Showing papers on "Thyroglobulin published in 2021"
TL;DR: In this paper, the authors proposed a case-by-case strategy for treating patients with intermediate-risk differentiated thyroid cancer (i.e., patients with high-risk DTC) and intermediate risk DTC, in which the risk of thyroid cancer death is < 1% and most recurrences can be cured.
Abstract: Considerable changes have occurred in the management of differentiated thyroid cancer (DTC) during the past four decades, based on improved knowledge of the biology of DTC and on advances in therapy, including surgery, the use of radioactive iodine (radioiodine), thyroid hormone treatment and availability of recombinant human TSH. Improved diagnostic tools are available, including determining serum levels of thyroglobulin, neck ultrasonography, imaging (CT, MRI, SPECT-CT and PET-CT), and prognostic classifications have been improved. Patients with low-risk DTC, in whom the risk of thyroid cancer death is <1% and most recurrences can be cured, currently represent the majority of patients. By contrast, patients with high-risk DTC represent 5-10% of all patients. Most thyroid cancer-related deaths occur in this group of patients and recurrences are frequent. Patients with high-risk DTC require more aggressive treatment and follow-up than patients with low-risk DTC. Finally, the strategy for treating patients with intermediate-risk DTC is frequently defined on a case-by-case basis. Prospective trials are needed in well-selected patients with DTC to demonstrate the extent to which treatment and follow-up can be limited without increasing the risk of recurrence and thyroid cancer-related death.
98 citations
TL;DR: In this paper, the authors studied 144 consecutive COVID-19 patients admitted to a single center in intensive or subintensive care units and found that the majority of patients had a normal TSH at admission, usually with normal FT4 and FT3.
Abstract: Objective: Alterations in thyroid function tests (TFTs) have been recorded during SARS-CoV-2 infection as associated to either a destructive thyroiditis or a non-thyroidal illness. Methods: We studied 144 consecutive COVID-19 patients admitted to a single center in intensive or subintensive care units. Those with previous thyroid dysfunctions or taking interfering drugs were excluded. Differently from previous reports, TSH, FT3, FT4, thyroglobulin (Tg), anti-Tg autoantibodies (TgAb) were measured at baseline and every 3-7 days. C-reacting protein (CRP), cortisol and IL-6 were also assayed. Results: The majority of patients had a normal TSH at admission, usually with normal FT4 and FT3. Low TSH levels were found either at admission or during hospitalization in 39% of patients, associated with low FT3 in half of the cases. FT4 and Tg levels were normal, and TgAb-negative. TSH and FT3 were invariably restored at the time of discharge in survivors, whereas were permanently low in most deceased cases, but only FT3 levels were predictors of mortality. Cortisol, CRP and IL-6 levels were higher in patients with low TSH and FT3 levels. Conclusions: Almost half of our COVID-19 patients without interfering drugs had normal TFTs both at admission and during follow-up. In this series, the transient finding of low TSH with normal FT4 and low FT3 levels, inversely correlated with CRP, cortisol and IL-6 and associated with normal Tg levels, is likely due to the cytokine storm induced by SARS-Cov-2 with a direct or mediated impact on TSH secretion and deiodinase activity, and likely not to a destructive thyroiditis.
44 citations
TL;DR: In this paper, the authors present a case of subacute thyroiditis which presented after administration of the mRNA COVID-19 vaccine and the patient was prescribed prednisone 40mg daily and propranolol 20mg as needed for symptoms.
Abstract: Introduction: Subacute thyroiditis is a well-documented clinical condition which typically presents 1-2 weeks after an acute viral illness. Presenting symptoms are classically those of thyrotoxicosis but with associated tenderness in the thyroid. Treatment of acute symptoms is possible and the thyroid function will generally normalize with time. Subacute thyroiditis has rarely been reported after administration of viral vaccinations such as the seasonal flu vaccine. We present a case of subacute thyroiditis which presented after administration of the mRNA COVID-19 vaccine.
Case: Patient is a 42yo female with no past medical history. She received the first dose of the Pfizer/BioNTech mRNA vaccine for COVID-19 on 12/22/20. Five days later, the patient complained of sore throat and palpitations. These symptoms progressed and she was evaluated in an urgent care on 12/31/20 where she was found to have tachycardia. Infectious work-up, including PCR for COVID-19, was negative and she was sent home. She took ibuprofen with some improvement of her symptoms. The following day she went to the ED; she was found to have a heart rate in the 130s with sinus tachycardia on EKG. Thyroid function testing was done which revealed TSH <0.01, fT4 4.58, fT3 11.8. Her TPO antibody was <28 and inflammatory markers were elevated including sed rate of 62. The patient was prescribed prednisone 40mg daily and propranolol 20mg as needed for symptoms. She reports rapid improvement of symptoms with prednisone. On 1/21/20, thyroid function showed TSH <0.01, fT4 down to 3.2, tT3 normal at 135. Thyroglobulin was elevated at 140.8 with negative thyroglobulin antibody, TRAb and TSI. Her inflammatory markers had decreased with sed rate of 26 and normal C-reactive protein. She had improved symptoms.
Discussion: Cases of subacute thyroiditis are most commonly associated with upper respiratory viruses but cases have been reported with traditional inactivated viral vaccines or live-attenuated vaccines such as those for annual influenza. We present the case of a 42-year-old female who has presented with a classic case of subacute thyroiditis which occurred in the time frame after receiving the Pfizer mRNA vaccine for COVID-19. Research has been ongoing for decades regarding development of mRNA vaccines but the mRNA vaccines for the SARS-CoV-2 virus have been the first to be widely distributed to the general population. Thyroiditis has not been reported as a common side effect but the cross recognition between the coronavirus spike protein targeted with the mRNA vaccine and healthy thyroid cell antigens exists as evidenced by this case.
Sources: 1. Prummel M, Strieder T, Wiersinga WM. The environment and autoimmune thyroid diseases. Eur J Endocrinol. 2004;150:605-618. Altay FA, Guz G, Altay M. 2. Subacute thyroiditis following seasonal influenza vaccination. Hum Vaccin Immunother. 2016;12(4):1033-1034.
42 citations
TL;DR: In this paper, the authors evaluated the prevalence and predictors of post-acute sequelae of coronavirus disease 2019 (COVID-19) and the potential role of thyroid function and autoimmunity in LC.
32 citations
TL;DR: In this article, a mouse model of thyroid-irAE was analyzed and the frequencies of central and effector memory CD4+ T cell subsets and the secretion of interferon-γ after stimulation with thyroglobulin were increased in the cervical lymph nodes of mice with thyroidirAE compared with controls.
Abstract: Immune-related adverse events induced by anti-programmed cell death-1 antibodies (PD-1-Ab), including destructive thyroiditis (thyroid-irAE), are thought to be caused by activated T cells. However, the T cell subsets that are directly responsible for damaging self-organs remain unclear. To clarify which T cell subsets are involved in the development of thyroid-irAE, a mouse model of thyroid-irAE was analyzed. PD-1-Ab administration 2.5 months after immunization with thyroglobulin caused destructive thyroiditis. Thyroiditis was completely prevented by previous depletion of CD4+ T cells and partially prevented by depleting CD8+ T cells. The frequencies of central and effector memory CD4+ T cell subsets and the secretion of interferon-γ after stimulation with thyroglobulin were increased in the cervical lymph nodes of mice with thyroid-irAE compared with controls. Histopathological analysis revealed infiltration of CD4+ T cells expressing granzyme B in thyroid glands and major histocompatibility complex class II expression on thyrocytes in mice with thyroid-irAE. Adoptive transfer of CD4+ T cells from cervical lymph nodes in mice with thyroid-irAE caused destruction of thyroid follicular architecture in the irradiated recipient mice. Flow cytometric analyses showed that the frequencies of central and effector memory CD4+ T cells expressing the cytotoxic marker CD27 were higher in peripheral blood mononuclear cells collected from patients with thyroid-irAE induced by PD-1-Ab versus those without. These data suggest a critical role for cytotoxic memory CD4+ T cells activated by PD-1-Ab in the pathogenesis of thyroid-irAE.
32 citations
TL;DR: In this article, a literature review was conducted of gene defects causing congenital hypothyroidism (CH), which is a state of inadequate thyroid hormone production detected at birth, caused either by absent, underdeveloped or ectopic thyroid gland (dysgenesis), or by defected thyroid hormone biosynthesis (Dyshormonogenesis).
Abstract: Congenital primary hypothyroidism (CH) is a state of inadequate thyroid hormone production detected at birth, caused either by absent, underdeveloped or ectopic thyroid gland (dysgenesis), or by defected thyroid hormone biosynthesis (dyshormonogenesis). A genetic component has been identified in many cases of CH. This review summarizes the clinical and biochemical features of the genetic causes of primary CH. A literature review was conducted of gene defects causing congenital hypothyroidism. Mutations in five genes have predominantly been implicated in thyroid dysgenesis (TSHR, FOXE1, NKX2-1, PAX8, and NKX2-5), the primary cause of CH (85%), and mutations in seven genes in thyroid dyshormonogenesis (SLC5A5, TPO, DUOX2, DUOXA2, SLC6A4, Tg, and DEHAL1). These genes encode for proteins that regulate genes expressed during the differentiation of the thyroid, such as TPO and Tg genes, or genes that regulate iodide organification, thyroglobulin synthesis, iodide transport, and iodotyrosine deiodination. Besides thyroid dysgenesis and dyshormonogenesis, additional causes of congenital hypothyroidism, such as iodothyronine transporter defects and resistance to thyroid hormones, have also been associated with genetic mutations. The identification of the underlying genetic defects of CH is important for genetic counseling of families with an affected member, for identifying additional clinical characteristics or the risk for thyroid neoplasia and for diagnostic and management purposes.
25 citations
TL;DR: In this paper, the association between maternal thyroid dysfunction and the risk of pre-eclampsia (PE) and gestational diabetes mellitus (GDM) was assessed by multivariate logistic regression.
23 citations
TL;DR: It is argued that the use of the validation technique also influences both: measures of the model quality and the threshold value, and iterative methods (such as sampling and bootstrap) seem to produce more stable outcomes.
23 citations
TL;DR: Lung metastasis are mostly present at diagnosis of DTC and higher suspicion should be maintained in CAYA who are younger, have LN disease, and have elevated post-operative thyroglobulin.
Abstract: Background: Lung metastasis from differentiated thyroid cancer (DTC) in children and young adults (CAYA) is estimated at 25%, which is 3–4 times higher than in adults. Lung metastases may respond t...
21 citations
TL;DR: In this article, the authors describe the molecular mechanisms involved in radio-iodide therapy and how the alteration of these mechanisms in thyroid tumor progression affects the diagnosis and results of therapy in the clinic.
Abstract: Thyroid radio-iodide therapy (RAI) is one of the oldest known and used targeted therapies. In thyroid cancer, it has been used for more than eight decades and is still being used to improve thyroid tumor treatment to eliminate remnants after thyroid surgery, and tumor metastases. Knowledge at the molecular level of the genes/proteins involved in the process has led to improvements in therapy, both from the point of view of when, how much, and how to use the therapy according to tumor type. The effectiveness of this therapy has spread into other types of targeted therapies, and this has made sodium/iodide symporter (NIS) one of the favorite theragnostic tools. Here we focus on describing the molecular mechanisms involved in radio-iodide therapy and how the alteration of these mechanisms in thyroid tumor progression affects the diagnosis and results of therapy in the clinic. We analyze basic questions when facing treatment, such as: (1) how the incorporation of radioiodine in normal, tumor, and metastatic thyroid cells occurs and how it is regulated; (2) the pros and cons of thyroid hormonal deprivation vs. recombinant human Thyroid Stimulating Hormone (rhTSH) in radioiodine residence time, treatment efficacy, thyroglobulin levels and organification, and its influence on diagnostic imaging tests and metastasis treatment; and (3) the effect of stunning and the possible causes. We discuss the possible incorporation of massive sequencing data into clinical practice, and we conclude with a socioeconomical and clinical vision of the above aspects.
20 citations
TL;DR: In this article, thyroid-lineage-specific cells were cultured as organoids capable of self-renewal and which expressed proliferation and putative stem cell and thyroid characteristics, without a change in the expression of thyroid tumor-related genes.
Abstract: Total thyroidectomy as part of thyroid cancer treatment results in hypothyroidism requiring lifelong daily thyroid hormone replacement. Unbalanced hormone levels result in persistent complaints such as fatigue, constipation, and weight increase. Therefore, we aimed to investigate a patient-derived thyroid organoid model with the potential to regenerate the thyroid gland. Murine and human thyroid-derived cells were cultured as organoids capable of self-renewal and which expressed proliferation and putative stem cell and thyroid characteristics, without a change in the expression of thyroid tumor-related genes. These organoids formed thyroid-tissue-resembling structures in culture. (Xeno-)transplantation of 600,000 dispersed organoid cells underneath the kidney capsule of a hypothyroid mouse model resulted in the generation of hormone-producing thyroid-resembling follicles. This study provides evidence that thyroid-lineage-specific cells can form organoids that are able to self-renew and differentiate into functional thyroid tissue. Subsequent (xeno-)transplantation of these thyroid organoids demonstrates a proof of principle for functional miniature gland formation.
TL;DR: In this paper, a case of TENIS with detectable metastases in the larynx and lung on the CT scan was performed for further detection of tumor recurrence and metastases, which showed intense 68Ga-FAPI activity in the metastatic lesions.
Abstract: Differentiated thyroid cancer with thyroglobulin elevation and negative iodine scintigraphy (TENIS) syndrome is a diagnostic and therapy dilemma. In this study, we present a case of TENIS with detectable metastases in the larynx and lung on the CT scan. 68Ga-fibroblast activation protein inhibitor (FAPI) PET/CT was performed for further detection of tumor recurrence and metastases, which showed intense 68Ga-FAPI activity in the metastatic lesions. To the best of our knowledge, this is the first case of TENIS presenting with FAPI-avid metastatic lesions, demonstrating its usefulness for localizing recurrent or metastatic lesions in patients with TENIS.
TL;DR: In this paper, the thyroid function in carefully selected cohorts of COVID-19 positive and negative patients was studied and the thyroid hormone patterns were identified as consistent with non-thyroidal illness syndrome (NTIS), thyrotoxicosis and hypothyroidism.
Abstract: OBJECTIVE: Following evolution of COVID-19 pandemic, reports pointed on a high prevalence of thyroiditis related thyrotoxicosis. Interpretation of thyroid tests during illness, however, is hampered by changes occurring in the context of non-thyroidal illness syndrome (NTIS). In order to elucidate these findings, we studied thyroid function in carefully selected cohorts of COVID-19 positive and negative patients. DESIGN: Cohort observational study. METHODS: We measured TSH, FT4, T3 within 24hours of admission in 196 patients without thyroid disease and/or confounding medications. 102 patients were SARS-CoV-2 positive; 41 admitted in the ICU, 46 in the ward and 15 outpatients. Controls consisted of 94 SARS-CoV-2 negative patients; 39 in the ICU and 55 in the ward. We designated the thyroid hormone patterns as consistent with NTIS, thyrotoxicosis and hypothyroidism. RESULTS: A NTIS pattern was encountered in 60% of ICU and 36% of ward patients, with similar frequencies between SARS-CoV-2 positive and negative patients (46.0% vs 46.8%, p=NS). A thyrotoxicosis pattern was observed in 14.6% SARS-CoV-2 ICU patients vs. 7.7% in ICU negative (p=NS) and, overall in 8.8% of SARS-CoV-2 positive vs. 7.4% of negative patients. In these patients thyroglobulin levels were similar to those with normal thyroid function or NTIS. The hypothyroidism pattern was rare. CONCLUSIONS: NTIS pattern is common and relates to the severity of disease rather than SARS-CoV-2 infection. A thyrotoxicosis pattern is less frequently observed with similar frequency between patients with and without COVID-19. It is suggested that thyroid hormone monitoring in COVID-19 should not differ from other critically ill patients.
TL;DR: In this paper, the authors summarized the evidences on the role of PET/CT in management of patients with differentiated thyroid cancer, focusing on potential applications and elucidating some still debating points.
Abstract: The standard treatment of differentiated thyroid cancer (DTC) consists of surgery followed by iodine-131 (131I) administration. Although the majority of DTC has a very good prognosis, more aggressive histologic subtypes convey a worse prognosis. Follow-up consists of periodically measurements of serum thyroglobulin, thyroglobulin antibodies and neck ultrasound and 123I/131I whole-body scan. However, undifferentiated thyroid tumors have a lower avidity for radioiodine and the ability of DTC to concentrate 131I may be lost in metastatic disease. Positron emission tomography (PET)/computed tomography (CT) has been introduced in the evaluation of patients with thyroid tumors and the 2-[18F]-fluoro-2-deoxyd-glucose (18F-FDG) has been largely validated as marker of cell's metabolism. According to the 2015 American Thyroid Association guidelines, 18F-FDG PET/CT is recommended in the follow-up of high-risk patients with elevated serum thyroglobulin and negative 131I imaging, in the assessment of metastatic patients, for lesion detection and risk stratification and in predicting the response to therapy. It should be considered that well-differentiated iodine avid lesions could not concentrate 18F-FDG, and a reciprocal pattern of iodine and 18F-FDG uptake has been observed. Beyond 18F-FDG, other tracers are available for PET imaging of thyroid tumors, such as Iodine-124 (124I), 18F-tetrafluoroborate and Gallium-68 prostate-specific membrane antigen. Moreover, the recent introduction of PET/MRI, offers now several opportunities in the field of patients with DTC. This review summarizes the evidences on the role of PET/CT in management of patients with DTC, focusing on potential applications and on elucidating some still debating points.
TL;DR: In a short-term follow-up, thyroid function spontaneously normalized in most subjects with SARS-CoV-2-related thyrotoxicosis, however, thyroid hypoecogenicity was found in a remarkable number of them and future longer-term studies are needed to clarify whether this ultrasonographic alteration may predispose to develop late-onset thyroid dysfunction.
Abstract: To evaluate the post- coronavirus disease-19 (COVID-19) outcome of thyroid function in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related thyrotoxicosis. This was a single-center prospective study involving 29 patients (11 females, 18 males; median age 64 years, range: 43–85) with thyrotoxicosis diagnosed after hospitalization for COVID-19 and then followed-up for a median period of 90 days (range: 30–120) after hospital discharge. At follow-up, patients were evaluated for serum thyrotropin (TSH), free-thyroxine (FT4), free-triiodiothyronine (FT3), TSH receptor antibodies (TRAb), thyroglobulin antibodies (TgAb), thyroperoxidase antibodies (TPOAb) and ultrasonographic thyroid structure. After recovery of COVID-19, serum TSH values significantly increased (P < 0.001) and FT4 values significantly decreased (P = 0.001), without significant change in serum FT3 (P = 0.572). At follow-up, 28 subjects (96.6%) became euthyroid whereas overt hypothyroidism developed in one case. At the ultrasound evaluation of thyroid gland, hypoecogenicity was found in 10 patients (34.5%) and in these cases serum TSH values tended to be higher than those without thyroid hypoecogenity (P = 0.066). All subjects resulted to be negative for TgAb, TPOAb and TRAb. In a short-term follow-up, thyroid function spontaneously normalized in most subjects with SARS-CoV-2-related thyrotoxicosis. However, thyroid hypoecogenicity was found in a remarkable number of them and future longer-term studies are needed to clarify whether this ultrasonographic alteration may predispose to develop late-onset thyroid dysfunction.
TL;DR: In this article, the demographical, histopathological, and immunohistochemical features of the largest case series, consisting of 33 tumors, were reviewed and it was shown that these tumors represent a distinct form of thyroid carcinoma unrelated to other neoplasms of thyroid follicular cells.
Abstract: Tumors with papillary cribriform and morular architecture were initially considered to be variants of papillary thyroid carcinoma; however, recent observations have challenged this view. In this study, we reviewed the demographical, histopathological, and immunohistochemical features of the largest case series, consisting of 33 tumors. The age at time of pathological diagnosis ranged from 18 to 59 (mean 33) years, and all patients except one were female. Sixteen patients had multifocal and fifteen had unifocal disease. The status of focality was unavailable in two patients. Tumors were well-circumscribed, ranging in size from 0.1 to 8.0 cm. The cribriform component was admixed with morulae in the majority, except seven had a cribriform-predominant architecture and two had predominantly solid growth. Variable degrees of nuclear enlargement, elongation, overlapping, and grooves were seen but florid nuclear convolution, intranuclear pseudoinclusions, and optically clear nuclei due to chromatin margination were not appreciated. There was no or little colloid material within the cribriform spaces. Two solid tumors had high-grade features. Immunohistochemical studies showed beta-catenin nuclear and cytoplasmic positivity in all cases. The cribriform component was positive for TTF1 and negative for thyroglobulin. PAX8 was absent in half of these tumors and focal in the remainder. Morulae were positive for keratin 5 and CD5 and negative for p63, p40, TTF1, and PAX8. Molecular studies revealed germline APC mutations in 12 tumors and were negative in 5 sporadic tumors in a subset of tested tumors. Irrespective of the antibody used in this cohort, all cribriform-morular carcinomas express TTF1; however, PAX8 immunoreactivity is weak, focal or negative, and all tumors lack thyroglobulin reactivity; these findings raise questions about tumor cell origin and may indicate that these are not of thyroid follicular epithelial differentiation. We postulate that morulae may represent divergent thymic/ultimobranchial pouch-related differentiation. Given their unique cytomorphology, immunohistochemical profiles, and genetic features that have little overlap with traditional follicular cell-derived thyroid carcinomas, we propose that these tumors represent a distinct form of thyroid carcinoma unrelated to other neoplasms of thyroid follicular cells.
TL;DR: In this article, the value of serum thyroglobulin/antithymolobulin (Tg/ANTithyroglobalobulin antibody [ATg]) for papillary thyroid carcinoma (PTC) surveillance after lobectomy was investigated.
Abstract: Background: The value of serum thyroglobulin/antithyroglobulin (Tg/antithyroglobulin antibody [ATg]) for papillary thyroid carcinoma (PTC) surveillance after lobectomy was investigated. We aimed to...
TL;DR: This monograph aims to provide a history of cancer research in Ecuador and some of the techniques used, as well as some of their applications, that have been developed in recent years.
Abstract: In contrast to the rapid increase in thyroid cancer incidence, the mortality has remained low and stable over the last decades. In Ecuador, however, thyroid cancer mortality has increased. The objective of this study is to determine possible drivers of high rates of thyroid cancer mortality, through a cross-sectional analysis of all patients attending a thyroid cancer referral center in Ecuador. From June 2014 to December 2017, a cross-sectional study was conducted at the Hospital de Especialidades Eugenio Espejo, a regional reference public hospital for endocrine neoplasia in adults in Quito, Ecuador. We identified the mechanism of detection, histopathology and treatment modalities from a patient interview and review of clinical records. Among 452 patients, 74.8% were young adults and 94.2% (426) were female. 13.7% had a family history of thyroid cancer, and patients’ median tumor size was 2 cm. The incidental finding was 54.2% whereas 45.8% was non-incidental. Thyroid cancer histology reported that 93.3% had papillary thyroid cancer (PTC), 2.7% follicular, 1.5% Hurtle cells, 1.6% medullary, 0.7% poor differentiated, and 0.2% anaplastic carcinoma. The mean MACIS (metastasis, age, completeness, invasion, and size) score was 4.95 (CI 4.15–5.95) with 76.2% of the thyroid cancer patients having MACIS score less than or equal to 6. The very low and low risk of recurrence was 18.1% (79) and 62% (271) respectively. An analysis of 319 patients with non-metastatic thyroid cancer showed that 10.7% (34) of patients had surgical complications. Moreover, around 62.5% (80 from 128 patients with thyroglobulin laboratory results) of TC patients had a stimulated-thyroglobulin value equal or higher than 2 ng/ml. Overall, a poor surgical outcome was present in 35.1% (112) patients. Out of 436 patients with differentiated thyroid carcinoma, 86% (375) received radioactive iodine. Thyroid cancer histological characteristics and method of diagnosis are like those described in other reports without any evidence of the high frequency of aggressive thyroid cancer histology. However, we observed evidence of overtreatment and poor surgical outcomes that demand additional studies to understand their association with thyroid cancer mortality in Ecuador.
TL;DR: Wang et al. as mentioned in this paper investigated the relationship between thyroid autoantibody positivity and vitamin D deficiency via a large epidemiological survey and found that increased likelihood of thyroid peroxidase antibodies (i-TPOAb) positivity was associated with 25OHD deficiency (odds ratio [OR]: 2.428, 95% confidence interval [CI]: 1.828-1.733; p = 0.009).
Abstract: The pathogenesis of Hashimoto’s thyroiditis (HT) is unclear, although some studies have identified an association between vitamin D deficiency and thyroid autoantibody positivity. This study aimed to investigate vitamin D status, and its relationships with thyroid autoantibody positivity and HT, via a large epidemiological survey. The epidemiological survey was conducted in Tianjin, China. All participants underwent testing for serum 25-hydroxyvitamin D (25OHD), thyroid function, and thyroid autoantibodies, and some participants underwent testing to evaluate CD4+ T-cell differentiation and concentrations of related cytokines. The study included 1812 participants and revealed prevalences of 13.1% for thyroid peroxidase antibodies (i-TPOAb) and 14.0% for thyroglobulin antibodies (i-TgAb). Logistic regression analysis revealed that thyroid autoantibody positivity was associated with sex, age, and 25OHD classification. An increased likelihood of i-TPOAb positivity was associated with 25OHD deficiency (odds ratio [OR]: 2.428, 95% confidence interval [CI]: 1.383–4.261) and 25OHD inadequacy (OR: 1.198, 95% CO: 0.828–1.733; p = 0.008). An increased likelihood of i-TgAb positivity was associated with 25OHD deficiency (OR: 2.366, 95% CI: 1.366–4.099) and 25OHD inadequacy (OR: 1.263, 95% CI: 0.883–1.807; p = 0.009). Relative to healthy subjects, patients with HT had significantly higher proportions of Th1 and Th17 cells, as well as higher concentrations of related cytokines. This study revealed that vitamin D deficiency was associated with thyroid autoantibody positivity, and that vitamin D deficiency seems to be involved in the pathological mechanism underlying HT. Large randomized controlled trials are needed to investigate the effects of vitamin D supplementation on HT.
TL;DR: In this paper, the EuBIVAS-based BV estimates for thyroid biomarkers were used for the diagnosis of thyroid disorders and for the monitoring and treatment of patients with these diseases.
Abstract: Objectives Thyroid biomarkers are fundamental for the diagnosis of thyroid disorders and for the monitoring and treatment of patients with these diseases The knowledge of biological variation (BV) is important to define analytical performance specifications (APS) and reference change values (RCV) The aim of this study was to deliver BV estimates for thyroid stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), thyroglobulin (TG), and calcitonin (CT) Methods Analyses were performed on serum samples obtained from the European Biological Variation Study population (91 healthy individuals from six European laboratories; 21-69 years) on the Roche Cobas e801 at the San Raffaele Hospital (Milan, Italy) All samples from each individual were evaluated in duplicate within a single run The BV estimates with 95% CIs were obtained by CV-ANOVA, after analysis of variance homogeneity and outliers Results The within-subject (CV I ) BV estimates were for TSH 177%, FT3 50%, FT4 48%, TG 103, and CT 130%, all significantly lower than those reported in the literature No significant differences were observed for BV estimates between men and women Conclusions The availability of updated, in the case of CT not previously published, BV estimates for thyroid markers based on the large scale EuBIVAS study allows for refined APS and associated RCV applicable in the diagnosis and management of thyroid and related diseases
TL;DR: In this paper, the role of thyroid autoantibodies (TgAb) in the management of differentiated thyroid carcinomas (DTCs) is discussed, and the evaluation of TgAb trend over time (i.e., surrogate tumor marker) is recommended in patients with positive TgAB and potentially interfering Tg results.
Abstract: Introduction Differentiated thyroid carcinomas (DTCs) are treated with (near-)total thyroidectomy and radioiodine therapy. Recently, the use of highly sensitive thyroglobulin (hsTg) assays has simplified DTC follow-up and improved patients' quality of life. More limited approaches are currently applied in low-risk patients requiring interpretations of Tg results in different clinical scenarios. Finally, Tg assays are hampered by interference from thyroglobulin autoantibodies (TgAb). Areas covered The role of Tg measurement in DTC patients treated with complete thyroid ablation, thyroidectomy alone, or lobectomy is summarized. The management of patients carrying positive TgAb is also addressed. Expert opinion Patients with undetectable hsTg after total thyroid ablation are safely managed by periodic hsTg measurement, combined with selective use of imaging procedures in few cases. Serum hsTg trend remains informative in patients treated without radioiodine ablation. However, reliable reference values are urgently needed in this setting. The role of hsTg is debated in patients who have undergone lobectomy due to the amount of Tg released by a functioning thyroid lobe. The evaluation of TgAb trend over time (i.e. surrogate tumor marker) is recommended in patients with positive TgAb and potentially interfering Tg results.
TL;DR: Yanghe decoction (YH) is a traditional Chinese herbal formulation which has various anti-inflammatory effects as discussed by the authors, which has been used for the treatment of autoimmune diseases such as ankylosing spondylitis.
Abstract: Inflammation is an important contributor to autoimmune thyroiditis. Yanghe decoction (YH) is a traditional Chinese herbal formulation which has various anti-inflammatory effects. It has been used for the treatment of autoimmune diseases such as ankylosing spondylitis In this study we aimed to investigate the effects of YH on autoimmune thyroiditis in a rat model and elucidate the underlying mechanisms. The experimental autoimmune thyroiditis (EAT) model was established by thyroglobulin (pTG) injections and excessive iodine intake. Thyroid lesions were observed using hematoxylin and eosin (H and E) staining and serum TgAb, TPOAb, TSH, T3, and T4 levels were measured by enzyme-linked immunosorbent assay IL-35 levels were evaluated using real-time polymerase chain reaction (RT-PCR) and Th17/Treg balance in peripheral blood mononuclear cells (PBMCs) was determined by flow cytometry and RT-PCR. Changes in Wnt/β-catenin signaling were evaluated using Western blot. Immunofluorescence staining and western blot were employed to examine NLRP3 inflammasome activation in the thyroid. YH minimized thyroid follicle injury and decreased concentrations of serum TgAb, TPOAb, TSH, T3, and T4 in EAT model. The mRNA of IL-35 was increased after YH treatment. YH also increased the percentage of Treg cells, and decreased Th17 proportion as well as Th17/Treg ratio in PBMCs. Meanwhile, the mRNA levels of Th17 related cytokines (RORγt, IL-17A, IL-21, and IL-22) were suppressed and Treg related cytokines (FoxP3, TGF-β, and IL-10) were promoted in PBMCs. Additionally, the protein expressions of Wnt-1 and β-catenin were unregulated after YH treatment. NLRP3 immunostaining signal and protein levels of IL-17, p-NF-κB, NLRP3, ASC, cleaved-Caspase-1, cleaved-IL-1β, and IL-18 were downregulated in the thyroid after YH intervention. Overall, the present study demonstrated that YH alleviated autoimmune thyroiditis in rats by improving NLRP3 inflammasome and immune dysregulation.
TL;DR: In this paper, a mouse thyroid injury model was used to gain insight into the mechanism of thyroid regeneration and the role of thyroid stem cells and thyroid progenitor cells in this process.
Abstract: Background Many tissues, including the thyroid, contain resident (adult) stem cells that are responsible for regeneration and repair after injury. The mechanisms of thyroid regeneration and the role of thyroid stem cells and thyroid progenitor cells in this process are not well understood. We have now used a new mouse thyroid injury model to gain insight into this phenomenon. Methods Tamoxifen induced TPO-Cre mice (TPOCreER2) were crossed with inducible Diphtheria Toxin Receptor homozygous mice (ROSA26iDTR) to give rise to TPOCreER2/iDTR mice, allowing for the Cre-mediated expression of the DTR and rendering TPO expressing thyroid cells highly sensitive to diphtheria toxin (DT). This model of TPOCreER2/iDTR mice allowed us to study the repair/regeneration of thyroid follicles after diphtheria toxin induced thyroid damage by measuring serum thyroid hormones and cell fate. Results In TPOCreER2/iDTR double transgenic mice we observed severe thyroid damage as early as 2 weeks after initiating intraperitoneal DT injections. There was marked thyroid tissue apoptosis and a ~50% drop in serum T4 levels (from 5.86 to 2.43 ug/dl) and a corresponding increase in serum TSH (from 0.18 to 8.39 ng/dl). In addition, there was a ~50% decrease in transcription of thyroid specific genes (thyroglobulin, TSH receptor, and sodium-iodide symporter). After suspending the DT administration, the thyroid rapidly recovered over a 4-week period during which we observed a transient surge in stem cell marker expression (including Oct4, Nanog, Sox2, and Rex1). In addition, cells immunostaining with stem cell markers Oct4 and Ssea-1 were found in clusters around new thyroid follicles in TPOCreER2/iDTR double transgenic mice. Furthermore, the presence of clusters of thyroid progenitor cells was also identified by Pax8 staining of thyroglobulin negative cells. This recovery of the injured gland was followed by a rapid and sequential restoration of thyroid function. Conclusion These data demonstrate that a new model of thyroid cell damage induced by DT can be used to study the mobilization of resident adult stem cells. Furthermore, the model clearly demonstrates the involvement of both stem and progenitor cells in the in vivo regeneration of the thyroid after severe destruction.
TL;DR: TSH levels did not change with age, and the TSH level of females was higher than that of males, and BMI, smoking status, education levels, and marital status were associated with TSH.
Abstract: The aim of the present study was to describe the distributions of serum thyroid- stimulating hormone (TSH) levels in thyroid disease-free adults from areas with different iodine levels in China. Meanwhile, we aimed to evaluate the influence of age and gender on the distribution of TSH, assess the relationship between concentrations of TSH and free thyroxine (FT4), and analyze the factors that may affect TSH levels. 2020 adults were included from April 2016 to June 2019. Urinary iodine concentration, serum iodine concentration, serum TSH, FT4, free triiodothyronine, thyroid peroxidase antibodies and thyroglobulin antibodies were measured, and thyroid ultrasonography was performed. The median of TSH in iodine-fortification areas (IFA), iodine-adequate areas (IAA), iodine-excessive areas (IEA) were 2.32, 2.11 and 2.34 mIU/L, respectively. Serum TSH concentrations were significantly higher in IFA and IEA than that in IAA (p = 0.005 and < 0.0001). The TSH values of most adults were distributed within the range of 1.01–3.00 mIU/L with the same trend in three groups. In our study, TSH levels did not change with age, and the TSH level of females was higher than that of males (p < 0.0001). There was a negative correlation between FT4 and TSH in IAA (r = − 0.160, p < 0.0001) and IEA (r = − 0.177, p < 0.0001), but there was no correlation between FT4 and TSH in IFA (r = − 0.046, p = 0.370). BMI, smoking status, education levels, and marital status were associated with TSH. Our study provides a basis for establishing the reference intervals of TSH in different iodine level areas.
TL;DR: In this paper, single-particle cryogenic electron microscopy (cryoEM) was used to generate a high-resolution reconstruction of bovine thyroglobulin (2.3
Abstract: Thyroglobulin is a homodimeric glycoprotein that is essential for the generation of thyroid hormones in vertebrates. Upon secretion into the lumen of follicles in the thyroid gland, tyrosine residues within the protein become iodinated to produce monoiodotyrosine (MIT) and diiodotyrosine (DIT). A subset of evolutionarily conserved pairs of DIT (and MIT) residues can then engage in oxidative coupling reactions that yield either thyroxine (T4; produced from coupling of a DIT `acceptor' with a DIT `donor') or triiodothyronine (T3; produced from coupling of a DIT acceptor with an MIT donor). Although multiple iodotyrosine residues have been identified as potential donors and acceptors, the specificity and structural context of the pairings (i.e. which donor is paired with which acceptor) have remained unclear. Here, single-particle cryogenic electron microscopy (cryoEM) was used to generate a high-resolution reconstruction of bovine thyroglobulin (2.3 A resolution in the core region and 2.6 A overall), allowing the structural characterization of two post-reaction acceptor–donor pairs as well as tyrosine residues modified as MIT and DIT. A substantial spatial separation between donor Tyr149 and acceptor Tyr24 was observed, suggesting that for thyroxine synthesis significant peptide motion is required for coupling at the evolutionarily conserved thyroglobulin amino-terminus.
TL;DR: An Argentine patient with congenital hypothyroidism, enlarged thyroid gland and low levels of serum TG is reported and it is demonstrated that the c.3001+5G>A mutation causes a rare genotype, altering the splicing of the pre-mRNA.
TL;DR: In this article, a review aims to unravel pregnancy induced physiological challenges that could provide basis for the development of Gestational Hypothyroidism (GHT) during pregnancy, including increased renal clearance of iodine leading to low iodine state and an elevated estrogen level leading to an increase in circulating thyroglobulin level and a decrease in free thyroxine level.
Abstract: Pregnancy is a complex state with many endocrinological challenges to a woman's physiology. Gestational Hypothyroidism (GHT) is an emerging condition where insufficiency of the thyroid gland has developed during pregnancy in a previously euthyroid woman. It is different to overt hypothyroidism, where marked elevation of thyroid-stimulating hormone with corresponding reduction in free thyroxine levels, is well known to cause detrimental effects to both the mother and the baby. During the past couple of decades, it has been shown that GHT is associated with multiple adverse maternal and fetal outcomes such as miscarriage, pre-eclampsia, placental abruption, fetal loss, premature delivery, neurocognitive and neurobehavioral development. However, three randomized controlled trials and a prospective cohort study performed within the last decade, show that there is no neurodevelopmental improvement in the offspring of mothers who received levothyroxine treatment for GHT. Thus, the benefit of initiating treatment for GHT is highly debated within the clinical community as there may also be risks associated with over-treatment. In addition, regulatory mechanisms that could possibly lead to GHT during pregnancy are not well elucidated. This review aims to unravel pregnancy induced physiological challenges that could provide basis for the development of GHT. During pregnancy, there is increased renal clearance of iodine leading to low iodine state. Also, an elevated estrogen level leading to an increase in circulating thyroglobulin level and a decrease in free thyroxine level. Moreover, placenta secretes compounds such as human chorionic gonadotropin (hCG), placental growth factor (PIGF) and soluble FMS-like tyrosine kinase-1 (s-Flt1) that could affect the thyroid function. In turn, the passage of thyroid hormones and iodine to the fetus is highly regulated within the placental barrier. Together, these mechanisms are hypothesized to contribute to the development of intolerance of thyroid function leading to GHT in a vulnerable individual.
TL;DR: In this paper, the authors compared insulin secretion, insulin resistance (IR) and thyroid function in patients with polycystic ovary syndrome (PCOS) with and without Hashimoto's thyroiditis (HT).
Abstract: Objective The incidence of Hashimoto's thyroiditis (HT) in patients with polycystic ovary syndrome (PCOS) is significantly higher than in normal controls, and there is a risk of more severe metabolic symptoms when the two diseases occur together. This study compares insulin secretion, insulin resistance (IR) and thyroid function in patients with PCOS with and without HT. Methods A total of 164 patients (52 patients with HT (HT+) and 112 patients without HT diagnosed PCOS at our hospital were enrolled for testing of oral glucose tolerance, insulin release, thyroid function, the presence of thyroglobulin and thyroid peroxidase antibodies, and blood lipid levels. Results Patients with PCOS and HT had higher insulin secretion and IR levels than those without HT, while free thyroxine and thyrotropin levels were significantly lower. The ratio of free thyroxine to thyrotropin was higher in patients with HT. Conclusion HT may related with IR and relatively low thyroid function in patients with PCOS. Thus, thyroid function and autoimmune status in patients with PCOS should be evaluated in clinical practice.
TL;DR: In this article, the authors investigated the impact of exogenous vitamin D on thyroid autoimmunity and thyroid function in men with early-onset androgenic alopecia.
TL;DR: Keap1KD mice develop age-dependent diffuse goiter with elevated TSH levels, and the precise mechanism accounting for the thyroidal phenotype remains to be elucidated, but it may involve enhanced Tg solubilization and excessive lysosomal Tg degradation.
Abstract: Background: Familial nontoxic multinodular goiter (MNG) is a rare disease. One of the associated genes is Kelch-like ECH-associated protein 1 (KEAP1), which encodes the main inhibitor of nuclear factor erythroid 2-related transcription factor 2 (Nrf2), a central mediator of antioxidant responses. The association of KEAP1 with familial MNG is based on only two loss-of-function mutations identified in two families, only one of which included proper phenotyping and adequate demonstration of co-segregation of the phenotype and the mutation. There is no experimental evidence from model organisms to support that decreased Keap1 levels can, indeed, cause goiter. This study used mice hypomorphic for Keap1 to test whether decreased Keap1 expression can cause goiter, and to characterize the activation status of Nrf2 in their thyroid. Methods: C57BL/6J Keap1flox/flox (Keap1 knock-down [Keap1KD]) mice were studied at 3 and 12 months of age. Plasma and thyroid glands were harvested for evaluation of thyroid function tests and for gene and protein expression by real-time polymerase chain reaction and immunoblotting, respectively. Results: Keap1KD mice showed diffuse goiter that began to develop in early adult life and became highly prominent and penetrant with age. The goiter was characterized by a markedly increased size of thyroid follicles, most notably of the colloid compartment, and by absence of thyroid nodules or hyperplasia. Keap1KD mice also showed decreased T4 levels in early adult life that were eventually well compensated over time by increased thyrotropin (TSH) levels. Nrf2 was activated in the thyroid of Keap1KD mice. Despite a known stimulatory effect of Nrf2 on thyroglobulin (Tg) gene transcription and Tg protein abundance, the expression levels were decreased in the thyroid of Keap1KD mice. No clear patterns were observed in the expression profiles of other thyroid hormone synthesis-specific factors, with the exception of Tg-processing and Tg-degrading cathepsins, including an increase in mature forms of cathepsins D, L, and S. Conclusions: Keap1KD mice develop age-dependent diffuse goiter with elevated TSH levels. The precise mechanism accounting for the thyroidal phenotype remains to be elucidated, but it may involve enhanced Tg solubilization and excessive lysosomal Tg degradation.