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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Graves&#8217; hyperthyroidism &#40;GH&#41; is the most common form of hyperthyroidism in populations with an adequate iodine intake&#44; which&#44; despite incidence peaks between 30 and 50 years of age&#44; can affect individuals of any age&#46; Untreated GH is associated with increased mortality and morbidity&#59; timely treatment of GH is therefore critical&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">The therapeutic options for patients with GH include antithyroid drugs &#40;ATDs&#41;&#44; such as methimazole&#44; carbimazole and propylthiouracil&#44; whose purpose is to recover euthyroidism while the autoimmune process resolves&#46; The options also include radioactive iodine &#40;RAI&#41; therapy and total thyroidectomy &#40;TT&#41;&#44; whose purpose is to induce permanent hypothyroidism followed by thyroid hormone replacement&#46; Although each of these options has been shown effective&#44; all have a number of drawbacks&#46; Currently&#44; the first option for treating newly diagnosed cases of GH is administering ATDs&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">1</span></a> However&#44; there is no consensus on the optimal therapy for patients with recurrent GH&#46; The discussion between physician and patient as to the best therapeutic option should consider the following aspects&#44; as recommended by the main therapeutic protocols<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">2</span></a>&#58;</p><p id="par0015" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">The natural course of GH</span>&#58; As happens with other autoimmune diseases&#44; GH activity can oscillate over the course of the disease&#59; patients can enter a remission phase without undergoing any type of specific treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">3</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">GH that transforms into Hashimoto&#39;s thyroiditis</span>&#58; Although Graves&#8217; disease and Hashimoto&#39;s thyroiditis were initially considered 2 separate processes&#44; they are now considered different manifestations of the same disease&#46; It is well known that the natural course of GH can result in hypothyroidism in 10&#8211;20&#37; of patients&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">4</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Long-term thionamide-induced remission of GH</span>&#58; The evidence on this finding shows that treatment with ATDs is usually accompanied by GH remission beyond the disease&#39;s natural history&#46; In terms of the underlying mechanism&#44; it is unclear whether this remission is due to the immunomodulatory effect of ATDs or is associated with the euthyroidism induced by these drugs&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">5</span></a><ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">&#8211;</span><p id="par0030" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Risk factors that predict a GH relapse after interrupting ATD therapy</span>&#58; The following factors are associated with a greater risk of relapse after withdrawing ATDs&#58; young age&#44; male sex&#44; tobacco use&#44; large goiter&#44; biochemistry indicating severe GH&#44; high levels of thyroid-stimulating immunoglobulins and&#44; more recently&#44; some genetic markers&#46; However&#44; none of these parameters has been shown to be useful for determining patients&#8217; individual prognoses&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">6</span></a></p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">&#8211;</span><p id="par0035" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">The response of patients with recurrent GH to other ATD cycles</span>&#58; Generally&#44; physicians believe that patients with recurrent GH do not usually respond effectively to new ATD cycles&#44; which leads them to choose RAI for these cases&#46; However&#44; previous and recent studies have demonstrated that a second ATD cycle in patients with recurrent GH leads to satisfactory long-term remission&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">7</span></a></p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">&#8211;</span><p id="par0040" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">The objective of RAI therapy and TT</span> is to reduce the functional mass of the thyroid tissue&#44; which results in athyreotic hypothyroidism &#40;AH&#41; whose management is complicated&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">8</span></a> Thyroid function should be monitored after ablation and the AH treated for life&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">&#8211;</span><p id="par0045" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">The 3 therapeutic options are associated with problems and complications</span>&#58; The main problem with ATD therapy is relapses&#44; which occur in approximately 50&#37; of patients who discontinue the drug&#46; Given that the objective of RAI and TT is for the patient to develop hypothyroidism&#44; we cannot consider athyreotic hypothyroidism as a complication&#46; The main problem with RAI therapy is related to the progression of Graves&#8217; ophthalmopathy&#44; especially in patients who smoke and those with active ocular disease&#46; The safety and efficacy of TT is highly dependent on the surgeon&#39;s skill and experience&#46; RAI is related to increased morbidity and mortality due to cardiovascular disease&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">9</span></a> The clinical factors favoring TT are the large goiter with compression symptoms&#44; concurrent thyroid nodules suspected of malignancy and worsening ophthalmopathy&#46; <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a> lists the complications associated with each treatment&#46;<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">10&#8211;12</span></a></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">&#8211;</span><p id="par0050" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Long-term studies have shown the advantages of GH therapy with methimazole over</span><span class="elsevierStyleItalic">RAI</span><a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">13</span></a>&#58; A systematic review and recent meta-analysis confirmed that long-term ADT therapy &#40;&#62;24 months&#41; is safe and effective&#44; although mainly in adults&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">14</span></a> Another study compared the efficacy and long-term safety of therapy with low-dose methimazole &#40;initial dose of 10&#8211;20<span class="elsevierStyleHsp" style=""></span>mg and maintenance dose of 2&#46;5&#8211;7&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#41; compared with RAI therapy in patients with GH relapse&#46; In this article&#44; the authors observed that in the low-dose methimazole group&#44; the rate of euthyroidism was higher than in the RAI group&#46; In contrast&#44; the rate of manifest and subclinical hypothyroidism was higher in the RAI group&#46; As has been previously observed&#44; RAI therapy was associated with a lack of improvement or worsening of Graves&#8217; ophthalmopathy&#46; None of the patients in the methimazole group developed relevant adverse effects&#46; RAI therapy was also associated with weight gain&#44; especially after 24 months of follow-up&#44; which is probably because the number of patients with subclinical and manifest hypothyroidism in this group was larger&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">15</span></a></p></li></ul></p><p id="par0055" class="elsevierStylePara elsevierViewall">In conclusion and considering the above&#44; extended low-dose metamizole is the best option for treating patients with recurrent GH in standard practice&#46;</p></span>"
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Reasons to consider low-dose of methimazole as the best option to treat patients with recurrent Graves’ hyperthyroidism
Razones por las que considerar a las dosis bajas de metimazol como la mejor opción para tratar a los pacientes con hipertiroidismo de Graves recurrente
R.V. García-Mayora,b
a Unidad de Endocrinología, Hospital HM Vigo, Vigo, Pontevedra, Spain
b Instituto de Investigación Sanitaria Galicia Sur, Vigo, Pontevedra, Spain
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Advantages and disadvantages of the 3 therapeutic modalities for treating patients with recurrent Graves&#8217; hyperthyroidism&#46;</p> <p id="spar0010" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>&#58; MMI&#58; methimazole&#59; RAI&#58; radioactive iodine&#59; TT&#58; total thyroidectomy&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Graves&#8217; hyperthyroidism &#40;GH&#41; is the most common form of hyperthyroidism in populations with an adequate iodine intake&#44; which&#44; despite incidence peaks between 30 and 50 years of age&#44; can affect individuals of any age&#46; Untreated GH is associated with increased mortality and morbidity&#59; timely treatment of GH is therefore critical&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">The therapeutic options for patients with GH include antithyroid drugs &#40;ATDs&#41;&#44; such as methimazole&#44; carbimazole and propylthiouracil&#44; whose purpose is to recover euthyroidism while the autoimmune process resolves&#46; The options also include radioactive iodine &#40;RAI&#41; therapy and total thyroidectomy &#40;TT&#41;&#44; whose purpose is to induce permanent hypothyroidism followed by thyroid hormone replacement&#46; Although each of these options has been shown effective&#44; all have a number of drawbacks&#46; Currently&#44; the first option for treating newly diagnosed cases of GH is administering ATDs&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">1</span></a> However&#44; there is no consensus on the optimal therapy for patients with recurrent GH&#46; The discussion between physician and patient as to the best therapeutic option should consider the following aspects&#44; as recommended by the main therapeutic protocols<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">2</span></a>&#58;</p><p id="par0015" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">The natural course of GH</span>&#58; As happens with other autoimmune diseases&#44; GH activity can oscillate over the course of the disease&#59; patients can enter a remission phase without undergoing any type of specific treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">3</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">GH that transforms into Hashimoto&#39;s thyroiditis</span>&#58; Although Graves&#8217; disease and Hashimoto&#39;s thyroiditis were initially considered 2 separate processes&#44; they are now considered different manifestations of the same disease&#46; It is well known that the natural course of GH can result in hypothyroidism in 10&#8211;20&#37; of patients&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">4</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Long-term thionamide-induced remission of GH</span>&#58; The evidence on this finding shows that treatment with ATDs is usually accompanied by GH remission beyond the disease&#39;s natural history&#46; In terms of the underlying mechanism&#44; it is unclear whether this remission is due to the immunomodulatory effect of ATDs or is associated with the euthyroidism induced by these drugs&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">5</span></a><ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">&#8211;</span><p id="par0030" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Risk factors that predict a GH relapse after interrupting ATD therapy</span>&#58; The following factors are associated with a greater risk of relapse after withdrawing ATDs&#58; young age&#44; male sex&#44; tobacco use&#44; large goiter&#44; biochemistry indicating severe GH&#44; high levels of thyroid-stimulating immunoglobulins and&#44; more recently&#44; some genetic markers&#46; However&#44; none of these parameters has been shown to be useful for determining patients&#8217; individual prognoses&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">6</span></a></p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">&#8211;</span><p id="par0035" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">The response of patients with recurrent GH to other ATD cycles</span>&#58; Generally&#44; physicians believe that patients with recurrent GH do not usually respond effectively to new ATD cycles&#44; which leads them to choose RAI for these cases&#46; However&#44; previous and recent studies have demonstrated that a second ATD cycle in patients with recurrent GH leads to satisfactory long-term remission&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">7</span></a></p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">&#8211;</span><p id="par0040" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">The objective of RAI therapy and TT</span> is to reduce the functional mass of the thyroid tissue&#44; which results in athyreotic hypothyroidism &#40;AH&#41; whose management is complicated&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">8</span></a> Thyroid function should be monitored after ablation and the AH treated for life&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">&#8211;</span><p id="par0045" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">The 3 therapeutic options are associated with problems and complications</span>&#58; The main problem with ATD therapy is relapses&#44; which occur in approximately 50&#37; of patients who discontinue the drug&#46; Given that the objective of RAI and TT is for the patient to develop hypothyroidism&#44; we cannot consider athyreotic hypothyroidism as a complication&#46; The main problem with RAI therapy is related to the progression of Graves&#8217; ophthalmopathy&#44; especially in patients who smoke and those with active ocular disease&#46; The safety and efficacy of TT is highly dependent on the surgeon&#39;s skill and experience&#46; RAI is related to increased morbidity and mortality due to cardiovascular disease&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">9</span></a> The clinical factors favoring TT are the large goiter with compression symptoms&#44; concurrent thyroid nodules suspected of malignancy and worsening ophthalmopathy&#46; <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a> lists the complications associated with each treatment&#46;<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">10&#8211;12</span></a></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">&#8211;</span><p id="par0050" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Long-term studies have shown the advantages of GH therapy with methimazole over</span><span class="elsevierStyleItalic">RAI</span><a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">13</span></a>&#58; A systematic review and recent meta-analysis confirmed that long-term ADT therapy &#40;&#62;24 months&#41; is safe and effective&#44; although mainly in adults&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">14</span></a> Another study compared the efficacy and long-term safety of therapy with low-dose methimazole &#40;initial dose of 10&#8211;20<span class="elsevierStyleHsp" style=""></span>mg and maintenance dose of 2&#46;5&#8211;7&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#41; compared with RAI therapy in patients with GH relapse&#46; In this article&#44; the authors observed that in the low-dose methimazole group&#44; the rate of euthyroidism was higher than in the RAI group&#46; In contrast&#44; the rate of manifest and subclinical hypothyroidism was higher in the RAI group&#46; As has been previously observed&#44; RAI therapy was associated with a lack of improvement or worsening of Graves&#8217; ophthalmopathy&#46; None of the patients in the methimazole group developed relevant adverse effects&#46; RAI therapy was also associated with weight gain&#44; especially after 24 months of follow-up&#44; which is probably because the number of patients with subclinical and manifest hypothyroidism in this group was larger&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">15</span></a></p></li></ul></p><p id="par0055" class="elsevierStylePara elsevierViewall">In conclusion and considering the above&#44; extended low-dose metamizole is the best option for treating patients with recurrent GH in standard practice&#46;</p></span>"
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