Vitamin D and autoimmune thyroiditis

Размещено на http://allbest.ru

VITAMIN D AND AUTOIMMUNE THYROIDITIS

^{1Pivtorak K.V., 2}Ivanhuk O.V.

¹National Pirogov Memorial Medical University (Vinnytsya, Ukraine)

^{2Municipal Non-commercial Enterprise Emergency medical care hospital (Vinnytsya, Ukraine)}

The primary role of vitamin D is the regulation of bone metabolism and the homeostasis of calcium and phosphorus. Over the past several decades, the importance of vitamin D in a variety of aspects unrelated to the skeletal formation has been studied, including the beneficial effects of vitamin D on endothelial dysfunction, insulin resistance and diabetes prevention, beneficial effects on the immune response in infectious diseases including tuberculosis, and immunomodulatory effects in autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, metabolic syndrome, cardiovascular disease, cancer, and all-cause mortality. Vitamin D prevents and promotes remission in patients with multiple sclerosis and improves the function of the gonads. The extensive range of vitamin D action is due to the presence of its receptors in many tissues. Recent evidence has shown a connection between low vitamin D levels and autoimmune thyroid diseases, such as Hashimoto's thyroiditis. This review aims to follow the role of vitamin D in the course of autoimmune thyroid disease. Vitamin D deficiency is one of the environmental risk factors for autoimmune thyroid diseases. Despite recent evidence that low serum 25-hydroxyvitamin D levels may influence the development of autoimmune thyroid disorders, the relationship between vitamin D deficiency and autoimmune thyroiditis and the incidence of hypothyroidism remains unclear. Further studies are needed to evaluate vitamin D's preventive and therapeutic effects in autoimmune thyroid diseases.

Key words: autoimmune thyroiditis, vitamin D, autoimmune diseases, metabolic-associated diseases, thyroid gland.

Introduction

In recent years, the relevance of vitamin D as an immune regulator has been emphasized. The immune system can generate an active compound of vitamin D, which has an immunomodulatory effect, thanks to the expression of 1-hydroxylase (CYP27B1) in cells. Vitamin D inhibits the production of inflammatory cytokines, such as interleukin 1, 6, 8, 12 and tumour necrosis factor. In addition, vitamin D facilitates the induction of regulatory T cells to reduce T cell-dependent immune responses in autoimmune diseases [1]. The CYP27B1 enzyme is not only found in the small intestine, skeleton and kidneys, as previously thought, but in almost all body cells, including the thyroid gland and immune cells [2]. Recent evidence suggests that vitamin D is also involved in preventing infections by reducing the proliferation of pathogens through the formation of neutrophil extracellular traps [3]. Vitamin D3 is synthesized in the skin (about 80%) under the influence of sunlight (UV radiation), while vitamin D2 is produced by plants, fungi and yeast (about 20%) [4]. Humans obtain vitamin D from three different sources: synthesis in the skin, food, and various dietary supplements. 25(OH)D3 is measured and used to indicate vitamin D status in the body. The first hydroxylation occurs in the liver and the second - in the kidneys, where calcidiol is hydroxylated to calcitriol, the biologically active form of vitamin D [5].

Some studies have shown that vitamin D protects against autoimmune diseases and thyroid malignancies, but the mechanism has not been elucidated [6]. It was found that vitamin D deficiency is observed in all races and all age groups [7]. Vitamin D deficiency is more common in people with obesity or obesity-related diseases such as diabetes and non-alcoholic fatty liver disease [8]. Therefore, vitamin D supplements can also potentially treat these pathologies [9].

hashimoto chronic autoimmune thyroiditis vitamin d genetics environmental factors

The aim of the study.

A literature review to investigate the relationship between Hashimoto's thyroiditis and vitamin D deficiency and to explore the relationship between them and associated exposure factors.

Main part

Hashimoto's thyroiditis is chronic autoimmune thyroiditis accompanied by lymphocytic infiltration, which can eventually destroy thyroid tissue [10]. Some studies suggest that autoimmune thyroiditis (AIT) results from a synergistic effect of genetics and environmental factors, but the exact mechanism is still unclear [11]. Other clinical studies have shown that AIT is associated with the occurrence of papillary thyroid carcinoma [12]. Currently, the incidence of AIT, which is asymptomatic in most patients, is also increasing. Therefore, understanding the incidence of AIT in the healthy population and its relationship with other relevant indicators contributes to the in-depth study of this disease.

In the last decade, there has been a clear tendency to increase the incidence of autoimmune thyroiditis in younger age groups. Antibodies to thyroid peroxidase circulate freely in the blood and are detected in 10-15% of healthy patients with euthyroidism in the laboratory [13].

More and more research confirms the critical role of sufficient vitamin D in human health. Vitamin D has also been associated with the development of inflammation, and vitamin D supplementation is beneficial in reducing the inflammatory response [14]. Recently, specific receptors for hormonally active forms of vitamin D were discovered, which are synthesized in non-classical tissues and cells, causing a more comprehensive range of physiological effects [15].

Two variants of the effect of vitamin D on the course of physiological processes in the body are considered: genomic and unrelated to the genome. The genomic mechanism of action consists of the fact that the intermediate products of vitamin D synthesis exert their effect in a very similar way to the mechanism of action of steroid hormones [16]. The impact on the cell membrane manifests the implementation of another effect of vitamin D. Cholecalciferol has been shown to directly or indirectly regulate the formation of proteins, lipids, hormones, and receptor proteins [17]. It has been established that vitamin D takes part in the differentiation and formation of cells of various tissues and organs, as well as in the processes of forming the immune system response [2].

Autoimmune diseases are one of the leading causes of disability and death after cardiovascular and oncological diseases. In most cases, the cause and mechanism of autoimmune pathology remain not fully elucidated even today. Many factors influence autoimmune disorders' pathogenesis, including dysmetabolic processes associated with vitamin D. Scientific studies claim that vitamin D is essential in forming immune system responses in various autoimmune and inflammatory diseases [18].

The thyroid gland (TG) is an organ that is one of the leading parts of the neuroendocrine and immune system, which is essential at various stages of a person's life. The increase in interest in the problems of the pathology of the thyroid gland in recent years is explained by its rapidly growing prevalence among the population of our country, which plays a significant social significance in these diseases. As a result of substantial achievements of thyroidology as a science, ideas about the essence of thyroid gland diseases have undergone severe changes [2]. The rapid increase in the number of thyroid gland diseases is due to the adverse influence of environmental factors and the deterioration of the general ecological background against the background of reduced immunological protection of the body. Environmental factors associated with autoimmune thyroiditis include radiation, smoking, viral infections, drug use, and stress [19]. The radiation emission resulting from the disaster at the Chornobyl NPP affected the thyroid gland first, which is due to a massive impact of iodine isotopes, the accumulation of which in the thyroid gland determines their tropism to this organ and is a real pathogenetic factor in the pathology of the thyroid tissue in the short and remote periods after exposure. It is common knowledge that thyroid gland diseases occupy the first place in the structure of endocrinopathies, and autoimmune pathology of the thyroid gland is found more often than other autoimmune diseases. The prevalence of autoimmune endocrine thyroid pathology, including autoimmune thyroiditis, Graves' disease, and postpartum thyroiditis, reaches about 5% of the population [20].

Several mechanisms explain the low concentration of vitamin D in patients with autoimmune thyroiditis and hypothyroidism: firstly, the low vitamin D content can be caused by its poor absorption from the intestine; secondly, not quite proper activation of vitamin D by the body [21].

When conducting clinical research [22], it was established that there is a clear connection between vitamin D deficiency and the autoimmune pathology of the thyroid gland. In one of the simultaneous studies, 119 people have examined: 62 patients with autoimmune thyroid pathology (autoimmune thyroiditis and Graves' disease), 32 patients without autoimmune thyroid pathology (nodular or diffuse goiter without hormonal dysfunction) and 25 people without pathology. The confirmation of an autoimmune disease of the thyroid gland was an increased titer of antibodies to TPO and thyrotropin (TSH) receptors. Deficiency or insufficiency of vitamin D was found in 82.9% of patients with diseases of the thyroid gland of various origins. Among patients in the control group, this level was 64%. At the same time, among patients with autoimmune thyroid gland pathology, the number of patients with vitamin D deficiency was 88.7%. Also, a direct connection between the level of TSH and the supply of vitamin D in the body has been established. Thus, the concentration of TSH in autoimmune thyroiditis was 7.8 mIU/l with an existing vitamin D deficiency (less than 20 ng/ml) and 3.4 mIU/l - with a normal concentration of vitamin D in the body. In patients without autoimmune thyroid gland pathology, there was no correlation between the concentration of TSH and the level of vitamin D in the blood. The results indicate the practicality of conducting a screening determination of the vitamin D concentration in the blood of patients with autoimmune thyroid pathology.

One study involved 75,436 patients who underwent a physical examination and serum thyroid hormone levels; however, only 5,656 patients had vitamin D concentrations determined. Thyroid dysfunction was significantly correlated with body mass index, abdominal circumference, and circulating TSH levels using multiple regression analysis. The TSH levels were higher in the vitamin D insufficiency and deficiency group. Conversely, free triiodothyronine and thyroxine levels were lower in these patients than in those with sufficient levels [23].

A randomized clinical trial conducted by Chahordoli included 42 women with Hashimoto's thyroiditis who were divided into vitamin D and placebo groups. The first group was estimated to receive 50,000 IU of vitamin D, while the second received a placebo weekly for three months. Laboratory parameters, such as the concentration of vitamin D, calcium, ATPO, A-TG, and thyroid hormones, were evaluated at the study's beginning and end using an enzyme immunoassay. In the first group, a significant decrease in A-TG and TSH was found after treatment, but there were no significant differences in ATPO levels between the two groups (p=0.08). The level of free hormones also changed insignificantly. Thus, it was concluded that vitamin D preparations were beneficial in reducing disease activity; however, additional evidence provided by controlled long-term studies is essential to establish its relevance in clinical practice [24].

In a study by Behera, 23 patients received doses of 60,000 IU per week of vitamin D for eight weeks, followed by the same dose once a month for four months. After six months, the concentration of antibodies to TPO and thyroid hormones in blood serum was again measured. The increase in vitamin D was statistically significant: from 15.33±5.71 ng/ml to 41.22±12.24 ng/ml. TPO antibody titers showed a statistically significant increase from 746.8±332.2 to 954.1±459.8 IU/ml (p=0.006), while TSH values showed a statistically significant decrease from 7.23±3.16 to 3.04±2.62 mlU/l (p=0.01) [25].

In a meta-analysis that included 25 studies involving 2695 cases and 2263 controls, patients with Hashimoto's thyroiditis had lower serum vitamin D levels than controls. The odds ratio of Hashimoto's thyroiditis was determined in individuals with vitamin D deficiency compared to control groups (1.94-5.3; p=5.7 x 10-6). These findings were consistent across all included studies - European and Asian, adult and pediatric, and medium- and high-quality studies. Higher differences in 25(OH)D values between groups were associated with sub-equatorial latitudes (<35° N/S, p=3.4 x 10-4) and moderate-income economies (gross national income 1000<USD< 12000, p=0.012). Gross national income (p=3.5 x 10-6) and mean serum thyrotropin levels in patients (p=0.017 in 21 studies) showed nonlinear moderation. The main finding illustrates a significant association between Hashimoto's thyroiditis and vitamin D. It partially explains the previous mixed evidence, contributing significantly to identifying factors associated with heterogeneity, highlighting under which conditions the strongest association exists [15].

In the meta-analysis by Taheriniya, although 6123 data sets were reviewed, only 42 patients met the inclusion criteria for this systematic review and meta-analysis. Lower vitamin D levels correlated with autoimmune thyroid diseases (p=0.013) [26].

A low concentration of vitamin D is the primary phenomenon involved in the pathogenesis of the disease. In other autoimmune diseases, vitamin D deficiency in the blood can be explained by malabsorption syndrome or lack of sufficient insolation due to skin pathology. In most cases, patients with the pathology of the thyroid gland do not have skin diseases and malabsorption. One of the possible explanations for the low concentration of vitamin D in the blood of such patients may be the accelerated metabolism of bone tissue [27]. In addition, high serum calcium and phosphorus levels and low levels of circulating parathyroid hormone can inhibit renal 25(OH) D1-a hydroxylase function. In general, vitamin D can help prevent or correct hypothyroidism and improve thyroid function [28].

In addition, it is noted that the vitamin D level is significantly lower among patients under 40. Some issues should be considered when interpreting the results. For example, when interpreting the results - seasonal fluctuations of vitamin D in the serum. This fact is confirmed in many works [29]. In addition, vitamin D bioavailability is reduced in overweight or obese individuals, but this factor has not been considered in most cases [30, 31].

Today, it is known that the role of vitamin D in immunity consists in the production of anti-inflammatory and immunoregulatory markers through the expression of vitamin D receptors in the nucleus of cells, which participates in the functioning of cellular immunity, stimulating innate and adaptive immune responses. Vitamin D receptor polymorphisms are associated with the susceptibility of individuals to thyroid diseases such as hypothyroidism. These receptors modulate the effects of vitamin D, both specific and intracellular. Polymorphism of the vitamin D receptor gene can reduce the activity of the last one. Using a meta-analysis, Wang et al. reported a significant association between vitamin D receptor gene polymorphisms and autoimmune thyroid diseases in different ethnic groups [32].

In modern medicine, vitamin D is a marker of the general state of health. Its deficiency has led to metabolic disorders, the development of autoimmune pathology, cardiovascular diseases, cancer, and mortality from all causes [33].

Conclusions

Despite some inconsistency in research results to date, most evidence suggests an association between low vitamin D levels and an increased risk of disease and/or higher antibody titers and/or more incredible difficulty in treating it.

Polymorphisms in genes related to vitamin D function and metabolism also have some influence on the risk of developing autoimmune thyroiditis.

The development of autoimmune thyroiditis is facilitated by an increase in vitamin D deficiency, forming a vicious circle.

Currently, there is insufficient data to support that there is no harm or benefit from receiving excess levels. Thus, a responsible approach is striving to achieve a vitamin D supply level within the reference ranges proposed in international guidelines.

Prospects for further research. In the future, additional data involving more individuals with comorbid pathology, the global scope of studies, and year-round monitoring of vitamin D levels will be needed to provide more unified recommendations for patients with autoimmune thyroiditis.

Размещено на Allbest.ru