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Selenium in thyroid disorders — essential knowledge for clinicians

Abstract

In the 1990s, selenium was identified as a component of an enzyme that activates thyroid hormone; since this discovery, the relevance of selenium to thyroid health has been widely studied. Selenium, known primarily for the antioxidant properties of selenoenzymes, is obtained mainly from meat, seafood and grains. Intake levels vary across the world owing largely to differences in soil content and factors affecting its bioavailability to plants. Adverse health effects have been observed at both extremes of intake, with a narrow optimum range. Epidemiological studies have linked an increased risk of autoimmune thyroiditis, Graves disease and goitre to low selenium status. Trials of selenium supplementation in patients with chronic autoimmune thyroiditis have generally resulted in reduced thyroid autoantibody titre without apparent improvements in the clinical course of the disease. In Graves disease, selenium supplementation might lead to faster remission of hyperthyroidism and improved quality of life and eye involvement in patients with mild thyroid eye disease. Despite recommendations only extending to patients with Graves ophthalmopathy, selenium supplementation is widely used by clinicians for other thyroid phenotypes. Ongoing and future trials might help identify individuals who can benefit from selenium supplementation, based, for instance, on individual selenium status or genetic profile.

Key points

  • Epidemiological data have suggested increased prevalence of benign thyroid disease with low selenium status, but the optimum range of intake is likely to be narrow, warranting a cautious approach to recommending selenium supplementation.

  • The effects of selenium supplementation might be mediated via repletion of antioxidant or immune-modulating selenoproteins, and polymorphisms in genes that encode selenoproteins might determine susceptibility to supplementation.

  • In chronic autoimmune thyroiditis, selenium supplementation reduces circulating levels of thyroid autoantibodies; however, evaluation of clinically important primary outcomes has not shown improvement and should be prioritized in future trials.

  • Observational studies have indicated that low selenium status is an iodine-independent risk factor for goitre; however, this finding has not been followed up by intervention trials in humans.

  • In Graves disease, selenium supplementation might facilitate biochemical restoration of euthyroidism and reduce ocular involvement, but these results need to be confirmed.

  • Treatment with selenium supplementation is widely used by clinicians across the spectrum of autoimmune thyroid diseases, despite the fact that it is recommended only in the treatment of mild Graves orbitopathy.

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Fig. 1: Selenoproteins are vital to the thyroid.
Fig. 2: Selenium intake in different countries.
Fig. 3: U-shaped relationship between selenium status and disease risk.

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Acknowledgements

The authors acknowledge the long-term collaboration within the ThyQoL group (T. Watt, Å.K. Rasmussen, P. Cramon, J. Bjørner, M. Grønvold, F. Pociot, U. Feldt-Rasmussen), which at present, among a number of efforts, is investigating the potential benefit of selenium supplementation in Graves disease and chronic autoimmune thyroiditis.

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All the authors researched data for the article, made substantial contributions to the discussion of content and reviewed and/or edited the manuscript before submission. K.H.W., M.P.R. and L.H. wrote the article.

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Correspondence to Laszlo Hegedüs.

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Glossary

Selenoproteins

Proteins that include a selenocysteine residue in their amino acid sequence.

Chronic autoimmune thyroiditis

Patients with thyroid autoantibodies with or without goitre and with or without hypothyroidism.

Selenium speciation

The chemical form or compound in which selenium occurs in food, in the environment or in the body.

Neutron activation analysis

An analytical method that uses a neutron beam to determine the concentrations of elements in a substance.

Blind staggers

Severe selenosis among animals, particularly livestock, characterized by impaired vision and an unsteady gait.

Selenosis

Poisoning due to excessive intake of selenium.

Thyroid-Specific Patient Reported Outcome (ThyPRO) questionnaire

The first thyroid disease-specific questionnaire developed to measure health-related quality of life across the spectrum of benign thyroid diseases.

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Winther, K.H., Rayman, M.P., Bonnema, S.J. et al. Selenium in thyroid disorders — essential knowledge for clinicians. Nat Rev Endocrinol 16, 165–176 (2020). https://doi.org/10.1038/s41574-019-0311-6

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