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Thyroid as a target of adjuvant autoimmunity/inflammatory syndrome due to mRNA-based SARS-CoV2 vaccination: from Graves' disease to silent thyroiditis.
Pujol, A, Gómez, LA, Gallegos, C, Nicolau, J, Sanchís, P, González-Freire, M, López-González, ÁA, Dotres, K, Masmiquel, L
Journal of endocrinological investigation. 2022;(4):875-882
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Abstract
BACKGROUND As COVID-19 became a pandemic, the urgent need to find an effective treatment vaccine has been a major objective. Vaccines contain adjuvants which are not exempt from adverse effects and can trigger the autoimmune/inflammatory syndrome induced by adjuvants (ASIA). There is very little information about autoimmune endocrine disease and the ASIA after the use of mRNA-based SARS-CoV2 vaccination. CASE SERIES We report three cases and also review the literature showing that the thyroid gland can be involved in the ASIA induced by the mRNA-based SARS-CoV2 vaccination. We present the first case to date of silent thyroiditis described in the context of SARS-CoV2 vaccination with Pfizer/BioNTech. Also, we discuss the first subacute thyroiditis in the context of SARS-CoV2 vaccination with the Moderna's vaccine. Finally, we provide another case to be added to existing evidence on Graves' disease occurring post-vaccination with the Pfizer/BioNTech vaccine. DISCUSSION Adjuvants play an important role in vaccines. Their ability to increase the immunogenicity of the active ingredient is necessary to achieve the desired immune response. Both the Moderna and the Pfizer/BioNTech vaccines use mRNA coding for the SARS-CoV2 S protein enhanced by adjuvants. In addition, the cross-reactivity between SARS-CoV2 and thyroid antigens has been reported. This would explain, at least, some of the autoimmune/inflammatory reactions produced during and after SARS-CoV2 infection and vaccination. CONCLUSION The autoimmune/inflammatory syndrome induced by adjuvants involving the thyroid could be an adverse effect of SARS-CoV2 vaccination and could be underdiagnosed.
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Celiac Disease and the Thyroid: Highlighting the Roles of Vitamin D and Iron.
Starchl, C, Scherkl, M, Amrein, K
Nutrients. 2021;(6)
Abstract
Celiac disease (CD) and autoimmune thyroid diseases (AITD) like Hashimoto's thyroiditis (HT) and Graves' disease (GD) frequently coexist, entailing numerous potential impacts on diagnostic and therapeutic approaches. Possible correlations might exist through gut microbiota, regulating the immune system and inflammatory responses, promoting autoimmune diseases, as well as shared cytokines in pathogenesis pathways, cross-reacting antibodies or malabsorption of micronutrients that are essential for the thyroid like iron or vitamin D. Vitamin D deficiency is a common finding in patients with AITD, but might protect from autoimmunity by wielding immunoregulatory and tolerogenic impacts. Additionally, vitamin D is assumed to be involved in the onset and progression of CD, presumably plays a substantial protective role for intestinal mucosa and affects the thyroid via its immunomodulatory effects. Iron is an essential micronutrient for the thyroid gland needed for effective iodine utilization by the iron-dependent enzyme thyroid iodine peroxidase (TPO). Despite being crucial for thyroid hormone synthesis, iron deficiency (ID) is a common finding in patients with hypothyroidism like HT and is frequently found in patients with CD. A literature research was conducted to examine the interplay between CD, AITD, vitamin D and iron deficiency. This narrative review highlights the relevant correlation of the two disease entities CD and AITD, their reciprocal impact and possible therapeutic options that should be further explored by future studies.
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Effects of an Iodine-Containing Prenatal Multiple Micronutrient on Maternal and Infant Iodine Status and Thyroid Function: A Randomized Trial in The Gambia.
Eriksen, KG, Andersson, M, Hunziker, S, Zimmermann, MB, Moore, SE
Thyroid : official journal of the American Thyroid Association. 2020;(9):1355-1365
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Abstract
Background: Iodine supplementation is recommended to pregnant women in iodine-deficient populations, but the impact in moderate iodine deficiency is uncertain. We assessed the effect of an iodine-containing prenatal multiple micronutrient (MMN) supplement in a rural Gambian population at risk of moderate iodine deficiency. Materials and Methods: This study uses data and samples collected as a part of the randomized controlled trial Early Nutrition and Immune Development (ENID; ISRCTN49285450) conducted in Keneba, The Gambia. Pregnant women (<20 weeks gestation) were randomized to either a daily supplement of MMNs containing 300 μg of iodine or an iron and folic acid (FeFol) supplement. Randomization was double blinded (participants and investigators). The coprimary outcomes were maternal urinary iodine concentration (UIC) and serum thyroglobulin (Tg), assessed at baseline and at 30 weeks' gestation. Secondary outcomes were maternal serum thyrotropin (TSH), total triiodothyronine (TT3), total thyroxine (TT4) (assessed at baseline and at 30 weeks' gestation), breast milk iodine concentration (BMIC) (assessed at 8, 12, and 24 weeks postpartum), infant serum Tg (assessed at birth [cord], 12, and 24 weeks postpartum), and serum TSH (assessed at birth [cord]). The effect of supplementation was evaluated using mixed effects models. Results: A total of 875 pregnant women were enrolled between April 2010 and February 2015. In this secondary analysis, we included women from the MMN (n = 219) and FeFol (n = 219) arm of the ENID trial. At baseline, median (interquartile range or IQR) maternal UIC and Tg was 51 μg/L (33-82) and 22 μg/L (12-39), respectively, indicating moderate iodine deficiency. Maternal MMN supplement increased maternal UIC (p < 0.001), decreased maternal Tg (p < 0.001), and cord blood Tg (p < 0.001) compared with FeFol. Maternal thyroid function tests (TSH, TT3, TT4, and TT3/TT4 ratio) and BMIC did not differ according to maternal supplement group over the course of the study. Median (IQR) BMIC, maternal UIC, and infant Tg in the MMN group were 51 μg/L (35-72), 39 μg/L (25-64), and 87 μg/L (59-127), respectively, at 12 weeks postpartum, and did not differ between supplement groups. Conclusions: Supplementing moderately iodine-deficient women during pregnancy improved maternal iodine status and reduced Tg concentration. However, the effects were not attained postpartum and maternal and infant iodine nutrition remained inadequate during the first six months after birth. Consideration should be given to ensuring adequate maternal status through pregnancy and lactation in populations with moderate deficiency.
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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.
Chahardoli, R, Saboor-Yaraghi, AA, Amouzegar, A, Khalili, D, Vakili, AZ, Azizi, F
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2019;(5):296-301
Abstract
Hashimoto's thyroiditis (HT) is the most prevalent autoimmune disorder characterized by the destruction of thyroid cells caused by leukocytes and antibody-mediated immune processes accompanied by hypothyroidism. In recent years, evidence has emerged pointing to various roles for vitamin D, including, proliferation and differentiation of normal and cancer cells, cardiovascular function, and immunomodulation. Vitamin D deficiency has been especially demonstrated in HT patients. 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 and divided into vitamin D and placebo groups. Patients in the vitamin D and placebo groups received 50 000 IU vitamin D and placebo pearls, weekly for 3 months, respectively. The serum levels of 25-hydroxy vitamin D [25(OH) D], Ca++ion, anti-thyroperoxidase antibody (anti-TPO Ab), anti-thyroglobulin antibody (anti-Tg Ab), T4, T3, and TSH were measured at the baseline and at the end of the study using enzyme-linked immunosorbent assays. 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.
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Longitudinal Trajectories of Gestational Thyroid Function: A New Approach to Better Understand Changes in Thyroid Function.
Pop, V, Broeren, M, Wijnen, H, Endendijk, J, van Baar, A, Wiersinga, W, Williams, GR
The Journal of clinical endocrinology and metabolism. 2018;(8):2889-2900
Abstract
CONTEXT Most studies of thyroid function changes during pregnancy use a cross-sectional design comparing means between groups rather than similarities within groups. OBJECTIVE Latent class growth analysis (LCGA) is a novel approach to investigate longitudinal changes that provide dynamic understanding of the relationship between thyroid status and advancing pregnancy. DESIGN Prospective observational study with repeated assessments. SETTING General community. PATIENTS Eleven hundred healthy women were included at 12 weeks' gestation. MAIN OUTCOME MEASURES The existence of both free T4 (fT4) and TSH trajectories throughout pregnancy determined by LCGA. RESULTS LCGA revealed three trajectory classes. Class 1 (n = 1019; 92.4%), a low increasing TSH reference group, had a gradual increase in TSH throughout gestation (from 1.1 to 1.3 IU/L). Class 2 (n = 30; 2.8%), a high increasing TSH group, displayed the largest increase in TSH (from 1.9 to 3.3 IU/L). Class 3 (n = 51; 4.6%), a decreasing TSH group, had the largest fall in TSH (from 3.2 to 2.4 IU/L). Subclinical hypothyroidism at 12 weeks occurred in up to 60% of class 3 women and was accompanied by elevated thyroid peroxidase antibodies (TPO-Ab) titers (50%) and a parental history of thyroid dysfunction (23%). In class 2, 70% of women were nulliparous compared with 46% in class 1 and 49% in class 3. CONCLUSIONS LCGA revealed distinct trajectories of longitudinal changes in fT4 and TSH levels during pregnancy in 7.4% of women. These trajectories were correlated with parity and TPO-Ab status and followed patterns that might reflect differences in pregnancy-specific immune tolerance between nulliparous and multiparous women.
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The effect of a ketogenic diet versus a high-carbohydrate, low-fat diet on sleep, cognition, thyroid function, and cardiovascular health independent of weight loss: study protocol for a randomized controlled trial.
Iacovides, S, Meiring, RM
Trials. 2018;(1):62
Abstract
BACKGROUND Many physiological health benefits observed after following a ketogenic diet (KD) can be attributed to the associated weight loss. The KD has become more prominent as a popular health choice, not only in obese/overweight individuals, but also in healthy adults. The study aims to determine the effects of a KD, independent of weight loss, on various aspects of physiological health including: sleep, thyroid function, cognition, and cardio-metabolic health. The study will also aim to determine whether a change in basal metabolic rate may be associated with any changes observed. METHODS Twenty healthy men and women between 18 and 50 years of age will take part in this study. In a randomized controlled, cross-over design, participants will follow two isocaloric diets: a high-carbohydrate, low-fat diet (55% CHO, 20% fat, 25% protein) and a KD (15% CHO, 60% fat, 25% protein). Each dietary intervention will last for a minimum of 3 weeks, with a 1-week washout period in between. Before and after each diet, participants will be assessed for sleep quality, cognitive function, thyroid function, and basal metabolic rate. A blood sample will also be taken for the measurement of cardio-metabolic and immune markers. DISCUSSION The present study will help in understanding the potential effects of a KD on aspects of physiological health in healthy adults, without the confounding factor of weight loss. The study aims to fill a significant void in the academic literature with regards to the benefits and/or risks of a KD in a healthy population, but will also explore whether diet-related metabolic changes may be responsible for the changes observed in physiological health. TRIAL REGISTRATION Pan African Clinical Trial Registry ( www.pactr.org ), trial number: PACTR201707002406306 . Registered on 20 July 2017.
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Selenium: an element for life.
Duntas, LH, Benvenga, S
Endocrine. 2015;(3):756-75
Abstract
This review aims to illustrate the importance of selenium (Se) for maintenance of overall health, especially for the thyroid, immunity, and homeostasis. Furthermore, it outlines the role of Se in reproduction and in virology and discusses the effects of Se supplementation in critical illness. The multifaceted aspects of this essential nutrient have attracted worldwide clinical and research interest in the last few decades. Se exerts its activity in the form of the aminoacid selenocysteine incorporated in selenoproteins. The impact of Se administration should be considered in relation to its apparent U shaped effects, i.e., exhibiting major advantages in Se-deficient individuals but specific health risks in those with Se excess. Addition of selenium to the administration of levothyroxine may be useful in patients with low Se intake and with mild-form or early-stage Hashimoto's thyroiditis (HT). Serum Se concentration (possibly also at tissue level) decreases in inflammatory conditions and may vary with the severity and duration of the inflammatory process. In such cases, the effect of Se supplementation seems to be useful and rational. Meanwhile, Se's ability to improve the activity of T cells and the cytotoxicity of natural killer cells could render it effective in viral disease. However, the evidence, and this should be stressed, is at present conflicting as to whether Se supplementation is of benefit in patients with HT, though there are indications that it is advantageous in cases of mild/moderate Graves' Orbitopathy. The role of Se in type 2 diabetes mellitus (T2DM) is ambiguous, driven by both Se intake and serum levels. The evidence that insulin and glycaemia influence the transport and activity of Se, via regulatory activity on selenoproteins, and that high serum Se may have a diabetogenic effect suggests a 'Janus-effect' of Se in T2DM. Though the evidence is not as yet clear-cut, the organic form (selenomethionine), due to its pharmacokinetics, is likely to be more advantageous in long-term prevention, and supplementation efforts, while the inorganic form (sodium selenite) has proven effective in an acute, e.g., sepsis, clinical setting. Recent data indicate that functional selenoprotein single-nucleotide polymorphisms (SNPs) may interfere with Se utilization and effectiveness.
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Mechanisms in endocrinology: thyroid and polycystic ovary syndrome.
Gaberšček, S, Zaletel, K, Schwetz, V, Pieber, T, Obermayer-Pietsch, B, Lerchbaum, E
European journal of endocrinology. 2015;(1):R9-21
Abstract
Thyroid disorders, especially Hashimoto's thyroiditis (HT), and polycystic ovary syndrome (PCOS) are closely associated, based on a number of studies showing a significantly higher prevalence of HT in women with PCOS than in controls. However, the mechanisms of this association are not as clear. Certainly, genetic susceptibility contributes an important part to the development of HT and PCOS. However, a common genetic background has not yet been established. Polymorphisms of the PCOS-related gene for fibrillin 3 (FBN3) could be involved in the pathogenesis of HT and PCOS. Fibrillins influence the activity of transforming growth factor beta (TGFβ). Multifunctional TGFβ is also a key regulator of immune tolerance by stimulating regulatory T cells (Tregs), which are known to inhibit excessive immune response. With lower TGFβ and Treg levels, the autoimmune processes, well known in HT and assumed in PCOS, might develop. In fact, lower levels of TGFβ1 were found in HT as well as in PCOS women carrying allele 8 of D19S884 in the FBN3 gene. Additionally, vitamin D deficiency was shown to decrease Tregs. Finally, high estrogen-to-progesterone ratio owing to anovulatory cycles in PCOS women could enhance the immune response. Harmful metabolic and reproductive effects were shown to be more pronounced in women with HT and PCOS when compared with women with HT alone or with controls. In conclusion, HT and PCOS are associated not only with respect to their prevalence, but also with regard to etiology and clinical consequences. However, a possible crosstalk of this association is yet to be elucidated.
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Cutting edge: the etiology of autoimmune thyroid diseases.
Eschler, DC, Hasham, A, Tomer, Y
Clinical reviews in allergy & immunology. 2011;(2):190-7
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Abstract
Significant progress has been made in our understanding of the mechanisms leading to autoimmune thyroid diseases (AITD). For the first time, we are beginning to unravel these mechanisms at the molecular level. AITD, including Graves' disease (GD) and Hashimoto's thyroiditis (HT), are common autoimmune diseases affecting the thyroid. They have a complex etiology that involves genetic and environmental influences. Seven genes have been shown to contribute to the etiology of AITD. The first AITD gene discovered, HLA-DR3, is associated with both GD and HT. More recently, this association was dissected at the molecular level when it was shown that substitution of the neutral amino acids Ala or Gln with arginine at position beta 74 in the HLA-DR peptide binding pocket is the specific sequence change causing AITD. Non-MHC genes that confer susceptibility to AITD can be classified into two groups: (1) immune-regulatory genes (e.g., CD40, CTLA-4, and PTPN22); (2) thyroid-specific genes-thyroglobulin and TSH receptor genes. These genes interact with environmental factors, such as infection, likely through epigenetic mechanisms to trigger disease. In this review, we summarize the latest findings on disease susceptibility and modulation by environmental factors.
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Thyroid function and pregnancy: before, during and beyond.
Kennedy, RL, Malabu, UH, Jarrod, G, Nigam, P, Kannan, K, Rane, A
Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology. 2010;(8):774-83
Abstract
Thyroid disturbances are common in women during the reproductive years of their lives. Autoimmunity and altered iodine status together account for a high proportion of the abnormalities. Autoimmune thyroid disease is present in around 4% of young females, and up to 15% are at risk because they are thyroid antibody-positive. There is a strong relationship between thyroid immunity on the one hand and infertility, miscarriage, and thyroid disturbances in pregnancy and postpartum on the other hand. Suboptimal iodine status affects a large proportion of the world's population, and pregnancy further depletes iodine stores. There is controversy surrounding the degree to which iodine should be supplemented and the duration of supplementation. Recent studies have helped to clarify the relationship between maternal thyroid status and neuropsychological development of the child. The role of other environmental factors including smoking and selenium status is also now recognised. Universal screening for thyroid hormone abnormalities is not routinely recommended at present. However, measurement of thyroid function and autoantibodies should certainly be considered in those who are at high risk of thyroid disease and in those whose pregnancy is otherwise high risk. The practicing clinician needs to be aware of the thyroid changes which accompany pregnancy.