Thyroid Health Coaching
List of published research
We don’t have a lack of information. We have a lack of accurate and valuable information. If you are interested in reading more about the actual published research, you can find the summary and the link to the research below.
The topics listed below are:
- General
- Absorption
- Autoimmunity & Thyroid antibodies
- Biotin
- Deiodeinases
- Diet
- Environment
- Genetics
- Grave’s Disease
- Gut health & Microbiota
- Hairloss
- Hashimoto’s Thyroiditis
- History
- Hyperthyroidism
- Illness
- Immunity and Antibodies
- Inflammation
- Insulin & Insulin Resistance
- Intestinal Permeability (aka Leaky Gut)
- Iodine
- Iron
- Leaky Gut (see Intestinal Permeability)
- Leptin
- Menstruation
- Metabolism
- Metmorfin
- Nutrition
- Obesity
- PCOS
- Pregnancy
- Radiation
- Reverse T3
- Riedel’s thyroiditis
- Selenium
- Statistics
- Stress
- T3 Hormones
- Thyroid Hormones
- Thyroid Antibodies (see Autoimmunity & Thyroid Antibodies)
- Viral diseases
- Vitamin D
- Workplace
- Zinc
General
Adult Hypothyroidism
2014. The full-blown expression of hypothyroidism is known as myxedema. Author W.M Wiersinga.
Prevalence and Consequences of Thyroid Dysfunction
Extract from book “Medicare Coverage of Routine Screening for Thyroid Dysfunction.”
Absorption
Factors Affecting Gastrointestinal Absorption of Levothyroxine: A Review
A study of studies, where the authors reviewed all the relevant published research relating to the factors that affect the gastrointestinal absorption of levothyroxine (synthetic T4). They found several factors that significantly impact absorption: gastrointestinal disorders (such as celiac disease, lactose intolerance, and H. pylori infection), soybeans, coffee, medications (such as cholestyramine, colesevelam, lanthanum, calcium carbonate, calcium citrate, calcium acetate, iron sulfate, ciprofloxacin, aluminum hydroxide, sevelamer, or proton pump inhibitors).
Gastrointestinal Malabsorption of Thyroxine
The authors examined the pharmacologic features of T4 preparations and their linkage with the intestinal absorption of the hormone. They also reviewed the interfering role of nutrients, foods, and drugs on T4 absorption within the gastric and intestinal levels, as well as the impact of gastrointestinal disorders on T4 treatment efficacy. They also listed the binding ingredients (excipients) of each T4 preparation and mentioned that these binding ingredients can also impact absorption rates.
Autoimmunity & Thyroid Antibodies
Thyroid autoimmunity
2014. Wilmar M Wiersinga. Autoimmune thyroid disease (AITD) is a multifactorial disease in which autoimmunity against thyroid antigens develops against a particular genetic background facilitated by exposure to environmental factors.
Long-term follow-up of antithyroid peroxidase antibodies in patients with chronic autoimmune thyroiditis (Hashimoto's thyroiditis) treated with levothyroxine
2008. A number of studies show that the serum levels of antithyroid peroxidase antibodies (TPO-Ab) in patients with Hashimoto’s thyroiditis decline during levothyroxine treatment, but do not provide quantitative data or report the fraction of patients in whom test for TPO-Ab became negative (“normalization percentage”). The objective of the present study was to provide this information.
Serum TPO-Ab levels decline in most patients with Hashimoto’s thyroiditis who are taking levothyroxine, but after a mean of 50 months, TPO-Ab became negative in only a minority of patients.
Thyroid Autoimmunity: Role of Anti-thyroid Antibodies in Thyroid and Extra-Thyroidal Diseases
2017. Thyroid autoantibodies are not only frequently detected in patients with AITD but also in subjects without manifest thyroid dysfunction. The high prevalence raises questions regarding a potential role in extra-thyroidal diseases. This review summarizes the etiology and mechanism of AITD and addresses prevalence of antibodies against thyroid peroxidase, thyroid-stimulating hormone receptor (TSHR), and anti-thyroglobulin and their action outside the thyroid.
Thyroid antibodies: which, why, when and who?
2014. Clinical laboratories are asked to measure a number of different thyroid antibody types. This editorial will try to address the title questions by concentrating on which antibodies we measure, why they might be useful, when it is useful to measure them and who is best suited to do so.
Link: https://www.tandfonline.com/doi/full/10.1586/1744666X.2.5.665
Biotin
Biotin Treatment Mimicking Graves’ Disease
2016. Thus, high-dose biotin treatment can cause insidiously misleading laboratory results by fully mimicking the typical laboratory pattern of Graves’ disease and sometimes persisting for several days after biotin application.
Deiodinases
Metabolism of Thyroid Hormone
2017. Thyroid hormones are metabolized by different pathways: glucuronidation, sulfation, and deiodination, the latter being the most important. Three enzymes catalyzing deiodination have been identified, called type 1 (D1), type 2 (D2) and type 3 (D3) iodothyronine deiodinases. D1 and D2 have outer ring deiodinase activity, converting the prohormone T4 to its bioactive form T3 and degrading rT3.
D1 is largely expressed in liver and kidney. Its main role is clearance of rT3 from the circulation and it also contributes to production of plasma T3. D2 is importantly expressed in the central nervous system, pituitary, brown adipose tissue and muscle and, generally, its expression reciprocally responds to changes in thyroid state. D2 serves to adapt cellular thyroid state to changing physiological needs. D3 is importantly expressed in fetal tissues and in adult brain tissue. In addition, D3 can be re-expressed under certain pathological conditions such as critical illness or in specific cancers.
Deiodinases and the Three Types of Thyroid Hormone Deiodination Reactions
2021. Thyroid hormone (TH) signaling is strictly regulated by iodothyronine deiodinase activity, which both preserves the circulating levels of the biologically active triiodothyronine (T3) and regulates TH homeostasis at the local level, in a cell- and time-dependent manner. Three deiodinases have been identified. his review analyzes the complex role of deiodinases in physiological and pathological contexts, exploring new challenges and opportunities deriving from a deeper knowledge of the dynamics underlying their roles and functions.
Diet
The importance of nutritional factors and dietary management of Hashimoto's thyroiditis
2020. Dietotherapy of Hashimoto’s is based on the proper nourishment of the body and regulation of the immune system by an anti-inflammatory diet. Observational and controlled trials have shown frequent nutrition deficiencies in HT patients. In literature, there is evidence for selenium, potassium, iodine, copper, magnesium, zinc, iron, vitamin A, C, D and B. The role of the proper level of protein intake, dietary fibre and unsaturated fatty acids, especially the n-3 family, has been indicated. HT patients should often eliminate lactose because of intolerance and interactions with levothyroxine and gluten because of possible interactions of gliadin with thyroid antigens. The article describes the nutrition factors of HT patients, and share nutrition recommendations for diet therapy.
Doubtful Justification of the Gluten-Free Diet in the Course of Hashimoto’s Disease
The popularization of the gluten-free diet brings with it a fashion for its use, which can harm the treatment of Hashimoto’s disease. The few studies in this regard do not confirm positive changes resulting from a gluten-free diet. At the same time, the presence of other comorbid autoimmune diseases in this group of patients is increasing. This may have important implications for the interpretation of test results and the need for a gluten-free diet in some patients. When analyzing the available literature, we found no basis for introducing a gluten-free diet for the standard management of Hashimoto patients. The recommended diet is instead an anti-inflammatory diet that levels the supply (to compensate for deficiencies) of vitamin D, iodine, and selenium, which are found in plant products rich in polyphenols, antioxidants, and omega-3 fatty acids, as illustrated in this article.
The importance of gluten exclusion in the management of Hashimoto’s thyroiditis
2021. The study aimed to analyze and describe available knowledge regarding the effect of gluten or a gluten-free diet on thyroid autoimmunity in HT with or without celiac disease. Gluten exclusion might increase the risk of HT development because of the potential nutritional deficiencies related to the low quality of gluten-free products. Gluten intake from crops grown on selenium-depleted soil increases the risk of HT development. Only a few studies suggest that GFD would be beneficial for HT patients, even without the coexistence of CD. The strongest connection between gluten intake and thyroid destruction seems to be based on a mechanism of molecular mimicry between gut and thyroid tissue transglutaminase.
Studies conducted so far do not support the claim that HT patients should eliminate gluten from their diet. In view of the limited number of studies, with major limitations and ambiguous results, a gluten-free diet is not recommended.
Low-Glycemic Load Diets and Thyroid Function: A Narrative Review and Future Perspectives
Nutrition and calorie intake are associated with subtle changes of thyroid function tests in subjects with an intact Hypothalamic-Pituitary-Thyroid axis. Iodine deficiency and extreme fluctuations in calorie intake, such as those that occur during periods of starvation or overfeeding could lead to alterations in thyroid hormones. The dietary macronutrient and micronutrient composition could also influence the thyroid function. Recently, Low-Glycemic Load (LGL) diets have become very popular and are effective in the treatment and/or prevention of several medical conditions, including diabetes, obesity, cardiovascular disease, and epilepsy. In this review, we report on the available data from the literature regarding the association between LGL diets and thyroid function or dysfunction. Several studies conducted in this field to date have yielded inconsistent results.
Environment
Environmental Triggers of Autoimmune Thyroiditis
2010. Autoimmune thyroiditis is among the most prevalent of all the autoimmunities. Autoimmune thyroiditis is multifactorial with contributions from genetic and environmental factors. Much information has been published about the genetic predisposition to autoimmune thyroiditis both in experimental animals and humans.
The best-established environmental factor is excess dietary iodine. Increased iodine consumption is strongly implicated as a trigger for thyroiditis, but only in genetically susceptible individuals. However, excess iodine is not the only environmental agent implicated as a trigger leading to autoimmune thyroiditis. There are a wide variety of other synthetic chemicals that affect the thyroid gland or have the ability to promote immune dysfunction in the host.
Effects of the Environment, Chemicals and Drugs on Thyroid Function
2016. This chapter reviews effects on the thyroid produced by changes in the external environment, chemicals and drugs. Environmental temperature, high altitude and anoxia, Alterations in light, nutrition, starvation and fasting, protein-calorie maltrition, overfeeding & obesity, minerals, physical & emotional stress, chemicals and drugs, alterations of immunity.
Genetics
Genetic defects in thyroid hormone synthesis
2001. Thyroid hormone synthesis requires a normally developed thyroid gland, a properly functioning hypothalamic-pituitary-thyroid axis, and sufficient iodine intake. This article focuses on genetic defects in this axis. Defects that are primarily of developmental origin are discussed in our associated article in this issue. Defects in hormone synthesis usually are associated with the development of a goiter, provided that the bioactivity and action of thyrotropin (TSH) are not impaired. In contrast, hypoplasia of the gland may be caused by developmental defects, bioinactive TSH, or resistance to TSH at the level of the receptor or its signaling pathway. At the other end of the spectrum, hyperthyroidism may result from gain of function mutations in genes regulating growth and function.
Graves Disease
Hashimoto's thyroiditis following Graves' disease
2010. Approximately 15-20% of patients with Graves’ disease had been reported to have spontaneous hypothyroidism resulting from the chronic thyroiditis (Hashimoto’s disease). Pathogenesis for chronic thyroiditis following anti-thyroid drug treatment in patients with Graves’ disease remains unclear. In three cases, Hashimoto’s thyroiditis occurs in 7 to 25 years after the treatment of Grave’s disease; while the other case has it only after few months of Grave’s disease treatment. The diagnosis of Hashimoto’s disease (chronic thyroiditis) was based on clinical manifestation, high TSHs level, positive thyroid peroxidase antibody and thyroglobulin antibody, and supported by positive results of fine needle aspiration biopsy. Moreover, the result of histopathological test has also confirmed the diagnosis in two cases. All cases have been successfully treated by levothyroxine treatment.
Gut Health & Microbiota
The Interplay between the Gut Microbiome and the Immune System in the Context of Infectious Diseases throughout Life and the Role of Nutrition in Optimizing Treatment Strategies
2021. Infectious diseases and infections remain a leading cause of death in low-income countries and a major risk to vulnerable groups, such as infants and the elderly. The immune system plays a crucial role in the susceptibility, persistence, and clearance of these infections. With 70–80% of immune cells being present in the gut, there is an intricate interplay between the intestinal microbiota, the intestinal epithelial layer, and the local mucosal immune system.
The now well-recognized impact of nutrition on the composition of the gut microbiota and the immune system elucidates the role nutrition can play in improving health.
This review describes the mechanisms involved in maintaining the intricate balance between the microbiota, gut health, the local immune response, and systemic immunity, linking this to infectious diseases throughout life, and highlights the impact of nutrition in infectious disease prevention and treatment.
Microbiota and Thyroid Interaction in Health and Disease
2019. An altered microbiota composition increases the prevalence of Hashimoto’s thyroiditis (HT) and Graves’ disease (GD). Microbes influence thyroid hormone levels by regulating iodine uptake, degradation, and enterohepatic cycling. In addition, there is a pronounced influence of minerals on interactions between host and microbiota, particularly selenium, iron, and zinc. In manifest thyroid disorders, the microbiota may affect L-thyroxine uptake and influence the action of propylthiouracil (PTU). Although it is relatively well documented that thyroid disorders are linked to the composition of the microbiota, the role of specific genera and the potential use of therapies targeting the microbiota are less clear.
Thyroid-Gut-Axis: How Does the Microbiota Influence Thyroid Function?
2020. A healthy gut microbiota not only has beneficial effects on the activity of the immune system, but also on thyroid function. Thyroid and intestinal diseases prevalently coexist—Hashimoto’s thyroiditis (HT) and Graves’ disease (GD) are the most common autoimmune thyroid diseases (AITD) and often co-occur with Celiac Disease (CD) and Non-celiac wheat sensitivity (NCWS). This can be explained by the damaged intestinal barrier and the following increase of intestinal permeability, allowing antigens to pass more easily and activate the immune system or cross-react with extraintestinal tissues, respectively.
Supplementation of probiotics showed beneficial effects on thyroid hormones and thyroid function in general. A literature research was performed to examine the interplay between gut microbiota and thyroid disorders that should be considered when treating patients suffering from thyroid diseases. Multifactorial therapeutic and preventive management strategies could be established and more specifically adjusted to patients, depending on their gut bacteria composition. Future well-powered human studies are warranted to evaluate the impact of alterations in gut microbiota on thyroid function and diseases.
Hair Loss
Human female hair follicles are a direct, nonclassical target for thyroid-stimulating hormone
2009. Pituitary thyroid-stimulating hormone (TSH) regulates thyroid hormone synthesis via receptors (TSH-R) expressed on thyroid epithelial cells. As the hair follicle (HF) is uniquely hormone-sensitive and, hypothyroidism with its associated, increased TSH serum levels clinically can lead to hair loss, we asked whether human HFs are a direct target for TSH.
Zinc Deficiency Associated with Hypothyroidism: An Overlooked Cause of Severe Alopecia
Hypothyroidism is a common and well-recognized cause of diffuse hair loss. Zinc and other trace elements such as copper and selenium are required for the synthesis of thyroid hormones, and deficiency of these can result in hypothyroidism. Conversely, thyroid hormones are essential for the absorption of zinc, and hence hypothyroidism can result in acquired zinc deficiency. The hair loss attributed to hypothyroidism may not improve with thyroxine unless zinc supplements are added, as demonstrated in our case.
Effect of a nutritional supplement on hair loss in women
2015. Female pattern hair loss is a frequent and distressing condition. To evaluate vs. control, the effects on hair loss of a 6-month supplementation with specific omega 3&6 and antioxidants.
120 female subjects in a 6-month, randomized, comparative study. A 6-month supplementation with omega 3&6 and antioxidants acts efficiently against hair loss in improving hair density and reducing the telogen percentage and the proportion of miniaturized anagen hair.
Hair Loss: Common Causes and Treatment
2017. Summary discussion.
Hashimoto's Thyroiditis
Hashimoto's Thyroiditis: Continued Education
Updated 2023. This activity reviews the pathophysiology, diagnosis, and management of Hashimoto thyroiditis and highlights the role of the interprofessional team in caring for patients with this condition.
Hashimoto's Thyroiditis: From Genes to the Disease
2011. Hashimoto’s thyroiditis (HT) is the most prevalent autoimmune thyroid disorder. Intrathyroidal lymphocytic infiltration is followed by a gradual destruction of the thyroid gland which may lead to subclinical or overt hypothyroidism. Biochemical markers of the disease are thyroid peroxidase and/or thyroglobulin autoantibodies in the serum which are present with a higher prevalence in females than in males and increase with age. Although exact mechanisms of aetiology and pathogenesis of the disorder are not completely understood, a strong genetic susceptibility to the disease has been confirmed predominantly by family and twin studies. Several genes were shown to be associated with the disease occurrence, progression, and severity.
Hashimoto thyroiditis: an evidence-based guide to etiology, diagnosis and treatment
2022. Hashimoto thyroiditis (HT) is a common autoimmune disorder, affecting women 7–10 times more often than men, that develops because of genetic susceptibility, X chromosome inactivation patterns modulated by environmental factors as well as microbiome composition, and leads to an imbalance in self-tolerance mechanisms.
The Influence of Nutritional Intervention in the Treatment of Hashimoto's Thyroiditis-A Systematic Review
Diet can be a complementary treatment for Hashimoto’s disease by affecting thyroid function and anti-inflammatory properties. It is still unclear which dietary strategy would be the most beneficial. The aim of this systematic review is to examine all the data currently available in the literature on the effects of nutritional intervention on biochemical parameters (anti-thyroid antibody and thyroid hormones levels) and characteristic symptoms in the course of Hashimoto’s thyroiditis. 9 studies were included for further analysis.
An improvement was observed during an energy deficit and after the elimination of selected ingredients (e.g., gluten, lactose, or goitrogens), as well as after the intervention of Nigella sativa. These interventions improved antibody levels against peroxidase (anti-TPO), (thyrotropin) TSH, and free thyroxine (fT4). No improvement was seen on the iodine-restricted diet.
Therefore, there is a great need for further experimental studies to determine whether any nutritional interventions are beneficial in Hashimoto’s disease.
Multiple nutritional factors and thyroid disease, with particular reference to autoimmune thyroid disease
2019. Aiming to investigate the effect of iodine, iron and selenium in the risk, pathogenesis and treatment of thyroid disease, PubMed and the Cochrane Library were searched for relevant publications to provide a narrative review.
There is evidence from observational studies and randomised controlled trials that selenium, probably as selenoproteins, can reduce TPO-antibody concentration, hypothyroidism and postpartum thyroiditis. Appropriate status of iodine, iron, and selenium is crucial to thyroid health.
Can Supplementation with Vitamin D Modify Thyroid Autoantibodies (Anti-TPO Ab, Anti-Tg Ab) and Thyroid Profile (T3, T4, TSH) in Hashimoto's Thyroiditis? A Double Blind, Randomized Clinical Trial
2019. The aim of this study was to investigate the effect of vitamin D on circulating thyroid autoantibodies and thyroid hormones profile (T4, T3, and TSH) in females with HT. Forty-two women with HT disease were enrolled in this randomized clinical trial study.
The results of this study showed a significant reduction of anti-Tg Ab and TSH hormone in the Vitamin D group compared to the start of the study; however, there was a no significant reduction of anti-TPO Ab in the Vitamin D group compared to the placebo group (p=0.08). No significant changes were observed in the serum levels of T3 and T4 hormones. Therefore, vitamin D supplementation can be helpful for alleviation of the disease activity in HT patients; however, further well controlled, large, longitudinal studies are needed to determine whether it can be introduced in clinical practice.
A Prospective Study to Evaluate the Possible Role of Cholecalciferol Supplementation on Autoimmunity in Hashimoto's Thyroiditis
2023. Most studies have shown an association between low vitamin D status and pathogenesis of AITD, especially HT. However, there are only few preliminary interventional studies for HT. whether vitamin D supplementation is beneficial for AITD or HT, should be evaluated. Treatment of HT mainly based on thyroid hormone supplementation, so if a beneficial role of vitamin D supplementation is identified/ confirmed, it will be helpful in the treatment of patients with HT and may be a part of treatment of HT patients.
The 8 weeks randomized; double-blind, placebo-controlled clinical trial demonstrates a negative correlation between Serum 25 hydroxy vitamin D vs anti TPO antibody level. Treatment with 60,000 IU cholecalciferol weekly for 8 weeks, is associated with significant decrease in antithyroid antibody titers. It also improved serum TSH level compared with the placebo, i.e. supplementary treatment with cholecalciferol seems to have beneficial effects on AITD. However, large multicentre studies are needed to investigate the impact of vitamin D supplementary treatment on meaningful long-term clinical end points in AITD.
Link: https://pubmed.ncbi.nlm.nih.gov/37116030/
The interplay of oxidative stress and immune dysfunction in Hashimoto's thyroiditis and polycystic ovary syndrome: a comprehensive review
In recent years, there has been a significant increase in the concomitant incidence of Hashimoto’s thyroiditis (HT) and polycystic ovary syndrome (PCOS), both in terms of incidence, etiology, and clinical consequences. PCOS patients suffering from autoimmune thyroid diseases show insulin resistance, impaired glucose tolerance, weight gain, and metabolic and reproductive complications. Studies have shown that chronic stress and its consequence, i.e. oxidative stress, play an important role in the pathomechanism of both disorders. It has also been shown that long-term exposure to stress triggers biological mechanisms, in particular related to the regulation of the inflammatory cascade, which plays a key role in autoimmune diseases. The paper is a review of the literature on the role of chronic stress, oxidative stress, and immune processes in the pathogenesis of HT and PCOS. In addition, the review is a source of knowledge about the treatment of these diseases, and in particular the use of antioxidants in therapeutic management.
History
Use of levothyroxine in the management of hypothyroidism: A historical perspective
2022. A review of the history of levothyroxine and how it became the standard of care for hypothyroidism.
Link: https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2022.1054983/full
Hyperthyroidism
Hyperthyroidism (primary)
2008. Hyperthyroidism is characterised by high levels of serum thyroxine and triiodothyronine, and low levels of thyroid-stimulating hormone. The main causes of hyperthyroidism are Graves’ disease, toxic multinodular goitre, and toxic adenoma. About 20 times more women than men have hyperthyroidism.
In this systematic review we present information relating to the effectiveness and safety of the following interventions: adding thyroxine to antithyroid drugs (carbimazole, propylthiouracil, and thiamazole), antithyroid drugs (carbimazole, propylthiouracil, and thiamazole), radioactive iodine, and thyroidectomy.
Illness
The hypothalamus-pituitary-thyroid axis in critical illness
2009. Critically ill patients show uniform disturbances in the hypothalamus-pituitary-thyroid axis. There is clear evidence that circulating and tissue TH levels are low and this is called the low T3 syndrome or non-thyroidal illness syndrome. The clinical importance of the low T3 syndrome is still not very clear because it can either protect against or aggravate the catabolic state.
Effect of severe, chronic illness on thyroid function
1974. Most clinically euthyroid patients with severe, chronic, non-thyroidal illnesses (i.e., ” sick euthyroid ” patients) have abnormal thyroid-function tests, and consequently assessment of their thyroidal status may be very difficult. The most striking abnormality detected in 75 sick euthyroid patients was a highly significant reduction in the mean total serum-triiodothyronine (T3) levels, with most patients having total T3 levels in the hypothyroid range. The severity of the illness correlated well with the reduction in total serum-T3 levels.
Link: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(74)92070-4/fulltext
Thyroid function during critical illness
2011. The metabolic support of the critically ill patient is a relatively new target of active research and little is as yet known about the effects of critical illness on metabolism. The nonthyroidal illness syndrome, also known as the low T3 syndrome or euthyroid sick syndrome, describes a condition characterized by abnormal thyroid function tests encountered in patients with acute or chronic systemic illnesses. Data on the beneficial effect of thyroid hormone treatment on outcome in critically ill patients are so far controversial. Thyroid function generally returns to normal as the acute illness resolves.
Immunity & Antibodies
Mechanisms of Autoantibody-Induced Pathology
2017. Autoantibodies are frequently observed in healthy individuals. In a minority of these individuals, they lead to manifestation of autoimmune diseases, such as rheumatoid arthritis or Graves’ disease. Overall, more than 2.5% of the population is affected by autoantibody-driven autoimmune disease. To foster knowledge in autoantibody-induced pathology and to encourage development of urgently needed novel therapeutic strategies, we here categorized autoantibodies according to their effects.
Inflammation
Thyroid Hormones, Oxidative Stress, and Inflammation
2016. Inflammation and oxidative stress (OS) are closely related processes, as well exemplified in obesity and cardiovascular diseases. OS is also related to hormonal derangement in a reciprocal way. Among the various hormonal influences that operate on the antioxidant balance, thyroid hormones play particularly important roles, since both hyperthyroidism and hypothyroidism have been shown to be associated with OS in animals and humans. In this context, the nonthyroidal illness syndrome (NTIS) that typically manifests as reduced conversion of thyroxine (T4) to triiodothyronine (T3) in different acute and chronic systemic conditions is still a debated topic. The pathophysiological mechanisms of this syndrome are reviewed, together with the roles of deiodinases, the enzymes responsible for the conversion of T4 to T3, in both physiological and pathological situations.
The causal relationship between 41 inflammatory cytokines and hypothyroidism: bidirectional two-sample Mendelian randomization study
2024. Investigating the association between inflammatory cytokines and hypothyroidism remains challenging due to limitations in traditional observational studies. In this study, we employed Mendelian randomization (MR) to assess the causal relationship between 41 inflammatory cytokines and hypothyroidism.
Our study suggests that IL-7 and MIP-1β may play a role in the pathogenesis of hypothyroidism, and that hypothyroidism may induce a systemic inflammatory response involving multiple cytokines. These findings may have implications for the prevention and treatment of hypothyroidism and its complications.
Link: https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2023.1332383/full
Beyond low plasma T3: local thyroid hormone metabolism during inflammation and infection
2011. Decreased serum thyroid hormone concentrations in severely ill patients were first reported in the 1970s, but the functional meaning of the observed changes in thyroid hormone levels, together known as nonthyroidal illness syndrome (NTIS), remains enigmatic. Although the common view was that NTIS results in overall down-regulation of metabolism in order to save energy, recent work has shown a more complex picture. NTIS comprises marked variation in transcriptional and translational activity of genes involved in thyroid hormone metabolism, ranging from inhibition to activation, dependent on the organ or tissue studied.
Insulin & Insulin Resistance
Association of thyroid function with insulin resistance: data from two population-based studies
2022. The objective of this study was to investigate the association of thyroid function with insulin resistance with particular consideration of possible age-related effect modifications.
A sample of 4193 participants from two independent epidemiological studies, the Study of Health in Pomerania-TREND-0 and the Berlin Aging Study II, was included in this cross-sectional analysis.
The main finding of this study was a consistent association of fT3 with almost all markers of insulin resistance. However, this effect seems to be wearing off in higher age highlighting a potential age-related modification of the interaction between thyroid function and glucose metabolism.
Hyperinsulinemia and insulin resistance is associated with low T₃/T₄ ratio in pre diabetic euthyroid Pakistani subjects
2012. To investigate the relationship of thyroid hormones in glucose homeostasis in impaired glucose-tolerant subjects with normal thyroid functions. Marked hyperinsulinemia and insulin resistance were observed in IGT subjects. Hyperinsulinemia and insulin resistance are associated with low T₃/T₄ ratio in pre-diabetic euthyroid Pakistani subjects.
Intestinal Permeability (aka Leaky Gut)
All disease begins in the (leaky) gut: role of zonulin-mediated gut permeability in the pathogenesis of some chronic inflammatory diseases
2020. Alessio Fasano. Apart from genetic makeup and exposure to environmental triggers, inappropriate increase in intestinal permeability (which may be influenced by the composition of the gut microbiota), a “hyper-belligerent” immune system responsible for the tolerance–immune response balance, and the composition of gut microbiome and its epigenetic influence on the host genomic expression have been identified as three additional elements in causing CIDs (chronic inflammatory diseases).
Pre-clinical and clinical studies have shown that the zonulin family, a group of proteins modulating gut permeability, is implicated in a variety of CIDs, including autoimmune, infective, metabolic, and tumoral diseases. These data offer novel therapeutic targets for a variety of CIDs in which the zonulin pathway is implicated in their pathogenesis.
Iodine
Iodine: an environmental trigger of thyroiditis
2002. A body of clinical and epidemiologic evidence points to excessive ingestion of iodine as an environmental agent. In genetically determined thyroiditis in animals, iodine enrichment has been shown to increase the incidence and severity of disease.
GLOBAL ENDOCRINOLOGY: Global perspectives in endocrinology: coverage of iodized salt programs and iodine status in 2020
2021. odine deficiency has multiple adverse effects on growth and development. Diets in many countries cannot provide adequate iodine without iodine fortification of salt. In 2020, 124 countries have legislation for mandatory salt iodization and 21 have legislation allowing voluntary iodization. As a result, 88% of the global population uses iodized salt.
The number of countries with adequate iodine intake has nearly doubled from 67 in 2003 to 118 in 2020. However, 21 countries remain deficient, while 13 countries have excessive intakes, either due to excess groundwater iodine, or over-iodized salt.
Iodide induces thyroid autoimmunity in patients with endemic goitre: a randomised, double-blind, placebo-controlled trial
1998. A subset of individuals, on exposure to iodine, develop thyroid dysfunction. In this double-blind trial, we evaluated the efficacy and tolerability of low-dose iodine compared with those of levo-thyroxine (T4) in patients with endemic goitre.
The Relationship between High Iodine Consumption and Levels of Autoimmune Thyroiditis-Related Biomarkers in a Chinese Population: a Meta-Analysis
To comprehensively evaluate the relationship between high iodine concentration and biomarker abnormalities related to autoimmune thyroiditis in a Chinese population. A total of 16 cross-sectional articles were included in this study, including 9061 participants. High iodine can increase the risk of abnormal levels of TPOAb, TGAb, and TSH related to autoimmune thyroiditis in pregnant women, lactating women, and children in China.
Relationship between mild iodine deficiency in pregnant women and thyroid function: A meta-analysis
Pregnant women are among the key groups in iodine nutrition evaluation. The purpose of the present study was to summarize the evidence supporting the relationship between mild iodine deficiency (UIC: 100-150 μg/L) in pregnant women and levels of thyroid function tests.
Mild iodine deficiency is associated with an increase in FT3，FT4 and TgAb levels in pregnant women. Mild iodine deficiency may increase the risk of thyroid dysfunction in pregnant women.
The role of iodine in the evolution of thyroid disease in Greece: from endemic goiter to thyroid autoimmunity
Greece is a country with a recent history of moderate iodine deficiency, endemic goiter being prevalent in the 1960s in inhabitants of mountainous regions. Despite recognition of the problem, an iodine prophylaxis program was never officially implemented. Instead, “silent iodine prophylaxis” took place during the 1980s and 1990s with Greece’s improvement in socioeconomic conditions. This resulted in the elimination of iodine deficiency and a parallel decrease in the prevalence of goiter among schoolchildren in formerly iodine deficient areas. However, the transition from iodine deficiency to iodine sufficiency or excess was followed by the emergence of autoimmune thyroiditis, especially among young girls, indicating that exposure to excess iodine may trigger thyroid autoimmunity.
Iron
Relationship between Iron Deficiency and Thyroid Function: A Systematic Review and Meta-Analysis
Iron deficiency (ID) is the most prevalent nutritional deficiency worldwide. Low levels of serum ferritin (SF) could affect the thyroid gland and its functioning. The purpose of this systematic review and meta-analysis is to summarize the main currently available evidence and analyze data on the relationship between ID and thyroid function.
Studies currently published in the literature indicate a possible relationship between iron deficiency, thyroid function, and autoimmunity, especially in some patient groups. Data analysis shows that thyroid hormone levels are lower in patients with ID and, in particular, in pregnant women.
The relationship between iron status and thyroid hormone concentration in iron-deficient adolescent Iranian girls
Extensive data from animal and human studies indicate that iron deficiency impairs thyroid metabolism. The aim of this study was to determine thyroid hormone status in iron-deficient adolescent girls. Hematological indices for iron status confirmed that all subjects were iron-deficient. There was a significant correlation between T4 and ferritin and between TSH and ferritin. The results indicate that the degree of iron deficiency may affect thyroid hormone status in iron-deficient adolescent girls.
Effects of administration of iron, iodine and simultaneous iron-plus-iodine on the thyroid hormone profile in iron-deficient adolescent Iranian girls
A double-blind randomized intervention study, to investigate whether iron supplementation can improve thyroid hormone function in iron-deficient adolescent girls. Our results indicate that improvement of iron status was accompanied by an improvement in some indices of thyroid hormones.
Role of gastric secretion in iron absorption.
1969. Abstract available online.
Probiotic strain Lactobacillus plantarum 299v increases iron absorption from an iron-supplemented fruit drink: a double-isotope cross-over single-blind study in women of reproductive age
2015. Adding probiotics to foods could be one way to increase iron absorption. The aim of this study was to test the hypothesis that non-haem iron absorption from a fruit drink is improved by adding Lactobacillus plantarum 299v (Lp299v).
In conclusion, intake of probiotics can increase iron absorption by approximately 50 % from a fruit drink having an already relatively high iron bioavailability.
Reduction of phytic acid and enhancement of bioavailable micronutrients in food grains
2013. Iron and zinc deficiencies are the major health problems worldwide. Phytic acid is the major storage form of phosphorous in cereals, legumes, oil seeds and nuts. Phytic acid is known as a food inhibitor which chelates micronutrient and prevents it to be bioavailabe for monogastric animals, including humans, because they lack enzyme phytase in their digestive tract.
Several methods have been developed to reduce the phytic acid content in food.These include genetic improvement as well as several pre-treatment methods such as fermentation, soaking, germination and enzymatic treatment of grains with phytase enzyme.
Leaky Gut
Go to Intestinal Permeability.
Leptin
Leptin, nutrition, and the thyroid: the why, the wherefore, and the wiring
2000.
Investigations of thyroid hormones and antibodies in obesity: leptin levels are associated with thyroid autoimmunity independent of bioanthropometric, hormonal, and weight-related determinants
2010. Obesity can alter the thyroid hormone status as a result of a dysregulated endocrine loop between the hypothalamo-pituitary unit and adipose tissue. The adipocytokine leptin has been shown to promote autoimmunity; hence, we aimed to clarify whether leptin excess of obesity could increase the susceptibility to develop autoimmune thyroid disease (AITD).
Free thyroid hormones, TSH, thyroglobulin, and antithyroid antibodies levels were tested in 165 obese and 118 lean subjects.
Obesity increases the susceptibility to harbor AITD with an emerging role for leptin as a peripheral determinant, which needs to be confirmed in future investigations.
The role of leptin in health and disease
2017. Leptin is a master regulator of energy balance and body adiposity. Additionally, leptin exerts important control on glucose homeostasis, thermogenesis, autonomic nervous system and neuroendocrine axes. In metabolic diseases, such as obesity and diabetes mellitus, leptin signaling may be compromised, indicating the important role of this hormone in the etiology and pathophysiological manifestations of these conditions. In the present manuscript, we reviewed important concepts of leptin signaling, as well as about the effects of leptin on several biologic functions. We also discussed the possible therapeutic use of leptin administration and how our current obesogenic environment contributes to the development of leptin resistance.
Leptin resistance: underlying mechanisms and diagnosis
2019. Leptin and its receptors have been identified as key regulators of body weight and energy homeostasis. A decrease in tissue sensitivity to leptin leads to the development of obesity and metabolic disorders, such as insulin resistance and dyslipidemia. In this review, we analyze the existing data on the methods used to diagnose leptin resistance.
Menstruation
Hypothyroidism and Its Impact on Menstrual Irregularities in Reproductive-Age Women: A Comprehensive Analysis at a Tertiary Care Center
2024. This study aims to comprehensively analyze the association between hypothyroidism and menstrual irregularities in women attending a tertiary care center. The study included 120 women aged 18-45 who presented with menstrual abnormalities.
This study underscores a notable link between hypothyroidism and menstrual irregularities in women of reproductive age. The results highlight the necessity of routine thyroid function screenings for women experiencing menstrual abnormalities, facilitating precise diagnosis and suitable treatment.
Metabolism
Thyroid Hormone Regulation of Metabolism
The authors looked at thyroid hormones and their impact on metabolism. Thyroid hormones regulate metabolic processes essential for normal growth and development as well as regulating metabolism in the adult. Hyperthyroidism, excess thyroid hormone, promotes a hypermetabolic state characterized by increased resting energy expenditure, weight loss, reduced cholesterol levels, increased lipolysis, and gluconeogenesis. Hypothyroidism, reduced thyroid hormone levels, is associated with hypometabolism characterized by reduced resting energy expenditure, weight gain, increased cholesterol levels, reduced lipolysis, and reduced gluconeogenesis.
Metmorfin
Metformin ameliorates insulin resistance, thyroid nodules and thyroid function
2023. To evaluate the ameliorative impact of metformin on insulin resistance (IR), as well as thyroid nodules (TNs) and function in TN patients with IR. The clinical data of 128 TN patients with IR admitted to Yantai Laiyang Central Hospital from July 2018 to March 2020 were retrospectively analyzed.
Metformin could significantly improve IR and oxidative stress levels, regulate TSH levels, and shrink TNs in TN patients with IR, with high safety. The administration of metformin and FT4 were identified as protective factors for positive prognosis.
The Effect of Metformin on Thyroid-Associated Serum Hormone Levels and Physiological Indexes: A Meta-Analysis
2019. The objective of this analysis is to evaluate the effect of metformin treatment on serum TSH, free triiodothyronine (FT3), and free thyroxine (FT4) levels and other associated physiological indices. Six RCTs were included. A total of 494 patients met the inclusion criteria.
Metformin treatment can significantly lower the serum TSH levels, and this effect was much clearer after a 12-month treatment duration and in people with normal thyroid function. However, metformin cannot significantly change the serum FT4 levels or lower serum FT3 levels in people with non-thyroid cancer diseases. In addition, metformin can significantly increase DBP, but it has no clear effect on SBP or BMI.
The Association between Vitamin D Status and the Impact of Metformin on Hypothalamic-Pituitary-Thyroid Axis Activity in Women with Subclinical Hypothyroidism
2024. The aim of this prospective cohort study was to investigate whether vitamin D status determines the effect of metformin on hypothalamic-pituitary-thyroid axis activity in levothyroxine-naïve women. The study included three groups of women of reproductive age with subclinical non-autoimmune hypothyroidism.
The drug did not affect circulating levels of 25OHD, free and total thyroid hormones, prolactin, other structure parameters of thyroid homeostasis, and markers of thyroid hormone action. The obtained results allow us to conclude that low vitamin D status in young women mitigates the impact of metformin on thyrotroph secretory function.
Nutrition
Multiple nutritional factors and thyroid disease, with particular reference to autoimmune thyroid disease
2018. It is presently accepted that genetic susceptibility, and environmental factors, including nutritional factors and immune disorders, contribute to the development of AITD. Aiming to investigate the effect of iodine, iron and selenium in the risk, pathogenesis and treatment of thyroid disease.
Appropriate status of iodine, iron and selenium is crucial to thyroid health.
Obesity
Obesity and thyroid function
2009. A moderate elevation of thyrotropin (TSH) concentrations, which is associated with triiodothyronine (T3) values in or slightly above the upper normal range, is frequently found in obese humans. These alterations seem rather a consequence than a cause of obesity since weight loss leads to a normalization of elevated thyroid hormone levels.
Hypothyroidism and obesity: An intriguing link
2016. According to common perception, hypothyroidism is held responsible for obesity. However, linking them causally is controversial. Overt hypothyroidism is associated with modest weight gain, but there is a lack of clarity regarding subclinical hypothyroidism. Novel view indicates that changes in thyroid-stimulating hormone (TSH) could well be secondary to obesity. The increasing prevalence of obesity further confounds definition of normal TSH range in population studies. Thyroid autoantibody status may help in establishing the diagnosis of subclinical hypothyroidism in obesity. High leptin levels may play a role in the hyperthyrotropinemia of obesity and also increase susceptibility to thyroid autoimmunity and subsequent hypothyroidism. There is at most a modest effect of L-T4 treatment in overt hypothyroidism in inducing weight loss; benefit in subclinical hypothyroidism is not established with no data supporting thyroid hormone use in euthyroid obese patients.
Investigations of thyroid hormones and antibodies in obesity: leptin levels are associated with thyroid autoimmunity independent of bioanthropometric, hormonal, and weight-related determinants
2010. Obesity can alter the thyroid hormone status as a result of a dysregulated endocrine loop between the hypothalamo-pituitary unit and adipose tissue. The adipocytokine leptin has been shown to promote autoimmunity; hence, we aimed to clarify whether leptin excess of obesity could increase the susceptibility to develop autoimmune thyroid disease (AITD).
Free thyroid hormones, TSH, thyroglobulin, and antithyroid antibodies levels were tested in 165 obese and 118 lean subjects.
Obesity increases the susceptibility to harbor AITD with an emerging role for leptin as a peripheral determinant, which needs to be confirmed in future investigations.
Pathogenic potential of adipose tissue and metabolic consequences of adipocyte hypertrophy and increased visceral adiposity
2008. When caloric intake exceeds caloric expenditure, the positive caloric balance and storage of energy in adipose tissue often causes adipocyte hypertrophy and visceral adipose tissue accumulation. These pathogenic anatomic abnormalities may incite metabolic and immune responses that promote Type 2 diabetes mellitus, hypertension and dyslipidemia.
This review describes the consequences of pathogenic fat cell hypertrophy and visceral adiposity, emphasizing the mechanistic contributions of genetic and environmental predispositions, adipogenesis, fat storage, free fatty acid metabolism, adipocyte factors and inflammation.
Hypothalamic circuits regulating appetite and energy homeostasis: pathways to obesity
2017. The ‘obesity epidemic’ represents a major global socioeconomic burden that urgently calls for a better understanding of the underlying causes of increased weight gain and its associated metabolic comorbidities, such as type 2 diabetes mellitus and cardiovascular diseases. Improving our understanding of the cellular basis of obesity could set the stage for the development of new therapeutic strategies.
This At a Glance article gives an overview of the recent knowledge, mainly derived from rodent models, regarding the CNS-dependent regulation of energy and glucose homeostasis, and illustrates how dysregulation of the neuronal networks involved can lead to overnutrition and obesity.
Dietary inflammatory index and anthropometric measures of obesity in a population sample at high cardiovascular risk from the PREDIMED (PREvención con DIeta MEDiterránea) trial
2015. The dietary inflammatory index (DII) is a new tool to assess the inflammatory potential of the diet. In the present study, we aimed to determine the association between the DII and BMI, waist circumference and waist:height ratio (WHtR). We conducted a cross-sectional study of 7236 participants recruited into the PREvención con DIeta MEDiterránea trial.
In conclusion, the present study shows a direct association between the DII and indices of obesity, and supports the hypothesis that diet may have a role in the development of obesity through inflammatory modulation mechanisms.
PCOS
The interplay of oxidative stress and immune dysfunction in Hashimoto's thyroiditis and polycystic ovary syndrome: a comprehensive review
2023. In recent years, there has been a significant increase in the concomitant incidence of Hashimoto’s thyroiditis (HT) and polycystic ovary syndrome (PCOS), both in terms of incidence, etiology, and clinical consequences. PCOS patients suffering from autoimmune thyroid diseases show insulin resistance, impaired glucose tolerance, weight gain, and metabolic and reproductive complications. Studies have shown that chronic stress and its consequence, i.e. oxidative stress, play an important role in the pathomechanism of both disorders. It has also been shown that long-term exposure to stress triggers biological mechanisms, in particular related to the regulation of the inflammatory cascade, which plays a key role in autoimmune diseases. The paper is a review of the literature on the role of chronic stress, oxidative stress, and immune processes in the pathogenesis of HT and PCOS. In addition, the review is a source of knowledge about the treatment of these diseases, and in particular the use of antioxidants in therapeutic management.
Thyroid function and polycystic ovary syndrome: a Mendelian randomization study
2004. Multiple evidence suggests that thyroid function is associated with polycystic ovary syndrome (PCOS), but whether thyroid function is causally related to PCOS is unclear. To investigate whether the association reflect causality, a Mendelian randomization (MR) analysis was conducted. A sample size of 16,380,318 individuals.
Our findings demonstrate a cause-and-effect connection between PCOS and hyperthyroidism. The study established foundation for further investigation for interaction between thyroid function and PCOS.
Pregnancy
Relationship between mild iodine deficiency in pregnant women and thyroid function: A meta-analysis
Pregnant women are among the key groups in iodine nutrition evaluation. The purpose of the present study was to summarize the evidence supporting the relationship between mild iodine deficiency (UIC: 100-150 μg/L) in pregnant women and levels of thyroid function tests.
Mild iodine deficiency is associated with an increase in FT3，FT4 and TgAb levels in pregnant women. Mild iodine deficiency may increase the risk of thyroid dysfunction in pregnant women.
Maternal subclinical hypothyroidism, thyroid autoimmunity, and the risk of miscarriage: a prospective cohort study
In this prospective cohort study, we screened 3315 women at low risk for thyroid dysfunction at four to eight weeks’ gestation from iodine-sufficient areas of China between January 2012 and September 2012.
Women with subclinical hypothyroidism and thyroid autoimmunity are at an increased risk of miscarriage between four and eight gestational weeks. Women with a combination of subclinical hypothyroidism and thyroid autoimmunity were found to have the highest risk and earlier gestational ages of miscarriage.
The influence of selenium supplementation on postpartum thyroid status in pregnant women with thyroid peroxidase autoantibodies
Pregnant women who are positive for thyroid peroxidase antibodies [TPOAb(+)] are prone to develop postpartum thyroid dysfunction (PPTD) and permanent hypothyroidism. Selenium (Se) decreases thyroid inflammatory activity in patients with autoimmune thyroiditis. The results showed that Se supplementation during pregnancy and in the postpartum period reduced thyroid inflammatory activity and the incidence of hypothyroidism.
[Thyroid disorders in pregnancy and after delivery]
Pregnant women who are positive for thyroid peroxidase antibodies [TPOAb(+)] are prone to develop postpartum thyroid dysfunction (PPTD) and permanent hypothyroidism. Selenium (Se) decreases thyroid inflammatory activity in patients with autoimmune thyroiditis. The results showed that Se supplementation during pregnancy and in the postpartum period reduced thyroid inflammatory activity and the incidence of hypothyroidism.
Radiation
Hypothyroidism after radiation exposure: brief narrative review
2007. In this paper, the pathophysiology, clinical presentation, diagnosis and management of different thyroid diseases during pregnancy and postpartum period are reviewed. Particular attention is devoted to the results of recently published studies.
Exposing the Thyroid to Radiation: A Review of Its Current Extent, Risks, and Implications
2010. Paralleling the increase in the incidence of papillary thyroid cancer is an increasing use of medical radiation. At present it is unclear to what extent, if any, these two are related. This review summarizes the current sources of thyroid radiation exposure, radiation risks to the thyroid gland, strategies for reducing radiation exposure to the thyroid, and ways that endocrinologists can participate in this effort.
Link: https://pmc.ncbi.nlm.nih.gov/articles/PMC3365850/
Reverse T3
Qualitative and quantitative differences in the pathways of extrathyroidal triiodothyronine generation between euthyroid and hypothyroid rats.
This paper shows that rT3 is a T3 blocker and is not an inactive metabolite.
Riedel's thyroiditis
Clinical review: Riedel's thyroiditis: a clinical review
2011. Riedel’s thyroiditis is a rare inflammatory process involving the thyroid and surrounding cervical tissues and is associated with various forms of systemic fibrosis.
Selenium
Selenium Supplementation Significantly Reduces Thyroid Autoantibody Levels in Patients with Chronic Autoimmune Thyroiditis: A Systematic Review and Meta-Analysis
Selenium supplementation may decrease circulating thyroid autoantibodies in patients with chronic autoimmune thyroiditis (AIT), but the available trials are heterogenous. This study expands and critically reappraises the knowledge on this topic. 16 controlled trials were included in the systematic review.
Selenium supplementation reduced serum TPOAb levels after 3, 6, and 12 months in an LT4-treated AIT population, and after three months in an untreated AIT population. Whether these effects correlate with clinically relevant measures remains to be demonstrated.
Selenium and thyroid diseases
Some clinical studies have shown that lack of selenium will increase the prevalence of several kinds of thyroid diseases. Selenium treatment in patients with Graves’ orbitopathy has been shown to delay disease progression and improve the quality of life. Selenium supplementation in Hashimoto’s thyroiditis was associated with the decreased levels of anti-thyroid peroxidase antibody and improved thyroid ultrasound structure.
However, published results remain the conflicting and more clinical evidence is still needed to determine the clinical significance of selenium. This article reviews the strong association between selenium and thyroid disease and provides new ideas for the clinical management of selenium in thyroid disease.
Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10080082/
Thyroid function in patients with selenium deficiency exhibits high free T4 to T3 ratio
We retrospectively investigated the thyroid function in 22 patients with selenium deficiency. There appeared to be a positive correlation between the decreased rate of selenium levels and FT4/FT3 ratio, thereby indicating that patients with severe selenium deficiency also exhibited abnormal thyroid hormone levels.
The influence of selenium supplementation on postpartum thyroid status in pregnant women with thyroid peroxidase autoantibodies
Pregnant women who are positive for thyroid peroxidase antibodies [TPOAb(+)] are prone to develop postpartum thyroid dysfunction (PPTD) and permanent hypothyroidism. Selenium (Se) decreases thyroid inflammatory activity in patients with autoimmune thyroiditis. The results showed that Se supplementation during pregnancy and in the postpartum period reduced thyroid inflammatory activity and the incidence of hypothyroidism.
Low Population Selenium Status Is Associated With Increased Prevalence of Thyroid Disease
The objective was to investigate whether the prevalence of thyroid disease differed in two areas that were similar, except for very different soil/crop selenium concentrations. ow selenium status is associated with increased risk of thyroid disease. Increased selenium intake may reduce the risk in areas of low selenium intake that exist not only in China but also in many other parts of the world.
Low selenium status in the elderly influences thyroid hormones
We measured serum selenium and erythrocyte glutathione peroxidase (as indices of selenium status), thyroid hormones and thyroid-stimulating hormone in 109 healthy euthyroid subjects (52 women, 57 men). The main result of the double-blind placebo-controlled trial was a significant improvement of selenium indices and a decrease in the T4 level in selenium-treated subjects; serum selenium, erythrocyte glutathione peroxidase activity and thyroid hormones did not change in placebo-treated subjects. We concluded that selenium status influences thyroid hormones in the elderly, mainly modulating T4 levels.
Effects of selenium supplementation on thyroid hormone metabolism in phenylketonuria subjects on a phenylalanine restricted diet
In this study, a group of phenylketonuria subjects with a low selenium status, but a normal iodine intake were supplemented with selenium to investigate changes in their thyroid hormone metabolism. After 3 wk of selenium supplementation, both the concentrations of the prohormone thyroxine (T4) and the metabolic inactive reverse triiodothyronine (rT3) decreased significantly.
Influence of zinc and selenium deficiency on parameters relating to thyroid hormone metabolism
48 weaned male Sprague-Dawley rats were divided into 4 groups of 12 animals (zinc-deficient; zinc-adequate, pair-fed with zinc-deficient group; selenium-deficient; selenium-adequate) for 40 days. The study data show that both zinc and selenium deficiency affect the metabolism of thyroid hormones.
Insufficient evidence to support the clinical efficacy of selenium supplementation for patients with chronic autoimmune thyroiditis
This study critically reappraises the documentation on the clinical efficacy of selenium supplementation in chronic autoimmune thyroiditis (AIT) with the goal of improving the normalization of the treatment of this disease.
Current evidence does not justify the emerging use of selenium supplementation in the treatment of AIT, despite it resulting in a decrease in autoantibody levels.
Statistics
Hypothyroidism Prevalence in the United States: A Retrospective Study Combining National Health and Nutrition Examination Survey and Claims Data, 2009-2019
2022. This study aimed to update estimates of HT prevalence in the United States by retrospective analysis of 2 datasets.
Between 2009 and 2012, HT prevalence remained around 9.6% of the US population. The administrative claims dataset showed that HT prevalence grew from 9.5% in 2012 to 11.7% in 2019 and that >78% of patients received thyroxine (T4) monotherapy. Similarly, the NHANES dataset showed that T4 replacement therapy was the most common treatment for HT. From 2012-2019, patients with untreated HT grew from 11.8% to 14.4%. The prevalence of HT in the United States has steadily increased since 2009. Likewise, the percentage of hypothyroid-diagnosed patients not receiving treatment also increased, suggesting that the increased prevalence may be due to increased cases of subclinical HT.
Stress
Association of stress and primary hypothyroidism
2024. Hypothyroidism is the result of impaired production and secretion of thyroid hormones. The cardiovascular system is affected by fluctuations in thyroid hormone levels. Stressful events or stressors can affect the hypothalamic-pituitary-thyroid (HPT) axis and psychological and physiological responses. Stress increases thyroid hormone levels while decreasing TSH levels, which exacerbates autoimmune thyroid disease.
A total of 77 newly diagnosed hypothyroid patients (TSH >5.0 mIU/L) and 77 healthy adults (TSH 0.5-5.0 mIU/L) were enrolled.
A Cross-Sectional Study of the Relationship Between Perceived Stress and Thyroid Function Among Apparently Normal Women in the Reproductive Age
2024. Chronic stress can lead to the development of autoimmune disorders affecting the thyroid gland. 114 working women aged 20-49 who consented to the study and had no personal or family history of medical illness or thyroid disease were randomly selected. Stress levels were measured using a Perceived Stress Scale (PSS), and thyroid parameters (total triiodothyronine [T3], total thyroxine [T4], and thyroid-stimulating hormone [TSH]) in blood samples were assessed.
The study examined the link between stress and thyroid health in women of childbearing age, revealing a trend where higher stress levels corresponded with increased TSH levels, though not significantly. It also found that older age, higher BMI, and longer duration of marriage were linked to a greater occurrence of SCH (subclinical hypothyroidism). These findings underscore the potential influence of lifestyle factors and stress on thyroid function, suggesting that stress management and demographic factors should be considered in managing thyroid health.
Hypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress
2002. Activation of the stress system leads to behavioral and peripheral changes that improve the ability of the organism to adjust homeostasis and increase its chances for survival. A detailed explanation.
T3 Hormones
Defending plasma T3 is a biological priority
2014. Triiodothyronine (T3), the active form of thyroid hormone is produced predominantly outside the thyroid parenchyma secondary to peripheral tissue deiodination of thyroxine (T4), with <20% being secreted directly from the thyroid. In healthy individuals, plasma T3 is regulated by the negative feedback loop of the hypothalamus-pituitary-thyroid axis and by homoeostatic changes in deiodinase expression. Therefore, with the exception of a minimal circadian rhythmicity, serum T3 levels are stable over long periods of time. Studies in rodents indicate that different levels of genetic disruption of the feedback mechanism and deiodinase system are met with increase in serum T4 and thyroid-stimulating hormone (TSH) levels, while serum T3 levels remain stable. These findings have focused attention on serum T3 levels in patients with thyroid disease, with important clinical implications affecting therapeutic goals and choice of therapy for patients with hypothyroidism. Although monotherapy with levothyroxine is the standard of care for hypothyroidism, not all patients normalize serum T3 levels with many advocating for combination therapy with levothyroxine and liothyronine. The latter could be relevant for a significant number of patients that remain symptomatic on monotherapy with levothyroxine, despite normalization of serum TSH levels.
The Non-Thyroidal Illness Syndrome
2015. NTIS refers to a syndrome found in seriously ill or starving patients with low fT3, usually elevated RT3, normal or low TSH, and if prolonged, low fT4. It is found in a high proportion of patients in the ICU setting, and correlates with a poor prognosis if TT4 is <4ug/dl.
Although recognized for nearly 4 decades, interpretation of the syndrome is contested, because of lack of data. Some observes, totally without data, argue that it is a protective response and should not be treated. Other observers (as in this review) present available data suggesting, but not proving, that thyroid hormone replacement is appropriate, not harmful, and may be beneficial. The best form of treatment (TRH,TSH,or T3+T4) and possible accompanying treatments (GHRH, Cortisol, nutrition, insulin) lack consensus. In this review current data are laid out for reader’s review and judgment.
Thyroid Hormones
Mechanisms of thyroid hormone action
2012. Our understanding of thyroid hormone action has been substantially altered by recent clinical observations of thyroid signaling defects in syndromes of hormone resistance and in a broad range of conditions, including profound mental retardation, obesity, metabolic disorders, and a number of cancers. The mechanism of thyroid hormone action has been informed by these clinical observations as well as by animal models and has influenced the way we view the role of local ligand availability; tissue and cell-specific thyroid hormone transporters, corepressors, and coactivators; thyroid hormone receptor (TR) isoform–specific action; and cross-talk in metabolic regulation and neural development. In some cases, our new understanding has already been translated into therapeutic strategies, especially for treating hyperlipidemia and obesity, and other drugs are in development to treat cardiac disease and cancer and to improve cognitive function.
Thyroid Antibodies
See “Autoimmunity & Thyroid Antibodies”.
Viral diseases
The association of subacute thyroiditis with viral diseases: a comprehensive review of literature
2023. Subacute thyroiditis (SAT), also known as de Quatrain’s thyroiditis or granulomatous thyroiditis, is an inflammatory disease of the thyroid. Most of the time, it manifests in the thirties to fifties and is more common in women. SAT can have either viral or post-viral origin. Some viruses, like influenza, COVID-19, Epstein-Barr virus, cytomegalovirus, hepatitis, coxsackievirus 16, and mumps virus, have been linked to SAT development. The COVID-19 pandemic has affected people’s lives all around the world and has changed our attitude toward the treatment of many diseases. It has also made us look deeper into the subject in a way that we would be able to treat this sort of disease with a newer insight.
Vitamin D
Can Supplementation with Vitamin D Modify Thyroid Autoantibodies (Anti-TPO Ab, Anti-Tg Ab) and Thyroid Profile (T3, T4, TSH) in Hashimoto's Thyroiditis? A Double Blind, Randomized Clinical Trial
2019. The aim of this study was to investigate the effect of vitamin D on circulating thyroid autoantibodies and thyroid hormones profile (T4, T3, and TSH) in females with HT. Forty-two women with HT disease were enrolled in this randomized clinical trial study.
The results of this study showed a significant reduction of anti-Tg Ab and TSH hormone in the Vitamin D group compared to the start of the study; however, there was a no significant reduction of anti-TPO Ab in the Vitamin D group compared to the placebo group (p=0.08). No significant changes were observed in the serum levels of T3 and T4 hormones. Therefore, vitamin D supplementation can be helpful for alleviation of the disease activity in HT patients; however, further well controlled, large, longitudinal studies are needed to determine whether it can be introduced in clinical practice.
The Association between Vitamin D Status and the Impact of Metformin on Hypothalamic-Pituitary-Thyroid Axis Activity in Women with Subclinical Hypothyroidism
2024. The aim of this prospective cohort study was to investigate whether vitamin D status determines the effect of metformin on hypothalamic-pituitary-thyroid axis activity in levothyroxine-naïve women. The study included three groups of women of reproductive age with subclinical non-autoimmune hypothyroidism.
The drug did not affect circulating levels of 25OHD, free and total thyroid hormones, prolactin, other structure parameters of thyroid homeostasis, and markers of thyroid hormone action. The obtained results allow us to conclude that low vitamin D status in young women mitigates the impact of metformin on thyrotroph secretory function.
A Prospective Study to Evaluate the Possible Role of Cholecalciferol Supplementation on Autoimmunity in Hashimoto's Thyroiditis
2023. Most studies have shown an association between low vitamin D status and pathogenesis of AITD, especially HT. However, there are only few preliminary interventional studies for HT. whether vitamin D supplementation is beneficial for AITD or HT, should be evaluated. Treatment of HT mainly based on thyroid hormone supplementation, so if a beneficial role of vitamin D supplementation is identified/ confirmed, it will be helpful in the treatment of patients with HT and may be a part of treatment of HT patients.
The 8 weeks randomized; double-blind, placebo-controlled clinical trial demonstrates a negative correlation between Serum 25 hydroxy vitamin D vs anti TPO antibody level. Treatment with 60,000 IU cholecalciferol weekly for 8 weeks, is associated with significant decrease in antithyroid antibody titers. It also improved serum TSH level compared with the placebo, i.e. supplementary treatment with cholecalciferol seems to have beneficial effects on AITD. However, large multicentre studies are needed to investigate the impact of vitamin D supplementary treatment on meaningful long-term clinical end points in AITD.
Link: https://pubmed.ncbi.nlm.nih.gov/37116030/
Workplace
he Impact of Thyroid Diseases on the Working Life of Patients: A Systematic Review
2020. Thyroid diseases are characterized by a wide range of physical and mental symptoms that can affect biological function, emotional and social life of patients. However, their impact on work functioning is not yet fully understood. Therefore, this review aims to address the way in which thyroid diseases can affect occupational outcomes, i.e., the employment rate, sick leave, working capacity and work income of patients.
Hyperthyroid and hypothyroid patients presented a greater risk of long-term sick leave than controls, depending on the severity of the disease.
The Impact of Employer Sympathy on Women's Labour Market Prospects: A Focus on Thyroid Conditions
Understanding the impact of employer sympathy on women’s productivity and labour market prospects is crucial for fostering inclusive workplaces. Despite the evidence on the adverse labour market effects of thyroid dysfunctions, predominantly on women, a gap exists in understanding the role of employer sympathy in supporting women with these conditions. Using unique UK questionnaire data on thyroid patients, this study is the first to explore this relationship. The results confirm that employer sympathy mitigates the adverse effects of thyroid dysfunctions on employee engagement, subsequently improving labour market prospects. This research provides valuable insights at the intersection of health conditions, gender, and work performance, offering guidance for employers and HRM professionals to enhance workplace support for women with thyroid conditions, ultimately enhancing wellbeing and productivity.
Link:
https://www.abdn.ac.uk/news/23192/
https://aura.abdn.ac.uk/bitstream/handle/2164/22792/DP_24-2.pdf
Hyperthyroidism is associated with work disability and loss of labour market income. A Danish register-based study in singletons and disease-discordant twin pairs
Hyperthyroidism is associated with severe work disability as reflected by an 88% increased risk of receiving disability pension and a significant loss of labour market income. Similar results in monozygotic twins discordant for hyperthyroidism suggest that genetic confounding is unlikely.
Prevalence of thyroid dysfunction and its relationship to income level and employment status: a nationwide population-based study in Spain
The influence of socioeconomic conditions on the prevalence of thyroid dysfunction in the population has been scarcely studied to date. The aim of this study has been to evaluate the influence of income level and employment status on the prevalence of hypothyroidism and hyperthyroidism.
Conclusion: Socioeconomic conditions are related to the prevalence of thyroid dysfunction. Low-income or unemployed people have a higher frequency of both hypothyroidism and hyperthyroidism.
Hypothyroidism is a predictor of disability pension and loss of labor market income: a Danish register-based study
2014. Hypothyroidism is associated with an increased somatic and psychiatric disease burden. Whether there are any socioeconomic consequences of hypothyroidism, such as early retirement or loss of income, remains unclarified.
A diagnosis of hypothyroidism before the age of 60 is associated with loss of labor market income and an 89% increased risk of receiving a disability pension.
Zinc
Zinc Deficiency Associated with Hypothyroidism: An Overlooked Cause of Severe Alopecia
Hypothyroidism is a common and well-recognized cause of diffuse hair loss. Zinc and other trace elements such as copper and selenium are required for the synthesis of thyroid hormones, and deficiency of these can result in hypothyroidism. Conversely, thyroid hormones are essential for the absorption of zinc, and hence hypothyroidism can result in acquired zinc deficiency. The hair loss attributed to hypothyroidism may not improve with thyroxine unless zinc supplements are added, as demonstrated in our case.
The Role of Zinc in Thyroid Hormones Metabolism
2019. Thyroid hormones play an important role in body homeostasis by facilitating metabolism of lipids and glucose, regulating metabolic adaptations, responding to changes in energy intake, and controlling thermogenesis. Proper metabolism and action of these hormones requires the participation of various nutrients. Among them is zinc, whose interaction with thyroid hormones is complex.
In the present review, we aim to shed light on the regulatory effects of zinc on thyroid hormones. Scientific evidence shows that zinc plays a key role in the metabolism of thyroid hormones, specifically by regulating deiodinases enzymes activity, thyrotropin releasing hormone (TRH) and thyroid stimulating hormone (TSH) synthesis, as well as by modulating the structures of essential transcription factors involved in the synthesis of thyroid hormones. Serum concentrations of zinc also appear to influence the levels of serum T3, T4 and TSH. In addition, studies have shown that Zinc transporters (ZnTs) are present in the hypothalamus, pituitary and thyroid, but their functions remain unknown.
Effects of Zinc and Selenium Supplementation on Thyroid Function in Overweight and Obese Hypothyroid Female Patients: A Randomized Double-Blind Controlled Trial
2015. Zinc (Zn) and selenium (Se) are essential trace elements involved in thyroid hormone metabolism. This study was conducted to investigate the effects of Zn and Se supplementation on thyroid function of overweight or obese female hypothyroid patients in a double-blind, randomized controlled trial. Sixty-eight female hypothyroid patients were randomly allocated to one of the 4 supplementation groups. This study showed some evidence of an effect of Zn alone or in combination with Se on the thyroid function of overweight or obese female hypothyroid patients.