European Journal of Cardiovascular Medicine

Hypothyroidism, a condition where the thyroid gland produces insufficient thyroid hormones, is a widespread disorder affecting millions of people globally. Thyroid hormones, particularly T3 and T4 , play a crucial role in regulating metabolic processes, growth, and development in the body. The most common cause of primary hypothyroidism is autoimmune thyroiditis, specifically Hashimoto’s thyroiditis, where the immune system attacks the thyroid gland. As a result, there is an impairment in the thyroid gland’s ability to produce sufficient amounts of thyroid hormones, leading to the compensatory elevation of TSH (1,2).

The global prevalence of hypothyroidism has been rising steadily, with an estimated 42 million people affected by thyroid disorders in India alone, as noted in epidemiological studies. The condition often presents with symptoms such as fatigue, weight gain, dry skin, constipation, and cold intolerance, which can severely impact the quality of life of those affected. Hypothyroidism can be categorized into subclinical hypothyroidism (elevated TSH levels but normal T3 and T4 levels) and overt hypothyroidism (elevated TSH levels with decreased T3 and T4 levels). While the clinical manifestations of overt hypothyroidism are well-recognized, subclinical hypothyroidism is often asymptomatic or has mild symptoms, making it harder to diagnose without laboratory testing (3-6).

Recent research has suggested that vitamin D deficiency may be associated with various autoimmune diseases, including thyroid disorders. Vitamin D, a fat-soluble vitamin, plays a vital role in calcium homeostasis and bone health. However, its effects extend far beyond the musculoskeletal system. Vitamin D is known to modulate immune responses and may influence the onset and progression of autoimmune diseases. The active form of vitamin D, 1,25-dihydroxyvitamin D, binds to the vitamin D receptor (VDR), which is widely expressed in human tissues, including immune cells and the thyroid gland. This receptor activity is thought to mediate many of the immune-regulatory effects of vitamin D, potentially playing a protective role in autoimmune thyroid disease, where the immune system mistakenly attacks the thyroid gland (7,8).

In recent years, the relationship between vitamin D and thyroid function has gained attention, especially in the context of hypothyroidism. Studies have shown that vitamin D deficiency is prevalent in patients with various forms of thyroid dysfunction, including autoimmune thyroiditis, Graves' disease, and hypothyroidism. However, the association between vitamin D deficiency and primary hypothyroidism, particularly its effect on thyroid function, remains inconclusive. While some studies have found a significant correlation between low vitamin D levels and increased TSH, others have failed to establish such a link. Moreover, the role of vitamin D supplementation in managing hypothyroidism, whether by improving thyroid function or preventing disease progression, is still under investigation (9,10).

The deficiency of vitamin D is especially concerning given its widespread prevalence. Despite living in sunny regions, many populations still experience inadequate vitamin D levels due to factors such as limited sun exposure, the use of sunscreen, cultural practices, and dietary habits that lack adequate vitamin D-rich foods like fatty fish, eggs, and fortified dairy products. Vitamin D deficiency has been linked not only to bone diseases such as osteoporosis and rickets but also to cardiovascular diseases, diabetes, and autoimmune disorders, including hypothyroidism. Furthermore, there is growing evidence suggesting that correcting vitamin D deficiency through supplementation may improve the clinical outcomes of various conditions, including autoimmune thyroid diseases (11).

Given these insights, the present study aims to investigate the association between vitamin D deficiency and thyroid function in patients with primary hypothyroidism. Specifically, the study examines the relationship between serum vitamin D levels and thyroid-stimulating hormone, along with thyroid hormones T3 and T4, in a cohort of patients diagnosed with primary hypothyroidism. By analyzing this correlation, the study seeks to contribute to the growing body of evidence on the potential role of vitamin D in thyroid health and explore the possibility of using vitamin D supplementation as an adjunctive therapy in managing hypothyroidism (12,13,14).

This study also seeks to highlight the importance of screening for vitamin D deficiency in patients with hypothyroidism, especially considering the potential benefits of vitamin D supplementation in improving thyroid function and overall health outcomes. While the evidence is still evolving, exploring the relationship between these two critical health factors thyroid function and vitamin D status may lead to more effective and holistic approaches to managing hypothyroidism.

Study Design and Duration:

This study was conducted over a period of 2 years from January 2023 to December 2024 In Andhra Medical College, King George Hospital, Visakhapatnam. The aim of the study was to investigate the relationship between vitamin D deficiency and thyroid function in patients diagnosed with primary hypothyroidism. All procedures were approved by the institutional review board before the start of the study.

Study Population: A total of 221 patients, aged between 20 to 60 years, who were diagnosed with primary hypothyroidism, participated in the study. Participants were recruited from the endocrinology outpatient department, King George hospital, Andhra medical college during the study period. The inclusion criteria for this study required that patients had a confirmed diagnosis of primary hypothyroidism and were within the age range of 20 to 60 years. Informed consent was obtained from each participant before their inclusion in the study. Exclusion criteria included patients currently undergoing treatment for hyperthyroidism, patients receiving thyroid hormone replacement therapy, and those taking medications such as glucocorticoids, estrogen, oral contraceptives, or iodine-based medications that could potentially interfere with thyroid function. Additionally, patients using calcium or vitamin D supplements were excluded from the study.

Data Collection:

After informed consent was obtained, each participant underwent a complete clinical examination, which included recording their medical history and performing a physical examination. Laboratory investigations were conducted to assess thyroid function and serum levels of 25-hydroxyvitamin D (25(OH) D) were measured using chemiluminescence immunoassay (CLIA) method. Based on the serum vitamin D levels, participants were categorized as follows: Deficient (<20 ng/ml), Insufficient (20-30 ng/ml), and Sufficient (>30 ng/ml).

Classification of Hypothyroidism:

 Participants were classified into three groups based on their serum TSH levels. Those with TSH levels ranging from 0.5-5 μIU/ml were classified as Euthyroid, those with TSH levels ranging from 5-15 μIU/ml as Subclinical Hypothyroidsm, and those with TSH levels greater than 15 μIU/ml as Overt Hypothyroidism.

Statistical Analysis:

Data were analyzed using SPSS version 16 for Windows. Descriptive statistics were computed for all variables, with continuous variables presented as mean ± standard deviation (SD) and categorical variables as frequencies and percentages. The relationship between vitamin D status and thyroid function (TSH, T3, and T4) was assessed using Pearson’s correlation coefficient. A p-value of less than 0.05 was considered statistically significant.

Ethical Considerations:

The study was conducted in full compliance with ethical standards, following the principles outlined in the Declaration of Helsinki. Ethical approval was obtained from the institutional review board of medical college and hospital. Informed consent was obtained from all study participants, ensuring that their participation was voluntary and that they were fully informed about the study’s objectives and procedures

Table 1: Demographic and Baseline Characteristics of the Study Population

Table 2: Distribution of Vitamin D Status in Patients with Primary Hypothyroidism

Comparison of Thyroid Function and Vitamin D Levels: The study compares thyroid hormone (TSH, T3, T4) levels across different groups based on their thyroid status. Vitamin D levels were found to be significantly lower in patients with more severe forms of hypothyroidism.

Table 3: Comparison of Vitamin D and Thyroid Function:

Correlation of Vitamin D Levels with TSH, T3, and T4: Pearson’s correlation analysis showed that vitamin D deficiency was negatively correlated with TSH, and positively correlated with T3 and T4 in the deficient group.

Table 4: Correlation of Vitamin D Levels with TSH, T3, and T4

The association between vitamin D deficiency and hypothyroidism has been an area of increasing interest due to the widespread prevalence of vitamin D deficiency and the rising rates of thyroid disorders. Our study, which examined 221 patients diagnosed with primary hypothyroidism, found a significant prevalence of vitamin D deficiency, with 69.64% of participants exhibiting vitamin D levels lower than 20 ng/ml. Moreover, the results revealed a significant negative correlation between vitamin D deficiency and thyroid-stimulating hormone, particularly in patients with more severe forms of hypothyroidism, such as overt hypothyroidism. This discussion will compare our findings with other published studies and explore potential mechanisms that could explain the observed associations (15,16).

The high prevalence of vitamin D deficiency in our study population is consistent with several studies conducted in different populations. In our cohort, 69.64% of the patients were classified as vitamin D deficient, which aligns with studies that have shown a high prevalence of vitamin D deficiency in patients with thyroid dysfunction.  Similarly, research by Goswami et al. (2009) demonstrated a correlation between low vitamin D levels and the severity of thyroid dysfunction, supporting the notion that vitamin D deficiency is more common in hypothyroid patients compared to the general population(17,18).

In contrast, some studies have reported lower prevalence rates. For example, a study conducted by Sudha et al. (2013) showed that only 24% of adults with subclinical hypothyroidism had vitamin D levels below 20 ng/ml. The discrepancy in prevalence rates across studies may be attributed to differences in geographic locations, dietary habits, and methodologies. In our study, the region's low sunlight exposure due to seasonal variations, along with dietary factors, may contribute to the higher rate of vitamin D deficiency. The general population’s reliance on limited dietary sources of vitamin D may also exacerbate this deficiency.

Our study found a significant negative correlation between vitamin D levels and TSH, with the most pronounced relationship observed in patients with overt hypothyroidism. This finding suggests that lower vitamin D levels are associated with higher TSH, indicating a potential link between vitamin D deficiency and thyroid dysfunction. This result is consistent with the findings of several other studies, such as the one by Shilpa et al. (2014), which demonstrated that hypothyroid patients with low vitamin D levels exhibited higher TSH levels(19,20).

A study by Rotondi et al. (2013) further corroborates these findings, suggesting that low vitamin D levels may aggravate thyroid function, particularly in autoimmune thyroid diseases, which are the leading cause of primary hypothyroidism. However, not all studies have found a significant relationship between vitamin D deficiency and thyroid function. For example, a study by Sadiya et al. (2015) did not observe a correlation between vitamin D levels and TSH in a cohort of patients with subclinical hypothyroidism. This inconsistency may be due to differences in study design, sample size, and patient characteristics, such as the severity of thyroid disease and the presence of autoimmune conditions.

Our study's findings highlight the potential role of vitamin D in modulating thyroid function, suggesting that vitamin D deficiency may be a contributing factor in the progression of hypothyroidism. It is possible that vitamin D could influence thyroid function directly through the vitamin D receptor (VDR), which is expressed in various tissues, including the thyroid gland. Alternatively, vitamin D may modulate immune responses, influencing the development of autoimmune thyroid diseases that can lead to hypothyroidism.

Although our study did not specifically examine autoimmune thyroid diseases, it is important to consider the role of vitamin D in autoimmune thyroiditis, a leading cause of primary hypothyroidism. Several studies have suggested that vitamin D deficiency is linked to autoimmune thyroid diseases such as Hashimoto's thyroiditis and Graves' disease. Vitamin D plays a crucial role in regulating the immune system, and its deficiency may increase the risk of autoimmune diseases by impairing immune tolerance and promoting inflammatory cytokine production.

A study by Zaletel et al. (2011) demonstrated that vitamin D deficiency was associated with the development of Hashimoto's thyroiditis and that supplementation may improve thyroid function in autoimmune thyroid disease. Furthermore, vitamin D's immunomodulatory effects may help reduce the inflammatory processes that contribute to thyroid damage in autoimmune thyroid disease. Although our study did not assess the autoimmune status of patients, the association between low vitamin D levels and hypothyroidism, particularly in overt hypothyroid patients, suggests that vitamin D supplementation may have potential benefits in managing autoimmune thyroid diseases (21).

The mechanisms by which vitamin D deficiency may influence thyroid function are complex and multifactorial. Vitamin D acts through its receptor (VDR) present in various tissues, including the thyroid gland, where it may directly regulate thyroid hormone production. Studies have shown that VDR activation can modulate the expression of genes involved in thyroid hormone synthesis. Thus, vitamin D may influence thyroid function at the cellular level.

Additionally, vitamin D has known immunomodulatory properties that may affect autoimmune thyroid diseases. It helps regulate the activity of T-helper cells and enhances the function of regulatory T-cells, which play a critical role in maintaining immune tolerance. In autoimmune thyroid diseases, an imbalance in these immune responses can lead to thyroid damage and dysfunction. Vitamin D deficiency may exacerbate this imbalance, promoting thyroid autoimmunity and contributing to hypothyroidism (22).

Vitamin D also plays a role in calcium homeostasis and bone metabolism, and low vitamin D levels can impair calcium absorption, leading to secondary metabolic disturbances that may further affect thyroid function. While the exact pathways remain unclear, it is likely that the interaction between vitamin D, thyroid function, and immune regulation contributes to the observed relationship between vitamin D deficiency and hypothyroidism.

Given the high prevalence of vitamin D deficiency in our study population, it is important for clinicians to assess vitamin D status in patients with hypothyroidism. Correcting vitamin D deficiency through supplementation may offer therapeutic benefits, particularly for those with subclinical or overt hypothyroidism. Several studies have suggested that vitamin D supplementation may improve thyroid function and reduce TSH levels in patients with subclinical hypothyroidism (23).

However, it is essential to recognize that vitamin D supplementation should not replace traditional thyroid hormone replacement therapy for patients with overt hypothyroidism. While vitamin D may have a supportive role in managing thyroid function, it is unlikely to serve as a primary treatment for hypothyroidism. Therefore, clinicians should adopt a holistic approach to managing hypothyroidism, considering vitamin D supplementation alongside standard thyroid hormone therapy (24).

Limitations and Future Research:

There are several limitations to this study. Firstly, the cross-sectional design limits the ability to establish causality between vitamin D deficiency and hypothyroidism. Longitudinal studies are needed to better understand the temporal relationship between these variables. Secondly, our study did not assess autoimmune thyroid disease, which could provide valuable insights into the role of vitamin D in autoimmune thyroid disorders. Future research should aim to investigate the effects of vitamin D supplementation on thyroid function in a variety of patient populations, including those with autoimmune thyroid diseases.

In conclusion, our study confirms the high prevalence of vitamin D deficiency among patients with primary hypothyroidism and identifies a significant negative correlation between vitamin D levels and TSH, particularly in those with more severe hypothyroidism. While the mechanisms linking vitamin D deficiency and hypothyroidism remain complex, vitamin D’s potential role in immune regulation and thyroid hormone synthesis warrants further investigation. Clinicians should consider monitoring vitamin D levels in hypothyroid patients and discuss the potential benefits of supplementation in improving thyroid function, particularly for those with vitamin D deficiency. Further research is needed to establish the causal relationship between vitamin D deficiency and hypothyroidism and to explore the therapeutic potential of vitamin D supplementation.

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