Serum Selenium Is Low in Newly Diagnosed Graves' Disease

A Population-Based Study

Inge Bülow Pedersen; Nils Knudsen; Allan Carlé; Lutz Schomburg; Josef Köhrle; Torben Jørgensen; Lone Banke Rasmussen; Lars Ovesen; Peter Laurberg


Clin Endocrinol. 2013;79(4):584-590. 

In This Article

Abstract and Introduction


Context Selenium deficiency may play an important role in the initiation and progression of autoimmune thyroid disease.

Objective To compare serum selenium (s-Se) values in patients with newly diagnosed autoimmune thyroid disease and controls from the Danish population.

Design and settings S-Se was measured in triplicate by a fluorimetric method.

Participants Patients with newly diagnosed Graves' disease (GD) (n = 97) or autoimmune overt hypothyroidism (AIH) (n = 96), euthyroid subjects with high serum levels of thyroid peroxidase antibody (TPO-Ab) (TPO-Ab > 1500 U/ml, n = 92) and random controls (n = 830).

Main outcome measure Differences in s-Se values.

Results S-Se was lower in patients with GD than in controls (mean (SD), GD: 89·9 μg/l (18·4); controls: 98·8 μg/l (19·7), P < 0·01). This was confirmed in a multivariate logistic regression model adjusting for age, sex, mineral supplements, smoking, geographical region and time of sampling (P < 0·01). In a linear model, s-Se was similar in patients with AIH (mean (SD): 98·4 μg/l (24·9)) and in controls (P = 0·86). In the multivariate model however, s-Se was marginally lower in patients with AIH compared to controls (P = 0·04). There was no significant difference in s-Se between euthyroid participants with high TPO-Ab and random controls (linear: P = 0·97; multivariate: P = 0·27).

Conclusion Patients with newly diagnosed GD and AIH had significantly lower s-Se compared with random controls. Our observation supports the postulated link between inadequate selenium supply and overt autoimmune thyroid disease, especially GD.


Autoimmune thyroid diseases (AITD) are the most common autoimmune disorders in the population. Several studies including twin studies and epidemiological studies have demonstrated that genetic factors are crucial determinants in the susceptibility to autoimmune disease. However, on a given genetic background, environmental and endogenous factors such as age and previous parities play an important role in the development and maintenance of AITD. Among the many environmental factors that have been suggested to influence the development of thyroid autoimmunity, the iodine intake may be the most important. Other suggested risk factors include smoking, oestrogens, drugs, stressful life events, irradiation, infection, allergy, alcohol consumption and selenium deficiency.[1]

Selenium is an essential trace mineral and an essential nutrient for synthesis of the amino acid selenocysteine which is incorporated into a number of selenoproteins. Until now, 25 human genes encoding selenoproteins are known, of which most are enzymes.[2] The thyroid gland is one of the organs with the highest content of selenium per mass unit due to the presence of several selenoproteins involved in thyroid hormone metabolism. Selenium-containing glutathione peroxidases may play an important role in the antioxidant defence of the thyroid gland by protecting the thyrocytes from any excess hydrogen peroxide (H2O2) produced during thyroid hormone synthesis. In cases of severe iodine deficiency (ID), thyroidal iodine autoregulation and the high serum TSH stimulate the production of H2O2. When the selenium availability is below a certain value, the glutathione peroxidase activity may be insufficient to remove the excess H2O2, which may be one of the mechanisms involved in thyroid gland destruction as seen in areas with combined iodine and selenium deficiency.[3] However, results from a recently published mouse model in which all thyroid selenoproteins were genetically deleted questioned the importance of thyroid glutathione peroxidase expression.[4] An alternative explanation highlights the effects of selenium on the immune system, postulating that selenium deficiency likely constitutes a risk factor for a feed-forward derangement of the derailed immune system–thyroid interaction in AITD.[5,6]

Furthermore, selenium is an essential part of the iodothyronine deiodinase (DIO) enzymes, and selenium deficiency is followed by a decreased conversion of thyroxine (T4) to the active hormone triiodothyronine (T3). This interaction has – as far as we know – never been observed in humans. As DIO enzymes are high in the hierarchical supply of selenoproteins, a nutritional selenium deficiency seems not to affect their expression.

A special field where selenium deficiency may play an important role is in the initiation and progression of autoimmune thyroid disease in genetically predisposed individuals. Both cell-mediated and the humoral immune response may be impaired in selenium deficiency, and it has been suggested that this effect of selenium deficiency is present already at mild and moderate selenium deficiency.[5,6]

In Denmark, selenium deficiency appears not to be a general problem.[7] The aim of our study was to evaluate signs of selenium deficiency in patients with autoimmune thyroid disease by comparing serum selenium (s-Se) values in patients with newly diagnosed Graves' disease (GD), autoimmune overt hypothyroidism (AIH) and controls from the Danish population.