今日の臨床サポート

橋本病

著者: 伊藤光泰 名駅前診療所保健医療センター

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:2021/01/07
参考ガイドライン:
  1. 日本甲状腺学会:甲状腺疾患診断ガイドライン2013 慢性甲状腺炎(橋本病)の診断ガイドライン
患者向け説明資料

概要・推奨   

  1. 橋本病の診断には甲状腺超音波よりも血中抗甲状腺抗体の測定が重要である(推奨度1)。
  1. 橋本病による甲状腺機能低下症に対して食事中のヨードを制限すると甲状腺機能低下症が改善するので、ヨード過剰が疑われる場合にはまずヨード制限をすることが勧められる(推奨度1)
  1. 750μg/日以上のヨード摂取は、特に甲状腺機能低下症境界領域にある患者には有害な作用をもたらす。マイクロゾーム(TPO)抗体陽性の人はヨードの摂取を控えるように勧める(推奨度1)
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  1. 甲状腺機能低下症に対するL-T4補充療法をL-T3とL-T4の併用に切り替えても健康感、認知機能への効果は変わらないので、変更する必要はない(推奨度3)。
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  1. 甲状腺自己免疫は甲状腺機能低下症あるいは不妊に関連するので、甲状腺疾患の既往あるいは家族歴のある場合、甲状腺腫のある場合、ほかの自己免疫疾患のある場合、不妊あるいは甲状腺疾患を疑う症状・所見がある場合には、甲状腺自己抗体と血清TSHとFT4の測定が推奨される(推奨度2)。ただし、スクリーニング検査と介入治療までは現時点で推奨されていない(推奨度3)。
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  1. L-T4は食事の影響を受けにくい早朝空腹時が望ましい(推奨度2)。
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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:
伊藤光泰 : 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、橋本病とIgG4関連疾患あるいは甲状腺原発のリンパ腫について加筆修正を行った。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 橋本病とは、甲状腺の自己免疫疾患の一種で、自己抗体とリンパ球湿潤を伴う組織破壊を認める疾患である。
  1. 橋本病は、びまん性の甲状腺腫を認め、血液検査で自己抗体である抗甲状腺マイクロゾーム〔または甲状腺ペルオキシダーゼ(TPO)〕抗体か、抗サイログロブリン抗体が陽性であることにより診断する。
  1. 抗体が陰性であっても、細胞診でリンパ球浸潤を認めることにより診断することもできる。
  1. びまん性甲状腺腫大は、 バセドウ病 など他の原因が認められないことを確認しておく。
  1. 甲状腺腫または、甲状腺機能低下症の症状を認める患者の初診時のフローチャート:アルゴリズム
  1. 疾患の頻度は高く、わが国においては50歳以上の女性で20%以上にみられるとされる。米国の調査では5.1%とされる。女性は男性の3.7~12.5倍と、頻度が高い。
  1.  甲状腺機能低下症 を合併することもあり、合併例ではこれも診断し、併せて治療を開始することが勧められる。
  1. 甲状腺機能が正常であっても、妊娠・出産を契機に一過性あるいは永続性に甲状腺機能低下症や 甲状腺機能亢進症 を発症することがあるので、妊娠・出産の可能性があるときには経過を見ることが勧められる。
  1. 甲状腺機能が正常でも、加齢とともに低下症になっていくことがあるので、定期的に診断し、経過観察することが勧められる。
  1. ヨードの過剰摂取により 甲状腺機能低下症 になりやすいので、日常生活の指導を行うことが勧められる。
  1. 抗甲状腺自己抗体(特に抗TPO抗体)陽性例では妊娠中の合併症に注意する。
  1. 潜在性甲状腺機能低下症は妊娠時合併症を生じやすいので、妊娠前にTSHは2.5を超えないようにする。
 
  1. 甲状腺自己免疫は甲状腺機能低下症と関連し流産、早産などの合併症に関連するので、抗甲状腺自己抗体陽性の妊娠では流産や早産に注意が必要である(推奨度2)
  1. 研究背景:甲状腺自己免疫と流産に関する多くの観察研究がある。これらの研究は、流産例は甲状腺自己抗体の陽性者が陰性者より明らかに多いことを示している。
  1. 研究事例:Poppe KとGlinoer Dは1990年から2001年の13の報告を検討し、12の報告で、流産例は甲状腺自己抗体陽性例が陰性例より多いことを示した。13の報告のうち10の報告では統計学的に有意な差であった[1]。一方、抗甲状腺抗体陽性あるいはTSH2.5mIU/L以上の潜在性甲状腺機能低下症は影響しないとする報告もある。Negroらの報告ではL-T4治療で甲状腺機能正常者は甲状腺機能正常の抗体陽性者および対照群と流産率に差がなかった[2]
  1. 結論:甲状腺自己抗体が陽性の妊娠では流産に注意する。流産を繰り返す症例では甲状腺自己抗体の測定が有用である。
 
  1. 妊娠初期の潜在性を含む甲状腺機能低下症と抗甲状腺自己抗体の存在は妊娠合併症を伴いやすいので、TSHを含めて甲状腺機能を正常に保つことが勧められる(推奨度1)
  1. 研究背景:母体と胎児が甲状腺機能低下症であることは胎児に重篤な障害を生じる。甲状腺自己免疫は妊娠中に早産などの合併症を生じやすい。
  1. 研究事例:Negro Rらは984例の妊婦を対象に、11.7%の抗TPO抗体陽性例を無作為に2群に分けL-T4投与群(57例)と非投与群(58例)および抗体陰性群で妊娠中の合併症の発生率を前向き試験で調べた。抗TPO抗体陽性群は陰性群よりTSH値が高かった。L-T4投与群は非投与群に比べてTSHが低くなり、合併症の発生率も低く抗体陰性群と同様であった[3]
  1. Van den Boogaard Eらは43の論文のシステマチックレビューとそのうちの38をメタ解析して、妊娠初期の潜在性甲状腺機能低下症では妊娠高血圧症候群のオッズ比が1.7(95%CI:1.1~2.6)、周産期死亡率のオッズ比が2.7(95%CI:1.6~4.7)と高いことを示した[4]。メタ解析では、抗甲状腺自己抗体の存在は説明不可能な受胎力の低下(オッズ比1.5、95%CI:1.1~2.0)、流産(オッズ比3.73、95%CI:1.8~7.6)、習慣流産(オッズ比2.3、95%CI:1.5~3.5)、早産(オッズ比1.9、95%CI:1.1~3.5)、母体の分娩後甲状腺炎(オッズ比11.5、95%CI:5.6~24)とリスクを高めることを示した。
  1. 結論:妊娠中の甲状腺機能低下症は、たとえ潜在性であっても避けるべきである。妊娠前にTSHは2.5mIU/Lを超えないようにしておくべきである。抗TPO抗体陽性例にL-T4を投与することで妊娠に伴う合併症の発症率を抑えることができる。
 
  1. 抗TPO抗体陽性の妊婦は出産3~6カ月後に血清TSHを測定すべきである(推奨度1)
  1. 研究背景:抗甲状腺自己抗体のある妊婦は出産後に甲状腺機能異常を起こす頻度が高い。
  1. 研究事例:抗TPO抗体陽性の妊婦は出産後甲状腺機能異常を起こす頻度が高いので血清TSHを測定する。1型糖尿病の妊婦も出産後甲状腺機能異常を起こす頻度が一般妊婦より3倍高い。出産後甲状腺機能異常の既往を有する妊婦は5~10年後の間に永続性の甲状腺機能低下症をおこす頻度が高い。
  1. 結論:抗TPO抗体陽性、1型糖尿病、および出産後甲状腺機能異常の既往のある妊婦は出産3~6カ月後に血清TSHを測定すべきである。
 
  1. 橋本病による甲状腺機能低下症に対して食事中のヨードを制限すると甲状腺機能低下症が改善するので、ヨード過剰が疑われる場合にはまずヨード制限をすることが勧められる(推奨度1)
  1. 研究背景:過剰なヨード摂取が橋本病において甲状腺機能低下症を引き起こすことが知られている。
  1. 研究事例:Yoon SJらは橋本病の患者を2群に分け、1群は100μg/日以下のヨード制限食にして、もう1群はヨード制限なしとしたところ、3カ月後にヨード制限食の群では78.3%に甲状腺機能の改善がみられた[5]
  1. 結論:橋本病による甲状腺機能低下症では、ヨード制限により甲状腺機能が回復する。制限前にTSHが低く尿中ヨードが高い患者は、回復する可能性が高いのでヨード制限が勧められる。
  1. 追記:妊娠可能な女性の平均ヨード摂取量は150μg/日が推奨されている。妊娠および授乳期には平均250μg/日の摂取が推奨されている。
 
  1. 橋本病では血清25-水酸化ビタミンDの低下がみられ、ビタミンD の投与により血清TSHと抗サイログロブリン抗体の低下がみられるため血清25-水酸化ビタミンDの測定を考慮する。
  1. 研究背景:ビタミンDが免疫応答に関与することが知られるようになり自己免疫疾患である橋本病と血清ビタミンDとの関連の研究についてメタ解析された。
  1. 研究事例:Stefanic Mらは26の橋本病における血清25-水酸化ビタミンDの研究をメタ解析して25について低下を認めた[6]
  1. 結論:血中25-水酸化ビタミンDは橋本病と関連性がある。
  1. 追記:Chahardoli Rらは橋本病に5万国際単位のビタミンDまたはプラセボを投与して甲状腺機能と抗甲状腺抗体を測定した無作為2重盲検試験を行った。ビタミンDの投与により血清TSHと抗サイログロブリン抗体の低下がみられたが抗甲状腺ペルオキシダーゼ抗体には変化がなかったためビタミンDによる橋本病の病態への影響はまだ結論が出ていない[7]
 
  1. 橋本病の一部にIgG4陽性細胞が甲状腺内に浸潤したIgG4関連疾患とされる慢性甲状腺炎があり乳頭癌の合併が多いことに注意する。
  1. 研究背景:IgG4関連疾患の中にRiedel甲状腺炎に類似した橋本病の所見を呈するものがありその臨床像が検討された。
  1. 研究事例:Li YらはIgG4陽性細胞を有する橋本病を対象例と比較して男性に多く、機能低下症への進行が強く、超音波像で低エコー像が強いこと、抗体価が高いことを認め[8]、Yu YらはIgG4陽性橋本病では乳頭癌の合併が多いことを認めた[9]
  1. 結論:橋本病の一部にIgG4関連甲状腺炎があり異なる臨床像を呈する。症例数が少ないためより多くの検討が必要である。
病歴・診察のポイント  
  1. 耐寒性低下、体重増加、便秘、月経不順など不定愁訴と間違えやすい症状が多いので注意する。

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文献 

著者: Kris Poppe, Daniel Glinoer
雑誌名: Hum Reprod Update. 2003 Mar-Apr;9(2):149-61.
Abstract/Text In the present review, an attempt was made to describe current knowledge and concepts concerning the complex relationships that link thyroid autoimmunity (TAI) and hypothyroidism with female and male infertility, as well as abnormalities occurring during pregnancy, such as pregnancy loss and maternal and fetal repercussions associated with hypothyroidism. In the case of infertility, although the clinical relevance of TAI is somewhat controversial, when all available information is considered the results strongly suggest that when infertility is due to well-defined female causes, autoimmunity is involved and TAI constitutes a useful marker of the underlying immune abnormality, independently of thyroid function disorders. In the case of pregnancy loss, the vast majority of available studies clearly establish that TAI (even with no overt thyroid dysfunction) is associated with a significant increase in miscarriage risk. To find an association, however, does not imply a causal relationship, and the aetiology of increased pregnancy loss associated with TAI remains presently not completely understood. With regard to maternal repercussions during gestation, the main risk associated with TAI is the occurrence of hypothyroidism and obstetric complications (premature birth, pre-eclampsia, etc.). Thus, systematic screening of TAI and hypothyroidism during early pregnancy, monitoring of thyroid function with/without L-thyroxine treatment and follow-up during post-partum have proved helpful and important in order to manage these patients adequately. Finally, with regard to potential repercussions affecting the offspring, recent evidence suggests that thyroid maternal underfunction, even when considered mild (or subclinical), may be associated with an impairment of fetal brain development. When present only during the first half of gestation, maternal hypothyroxinaemia is a risk factor for impaired fetal brain development, due to insufficient transfer of maternal thyroid hormones to the feto-placental unit. When hypothyroidism is not restricted to the first trimester and worsens as gestation progresses (as in untreated hypothyroidism), the fetus may also be deprived of adequate amounts of thyroid hormones during later neurological maturation and development, leading to poorer school performance and lower IQ.

PMID 12751777  Hum Reprod Update. 2003 Mar-Apr;9(2):149-61.
著者: Roberto Negro, Alan Schwartz, Alex Stagnaro-Green
雑誌名: J Clin Endocrinol Metab. 2016 Oct;101(10):3685-3690. doi: 10.1210/jc.2016-1803. Epub 2016 Jul 26.
Abstract/Text BACKGROUND: Thyroid disease during pregnancy is associated with multiple adverse maternal and fetal outcomes. In particular, multiple observational studies have demonstrated an association between the presence of thyroid antibodies in euthyroid women in the first trimester of miscarriage and an increased rate of spontaneous miscarriage and preterm delivery. The present study is a prospective intervention trial of the effect of levothyroxine on the rate of miscarriage and preterm delivery in euthyroid thyroid-antibody positive women in the first trimester of pregnancy.
METHODS: A total of 8530 women in the first trimester of pregnancy in Southern Italy were screened for TSH and thyroid antibodies. Group A consisted of 198 euthyroid thyroid antibody positive women treated with levothyroxine, group B consisted of 195 untreated euthyroid thyroid antibody positive women, and group C consisted of 197 untreated thyroid antibody negative women.
RESULTS: The rate of miscarriage did not differ between the 3 groups (11.6%, 14.9%, and 8.1 %, P = .11). The rate of preterm delivery between the 3 groups was 6.9%, 10.8%, and 2.8% and was statistically significant (P = .01). The rate of preterm delivery was significantly different between groups B and C (P = .02) but was not significantly different between groups A and B (P = .27).
CONCLUSIONS: In conclusion, the present study found that levothyroxine intervention had no impact on the rate of miscarriage and preterm delivery in euthyroid thyroid antibody positive women.

PMID 27459527  J Clin Endocrinol Metab. 2016 Oct;101(10):3685-3690. do・・・
著者: Roberto Negro, Gianni Formoso, Tiziana Mangieri, Antonio Pezzarossa, Davide Dazzi, Haslinda Hassan
雑誌名: J Clin Endocrinol Metab. 2006 Jul;91(7):2587-91. doi: 10.1210/jc.2005-1603. Epub 2006 Apr 18.
Abstract/Text CONTEXT: Euthyroid women with autoimmune thyroid disease show impairment of thyroid function during gestation and seem to suffer from a higher rate of obstetrical complications.
OBJECTIVE: We sought to determine whether these women suffer from a higher rate of obstetrical complications and whether levothyroxine (LT(4)) treatment exerts beneficial effects.
DESIGN: This was a prospective study.
SETTING: The study was conducted in the Department of Obstetrics and Gynecology.
PATIENTS: A total of 984 pregnant women were studied from November 2002 to October 2004; 11.7% were thyroid peroxidase antibody positive (TPOAb(+)).
INTERVENTION: TPOAb(+) patients were divided into two groups: group A (n = 57) was treated with LT(4), and group B (n = 58) was not treated. The 869 TPOAb(-) patients (group C) served as a normal population control group.
MAIN OUTCOME MEASURES: Rates of obstetrical complications in treated and untreated groups were measured.
RESULTS: At baseline, TPOAb(+) had higher TSH compared with TPOAb(-); TSH remained higher in group B compared with groups A and C throughout gestation. Free T(4) values were lower in group B than groups A and C after 30 wk and after parturition. Groups A and C showed a similar miscarriage rate (3.5 and 2.4%, respectively), which was lower than group B (13.8%) [P < 0.05; relative risk (RR), 1.72; 95% confidence interval (CI), 1.13-2.25; and P < 0.01; RR = 4.95; 95% CI = 2.59-9.48, respectively]. Group B displayed a 22.4% rate of premature deliveries, which was higher than group A (7%) (P < 0.05; RR = 1.66; 95% CI = 1.18-2.34) and group C (8.2%) (P < 0.01; RR = 12.18; 95% CI = 7.93-18.7).
CONCLUSIONS: Euthyroid pregnant women who are positive for TPOAb develop impaired thyroid function, which is associated with an increased risk of miscarriage and premature deliveries. Substitutive treatment with LT(4) is able to lower the chance of miscarriage and premature delivery.

PMID 16621910  J Clin Endocrinol Metab. 2006 Jul;91(7):2587-91. doi: 1・・・
著者: Emmy van den Boogaard, Rosa Vissenberg, Jolande A Land, Madelon van Wely, Joris A M van der Post, Mariette Goddijn, Peter H Bisschop
雑誌名: Hum Reprod Update. 2011 Sep-Oct;17(5):605-19. doi: 10.1093/humupd/dmr024. Epub 2011 May 28.
Abstract/Text BACKGROUND: Thyroid dysfunction and thyroid autoimmunity are prevalent among women of reproductive age and are associated with adverse pregnancy outcomes. Preconception or early pregnancy screening for thyroid dysfunction has been proposed but is not widely accepted. We conducted a systematic review of the literature on the clinical significance of thyroid dysfunction and thyroid autoimmunity before conception and in early pregnancy.
METHODS: Relevant studies were identified by searching Medline, EMBASE and the Cochrane Controlled Trials Register.
RESULTS: From a total of 14 208 primary selected titles, 43 articles were included for the systematic review and 38 were appropriate for meta-analyses. No articles about hyperthyroidism were selected. Subclinical hypothyroidism in early pregnancy, compared with normal thyroid function, was associated with the occurrence of pre-eclampsia [odds ratio (OR) 1.7, 95% confidence interval (CI) 1.1-2.6] and an increased risk of perinatal mortality (OR 2.7, 95% CI 1.6-4.7). In the meta-analyses, the presence of thyroid antibodies was associated with an increased risk of unexplained subfertility (OR 1.5, 95% CI 1.1-2.0), miscarriage (OR 3.73, 95% CI 1.8-7.6), recurrent miscarriage (OR 2.3, 95% CI 1.5-3.5), preterm birth (OR 1.9, 95% CI 1.1-3.5) and maternal post-partum thyroiditis (OR 11.5, 95% CI 5.6-24) when compared with the absence of thyroid antibodies.
CONCLUSIONS: Pregnant women with subclinical hypothyroidism or thyroid antibodies have an increased risk of complications, especially pre-eclampsia, perinatal mortality and (recurrent) miscarriage. Future research, within the setting of clinical trials, should focus on the potential health gain of identification, and effect of treatment, of thyroid disease on pregnancy outcome.

PMID 21622978  Hum Reprod Update. 2011 Sep-Oct;17(5):605-19. doi: 10.1・・・
著者: Soo-Jee Yoon, So-Rae Choi, Dol-Mi Kim, Jun-Uh Kim, Kyung-Wook Kim, Chul-Woo Ahn, Bong-Soo Cha, Sung-Kil Lim, Kyung-Rae Kim, Hyun-Chul Lee, Kap-Bum Huh
雑誌名: Yonsei Med J. 2003 Apr 30;44(2):227-35.
Abstract/Text Lifelong thyroid hormone replacement is indicated in patients with hypothyroidism as a result of Hashimoto's thyroiditis. However, previous reports have shown that excess iodine induces hypothyroidism in Hashimoto's thyroiditis. This study investigated the effects of iodine restriction on the thyroid function and the predictable factors for recovery in patients with hypothyroidism due to Hashimoto's thyroiditis. The subject group consisted of 45 patients who had initially been diagnosed with hypothyroidism due to Hashimoto's thyroiditis. The subjects were divided randomly into two groups. One group was an iodine intake restriction group (group 1) (iodine intake: less than 100 micro g/day) and the other group was an iodine intake non-restriction group (group 2). The thyroid-related hormones and the urinary excretion of iodine were measured at the baseline state and after 3 months. After 3 months, a recovery to the euthyroid state was found in 78.3 % of group 1 (18 out of 23 patients), which is higher than the 45.5% from group 2 (10 out of 22 patients). In group 1, mean serum fT4 level (0.80 +/- 0.27 ng/dL at the baseline, 0.98 +/- 0.21 ng/dL after 3 months) and the TSH level (37.95 +/- 81.76 micro IU/mL at the baseline, 25.66 +/- 70.79 micro IU/mL after 3 months) changed significantly during this period (p < 0.05). In group 2, the mean serum fT4 level decreased (0.98 +/- 0.17 ng/dL at baseline, 0.92 +/- 0.28 ng/dL after 3 months, p < 0.05). In the iodine restriction group, the urinary iodine excretion values were higher in the recovered patients than in non-recovered patients (3.51 +/- 1.62 mg/L vs. 1.21 +/- 0.39 mg/ L, p=0.006) and the initial serum TSH values were lower in the recovered patients than in the non-recovered patients (14.28 +/- 12.63 micro IU/mL vs. 123.14 +/- 156.51 micro IU/mL, p=0.005). In conclusion, 78.3% of patients with hypothyroidism due to Hashimoto's thyroiditis regained an euthyroid state iodine restriction alone. Both a low initial serum TSH and a high initial urinary iodine concentration can be predictable factors for a recovery from hypothyroidism due to Hashimoto's thyroiditis after restricting their iodine intake.

PMID 12728462  Yonsei Med J. 2003 Apr 30;44(2):227-35.
著者: Mario Štefanić, Stana Tokić
雑誌名: Eur J Nutr. 2019 May 14;. doi: 10.1007/s00394-019-01991-w. Epub 2019 May 14.
Abstract/Text PURPOSE: Available evidence on the relation between vitamin D status and Hashimoto's thyroiditis (HT) remains inconsistent. We conducted a meta-analysis of serum 25-hydoxyvitamin [25(OH)D] concentrations in HT, and examined how the strength of this relationship varies as a function of several moderating factors.
METHODS: Twenty-six observational, case-control studies, published before Feb 20, 2018, were located using Google Scholar, PubMed, Web of Science, SCOPUS, LILACS and SCIELO. Study quality was assessed and random-effects models were used, along with univariate mixed-effect meta-regression, for all analyses.
RESULTS: The 25 studies (2695 cases, 2263 controls) confirmed lower serum 25(OH)D concentrations in HT compared to healthy controls, with Cohen's d - 0.62 (95% CI - 0.89, - 0.34; P = 1.5 × 10-5) and substantial heterogeneity between studies. HT showed an odds ratio (OR) of 3.21 (1.94-5.3; P = 5.7 × 10-6) for 25(OH)D deficiency (cut-off 20 ng/mL) against healthy controls. A corrected Cohen's d of - 0.43 [(- 0.76, - 0.09), P = 0.013] was obtained by trim-and-fill adjustment for publication bias. The association was consistent across Asian and European studies, pediatric and adult population, high- and moderate-quality studies. Near-equatorial latitudes (< 35° N/S, P = 3.4 × 10-4) and moderate-income economy (gross national income (GNI) 1000 < US$ < 12,000, P = 0.012) were associated with more discrepant 25(OH)D concentrations between the groups. Higher latitude (P = 0.0047), and higher mean body mass index (P = 0.006, 10 studies) were associated with smaller Cohen's d by univariate meta-regression, with evidence of nonlinear moderation by GNI (P = 3.5 × 10-6), and mean serum thyrotropin in affected individuals (P = 0.017, 21 studies).
CONCLUSION: The present work shows a significant association between circulating 25(OH)D and HT, partly resolves mixed findings by identifying the empirical moderators contributing to overall heterogeneity, and highlights HT patient groups and the conditions under which the association is strongest.

PMID 31089869  Eur J Nutr. 2019 May 14;. doi: 10.1007/s00394-019-01991・・・
著者: Reza Chahardoli, Ali-Akbar Saboor-Yaraghi, Atieh Amouzegar, Davood Khalili, Azita Zadeh Vakili, Fereidoun Azizi
雑誌名: Horm Metab Res. 2019 May;51(5):296-301. doi: 10.1055/a-0856-1044. Epub 2019 May 9.
Abstract/Text Hashimoto's thyroiditis (HT) is the most prevalent autoimmune disorder characterized by the destruction of thyroid cells caused by leukocytes and antibody-mediated immune processes accompanied by hypothyroidism. In recent years, evidence has emerged pointing to various roles for vitamin D, including, proliferation and differentiation of normal and cancer cells, cardiovascular function, and immunomodulation. Vitamin D deficiency has been especially demonstrated in HT patients. The aim of this study was to investigate the effect of vitamin D on circulating thyroid autoantibodies and thyroid hormones profile (T4, T3, and TSH) in females with HT. Forty-two women with HT disease were enrolled in this randomized clinical trial study and divided into vitamin D and placebo groups. Patients in the vitamin D and placebo groups received 50 000 IU vitamin D and placebo pearls, weekly for 3 months, respectively. The serum levels of 25-hydroxy vitamin D [25(OH) D], Ca++ion, anti-thyroperoxidase antibody (anti-TPO Ab), anti-thyroglobulin antibody (anti-Tg Ab), T4, T3, and TSH were measured at the baseline and at the end of the study using enzyme-linked immunosorbent assays. The results of this study showed a significant reduction of anti-Tg Ab and TSH hormone in the Vitamin D group compared to the start of the study; however, there was a no significant reduction of anti-TPO Ab in the Vitamin D group compared to the placebo group (p=0.08). No significant changes were observed in the serum levels of T3 and T4 hormones. Therefore, vitamin D supplementation can be helpful for alleviation of the disease activity in HT patients; however, further well controlled, large, longitudinal studies are needed to determine whether it can be introduced in clinical practice.

© Georg Thieme Verlag KG Stuttgart · New York.
PMID 31071734  Horm Metab Res. 2019 May;51(5):296-301. doi: 10.1055/a-・・・
著者: Yang Yu, Jing Zhang, Guizhi Lu, Ting Li, Yang Zhang, Nan Yu, Ying Gao, Yanming Gao, Xiaohui Guo
雑誌名: J Clin Endocrinol Metab. 2016 Apr;101(4):1516-24. doi: 10.1210/jc.2015-3783. Epub 2016 Feb 11.
Abstract/Text CONTEXT: Hashimoto's thyroiditis (HT) can be divided into IgG4-positive and IgG4-negative HT. The potential association between IgG4-positive HT and papillary thyroid carcinoma (PTC) remains poorly understood.
OBJECTIVE: The aim was to investigate the relationship between IgG4-positive HT and PTC and to compare the prognostic parameters of PTC patients with and without IgG4-positive HT.
DESIGN: This was a retrospective study.
PATIENTS AND SETTING: A total of 66 HT patients (18 HT-alone, 48 HT with PTC) with serum samples stored before the operation were collected. Another 18 PTC-alone patients were collected as controls.
MAIN OUTCOMES: Expression of IgG4, IgG, and TGF-β1 in thyroid tissues and serum levels of IgG4, TgAb IgG, TgAb IgG4, TPOAb IgG, and TPOAb IgG4 were measured.
RESULTS: Seventeen HT patients with PTC (35.4%) were IgG4-positive HT, whereas only one patient (5.6%) was found to be IgG4-positive in the HT-alone group. In contrast, there were only a few IgG4-positive plasma cells in the PTC-alone group. The association of IgG4-positive HT and PTC was statistically significant (P < .05). Moreover, serum levels of TgAb IgG4 and the ratios of TgAb IgG4 to TgAb IgG were significantly higher in the HT with PTC and the PTC-alone groups than in the HT-alone group (P < .05). Furthermore, in the HT with PTC group, the average tumor diameter of 17 IgG4-positive HT with PTC patients was 1.7 ± 0.8 cm, whereas of 31 IgG4-negative HT patients with PTC, the diameter was 1.2 ± 0.6 cm (P = .01). A considerably higher percentage of lymph node metastasis (41.2% vs 12.9%; P = .026) was found in PTC patients with IgG4-positive HT as compared with those with IgG4-negative HT.
CONCLUSION: PTC may be facilitated by preexisting autoimmune inflammation of IgG4-positive HT. IgG4-positive HT with PTC cases may have worse clinical outcomes. The high levels of TgAb IgG4 might present a risk factor for PTC.

PMID 26866571  J Clin Endocrinol Metab. 2016 Apr;101(4):1516-24. doi: ・・・
著者: Fotini K Kavvoura, Takashi Akamizu, Takuya Awata, Yoshiyuki Ban, Dimitry A Chistiakov, Irena Frydecka, Abbas Ghaderi, Stephen C Gough, Yuji Hiromatsu, Rafal Ploski, Pei-Wen Wang, Yoshio Ban, Tomasz Bednarczuk, Emma I Chistiakova, Marcin Chojm, Joanne M Heward, Hitomi Hiratani, Suh-Hang Hank Juo, Lidia Karabon, Shigehiro Katayama, Susumu Kurihara, Rue-Tsuan Liu, Ikuyo Miyake, Gholam-Hossein R Omrani, Edyta Pawlak, Matsuo Taniyama, Teruaki Tozaki, John P A Ioannidis
雑誌名: J Clin Endocrinol Metab. 2007 Aug;92(8):3162-70. doi: 10.1210/jc.2007-0147. Epub 2007 May 15.
Abstract/Text CONTEXT: Cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) polymorphisms have been widely examined for their associations with autoimmune thyroid diseases [Graves' disease (GD) and Hashimoto thyroiditis (HT)], but their relative population effect remains unclear.
OBJECTIVE: The aim was to generate large-scale evidence on whether the CTLA-4 polymorphisms (A49G and CT60) and haplotypes thereof increase the susceptibility to GD and/or HT.
DESIGN, SETTING, AND PARTICIPANTS: Meta-analyses of group-level data were reviewed from 32 (11,019 subjects) and 12 (4,479) published and unpublished studies for the association of the A49G polymorphism with GD and HT, respectively (PubMed and HuGeNet search until July 2006). There were 15 (n = 7246) and six (n = 3086) studies available for the CT60 polymorphism, respectively. Meta-analyses of individual-level data from 10 (4906 subjects) and five (2386) collaborating teams for GD and HT, respectively, were also reviewed.
MAIN OUTCOME MEASURES: Association of gene variants and haplotypes with GD and HT was measured.
RESULTS: Group-level data suggested significant associations with GD and HT for both A49G [odds ratios 1.49 (P = 6 x 10(-14)) and 1.29 (P = 0.001) per G allele, respectively] and CT60 [1.45 (P = 2 x 10(-9)) and 1.64 (P = 0.003) per G allele, respectively]. Results were consistent between Asian and Caucasian descent subjects. Individual-level data showed that compared with the AA haplotype, the risk conferred by the GG haplotype was 1.49 (95% confidence interval 1.31,1.70) and 1.36 (95% confidence interval 1.16,1.59) for GD and HT, respectively. Data were consistent with a dose-response effect for the G allele of CT60.
CONCLUSION: The CT60 polymorphism of CTLA-4 maps an important genetic determinant for the risk of both GD and HT across diverse populations.

PMID 17504905  J Clin Endocrinol Metab. 2007 Aug;92(8):3162-70. doi: 1・・・
著者: C C Chow, D I Phillips, J H Lazarus, A B Parkes
雑誌名: Clin Endocrinol (Oxf). 1991 May;34(5):413-6.
Abstract/Text OBJECTIVE The aim of the study was to evaluate the risk of exposure to an increase in dietary iodide intake amongst potentially susceptible population groups in Britain. DESIGN A randomized controlled trial was performed in healthy women and in women with underlying thyroid abnormalities due to subclinical Hashimoto's thyroiditis (diagnosed on the basis of antithyroid antibodies) or previous iodide deficiency of supplementation with 500 micrograms/day iodide (giving a total intake of approximately 750 micrograms/day) for 28 days versus placebo. PATIENTS Two hundred and twenty-five women aged 25-54, randomly selected from a general practice in Cardiff, were screened for thyroid microsomal antibody. Antibody positive women (n = 20), and antibody negative controls (n = 30) were recruited into the trial comparing iodide and placebo. In addition, groups of patients aged 60-75 randomly selected from the Cardiff practice (n = 29), an iodide sufficient area, and a practice in Dowlais (n = 35), a previously iodide deficient area, were also enrolled into the trial. MEASUREMENTS Changes in free thyroxine and thyrotrophin levels were measured after 14 and 28 days of iodide supplementation. RESULTS All the iodide supplemented groups responded in the same way with a small fall in free thyroxine and rise in thyrotrophin levels (combined fall in free thyroxine 14 days after the start of supplementation -1.22 (95% confidence interval -0.59 to -1.84) pmol/l and at 28 days -0.86 (-0.30 to -1.43) pmol/l and rise in thyrotrophin at 14 days 0.55 (0.19 to 0.92) mU/l and at 28 days 0.59 (0.12 to 1.07) mU/l). In two of the iodide supplemented subjects thyrotrophin levels rose above the laboratory reference range and in a further three subjects initially elevated thyrotrophin values increased further. In contrast, no changes in thyroid function were observed in the placebo treated controls and none developed biochemical hypothyroidism. CONCLUSIONS Dietary iodide intakes of 750 micrograms/day or more may adversely affect thyroid function, especially in individuals with borderline hypothyroidism.

PMID 2060151  Clin Endocrinol (Oxf). 1991 May;34(5):413-6.
著者: G J Kahaly, H P Dienes, J Beyer, G Hommel
雑誌名: Eur J Endocrinol. 1998 Sep;139(3):290-7.
Abstract/Text OBJECTIVE: Iodine is essential for normal thyroid function and the majority of individuals tolerate a wide range of dietary levels. However, a subset of individuals, on exposure to iodine, develop thyroid dysfunction. In this double-blind trial, we evaluated the efficacy and tolerability of low-dose iodine compared with those of levo-thyroxine (T4) in patients with endemic goitre.
METHODS: Sixty-two patients were assigned randomly to groups to receive iodine (0.5 mg/day) or T4 (0.125 mg/day) for 6 months. Subsequently, both groups were subject to placebo for another 6 months. Thyroid sonography, determination of thyroid-related hormones and antibodies, and urinary excretion of iodine were carried out at baseline and at 1, 6 and 12 months.
RESULTS: At 6 months, markedly increased urinary values of iodine were found in patients receiving iodine (36 microg/24 h at baseline, 415 microg/24 h at 6 months) compared with those receiving T4 (47 microg/ 24 h at baseline, 165 microg/24 h at 6 months; P < 0.0001 compared with iodine group). T4 administration engendered a greater (P < 0.01) decrease in thyroid volume (from 32 ml to 17 ml, P < 0.0001) than did intake of iodine (3 3 ml to 21 ml. P < 0.005). High microsomal and thyroglobulin autoantibody titres were present in six of 31 patients (19%) receiving iodine, and iodine-induced hypo- and hyperthyroidism developed in four and two of them, respectively. Fine-needle biopsy revealed marked lymphocyte infiltration in all six. After withdrawal of iodine thyroid dysfunction remitted spontaneously and antibody titres and lymphocyte infiltration decreased markedly. Follow-up of these six patients for an additional 3 years showed normalisation of antibody titres in four of them.
CONCLUSION: Although nearly comparable results were obtained with both treatment regimens regarding thyroid size, partly reversible iodine-induced thyroid dysfunction and autoimmunity were observed among patients with endemic goitre.

PMID 9758438  Eur J Endocrinol. 1998 Sep;139(3):290-7.
著者: W Reinhardt, M Luster, K H Rudorff, C Heckmann, S Petrasch, S Lederbogen, R Haase, B Saller, C Reiners, D Reinwein, K Mann
雑誌名: Eur J Endocrinol. 1998 Jul;139(1):23-8.
Abstract/Text OBJECTIVE: Several studies have suggested that iodine may influence thyroid hormone status, and perhaps antibody production, in patients with autoimmune thyroid disease. To date, studies have been carried out using large amounts of iodine. Therefore, we evaluated the effect of small doses of iodine on thyroid function and thyroid antibody levels in euthyroid patients with Hashimoto's thyroiditis who were living in an area of mild dietary iodine deficiency.
METHODS: Forty patients who tested positive for anti-thyroid (TPO) antibodies or with a moderate to severe hypoechogenic pattern on ultrasound received 250 microg potassium iodide daily for 4 months (range 2-13 months). An additional 43 patients positive for TPO antibodies or with hypoechogenicity on ultrasound served as a control group. All patients were TBII negative.
RESULTS: Seven patients in the iodine-treated group developed subclinical hypothyroidism and one patient became hypothyroid. Three of the seven who were subclinically hypothyroid became euthyroid again when iodine treatment was stopped. One patient developed hyperthyroidism with a concomitant increase in TBII titre to 17 U/l, but after iodine withdrawal this patient became euthyroid again. Only one patient in the control group developed subclinical hypothyroidism during the same time period. All nine patients who developed thyroid dysfunction had reduced echogenicity on ultrasound. Four of the eight patients who developed subclinical hypothyroidism had TSH concentrations greater than 3 mU/l. In 32 patients in the iodine-treated group and 42 in the control group, no significant changes in thyroid function, antibody titres or thyroid volume were observed.
CONCLUSIONS: Small amounts of supplementary iodine (250 microg) cause slight but significant changes in thyroid hormone function in predisposed individuals.

PMID 9703374  Eur J Endocrinol. 1998 Jul;139(1):23-8.
著者: Henry Völzke, Christian Schwahn, Henri Wallaschofski, Marcus Dörr
雑誌名: J Clin Endocrinol Metab. 2007 Jul;92(7):2421-9. doi: 10.1210/jc.2007-0179. Epub 2007 May 1.
Abstract/Text CONTEXT: Currently there is ongoing debate on whether subclinical and overt thyroid dysfunction may exert deleterious effects on the cardiovascular system with the consequence of increased mortality in affected individuals. We systematically review studies on the relation of thyroid dysfunction with all-cause and circulatory mortality questioning whether thyroid dysfunction is a causal factor for mortality.
METHODS: Two investigators independently searched the MEDLINE database. All case-control and cohort studies published in peer-reviewed journals were selected. Studies on nonthyroidal illness or low-T3 syndrome and reports from highly selected populations were not considered. Risk estimates from studies with appropriate adjustment for confounders were metaanalyzed.
RESULTS: Four among eight studies performed to investigate the association between hyperthyroidism and mortality revealed an increased risk of either all-cause or circulatory mortality. Only the minority of studies, however, adjusted analyses for relevant confounders besides age, sex, and race. Studies after radioiodine therapy were generally biased by indication. Findings from 11 studies that investigated the relation between hypothyroidism and mortality were highly discrepant and partly even mutually exclusive. Some of these discrepancies are explained by confounding and selection.
CONCLUSIONS: The currently available evidence for a causal relation of both hyperthyroidism and hypothyroidism with mortality is weak and should particularly not be used to decide whether patients with subclinical thyroid conditions should be treated. Very old individuals might represent an exception from this rule and may benefit from mildly reduced thyroid function, but this has to be substantiated by further research.

PMID 17473067  J Clin Endocrinol Metab. 2007 Jul;92(7):2421-9. doi: 10・・・
著者: Pavel Kolkhir, Elena Borzova, Clive Grattan, Riccardo Asero, Dmitry Pogorelov, Marcus Maurer
雑誌名: Autoimmun Rev. 2017 Dec;16(12):1196-1208. doi: 10.1016/j.autrev.2017.10.003. Epub 2017 Oct 14.
Abstract/Text BACKGROUND AND OBJECTIVE: Numerous autoimmune diseases (AIDs) have been linked to chronic spontaneous urticaria (CSU). Here, we provide the first extensive and comprehensive evaluation of the prevalence of AIDs in patients with CSU and vice versa.
METHODS: A Pubmed and Google Scholar search was performed to identify studies reporting the prevalence of various AIDs in CSU and vice versa published before April 2017.
RESULTS: The prevalence of individual AIDs in CSU is increased (≥1% in most studies vs ≤1% in the general population). AIDs with relatively high prevalence in the general population are also quite common in CSU patients, whereas those with low prevalence remain a rare finding in CSU. The rates of comorbidity in most studies were ≥1% for insulin-dependent diabetes mellitus, rheumatoid arthritis (RA), psoriasis and celiac disease (CD), ≥2% for Graves' disease, ≥3% for vitiligo, and ≥5% for pernicious anemia and Hashimoto's thyroiditis. Organ-specific AIDs are more prevalent in CSU than systemic (multiorgan or non organ-specific) AIDs. >2% of CSU patients have autoimmune polyglandular syndromes encompassing autoimmune thyroid disease (ATD) and vitiligo or pernicious anemia. Antithyroid and antinuclear antibodies are the most prevalent AID-associated autoantibodies in CSU. >15% of CSU patients have a positive family history for AIDs. The prevalence of urticarial rash in AID patients is >1% in most studies. This rash is more prevalent in eosinophilic granulomatosis with polyangiitis, ATD, systemic lupus erythematosus, RA and CD.
CONCLUSIONS: CSU patients have an increased risk of AIDs, especially adult female patients and those with a positive family history and a genetic predisposition for AIDs, who should be screened for signs and symptoms of AIDs.

Copyright © 2017 Elsevier B.V. All rights reserved.
PMID 29037900  Autoimmun Rev. 2017 Dec;16(12):1196-1208. doi: 10.1016/・・・
著者: L Brain, E H Jellinek, K Ball
雑誌名: Lancet. 1966 Sep 3;2(7462):512-4.
Abstract/Text
PMID 4161638  Lancet. 1966 Sep 3;2(7462):512-4.
著者: Ji Y Chong, Lewis P Rowland, Robert D Utiger
雑誌名: Arch Neurol. 2003 Feb;60(2):164-71.
Abstract/Text BACKGROUND: Hashimoto encephalopathy has been described as a syndrome of encephalopathy and high serum antithyroid antibody concentrations that is responsive to glucocorticoid therapy, but these could be chance associations.
OBJECTIVE: To study a patient with Hashimoto encephalopathy and to review the literature to determine whether Hashimoto encephalopathy is an identifiable syndrome.
DATA SOURCES AND EXTRACTION: We searched the MEDLINE database to June 2002 for "Hashimoto" or "autoimmune thyroiditis" and "encephalopathy" and examined all identified articles and articles referenced therein, including all languages. We included all patients with noninfectious encephalopathy (clouding of consciousness and impaired cognitive function) and high serum antithyroid antibody concentrations. We excluded patients if they did not meet these inclusion criteria or if their symptoms could be explained by another neurologic disorder. We recorded clinical features and the results of imaging, electroencephalographic, thyroid function, and cerebrospinal fluid studies.
DATA SYNTHESIS: We identified 85 patients (69 women and 16 men; mean age, 44 years) with encephalopathy and high serum antithyroid antibody concentrations. Among these patients, 23 (27%) had strokelike signs, 56 (66%) had seizures, 32 (38%) had psychosis, 66 (78%) had a high cerebrospinal fluid protein concentration, and 80 (98%) of 82 had abnormal electroencephalographic findings. Thyroid function varied from overt hypothyroidism to overt hyperthyroidism; the most common abnormality was subclinical hypothyroidism (30 patients [35%]). Among patients treated with glucocorticoids, 66 (96%) improved.
CONCLUSIONS: The combination of encephalopathy, high serum antithyroid antibody concentrations, and responsiveness to glucocorticoid therapy seems unlikely to be due to chance. However, there is no evidence of a pathogenic role for the antibodies, which are probably markers of some other autoimmune disorder affecting the brain.

PMID 12580699  Arch Neurol. 2003 Feb;60(2):164-71.
著者: B Singh, A R Shaha, H Trivedi, J F Carew, A Poluri, J P Shah
雑誌名: Surgery. 1999 Dec;126(6):1070-6; discussion 1076-7.
Abstract/Text BACKGROUND: This study was performed to assess the relationship between Hashimoto's thyroiditis and the development, presentation, management, and outcome of papillary thyroid carcinoma.
METHODS: Two complementary analytic methods were used. The clinical study was a retrospective case-control study, including patients seen with papillary thyroid carcinoma presenting during a 12-year period. We also used a systematic literature review to identify suitable reports and meta-analysis to statistically combine published results.
RESULTS: The prevalence of Hashimoto's thyroiditis is significantly higher in patients with papillary thyroid cancer (odds ratio, 1.89; 95% CI, 1.02-3.50). These patients typically have a dominant nodule, 44% of which are discovered incidentally on routine examinations. Fine-needle aspiration has a sensitivity of 91% for the identification of papillary cancer. The prognostic variables at the time of a diagnosis of papillary cancer and the approach to management are not altered by the presence of coexistent Hashimoto's thyroiditis. In addition, the rate of surgical complications was not higher in patients with coexistent Hashimoto's disease. Meta-analysis suggested a positive correlation between Hashimoto's disease and disease-free survival (r = 0.09; 95% CI, 0.05-0.12) and overall survival (r = 0.11; 95% CI, 0.07-0.15).
CONCLUSIONS: There is an increased prevalence of Hashimoto's thyroiditis in patients with papillary thyroid carcinoma. The presence of coexistent Hashimoto's thyroiditis does not affect the diagnostic evaluation or management of papillary thyroid cancers. The survival of patients who have papillary thyroid cancers may be superior in coexistent Hashimoto's thyroiditis.

PMID 10598190  Surgery. 1999 Dec;126(6):1070-6; discussion 1076-7.
著者: Shawn D Larson, Lindsey N Jackson, Taylor S Riall, Tatsuo Uchida, Robert P Thomas, Suimin Qiu, B Mark Evers
雑誌名: J Am Coll Surg. 2007 May;204(5):764-73; discussion 773-5. doi: 10.1016/j.jamcollsurg.2006.12.037. Epub 2007 Feb 23.
Abstract/Text BACKGROUND: The link between inflammation and cancer is well-established, but the link between Hashimoto thyroiditis (HT) and thyroid cancer remains controversial. The purpose of our study was to determine the incidence of patients with thyroid cancer and associated HT at our institution, to correlate our patient population demographics with the Surveillance, Epidemiology and End Results (SEER) database, and to assess the expression of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway in patients with HT.
STUDY DESIGN: Demographic and histologic data were collected from patients undergoing thyroid resection at the University of Texas Medical Branch from 1987 to 2002 and compared with the SEER database. Immunohistochemistry for phosphorylated Akt (a marker of PI3K activity), Akt isoforms and PTEN (an inhibitor of PI3K) was performed on paraffin-embedded blocks of resected thyroid tissue.
RESULTS: Our patient population demographics and thyroid cancer incidence by histologic type were similar to patients in the SEER database. Ninety-eight (37.7%) resected specimens had pathologic changes consistent with HT; 43 (43.8%) had an associated well-differentiated thyroid cancer. Increased phosphorylated Akt, Akt1, and Akt2 expression was noted in regions of HT and thyroid cancer compared with regions of normal surrounding thyroid tissue.
CONCLUSIONS: Patients with HT were three times more likely to have thyroid cancer, suggesting a strong link between chronic inflammation and cancer development. PI3K/Akt expression was increased in both HT and well-differentiated thyroid cancer, suggesting a possible molecular mechanism for thyroid carcinogenesis.

PMID 17481480  J Am Coll Surg. 2007 May;204(5):764-73; discussion 773-・・・
著者: Shelleg Dvorkin, Eyal Robenshtok, Dania Hirsch, Yulia Strenov, Ilan Shimon, Carlos A Benbassat
雑誌名: J Clin Endocrinol Metab. 2013 Jun;98(6):2409-14. doi: 10.1210/jc.2013-1309. Epub 2013 Apr 22.
Abstract/Text BACKGROUND: Evaluation of surgical specimens suggests that patients with Hashimoto thyroiditis (HT) have a higher prevalence of differentiated thyroid cancer. Although patients with HT are reported to present with earlier stage disease, there is controversy as to whether these patients have better prognosis when adjusted for histology and stage at presentation.
OBJECTIVES: To investigate differences between patients with differentiated thyroid cancer patients and without HT for aggressiveness of disease and clinical outcome, and the decline rate of antithyroglobulin antibodies titers over time.
METHODS: A retrospective study using the Rabin Medical Center Thyroid Cancer Registry. Seven hundred fifty-three patients were included and divided into 2 groups of patients with and without HT at diagnosis. Disease severity at presentation was evaluated using the entire cohort, whereas a control group matched for age, gender, histology, and stage was used to evaluate disease course and outcome.
RESULTS: HT was present in 14.2% (n = 107) of included patients and was associated with smaller primary tumor (17.9 vs 21.2 mm, P = .01) and less lymph node involvement (23% vs 34%, P = .02) at presentation. When matched groups were compared, patients with HT received less additional radioactive iodine (RAI) treatments (1.24 vs 1.45, P = .03) and showed lower rates of persistence at 1 year (13% vs 26%, P = .04) and higher rates of disease remission at the end of follow-up (90% vs 79%, P = .05). On multivariate analysis HT was predictive of a lower rate of lymph nodes involvement (odds ratio 0.34, 95% confidence interval 0.17-0.66) and persistent disease at the end of follow-up (odds ratio 0.48, 95% confidence interval 0.24-0.93). Antithyroglobulin antibodies slowly disappeared in most patients with no evidence of disease.
CONCLUSION: Our study demonstrates that HT is associated with a less aggressive form of differentiated thyroid cancer and a better long-term outcome.

PMID 23609834  J Clin Endocrinol Metab. 2013 Jun;98(6):2409-14. doi: 1・・・
著者: Haixia Guan, Nathalie Silva de Morais, Jessica Stuart, Sara Ahmadi, Ellen Marqusee, Mathew I Kim, Erik K Alexander
雑誌名: Eur J Endocrinol. 2019 Nov;181(5):539-544. doi: 10.1530/EJE-19-0424.
Abstract/Text Objective: To investigate the concordance of serologic and sonographic evidence of Hashimoto's thyroiditis with its gold standard histopathologic identification.
Design: We performed a retrospective analysis on a cohort of 825 consecutive patients in whom TPOAb and thyroid ultrasound were performed, and in whom thyroid nodule evaluation led to surgical and histopathologic analysis. The presence or absence of Hashimoto's thyroiditis on histopathology was correlated with serologic and sonographic markers. We further assessed the impact of low versus high titers of TPOAb upon this concordance.
Results: Of 825 patients, 277 (33.5%) had histologic confirmation of Hashimoto's thyroiditis, 235 patients (28.4%) had elevated serum levels of TPOAb, and 197 (23.8%) had sonographic evidence of diffuse heterogeneity. Of those with histopathologic evidence, only 64% had elevated TPOAb (sensitivity: 63.9%; specificity: 89.4%), while only 49% were sonographically diffusely heterogeneous (sensitivity: 49.1%; specificity: 88.9%). A subset of only 102 of 277 (37%) with histologically proven Hashimoto's thyroiditis was positive for both TPOAb and diffusely heterogeneous. Concordance analysis demonstrated that TPOAb and histopathology had higher agreement (κ = 0.55) than did ultrasound and histopathology (κ = 0.40) for the diagnosis of Hashimoto's thyroiditis. Higher titers of TPOAb correlated with a higher likelihood of Hashimoto's thyroiditis, with a best cutoff of 2.11-fold the upper normal level of TPOAb.
Conclusion: Only moderate concordance exists between serological evidence of Hashimoto's thyroiditis and histopathologic findings, though it increases with higher TPOAb concentration. Diffuse heterogeneity on ultrasound is a less-sensitive diagnostic tool than elevated TPOAb.

PMID 31536967  Eur J Endocrinol. 2019 Nov;181(5):539-544. doi: 10.1530・・・
著者: Stephanie Aleskow Stein, Leonard Wartofsky
雑誌名: J Clin Endocrinol Metab. 2013 Aug;98(8):3131-8. doi: 10.1210/jc.2013-1428. Epub 2013 May 28.
Abstract/Text CONTEXT: Although primary thyroid lymphoma is a rare cause of both thyroid malignancy and extranodal lymphoma, awareness of this disease is important in order to achieve an early diagnosis and implement treatment. We review the epidemiology, clinical presentation, diagnosis, and treatment of this rare disorder.
EVIDENCE ACQUISITION: This review is based on a search of PubMed and MDConsult for English language articles containing the term "primary thyroid lymphoma." The authors reviewed original and review articles and case series from all years of publication but focused on those published within the last 5 years.
EVIDENCE SYNTHESIS: Primary thyroid lymphoma should be suspected in patients with a rapidly enlarging neck mass, especially in women with Hashimoto's thyroiditis. Certain ultrasound features such as enhanced posterior echoes can suggest the diagnosis, but biopsy for confirmation is ultimately needed. With advances in immunophenotypic analysis, fine-needle aspiration can be used for diagnosis in the hands of experienced physicians. The most common type of primary thyroid lymphoma is diffuse large B-cell lymphoma, which behaves in a more aggressive manner than mucosa-associated lymphoid tissue lymphoma. Radiation therapy can be employed for treatment of localized mucosa-associated lymphoid tissue lymphoma, but a combination of chemotherapy and radiation is needed for disseminated disease or aggressive histological subtypes.
CONCLUSIONS: It is important to consider the diagnosis of primary thyroid lymphoma in patients presenting with an enlarging neck mass and a history of Hashimoto's thyroiditis. Advances in both diagnosis and treatment in recent years have altered our approach to the management of this disease.

PMID 23714679  J Clin Endocrinol Metab. 2013 Aug;98(8):3131-8. doi: 10・・・
著者: Robertas Bunevicius, Arthur J. Prange
雑誌名: Int J Neuropsychopharmacol. 2000 Jun;3(2):167-174. doi: 10.1017/S1461145700001826.
Abstract/Text We treated 26 hypothyroid women - 11 with autoimmune thyroiditis and 15 who had been treated for thyroid cancer - with their usual dose of thyroxine (T4) or with a regimen in which 50 &mgr;g of T4 had been replaced by 12.5 &mgr;g of triiodothyronine (T3). Patients were first randomly assigned to one regimen for 5 wk and then to a second regimen for an additional 5 wk. The substitution of T3 for a portion of T4 caused expected changes in concentrations of thyroid hormones and thyroid-stimulating hormone (TSH). After combined hormone treatment there were clear improvements in both cognition and mood, the latter changes being greater. The patients who had been treated for thyroid cancer showed more mental improvement than the women with autoimmune thyroiditis, perhaps because they were more dependent on exogenous hormone. Some mood improvements correlated positively with changes in TSH while others correlated negatively with changes in free T4.

PMID 11343593  Int J Neuropsychopharmacol. 2000 Jun;3(2):167-174. doi:・・・
著者: W Siegmund, K Spieker, A I Weike, T Giessmann, C Modess, T Dabers, G Kirsch, E Sänger, G Engel, A O Hamm, M Nauck, W Meng
雑誌名: Clin Endocrinol (Oxf). 2004 Jun;60(6):750-7. doi: 10.1111/j.1365-2265.2004.02050.x.
Abstract/Text OBJECTIVES: There is evidence from recent controlled clinical studies that replacement therapy of hypothyroidism with T4 in combination with a small amount of T3 may improve the well-being of the patients. As the issue is still the subject of controversial discussion, our study was assigned to confirm the superiority of a physiological combination of thyroid hormones (absorbed molar ratio 14 : 1) over T4 alone with regard to mood states and cognitive functioning.
DESIGN AND PATIENTS: After a run-in period with the T4 study medication for 4 weeks, a controlled, randomized, double-blind, two-period (each 12 weeks), cross-over study without washout between the treatment periods was performed in 23 hypothyroid patients (three males, 20 females, age 23-69 years, 21 subjects after surgery/radioiodine, two with autoimmune thyroiditis) to compare the effects of the previous individual T4 dose (100-175 micro g) with a treatment in which 5% of the respective T4 dose was substituted by T3.
MEASUREMENTS: Standard hormonal characteristics and standardized psychological tests to quantify mood and cognitive performance were measured after the run-in period and at the end of each treatment period. In 12 subjects, the concentration-time profiles of fT3 and fT4 were compared after the last administration of the respective study medication. TSH, fT3 and fT4 were measured with immunological assays.
CLINICAL RESULTS: Replacement therapy with T4 and T4/T3 was not different in all steady-state hormonal, metabolic and cardiovascular characteristics except for TSH, which was more suppressed after T4/T3. The efficacy of replacement therapy with the T4/T3 combination was not different from the T4 monotherapy with regard to all psychological test scores describing mood and cognitive functioning of the patients. Mood was even significantly impaired by the T4/T3 combination in eight subjects, with TSH < 0.02 mU/l, compared to patients with normal TSH (Beck Depression Inventory: 8.25 +/- 5.01 vs. 4.07 +/- 5.60, P = 0.026). PHARMACOKINETIC RESULTS: The area under the concentration-time curve (AUC(0-8h)) of fT3 was significantly higher after T4/T3 compared to the T4 monotherapy (42.8 +/- 9.03 pmol x h/l vs. 36.3 +/- 8.50 pmol x h/l, P < 0.05) and was significantly correlated to serum TSH (r(s) = -0.609, P < 0.05). After T4/T3, patients with a history of Graves' disease or autoimmune thyroiditis had significantly higher serum trough levels of fT3 whereas the fT4 concentrations were significantly lower in patients with a nonautoimmune background.
CONCLUSION: Replacement therapy of hypothyroidism with T4 plus T3 does not improve mood and cognitive performance compared to the standard T4 monotherapy. There is even a higher risk of signs of subclinical hyperthyroidism associated with impaired well-being of the patients, which is clearly caused by significant fluctuations in the steady-state fT3 serum concentrations.

PMID 15163340  Clin Endocrinol (Oxf). 2004 Jun;60(6):750-7. doi: 10.11・・・
著者: Bente C Appelhof, Eric Fliers, Ellie M Wekking, Aart H Schene, Jochanan Huyser, Jan G P Tijssen, Erik Endert, Henk C P M van Weert, Wilmar M Wiersinga
雑誌名: J Clin Endocrinol Metab. 2005 May;90(5):2666-74. doi: 10.1210/jc.2004-2111. Epub 2005 Feb 10.
Abstract/Text Controversy remains about the value of combined treatment with levothyroxine (LT4) and liothyronine (LT3), compared with LT4 alone in primary hypothyroidism. We compared combined treatment with LT4 and LT3 in a ratio of 5:1 or 10:1 with LT4 monotherapy. We conducted a double-blind, randomized, controlled trial in 141 patients (18-70 yr old) with primary autoimmune hypothyroidism, recruited via general practitioners. Inclusion criteria included: LT4 treatment for 6 months or more, a stable dose for 6 wk or more, and serum TSH levels between 0.11 and 4.0 microU/ml (mU/liter). Randomization groups were: 1) continuation of LT4 (n = 48); 2) LT4/LT3, ratio 10:1 (n = 46); and 3) LT4/LT3, ratio 5:1 (n = 47). Subjective preference of study medication after 15 wk, compared with usual LT4, was the primary outcome measure. Secondary outcomes included scores on questionnaires on mood, fatigue, psychological symptoms, and a substantial set of neurocognitive tests. Study medication was preferred to usual treatment by 29.2, 41.3, and 52.2% in the LT4, 10:1 ratio, and 5:1 ratio groups, respectively (chi2 test for trend, P = 0.024). This linear trend was not substantiated by results on any of the secondary outcome measures: scores on questionnaires and neurocognitive tests consistently ameliorated, but the amelioration was not different among the treatment groups. Median end point serum TSH was 0.64 microU/ml (mU/liter), 0.35 microU/ml (mU/liter), and 0.07 microU/ml (mU/liter), respectively [ANOVA on ln(TSH) for linear trend, P < 0.01]. Mean body weight change was +0.1, -0.5, and -1.7 kg, respectively (ANOVA for trend, P = 0.01). Decrease in weight, but not decrease in serum TSH was correlated with increased satisfaction with study medication. Of the patients who preferred combined LT4/LT3 therapy, 44% had serum TSH less than 0.11 microU/ml (mU/liter). Patients preferred combined LT4/LT3 therapy to usual LT4 therapy, but changes in mood, fatigue, well-being, and neurocognitive functions could not satisfactorily explain why the primary outcome was in favor of LT4/LT3 combination therapy. Decrease in body weight was associated with satisfaction with study medication.

PMID 15705921  J Clin Endocrinol Metab. 2005 May;90(5):2666-74. doi: 1・・・
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: L Fernandez-Soto, A Gonzalez, F Escobar-Jimenez, R Vazquez, E Ocete, N Olea, J Salmeron
雑誌名: Arch Intern Med. 1998 Jul 13;158(13):1445-8.
Abstract/Text BACKGROUND: Thyroid gland dysfunction has been reported to occur with variable frequency during interferon alfa (IFN-alpha) therapy in patients with the hepatitis C virus (HCV). We prospectively evaluated if the prevalence of autoimmune thyroid disease in patients with HCV differs from that in patients with the hepatitis B virus (HBV) before, at the end of, and 6 months after stopping treatment with IFN-alpha.
METHODS: One hundred thirty-four patients with HCV and 41 patients with HBV were studied. Measurements of serum free thyroxine, free triiodothyronine, thyrotropin, thyroid peroxidase antibodies (TPOAbs), thyroglobulin antibodies (TgAbs), and thyrotropin-binding inhibitory immunoglobulin were performed.
RESULTS: Positive levels of TPOAb and TgAb were found in 20% and 11% of patients with HCV compared with 5% and 3% of patients with HBV, respectively. At the end of IFN-alpha therapy, thyroid gland dysfunction was more prevalent in patients with HCV (12%) compared with those with HBV (3%), with thyrotropin levels significantly higher in the HCV group (P = .03). Titers of TPOAb, TgAb, and thyrotropin-binding inhibitory immunoglobulin increased significantly (P = .02, P = .04, and P = .02, respectively) at the end of IFN-alpha therapy in patients with HCV but not in those with HBV. Patients who developed thyroid gland dysfunction were predominantly female (P = .03), had decreased levels of free triiodothyronine (P<.001), and had a higher prevalence of TPOAb (P = .03) before treatment with IFN-alpha. Thyroid gland dysfunction was reversed in 60% of those with HCV 6 months after discontinuing treatment with IFN-alpha.
CONCLUSIONS: Patients with HCV are more susceptible than patients with HBV to autoimmune thyroid disease. Systematic screening of thyroid gland function and TPOAb titers in all patients with HCV before, during, and after IFN-alpha therapy appears warranted. This precaution is not necessary for patients with HBV.

PMID 9665354  Arch Intern Med. 1998 Jul 13;158(13):1445-8.
著者: Elizabeth N Pearce
雑誌名: J Clin Endocrinol Metab. 2012 Feb;97(2):326-33. doi: 10.1210/jc.2011-2532. Epub 2011 Dec 28.
Abstract/Text Thyroid hormone has multiple effects on the regulation of lipid synthesis, absorption, and metabolism. Studies consistently demonstrate elevated levels of serum total cholesterol, low-density lipoprotein cholesterol (LDL-C), apolipoprotein B, lipoprotein(a), and possibly triglycerides in individuals with overt hypothyroidism, all of which are reversible with levothyroxine therapy. Although it is estimated that 1 to 11% of all patients with dyslipidemia have subclinical hypothyroidism, the effects of subclinical hypothyroidism on serum lipid values are less clear. Apolipoprotein B levels may be increased in patients with subclinical hypothyroidism. Although some studies have demonstrated that total cholesterol and LDL-C levels are elevated in patients with subclinical hypothyroidism, others have not shown any effect of subclinical hypothyroidism on these lipid measurements. Serum triglycerides, lipid subparticle size, and LDL-C oxidizability may be altered in subclinical hypothyroidism, but these studies have also been inconsistent. The preponderance of evidence suggests that HDL-C and lipoprotein(a) levels are not altered in subclinically hypothyroid patients. Smoking and insulin resistance may modify the effects of subclinical hypothyroidism on serum lipid values. Clinical trials to date have not consistently shown a beneficial effect of levothyroxine treatment on serum lipid levels in subclinically hypothyroid patients.

PMID 22205712  J Clin Endocrinol Metab. 2012 Feb;97(2):326-33. doi: 10・・・
著者: Lily L Somwaru, Chevon M Rariy, Alice M Arnold, Anne R Cappola
雑誌名: J Clin Endocrinol Metab. 2012 Jun;97(6):1962-9. doi: 10.1210/jc.2011-3047. Epub 2012 Mar 21.
Abstract/Text CONTEXT: Studies of long-term outcomes of subclinical hypothyroidism have assessed only baseline thyroid function, despite natural transitions to euthyroidism and overt hypothyroidism over time.
OBJECTIVE: We provide estimates of persistence, resolution, and progression of subclinical hypothyroidism over 4 yr, stratified by baseline TSH, anti-thyroid peroxidase antibody (TPOAb) status, age, and sex.
DESIGN, SETTING, AND PARTICIPANTS: Participants were 3996 U.S. individuals at least 65 yr old enrolled in the Cardiovascular Health Study. Subclinical hypothyroidism was detected at baseline in 459 individuals not taking thyroid medication.
MAIN OUTCOME MEASURE: Thyroid function was evaluated at 2 and 4 yr and initiation of thyroid medication annually. Results were stratified by baseline TSH, TPOAb status, age, and sex.
RESULTS: Persistence of subclinical hypothyroidism was 56% at 2 and 4 yr. At 2 yr, resolution was more common with a TSH of 4.5-6.9 mU/liter (46 vs. 10% with TSH 7-9.9 mU/liter and 7% with TSH ≥10 mU/liter; P < 0.001) and with TPOAb negativity (48 vs. 15% for positive; P < 0.001). Higher TSH and TPOAb positivity were independently associated with lower likelihood of reversion to euthyroidism (P < 0.05). TSH of 10 mU/liter or higher was independently associated with progression to overt hypothyroidism (P < 0.05). Transitions between euthyroidism and subclinical hypothyroidism were common between 2 and 4 yr. Age and sex did not affect transitions.
CONCLUSIONS: Subclinical hypothyroidism persists for 4 yr in just over half of older individuals, with high rates of reversion to euthyroidism in individuals with lower TSH concentrations and TPOAb negativity. Future studies should examine the impact of transitions in thyroid status on clinical outcomes.

PMID 22438233  J Clin Endocrinol Metab. 2012 Jun;97(6):1962-9. doi: 10・・・
著者: Mary H Samuels, Irina Kolobova, Meike Niederhausen, Jeri S Janowsky, Kathryn G Schuff
雑誌名: J Clin Endocrinol Metab. 2018 May 1;103(5):1997-2008. doi: 10.1210/jc.2017-02668.
Abstract/Text Background: The brain is a critical target organ for thyroid hormone, but it is unclear whether variations in thyroid function within and near the reference range affect quality of life, mood, or cognition.
Methods: A total of 138 subjects with levothyroxine (L-T4)-treated hypothyroidism and normal thyrotropin (TSH) levels underwent measures of quality of life (36-Item Short Form Health Survey, Underactive Thyroid-Dependent Quality of Life Questionnaire), mood (Profile of Mood States, Affective Lability Scale), and cognition (executive function, memory). They were then randomly assigned to receive an unchanged, higher, or lower L-T4 dose in double-blind fashion, targeting one of three TSH ranges (0.34 to 2.50, 2.51 to 5.60, or 5.61 to 12.0 mU/L). Doses were adjusted every 6 weeks based on TSH levels. Baseline measures were reassessed at 6 months.
Results: At the end of the study, by intention to treat, mean L-T4 doses were 1.50 ± 0.07, 1.32 ± 0.07, and 0.78 ± 0.08 μg/kg (P < 0.001), and mean TSH levels were 1.85 ± 0.25, 3.93 ± 0.38, and 9.49 ± 0.80 mU/L (P < 0.001), respectively, in the three arms. There were minor differences in a few outcomes between the three arms, which were no longer significant after correction for multiple comparisons. Subjects could not ascertain how their L-T4 doses had been adjusted (P = 0.55) but preferred L-T4 doses they perceived to be higher (P < 0.001).
Conclusions: Altering L-T4 doses in hypothyroid subjects to vary TSH levels in and near the reference range does not affect quality of life, mood, or cognition. L-T4-treated subjects prefer perceived higher L-T4 doses despite a lack of objective benefit. Adjusting L-T4 doses in hypothyroid patients based on symptoms in these areas may not result in significant clinical improvement.

PMID 29509918  J Clin Endocrinol Metab. 2018 May 1;103(5):1997-2008. d・・・
著者: Thien-Giang Bach-Huynh, Bindu Nayak, Jennifer Loh, Steven Soldin, Jacqueline Jonklaas
雑誌名: J Clin Endocrinol Metab. 2009 Oct;94(10):3905-12. doi: 10.1210/jc.2009-0860. Epub 2009 Jul 7.
Abstract/Text CONTEXT: Patients treated with levothyroxine typically ingest it in a fasting state to prevent food impairing its absorption. The serum thyrotropin concentration is the therapeutic index of levothyroxine action.
OBJECTIVE: The study objective was to determine the effect of the timing of levothyroxine administration in relationship to food on serum thyrotropin levels.
DESIGN: Participants were randomized to one of six sequences, each consisting of three 8-wk regimens in a three-period crossover design. These regimens were in a fasting state, at bedtime, and with breakfast. The concentrations of TSH, free T(4), and total T(3) during each of the three timing regimens were documented. The primary outcome was the difference between serum TSH concentrations under fasting conditions compared with concentrations during the other 8-wk regimens.
SETTING: The study was conducted in an academic medical center.
PARTICIPANTS: Study participants were receiving levothyroxine for treatment of hypothyroidism or thyroid cancer.
RESULTS: Sixty-five patients completed the study. The mean thyrotropin concentration was 1.06 +/- 1.23 mIU/liter when levothyroxine was administered in the fasting state. When levothyroxine was taken with breakfast, the serum thyrotropin concentration was significantly higher (2.93 +/- 3.29 mIU/liter). When levothyroxine was taken at bedtime, the serum TSH concentration was also significantly higher (2.19 +/- 2.66 mIU/liter).
CONCLUSION: Nonfasting regimens of levothyroxine administration are associated with higher and more variable serum TSH concentrations. If a specific serum TSH goal is desired, thereby avoiding iatrogenic subclinical thyroid disease, then fasting ingestion of levothyroxine ensures that TSH concentrations remain within the narrowest target range.

PMID 19584184  J Clin Endocrinol Metab. 2009 Oct;94(10):3905-12. doi: ・・・
著者: J E Haddow, G E Palomaki, W C Allan, J R Williams, G J Knight, J Gagnon, C E O'Heir, M L Mitchell, R J Hermos, S E Waisbren, J D Faix, R Z Klein
雑誌名: N Engl J Med. 1999 Aug 19;341(8):549-55. doi: 10.1056/NEJM199908193410801.
Abstract/Text BACKGROUND: When thyroid deficiency occurs simultaneously in a pregnant woman and her fetus, the child's neuropsychological development is adversely affected. Whether developmental problems occur when only the mother has hypothyroidism during pregnancy is not known.
METHODS: In 1996 and 1997, we measured thyrotropin in stored serum samples collected from 25,216 pregnant women between January 1987 and March 1990. We then located 47 women with serum thyrotropin concentrations at or above the 99.7th percentile of the values for all the pregnant women, 15 women with values between the 98th and 99.6th percentiles, inclusive, in combination with low thyroxine levels, and 124 matched women with normal values. Their seven-to-nine-year-old children, none of whom had hypothyroidism as newborns, underwent 15 tests relating to intelligence, attention, language, reading ability, school performance, and visual-motor performance.
RESULTS: The children of the 62 women with high serum thyrotropin concentrations performed slightly less well on all 15 tests. Their full-scale IQ scores on the Wechsler Intelligence Scale for Children, third edition, averaged 4 points lower than those of the children of the 124 matched control women (P= 0.06); 15 percent had scores of 85 or less, as compared with 5 percent of the matched control children. Of the 62 women with thyroid deficiency, 48 were not treated for the condition during the pregnancy under study. The full-scale IQ scores of their children averaged 7 points lower than those of the 124 matched control children (P=0.005); 19 percent had scores of 85 or less. Eleven years after the pregnancy under study, 64 percent of the untreated women and 4 percent of the matched control women had confirmed hypothyroidism.
CONCLUSIONS: Undiagnosed hypothyroidism in pregnant women may adversely affect their fetuses; therefore, screening for thyroid deficiency during pregnancy may be warranted.

PMID 10451459  N Engl J Med. 1999 Aug 19;341(8):549-55. doi: 10.1056/N・・・

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