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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/cdn\/css\/http\/css_Xg7z6oCTVgud_Q0huYz9x9iiD5H_2YPSJ5z2ZViSWdY.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EGraves disease is the leading cause of hyperthyroidism in the United States, and its diagnosis and management can be difficult. Treatment decision-making is especially challenging in two specific populations of individuals with Graves disease: individuals with Graves ophthalmopathy and children\/adolescents with the disease.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EThyroid Disorders\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EGraves disease is the leading cause of hyperthyroidism in the United States (US), and its diagnosis and management can be difficult. Treatment decision-making is especially challenging in two specific populations of individuals with Graves disease: individuals with Graves ophthalmopathy and children\/adolescents with the disease.\u003C\/p\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003EManaging Graves Ophthalmopathy\u003C\/h2\u003E\n         \u003Cp id=\u0022p-3\u0022\u003EMore than half of individuals with Graves disease will have some degree of ophthalmopathy, and the clinical heterogeneity in ophthalmopathy calls for disease assessment as a crucial first step in management, said Rebecca S. Bahn, MD, Mayo Clinic, Rochester, Minnesota, USA. It is important to distinguish disease activity from severity, as immunosuppressive treatment is more effective when disease is active rather than severe. Active Graves eye disease is defined as a score of at least 3\/7 or 4\/10 on the Clinical Activity Score (CAS), whereas severity of disease is determined by clinical assessment of the degree of lid retraction, soft tissues, exophthalmos, diplopia, and corneal exposure.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-2\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003EMild Disease\u003C\/h2\u003E\n         \u003Cp id=\u0022p-4\u0022\u003ESymptomatic treatment is appropriate for most patients with mild Graves ophthalmopathy. Interventions include lubricant eye drops, eye ointment and taping of eyelids at night, sunglasses to decrease photophobia, prismatic correction for diplopia, and elevation of the head of the bed. Dr. Bahn added that diuretics are not useful and that glucocorticoids are rarely justified, as the risks in this group of patients outweigh the benefits. A smoking cessation program is an essential element of treatment.\u003C\/p\u003E\n         \u003Cp id=\u0022p-5\u0022\u003EThe antioxidant selenium has recently been studied as treatment for mild Graves ophthalmopathy. Although selenium at a dose of 100 \u03bcg twice daily led to a significant improvement in the scores on a Graves orbitopathy-specific quality-of-life questionnaire (p\u0026lt;0.001 compared with placebo) in a recent European study, the improvements in clinical assessment were modest, with a median reduction of 2 and 3 mm in eyelid aperture, [slight improvement] in soft tissue signs, and no improvement in eye muscle motility [Marcocci C et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2011]. No adverse events occurred. Dr. Bahn noted that selenium levels are marginally decreased in most areas of Europe and were not determined in the study. Thus, further evaluation of a selenium-sufficient US population is needed. She said that selenium can be discussed with patients who have mild Graves eye disease but added that clinicians should not \u201coversell any possible benefit.\u201d\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-3\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003EModerate-to-Severe Disease\u003C\/h2\u003E\n         \u003Cp id=\u0022p-6\u0022\u003EAccording to a 2008 European Group on Graves Orbitopathy (EUGOGO) consensus statement, pulses of intravenous glucocorticoids is the treatment of choice for moderate-to-severe Graves eye disease, defined as a CAS\u22653\/7 [Bartalena L et al. \u003Cem\u003EThyroid\u003C\/em\u003E 2008]. Dr. Bahn said that she uses the Kahaly regimen (500 mg weekly x 6 plus 250 mg weekly x 6) [Kahaly GJ et al. \u003Cem\u003EJCEM\u003C\/em\u003E 2005] and tends to reserve treatment for patients with a slightly higher clinical score than the EUGOGO group recommends (CAS\u22654\/7).\u003C\/p\u003E\n         \u003Cp id=\u0022p-7\u0022\u003ERituximab is being studied as a potential treatment for moderate-to-severe disease, and the drug has been beneficial in several uncontrolled series. Two parallel randomized controlled trials are currently underway, one of which Dr. Bahn is conducting with colleagues at the Mayo Clinic. Dr. Bahn feels that \u201cthe jury is still out\u201d on rituximab for the treatment of Graves eye disease but doubts it will be a \u201cblockbuster.\u201d She added that it may be beneficial only for specific subsets of patients and would not be appropriate for milder cases, especially because of the risk of potentially serious side effects. Until the results or more studies are available, rituximab should be used only as part of a randomized controlled trial or under expert supervision in selected patients for whom other therapies have failed.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-4\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003EManaging Graves Disease in Children\u003C\/h2\u003E\n         \u003Cp id=\u0022p-8\u0022\u003EFor children with Graves disease, medical therapy (antithyroid medications) is the firstline approach for more than 95% of children, to \u201cbuy time with the hope of remission,\u201d said Catherine Anne Dinauer, MD, Yale University School of Medicine, New Haven, Connecticut, USA. However, a durable remission is achieved in only a small percentage of children, making definitive treatment (radioactive iodine [RAI] or surgery) necessary for most children at some point. Dr. Dinauer said that controversies surround each treatment option, primarily related to the associated risks and benefits and the timing of definitive therapy.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-5\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003EMedical Therapy\u003C\/h2\u003E\n         \u003Cp id=\u0022p-9\u0022\u003EMethimazole (MMI) and propylthiouracil have been the most commonly used antithyroid medications. However, an unacceptable risk of severe liver injury in children has been reported with propylthiouracil, and a black box warning on the label became required in April 2010. The drug should never be used as firstline therapy, said Dr. Dinauer. MMI is thus the drug of choice.\u003C\/p\u003E\n         \u003Cp id=\u0022p-10\u0022\u003EAccording to recently published guidelines for the management of hyperthyroidism [Bahn R et al. \u003Cem\u003EThyroid\u003C\/em\u003E 2011], the recommended initial dose of MMI for children is 0.2\u20130.5 mg\/kg\/day (range, 0.1\u20131.0 mg\/kg\/day). A general dosing schema, based on age can be used:\u003C\/p\u003E\n         \u003Cul class=\u0022list-unord \u0022 id=\u0022list-1\u0022\u003E\u003Cli id=\u0022list-item-1\u0022\u003E\n               \u003Cp id=\u0022p-11\u0022\u003EInfants: 1.25 mg\/day\u003C\/p\u003E\n            \u003C\/li\u003E\u003Cli id=\u0022list-item-2\u0022\u003E\n               \u003Cp id=\u0022p-12\u0022\u003E1 to 5 years: 2.5 to 5 mg\/day\u003C\/p\u003E\n            \u003C\/li\u003E\u003Cli id=\u0022list-item-3\u0022\u003E\n               \u003Cp id=\u0022p-13\u0022\u003E5 to 10 years: 5 to 10 mg\/day\u003C\/p\u003E\n            \u003C\/li\u003E\u003Cli id=\u0022list-item-4\u0022\u003E\n               \u003Cp id=\u0022p-14\u0022\u003E10 to 18 years: 10 to 20 mg\/day\u003C\/p\u003E\n            \u003C\/li\u003E\u003C\/ul\u003E\n         \u003Cp id=\u0022p-15\u0022\u003EDr. Dinauer said that clinicians should use the lowest dose possible to achieve euthyroidism, with the dose titrated down once the free T4 or total T4 level becomes normal. The block-and-replace approach should not be used. The side effect profile of MMI is safer than propylthiouracil, but rare, serious side effects, such as Stevens-Johnson syndrome, can occur. Adverse events have been reported in about 19% of children, with approximately 90% of events occurring within the first 6 months of treatment.\u003C\/p\u003E\n         \u003Cp id=\u0022p-16\u0022\u003ETreatment is usually recommended for 1\u20132 years and can continue beyond 2 years if there is no treatment-related toxicity, thyromegaly is not worsening, and the patient is compliant and not ready for definitive treatment. Dr. Dinauer pointed out that remission rates among children are lower than those among adults. The remission rate is 25% (compared with 49% to 75% of adults) after treatment for less than 2 years and is 15% to 30% after treatment for 2 years or longer.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-6\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003EDefinitive Therapy: RAI Versus Surgery\u003C\/h2\u003E\n         \u003Cp id=\u0022p-17\u0022\u003EThe evidence does not support many long-term risks that have been thought to be associated with RAI in children. For example, Dr. Dinauer noted that studies have failed to demonstrate an increased risk of congenital anomalies in the offspring of individuals who have been treated with RAI in childhood or an increased risk of thyroid cancer when recommended doses have been used. In addition, there is no evidence to date that the use of RAI in childhood increases the risk of a nonthyroid malignancy; however, a large sample of children aged \u226410 years is needed to detect a small risk. Theoretical projections indicate a slight risk of cancer for children aged \u0026lt;5 years at the time of RAI treatment. Because of this, RAI should not be used for children aged \u0026lt;5 years.\u003C\/p\u003E\n         \u003Cp id=\u0022p-18\u0022\u003EThe RAI dose should be calculated according to the size of the thyroid size, with a dose \u0026gt;150 \u03bcCi of RAI\/g of thyroid tissue and a dose of 200\u2013300 \u03bcCi of RAI\/g for thyroids that are 50\u201380 g. For children aged 5 to 10 years, the dose should be \u0026lt;10 mCi; if the calculated dose is higher, surgery or medical therapy should be considered rather than reducing the dose on the basis of age. Dr. Dinauer said that there are no outcome data on the use of fixed doses versus calculated doses in children but that a fixed dose may be higher than the calculated dose and thus expose the child to higher-than-necessary radiation.\u003C\/p\u003E\n         \u003Cp id=\u0022p-19\u0022\u003EThere are several indications for surgery as definitive treatment: a thyroid that is larger than 80 g, patient age \u0026lt;5 years, noncompliance with medical or RAI safety regimens, a suspicious nodule or known cancer, need for immediate control of disease, and obstructive or compressive symptoms. Total or near-total thyroidectomy is the procedure of choice, as relapse rates are lower than for subtotal resection. Dr. Dinauer cautioned that while the rate of overall complications after thyroidectomy is similar for both children and adults, the rate of endocrine complications is higher for children, especially the youngest patients. Studies have shown that the complication rate, length of stay, and cost are lower when thyroidectomy is done by a high-volume surgeon (one who performs more than 30 endocrine procedures per year).\u003C\/p\u003E\n         \u003Cp id=\u0022p-20\u0022\u003EDr. Dinauer noted that there is no one \u201cright\u201d treatment path for children with Graves disease, and a stratified approach should be taken (\u003Ca id=\u0022xref-table-wrap-1-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 2\u003C\/a\u003E). For each child, clinicians should consider the age, clinical factors, and the risks of treatment options to determine the best course of action. She also urged clinicians to review and follow recently published management guidelines [Bahn R et al. \u003Cem\u003EThyroid\u003C\/em\u003E 2011].\u003C\/p\u003E\n         \u003Cdiv id=\u0022T1\u0022 class=\u0022table pos-float\u0022\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022\/\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/12285\/expansion?postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 html=\u00221\u0022 fragment=\u0022#\u0022 external=\u00221\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/12285\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/12285\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 2.\u003C\/span\u003E \n               \u003Cp id=\u0022p-21\u0022 class=\u0022first-child\u0022\u003EStratified Approach to Management of Graves Disease in Children.\u003C\/p\u003E\n            \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\n      \u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2011 MD Conference Express\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/11\/5\/20.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzm0qp\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_tables.js?nzm0qp\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}