Showing papers in "Thyroid in 2016"
TL;DR: One hundred twenty-four evidence-based recommendations were developed to aid in the care of patients with thyrotoxicosis and to share what the task force believes is current, rational, and optimal medical practice.
Abstract: Background Thyrotoxicosis has multiple etiologies, manifestations, and potential therapies. Appropriate treatment requires an accurate diagnosis and is influenced by coexisting medical conditions and patient preference. This document describes evidence-based clinical guidelines for the management of thyrotoxicosis that would be useful to generalist and subspecialty physicians and others providing care for patients with this condition. Methods The American Thyroid Association (ATA) previously cosponsored guidelines for the management of thyrotoxicosis that were published in 2011. Considerable new literature has been published since then, and the ATA felt updated evidence-based guidelines were needed. The association assembled a task force of expert clinicians who authored this report. They examined relevant literature using a systematic PubMed search supplemented with additional published materials. An evidence-based medicine approach that incorporated the knowledge and experience of the panel was used to update the 2011 text and recommendations. The strength of the recommendations and the quality of evidence supporting them were rated according to the approach recommended by the Grading of Recommendations, Assessment, Development, and Evaluation Group. Results Clinical topics addressed include the initial evaluation and management of thyrotoxicosis; management of Graves' hyperthyroidism using radioactive iodine, antithyroid drugs, or surgery; management of toxic multinodular goiter or toxic adenoma using radioactive iodine or surgery; Graves' disease in children, adolescents, or pregnant patients; subclinical hyperthyroidism; hyperthyroidism in patients with Graves' orbitopathy; and management of other miscellaneous causes of thyrotoxicosis. New paradigms since publication of the 2011 guidelines are presented for the evaluation of the etiology of thyrotoxicosis, the management of Graves' hyperthyroidism with antithyroid drugs, the management of pregnant hyperthyroid patients, and the preparation of patients for thyroid surgery. The sections on less common causes of thyrotoxicosis have been expanded. Conclusions One hundred twenty-four evidence-based recommendations were developed to aid in the care of patients with thyrotoxicosis and to share what the task force believes is current, rational, and optimal medical practice.
1,446 citations
TL;DR: A systematic review supports a widespread and persistent increase in TC incidence and evidence for over-detection of PTC as the predominant influence includes increased numbers of smaller size tumors and improved or unchanged survival.
Abstract: Background: A large proportion of global increase in thyroid cancer (TC) incidence has been attributed to increased detection of papillary thyroid cancer (PTC). Nonetheless, some reports support a real increase in incidence. This study aimed to perform a systematic review to evaluate the changing trends in TC incidence and summarize potential risk factors predisposing to this trend. Methods: Literature published in the English language between 1980 and August 2014 was searched via PubMed (MEDLINE) and OvidSP (EMBASE). Original studies on changes in TC incidence in defined geographic areas that described clear methods of case selection and population estimates were included. Data on incidence rates and risk factors were collected. Results: Of 4719 manuscripts, 60 studies were included, of which 31 were from Europe, 13 from North America, and the rest from Asia (n = 9), Oceania (n = 4), and South America (n = 3). Fifty-three articles reported a significant increase in incidence (highest was a 10-fold increa...
247 citations
TL;DR: The oncological outcomes of the immediately surgery and active surveillance groups were similarly excellent, but the incidences of unfavorable events were definitely higher in the immediate surgery group, and active Surveillance is now recommended as the best choice for patients with low-risk PMC.
Abstract: Background: The incidence of papillary microcarcinoma (PMC) of the thyroid is rapidly increasing globally, making the management of PMC an important clinical issue. Excellent oncological outcomes of active surveillance for low-risk PMC have been reported previously. Here, unfavorable events following active surveillance and surgical treatment for PMC were studied. Methods: From February 2005 to August 2013, 2153 patients were diagnosed with low-risk PMC. Of these, 1179 patients chose active surveillance and 974 patients chose immediate surgery. The oncological outcomes and the incidences of unfavorable events of these groups were analyzed. Results: In the active surveillance group, 94 patients underwent surgery for various reasons; tumor enlargement and the appearance of novel lymph node metastases were the reasons in 27 (2.3%) and six patients (0.5%), respectively. One of the patients with conversion to surgery had nodal recurrence, and five patients in the immediate surgery group had a recurrence in a c...
244 citations
TL;DR: SCH during pregnancy is associated with multiple adverse maternal and neonatal outcomes, and the value of levothyroxine therapy in preventing these adverse outcomes remains uncertain.
Abstract: Background: The impact of subclinical hypothyroidism (SCH) and of levothyroxine replacement in pregnant women with SCH is unclear. The aims of this study were to assess (i) the impact of SCH during pregnancy on maternal and neonatal outcomes, and (ii) the effect of levothyroxine replacement therapy in these patients. Methods: Ovid MEDLINE In-Process & Other Non-Indexed Citations, Ovid MEDLINE, the Cochrane Controlled Trials Register, Ovid EMBASE, Web of Science, and Scopus were searched from inception to January 2015. Randomized trials and cohort studies of pregnant women with SCH that examined adverse pregnancy and neonatal outcomes were included. Reviewers extracted data and assessed methodological quality in duplicate. Eighteen cohort studies at low-to-moderate risk of bias were included. Compared with euthyroid pregnant women, pregnant women with SCH were at higher risk for pregnancy loss (relative risk [RR] 2.01 [confidence interval (CI) 1.66–2.44]), placental abruption (RR 2.14 [CI 1.23–3.70]), prem...
244 citations
TL;DR: A risk-stratified clinical decision-making framework was developed by the thyroid cancer disease management team at Memorial Sloan Kettering Cancer Center as the lessons learned from Kuma Hospital in Japan were applied to a cohort of patients with probable or proven papillary microcarcinoma who were being evaluated for an active surveillance management approach in the United States.
Abstract: Background: The 2015 American Thyroid Association thyroid cancer management guidelines endorse an active surveillance management approach as an alternative to immediate biopsy and surgery in subcentimeter thyroid nodules with highly suspicious ultrasonographic characteristics and in cytologically confirmed very low risk papillary thyroid cancer (PTC). However, the guidelines provide no specific recommendations with regard to the optimal selection of patients for an active surveillance management approach. This article describes a risk-stratified clinical decision-making framework that was developed by the thyroid cancer disease management team at Memorial Sloan Kettering Cancer Center as the lessons learned from Kuma Hospital in Japan were applied to a cohort of patients with probable or proven papillary microcarcinoma (PMC) who were being evaluated for an active surveillance management approach in the United States. Summary: A risk-stratified approach to the evaluation of patients with probable or proven...
231 citations
TL;DR: The prevalence and spectrum of thyroid disorders has increased, reflecting possible adverse effects of increased iodine intake, and the prevalence of clinical hypothyroidism, subclinical hypothyroxine, and positive thyroid antibodies was significantly higher in MTAII cities than it was in AII cities.
Abstract: Background: The goal of eliminating iodine deficiency worldwide was successfully achieved in China after the implementation of a mandatory universal salt iodization program for the last 16 years. Thus, China has been assessed as a country with more than adequate iodine levels. This survey aimed to investigate the current iodine status in China and the effects of an increased iodine intake on the spectrum and prevalence of thyroid disorders. Methods: A total of 15,008 adult subjects from 10 cities in eastern and central China were investigated. Serum thyrotropin (TSH), thyroid peroxidase antibodies (TPOAb), thyroglobulin antibodies (TgAb), and urine iodine concentration (UIC) were measured, and an ultrasonography of the thyroid was performed in all subjects. Free thyroxine (fT4) and free triiodothyronine (fT3) levels were only measured if the serum TSH was outside the normal range. Results: The median UIC values were 197 μg/L in school-age children (SAC) and 205 μg/L in a cohort population. Six cities were...
205 citations
TL;DR: Remote-access thyroidectomy has a role in a small group of patients who fit strict selection criteria, and therefore should be done by surgeons performing a high volume of thyroid and robotic surgery.
Abstract: Background: Remote-access techniques have been described over the recent years as a method of removing the thyroid gland without an incision in the neck. However, there is confusion related to the number of techniques available and the ideal patient selection criteria for a given technique. The aims of this review were to develop a simple classification of these approaches, describe the optimal patient selection criteria, evaluate the outcomes objectively, and define the barriers to adoption. Methods: A review of the literature was performed to identify the described techniques. A simple classification was developed. Technical details, outcomes, and the learning curve were described. Expert opinion consensus was formulated regarding recommendations for patient selection and performance of remote-access thyroid surgery. Results: Remote-access thyroid procedures can be categorized into endoscopic or robotic breast, bilateral axillo-breast, axillary, and facelift approaches. The experience in the United Stat...
163 citations
TL;DR: A change in the cutoff age in the current AJCC/UICC staging system from 45 years to 55 years would lead to a downstaging of 12% of patients, and would improve the statistical validity of the model.
Abstract: Background: Age is a critical factor in outcome for patients with well-differentiated thyroid cancer. Currently, age 45 years is used as a cutoff in staging, although there is increasing evidence to suggest this may be too low. The aim of this study was to assess the potential for changing the cut point for the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) staging system from 45 years to 55 years based on a combined international patient cohort supplied by individual institutions. Methods: A total of 9484 patients were included from 10 institutions. Tumor (T), nodes (N), and metastasis (M) data and age were provided for each patient. The group was stratified by AJCC/UICC stage using age 45 years and age 55 years as cutoffs. The Kaplan–Meier method was used to calculate outcomes for disease-specific survival (DSS). Concordance probability estimates (CPE) were calculated to compare the degree of concordance for each model. Results: Using age 45 years as a cutoff, 10-y...
154 citations
National Institutes of Health1, American Cancer Society2, International Agency for Research on Cancer3, Karolinska Institutet4, Harvard University5, University of Minnesota6, City of Hope National Medical Center7, University of Bergen8, Shanghai Jiao Tong University9, United States Department of Veterans Affairs10, Cancer Council Victoria11, University of Melbourne12, Cancer Prevention Institute of California13, University of Toronto14, Cancer Care Ontario15, Washington University in St. Louis16, Ontario Institute for Cancer Research17, Imperial College London18, George Washington University19, Yeshiva University20, University of Illinois at Chicago21, Vanderbilt University22, Loma Linda University23, Maastricht University24, Fred Hutchinson Cancer Research Center25, University of Washington26, New York University27
TL;DR: It is suggested that greater height and excess adiposity throughout adulthood are associated with higher incidence of most major types of thyroid cancer, including the least common but most aggressive form, anaplastic carcinoma, and higher thyroid cancer mortality.
Abstract: Background: Greater height and body mass index (BMI) have been associated with an increased risk of thyroid cancer, particularly papillary carcinoma, the most common and least aggressive subtype. Few studies have evaluated these associations in relation to other, more aggressive histologic types or thyroid cancer-specific mortality. Methods: This large pooled analysis of 22 prospective studies (833,176 men and 1,260,871 women) investigated thyroid cancer incidence associated with greater height, BMI at baseline and young adulthood, and adulthood BMI gain (difference between young-adult and baseline BMI), overall and separately by sex and histological subtype using multivariable Cox proportional hazards regression models. Associations with thyroid cancer mortality were investigated in a subset of cohorts (578,922 men and 774,373 women) that contributed cause of death information. Results: During follow-up, 2996 incident thyroid cancers and 104 thyroid cancer deaths were identified. All anthropometric facto...
143 citations
TL;DR: The malignancy risk of thyroid nodules can be stratified by TIRADS according to US patterns by combining solidity, echogenicity, and suspicious US features.
Abstract: Background: Although ultrasonography (US) has an essential role in assessing the malignancy risk of thyroid nodules, a malignancy risk-stratification system has not been established. The purpose of this study was to develop a clinically feasible US risk-stratification system—the Thyroid Imaging Reporting and Data System (TIRADS)—primarily based on the solidity and echogenicity of thyroid nodules. Methods: From January 2010 to May 2011, a total of consecutive 2000 thyroid nodules (≥1 cm) with final diagnoses were enrolled from the database of low and high cancer volume institutions (1000 nodules from each institution). For the development of TIRADS, the type and predictive value of US predictors in the groups categorized by solidity and echogenicity were analyzed, and the US predictors were integrated and categorized according to the malignancy risk. Results: The suspicious US features of microcalcification, taller than wide shape, and spiculated/microlobulated margin were independently predictive of malig...
142 citations
TL;DR: PTMC is an indolent disease, but does pose a risk for LNM and local recurrence, and more aggressive treatment or more frequent follow-up could be considered for patients with unfavorable features, especially in the setting of involved lymph nodes at the time of surgical resection.
Abstract: Background: The treatment for patients with papillary thyroid microcarcinoma (PTMC) is controversial because PTMC is often found incidentally and its prognosis is very good. Lymph node metastasis (LNM) is one of the main predictors of recurrence and survival. This retrospective study aimed to identify clinical and pathologic factors that increase the risk of metastasis or recurrence, in order to isolate clinically unfavorable PTMCs to help guide therapy. Methods: Clinical and pathologic data were collected from 273 patients diagnosed with PTMC at The University of Chicago Medical Center between 2000 and 2011. Data points included age, sex, race/ethnicity, tumor size, multifocality, thyroiditis, extrathyroidal extension (ETE), surgical margins, preoperative clinical suspicion of cancer, central/lateral lymph nodes removed and lymph nodes with metastatic carcinoma, treatment, local recurrence, distant recurrence, and survival. Results: Multivariate logistic regression showed that age <45 years (odds ratio [...
TL;DR: The magnitude of association between thyroid cancer screening in South Korea and the incidence of thyroid cancer strongly suggests that screening is the most important driver of the epidemic of thyroidcancer, particularly among females.
Abstract: Background: The incidence of thyroid cancer has increased worldwide. The country where the incidence has increased most is South Korea. The goal of this study is to understand the magnitude of association between opportunistic thyroid cancer screening and thyroid cancer incidence, thyroid cancer subtype, and disease-specific mortality. Methods: We used the 2010 Korea Community Health Survey, which queried 226,873 individuals if they had been screened for thyroid cancer in the last two years. Thyroid cancer incidence data from 2008 to 2010 were obtained from the Korea Cancer registry data, and mortality data from 2007–2010 were obtained from the Statistics Korea database. The ecological association between thyroid screening and thyroid cancer incidence and mortality by age and sex were examined across Korea's 16 administrative regions by general linear regression models. Results: Between 2008 and 2010, the incidence of thyroid cancer was 64.1 per 100,000 individuals: the incidence in females was 107.3 and ...
TL;DR: Selenium supplementation reduced serum TPOAb levels after 3, 6, and 12 months in an LT4-treated AIT population, and after three weeks in an untreated AIT populations, whether these effects correlate with clinically relevant measures remains to be demonstrated.
Abstract: Background: Selenium supplementation may decrease circulating thyroid autoantibodies in patients with chronic autoimmune thyroiditis (AIT), but the available trials are heterogenous. This study expands and critically reappraises the knowledge on this topic. Methods: A literature search identified 3366 records. Controlled trials in adults (≥18 years of age) with AIT, comparing selenium with or without levothyroxine (LT4), versus placebo and/or LT4, were eligible. Assessed outcomes were serum thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) autoantibody levels, and immunomodulatory effects. After screening and full-text assessment, 16 controlled trials were included in the systematic review. Random-effects meta-analyses in weighted mean difference (WMD) were performed for 3, 6, and 12 months of supplementation in two different populations: one receiving LT4 therapy and one newly diagnosed and LT4-untreated. Heterogeneity was estimated using I2, and quality of evidence was assessed per outcome, using the ...
TL;DR: In this paper, the authors evaluated the efficacy and safety of ultrasound-guided radiofrequency ablation (RFA) for treating low-risk thyroid microcarcinoma (PTMC) in 92 patients.
Abstract: Background: Papillary thyroid microcarcinoma (PTMC) has a high incidence and a good prognosis. Surgical operation for all PTMC might be an overtreatment. The objective of this study was to evaluate the efficacy and safety of ultrasound (US)-guided radiofrequency ablation (RFA) for treating low-risk PTMC. Methods: Ninety-eight PTMC in 92 patients were included in this study. US and contrast-enhanced ultrasound (CEUS) examinations were performed before ablation. RFA was performed using the moving-shot technique. The ablation area exceeded the tumor edge to prevent marginal residue and recurrence. Patients were followed at 1, 3, 6, and 12 months and every six months thereafter. US and CEUS examinations were used to evaluate the ablation area. At three months after ablation, US-guided core-needle biopsy (CNB) was performed in the center, at the edge of the ablation area, and in the surrounding thyroid parenchyma to exclude recurrence. Results: The mean tumor volume was 118.8 ± 106.9 mm3. The mean volume reduc...
TL;DR: In thyroid FNAs with cytologic features concerning for PTC, NIFTP/FVPTC can be distinguished from cPTC in most cases by assessing a limited number of features.
Abstract: Background: The term noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) has been proposed to replace noninvasive follicular variant of papillary thyroid carcinoma (FVPTC) in recognition of the indolent behavior of this tumor. The ability to differentiate NIFTP from classical papillary thyroid carcinoma (cPTC) by fine-needle aspiration (FNA) would facilitate conservative management for NIFTP. The aim of this study was to determine if NIFTP can be distinguished prospectively from cPTC. Methods: From June 2015 to January 2016, thyroid FNAs with a diagnosis of “malignant” or “suspicious for malignancy” were prospectively scored for features associated with NIFTP/FVPTC (microfollicular architecture) or cPTC (papillae, psammomatous calcifications, sheet-like architecture, and nuclear pseudoinclusions) and categorized as NIFTP/FVPTC, cPTC, or indeterminate. Results were correlated with subsequent histologic diagnoses. Results: The study included 52 patients with 56 resected nodu...
TL;DR: Non-physiologic biotin supplementation may interfere with several immunoassays, including thyroid hormones, TSH, thyroglobulin, and TSH receptor binding inhibiting antibody, leading to erroneous diagnoses.
Abstract: Background: Accurate immunoassays measuring minute quantities of hormones are the cornerstone of the practice of endocrinology. Despite tremendous advances in this field, novel pitfalls in these tests emerge from time to time. Oral biotin can interfere with immunoassays of several hormones. The purpose of this report is to relate an extreme case of such interference. Patient findings: A patient with progressive multiple sclerosis was found to have extremely elevated free thyroxine, triiodothyronine, and suppressed thyrotropin (TSH) levels. His TSH receptor binding inhibiting antibody level was also elevated. This constellation of laboratory findings suggested a diagnosis of severe Graves' disease. All of the assays yielding abnormal results employed the biotin–streptavidin affinity in their design. The patient had no symptoms of hyperthyroidism, and detailed review of his medications revealed intake of megadoses of biotin. Temporary discontinuation of biotin treatment resulted in complete resolution of th...
TL;DR: Nearly half of the patients with 1-4 cm WDTC who are eligible for lobectomy under current guidelines would require completion TT based on pathological characteristics of the initial lobe, indicating a need to balance the relative benefits, risks, and costs of initial TT versus the possible need for reoperative completion TT.
Abstract: Background: The extent of thyroidectomy for low-risk well-differentiated thyroid cancer (WDTC) remains controversial. Historically, total thyroidectomy (TT) has been recommended for WDTC ≥1 cm in size. However, recent National Comprehensive Cancer Network and American Thyroid Association guidelines recognize unilateral thyroid lobectomy as a viable alternative for 1–4 cm cancers due to their otherwise favorable prognosis, with TT remaining the preferred option for tumors with unfavorable pathological characteristics. This study sought to determine how often a completion TT would be recommended based on these guidelines if lobectomy was initially performed in patients with 1–4 cm WDTC without preoperatively known risk factors. Methods: Patients who underwent thyroidectomy for 1–4 cm WDTC (January 2000 to January 2010) were retrospectively reviewed. Patients with preoperatively known high-risk characteristics, including gross extrathyroidal extension (ETE) on preoperative imaging, clinically apparent lymph ...
TL;DR: A meta-analysis shows that BRAF mutational status correlates with recurrence of PTMCs, highlighting the potential utility of genotyping in preoperative and postoperative planning and BRAF mutation may be helpful in risk-stratifying patients with PTMC for surgical management versus observation.
Abstract: Background: Given the increasing incidence of papillary thyroid carcinoma despite stable disease-specific mortality rates, the potential for the disease to reoccur is a key outcome to predict. The BRAFV600E mutation has been associated with recurrent disease in larger tumors. However, its correlation in papillary thyroid microcarcinoma (PTMC) is not clear in individual series. Methods: The MEDLINE, EMBASE, Web of Science, and Cochrane databases were searched for studies including patients with PTMC undergoing initial surgical treatment. Studies with at least two years of follow-up, BRAF genotyping (the comparator), and recurrence as an outcome were included, as were unpublished primary data on 485 patients from two institutions. The metameter analyzed was odds ratio (OR) for recurrence between patients with BRAFV600E versus BRAF wild type (BRAFwt). Results: The initial search identified 431 references. After screening of the abstracts for inclusion, 44 manuscripts were reviewed in full by two independent ...
TL;DR: The clinicopathological features and risk factors for distant metastasis in patients with papillary thyroid microcarcinomas (PTMCs) were evaluated and nine had synchronous metastasis and three had metachronous metastasi.
Abstract: Background: The recent increase in the incidence of thyroid cancer has been mainly attributed to papillary thyroid microcarcinomas (PTMCs), and many studies have suggested conservative strategies for the diagnosis and treatment of PTMC. However, PTMCs may be associated with distant metastasis. This study aimed to evaluate the clinicopathological features and identify the risk factors for distant metastasis in patients with PTMCs. Methods: The medical records of 8808 patients who were diagnosed with PTMC from 1999 to 2012 were reviewed, and 12 (0.1%) patients with distant metastasis were identified. Forty-one PTMC patients who initially had lateral cervical lymph node (LN) metastasis and were cured with no evidence of a distant metastasis were also selected as a control group. Results: Of the 12 patients with distant metastasis, nine had synchronous metastasis and three had metachronous metastasis. All 12 patients had primary tumors >0.5 cm and cervical LN metastasis at initial surgery. Ten patients had cl...
TL;DR: This study reports what is currently the largest series of BRAFK601E mutated thyroid nodules, identified in 39 patients and comprised 5.3% of all BRAF mutations noted in thyroidectomy specimens.
Abstract: Background: While the association of the BRAFV600E mutation with aggressive histopathological tumor features and clinical behavior has been extensively studied in papillary thyroid carcinoma (PTC), the BRAFK601E mutation has not been well characterized. This study reports what is currently the largest series of BRAFK601E mutated thyroid nodules. Methods: Histopathologic, cytologic, and molecular reports over a period of seven years (June 2007 to June 2014) were reviewed to identify thyroid cases with various types of BRAF mutations. All cases positive for the BRAFK601E mutation were reviewed to confirm histopathologic diagnosis and establish tumor variant, and clinical charts were reviewed to obtain clinical characteristics and follow-up information. Results: The BRAFK601E mutation was identified in 39 patients and comprised 5.3% of all BRAF mutations noted in thyroidectomy specimens. Twenty-seven out of 29 nodules (93%) with BRAFK601E mutated tumors with surgical pathology results available for review we...
TL;DR: In this paper, the authors assess the socio-demographic and clinical factors that most influence thyroid cancer-specific QOL domains and estimate the impact of different health conditions on HRQOL in a large cohort of YA TC survivors.
Abstract: Background: There is a lack of health-related quality of life (HRQOL) research in thyroid cancer (TC) survivors, especially young adults (YAs). This study aims to assess the socio-demographic and clinical factors that most influence TC-specific QOL domains and estimate the impact of different health conditions on HRQOL in a large cohort of YA TC survivors. Methods: TC survivors ≥17 years of age were recruited through the thyroid cancer survivor (ThyCa) Web site. Mean scores for the seven domains and six items of THYCA-QoL, MCS and PCS of SF-12v1, and derived SF-6D were compared between factors as well as age groups (YA: 17–39 years, adult ≥40 years), and to the normal population. Regression analyses estimated the relationship between the socio-demographic, clinical, and THYCA-QoL measures and HRQOL in YAs only. Results: Of 1028 survivors, 277 (27%) were YAs. Most YAs were female (93.5%), white (86.6%), insured (96.8%), married or in a stable relationship (69%), and listed a comorbidity (43.7%); all report...
TL;DR: In addition to predicting cancer prevalence, the TBS also imparts important prognostic information about cancer type, variant, and risk of recurrence, which extends the utility of TBS classification by fostering an improved understanding of the risk posed by any confirmed malignancy.
Abstract: Background: Since its inception, the Bethesda System for Reporting Thyroid Cytopathology (TBS) has been widely adopted. Each category conveys a risk of malignancy and recommended next steps, though it is unclear if each category also predicts the type and extent of malignancy. If so, this would greatly expand the utility of the TBS by providing prognostic information in addition to baseline cancer risk. Methods: All patients prospectively enrolled into the authors' thyroid nodule database from 1995 to 2013 with histologically proven malignancy were analyzed. The primary ultrasound-guided fine-needle aspiration cytology (AUS, atypia of unknown significance; FN, follicular neoplasm; SUSP, suspicious; M, malignant) was correlated with the type of thyroid cancer and histological features known to impact prognosis and recurrence, including lymph node metastasis (LNM), lymphovascular invasion, and extrathyroidal extension (ETE). Primary cytology was separately correlated with higher risk malignancy. Results: A ...
TL;DR: The results question the current notion of an increase of TSH with increasing age, and suggest the set point that determines TSH secretion as it relates to negative thyroid hormone feedback is modified by age, sex and TPOAb positivity.
Abstract: Background: Information on determinants and change of thyroid function over time is sparse and conflicting but crucial for clinical interpretation and research. Therefore, our aim was to systematic...
TL;DR: The potent endogenous thyroid hormone-derived biogenic amine 3-T1AM exerts marked cryogenic, metabolic, cardiac and central actions and represents a valuable lead compound linking endocrine, metabolic and neuroscience research to advance development of new drugs.
Abstract: Thyronamines (3-T1AM, T0AM) are endogenous compounds probably derived from L-thyroxine or its intermediate metabolites. Combined activities of intestinal deiodinases and ornithine decarboxylase generate 3-T1AM in vitro. Alternatively, 3-T1AM might be formed by the thyroid gland and secreted into the blood. 3-T1AM and T0AM concentrations have been determined by liquid chromatography-tandem mass spectrometry analysis (LC-MS/MS) in tissues, serum, and cell lines. However, large variations of 3-T1AM concentrations in human serum were reported by LC-MS/MS compared with a monoclonal antibody-based immunoassay. These differences might be caused by strong binding of the highly hydrophobic 3-T1AM to apolipoprotein B100. Pharmacological administration of 3-T1AM results in dose-dependent reversible effects on body temperature, cardiac function, energy metabolism, and neurological functions. The physiological relevance of these actions is unclear, but may occur at tissue concentrations close to the estimated endogenous concentrations of 3-T1AM or its metabolites T0AM or thyroacetic acid (TA1). A number of putative receptors, binding sites, and cellular target molecules mediating actions of the multi-target ligand 3-T1AM have been proposed. Among those are members of the trace amine associated receptor family, the adrenergic receptor ADRα2a, and the thermosensitive transient receptor potential melastatin 8 channel. Preclinical studies employing various animal experimental models are in progress, and more stable receptor-selective agonistic and antagonistic analogues of 3-T1AM are now available for testing. The potent endogenous thyroid hormone-derived biogenic amine 3-T1AM exerts marked cryogenic, metabolic, cardiac and central actions and represents a valuable lead compound linking endocrine, metabolic, and neuroscience research to advance development of new drugs.
TL;DR: Oxidants are increased and antioxidants decreased in euthyroid Hashimoto's thyroiditis patients, thus contributing to a better definition of the redox homoeostasis dysregulation in HT.
Abstract: Background: Oxidative stress, which occurs as a result of an imbalance between free-radical production and antioxidant defense mechanisms, has been implicated in the pathogenesis of several autoimmune disorders, including thyroid diseases. Importantly, it has been correlated to thyroid dysfunction. This study investigated the changes in oxidative balance in euthyroid Hashimoto's thyroiditis (HT) by means of specific serum tests, such as derived reactive oxygen metabolites (d-ROMs) and the biological antioxidant potential (BAP) test. In addition, advanced glycation end products (AGEs) and advanced oxidation protein products (AOPPs)—compounds formed by the transformation of proteins—were evaluated as potential new markers of oxidative stress in this disease. Methods: This study included 134 euthyroid subject: 71 newly diagnosed HT patients (63 females; Mage = 38 ± 13 years) and 63 age and sex-matched healthy controls. None of them were on thyroxine therapy. Results: Serum d-ROMs were elevated, and BAP decre...
TL;DR: It is argued that patients with ATD should be screened for CD, given this increased prevalence, and fixed-effects inverse variance-weighted models were used to examine heterogeneity in subgroups.
Abstract: Background: Several screening studies have indicated an increased prevalence of celiac disease (CD) among individuals with autoimmune thyroid disease (ATD), but estimates have varied substantially. Objective: The aim of this study was to examine the prevalence of CD in patients with ATD. Method: A systematic review was conducted of articles published in PubMed Medline or EMBASE until September 2015. Non-English papers with English-language abstracts were also included, as were research abstracts without full text available when relevant data were included in the abstract. Search terms included “celiac disease” combined with “hypothyroidism” or “hyperthyroidism” or “thyroid disease.” Fixed-effects inverse variance-weighted models were used. Meta-regression was used to examine heterogeneity in subgroups. Results: A pooled analysis, based on 6024 ATD patients, found a prevalence of biopsy-confirmed CD of 1.6% [confidence interval (CI) 1.3–1.9%]. Heterogeneity was large (I2 = 70.7%). The prevalence was higher...
TL;DR: This comprehensive analysis of ATCs using targeted massive parallel sequencing identified several novel mutations, such as loss of function mutations of NF2 or KMT2D and RASAL1 mutations were significantly associated with shorter ATC patient survival.
Abstract: Background: Anaplastic thyroid carcinoma (ATC), the most aggressive type of thyroid cancer, has no effective therapy. Due to its dismal prognosis, it is vital to understand the genetic alterations of ATC and identify effective molecular targets. Targeted next-generation sequencing was performed to investigate the mutational profile of ATC using a massive parallel sequencing approach. Methods: DNA from formalin-fixed, paraffin-embedded archival samples of 11 ATCs and normal matched pairs were used. A total of 48 genetic alterations were identified by targeted exome sequencing. These alterations were validated by mass spectrometric genotyping and direct Sanger sequencing. Results: The most commonly mutated gene was BRAF, identified in 10 samples (91%), all showing the V600E point mutation. A KRAS point mutation was observed in the one sample (9%) without the BRAFV600E mutation. All 11 ATCs harbored BRAF or RAS mutations, reflecting the possibility that differentiated thyroid carcinomas progress to ATCs afte...
TL;DR: The high prevalence of childhood thyroid cancer detected in this four-year study in Fukushima can be attributed to mass screening and clearly exceeds what is found incidentally anywhere else.
Abstract: Background: Thyroid nodules and cancers are rare in children compared with adults. However, after the 1986 Chernobyl Nuclear Power Plant accident, a rapid increase in childhood thyroid cancer was observed. To avoid any confusion and misunderstanding of data obtained in Fukushima after the 2011 nuclear accident, baseline prevalence of thyroid nodules and cancers should be carefully assessed with standardized criteria systematically, and comprehensively applied to the population perceived to be at risk. Aims: Under the official framework of the Fukushima Health Management Survey, the thyroids of children in Fukushima were examined using ultrasound, and the results collected in the first four years after the nuclear accident were analyzed in order to establish a baseline prevalence of childhood thyroid abnormalities, especially cancer. Subjects and methods: Of 367,685 people aged 18 years or younger as of April 1, 2011, who were living in Fukushima Prefecture at the time of the accident, 300,476 underwent th...
TL;DR: LT4 suppression therapy does not adversely affect energy expenditure or body composition in women, but LT4 replacement therapy is associated with a lower REE, despite TSH levels within the reference range, suggesting relative tissue hypothyroidism may contribute to impaired energy expenditure in LT4 therapy.
Abstract: Background: Thyrotropin (TSH)-suppressive doses of levothyroxine (LT4) have adverse effects on bone and cardiac function, but it is unclear whether metabolic function is also affected. The objective of this study was to determine whether women receiving TSH-suppressive LT4 doses have alterations in energy expenditure or body composition. Methods: This study was a cross-sectional comparison between three groups of women: 26 women receiving chronic TSH-suppressive LT4 doses, 80 women receiving chronic replacement LT4 doses, and 16 untreated euthyroid control women. Subjects underwent measurements of resting energy expenditure (REE), substrate oxidation, and thermic effect of food by indirect calorimetry; physical activity energy expenditure by accelerometer; caloric intake by 24-hour diet recall; and body composition by dual X-ray absorptiometry. Results: REE per kilogram lean body mass in the LT4 euthyroid women was 6% lower than that of the LT4-suppressed group, and 4% lower than that of the healthy contr...