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Selenium supplementation for Hashimoto's thyroiditis

  1. Esther J van Zuuren1,*,
  2. Amira Y Albusta2,
  3. Zbys Fedorowicz3,
  4. Ben Carter4,
  5. Hanno Pijl5

Editorial Group: Cochrane Metabolic and Endocrine Disorders Group

Published Online: 6 JUN 2013

Assessed as up-to-date: 2 OCT 2012

DOI: 10.1002/14651858.CD010223.pub2


How to Cite

van Zuuren EJ, Albusta AY, Fedorowicz Z, Carter B, Pijl H. Selenium supplementation for Hashimoto's thyroiditis. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD010223. DOI: 10.1002/14651858.CD010223.pub2.

Author Information

  1. 1

    Leiden University Medical Center, Department of Dermatology, Leiden, Netherlands

  2. 2

    AMA International University of Bahrain, College of Medicine, Manama, Bahrain

  3. 3

    The Cochrane Collaboration, UKCC (Bahrain Branch), Awali, Bahrain

  4. 4

    Cardiff University School of Medicine, Institute of Primary Care & Public Health, Cardiff, UK

  5. 5

    Leiden University Medical Centre, Department of Endocrinology, Leiden, Netherlands

*Esther J van Zuuren, Department of Dermatology, Leiden University Medical Center, PO Box 9600, B1-Q, Leiden, 2300 RC, Netherlands. E.J.van_Zuuren@lumc.nl.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 6 JUN 2013

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Abstract

  1. Top of page
  2. Abstract
  3. Plain language summary

Background

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).

Objectives

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.

 

Plain language summary

  1. Top of page
  2. Abstract
  3. 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.