Selenium Supplementation in Patients with Hashimoto Thyroiditis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Abstract

Background: Hashimoto thyroiditis (HT) is the most common cause of hypothyroidism in iodine-sufficient areas. Selenium is an essential trace element required for thyroid hormone synthesis and exerts antioxidant effects. Therefore, it may be of relevance in the management of HT. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the effect of selenium supplementation on thyroid function (thyrotropin [TSH], free and total thyroxine [fT4, T4], free and total triiodothyronine [fT3, T3]), thyroid antibodies (thyroid peroxidase antibodies [TPOAb], thyroglobulin antibodies [TGAb], thyrotropin receptor antibody [TRAb]), ultrasound findings (echogenicity, thyroid volume), immune markers, patient-reported outcomes, and adverse events in HT. The study protocol was registered on PROSPERO (CRD42022308377). We systematically searched MEDLINE, Embase, CINHAL, Web of Science, Google Scholar, and the Cochrane CENTRAL Register of Trials from inception to January 2023 and searched citations of eligible studies. Two independent authors reviewed and coded the identified literature. The primary outcome was TSH in patients without thyroid hormone replacement therapy (THRT); the others were considered secondary outcomes. We synthesized the results as standardized mean differences (SMD) or odds ratio (OR), assessed risk of bias using the Cochrane RoB 2 tool, and rated the evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Results: We screened 687 records and included 35 unique studies. Our meta-analysis found that selenium supplementation decreased TSH in patients without THRT (SMD -0.21 [confidence interval, CI -0.43 to -0.02]; 7 cohorts, 869 participants; I² = 0%). In addition, TPOAb (SMD -0.96 [CI -1.36 to -0.56]; 29 cohorts; 2358 participants; I² = 90%) and malondialdehyde (MDA; SMD -1.16 [CI -2.29 to -0.02]; 3 cohorts; 248 participants; I² = 85%) decreased in patients with and without THRT. Adverse effects were comparable between the intervention and control groups (OR 0.89 [CI 0.46 to 1.75]; 16 cohorts; 1339 participants; I² = 0%). No significant changes were observed in fT4, T4, fT3, T3, TGAb, thyroid volume, interleukin (IL)-2, and IL-10. Overall, certainty of evidence was moderate. Conclusions: In people with HT without THRT, selenium was effective and safe in lowering TSH, TPOAb, and MDA levels. Indications for lowering TPOAb were found independent of THRT.

Keywords: Hashimoto thyroiditis; TPOAb; TSH; autoimmune thyroiditis; selenium; systematic review and meta-analysis.

FIG. 1.

Flowchart for inclusion of the 35 studies adapted from the PRISMA 2020 statement. Six databases were systematically searched during the identification phase. Titles and/or abstracts were screened, and if records were eligible, the full text was assessed during the screening phase, resulting in the total number of studies included. Records refer to the title and/or abstract of a report. A report is a document that provides information about a study. AE, adverse event; Echo, ultrasound echogenicity; fT3, free triiodothyronine; fT4, free thyroxine; IM, immune markers including glutathione peroxidase, malondialdehyde, superoxide dismutase, total antioxidant capacity; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses; QoL, quality of life; T3, total triiodothyronine; T4, total thyroxine; TGAb, thyroglobulin antibodies; TPOAb, thyroid peroxidase antibodies; TRAb, thyrotropin receptor antibody; TSH, thyrotropin; Vol, thyroid volume.

FIG. 2.

Effect of selenium supplementation on TSH (mIU/L), stratified by thyroid status, in patients with Hashimoto thyroiditis without thyroid hormone replacement therapy (n = 869). Black rectangles represent SMD for each study; the size of the rectangle is proportional to the weight of the study for the pooled effect. Horizontal lines indicate CI. The black diamond summarizes the pooled SMD data. CI, confidence interval; Control, Control group receiving placebo or nothing; SMD, standardized mean differences.

FIG. 3.

Effect of selenium supplementation on TPOAb (IU/mL), stratified by thyroid hormone replacement therapy, in Hashimoto thyroiditis (n = 2358). Black rectangles represent SMD for each study; the size of the rectangle is proportional to the weight of the study for the pooled effect. Horizontal lines indicate CI. The black diamond summarizes the pooled SMD data. (1)/(2) Indicate cohorts 1 and 2 of the study.