Untreated GD Persistent Relapse Hyperthyroidism () At18(36)m After stopping MMI MMI(CBZ) or Definitive or treatment RAl or Tx or MVP on Th Table3.Adverse events of antithyroid drugs CI 21.66-108.22).In Caucasians,a different HLA-Ballele (B*27:05;OR7.3,95%CI3.81-l3.96)and rare NOX3 Com Aaila,porahrits MMICBd PTUrience similar incidence rates Fever 701 In a study c ing 71.379 ATD initiato gf711 Abnormalities of taste and smell MMI was associated in a dose-dependent manner with an increased risk for hepatitis and cholestasis.ATD are stopped and not restarted ifa patient develops major side effects.Patients should be given written instructions re- er,mouth s)and the neec nd ete Recommendations 10 Patients should be informed of potential side effectsof ATD and the necessity of informing the physician promptly if they should develop jaundice,light-col- Kahaly/Bartalena/Hegeduis/Leenhardt/ Poppe/Pearce 医脉通 http://guide.medlive.cn/
Kahaly/Bartalena/Hegedüs/Leenhardt/ Poppe/Pearce 172 Eur Thyroid J 2018;7:167–186 DOI: 10.1159/000490384 CI 21.66–108.22). In Caucasians, a different HLA-B allele (B*27:05; OR 7.3, 95% CI 3.81–13.96) and rare NOX3 variants have been tentatively associated [68, 69]. MMI (CBZ) and PTU exert dissimilar incidence rates of hepatotoxicity. PTU-associated hepatotoxicity occurs foremost in children in contrast to that associated with MMI, which is usually milder with a cholestatic pattern [70]. In a study comprising 71,379 ATD initiators [71], MMI was associated in a dose-dependent manner with an increased risk for hepatitis and cholestasis. ATD are stopped and not restarted if a patient develops major side effects. Patients should be given written instructions regarding the symptoms of possible agranulocytosis (e.g., sore throat, fever, mouth ulcers) and the need to stop treatment pending a complete blood count. The use of routine hematological and liver function tests is not useful, as the onset of agranulocytosis is abrupt [56]. Recommendations 10 Patients should be informed of potential side effects of ATD and the necessity of informing the physician promptly if they should develop jaundice, light-colTable 3. Adverse events of antithyroid drugs Common (1.0–5.0%) Skin rash Urticaria Arthralgia, polyarthritis Fever Transient mild leukopenia Rare (0.2–1.0%) Gastrointestinal Abnormalities of taste and smell Agranulocytosis Very rare (<0.1%) Aplastic anemia (PTU, CBZ) Thrombocytopenia (PTU, CBZ) Vasculitis, lupus-like, ANCA+ (PTU) Hepatitis (PTU) Hypoglycemia (anti-insulin Abs; PTU) Cholestatic jaundice (CBZ/MMI) PTU, propylthiouracil; MMI, methimazole; CBZ, carbimazole; ANCA, antineutrophil cytoplasmic antibody. negative Untreated GD Persistent Hyperthyroidism Relapse MMI (CBZ) Adults: 18 months Children: 36 months - MMI intolerance - Noncompliance Tx - Nodules - Goiter ˃50 mL - Active GO MMI for further 12 months Recent onset (adults & children) At 18 (36) months positive TSH-R-Ab After stopping MMI Long-term low-dose MMI Then TSH-R-Ab measurement Definitive treatment RAI or or or or or positive Personal decision RAI - Small thyroid - No / inactive GO Stop MMI RAI or Tx Tx Fig. 2. Algorithm for the management of a patient with Graves’ hyperthyroidism. GD, Graves’ disease; MMI, methimazole; CBZ, carbimazole; GO, Graves’ orbitopathy; RAI, radioactive iodine; Tx, total thyroidectomy. http://guide.medlive.cn/
ored stools,dark urine,fever,pharyngitis,or cystitis. 000o on in the MMI group (p<0.001) 11 In patients taking ATD,a differential white blood cell Graves'orbitopathy(GO)deterioration was higher post count should be obtained during febrile illness and/or RAI(p<0.0005)over all periods of follow-up (OR 21.1. pharyngitis,and liver function should be assessed in 95%CI 1.5-298,p<0.0003).Patients gained more weight those who experience jaundice,light-colored stools,or post-RAI(p<0. 05).Thus,low MMI doses were efficient dark urine.l,☑☑o○ han RAl trea Reta-Adrenergic rlockade cting be ta-blockers (ie ATDdid not exceed that of RA rolol).are useful to con trol adrenergic symptoms such as palpitations and trem- Recommendation or,especially in the early stages before ATD take effect. 13 Ifa patient with GD becomes hyperthyroid after com High doses of propranolol (40 mg 4 times daily)inhibit pleting a first course of ATD,definitive treatment with 山芒 Continue ong-term low-do can arepresentan ayor pat onsidered in all natien Subclinical graves'hyperthyroidism n is used increased doses are often needed in the thyro Endogenous mild or subclinical hyperthyroidism(SH) toxic state [2.5.6.721 is associated with increased risk of coronary heart disease mortality,incident atrial fibrillation,heart failure,frac Recommendation tures,and excess mortality in patients with serum TSH 12E a-adrenergic blockade is reco TS-R-Ab Relapse after yroi 3 of pro up to A meta nalysis [731 high relaps rate following ATD therapy (52.7%)in co aparison with er than 65 vears witha TSH that is persistently <0.1 mIU/L %coRaano to potentially avoid these serious adverse events and the risk of progression to overt hyperthyroidism.Treatment Another meta-analysisevalua ating 54 trials and 7,595 par- might be considered in patientsoder than 65 years with cipants showec eral risk fac .39 mlU/L t their increase 70) tal TOr Spuedictimseod and TSE king,thyr tion,and might als 5 year ially in PGREAT score for prese e of risk factors or hyperthyroidism relapsed within 2 years after ATD with. recommendations drawal.Lower age,higher serum TSH-R-Ab and free T4, 14Treatment of SH is recommended in Graves'patients larger goiters at diagnosis,PTPN22 C/T polymorphism >65 years with serum TSH levels that are persistently and HLA subtypes DQB1*02,DQA1*05,and DRB1*03 0.1mlU/ ,0000 e the first choice of treatment of Graves ong-term ATD SH.1.000 GD relapse after the dis soAahen 12-24 months 176).Either RAI treatment and L-T4 re With a mortality rate estimated at 10%,the life-threat- placement or MMI (2.5-7 mg/daily)were used.No no- ening thyroid storm demands a rapid diagnosis and table side effects were observed.Thyroid dysfunction was emergency treatment [84,85].The condition manifests 13 医通 http://guide.medlive.cn/
2018 ETA Guideline for the Management of Graves’ Hyperthyroidism Eur Thyroid J 2018;7:167–186 173 DOI: 10.1159/000490384 ored stools, dark urine, fever, pharyngitis, or cystitis. 1, ∅∅○○ 11 In patients taking ATD, a differential white blood cell count should be obtained during febrile illness and/or pharyngitis, and liver function should be assessed in those who experience jaundice, light-colored stools, or dark urine. 1, ∅∅○○ Beta-Adrenergic Blockade Propranolol (20–40 mg every 6 h) or longer acting beta-blockers (i.e., atenolol/bisoprolol), are useful to control adrenergic symptoms such as palpitations and tremor, especially in the early stages before ATD take effect. High doses of propranolol (40 mg 4 times daily) inhibit peripheral conversion of T4 to T3. Cardioselective betablockers with higher cardioprotective effects and superior prevention of atrial fibrillation represent an alternative choice, especially for patients with asthma. Anticoagulation with warfarin or direct oral anticoagulants should be considered in all patients with atrial fibrillation. If digoxin is used, increased doses are often needed in the thyrotoxic state [2, 5, 6, 72]. Recommendation 12 Beta-adrenergic blockade is recommended in all suitable patients with Graves’ hyperthyroidism. 1, ∅∅∅∅ Relapse after a Course of ATD Treatment A meta-analysis [73] has confirmed the high relapse rate following ATD therapy (52.7%) in comparison with RAI (15%, OR 6.25) or surgery (10%, OR 9.09), along with a significant side-effect profile for these drugs (13%). Another meta-analysis evaluating 54 trials and 7,595 participants showed several risk factors predicting persistence (49%) in GD [74]. Orbitopathy, smoking, thyroid volume, free T4, total T3, and TSH-R-Ab were significantly associated with relapse. In a prospective study introducing the quantitative predictive “GREAT” score for GD [75], 37% of patients with a first episode of Graves’ hyperthyroidism relapsed within 2 years after ATD withdrawal. Lower age, higher serum TSH-R-Ab and free T4, larger goiters at diagnosis, PTPN22 C/T polymorphism, and HLA subtypes DQB1*02, DQA1*05, and DRB1*03 were independent predictors for recurrence. On the other hand, the benefits of long-term ATD treatment after recurrence were shown in patients with GD relapse after the discontinuation of ATD therapy for 12–24 months [76]. Either RAI treatment and L-T4 replacement or MMI (2.5–7 mg/daily) were used. No notable side effects were observed. Thyroid dysfunction was predominant in the RAI group (p < 0.001), and euthyroidism was more common in the MMI group (p < 0.001). Graves’ orbitopathy (GO) deterioration was higher postRAI (p < 0.0005) over all periods of follow-up (OR 21.1, 95% CI 1.5–298, p < 0.0003). Patients gained more weight post-RAI (p < 0.005). Thus, low MMI doses were efficient, safe, and offered better outcomes for GO than RAI treatment. In another trial [77], long-term MMI treatment of GD was safe, while the complications and expenses of ATD did not exceed that of RAI. Recommendation 13 If a patient with GD becomes hyperthyroid after completing a first course of ATD, definitive treatment with RAI or thyroidectomy is recommended. Continued long-term low-dose MMI can be considered in patients not in remission who prefer this approach. 1, ∅∅∅○ Subclinical Graves’ Hyperthyroidism Endogenous mild or subclinical hyperthyroidism (SH) is associated with increased risk of coronary heart disease mortality, incident atrial fibrillation, heart failure, fractures, and excess mortality in patients with serum TSH levels <0.1 mIU/L [78–82]. In addition, in the presence of TSH-R-Ab indicating “subclinical” GD, the rate of progression to overt hyperthyroidism is up to 30% in the subsequent 3 years [83]. Therefore, despite the absence of randomized trials, treatment is indicated in patients older than 65 years with a TSH that is persistently <0.1 mIU/L to potentially avoid these serious adverse events and the risk of progression to overt hyperthyroidism. Treatment might be considered in patients older than 65 years with TSH levels of 0.1–0.39 mIU/L because of their increased risk of atrial fibrillation, and might also be reasonable in younger (<65 years) symptomatic patients with TSH <0.1 mIU/L because of the risk of progression, especially in the presence of risk factors or comorbidity. Recommendations 14 Treatment of SH is recommended in Graves’ patients >65 years with serum TSH levels that are persistently <0.1 mIU/L. 1, ∅∅○○ 15 ATD should be the first choice of treatment of Graves’ SH. 1, ∅∅○○ Thyroid Storm With a mortality rate estimated at 10%, the life-threatening thyroid storm demands a rapid diagnosis and emergency treatment [84, 85]. The condition manifests http://guide.medlive.cn/