horne et al 2004, Botella-Carretero et al 2004. Potential THST side effects may include osteoporosis (Schneider & Reiners 2003), and of special concern, cardiovascular complications, particularly ventricular hypertrophy (Biondi et al 1993, Fazio et al 1995, Matuszewska et al 2001).…”

Section: Goal Of Ablation Rationalementioning

confidence: 99%

Juvenile differentiated thyroid carcinoma and the role of radioiodine in its treatment: a qualitative review

Jarząb¹,

Handkiewicz-Junak²,

Włoch³

2005

Endocr Relat Cancer

171

160

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Well under 15% of differentiated thyroid carcinoma (DTC) is diagnosed at £18 years of age. The population is heterogenous and the differences between prepubertal children and pubertals and adolescents are to be considered. Although very little has been reported on children with sporadic DTC under the age of 10 years, juvenile DTC has at least some undeniable differences with adult DTC: (1) larger primary tumor at diagnosis; (2) metastatic pattern and features, namely: (a) greater prevalence of neck lymph node and distant metastases at diagnosis, (b) lungs almost the sole distant metastatic site, (c) pulmonary metastases nearly always functional; (3) closer-to-normal and more frequent sodium-iodide symporter (NIS) expression; and (4) higher recurrence rate but longer overall survival. These differences are especially distinct in prepubertal children. The goals of primary treatment of juvenile DTC are to eradicate disease and extend not only overall, but recurrence-free survival (RFS). Extending RFS is itself a desirable goal in children because it improves quality-of-life, alleviates anxiety during psychologically formative years, reduces medical resource consumption, and may increase overall survival. Primary treatment of DTC generally comprises a combination of surgery, radioiodine ( 131 I) ablation, and thyroid hormone therapy applied at varying levels of intensity. Therapeutic decision-making must rely on retrospective adult and/or pediatric outcome studies and on treatment guidelines formulated mostly for adults. Differences between juvenile and adult DTC and physiology dictate distinct treatment strategies for children. We, and many others, advocate a routine intensive approach because of the more advanced disease at diagnosis, propensity for recurrence, and greater radioiodine responsiveness in children, as well as published evidence of significant survival benefits, especially regarding RFS. This intensive approach consists of total thyroidectomy and central lymphadenectomy in all cases, completed by modified lateral lymphadenectomy when necessary and followed by radioiodine administration. However, absence of prospective studies and of universal proof of overall causespecific survival benefits of this approach have led some to propose more conservative strategies. Most European centers give radioiodine ablation to the vast majority of juvenile DTC patients. Ablation seeks to destroy any residual cancer, including microfoci, as well as healthy thyroid remnant. Large studies have documented the procedure to decrease cause-specific death rates and, in children, to significantly lessen locoregional recurrence rates (by factors of 2-11) independent of the extent of surgery. There is universal agreement on treating inoperable functional metastases with large radioiodine activities. Treatment is especially effective in small tumor foci up to 1 cm in diameter, and should be administered every 6-12 months until complete response, loss of functionality, or attainment of cumulative activities between 18.5-3...

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“…In the present study, vWF and fibrinogen as markers of endothelial dysfunction were more higher in subclinical hyperthyroidism than in overt hypothyroidism, and there was positive correlation between changes of aortic stiffness index, vWF and fibrinogen during transition from subclinical hyperthyroidism to hypothyroidism. These changes may be associated with relative hypercoagulability and increased thromboembolic risk [46]. Most previous studies used isovolumic relaxation time to evaulate diastolic dysfunction in subclinical hypo-and hyperthyroidism.…”

Section: Referencesmentioning

confidence: 99%

Aortic stiffness and left ventricular function in patients with differentiated thyroid cancer

Gazdag

Nagy

Erdei

et al. 2014

J Endocrinol Invest

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Abstract:Objective: The aim of this study was to investigate aortic stiffness and left ventricular systolic and diastolic function in patients with differentiated thyroid cancer (DTC) on thyroxin (L-T4) therapy and after L-T4 withdrawal in order to assess the cardiovascular impact of long-term subclinical hyperthyroidism and short-term overt hypothyroidism. Design: Twenty four patients who had had total thyroidectomy and radioiodine ablation for differentiated thyroid cancer were studied on two occasions: on TSH suppressive L-T4 therapy (sTSH 0.24±0.11 mU/L), and four weeks after L-T4 withdrawal (sTSH 89.82±29.36 mU/L). Echocardiography was performed and thyroid function, serum thyroglobulin, lipid parameters, homocystine, C-reactive protein, fibrinogen and von Willebrandt factor activity (vWF) were measured. Twenty two healthy volunteers matched for age and sex served as euthyroid controls. Results: Aortic stiffness was increased both in hypothyroidism (6.04±2.88 cm2/dyn/103, p< 0.05) and subclinical hyperthyroidism (9.27±4.81 cm2/dyn/103, p<0.05) vs. controls (3.92±1.84 cm2/dyn/103). Subclinical hyperthyroidism had a more marked effect (p<0.05). LV dimensions and ejection fractions were similar before and after L-T4 withdrawal. The E'/A' was higher in euthyroid controls (1.34±1.02) as compared to both subclinical hyperthyroidism (1.0±0.14, p<0.05) and overt hypothyroidism (1.13±0.98, p<0.05). Change of aortic stiffness correlated with change of free-thyroxine (fT4), vWF and fibrinogen levels in a positive manner. Conclusion: Long-term thyrotropin-suppression therapy has continuous adverse effects on the arterial wall. The degree of TSH suppression in patients with DTC should be kept at the possible minimum, based on individually determined potential benefits and risks of treatment, especially in patients with cardiovascular comorbidities. Dear Professor Bartalena,We would like to thank you for the suggestions which have contributed to the improvement of our paper entitled "Aortic stiffness and left ventricular function in patients with differentiated thyroid cancer", JENI-D-14-00120 .We have corrected the manuscript and we hope that you will find it worth publishing in the Journal of Endocrinological Investigation.We provide a detailed point-by-point response to each of the referees' concerns, describing exactly how we responded to each point and where you can find the amendment in the revised manuscript.Thank you very much for your patience and kind help. •How many time elapsed from thyroidectomy/RAI ablation and the current tests?20±12,6 months elapsed before the start of this study. This information has been added to page 4, line 47.•What was the thyroglobulin serum level at the time of aortic examination? In other words, were all the patients without evidence of persistent/recurrent disease (also by the biochemical point of view)? / Did the Authors evaluate the level of serum anti-Tg antibodies?The first off-T4 Tg measurrment was at least 6 months after RAI in parallel with anti-Tg antibody. Four of twenty...

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Is Thyroid Hormone Suppression Therapy Prothrombotic?

Cited by 58 publications

References 28 publications

Cerebral Venous Sinus Thrombosis in a Patient With Graves’ Disease

Cerebral Venous Sinus Thrombosis in a Patient With Graves’ Disease

Juvenile differentiated thyroid carcinoma and the role of radioiodine in its treatment: a qualitative review

Aortic stiffness and left ventricular function in patients with differentiated thyroid cancer

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