今日の臨床サポート

甲状腺機能亢進症・バセドウ病

著者: 吉村弘 伊藤病院

監修: 平田結喜緒 公益財団法人 兵庫県予防医学協会 健康ライフプラザ

著者校正/監修レビュー済:2021/01/13
参考ガイドライン:
  1. 日本甲状腺学会:バセドウ病治療ガイドライン2019
患者向け説明資料

概要・推奨   

  1. FT3・FT4高値、TSH低下の検査結果では、TRAb(感度、特異度とも95%以上)を測定し、バセドウ病と他の甲状腺中毒症を起こす疾患の鑑別を行うことが勧められる(推奨度1)(エビデンスレベル CJ)
  1. バセドウ病の薬物治療の第一選択薬は、妊娠初期(器官形成期の4週0日から15週6日)を除き、チアマゾールとする(推奨度1)(エビデンスレベル JG)。
  1. 妊娠初期は催奇形性の観点から妊娠5週0日から9週6日まではチアマゾールを避けるべきである(推奨度1(エビデンスレベル OJG)。
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  1. バセドウ病の初期治療では、軽症(例えばFT4が5ng/dl以下の症例)ではチアマゾール15mg/日、中等度から重症(例えばFT4が5ng/dl以上の例)ではチアマゾール15mg/日とヨウ化カリウム丸[50mg]1錠で治療開始することが勧められる(推奨度1)(エビデンスレベル RsJ)。
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薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
吉村弘 : 特に申告事項無し[2021年]
監修:平田結喜緒 : 特に申告事項無し[2021年]

改訂のポイント:
  1. 定期レビューを行い「バセドウ病診断フローチャート」について修正を行った。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 甲状腺中毒症は、組織内での甲状腺ホルモン作用が上昇し全身の代謝が亢進する病態の総称であり、下記の3種類がある。
  1. 甲状腺機能亢進症
  1. 破壊性甲状腺炎
  1. 外部からの甲状腺ホルモン過剰摂取
  1. 甲状腺機能亢進症では、甲状腺ホルモンの産生・分泌が亢進するために、甲状腺ホルモン作用が過剰な状態となる。
  1. 甲状腺機能亢進症で、最も多い疾患は、バセドウ病(グレーブス病)である。その他の鑑別として、中毒性結節性甲状腺腫、ヒト絨毛性ゴナドトロピン(hCG)高値による妊娠初期の一過性甲状腺機能亢進症、まれではあるがTSH産生下垂体腫瘍、甲状腺ホルモン不応症、TSHレセプター遺伝子異常症などがある。
  1. 破壊性甲状腺炎では、甲状腺の破壊により血液中に甲状腺ホルモンが漏れ出すために甲状腺中毒症状を呈す。原因疾患としては、無痛性甲状腺炎、亜急性甲状腺炎、橋本病の急性増悪がある。
  1. 甲状腺中毒症で、バセドウ病との鑑別で最も重要なのは、無痛性甲状腺炎である。
  1. 甲状腺機能亢進症を生じる疾患の一部である甲状腺ホルモン不応症、下垂体性TSH分泌亢進症は指定難病であり、重症度分類で重症の場合などでは申請し認定されると、保険料の自己負担分の一部が公費負担として助成される。
    平成27年1月施行
    平成27年1月施行
  1. 難病法に基づく医療費助成制度
病歴・診察のポイント  
  1. ヨウ素の過剰摂取の有無(昆布、昆布だし、根昆布、ヨウ素を含むうがい薬)、卵管造影検査の既往を確認する。

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文献 

著者: Taku Kashiwai, Yoh Hidaka, Toru Takano, Ke-ita Tatsumi, Yukiko Izumi, Yuki Shimaoka, Hisato Tada, Keiko Takeoka, Nobuyuki Amino
雑誌名: Endocr J. 2003 Feb;50(1):45-9.
Abstract/Text Although many researchers have reported clinical and laboratory parameters for prediction of remission in Graves' disease during or after anti-thyroid drug therapy, there is no reliable one to assure the complete remission. We prospectively examined a practical therapy with minimum maintenance dose of anti-thyroid drugs for prediction of remission in Graves' disease. Fifty-seven patients with Graves' disease were treated with anti-thyroid drugs at the initial dose of 30 mg/day of methimazole (MMI) or 300 mg/day of propylthiouracil (PTU). Then, doses were gradually decreased, and finally discontinued when the patients were able to maintain euthyroid (normal FT4 and TSH) for at least 6 months with the minimum maintenance dose (MMI 5 mg every other day or PTU 50 mg every other day). After discontinuation of drugs, FT4, FT3, TSH and TSH-binding inhibitory immunoglobulin (TBII) were measured every one to two months for the first 6 months and every 3-4 months for the next 18 months to confirm continuous remission. After 2 years of drug cessation, 46 (81%) of 57 patients were in remission and the other 11 patients had relapsed into thyrotoxicosis. At the time of drug discontinuation, the serum concentration of FT4, FT3 and TSH, titers of anti-thyroglobulin antibodies and anti-thyroid microsomal antibodies, goiter size were not different between the remission and relapse groups. At the time of drug cessation, the activities of TBII and thyroid-stimulating antibodies (TSAb) overlapped between the two groups, although they were significantly lower in the remission group than in the relapse group (p<0.01). Forty percent (4/10) of TBII positive patients and 71% (23/32) of TSAb positive patients continued to be in remission. On the other hand, thyrotoxicosis relapsed in 5 (11%) of 47 TBII negative and 2 (8%) of 25 TSAb negative patients. These data indicate that minimum maintenance therapy to keep euthyroid (normal FT4 and TSH) for 6 months is a practical measure for 81% prediction of remission in Graves' disease. The measurement of TBII or TSAb gave little additional information for predicting remission.

PMID 12733708  Endocr J. 2003 Feb;50(1):45-9.
著者: Jaeduk Yoshimura Noh, Naoko Miyazaki, Koichi Ito, Kyoko Takeda, Sonoe Hiramatsu, Shinji Morita, Akira Miyauchi, Tsukasa Murakami, Keiko Inomata, Shiro Noguchi, Tomoaki Satoh, Nobuyuki Amino
雑誌名: Thyroid. 2008 Nov;18(11):1157-64. doi: 10.1089/thy.2008.0119.
Abstract/Text BACKGROUND: Hyperthyroidism in Graves' disease is caused by autoantibodies to the TSH receptor (TSHR), and measurement of the TSHR autoantibody (TRAb) yields important information to diagnose and decide on the course of treatment of Graves' disease. We evaluated basic and clinical performance of a new, rapid, and fully automated electrochemiluminescence immunoassay Elecsys Anti-TSHR (Elecsys TRAb) for measuring serum TRAb.
METHODS: For evaluation of basic performance of the assay, we carried out intra- and interassay precision studies using five serum pools and three serum pools, respectively, and the assay was compared with four commercial TRAb assays. Clinical performance of the assay was evaluated with sera from 298 patients with untreated Graves' disease, 220 patients with destructive (painless and subacute) thyroiditis, and 332 healthy volunteers. The optimal cutoff point, which was calculated by receiver operating characteristic (ROC) analysis with the above subjects, was then used to classify an independent sample set of 80 patients with untreated Graves' disease, and 152 patients with destructive thyroiditis.
RESULTS: Intraassay coefficient of variation (CV) was 4.24% at 1.85 IU/L and interassay CV was 10.1% at 1.46 IU/L. All the correlation coefficient values calculated against four commercial assays were larger than 0.85. ROC analysis resulted in a specificity of 99.1% with a sensitivity of 97.0% at a decision limit of 1.86 IU/L from comparison with untreated Graves' disease and destructive thyroiditis. The cutoff point yielded a sensitivity of 87.5% and specificity of 96.7% with the independent sample set.
CONCLUSION: In spite of the short measuring time of only 27 minutes, the assay showed the same or better results with the existing commercial products. The short measuring time would contribute to speedy, preconsultation diagnosis of thyroid disease, especially of Graves' disease.

PMID 19014323  Thyroid. 2008 Nov;18(11):1157-64. doi: 10.1089/thy.2008・・・
著者: Nami Suzuki, Jaeduk Yoshimura Noh, Marino Hiruma, Akiko Kawaguchi, Mitsuha Morisaki, Hidemi Ohye, Miho Suzuki, Masako Matsumoto, Yo Kunii, Kenji Iwaku, Ai Yoshihara, Natsuko Watanabe, Kiminori Sugino, Kochi Ito
雑誌名: Thyroid. 2019 Oct;29(10):1390-1398. doi: 10.1089/thy.2019.0045. Epub 2019 Oct 1.
Abstract/Text Background: The prevalence of antithyroid drug (ATD)-related drug-induced liver injury (DILI) has been reported to vary among patients in several countries. The purpose of this study was to summarize the prevalence of liver injury induced by ATD and to determine the actual prevalence of severe liver injury. Methods: The medical records of 18,558 patients who were newly diagnosed with Graves' disease between January 2005 and December 2016 were retrospectively reviewed. Severe DILI was defined as alanine aminotransferase (ALT) 8 times higher than the upper limit of normal (ULN) or total bilirubin (T-bil) 3 times higher than the ULN. The most severe DILI was defined as ALT higher than 20 times the ULN or T-bil higher than 10 times the ULN. Results: A total of 461 subjects (470 cases) were analyzed, and they consisted of 10 males and 451 females, with a median age of 37 years (range 10-82 years). Nine of 461 patients had severe DILI with both drugs. The total prevalence of severe DILI in this study was 2.5%, and the prevalence of DILI by drug was 1.4% with metimazole (MMI) (n = 198) and 6.3% with propylthiouracil (PTU) (n = 272) (p < 0.001). The prevalence of the most severe ATD-related DILI was 0.22% (n = 40), and the prevalence for each drug was 0.08% with MMI (n = 11) and 0.68% with PTU (n = 29). The median time to DILI development was 30 days (range 7-314 days), and all patients recovered from DILI, with no fatalities. The prevalence of MMI-related DILI was significantly age dependent (p < 0.001). Conclusions: Though there were no fatalities in this study, the prevalence of PTU-related severe DILI was significantly higher than that of MMI-related severe DILI.

PMID 31573408  Thyroid. 2019 Oct;29(10):1390-1398. doi: 10.1089/thy.20・・・
著者: K Yoshiuchi, H Kumano, S Nomura, H Yoshimura, K Ito, Y Kanaji, T Kuboki, H Suematsu
雑誌名: Psychosom Med. 1998 Sep-Oct;60(5):592-6.
Abstract/Text OBJECTIVE: Although psychological stress and smoking have been proposed as factors contributing to Graves' disease, their independent roles in the course of this disease have not been determined. We assessed the association between the course of Graves' disease and psychosocial factors by using multivariate analysis.
METHODS: We investigated the association between the short-term outcome of Graves' disease (assessed 12 months after the beginning of antithyroid drug therapy) and stressful life events, daily hassles, smoking, drinking habits, coping skills, and social support (before and 6 months after beginning therapy) in 230 patients (182 women and 48 men) with newly diagnosed Graves' disease, using a logistic regression model.
RESULTS: After adjustment for smoking, coping skills, and thyroid function, daily hassles scores in women at 6 months after beginning therapy were significantly associated with a hyperthyroid state 12 months after beginning therapy. The relative risk was 3.9 for women with higher daily hassles scores compared with women with lower daily hassles scores (95% confidence interval, 1.1 to 13.2; p < .05). Smoking was not significantly associated with a hyperthyroid state 12 months after beginning therapy in either women or men.
CONCLUSIONS: Chronic psychological stress is associated with the course of Graves' disease in women.

PMID 9773763  Psychosom Med. 1998 Sep-Oct;60(5):592-6.
著者: Peter Vestergaard
雑誌名: Eur J Endocrinol. 2002 Feb;146(2):153-61.
Abstract/Text BACKGROUND: Smoking has been associated with Graves' disease, but it remains unclear if the association is present in other thyroid disorders.
OUTCOME VARIABLES: Graves' disease, Graves' ophthalmopathy, toxic nodular goitre, non-toxic goitre, post-partum thyroid disease, Hashimoto's thyroiditis, or hypothyroidism.
MATERIAL AND METHODS: A search of MEDLINE identified 25 studies on the association between smoking and thyroid diseases.
RESULTS: In Graves' disease eight studies were available showing an odds ratio (OR) of 3.30 (95% confidence interval (CI): 2.09-5.22) in current smokers compared with never smokers. In ex-smokers there was no significant excess risk of Graves' disease (OR=1.41, 95% CI: 0.77-2.58). The OR associated with ever smoking in Graves' ophthalmopathy (4.40, 95% CI: 2.88-6.73, six studies) was significantly higher than in Graves' disease (1.90, 95% CI: 1.42-2.55, two-sided P-value <0.01). Ever smoking was not associated with toxic nodular goitre (OR=1.27, 95% CI: 0.69-2.33, three studies), while there was an increased risk of non-toxic goitre in smokers if men were excluded (OR=1.29, 95% CI: 1.01-1.65, eight studies). The risk associated with smoking was significantly lower in men than in women for both Graves' disease and non-toxic goitre. Hashimoto's thyroiditis and post-partum thyroid dysfunction were also associated with smoking while the association with hypothyroidism did not reach statistical significance.
CONCLUSIONS: Cessation of smoking seems associated with a lower risk of Graves' disease than current smoking. Smoking increases the risk of Graves' ophthalmopathy beyond the risk associated with Graves' disease alone. Smoking cessation may lead to a decrease in morbidity from Graves' disease, especially in women.

PMID 11834423  Eur J Endocrinol. 2002 Feb;146(2):153-61.
著者: Shotaro Sato, Jaeduk Yoshimura Noh, Shiori Sato, Miho Suzuki, Shigemitsu Yasuda, Masako Matsumoto, Yo Kunii, Koji Mukasa, Kiminori Sugino, Koichi Ito, Shigenobu Nagataki, Matsuo Taniyama
雑誌名: Thyroid. 2015 Jan;25(1):43-50. doi: 10.1089/thy.2014.0084.
Abstract/Text BACKGROUND: Methimazole (MMI) is usually used at an initial dose of 30 mg/day for severe Graves' disease (GD) hyperthyroidism, but adverse effects are more frequent at this dose than at MMI 15 mg/day.
OBJECTIVES: We designed a regimen to address the lack of a primary therapeutic effect of the MMI 15 mg/day by combining it with inorganic iodine at 38.2 mg/day. Our aim was to compare the two regimens (MMI 15 mg+inorganic iodine at 38.2 mg/day (M15+I) vs. MMI 30 mg/day (M30)) in terms of therapeutic effect, adverse effects, and remission rate.
DESIGN AND PATIENTS: In a prospective study, 310 patients with untreated GD (serum free thyroxine (fT4) ≥5 ng/dL) were assigned to one of the two regimens. Potassium iodide was discontinued in the M15+I group as soon as the serum fT4 level was within the reference range (0.8-1.6 ng/dL).
RESULTS: Percentages of patients achieving an fT4 level within reference range in ≤30, ≤60, or 90 days on the study treatment regimens were 45.3%, 73.9%, and 82.0% respectively for the M15+I group, and 24.8%, 63.1%, and 75.2% respectively for the M30 group. Hence, the proportions of patients achieving this goal in ≤30 or ≤60 days were significantly larger in the M15+I group. Adverse effects that required discontinuation of MMI were more frequent in the M30-treated than in the M15+I-treated group (14.8% vs. 7.5%; p=0.0387). The remission rates in the M15+I and M30 groups were 19.9% and 14.8%-higher in the former, but the difference did not reach statistical significance.
CONCLUSION: The results of this study raise the possibility that M15+I is superior to M30 as a primary treatment for moderate to severe hyperthyroidism caused by GD.

PMID 25178068  Thyroid. 2015 Jan;25(1):43-50. doi: 10.1089/thy.2014.00・・・
著者: Ai Yoshihara, JaedukYoshimura Noh, Takuhiro Yamaguchi, Hidemi Ohye, Shiori Sato, Kenichi Sekiya, Yuka Kosuga, Miho Suzuki, Masako Matsumoto, Yo Kunii, Natsuko Watanabe, Koji Mukasa, Kunihiko Ito, Koichi Ito
雑誌名: J Clin Endocrinol Metab. 2012 Jul;97(7):2396-403. doi: 10.1210/jc.2011-2860. Epub 2012 Apr 30.
Abstract/Text BACKGROUND: Several reports have suggested that propylthiouracil (PTU) may be safer than methimazole (MMI) for treating thyrotoxicosis during pregnancy because congenital malformations have been associated with the use of MMI during pregnancy.
OBJECTIVES: We investigated whether in utero exposure to antithyroid drugs resulted in a higher rate of major malformations than among the infants born to a control group of pregnant women.
METHODS: We reviewed the cases of women with Graves' disease who became pregnant. The pregnancy outcomes of 6744 women were known, and there were 5967 live births. MMI alone had been used to treat 1426 of the women, and 1578 women had been treated with PTU alone. The 2065 women who had received no medication for the treatment of Graves' disease during the first trimester served as the control group. The remaining women had been treated with potassium iodide, levothyroxine, or more than one drug during the first trimester. The antithyroid drugs were evaluated for associations with congenital malformations.
RESULTS: The overall rate of major anomalies in the MMI group was 4.1% (50 of 1231), and it was significantly higher than the 2.1% (40 of 1906) in the control group (P = 0.002), but there was no increase in the overall rate of major anomalies in the PTU group in comparison with the control group (1.9%; 21 of 1399; P = 0.709). Seven of the 1231 newborns in the MMI group had aplasia cutis congenita, six had an omphalocele, seven had a symptomatic omphalomesenteric duct anomaly, and one had esophageal atresia. Hyperthyroidism in the first trimester of pregnancy did not increase the rate of congenital malformation.
CONCLUSIONS: In utero exposure to MMI during the first trimester of pregnancy increased the rate of congenital malformations, and it significantly increased the rate of aplasia cutis congenita, omphalocele, and a symptomatic omphalomesenteric duct anomaly.

PMID 22547422  J Clin Endocrinol Metab. 2012 Jul;97(7):2396-403. doi: ・・・
著者: T Hiraiwa, M Ito, A Imagawa, J Takamatsu, K Kuma, A Miyauchi, T Hanafusa
雑誌名: J Endocrinol Invest. 2006 Apr;29(4):380-4.
Abstract/Text The close relationship between iodine intake and the effects of anti-thyroid drugs (ATD) for Graves' disease (GD) has been well established. However, it remains unknown whether restriction of dietary iodine improves the effect of ATD. This study aimed to clarify this issue in Japanese patients with GD who routinely ingest large amounts of dietary iodine. We performed a prospective clinical study in 81 patients with newly diagnosed GD who were divided into an iodine restricted group and a control group. Urinary iodine, thyroid hormones and TSH receptor antibody were measured during the first 8 weeks of ATD therapy. Urinary iodine concentrations in the iodine restricted group were significantly lower than in the control group (p=0.043). However, there were no significant differences in the decrease of thyroid hormones and TSH receptor antibody between the two groups. Restriction of dietary iodine does not ameliorate the effect of ATD therapy for GD in an area of excessive iodine intake.

PMID 16699308  J Endocrinol Invest. 2006 Apr;29(4):380-4.
著者: Kazuna Takata, Sumihisa Kubota, Shuji Fukata, Takumi Kudo, Eijun Nishihara, Mitsuru Ito, Nobuyuki Amino, Akira Miyauchi
雑誌名: Thyroid. 2009 Jun;19(6):559-63. doi: 10.1089/thy.2008.0364.
Abstract/Text BACKGROUND: Antithyroid drugs (ATDs) are prescribed as the initial therapy for the majority of patients with Graves' disease in many areas of the world. Although, it is well known that agranulocytosis is one of the most serious side effects of ATDs, there has not yet been any conclusive evidence that the prevalence of agranulocytosis induced by ATDs is dose related. This study was performed to determine if the prevalence of agranulocytosis is different depending on the starting dosage of ATDs in patients with Graves' disease.
METHODS: Until 1996, we had typically prescribed 30 mg/d of methimazole (MMI) as the initial dosage for the treatment of Graves' disease at our institution. We changed the initial MMI dosage to 15 mg/d as a general rule in 1997. As a consequence, we acquired two groups of patients with Graves' disease who received different dosages of MMI. We retrospectively compared the prevalence of MMI-induced agranulocytosis in patients who received 15 mg/d of MMI to those who received 30 mg/d of MMI.
RESULTS: There were 2087 subjects treated with 30 mg/d of MMI and 2739 treated with 15 mg/d of MMI. The prevalence of agranulocytosis in the 30 mg/d group was significantly higher than in the 15 mg/d group (0.814% vs. 0.219%, respectively, p < 0.01). The prevalence of agranulocytosis plus neutropenia in the 30 mg/d group was also significantly higher than in the 15 mg/d group (1.581% vs. 0.474%, respectively, p < 0.001).
CONCLUSIONS: It is very likely that MMI-induced agranulocytosis occurs with a larger dosage of MMI and is dose related. Considering both the effectiveness and the risk of serious side effects, we recommend 15 mg/d of MMI as the starting dosage for the treatment of Graves' disease.

PMID 19445623  Thyroid. 2009 Jun;19(6):559-63. doi: 10.1089/thy.2008.0・・・
著者: J Tajiri, S Noguchi, T Murakami, N Murakami
雑誌名: Arch Intern Med. 1990 Mar;150(3):621-4.
Abstract/Text This study was aimed at establishing the importance of routine monitoring of white blood cell counts in patients with Graves' disease receiving antithyroid drug treatment. In the 12-year period from 1975 to 1987, 15,398 patients with Graves' disease receiving treatment with antithyroid drugs were seen at our clinic. Of these, 55 (0.4%) were found to have agranulocytosis. Agranulocytosis was defined as a granulocyte count of 0.5 x 10(9)/L or less. In only 12 of the 55 patients was agranulocytosis detected after the occurrence of infection (symptomatic; classic agranulocytosis). The remaining 43 patients were asymptomatic when agranulocytosis was detected during routine white blood cell count monitoring. However, 14 of these 43 patients became symptomatic several days after withdrawal of antithyroid drug treatment despite antimicrobial treatment (asymptomatic to symptomatic). Twenty-nine patients who were treated appropriately had no symptom of infection throughout the course of the disease, despite the absence of or an extremely small number of granulocytes in circulation (asymptomatic). These results suggest that a "routine monitoring" of the white blood cell count could be the most effective way of predicting and detecting agranulocytosis due to antithyroid drug treatment.

PMID 2310281  Arch Intern Med. 1990 Mar;150(3):621-4.
著者: Jaeduk Yoshimura Noh, Shigemitu Yasuda, Shotaro Sato, Masako Matsumoto, Yo Kunii, Yoshihiko Noguchi, Koji Mukasa, Kunihiko Ito, Koichi Ito, Osamu Sugiyama, Hiroshi Kobayashi, Shigeru Nihojima, Masaru Okazaki, Shunji Yokoyama
雑誌名: J Clin Endocrinol Metab. 2009 Aug;94(8):2806-11. doi: 10.1210/jc.2008-2700. Epub 2009 Jun 2.
Abstract/Text CONTEXT: The clinical characteristics of myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA)-associated vasculitis caused by antithyroid drugs are still unclear because most reports describe only a small number of patients.
OBJECTIVE: The objective was to analyze a large number of patients with MPO-ANCA-associated vasculitis to determine the time of onset, the drug and dose taken, the clinical symptoms, the relationship between the clinical symptoms and the MPO-ANCA titer, and the incidence.
DESIGN: We analyzed 92 patients in whom the adverse reaction of MPO-ANCA-associated vasculitis was reported to Chugai Pharmaceutical, a company that markets antithyroid drugs.
RESULTS: Of the 92 patients, 41 (44.6%) had single-organ failure, 32 (34.8%) had two-organ failure, 13 (14.1%), had three-organ failure, and two (2.2%) had four-organ failure. The number of organs involved was unknown in the other four patients (4.3%). The median time of onset was 42 months (range, 1-372 months) after starting drug treatment. The median dose at onset of MPO-ANCA-associated vasculitis was 15 mg/d (range, 2.5-45 mg/d) for methimazole and 200 mg/d (50-450 mg/d) for propylthiouracil. The severity and number of organs involved were not correlated with the MPO-ANCA titer. The incidence was between 0.53 and 0.79 patients per 10,000, and the ratio of the estimated incidences for methimazole and propylthiouracil was 1:39.2.
CONCLUSIONS: The time of onset of MPO-ANCA-associated vasculitis and the dose at onset varied. The severity and number of organs involved were not correlated with the MPO-ANCA titer, indicating a need for vigilance even when the MPO-ANCA titer is only weakly positive.

PMID 19491223  J Clin Endocrinol Metab. 2009 Aug;94(8):2806-11. doi: 1・・・

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