Selenium supplementation for Hashimoto's thyroiditis

  • Review
  • Intervention




Hashimoto's thyroiditis is a common auto-immune disorder. The most common presenting symptoms may include anxiety, negative mood, depression, dry skin, cold intolerance, puffy eyes, muscle cramps and fatigue, deep voice, constipation, slow thinking and poor memory. Clinical manifestations of the disease are defined primarily by low levels of thyroid hormones; therefore it is treated by hormone replacement therapy, which usually consists of levothyroxine (LT4). Selenium might reduce antibody levels and result in a decreased dosage of LT4 and may provide other beneficial effects (e.g. on mood and health-related quality of life).


To assess the effects of selenium supplementation on Hashimoto's thyroiditis.

Search methods

We searched the following databases up to 2 October 2012: CENTRAL in The Cochrane Library (2012, Issue 10), MEDLINE, EMBASE, and Web of Science; we also screened reference lists of included studies and searched several online trial registries for ongoing trials (5 November 2012).

Selection criteria

Randomised controlled clinical trials that assessed the effects of selenium supplementation for adults diagnosed with Hashimoto's thyroiditis.

Data collection and analysis

Study selection, data extraction, assessment of risk of bias, and analyses were carried out by two independent review authors. We assessed the quality of the evidence of included studies using GRADE. We were unable to conduct a meta-analysis because clinical heterogeneity between interventions that were investigated is substantial.

Main results

Four studies at unclear to high risk of bias comprising 463 participants were included. The mean study duration was 7.5 months (range 3 to 18 months). One of our primary outcomes-'change from baseline in health related quality of life'-and two of our secondary outcomes-'change from baseline in LT4 replacement dosage at end of the study' and 'economic costs'-were not assessed in any of the studies. One study at high risk of bias showed statistically significant improvement in subjective well-being with sodium selenite 200 μg plus titrated LT4 compared with placebo plus titrated LT4 (relative risk (RR) 4.67, 95% confidence interval (CI) 1.61 to 13.50; P = 0.004; 36 participants; number needed to treat (NNT) = 2 (95% CI 2 to 3)).

Selenomethionine 200 μg reduced the serum levels of anti-thyroid peroxidase antibodies compared with placebo in two studies (mean difference (MD) -917 U/mL, 95% CI -1056 to -778; P < 0.001; 85 participants) and (MD -345 IU/mL, 95% CI -359 to -331; P < 0.001; 169 participants). Pooling of the studies was not feasible due to marked clinical heterogeneity (I2 = 99%). In a further comparison within the first study where selenomethionine was combined with LT4 the reduction in TPO antibodies was even more noticeable (MD -1508 U/mL, 95% CI -1671 to -1345; P < 0.001; 86 participants). In a third study, where LT4 was added to both intervention arms, a reduction in serum levels of anti-thyroid peroxidase antibodies favoured the selenomethionine arm as well (MD -235 IU/mL, 95% CI -374 to -95; P = 0.001; 88 participants). Although the changes from baseline were statistically significant in these three studies, their clinical relevance is unclear. Serum antibodies were not statistically significantly affected in the study comparing sodium selenite 200 μg plus titrated LT4 with placebo plus titrated LT4 (MD -25, 95% CI -181 to 131; P = 0.75; 36 participants).

Adverse events were reported in two studies (1 of 85 and 1 of 88 participants, respectively). Selenium supplementation did not appear to have a statistically significant impact on the incidence of adverse events (RR 2.93, 95% CI 0.12 to 70.00; and RR 2.63, 95% CI 0.11 to 62.95).

Authors' conclusions

Results of these four studies show that evidence to support or refute the efficacy of selenium supplementation in people with Hashimoto's thyroiditis is incomplete. The current level of evidence for the efficacy of selenium supplementation in the management of people with Hashimoto's thyroiditis is based on four randomised controlled trials assessed at unclear to high risk of bias; this does not at present allow confident decision making about the use of selenium supplementation for Hashimoto's thyroiditis. This review highlights the need for randomised placebo-controlled trials to evaluate the effects of selenium in people with Hashimoto's thyroiditis and can ultimately provide reliable evidence to help inform clinical decision making.




橋本病は、高い頻度で認められる自己免疫疾患である。最も一般的な主症状は、不安、抑うつ、うつ病、皮膚乾燥、寒冷不耐症、目の腫脹、筋痙攣および疲労、低い声、便秘、思考速度低下、記憶力低下などである。本症の臨床所見は、主に甲状腺ホルモン濃度の低値によって決定されるため、通常はレボチロキシン(LT4)を用いたホルモン補充療法による治療が行われる。 セレンは抗体濃度を低下させる可能性があるため、LT4投与量の減量につながり、その他にも(気分および健康関連のQOLなどに対する)有益な効果をもたらす可能性がある。




次のデータベースを2012年10月2日まで検索した:コクラン・ライブラリ(2012年第10版)のCENTRAL </113>、MEDLINE、EMBASEおよびWeb of Science。また、対象研究の参考文献リストをスクリーニングし、進行中の試験については複数のオンライン試験登録データベースを検索した(2012年11月5日)。






バイアスのリスクが不明から高いと評価された、参加者463例を対象とした4件の研究を選択した。平均試験期間は7.5カ月(3〜18カ月)であった。主要アウトカムの1項目「健康関連のQOLのベースラインからの変化」ならびに副次的アウトカムの2項目「試験終了時におけるLT4<補充量のベースラインからの変化」および「費用」については、いずれの研究でも評価されていなかった。 バイアスのリスクが高い1件の研究では、亜セレン酸ナトリウム200µg+漸増LT4とプラセボ+漸増LT4(相対リスク[RR]4.67、95%信頼区間[CI]1.61〜13.50; P= 0.004;参加者36例;治療必要数(NNT) = 2 [95%CI 2〜3])を比較した結果、主観的健康状態において統計学的に有意な改善が認められた。

2件の研究で、セレノメチオニン200 µgはプラセボと比較して血清中抗甲状腺ペルオキシダーゼ抗体濃度を低下させた(平均差[MD]-917 U/mL、95%CI -1056〜-778;P < 0.001;参加者85例)および(MD -345 IU/mL、95%CI -359〜-331;P < 0.001;参加者169例)。臨床的異質性が顕著であった(I2 = 99%)ため、これらの研究を統合することはできなかった。 1番目の研究では、セレノメチオニン+LT4のより詳細な比較を行った結果、TPO抗体の低下がより顕著に認められた(MD -1508 U/mL、95%CI -1671〜-1345;P < 0.001;参加者86例)。 3番目の研究では、両介入群にLT4を補充したが、血清抗甲状腺ペルオキシダーゼ抗体濃度はセレノメチオニン群の方が低値を示した(MD - 235 IU/mL、95%CI -374〜-95;P = 0.001;参加者88例)。 これら3件の研究ではベースラインからの変化に統計学的有意性が認められたが、その臨床的関連性は不明である。亜セレン酸ナトリウム200 µg+漸増LT4をプラセボ+漸増LT4と比較した研究では、血清抗体濃度に統計学的有意性は認められなかった(MD -25、95%CI -181〜131;P = 0.75;参加者36例)。

2件の研究で有害事象が報告された(それぞれ参加者85例中1例および88例中1例)。セレン補充は、有害事象発現率に対して統計学的に有意な影響を与えないと考えられた(RR 2.93、95%CI 0.12〜70.00およびRR 2.63、95%CI 0.11〜62.95)。




《注意》この日本語訳は、臨床医、疫学研究者などによる翻訳のチェックを受けて公開していますが、訳語の間違いなどお気づきの点がございましたら、eJIM事務局までご連絡ください。なお、2013年6月からコクラン・ライブラリーのNew review, Updated reviewとも日単位で更新されています。eJIMでは最新版の日本語訳を掲載するよう努めておりますが、タイム・ラグが生じている場合もあります。ご利用に際しては、最新版(英語版)の内容をご確認ください。

Plain language summary

Selenium supplementation for Hashimoto's thyroiditis

Hashimoto's thyroiditis is a common disease in which a form of chronic inflammation of the thyroid gland results in reduced function of the gland. It is an auto-immune disorder, which means that a person's own immune system attacks the thyroid gland, so that it no longer makes adequate quantities of thyroid hormones (hypothyroidism). Common clinical manifestations include feeling cold, depressive mood, dry skin, puffy eyes, constipation, weight gain, slowed heart rate, joint and muscle pain and fatigue. Some but not all people with Hashimoto's thyroiditis have an enlarged gland, also called a goitre. Hashimoto's thyroiditis is more common in women than in men and tends to run in families. Other auto-immune diseases often occur simultaneously, such as vitiligo, rheumatoid arthritis and diabetes type 1. The disease does not always require treatment, but when it does, it is treated with synthetic thyroid hormone replacement (sometimes desiccated thyroid hormone is used, which is not synthetic). Selenium is an essential trace element that is required in small amounts for correct functioning of the immune system and the thyroid gland.

Four studies at unclear to high risk of bias comprising 463 participants were included. The mean study duration was 7.5 months (range 3 to 18 months). None of the studies addressed our key primary outcome-'health-related quality of life'. Two of our secondary outcomes-'change from baseline in levothyroxine (i.e. thyroid hormone) replacement dosage at end of the study' and 'economic costs'-were not assessed either. One study at high risk of bias showed a statistically significant improvement in subjective well-being with sodium selenite 200 μg plus levothyroxine compared with placebo plus levothyroxine (14/18 compared with 3/18, respectively). Selenomethionine 200 μg reduced the serum levels of anti-thyroid peroxidase antibodies in three studies, and although the changes from baseline were statistically significant, their clinical relevance is unclear. Adverse events were reported in two studies, and selenium supplementation did not lead to more adverse events than were seen with placebo. One adverse event was reported in both studies in the selenomethionine 200 μg plus LT4 arm versus none in the control arm.

In conclusion, the results of these four studies do not provide enough evidence to support the use of selenium in the treatment of Hashimoto's thyroiditis.

Laički sažetak

Uzimanje dodataka selena za Hashimotov tireoiditis

Hashimotov tireoiditis je česta bolest kod koje dolazi do dugotrajne (kronične) upale štitne žlijezde, što dovodi do smanjenog funkcioniranja žlijezde. To je autoimuna bolest, što znači da vlastiti imunološki sustav bolesnika nadapa štitnu žlijezdu, koja zbog toga više ne može proizvoditi odgovarajuće količine hormona štitne žlijezde (hipotiroidizam). Česte kliničke manifestacije bolesti uključuju osjećaj hladnoće, depresivno raspoloženje, suhu kožu, natečene oči, zatvor stolice, debljanje, usporen rad srca, bol u zglobovima i mišićima te umor. Dio osoba koje boluju od Hashimotovog tireoiditisa imaju povećanu žlijezdu, što se još naziva i guša. Hashimotov tireoidits češće se javlja kod žena nego u muškaraca i u nekim obiteljima postoji sklonost obolijevanju od te bolesti. Bolesnici u isto vrijeme mogu patiti i od drugih autoimunih bolesti kao što su vitiligo, reumatoidni artritis i dijabetes tipa 1. Bolest ne zahtijeva uvijek liječenje, ali kad je liječenje potrebno, onda se liječi davanjem zamjenskih hormona štitnjače (nekad se daje sušeni hormon štitnjače koji nije umjetno proizveden). Selen je esencijalni element u tragovima kojeg naše tijelo treba u malim količinama za uredno funkcioniranje imunološkog sustava i štitne žlijezde.

U ovaj sustavni pregled uključene su 4 studije nejasnog ili visokog rizika od pristranosti, u kojima je sudjelovalo ukupno 463 ispitanika. Srednje trajanje studija bilo je 7,5 mjeseci (3-18 mjeseci). Nijedna od tih studija nije ispitala kvalitetu života povezanu sa zdravljem. Druga dva glavna rezultata koja su autori sustavnog pregleda namjeravali mjeriti, uključujući promjenu u razini nadokndne doze levotiroksina (hormona štitnjače) i cijenu terapije - također nisu bile procijenjene. Jedna studija s visokim rizikom od pristranosti pokazala je statistički značajno povećanje u subjektivnom osjećanju kod ispitanika koji su uzimali 200 mikrograma selena zajedno s levotiroksinom u usporedbi s kombinacijom placeba i levotiroksina - 14 od 18 osoba u prvoj studiji u usporedbi s 3 od 18 osoba u drugoj. Selenmetionin od 200 mikrograma smanjio je razinu protutijela usmjerenih na anti-tiroidnu perokdisazu i iako je promjena u odnosu na prvo mjerenje bila značajna, klinička važnost tog rezultata nije jasna. Nuspojave nisu opisane u dvjema studijama, a u drugim dvjema studijama dodatak selena nije uzrokovao više nuspojava nego placebo. U objema studijama zabilježena je jedna nuspojava u skupini koja je primala 200 mikrograma selenmetionina u kombinaciji s LT4 skupininaspram niti jedne u kontrolnoj skupini.

Zaključno, rezultati 4 pronađene studije ne daju dovoljno dokaza koji bi poduprili uzimanje selena za liječenje Hashimotova tireoiditisa.

Bilješke prijevoda

Cochrane Hrvatska
Prevela: Livia Puljak
Ovaj sažetak preveden je u okviru volonterskog projekta prevođenja Cochrane sažetaka. Uključite se u projekt i pomozite nam u prevođenju brojnih preostalih Cochrane sažetaka koji su još uvijek dostupni samo na engleskom jeziku. Kontakt:



橋本病は一般的な疾患で、甲状腺の慢性炎症の一種によって甲状腺機能が低下する。本疾患は自己免疫疾患であり、自分自身の免疫系が甲状腺を攻撃するため、十分な量の甲状腺ホルモンが産生されなくなる(甲状腺機能低下症)。一般的な臨床症状は、寒気、憂うつな気分、皮膚乾燥、目の腫れ、便秘、体重増加、心拍数低下、関節痛や筋肉痛、疲労などである。橋本病患者の全員に、ゴイター(甲状腺腫)とも呼ばれる甲状腺肥大が認められるわけではない。 橋本病は男性よりも女性に多く、家族で遺伝する傾向がある。しばしば、白斑、関節リウマチ、1型糖尿病など、他の自己免疫疾患を同時に発症する場合がある。本疾患は必ずしも治療を必要としないが、治療が必要な場合は合成甲状腺ホルモンを補充する(乾燥甲状腺ホルモンが用いられる場合があるが、これは合成ではない)。セレンは必須微量元素で、免疫系や甲状腺の機能を正常化するために少量を必要とする。

バイアスのリスクが不明から高いと評価された、参加者463例を対象とした4件の研究を選択した。平均研究期間は7.5カ月(3〜18カ月)であった。いずれの研究でも、重要な主要アウトカムである「健康関連のQOL」を検討していなかった。副次的アウトカムのうち2項目「レボチロキシン(すなわち甲状腺ホルモン)補充量のベースラインから試験終了時における変化」および「費用」についても評価されていなかった。 バイアスのリスクが高い1件の研究では、亜セレン酸ナトリウム200 µg+レボチロキシンをプラセボ+レボチロキシンと比較した結果、主観的健康状態の改善に統計学的有意性が認められた(18例中14例に対して18例中3例)。3件の研究では、セレノメチオニン200 µgが血清中抗甲状腺ペルオキシダーゼ抗体濃度を低下させ、ベースラインからの変化に統計学的有意性が認められたが、この臨床的関連性は不明である。2件の研究で有害事象が報告されたが、セレン補充群とプラセボ群で認められた有害事象件数は同程度であった。いずれの研究でもセレノメチオニン200 µg + LT4群で有害事象が1件報告されたのに対し、対照群では有害事象が認められなかった。



《注意》この日本語訳は、臨床医、疫学研究者などによる翻訳のチェックを受けて公開していますが、訳語の間違いなどお気づきの点がございましたら、eJIM事務局までご連絡ください。なお、2013年6月からコクラン・ライブラリーのNew review, Updated reviewとも日単位で更新されています。eJIMでは最新版の日本語訳を掲載するよう努めておりますが、タイム・ラグが生じている場合もあります。ご利用に際しては、最新版(英語版)の内容をご確認ください。