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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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Synchronous intrathyroidal parathyroid carcinoma and thyroid carcinoma: case report and review of the literature.
De Falco, N, Santangelo, G, Chirico, F, Cangiano, A, Sommella, MG, Cosenza, A, Ronchi, A, Accardo, M, Pellino, G, Parmeggiani, D, et al
BMC endocrine disorders. 2021;(1):60
Abstract
BACKGROUND Parathyroid carcinoma is a rare endocrine malignancy, rarer when synchronous with a non medullary well differentiated thyroid carcinoma. Parathyroid carcinoma accounts of 0.005% of all malignant tumors and it is responsible for less than 1% of primary hyperparathyroidism. The intrathyroidal localization of a parathyroid gland is not frequent with a reported prevalence of 0.2%. Carcinoma of parathyroids with intrathyroidal localization represents an even rarer finding, reported in only 16 cases described in literature. The rare constellation of synchronous parathyroid and thyroid carcinomas has prompted us to report our experience and perform literature review. CASE PRESENTATION We herein report a case of a 63-years-old man with multinodular goiter and biochemical diagnosis of hyperparathyroidism. Total thyroidectomy with radio-guide technique using gamma probe after intraoperative sesta-MIBI administration and intraoperative PTH level was performed. The high radiation levels in the posterior thyroid lobe discovered an intrathyroidal parathyroid. Microscopic examination revealed a parathyroid main cell carcinoma at the posterior thyroidal left basal lobe, a classic papillary carcinoma at the same lobe and follicular variant of papillary carcinoma at the thyroidal right lobe. To the best of our knowledge, this is the first case documenting a synchronous multicentric non medullary thyroid carcinomas and intrathyroidal parathyroid carcinoma. CONCLUSIONS Our experience was reported and literature review underlining challenging difficulties in diagnostic workup and surgical management was carried out.
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Cryo-EM: A new dawn in thyroid biology.
Coscia, F, Taler-Verčič, A
Molecular and cellular endocrinology. 2021;:111309
Abstract
The thyroid gland accumulates the rare dietary element iodine and incorporates it into iodinated thyroid hormones, utilising several tightly regulated reactions and molecular mechanisms. Thyroid hormones are essential in vertebrates and play a central role in many biological processes, such as development, thermogenesis and growth. The control of these functions is exerted through the binding of hormones to nuclear thyroid hormone receptors that rule the transcription of numerous metabolic genes. Over the last 50 years, thyroid biology has been studied extensively at the cellular and organismal levels, revealing its multiple clinical implications, yet, a complete molecular understanding is still lacking. This includes the atomic structures of crucial pathway components that would be needed to elucidate molecular mechanisms. Here we review the currently known protein structures involved in thyroid hormone synthesis, regulation, transport, and actions. We also highlight targets for future investigations that will significantly benefit from recent advances in macromolecular structure determination by electron cryo-microscopy (cryo-EM). As an example, we demonstrate how cryo-EM was crucial to obtain the structure of the large thyroid hormone precursor protein, thyroglobulin. We discuss modern cryo-EM compared to other structure determination methods and how an integrated structural and cell biological approach will help filling the molecular knowledge gap in our understanding of thyroid hormone metabolism. Together with clinical, cellular and high-throughput 'omics' studies, atomic structures of thyroid components will provide an important framework to map disease mutations and to interpret and predict thyroid phenotypes.
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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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Dietary Intake of Endocrine Disrupting Substances Presents in Environment and Their Impact on Thyroid Function.
Sokal, A, Jarmakiewicz-Czaja, S, Tabarkiewicz, J, Filip, R
Nutrients. 2021;(3)
Abstract
According to the available data, environmental pollution is a serious problem all over the world. Between 2015 and 2016, pollution was responsible for approximately nine million deaths worldwide. They also include endocrine disrupting chemicals (EDCs) that can interfere with the functioning of the thyroid gland. They are characterized by high persistence in the environment. These substances can enter the body through the gastrointestinal tract, respiratory system, as well as contact with the skin and overcome the placental barrier. EDC can be found in food, water, and personal care products. They can get into food from the environment and as a result of their migration to food products and cosmetics from packaging. EDCs can disrupt the functioning of the thyroid gland through a number of mechanisms, including disrupting the activation of thyroid receptors and the expression of genes that are related to the metabolism, synthesis, and transport of thyroid hormones (HT). There is a need to strengthen the food safety policy that aimed at the use of appropriate materials in direct contact with food. At the same time, an important action is to reduce the production of all waste and, when possible, use biodegradable packaging, which may contribute to the improvement of the quality of the entire ecosystem and the health of food, thus reducing the risk of developing thyroid diseases.
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An overview of thyroid function tests in subjects with resistance to thyroid hormone and related disorders.
Tagami, T
Endocrine journal. 2021;(5):509-517
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Abstract
Confirmation of sustained syndrome of inappropriate secretion of thyrotropin (SITSH) is a milestone in diagnosis of β type of resistance to thyroid hormone (RTHβ). The differential diagnoses of RTHβ include TSH-producing pituitary adenoma (TSHoma) and familial dysalbuminemic hyperthyroxinemia (FDH), which also present SITSH. Recently, patients with RTHα caused by a mutation in thyroid hormone receptor α were reported and they did not present SITSH but a decline in the serum T4/T3 ratio. This review was aimed to overview thyroid function tests in RTH and related disorders. First, the characteristics of the thyroid function in RTHβ, TSHoma, and FDH obtained from a Japanese database are summarized. Second, the degrees of SITSH in patients with truncations and frameshifts were compared with those in patients with single amino acid deletions and single amino acid substitutions obtained from the literature. Third, the degrees of SITSH in homozygous patients were compared with those in heterozygous patients with cognate mutations. Finally, the FT3/FT4 ratios in RTHα are summarized. In principle, the TSH values in FDH were within the normal range and apparent FT4 values in FDH were much higher than in RTHβ and TSHoma. The FT3/FT4 values in RTHβ were significantly lower than in TSHoma. The degrees of SITSH in patients with truncations and frameshifts were more severe than those in patients with single amino acid deletions and single amino acid substitutions, and those in homozygous patients were more severe than those in heterozygous patients with cognate mutations. The FT3/FT4 ratios in RTHα were higher than 1.0.
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Pregnancy, thyroid, and the potential use of selenium.
Hubalewska-Dydejczyk, A, Duntas, L, Gilis-Januszewska, A
Hormones (Athens, Greece). 2020;(1):47-53
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Abstract
The management of pregnant women is a major concern of health care around the world. There is growing evidence regarding the influence of selenium (Se) on pregnancy and fetus outcomes. However, due to as yet insufficient evidence, lack of measurable markers to assess the effect of Se supplementation on the human metabolism, and Se's narrow therapeutic index, the majority of experts and the current guidelines published by several scientific societies do not recommend the use of Se in pregnancy and in women of childbearing age. Further research based on well-designed studies, including assessment of the complex interactions between different micronutrients and individual response to different doses of Se, is needed.
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Horner syndrome as a complication after thyroid microwave ablation: Case report and brief literature review.
Zhang, X, Ge, Y, Ren, P, Liu, J, Chen, G
Medicine. 2018;(34):e11884
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Abstract
RATIONALE Horner's syndrome (HS) can present as a complication of thyroid surgery, particularly after thyroid microwave ablation (MWA). HS presents clinically with eyelid ptosis, miosis, enophthalmos, anhidrosis, and vascular dilatation, all of which result from a damaged oculosympathetic chain. We aimed to try to avoid such devastating symptoms in future cases by exploring reasons for the destruction of the cervical sympathetic trunk. PATIENT CONCERNS HS has previously been reported in the literature as a complication of thyroid surgery. Here, we report the case of a 44-year-old female patient who presented with miosis and eyelid ptosis following thyroid MWA. DIAGNOSES This patient was subsequently diagnosed with HS. INTERVENTIONS Mecobalamin was administered immediately. OUTCOMES After 5 months of follow up, the patient's miosis and ptosis was incompletely relieved. LESSONS Although HS is a rare complication of thyroid MWA, surgeons must be aware of the anatomic relationship of the cervical sympathetic trunk and thyroid gland with adjacent structures. Moreover, we hope this case presentation enables surgeons to take measures to minimize the possibility of oculosympathetic damage. Long-term follow up and comprehensive assessments are important for the patient's prognosis.
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Biochemical Testing of the Thyroid: TSH is the Best and, Oftentimes, Only Test Needed - A Review for Primary Care.
Sheehan, MT
Clinical medicine & research. 2016;(2):83-92
Abstract
Disorders of thyroid function are common, and screening, diagnosis, and management are often performed by primary care providers. While management of significant biochemical abnormalities is reasonably straight forward, laboratory tests only slightly outside, or even within, the normal range are becoming more difficult to appropriately manage. A large part of this increasing difficulty in appropriate management is caused by patients requesting, and even demanding, certain tests or treatments that may not be indicated. Symptoms of thyroid dysfunction are non-specific and extremely prevalent in the general population. This, along with a growing body of information available to patients via the lay press and internet suggesting that traditional thyroid function testing is not reliable, has fostered some degree of patient mistrust. Increasingly, when a physician informs a patient that their thyroid is not the cause of their symptoms, the patient is dissatisfied and even angry. This review aims to clarify the interpretation of normal and mild abnormalities of thyroid function tests by describing pituitary-thyroid physiology and through an in depth review of, arguably, the three most important biochemical tests of thyroid function: TSH, free T4, and anti-TPO antibodies. It is important for primary care providers to have an understanding of the shortcomings and proper interpretation of these tests to be better able to discuss thyroid function with their patients.
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Consequences of iodine deficiency and excess in pregnant women: an overview of current knowns and unknowns.
Pearce, EN, Lazarus, JH, Moreno-Reyes, R, Zimmermann, MB
The American journal of clinical nutrition. 2016;(Suppl 3):918S-23S
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Abstract
Severe iodine deficiency during development results in maternal and fetal hypothyroidism and associated serious adverse health effects, including cretinism and growth retardation. Universal salt iodization is the first-line strategy for the elimination of severe iodine deficiency. Iodine supplementation is recommended for vulnerable groups in severely iodine-deficient regions where salt iodization is infeasible or insufficient. A recent clinical trial has informed best practices for iodine supplementation of severely iodine-deficient lactating mothers. Because of successful programs of universal salt iodization in formerly severely iodine-deficient regions around the world, public health concern has shifted toward mild to moderate iodine deficiency, which remains prevalent in many regions, especially among pregnant women. Observational studies have shown associations between both mild maternal iodine deficiency and mild maternal thyroid hypofunction and decreased child cognition. Iodine supplementation has been shown to improve indexes of maternal thyroid function, even in marginally iodine-deficient areas. However, no data are yet available from randomized controlled trials in regions of mild to moderate iodine insufficiency on the relation between maternal iodine supplementation and neurobehavioral development in the offspring; thus, the long-term benefits and safety of such supplementation are uncertain. Although it is clear that excessive iodine intake can cause alterations in thyroid function in susceptible individuals, safe upper limits for iodine intake in pregnancy have not been well defined. Well-designed, prospective, randomized controlled trials that examine the effects of iodine supplementation on maternal thyroid function and infant neurobehavioral development in mildly to moderately iodine-deficient pregnant women are urgently needed. In addition, clinical data on the effects of iodine excess in pregnant and lactating women are needed to inform current recommendations for safe upper limits on chronic iodine ingestion in general and on iodine supplementation in particular.