Thyroid diseases are the most common endocrine system disorders, affecting an estimated 5% of the US population, with Graves’ disease and Hashimoto’s thyroiditis accounting for a vast majority of cases.¹,²
Despite their prevalence, the underlying causes of thyroid autoimmunity remain complex and multifactorial, evolving over time and involving a perfect storm of risk factors: a genetic predisposition, environmental triggers, and an imbalanced immune system. ³
The role of micronutrient deficiencies in thyroid and immune health has garnered significant attention, as these deficiencies contribute to imbalances that impair intestinal barrier function and disrupt immune tolerance.³ At the same time, emerging research highlights the predictive value of autoantibodies in identifying autoimmune risks early, long before clinical symptoms appear.⁴,⁵
This article draws on research studies conducted by the Vibrant Wellness lab team to examine the intricate relationships between thyroid health, micronutrient balance, and autoantibodies. We’ll discuss the predictive value of autoantibodies, the impact of micronutrient imbalances on thyroid health, and actionable strategies for addressing hyperthyroidism, particularly in cases of Graves’ disease. Vibrant’s findings provide a unique perspective on how to leverage advanced testing to identify risks, guide interventions, and improve patient outcomes.
Table of Contents
Thyroid hormones are the master regulators of metabolic processes throughout the body, including:
The synthesis of thyroid hormones is regulated by the hypothalamus and pituitary glands, which secrete TRH and TSH, respectively, to stimulate thyroid hormone production and release from the thyroid gland in response to low thyroid hormone levels or other stimuli, including cold exposure and various stressors.² Production of TRH and TSH is controlled by negative feedback mechanisms, including sufficient thyroid hormone level and somatostatin.8
In circulation, the vast majority of thyroid hormones are attached to carrier proteins, while a very small proportion (<1%) remains unbound and readily available. The “free” hormone enters cells at binding sites and binds to nuclear receptors within these cells, activating gene transcription that ultimately increases the rate of metabolic processes.
For example, thyroid hormone agonizes the action of catecholamines by increasing beta receptor expression in tissues including the lung and heart, resulting in increased oxygen uptake and elevated heart rate. Spent thyroid hormones are transformed in the liver by sulfation and glucuronidation and are excreted in the bile.7
Both excessive and insufficient levels of active thyroid hormone each have deleterious metabolic effects that underline the importance of thyroid hormone balance for homeostasis.
Hyperthyroidism increases basal metabolic rate, resulting in symptoms like extreme weight loss, diarrhea or loose stools, heat intolerance, anxiety, heart palpitations, hyperreflexia, and orbitopathy.9
Conversely, hypothyroidism suppresses metabolic rate and can result in weight gain, dyslipidemia, cold intolerance, depression, fatigue, and hyporeflexia.7
Autoimmune diseases manifest over a number of years, developing from:
The early stages of autoimmune disease present a critical opportunity to intervene prior to overt disease and tissue damage by addressing nutrient imbalances and gastrointestinal barrier integrity.
Because autoantibodies are present during these prodromal disease stages, testing is an important step to quantify the risk of future disease. Those with a pre-existing autoimmune diagnosis can also benefit from autoantibody testing because of the substantial risk of developing a second autoimmune disease. Roughly 1 in 4 people with one autoimmune disease go on to develop additional autoimmune diseases.10
Anti-TPO antibodies (Ab) are an important precursor to the detection of autoimmune thyroid conditions in many people and, as such, are an important risk assessment marker alongside the conventional thyroid markers TSH and free T4 (FT4). While anti-Tg Ab is commonly found in conjunction with anti-TPO Ab in thyroid autoimmunity, anti-TPO Ab are more prevalent in Graves’ disease than are anti-Tg .11
The value of anti-TPO antibodies for quantification of autoimmune risk is illustrated by a retrospective study conducted by Vibrant Wellness.6 This study involved 4,581 individuals who were tested at Vibrant Labs for TSH, FT4, anti-TPO, and anti-Tg multiple times over a 2-year period and found that 68.6% of those who eventually exhibited hyperthyroidism and 73% of those who later exhibited hypothyroidism, were positive for anti-TPO antibodies an average of 277 days and 252 days, respectively, prior to onset of overt thyroid dysfunction, as diagnosed by abnormalities in TSH and FT4.
Autoimmune thyroid disease can precede secondary systemic autoimmune diseases, including systemic lupus erythematosus (SLE) and Sjögren’s syndrome. Monitoring specific autoantibodies in patients with pre-existing autoimmunity can offer valuable insights and guide treatment approaches.
A 2018 study from Vibrant Wellness demonstrated that monitoring anti-nuclear antibodies (ANA) and anti-extractable nuclear antigens (ENA), a subtype of ANA, in patients with pre-existing anti-TPO Ab can allow detection of prodromal-stage systemic autoimmune disease.5 This retrospective analysis of 14,825 individuals with thyroid-related symptoms who were tested by Vibrant and followed for a two-year period revealed that anti-TPO antibodies could be measured prior to the detection of the systemic autoimmune disease antibodies, ANA and anti-ENA, by 253 and 227 days, respectively. Anti-TPO positivity was found in 69% and 65% of individuals before the detection of ANA and anti-ENA, respectively.
Bottom line: Monitoring anti-TPO, ANA, and anti-ENA antibodies aids in detection and offers feedback on the effectiveness of current interventions to guide the next steps in autoimmune treatment plans. The Vibrant Wellness Autoimmune Zoomer provides a thorough assessment of the antigens and autoantibodies mentioned here, in addition to many more, that can help providers identify specific autoimmune pathologies to enable early and personalized interventions.
Micronutrients play crucial roles as cofactors and coenzymes in basic cellular functioning and are, therefore,
Clinically, there are two primary considerations for micronutrients as they relate to hyperthyroidism: micronutrient balance for optimal thyroid function and micronutrients needed for proper immune regulation. A recent review by Vibrant Labs discussed the relationship between hyperthyroidism and various micronutrient imbalances.2 Let’s examine two key micronutrients essential for thyroid health: iodine and selenium.
Research in autoimmunity, as well as population studies such as the NHANES survey, support achieving sufficiency and balance while avoiding excesses among nutrients for thyroid function.13 In this section, we will explore the connection between hyperthyroidism and two trace minerals with key roles in thyroid function: iodine and selenium. These two minerals are essential for thyroid hormone production and activation–conversely, excesses of these minerals have been associated with various adverse effects.
Because of its essential role as a constituent of thyroid hormone, iodine is carefully managed by the body, and both low and high levels can cause thyroid dysfunction. Iodine deficiency has long been recognized as a preventable cause of impaired neurodevelopment worldwide. However, rapid or excessive increases in iodine in previously iodine-deficient populations can inadvertently induce hyperthyroidism in some individuals.14,16
High iodine intake has been shown to provoke autoimmunity in animal models with a predisposition, and this corroborates the epidemiological data demonstrating a high incidence of Hashimoto’s thyroiditis and earlier onset of Graves’ disease in regions of high iodine intake.15
Furthermore, while non-autoimmune multinodular toxic goiter was found to be the primary cause of hyperthyroidism in a low iodine region of Denmark, Graves’ disease was still nearly as common in this region as it was in a high iodine region of Iceland, underlining the importance of sufficient but not excessive iodine intake.15
The thyroid gland contains a higher concentration of selenium than any other organ, owing to the presence of selenoproteins, including glutathione peroxidase, which protects the gland from oxidative stress by utilizing glutathione to neutralize the hydrogen peroxide produced during thyroid hormone synthesis. Selenium is also an essential component of deiodinases, the enzymes that remove iodine atoms from T4 to create the active form of thyroid hormone, T3. Because of its importance to thyroid function, as with iodine, there is evidence that the body retains mechanisms to conserve and recycle this mineral to compensate if intake is low.17
Similar to iodine, healthy selenium levels may be represented by a U-shaped curve, where disease risks increase with a low or high level. There is evidence that selenium repletion is beneficial for Graves’ disease, while high levels of selenium and long-term supplementation have been associated with increased risk of type 2 diabetes.18,19
One study found that modest supplementation of selenium at 60 ug daily alongside vitamins C, E, and beta-carotene speeded the attainment of euthyroidism in individuals with Graves’ disease treated with methimazole.20 Although this was a multi-ingredient protocol, selenium concentration in serum showed a significant correlation with glutathione peroxidase activity. Notably, this study was conducted in Croatia, where selenium in the soil is very low.
A second study of individuals from various European countries with mild Graves’ orbitopathy found that treatment with selenium at 100 ug twice daily for six months led to improvement of orbitopathy in 61% of participants, as compared with pentoxifylline 600 mg twice daily or placebo, which improved orbitopathy in 35% and 36% of participants, respectively.21 However, 7% of individuals experienced worsening symptoms with selenium supplementation, indicating that while selenium was beneficial for a majority, it is not without risk for everyone.
Vitamins A and D play important roles in immunological tolerance, the loss of which is a defining feature of autoimmunity. Now, let’s take a closer look at the relationship between these fat-soluble nutrients and hyperthyroidism.
Vitamin A is essential for proper immune system function and is also intertwined with thyroid function in a number of ways.
In the immune system, a key role of vitamin A is the promotion of naive T cell differentiation into regulatory T cells, which dampen pro-inflammatory cytokine production and are central to immunological tolerance.22 Reverse Mendelian randomization evidence suggests that genetic susceptibility to Graves’ disease is associated with low circulating vitamin A, meaning that vitamin A deficiency promotes the development of autoimmunity in the genetically predisposed. 23
In relation to the pituitary-thyroid axis, vitamin A has an intricate relationship with the stimulation and utilization of thyroid hormone. Relevant to hyperthyroidism, vitamin A is part of the negative feedback loop that modulates TSH production in the pituitary gland.24 Also, in a rat model of hyperthyroidism, vitamin A supplementation led to a beneficial downregulation of nuclear thyroid hormone receptors in the liver.25
Vitamin D deficiency or insufficiency is a well-established risk factor for autoimmunity and increased susceptibility to infections, which can themselves be triggers for autoimmunity. Moreover, vitamin D is known to modulate the immune response toward a Th2 phenotype and away from the Th1 phenotype that predominates in Graves’ and other autoimmune diseases.26
In females newly diagnosed with Graves’ disease, vitamin D level was negatively associated with thyroid volume and found to be significantly lower than in a disease-free control group, with a prevalence of vitamin D deficiency of 65.4% in the Graves’ disease group, compared to 32.4% in the control group.27
Vitamin D status may also impact the ability of individuals with Graves’ disease to achieve remission. In a group of 75 patients with Graves’ disease, the prevalence of vitamin D deficiency, defined as a serum vitamin D < 20 ng/mL, was 14.6% in those with active disease and 0% in those in remission. Additionally, vitamin D levels had a significant negative correlation with free T4 in this population.28
For autoimmune conditions, micronutrient balance is a key lever we can pull to positively impact disease progression. Addressing optimal micronutrient levels, particularly in vitamins A and D, can significantly improve immunological tolerance and thyroid health.
The Vibrant Micronutrient Panel provides a comprehensive assessment of intracellular and serum levels of the micronutrients discussed here, along with many others that are critical for thyroid and immune function. This advanced tool enables precise, personalized care plans that empower clinicians to deliver better outcomes for their patients.
The interplay between autoantibodies, micronutrient balance, and thyroid health underscores the complexity of managing autoimmune thyroid diseases like Graves’ disease. Research shows that autoantibodies, such as anti-TPO, ANA, and anti-ENA, provide valuable early indicators of disease risk, enabling clinicians to intervene before overt symptoms develop. Additionally, micronutrient imbalances—whether deficiencies or excesses—affect thyroid hormone synthesis, immune regulation, and the progression of autoimmunity.
Leveraging these insights in clinical practice allows for a more targeted approach to patient care. By using advanced testing to identify autoantibody patterns and assess intracellular and serum levels of critical micronutrients like iodine, selenium, vitamin A, and vitamin D, clinicians can develop personalized strategies to optimize thyroid function and enhance immunological tolerance.
Becky Buck Douville, MS, CN is a clinical nutritionist, and the founder of Osa Integrative Health, where she specializes in helping middle-aged and older adults optimize their metabolic health using functional medicine principles and personalized nutrition and lifestyle interventions. She is passionate about helping her clients uncover new pathways to healing and empowering her community with evidence-based information that cuts through the noise of wellness trends.
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Regulatory Statement:
The information presented in case studies have been de-identified in accordance with the HIPAA Privacy protection.
The general wellness test intended uses relate to sustaining or offering general improvement to functions associated with a general state of health while making reference to diseases or conditions. This test has been laboratory developed and its performance characteristics determined by Vibrant America LLC and Vibrant Genomics, a CLIA-certified and CAP-accredited laboratory performing the test. The lab tests referenced have not been cleared or approved by the U.S. Food and Drug Administration (FDA). Although FDA does not currently clear or approve laboratory-developed tests in the U.S., certification of the laboratory is required under CLIA to ensure the quality and validity of the test.