lowing 2 or more vears of atd therapy do not exceed transient in these es.a reasonable a roach is to 25%[157,158],and this necessitates longer-term ATD treatwith circulain-ecomun administration in most children.Furthermore,there is a detectable higher prevalence of adverse reactions to ATD in chil- dren and this means that PTU is no longer recommend Recommendations ed for use in childhood,owing to hepatic a lure in up to 49 Grave shyperthyroidism precipitated by an immuno 159 modulatory the apy is not a mandatory indication to total th op tha safety of RAl.particularly in postpubertal younger pe 50 Sequential monitoring of serum TSH-R-Ab levels can ple [160].Thus,long-term low-dose MMI (CBZ)fol be used to guide the duration of ATD therap lowed,if necessary,by surgery or RAI when the child reaches a suitable age(16 years or older)is frequently the (as a consequenc Perspectives and Conclusion y cto to account in On the ould modify the na al hist dulating it Recommendations enesis.These therapeutic agents include TSH-R 46 PTU should be avoided in children and adolescents.1, monoclonal Abs(164],immunomodulatory TSH-Rpep- 0000 tides,and small-molecule TSH-R ligands 165 that car 47 Long-term MMI(CBZ)should be the mainstay of block the thyroid-stimulating effect of TSH-R-Ab,thus H-R-Ab antagonists Ho er,the data ar 48 acting as T oo prelimin the n gh ha und ratio is not immune reconstitution orted by sufficient evidence i1661 Currently the ont The first demonstration of immune reconstitution mal management depends on patient preference and GD was in multiple sclerosis patients who had received specific patient clinical features such as age.history o lymphocyte-depleting alemtuzumab (Campath-H1) arrhythmia or ischemic heart disea size of goiter,anc ntib ody treatment [16 Ihis tr men cau Since eac the treatment unique lim GD as F quence GD ha d d be ith Hy effective highly active antiretroviral ther with hy perthyroidsmdevelopingasCD4yhplgy The target audience for this uideline are physician yte counts providing care for patients with GD.In this document ra- increase [162].Immune reconstitution GD has also tional medical practice is outlined.This guideline does not been observed in bone marrow transplant patients.In replace clinical judgment,individual decision making,or s manageable and,de pending on the wishes of the patient or family V.Rathe n the u not an ind shoul valuated me on to 人 ough initia optimal ided ere d.When th ed in the additional experience now s ggests that they can be be considered.The 50 recommendations that form these managed similarly to patients with"spontaneous"GD guidelines are presented together in Table 6. [163].However,as the immunological"insult"may be 2018 ETA Guideline for the Mar 179 of Graves'Hyperthyroidism nagement 医肺润 http://quide medlive.cn/2018 ETA Guideline for the Management of Graves’ Hyperthyroidism Eur Thyroid J 2018;7:167–186 179 DOI: 10.1159/000490384 lowing 2 or more years of ATD therapy do not exceed 25% [157, 158], and this necessitates longer-term ATD administration in most children. Furthermore, there is a higher prevalence of adverse reactions to ATD in chil￾dren and this means that PTU is no longer recommend￾ed for use in childhood, owing to hepatic failure in up to 1 in 2,000 children exposed [159]. If children develop adverse reactions while taking ATD, early surgery with total thyroidectomy is generally recommended. Over re￾cent years, more confidence has been gained about the safety of RAI, particularly in postpubertal younger peo￾ple [160]. Thus, long-term low-dose MMI (CBZ) fol￾lowed, if necessary, by surgery or RAI when the child reaches a suitable age (16 years or older) is frequently the sequence of therapy in this age group. Any episode of hyperthyroidism or hypothyroidism (as a consequence of treatment), will likely have an effect on educational progress, and this factor should be taken into account in all decision making. Recommendations 46 PTU should be avoided in children and adolescents. 1, ∅∅∅∅ 47 Long-term MMI (CBZ) should be the mainstay of treatment in children with GD. 1, ∅∅∅○ 48 Thyroidectomy is the primary definitive therapy in childhood, but in postpubertal children RAI can be considered. 2, ∅∅○○ Immune Reconstitution The first demonstration of immune reconstitution GD was in multiple sclerosis patients who had received lymphocyte-depleting alemtuzumab (Campath-H1) antibody treatment [161]. This treatment causes initial lymphopenia, but 12–24 months later 20–30% of pa￾tients developed TSH-R-Ab-positive GD, as lympho￾cyte populations recover. A similar pattern of GD has been observed in patients with HIV who have received effective highly active antiretroviral therapy, with hy￾perthyroidism developing as CD4 lymphocyte counts increase [162]. Immune reconstitution GD has also been observed in bone marrow transplant patients. In most cases, the hyperthyroidism is manageable and, de￾pending on the underlying condition, it is not an indi￾cation to discontinue the immunomodulatory therapy that precipitated it. Although initial reports suggested that definitive therapy was warranted in these patients, additional experience now suggests that they can be managed similarly to patients with “spontaneous” GD [163]. However, as the immunological “insult” may be transient in these cases, a reasonable approach is to treat with ATD until circulating TSH-R-Ab become un￾detectable. Recommendations 49 Graves’ hyperthyroidism precipitated by an immuno￾modulatory therapy is not a mandatory indication to stop that precipitating treatment, nor is it a mandatory indication for definitive therapy for hyperthyroidism. 1, ∅○○○ 50 Sequential monitoring of serum TSH-R-Ab levels can be used to guide the duration of ATD therapy in pa￾tients with immune reconstitution GD. 2, ∅○○○ Perspectives and Conclusions Ongoing preclinical and clinical trials are assessing the effectiveness of novel drugs and/or substances that could modify the natural history of GD by modulating its pathogenesis. These therapeutic agents include TSH-R monoclonal Abs [164], immunomodulatory TSH-R pep￾tides, and small-molecule TSH-R ligands [165] that can block the thyroid-stimulating effect of TSH-R-Ab, thus acting as TSH-R-Ab antagonists. However, the data are still too preliminary to predict whether these compounds will become available for the daily management of GD patients. Likewise, the use of biologicals, such as ritux￾imab, although based on a sound rationale, is not sup￾ported by sufficient evidence [166]. Currently the opti￾mal management depends on patient preference and specific patient clinical features such as age, history of arrhythmia or ischemic heart disease, size of goiter, and severity of thyrotoxicosis. Since each of the treatment modalities has unique limitations and adverse conse￾quences, physicians need to be familiar with the advan￾tages and disadvantages of each therapy in order to best counsel their patients. The target audience for this guideline are physicians providing care for patients with GD. In this document ra￾tional medical practice is outlined. This guideline does not replace clinical judgment, individual decision making, or the wishes of the patient or family. Rather, each recom￾mendation should be evaluated in light of these elements in order that optimal patient care is delivered. When the level of care required is best provided in centers where there is specific expertise, referral to such centers should be considered. The 50 recommendations that form these guidelines are presented together in Table 6. http://guide.medlive.cn/