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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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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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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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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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Thyroid and Fertility: Recent Advances.
Dosiou, C
Thyroid : official journal of the American Thyroid Association. 2020;(4):479-486
Abstract
Background: Thyroid disease is prevalent in women of reproductive age, while infertility is common in women with thyroid dysfunction. In this study, we review the recent advances in the field of thyroid and fertility since the publication of the 2017 American Thyroid Association pregnancy guidelines. Summary: Recent studies have confirmed associations of thyrotropin (TSH) elevation and/or thyroid autoimmunity with infertility and low ovarian reserve in subsets of women, and have led to a better understanding of the pathogenesis linking thyroid autoimmunity with infertility. Even though the benefit of treating patients with TSH >4 mIU/L has been confirmed in a large retrospective cohort study, two large randomized controlled trials have failed to show benefit of thyroid hormone on obstetrical outcomes in euthyroid women with thyroid autoimmunity. New data have emerged regarding the potential gonadal toxicity of radioactive iodine (RAI), based on its impact on ovarian reserve and sperm chromosomal abnormalities. Conclusions: There is continued evidence supporting an important role of thyroid hormone in regulation of reproductive tissues at many levels. Recent randomized trials have failed to identify a benefit of thyroid hormone in euthyroid women with thyroid autoimmunity. Further research in the field is needed to more completely delineate the relevant pathways and identify women who may benefit from levothyroxine treatment. The impact of RAI on fertility also merits further investigation.
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Thyrotoxicosis: Diagnosis and Management.
Sharma, A, Stan, MN
Mayo Clinic proceedings. 2019;(6):1048-1064
Abstract
Thyrotoxicosis is the clinical manifestation of excess thyroid hormone action at the tissue level due to inappropriately high circulating thyroid hormone concentrations. Hyperthyroidism, a subset of thyrotoxicosis, refers specifically to excess thyroid hormone synthesis and secretion by the thyroid gland. We performed a review of the literature on these topics utilizing published data in PubMed and MEDLINE. In this review, we discuss the more common etiologies of thyrotoxicosis, focusing on the current approach to diagnosis and management, new trends in those directions, and potential upcoming changes in the field.
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Congenital Hypothyroidism.
Wassner, AJ
Clinics in perinatology. 2018;(1):1-18
Abstract
Congenital hypothyroidism is common and can cause severe neurodevelopmental morbidity. Prompt diagnosis and treatment are critical to optimizing long-term outcomes. Universal newborn screening is an important tool for detecting congenital hypothyroidism, but awareness of its limitations, repeated screening in high-risk infants, and a high index of clinical suspicion are needed to ensure that all affected infants are appropriately identified and treated. Careful evaluation will usually reveal the etiology of congenital hypothyroidism, which may inform treatment and prognosis. Early and adequate treatment with levothyroxine results in excellent neurodevelopmental outcomes for most patients with congenital hypothyroidism.