Effect of selenium supplementation on the development of Hashimoto thyroiditis – a review of the literature

INTRODUCTION

Hashimoto’s thyroiditis is a chronic inflammatory condition that affects the thyroid gland. Today it is considered the most common autoimmune disease, the most common endocrine disorder, and the most common cause of hypothyroidism [1-5]. Overt hypothyroidism occurs with a frequency of 0.2% to 5.3% within the European population. In the United States, on the other hand, the percentage is lower, ranging from 0.3% to 3.7% of the population. Values depend on geographic location, genetic factors, age, and gender, among other factors. Hypothyroidism affects men about 10 times less often than women. The likelihood of developing the disease increases with age. For example, in women ≥ 75 years of age, the risk increases by 20% [6, 7]. Based on aetiology, Hashimoto’s thyroiditis can be primary or secondary.

TYPES OF HASHIMOTO’S DISEASE

Primary Hashimoto’s thyroiditis is the most common form of thyroiditis and refers to cases among which no clear cause can be identified. Clinically, the most common symptom faced by patients is enlargement of the gland (goitre), proceeding with or without hypothyroidism, and a marked lymphocytic infiltration of the thyroid gland. The primary form can be isolated, but also occurs in combination with other autoimmune diseases (in particular, type 1 diabetes and Sjögren’s syndrome can be distinguished here), or with other diseases affecting the thyroid gland (including papillary thyroid carcinoma) [8, 9].
The secondary form of Hashimoto’s thyroiditis, on the other hand, includes those disease entities among which the agent responsible for its presence can be clearly identified. Often, it is induced by the administration of immunomodulatory drugs. It has been shown that the administration of interferon , used to treat hepatitis C infections, can induce or exacerbate the symptoms of thyroiditis [10].

PATHOMECHANISM OF HASHIMOTO’S THYROIDITIS

Hashimoto’s thyroiditis occurs when the immune system produces antibodies that destroy the cells of the thyroid parenchyma. Pathological changes affecting the thyroid gland in the course of Hashimoto’s disease involve both the interstitium around the thyroid follicles and the cells themselves. In the course of this disease, there is interstitial infiltration of the gland by mononuclear cells, mainly lymphocytes, but also plasma cells and macrophages, which contributes to thyrocyte damage [9]. As a consequence of the above changes, there is an insufficient production of thyroid hormones and a compensatory proliferation of intact follicular cells to maintain the body’s normal hormonal balance [11].

SELENIUM AS A TRACE ELEMENT

Micronutrients, or trace elements, are chemical elements that occur in plant and animal organisms in trace amounts. In humans, the requirement for micronutrients is less than 100 mg per day. Among this group can be distinguished selenium, which is a relevant micronutrient for the organism [12]. In the 1980s, sodium selenite supplementation was shown to have a beneficial effect on the course of, among others, Kashin-Beck disease, in which cartilage tissue dies off, and Keshan disease (endemic juvenile cardiomyopathy), the cause of which was found to be selenium deficiency. It is noteworthy that although selenium supplementation in people with selenium deficiency can have positive effects, in people with normal levels in the body, it can contribute to the development of certain diseases [13].
Selenium has an important function in thyroid hormone-related metabolism. It is also involved in combating oxidative stress [14]. Selenocysteine is an amino acid included in selenoproteins. Glutathione peroxidase (GPx), thioredoxin reductase (TXNRD), and iodothyronine deiodinase (DIO) are just some of the selenoproteins found in humans so far known.

SELENIUM’S PROPERTIES IN THYROID FUNCTION

Thyroid peroxidase, via hydrogen peroxide, activates iodine ions entering the thyrocytes. At the same time, under the action of this enzyme, the activated iodine attaches to tyrosine residues located on thyroglobulin molecules, in effect leading to the formation of mono-iodotyrosine and diiodotyrosine. From the latter, coupling results in the formation of triiodothyronine and thyroxine [15, 16]. Thyroid hormone synthesis is a process that under physiological conditions is limited by the production of hydrogen peroxide by thyrocytes. In a situation where iodine deficiency occurs, thyroxine-influenced thyrocytes begin to produce increased amounts of iodine. This results in gradual damage to thyroid cells. Selenoproteins such as GPx and TXNRD, as free radical scavengers, have the ability to destroy excessive hydrogen peroxide, which protects the cell membrane, thereby helping to reduce oxidative stress. In a situation where there is selenium deficiency, GPx activity decreases. At the same time, the degradation of excessively produced hydrogen peroxide is slowed down. Increased sensitivity of thyrocytes to oxidative stress can lead to their necrosis [17]. Selenium deficiency reduces the activity of iodothyronine deiodinases. This results in a lack of thyroxine activation, thus preventing the proper function of thyroid hormones.

SELENIUM IN THE HUMAN BODY

Selenium occurs in the body in many forms and can be excreted from the body through the lungs, but also through urine or faeces. Commonly, the material for laboratory tests for selenium is urine, blood, and hair [18, 19]. Serum selenium concentration is not the best measure of its content in tissues. Therefore, even the right amount of selenium in serum does not guarantee the right amount of this micronutrient in organs, including the thyroid. A better biomarker reflecting selenium levels in the body is the main protein that transports and stores it, selenoprotein. In a situation where there is a selenium deficiency, the amount of selenoprotein will decrease first. In contrast, in a situation in which selenium is supplemented, the body will first increase selenoprotein stores and only in the next stage will the amount of selenium in the blood serum increase [20, 21]. The selenium present in hair reflects the saturation of the body with selenium over a period of several weeks to even several months. A study was conducted in China, which concluded that selenium content in hair < 0.20 mg/kg body weight was characteristic of selenium deficiency in the body. In contrast, its content of ≥ 0.50 mg/kg body weight indicated a normal amount of selenium [22].

AIM OF THE WORK AND REVIEW METHODS

Given that reduced selenium concentrations in human blood may be an independent risk factor for thyroid disease, we decided to review the literature and try to assess the effect of selenium supplementation on the development of Hashimoto’s thyroiditis. To do this, we used scientific publications published in PubMed, Google Scholar, the available literature, as well as other commonly available sources by typing the search terms: selenium, thyroid diseases, oxidative stress. We have included 47 works in the review, most of which were published after the year 2000. The subject matter of the works was the main criterion for selection based on which we made our choice. Excluded from the database of available articles were those whose topics differed significantly from those we covered and those published before 2000, with the exception of 3. We decided to include these 3 works in the bibliography because we believe they contain relevant data for the subject matter.

DESCRIPTION OF A STATE OF KNOWLEDGE

EFFECT OF SELENIUM ON THE IMMUNE SYSTEM

Selenium, as a trace element, has been identified as an important risk factor for Hashimoto’s thyroiditis [23]. At the same time, some of the studies conducted so far indicate that patients struggling with this disease have reduced selenium levels [24, 25]. In one experiment conducted in the Ankara region of Turkey, an area characterised by high iodine content, selenium deficiency was detected among patients with subclinical hypothyroidism. This may be due to reduced enzyme activity, including that of glutathione peroxidase, which has potent antioxidant effects that guarantee the integrity of cell membranes [11].
Selenium deficiency is commonly associated with impaired immune function. In a cellular-type immune response, selenium can reduce the number of antibodies produced by the thyroid gland by regulating secreted, activated T cells [26]. Therefore, selenium deficiency may enhance the immune response. In a study conducted in 2022, a possible therapeutic effect of selenium on the development of Hashimoto’s disease was identified. Namely, selenium supplementation at a dose of 100 µg/day, positively affects the functioning of thyroid function, by decreasing the level of interferon γ and increasing interleukin 1β levels [27].

SELENIUM SUPPLEMENTATION AND ITS EFFECT ON THYROID FUNCTION

Furthermore, in 2017, researchers conducted a study on the immune function of selenomethionine. The study sample consisted of 21 patients suffering from Hashimoto’s disease, but with normal thyroid function. They were treated with myo-inositol and selenium (600 mg/83 µg) tablets, twice a day, for a period of 6 months. After treatment, there was a significant reduction in thyrotropin levels. At the same time, interestingly, there was also a significant reduction in the concentration of the chemokine CXCL10. Interferon  stimulates thyroid cells to secrete CXCL10. In turn, its serum levels often correlate with the percentage of lymphocytes and monocytes infiltrating thyroid tissue, which is proportional to the degree of thyroid damage [28, 29]. The immunomodulatory effect of myo-inositol in combination with selenium on CXCL10 suggests that it may contribute to reducing immune reactivity [30].
Hashimoto’s thyroiditis is an autoimmune disease and is therefore characterised by, among other things, increased production of antibodies to thyroid peroxidase. This may suggest that an abnormal humoral-type immune response may be one of the risk factors associated with this pathology. One clinical study showed that selenium supplementation led to a reduction in thyroid peroxidase antibody titres, which significantly improved patients’ quality of life [31-34]. It is noteworthy that the patients in the study, with high levels of anti-thyroid peroxidase antibodies (> 200), also had reduced levels of anti-thyroglobulin antibodies. Based on this, it can be concluded that patients with higher antibody values may experience greater benefit from selenium supplementation.
At the same time, M. Nordio and S. Basciani showed that supplementation with myo-inositol in combination with selenium for a period of 6 months significantly contributed to a decrease in serum thyrotropin levels. At the same time, it is noteworthy that in the study group treated with selenium alone, without association with myo-inositol, no reduction in the amount of thyrotropin produced was observed [32].
Although mild hypothyroidism can often be asymptomatic, nearly 30% of patients struggling with the condition may experience unpleasant symptoms related to depressed mood, fatigue, muscle weakness, and increased sleepiness. At the same time, insufficient selenium levels in the body are associated with negative moods [35]. In a study, patients receiving selenium reported significant improvements in mood. This may be explained by selenium’s key role in brain function and the association of selenium deficiency with old age and cognitive decline [35, 36].
A particularly vulnerable population with Hashimoto’s disease are women during pregnancy and childbirth. Pregnant women with positive, high values of thyroid peroxidase antibodies are more likely to suffer from miscarriage, preterm labour, and the development of postpartum thyroid dysfunction [37]. A study showed that selenium supplementation at a dose of 200 µg/day, during labour and postpartum, decreased the incidence of both hypothyroidism and postpartum thyroid dysfunction [38].
Among patients struggling with Hashimoto’s thyroiditis, levothyroxine is the most common treatment. In an ongoing experiment involving 60 patients with Hashimoto’s disease, the combination of levothyroxine and selenium supplementation was more effective than the use of levothyroxine alone in the therapy used [39]. Wichman et al. showed that selenium supplementation effectively reduced thyroid peroxidase antibodies at 3, 6, and 12 months and thyroglobulin antibodies at 12 months in levothyroxine-treated patients [40].
The production of thyroid peroxidase antibodies was also shown to be significantly reduced in patients receiving 200 µg selenomethionine, but not in those receiving 200 µg sodium selenite. This difference may be due to the fact that the absorption of sodium selenite is about two-thirds that of selenomethionine [40].

OVERDOSE OF SELENIUM SUPPLEMENTS

However, it is also important to mention the possibility of consuming too much selenium, which can have adverse effects on human health. Consuming about 330 g of selenium per day can prove toxic not only to growth hormone and insulin-like growth factor type 1 metabolism, but also to thyroid hormones [41, 42]. Possible side effects of selenium overdose include nail and hair loss, anorexia, diarrhoea, depression, haemorrhage, liver and kidney necrosis, and blindness, among others [43]. Selenium intake, considered a safe dose, is 50-400 µg/day, while 850-900 µg/day may be considered toxic [44].

RESTRICTIONS ON THE USE OF SELENIUM SUPPLEMENTS

One of the risk factors for Hashimoto’s disease may be the wrong amount of selenium present in the body. However, current scientific evidence does not support selenium supplementation as part of a therapeutic plan for the treatment of this disease, despite selenium’s apparent ability to improve immune system function. If, in fact, the use of selenium supplements is required, it should be preceded by the determination of the actual concentration of this microelement in the body via laboratory methods, while taking into account the patient’s gender, age, and body weight [46].
It remains interesting that selenium supplementation in a patient suffering from Hashimoto’s thyroiditis, who additionally exhibits iodine deficiency, will not produce the expected results. In a study conducted in northern Congo, deterioration of thyroid function was observed in iodine-deficient patients undergoing selenium supplementation [47, 48]. Therefore, with this in mind, in addition to the above-mentioned factors that may determine the need for selenium supplementation, the patient’s iodine concentration should still be determined, such as in the daily urine collection [43]. In conclusion, the use of selenium in the form of selenomethionine will be beneficial in patients with deficiency of this microelement, with a concomitant adequate intake of iodine.

CONCLUSIONS

Selenium, which belongs to the micronutrients, is an essential element for the synthesis of selenoproteins, which include selenocysteine. In adults, 1 g of thyroid tissue has the highest selenium content compared to any other organ. Most of the widely known selenoproteins, such as glutathione peroxidase, are expressed in the thyroid gland and are involved in metabolising thyroid hormones, defending the organ against oxidative stress, and maintaining homeostasis within thyrocytes. Clinical studies conducted to date have shown that a lack, or deficiency, of selenium will increase the incidence of hypothyroidism, among other conditions. Selenium supplementation in Hashimoto’s thyroiditis is associated with reduced production of antibodies against thyroid peroxidase, while improving thyroid structure. However, before introducing selenium into the treatment plan for patients with Hashimoto’s disease, a variety of additional aspects must be considered, including the patient’s age, gender, weight, and saturation of the body with selenium and iodine. It is also important to remember to choose the right dosage – selenium consumed excessively can prove toxic to the body. This is especially important in recent years, when the problem of hypothyroidism affects an increasing percentage of people.

Disclosures

This research received no external funding.
Institutional review board statement: Not applicable.
The authors declare no conflict of interest.

References