Selenium supplementation for Graves–Basedow disease and orbitopathy: A review

Selenium supplementation boosts thyroid hormone levels (TSH, FT4, FT3), reduces thyroid autoantibodies (TPOAb, TgAb, TRAb), and enhances clinical outcomes—such as quality of life, reduced ocular involvement, and slower disease progression—in patients with GBD and GBD orbitopathy.

Autoimmune thyroid diseases represent the most common form of organ-specific autoimmunity, with Graves–Basedow disease (GBD) and Hashimoto’s thyroiditis constituting the two major clinical entities. GBD is driven by loss of immune tolerance to the thyrotropin receptor (TSHR), resulting in pathogenic TSHR antibodies that stimulate thyroid hormone overproduction. Clinically, GBD manifests with hyperthyroidism, diffuse goiter, ophthalmopathy, and, less frequently dermopathy. Global prevalence ranges from 0.5% to 2%, with a greater burden among females.

Nutritional influences, particularly micronutrient status, have been identified as key modifiers of autoimmune thyroid disease risk. Selenium is of particular relevance because the thyroid gland holds the highest selenium density per gram among human tissues. Selenium is incorporated into selenoproteins involved in antioxidant defense, thyroid hormone activation, and immune regulation. Deficiency has been linked to dysregulation of Th1/Th2 immune activity, reduced regulatory T lymphocytes function, increased oxidative stress, and impaired conversion of thyroxine (T4) to triiodothyronine (T3).

Multiple studies demonstrate that individuals with GBD exhibit lower serum selenium concentrations compared with healthy controls. This has led to the hypothesis that selenium supplementation may attenuate autoimmune activity, boost thyroid hormone balance, and reduce the severity of Graves’ orbitopathy. The therapeutic role of selenium is now of growing interest, but clinical practice guidelines remain inconsistent due to variation in trial methodologies and outcomes.

Objective

This scoping review sought to synthesize clinical evidence and evaluate selenium supplementation in GBD—with or without orbitopathy—across biochemical, immunological, and clinical outcome measures.

[1] Study design

The research was assessed by following the Preferred Reporting Items for systematic reviews and meta-analyses (PRISMA) and the modified version of the Population, Interventions, Comparators, and Outcomes (PICO) framework (Figure 1).

[2] Data sources and search strategy

A comprehensive search of Google Scholar, PubMed/Medline, Scopus, Biosis, ProQuest, and Web of Science was performed for English-language studies issued from January 2000 to March 2025. The search terms included combinations of:

• Graves–Basedow disease
• Graves’ disease
• Hyperthyroidism
• Selenium
• Selenium supplementation
• Effectiveness
• Outcomes

[3] Screening and selection

Three independent reviewers screened titles and abstracts using the Rayyan web tool. Full texts were evaluated via the Joanna Briggs Institute (JBI) Critical Appraisal Checklist. Disagreements were resolved through consensus.

[4] Inclusion criteria

• Studies involving selenium use and/or GBD or GBD orbitopathy.
• Human studies involving adult participants.
• Any geographic location or setting.
• Study types including clinical trials, systematic reviews, meta-analyses, reviews, and scoping reviews.
• Data extracted using a standardized predefined Excel template.
• Publications written in English.

[5] Exclusion criteria

• Studies originating from databases other than those specified.
• Studies involving populations such as pregnant women or animals.
• Non-eligible study types including conference abstracts, commentaries, preprints, letters to the editor, non-peer-reviewed articles, and letters.
• Studies using other forms of data extraction methods not aligned with the predefined template.
• Publications written in non-English language.

[6] Data extraction

Extracted data were recorded in a standardized Excel spreadsheet, including:

• Study design and setting
• Sample size and volunteer characteristics
• Selenium dose and formulation
• Duration of follow-up
• Baseline selenium levels
• Biochemical and clinical outcomes

[7] Endpoints

Studies involving GBD patients mainly focused on biochemical and clinical markers before and after selenium supplementation. The key parameters evaluated included:

• Thyroid hormone levels (Thyroid-stimulating hormone [TSH], FT4, FT3).
• Autoantibody concentrations (Thyroid peroxidase antibodies [TPOAb], Thyroglobulin antibodies [TgAb], Thyrotropin receptor antibodies [TRAb]).
• Rates of disease remission and relapse.
• Overall control of hyperthyroidism from both clinical and laboratory perspectives.

In contrast, studies involving patients with Graves-Basedow orbitopathy assessed selenium’s effect on ophthalmic and quality-of-life outcomes. The measures reported included:

• Clinical activity score (CAS) to reflect disease activity.
• Alterations in vision-related and general quality-of-life scores (Graves’ ophthalmopathy – quality of life [GO-QOL] total, visual function subscale, psychological function subscale).
• Alteration in eyelid aperture and documented improvements over time.
• Measures of exophthalmos (proptosis), including both reduction and degree of improvement.

[8] Statistical approach

Due to marked heterogeneity in study design, follow-up duration, and outcome definitions, no meta-analysis was performed. Results were synthesized descriptively.

[1] Study selection and characteristics

• Total clinical trials: 15
  (a) 11 trials with participants having GBD
  (b) 4 trials with participants having GBD orbitopathy

• Sample size
  Mostly <100 participants; predominantly women

• Age
  (a) GBD trials: Mean age 39.1 years (selenium group) vs. 39.7 years (control group)
  (b) GBD orbitopathy trials: Mean age 42.2 years (selenium group) vs. 44.6 years (control group)

• Follow-up duration
  4 weeks – 5 years

[2] Selenium status and dosing

• Baseline selenium concentrations:
  (a) The levels were assessed in 4 out of 11 GBD studies. Selenium concentrations were normal in 3 studies and low in 1 study.
  (b) The levels were assessed in 2 out of 4 GBD orbitopathy studies. Both reported normal selenium levels. In 1 study, concentrations were estimated only in the intervention group.
• Selenium's dosage range:
  It varied widely but commonly ranged from 60 to 300 µg/day.
• Formulations
  Various forms of selenium were administered, including selenite, selenium yeast, selenium glycinate, selenomethionine, a combination of selenomethionine and selenium yeast, L-selenomethionine, antioxidant capsules, and selenious yeast.

[3] Concomitant or previously utilized strategy for GBD

• In 10 of the 11 studies involving GBD patients, methimazole was employed as the baseline treatment.
• In one of these studies, antioxidants were used as the baseline management instead of methimazole.
• In the studies focusing on GBD orbitopathy, the individuals had previously been treated with radioactive iodine, methimazole, or thyroidectomy and stayed euthyroid throughout the studies.

[4] Clinical outcomes following selenium intervention

• Positive results were reported in 9 of the 11 GBD studies and in all 4 GBD orbitopathy studies, with at least one significant and favorable outcome witnessed in those who received selenium.
• Outcomes included achieving a euthyroid state, reductions in FT3 and FT4 levels, increases in TSH, and decreases in TgAb, TPOAb, and TRAb titers.
• Selenium also enhanced the effect of antithyroid drugs, particularly in those with recurrent GBD or suboptimal selenium and vitamin D levels, and reduced the incidence of hypothyroidism in some studies.
• All four studies on those with GBD orbitopathy reported at least two favorable clinical outcomes following selenium use.
• CAS improved in three of four studies at 6 months and in both studies at 12 months.
• Total GO–QOL scores exhibited improvement in one of two studies at 6 months and one of two studies at 12 months.
• Visual functioning scores improved in one of three studies at 6 months and one of two studies at 12 months.
• Psychological functioning scores improved in one of three studies at 6 months and one of two studies at 12 months.
• Palpebral (eyelid) aperture changes displayed improvement in one of two studies at 6 months, while exophthalmos changes or improvement were not observed in the studies at 6 months.​​​​​​​

This review synthesizes two decades of clinical evidence evaluating selenium supplementation in GBD and GBD orbitopathy. Across the included trials, selenium was associated with improvements in thyroid hormone profiles and reductions in autoimmune antibody titers. These findings align with mechanistic data showing that selenium-dependent enzymes regulate thyroid hormone activation, reduce oxidative stress, and support immune homeostasis.

The observed improvements in orbitopathy outcomes are biologically plausible given selenium’s antioxidant properties and its role in modulating fibroblast and cytokine activity in orbital tissues. The collective findings suggest that selenium may serve as a beneficial adjunct, particularly in patients residing in selenium-deficient regions or presenting with active orbitopathy. Future research must prioritize:

• Randomized trials with adequate sample sizes
• Standardization of selenium dose and formulation
• Stratification by baseline selenium status
• Long-term follow-up to determine relapse and remission patterns

Additionally, research should also examine whether selenium has an additive or synergistic effect when combined with existing nonsurgical therapies for Graves orbitopathy—such as glucocorticoids, immunomodulators, biologics, radiation, or surgical intervention—and whether supplementation could minimize the need for more intensive treatments.