as decompensation of multiple organs with impaired ralysis are candidates for RAI.Only one study has com- consciousness,high fever,heart failure,diarrhea,and pared the ATD,surgery,and RAI head-to-head [90].In in pa- tients with severe Graves't ferences in sic m, e p which Point Scale” the aim of ranid hynothyroidism other side-effects are manifestations,with a point total of 245 consistent with not different from those in adults [95].RAIis contraindi- thyroid storm,25-44 points classified as impending thy- cated in pregnancy and during breast feeding,and con roid storm,and <25 points indicating that thyroid storm ception should be postponed until at least 6 months after onw mental effectso idity a aormvynalgothscoanod the therapy.There is noevidence of det ty rate ong-term ty,misc ns,or c quently offe MMI mu month per dnisol nle iv heta-hlocker anolol 4p thyroidism and postponing hypot mon cause of death from thyroid storm was multiple or- many have given up meticulous dose calculation and of- gan failure,followed by heart and respiratory failure,ar- fer fixed activities of,for example,185,370,or 555 MBq rhythmia,disseminated intravascular coagulation,gas based on validated clinical parameters,such as thyroic size89. Effect o y tion in 3-12 month 16A multimodality treatment after RAI ther in 50-90%of patients [89].The patient used,including ATD therapy,glucocorticoid administration,beta-adrener should bein med that repeated doses of RAI may be needed.The incidence rate of hypothyroidism is 5-50% gic blockade,cooling blankets,volume resuscitation, after the first vear,and is positively associated with the nutritional support,respiratory care,and monitoring thyroid RAI dose.This s is followed by a yearly hypothy in an intensive care unit.1,C ism rate of 3-5%,wh ch is largely independent of the RA 97 Even w been few since 19 h sm is there have ble 198).Thy ective trials le ntra ndicated in lar dose,efficacy,and partially retrosternal or intrathoracic.ATD should be side-effects ).The cellular effect of the ionizing radia- temporarily paused for a week before and after RAI ther- tionleads to genetic damage,mutations,or celldeath.The apy [99]. DNA damage from radiation is mediated via a combi nation of direct ects,thi Adverse Effects of RAI Therapy thyroid fu here may be th d pain,swelli cals.Thi n and/o on orb3andsaloaden rideal methods of 100,101.I 102 radio e do es not ir tality (89) e is nei predicting the clinical response to RAI therapy 6 ed thyroid ca nor total ca mortality following RAI therapy 1031.Posttherapy thv Indications and Applied RAI Dose roid storm is extremely rare,and in non-ATD-pretreated Patients with side-effectstoor recurrenceafteracourse patients TH levels are normally not elevated post-RAl of ATD,cardiac arrhythmias,and thyrotoxic periodic pa- but decline after a few days 104.Transient hyperthy Kahaly/Bartalena/Hegeduis/Leenhardt/ Poppe/Pearce 医通 http://guide.medlive.cn/ Kahaly/Bartalena/Hegedüs/Leenhardt/ Poppe/Pearce 174 Eur Thyroid J 2018;7:167–186 DOI: 10.1159/000490384 as decompensation of multiple organs with impaired consciousness, high fever, heart failure, diarrhea, and jaundice. Diagnostic criteria for thyroid storm in pa￾tients with severe Graves’ thyrotoxicosis include hyper￾pyrexia, tachycardia, arrhythmia, congestive heart fail￾ure, agitation, delirium, psychosis, stupor, coma, nausea, vomiting, diarrhea, hepatic failure, and the presence of an identified precipitant [86]. The “Burch-Wartofsky Point Scale” system grades the severity of individual manifestations, with a point total of ≥45 consistent with thyroid storm, 25–44 points classified as impending thy￾roid storm, and <25 points indicating that thyroid storm as unlikely. Nationwide surveys in Japan have revealed the high morbidity and mortality rates of this condition and have subsequently offered a multimodality treat￾ment, including intravenous MMI or PTU (40 or 400 mg every 8 h), glucocorticoids (methylprednisolone 50 mg i.v.), beta-blockers (propranolol 40 mg every 6 h), and monitoring in an intensive care unit [87]. The most com￾mon cause of death from thyroid storm was multiple or￾gan failure, followed by heart and respiratory failure, ar￾rhythmia, disseminated intravascular coagulation, gas￾trointestinal perforation, hypoxic brain syndrome, and sepsis [88]. Recommendation 16 A multimodality treatment approach to GD patients with thyroid storm should be used, including ATD therapy, glucocorticoid administration, beta-adrener￾gic blockade, cooling blankets, volume resuscitation, nutritional support, respiratory care, and monitoring in an intensive care unit. 1, ∅∅○○ RAI Treatment RAI has been used since 1941; however, there have been few well-designed prospective trials, leaving many questions about indications, optimal dose, efficacy, and side-effects [89]. The cellular effect of the ionizing radia￾tion leads to genetic damage, mutations, or cell death. The DNA damage from radiation is mediated via a combi￾nation of direct effects, through breakage of molecular bonds, or indirectly through the formation of free radi￾cals. This leads to a decrease in thyroid function and/or reduction in thyroid size. There are neither good mea￾sures of individual radiosensitivity nor ideal methods of predicting the clinical response to RAI therapy. Indications and Applied RAI Dose Patients with side-effects to or recurrence after a course of ATD, cardiac arrhythmias, and thyrotoxic periodic pa￾ralysis are candidates for RAI. Only one study has com￾pared the ATD, surgery, and RAI head-to-head [90]. In that randomized study, the risk of relapse was highest af￾ter ATD, but there were no significant differences in sick leave or satisfaction with the therapy. There are contra￾dictory reports pertaining to the cost effectiveness of GD treatment [91–94]. Some centers use RAI in pediatric pa￾tients, in which case ablative doses should be used with the aim of rapid hypothyroidism. Other side-effects are not different from those in adults [95]. RAI is contraindi￾cated in pregnancy and during breast feeding, and con￾ception should be postponed until at least 6 months after the therapy. There is no evidence of detrimental effects on long-term fertility, miscarriage, stillbirths, or congenital defects in the offspring [96]. The same 6-month period applies for males. ALARA (as low as reasonably achiev￾able) is an important principle with radiation treatment, but an elusive goal when balancing rapid relief of hyper￾thyroidism and postponing hypothyroidism. Therefore, many have given up meticulous dose calculation and of￾fer fixed activities of, for example, 185, 370, or 555 MBq, based on validated clinical parameters, such as thyroid size [89]. Effect on Thyroid Function and Size Thyroid function is normalized within 3–12 months after RAI therapy in 50–90% of patients [89]. The patient should be informed that repeated doses of RAI may be needed. The incidence rate of hypothyroidism is 5–50% after the first year, and is positively associated with the thyroid RAI dose. This is followed by a yearly hypothy￾roidism rate of 3–5%, which is largely independent of the RAI dose [97]. Even with low-dose RAI, which increases persistent/recurrent disease, hypothyroidism is inevita￾ble [98]. Thyroid size is normalized within a year of RAI [97]. RAI is not contraindicated in large goiters, even if partially retrosternal or intrathoracic. ATD should be temporarily paused for a week before and after RAI ther￾apy [99]. Adverse Effects of RAI Therapy There may be thyroid pain, swelling, and sialoadenitis. GD is associated with increased morbidity and mortality [100, 101]. Its treatment decreases mortality [102], while RAI per se does not increase mortality [89]. There is nei￾ther evidence of increased thyroid cancer nor total cancer mortality following RAI therapy [103]. Posttherapy thy￾roid storm is extremely rare, and in non-ATD-pretreated patients TH levels are normally not elevated post-RAI, but decline after a few days [104]. Transient hyperthy￾http://guide.medlive.cn/