Significant SNPs have limited prediction ability for thyroid cancer

PubMed Central

Guo, Shicheng; Wang, Yu-Long; Li, Yi; Jin, Li; Xiong, Momiao; Ji, Qing-Hai; Wang, Jiucun

2014-01-01

Recently, five thyroid cancer significantly associated genetic variants (rs965513, rs944289, rs116909374, rs966423, and rs2439302) have been discovered and validated in two independent GWAS and numerous case–control studies, which were conducted in different populations. We genotyped the above five single nucleotide polymorphisms (SNPs) in Han Chinese populations and performed thyroid cancer-risk predictions with nine machine learning methods. We found that four SNPs were significantly associated with thyroid cancer in Han Chinese population, while no polymorphism was observed for rs116909374. Small familial relative risks (1.02–1.05) and limited power to predict thyroid cancer (AUCs: 0.54–0.60) indicate limited clinical potential. Four significant SNPs have limited prediction ability for thyroid cancer. PMID:24591304

Adjuvant Chemotherapy Improves the Probability of Freedom From Recurrence in Patients With Resected Stage IB Lung Adenocarcinoma.

PubMed

Hung, Jung-Jyh; Wu, Yu-Chung; Chou, Teh-Ying; Jeng, Wen-Juei; Yeh, Yi-Chen; Hsu, Wen-Hu

2016-04-01

The benefit of adjuvant chemotherapy remains controversial for patients with stage IB non-small-cell lung cancer (NSCLC). This study investigated the effect of adjuvant chemotherapy and the predictors of benefit from adjuvant chemotherapy in patients with stage IB lung adenocarcinoma. A total of 243 patients with completely resected pathologic stage IB lung adenocarcinoma were included in the study. Predictors of the benefits of improved overall survival (OS) or probability of freedom from recurrence (FFR) from platinum-based adjuvant chemotherapy in patients with resected stage IB lung adenocarcinoma were investigated. Among the 243 patients, 70 (28.8%) had received platinum-based doublet adjuvant chemotherapy. A micropapillary/solid-predominant pattern (versus an acinar/papillary-predominant pattern) was a significantly worse prognostic factor for probability of FFR (p = 0.033). Although adjuvant chemotherapy (versus surgical intervention alone) was not a significant prognostic factor for OS (p = 0.303), it was a significant prognostic factor for a better probability of FFR (p = 0.029) on multivariate analysis. In propensity-score-matched pairs, there was no significant difference in OS between patients who received adjuvant chemotherapy and those who did not (p = 0.386). Patients who received adjuvant chemotherapy had a significantly better probability of FFR than those who did not (p = 0.043). For patients with a predominantly micropapillary/solid pattern, adjuvant chemotherapy (p = 0.033) was a significant prognostic factor for a better probability of FFR on multivariate analysis. Adjuvant chemotherapy is a favorable prognostic factor for the probability of FFR in patients with stage IB lung adenocarcinoma, particularly in those with a micropapillary/solid-predominant pattern. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Impact of free tumor clusters on prognosis after resection of pulmonary adenocarcinoma.

PubMed

Morimoto, Junichi; Nakajima, Takahiro; Suzuki, Hidemi; Nagato, Kaoru; Iwata, Takekazu; Yoshida, Shigetoshi; Fukuyo, Masaki; Ota, Satoshi; Nakatani, Yukio; Yoshino, Ichiro

2016-07-01

Pulmonary adenocarcinoma with a micropapillary component (MPC) has aggressive malignant behavior even if resectable. The aim of this study was to determine clinicopathologic features of patients who underwent surgery for pulmonary adenocarcinoma harboring MPCs, with particular focus on coexistent free tumor clusters (FTCs). We retrospectively reviewed 444 patients with pulmonary adenocarcinoma who underwent surgery from March 2007 to July 2013. An MPC was defined as a >5% micropapillary pattern. We also defined FTCs to be a group of more than 3 small clusters containing <20 nonintegrated micropapillary tumor cells that were spreading within air spaces, >3 mm apart from the main tumor. The clinicopathologic characteristics of patients with and without FTCs were retrospectively investigated in MPC-positive patients. MPCs were identified in 67 patients (15.1%), 31 of whom (46.3%) were positive for FTCs. The distance between the furthest edge of FTCs and main tumors did not exceed the diameter of the main tumor in each case (average, 7.3 mm). Locoregional recurrences were frequently observed in FTC-positive patients. FTC-positive patients experienced a significantly lower 5-year recurrence-free survival rate compared with FTC-negative/MPC-positive patients (20.4% vs 52.2%, P < .001). Recurrence-free survival of FTC-negative and -positive patients was equivalent to that of patients with p-T2 and p-T3 MPC-negative adenocarcinoma, respectively. Coexistence of FTCs resulted in a further negative impact on postoperative prognosis among MPC-positive adenocarcinomas and should be considered for upstaging the p-T factor and during evaluation of surgical margins. Copyright © 2016. Published by Elsevier Inc.

Thyroid gland involvement in advanced laryngeal cancer: association with clinical and pathologic characteristics.

PubMed

Hilly, Ohad; Raz, Raanan; Vaisbuch, Yona; Strenov, Yulia; Segal, Karl; Koren, Rumelia; Shvero, Jacob

2012-11-01

Indications for thyroidectomy during laryngectomy are controversial. We examined whether clinicopathologic features can predict thyroid gland involvement, and the prognostic effect of thyroid gland involvement in patients undergoing total laryngectomy. The study set out to review preoperative assessment, operation findings, pathologic findings, and follow-up data. Thyroid gland involvement was found in 11 of 53 patients (21%) undergoing total laryngectomy and thyroidectomy. Preoperative work-up failed to predict thyroid gland involvement. Thyroid gland involvement was associated with salvage procedures (p = .025), paratracheal metastases (p = .003), and poor overall survival (hazard ratio = 2.74, p = .008). Thyroid gland involvement in patients undergoing total laryngectomy is frequent and is associated with poor prognosis. Preoperative assessment failed to predict thyroid gland involvement. We believe that thyroidectomy should be considered in cases with paratracheal lymphatic spread irrespective of tumor location within the larynx. Copyright © 2011 Wiley Periodicals, Inc.

Predictive factors of thyroid cancer in patients with Graves' disease.

PubMed

Ren, Meng; Wu, Mu Chao; Shang, Chang Zhen; Wang, Xiao Yi; Zhang, Jing Lu; Cheng, Hua; Xu, Ming Tong; Yan, Li

2014-01-01

The best preoperative examination in Graves' disease with thyroid cancer still remains uncertain. The objectives of the present study were to investigate the prevalence of thyroid cancer in Graves' disease patients, and to identify the predictive factors and ultrasonographic features of thyroid cancer that may aid the preoperative diagnosis in Graves' disease. This retrospective study included 423 patients with Graves' disease who underwent surgical treatment from 2002 to 2012 at our institution. The clinical features and ultrasonographic findings of thyroid nodules were recorded. The diagnosis of thyroid cancer was determined according to the pathological results. Thyroid cancer was discovered in 58 of the 423 (13.7 %) surgically treated Graves' disease patients; 46 of those 58 patients had thyroid nodules, and the other 12 patients were diagnosed with incidentally discovered thyroid carcinomas without thyroid nodules. Among the 58 patients with thyroid cancer, papillary microcarcinomas were discovered in 50 patients, and multifocality and lymph node involvement were detected in the other 8 patients. Multivariate regression analysis showed younger age was the only significant factor predictive of metastatic thyroid cancer. Ultrasonographic findings of calcification and intranodular blood flow in thyroid nodules indicate that they are more likely to harbor thyroid cancers. Because the influencing factor of metastatic thyroid cancers in Graves' disease is young age, every suspicious nodule in Graves' disease patients should be evaluated and treated carefully, especially in younger patients because of the potential for metastasis.

Prediction of thyroidal 131I effective half-life in patients with Graves' disease.

PubMed

Zhang, Ruiguo; Zhang, Guizhi; Wang, Renfei; Tan, Jian; He, Yajing; Meng, Zhaowei

2017-10-06

Calculation of effective thyroidal half-life (Teff) of iodine-131( 131 I) is cumbersome and tedious. The aim of this study was to investigate factors that could be used to predict Teff and to develop a Teff prediction model in Graves' disease patients. A total of 256 patients with GD were involved in this study. We investigated the influences of age, gender, disease duration, thyroid weight, antithyroid drugs, antithyroid drugs discontinuation period (ADP), thyroid function indexes, thyroid autoantibodies, thyroid-stimulating hormone receptor antibody (TRAb) level and radioactive iodine uptake (RAIU) values before 131 I therapy on Teff, applying univariate and multivariate analyses. Teff correlated negatively with thyroid peroxidase antibody, TRAb and thyroid weight, as well as positively with 24-hour, 48-hour, and 72-hour RAIU. Additionally, a longer ADP (especially≥ 14d) or without antithyroid drugs before 131 I therapy led to a longer Teff. Stepwise multiple linear regression analysis showed that 24-hour and 72-hour RAIU were statistically significant predictors of Teff ( P <0.001). The relationship was: predictive Teff=5.277+0.295×72-hour RAIU-0.217×24-hour RAIU (r =0.865, P < 0.001). The present results indicate that prediction of Teff from 24-hour and 72-hour RAIU is feasible in patients with Graves' disease, with high prediction accuracy.

Thyroid Gland Involvement in Carcinoma Larynx and Hypopharynx-Predictive Factors and Prognostic Significance.

PubMed

Iype, Elizabeth Mathew; Jagad, Vijay; Nochikattil, Santhosh Kumar; Varghese, Bipin T; Sebastian, Paul

2016-02-01

Intraoperative management of thyroid gland in laryngeal and hypopharyngeal cancer is controversial. The objectives of this study were to determine the incidence of thyroid gland invasion in patients undergoing surgery for laryngeal or hypopharyngeal carcinoma, to assess predictive factors and to assess the prognosis in patients with and without thyroid gland invasion. One hundred and thirty-three patients who underwent surgery for carcinoma larynx and hypopharynx from 2006 to 2010 were reviewed retrospectively. Surgical specimens were examined to determine the incidence of thyroid gland invasion and predictive factors were analysed. The recurrence rate and the survival in patients with and without thyroid gland invasion were also analysed. Out of the 133 patients with carcinoma larynx and hypopharynx who underwent surgery, histological thyroid gland invasion was observed in 28/133 (21%) patients. Significant relationship was found between histological thyroid gland invasion and preoperative evidence of thyroid cartilage erosion by CT scan and also when gross thyroid gland involvement observed during surgery. There is significant association between thyroid gland invasion when there is upper oesophageal or subglottic involvement. After analysing the retrospective data from our study, we would like to suggest that thyroid gland need not be removed routinely in all laryngectomies, unless there is advanced disease with thyroid cartilage erosion and gross thyroid gland involvement or disease with significant subglottic or oesophageal involvement.

Thyroid nodule management: clinical, ultrasound and cytopathological parameters for predicting malignancy

PubMed Central

Maia, Frederico F. R.; Zantut-Wittmann, Denise Engelbrecht

2012-01-01

Although fine-needle aspiration cytology is considered to be the reference method for evaluating thyroid nodules, the results are inaccurate in approximately 10-30% of cases. Several studies have attempted to predict the risk of malignancy in thyroid nodules based on age, nodularity, thyrotropin values, thyroid autoimmune disease, hot/cold nodule status, and ultrasound parameters. However, no consensus has been found, and none of these parameters has significantly affected patient management. The management of indeterminate thyroid nodules and re-biopsies of nodules with initially benign cytological results remain important and controversial topics of discussion. The Bethesda cytological system and several studies on the use of molecular markers to predict malignancy from cytological samples of thyroid nodules need further clarification. More in-depth discussions among and continuous education of the specialists involved in treating thyroid disease are necessary to improve the management of these patients. This review aims to examine the clinical, laboratory, ultrasound, and scintigraphic parameters that can be used for thyroid nodule management. PMID:22948464

Real-time shear wave elastography may predict autoimmune thyroid disease.

PubMed

Vlad, Mihaela; Golu, Ioana; Bota, Simona; Vlad, Adrian; Timar, Bogdan; Timar, Romulus; Sporea, Ioan

2015-05-01

To evaluate and compare the values of the elasticity index as measured by shear wave elastography in healthy subjects and in patients with autoimmune thyroid disease, in order to establish if this investigation can predict the occurrence of autoimmune thyroid disease. A total of 104 cases were included in the study group: 91 women (87.5%), out of which 52 (50%) with autoimmune thyroid disease diagnosed by specific tests and 52 (50%) healthy volunteers, matched for age and gender. For all the subjects, three measurements were performed on each thyroid lobe and a mean value was calculated. The data were expressed in kPa. The investigation was performed with an Aixplorer system (SuperSonic Imagine, France), using a linear high-resolution 15-4 MHz transducer. The mean value for the elasticity index was similar in the right and the left thyroid lobes, both in normal subjects and in patients with autoimmune thyroid disease: 19.6 ± 6.6 vs. 19.5 ± 6.8 kPa, p = 0.92, and 26.6 ± 10.0 vs. 25.8 ± 11.7 kPa, p = 0.71, respectively. This parameter was significantly higher in patients with autoimmune thyroid disease than in controls (p < 0.001). For a cut-off value of 22.3 kPa, which resulted in the highest sum of sensitivity and specificity, the elasticity index assessed by shear wave elastography had a sensitivity of 59.6% and a specificity of 76.9% (AUROC = 0.71; p < 0.001) for predicting the presence of autoimmune thyroid disease. Quantitative elasticity index measured by shear wave elastography was significantly higher in autoimmune thyroid disease than in normal thyroid parenchyma and may predict the presence of autoimmune thyroid disease.

How reliably can computed tomography predict thyroid invasion prior to laryngectomy?

PubMed

Harris, Andrew S; Passant, Carl D; Ingrams, Duncan R

2018-05-01

There is little evidence to support the removal of thyroid tissue during total laryngectomy. Although oncological control of the tumor is the priority, thyroidectomy can lead to hypothyroidism and hypoparathyroidism. This study aimed to test the usefulness of preoperative computed tomography in predicting histological invasion of the thyroid. Ambispective cohort study. All patients undergoing total laryngectomy for squamous cell carcinoma at one center from 2006 to 2016 were included. Data were recorded prospectively as part of the patients' standard care, but were collated retrospectively, giving this study an ambispective design. The histology report for thyroid invasion was taken as the gold standard. The computed tomography report was categorized by invasion of tumor into intralaryngeal, laryngeal cartilage involvement, and extralaryngeal tissues. Seventy-nine patients were included. Nine patients had thyroid involvement on histology, translating to an incidence of 11.29% in this population. The positive predictive value for cartilage involvement on computed tomography for thyroid invasion was 52.9% (95% confidence interval [CI]: 28.5%-76.1%) and the negative predictive value was 100% (95% CI: 92.7%-100%).The positive predictive value for extralaryngeal spread on computed tomography for thyroid involvement was 100% (95% CI: 62.9%-100%), and the negative predictive value was also 100% (95% CI: 93.5%-100%). This study has shown that preoperative computed tomography is an effective method of ruling out thyroid gland invasion. The absence of extralaryngeal spread on computed tomography has been shown to be the most useful finding, with a high negative predictive value and a narrow 95% CI. 4. Laryngoscope, 128:1099-1102, 2018. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Palatine tonsillar metastasis of a small pulmonary adenocarcinoma showing an invasive micropapillary carcinoma pattern and Pagetoid spread at the tonsil: a case suggesting retrograde lymphatic metastasis from bulky lymph node metastases of the neck.

PubMed

Tajima, Shogo; Koda, Kenji

2015-01-01

Metastasis rarely occurs in the palatine tonsils. Among primary pulmonary carcinoma subtypes, small cell carcinoma more frequently metastasizes to this site. Herein, we present an exceedingly rare case of a small pulmonary adenocarcinoma that metastasized to the cervical lymph nodes and the right palatine tonsil in a 62-year-old man. In spite of the small size of the primary site, such extensive metastasis may have occurred because of the invasive micropapillary carcinoma pattern seen in the metastatic sites. The manner of metastasis to the palatine tonsil was considered retrograde lymphatic metastasis originating from carcinoma cells in the cervical lymph nodes. Furthermore, Pagetoid spread was observed at the palatine tonsil. Although there have been only a few cases showing retrograde lymphatic metastasis and Pagetoid spread at the metastatic site, we should be careful when speculating about the primary site based on such metastatic sites, especially when dealing with a biopsy sample exhibiting Pagetoid spread.

Micropapillary Structures in Colorectal Cancer: An Anoikis-resistant Subpopulation.

PubMed

Patankar, Madhura; Väyrynen, Sara; Tuomisto, Anne; Mäkinen, Markus; Eskelinen, Sinikka; Karttunen, Tuomo J

2018-05-01

Micropapillary structures (MIPs) are focal piles of columnar cells without extracellular matrix contact, and common in serrated colorectal carcinoma (CRC). In order to characterize biology of MIPs in colorectal cancer (CRC), the proliferation and apoptosis rates, and survivin expression were compared between MIPs and other cancer epithelial cells of CRC (non-MIPs). We assessed 46 samples of normal colorectal mucosa, 62 carcinomas and 54 polyps for proliferation (Ki67), apoptosis (M30), and survivin expression by immunohistochemistry. MIPs in carcinoma showed lower rates of proliferation and apoptosis than non-MIPs. A low rate of apotosis in MIPs was associated with poor prognosis in local carcinoma. In normal crypts, nuclear-to-cytoplasmic transition of survivin indicated epithelial cell maturation. Cancer cases showed increased cytoplasmic expression of survivin than normal mucosa and polyps. However, MIPs showed lower nuclear and cytoplasmic survivin expression than non-MIPs. Our findings suggest that MIPs represent a biologically distinct subpopulation of carcinoma cells with features of anoikis resistance and possibly quiescence. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Sonographic findings predictive of central lymph node metastasis in patients with papillary thyroid carcinoma: influence of associated chronic lymphocytic thyroiditis on the diagnostic performance of sonography.

PubMed

Yoo, Yeon Hwa; Kim, Jeong-Ah; Son, Eun Ju; Youk, Ji Hyun; Kwak, Jin Young; Kim, Eun-Kyung; Park, Cheong Soo

2013-12-01

To analyze sonographic findings suggesting central lymph node metastasis of papillary thyroid carcinoma and to evaluate the influence of associated chronic lymphocytic thyroiditis on the diagnostic performance of sonography for predicting central lymph node metastasis. A total of 124 patients (101 female and 23 male; mean age, 47.5 years; range, 21-74 years) underwent sonographically guided fine-needle aspiration in central lymph nodes from January 2008 to July 2011. Sonographic features of size, shape, margin, thickening of the cortex, cortical echogenicity, presence of a hilum, cystic changes, calcification, and vascularity of enlarged lymph nodes were analyzed before fine-needle aspiration and classified into 2 categories (probably benign and suspicious). Sonographic findings were correlated with the pathologic diagnosis and associated chronic lymphocytic thyroiditis. Receiver operating characteristic curve analysis was performed to assess the diagnostic performance of sonography for predicting central lymph node metastasis according to the associated thyroiditis. Fifty-one lymph nodes (39.5%) were malignant, and 73 (60.5%) were benign. On univariate analysis, size, shape, margin, cortical thickening, cortical echogenicity, cystic changes, calcification, and vascularity were significantly different between the benign and metastatic nodes (P < .05). On multivariate analysis, eccentric cortical thickening (odds ratio, 26.59; 95% confidence interval [CI], 3.26-216.66) and hyper echogenicity of the cortex (odds ratio, 18.46; 95% CI, 2.44-139.64) were significantly associated with malignant nodes (P < .05). The area under the curve values for sonography for predicting metastasis were 0.756 (95% CI, 0.618-0.894) in chronic lymphocytic thyroiditis-positive patients and 0.971 (95% CI, 0.938-1.000) in negative patients. Eccentric cortical thickening and cortical hyperechogenicity were the sonographic findings predictive of central lymph node metastasis from papillary thyroid carcinoma. The diagnostic performance of sonography for predicting metastasis was superior in chronic lymphocytic thyroiditis-negative patients than in positive patients.

Logistic regression analysis of conventional ultrasonography, strain elastosonography, and contrast-enhanced ultrasound characteristics for the differentiation of benign and malignant thyroid nodules

PubMed Central

Deng, Yingyuan; Wang, Tianfu; Chen, Siping; Liu, Weixiang

2017-01-01

The aim of the study is to screen the significant sonographic features by logistic regression analysis and fit a model to diagnose thyroid nodules. A total of 525 pathological thyroid nodules were retrospectively analyzed. All the nodules underwent conventional ultrasonography (US), strain elastosonography (SE), and contrast -enhanced ultrasound (CEUS). Those nodules’ 12 suspicious sonographic features were used to assess thyroid nodules. The significant features of diagnosing thyroid nodules were picked out by logistic regression analysis. All variables that were statistically related to diagnosis of thyroid nodules, at a level of p < 0.05 were embodied in a logistic regression analysis model. The significant features in the logistic regression model of diagnosing thyroid nodules were calcification, suspected cervical lymph node metastasis, hypoenhancement pattern, margin, shape, vascularity, posterior acoustic, echogenicity, and elastography score. According to the results of logistic regression analysis, the formula that could predict whether or not thyroid nodules are malignant was established. The area under the receiver operating curve (ROC) was 0.930 and the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 83.77%, 89.56%, 87.05%, 86.04%, and 87.79% respectively. PMID:29228030

Logistic regression analysis of conventional ultrasonography, strain elastosonography, and contrast-enhanced ultrasound characteristics for the differentiation of benign and malignant thyroid nodules.

PubMed

Pang, Tiantian; Huang, Leidan; Deng, Yingyuan; Wang, Tianfu; Chen, Siping; Gong, Xuehao; Liu, Weixiang

2017-01-01

The aim of the study is to screen the significant sonographic features by logistic regression analysis and fit a model to diagnose thyroid nodules. A total of 525 pathological thyroid nodules were retrospectively analyzed. All the nodules underwent conventional ultrasonography (US), strain elastosonography (SE), and contrast -enhanced ultrasound (CEUS). Those nodules' 12 suspicious sonographic features were used to assess thyroid nodules. The significant features of diagnosing thyroid nodules were picked out by logistic regression analysis. All variables that were statistically related to diagnosis of thyroid nodules, at a level of p < 0.05 were embodied in a logistic regression analysis model. The significant features in the logistic regression model of diagnosing thyroid nodules were calcification, suspected cervical lymph node metastasis, hypoenhancement pattern, margin, shape, vascularity, posterior acoustic, echogenicity, and elastography score. According to the results of logistic regression analysis, the formula that could predict whether or not thyroid nodules are malignant was established. The area under the receiver operating curve (ROC) was 0.930 and the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 83.77%, 89.56%, 87.05%, 86.04%, and 87.79% respectively.

Pre-operative ultrasound identification of thyroiditis helps predict the need for thyroid hormone replacement after thyroid lobectomy.

PubMed

Morris, Lilah F; Iupe, Isabella M; Edeiken-Monroe, Beth S; Warneke, Carla L; Hansen, Mandy O; Evans, Douglas B; Lee, Jeffrey E; Grubbs, Elizabeth G; Perrier, Nancy D

2013-01-01

To evaluate whether pre-operative thyroiditis identified by ultrasound (US) could help predict the need for thyroid hormone replacement (THR) following thyroid lobectomy. Data from patients who underwent thyroid lobectomy in 2006-2011, were not taking THR pre-operatively, and had ≥1 month of follow-up were reviewed retrospectively. THR was prescribed for relatively elevated thyroid-stimulating hormone (TSH) and hypothyroid symptoms. The Kaplan-Meier method was used to estimate the percentage of patients who required THR at 6, 12, 18, and 24 months postoperatively, and Cox proportional hazards regression models were used to evaluate prognostic factors for requiring post-thyroid lobectomy THR. During follow-up, 45 of 98 patients required THR. Median follow-up among patients not requiring THR was 11.6 months (range, 1.2 to 51.3 months). Six months after thyroid lobectomy, 22% of patients were taking THR (95% confidence interval [CI], 15-32%); the proportion increased to 46% at 12 months (95% CI, 36-57%) and 55% at 18 months (95% CI, 43-67%). On univariate analysis, significant prognostic factors for postoperative THR included a pre-operative TSH level >2.5 μ international units [IU]/mL (hazard ratio [HR], 2.8; 95% CI, 1.4-5.5; P = .004) and pathology-identified thyroiditis (HR, 2.4; 95% CI, 1.3-4.3; P = .005). Patients with both pre-operative TSH >2.5 μIU/mL and US-identified thyroiditis had a 5.8-fold increased risk of requiring postoperative THR (95% CI, 2.4-13.9; P<.0001). A pre-operative TSH level >2.5 μIU/mL significantly increases the risk of requiring THR after thyroid lobectomy. Thyroiditis can add to that prediction and guide pre-operative patient counseling and surgical decision making. US-identified thyroiditis should be reported and post-thyroid lobectomy patients followed long-term (≥18 months).

Thyroiditis de Quervain. Are there predictive factors for long-term hormone-replacement?

PubMed

Schenke, S; Klett, R; Braun, S; Zimny, M

2013-01-01

Subacute thyroiditis is a usually self-limiting disease of the thyroid. However, approximately 0.5-15% of the patients require permanent thyroxine substitution. Aim was to determine predictive factors for the necessity of long-term hormone-replacement (LTH). We retrospectively reviewed the records of 72 patients with subacute thyroiditis. Morphological and serological parameters as well as type of therapy were tested as predictive factors of consecutive hypothyroidism. Mean age was 49 ± 11 years, f/m-ratio was 4.5 : 1. Thyroid pain and signs of hyperthyroidism were leading symptoms. Initial subclinical or overt hyperthyroidism was found in 20% and 37%, respectively. Within six months after onset 15% and 1.3% of the patients developed subclinical or overt hypothyroidism, respectively. At latest follow-up 26% were classified as liable to LTH. At onset the thyroid was enlarged in 64%, and at latest follow-up in 8.3%, with a significant reduction of the thyroid volume after three months. At the endpoint the thyroid volume was less in patients in the LTH group compared with the non-LTH group (41.7% vs. 57.2% of sex-adjusted upper norm, p = 0.041). Characteristic ultrasonographic features occurred in 74% of the patients in both lobes. Serological and morphological parameters as well as type of therapy were not related with the need of LTH. In this study the proportion of patients who received LTH was 26%. At the endpoint these patients had a lower thyroid volume compared with euthyroid patients. No predictive factors for LTH were found.

Acoustic Radiation Force Impulse Quantification in the Evaluation of Thyroid Elasticity in Pediatric Patients With Hashimoto Thyroiditis.

PubMed

Yucel, Serap; Ceyhan Bilgici, Meltem; Kara, Cengiz; Can Yilmaz, Gulay; Aydin, H Murat; Elmali, Muzaffer; Tomak, Leman; Saglam, Dilek

2018-05-01

To evaluate the parenchymal elasticity of the thyroid gland with acoustic radiation force impulse imaging in pediatric patients with Hashimoto thyroiditis and to compare it with healthy volunteers. Twenty-six patients with Hashimoto thyroiditis and 26 healthy volunteers between 6 and 17 years were included. The shear wave velocity (SWV) values of both thyroid lobes in both groups were evaluated. The age and sex characteristics of the controls and patients with Hashimoto thyroiditis were similar. The SWV of the thyroid gland in patients with Hashimoto thyroiditis (mean ± SD, 1.67 ± 0.63 m/s) was significantly higher than that in the control group (1.30 ± 0.13 m/s; P < .001). There was no significant difference between the thyroid lobes in both groups. A receiver operating characteristic curve analyses showed an optimal cutoff value of 1.41 m/s, with 73.1% sensitivity, 80.8% specificity, a 79.2 % positive predictive value, and a 75.0% negative predictive value (area under the curve, 0.806; P < .001). In patients with Hashimoto thyroiditis, there was a positive correlation between the SWV values versus anti-thyroperoxidase (Pearson r = 0.46; P = .038). There were no correlations between age, body mass index, thyroid function test results, and anti-thyroglobulin values and versus SWV values. Also, no significant differences were seen between the groups for gland size, gland vascularity, and l-thyroxine treatment. Acoustic radiation force impulse elastography showed a significant difference in the stiffness of the thyroid gland between children with Hashimoto thyroiditis and the healthy group. Using acoustic radiation force impulse elastography immediately after a standard ultrasound evaluation may predict chronic autoimmune thyroiditis. © 2017 by the American Institute of Ultrasound in Medicine.

Taller-than-wide sign for predicting thyroid microcarcinoma: comparison and combination of two ultrasonographic planes.

PubMed

Chen, Shun-Ping; Hu, Yuan-Ping; Chen, Bin

2014-09-01

The aims of this study were to investigate the accuracy of using the taller-than-wide (TTW) sign in two ultrasonographic planes to predict thyroid microcarcinoma, and to confirm the hypothesis that the presence of a TTW sign in both the transverse and longitudinal ultrasonographic planes strongly suggests thyroid microcarcinoma. Nine hundred forty-two thyroid nodules ≤1 cm were submitted to surgical-histopathologic and ultrasonographic examination. TTW signs were divided into three types based on their detection only in the transverse plane (TTTW type, n = 100), only in the longitudinal plane (LTTW type, n = 61) or in both planes (BTTW type, n = 131). The areas under the receiver operating characteristic curves (A(z)) for the three different TTW signs, as well as for the combination of all TTW signs (ATTW, n = 292), were compared. The results indicated that the A(z) values of the TTTW, LTTW, BTTW and ATTW signs in predicting thyroid microcarcinoma were 0.544, 0.531, 0.627 and 0.702, respectively. The ATTW sign was the most accurate (p < 0.05), and the BTTW sign was 100% accurate for predicting thyroid microcarcinoma. However, there was no significant difference between the A(z) values for the TTTW and LTTW signs (p > 0.05). Therefore, both the LTTW and TTTW signs are reliable markers of thyroid microcarcinoma. The BTTW sign strongly suggests thyroid microcarcinoma. Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Cancer risk estimation in Belarussian children due to thyroid irradiation as a consequence of the Chernobyl nuclear accident

DOE Office of Scientific and Technical Information (OSTI.GOV)

Buglova, E.; Kenigsberg, J.E.; Sergeeva, N.V.

1996-07-01

The thyroid doses received by the juvenile population of Belarus following the Chernobyl accident ranged up to about 10 Gy. The thyroid cancer risk estimate recommended in NCRP Report No. 80 was used to predict the number of thyroid cancer cases among children during 1990-1992 in selected Belarussian regions and cities. The results obtained using this risk estimate show an excess of thyroid cancer cases being registered vs. the predicted cases. Thyroid cancer incidence rate among boys under investigation is higher than among girls in the postaccident period. The excess of the observed over the expected incidence in the generalmore » juvenile population is caused by the high thyroid cancer incidence rate among boys. These results, which can be considered part of the first stage of a thorough thyroid cancer risk estimation after the Chernobyl accident, demonstrate the critical need to complete these studies in depth. 6 refs., 5 figs., 3 tabs.« less

18F-FDG PET/CT Can Predict Development of Thyroiditis due to Immunotherapy for Lung Cancer.

PubMed

Eshghi, Naghmehossadat; Garland, Linda; Nia, Emily Saghar; Betancourt, Robert; Krupinski, Elizabeth; Kuo, Phillip H

2018-03-29

Objective: For patients undergoing immunotherapy with nivolumab for lung cancer, determine if increased 18 F-FDG uptake in the thyroid gland predicts development of thyroiditis with subsequent hypothyroidism. Secondarily, determine if 18 F-FDG uptake in the thyroid gland correlates with administered cycles of nivolumab. Materials and Methods: Retrospective chart review over 2 years found 18 lung cancer patients treated with nivolumab and with 18 F-FDG PET/CT scans pre- and during therapy. Standardized uptake value (SUV) mean and maximum and total lesion glycolysis (TLG) of the thyroid gland were measured. SUVs were also measured for the pituitary gland, liver and spleen. Patients obtained monthly thyroid testing. PET/CT parameters were analyzed by unpaired t-test for differences between two groups (patients who developed hypothyroidism and those who did not). Correlation between development of thyroiditis and number of cycles of nivolumab received was also tested. Results: Six of eighteen patients developed hypothyroidism. T-test comparing the two groups (patients who developed hypothyroidism and those who did not) demonstrated significant differences in SUVmean ( P = 0.04), SUV max ( P = 0.04) and TLG ( P = 0.02) of the thyroid gland. Two of four patients who developed thyroiditis and had increased 18 F-FDG uptake in the thyroid gland, had normal TSH at time of follow-up 18 F-FDG PET/CT. Patients who developed thyroiditis with subsequent hypothyroidism stayed longer on therapy (10.6 cycles) compared to patients without thyroiditis (7.6 cycles), but the trend was not statistically significant. No significant difference in PET/CT parameters was observed for pituitary gland, liver or spleen. Conclusion: 18 F-FDG PET/CT can predict the development of thyroiditis with subsequent hypothyroidism before laboratory testing. Further study is required to confirm the positive trend between thyroiditis and duration of therapy. Copyright © 2018 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Radiologic-Pathologic Correlation of Solid Portions on Thin-section CT Images in Lung Adenocarcinoma: A Multicenter Study.

PubMed

Yanagawa, Masahiro; Kusumoto, Masahiko; Johkoh, Takeshi; Noguchi, Masayuki; Minami, Yuko; Sakai, Fumikazu; Asamura, Hisao; Tomiyama, Noriyuki

2018-05-01

Measuring the size of invasiveness on computed tomography (CT) for the T descriptor size was deemed important in the 8th edition of the TNM lung cancer classification. We aimed to correlate the maximal dimensions of the solid portions using both lung and mediastinal window settings on CT imaging with the pathologic invasiveness (> 0.5 cm) in lung adenocarcinoma patients. The study population consisted of 378 patients with a histologic diagnosis of adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), invasive adenocarcinoma (IVA)-lepidic, IVA-acinar and/or IVA-papillary, and IVA-micropapillary and/or solid adenocarcinoma. A panel of 15 radiologists was divided into 2 groups (group A, 9 radiologists; and group B, 6 radiologists). The 2 groups independently measured the maximal and perpendicular dimensions of the solid components and entire tumors on the lung and mediastinal window settings. The solid proportion of nodule was calculated by dividing the solid portion size (lung and mediastinal window settings) by the nodule size (lung window setting). The maximal dimensions of the invasive focus were measured on the corresponding pathologic specimens by 2 pathologists. The solid proportion was larger in the following descending order: IVA-micropapillary and/or solid, IVA-acinar and/or papillary, IVA-lepidic, MIA, and AIS. For both groups A and B, a solid portion > 0.8 cm in the lung window setting or > 0.6 cm in the mediastinal window setting on CT was a significant indicator of pathologic invasiveness > 0.5 cm (P < .001; receiver operating characteristic analysis using Youden's index). A solid portion > 0.8 cm on the lung window setting or solid portion > 0.6 cm on the mediastinal window setting on CT predicts for histopathologic invasiveness to differentiate IVA from MIA and AIS. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

ROLE OF MOLECULAR MARKERS IN THYROID NODULE MANAGEMENT: THEN AND NOW.

PubMed

Nikiforov, Yuri E

2017-08-01

To describe the evolution and clinical utility of molecular testing for thyroid nodules and cancer achieved over the last 2 decades. Scientific reports on thyroid cancer genetics and molecular diagnostics in thyroid nodules. Over the last 2 decades, our understanding of the genetic mechanisms of thyroid cancer has dramatically expanded, such that most thyroid cancers now have known gene driver events. This knowledge provides the basis for establishing and further improving molecular tests for thyroid nodules and cancer and for the introduction of new entities such as noninvasive follicular thyroid neoplasm with papillary-like nuclear features. The progress with molecular tests for thyroid nodules started in the 1990s from demonstrating feasibility of detecting various molecular alterations in fine-needle aspiration (FNA) material collected from thyroid nodules. It was followed by the introduction of the first single-gene mutational markers, such as BRAF, and a small mutational panel into clinical practice in the mid 2000s. Currently, several more advanced molecular tests are available for clinical use. They are based on multiple molecular markers and have increasing impact on the clinical management of patients with thyroid nodules. The evolution of molecular tests for thyroid nodules followed the discovery of various diagnostic and prognostic molecular markers of thyroid cancer that can be applied to thyroid FNA samples to inform more individualized management of these patients. FNA = fine-needle aspiration miRNA = micro RNA NGS = next-generation sequencing NIFTP = noninvasive follicular thyroid neoplasm with papillary-like nuclear features NPV = negative predictive value PPV = positive predictive value PTC = papillary thyroid carcinoma RAI = radioactive iodine.

Preoperative Serum Thyrotropin to Thyroglobulin Ratio Is Effective for Thyroid Nodule Evaluation in Euthyroid Patients.

PubMed

Wang, Lina; Li, Hao; Yang, Zhongyuan; Guo, Zhuming; Zhang, Quan

2015-07-01

This study was designed to assess the efficiency of the serum thyrotropin to thyroglobulin ratio for thyroid nodule evaluation in euthyroid patients. Cross-sectional study. Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China. Retrospective analysis was performed for 400 previously untreated cases presenting with thyroid nodules. Thyroid function was tested with commercially available radioimmunoassays. The receiver operating characteristic curves were constructed to determine cutoff values. The efficacy of the thyrotropin:thyroglobulin ratio and thyroid-stimulating hormone for thyroid nodule evaluation was evaluated in terms of sensitivity, specificity, positive predictive value, positive likelihood ratio, negative likelihood ratio, and odds ratio. In receiver operating characteristic curve analysis, the area under the curve was 0.746 for the thyrotropin:thyroglobulin ratio and 0.659 for thyroid-stimulating hormone. With a cutoff point value of 24.97 IU/g for the thyrotropin:thyroglobulin ratio, the sensitivity, specificity, positive predictive value, positive likelihood ratio, and negative likelihood ratio were 78.9%, 60.8%, 75.5%, 2.01, and 0.35, respectively. The odds ratio for the thyrotropin:thyroglobulin ratio indicating malignancy was 5.80. With a cutoff point value of 1.525 µIU/mL for thyroid-stimulating hormone, the sensitivity, specificity, positive predictive value, positive likelihood ratio, and negative likelihood ratio were 74.0%, 53.2%, 70.8%, 1.58, and 0.49, respectively. The odds ratio indicating malignancy for thyroid-stimulating hormone was 3.23. Increasing preoperative serum thyrotropin:thyroglobulin ratio is a risk factor for thyroid carcinoma, and the correlation of the thyrotropin:thyroglobulin ratio to malignancy is higher than that for serum thyroid-stimulating hormone. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.

Negative Feedback Control of Pituitary Thyroid-stimulating Hormone Synthesis and Secretion by Thyroid Hormones during Metamorphosis in Xenopus laevis

EPA Science Inventory

A basic understanding of the endocrinology of the hypothalamic-pituitary-thyroid (HPT) axis of anuran larvae is necessary for predicting the consequences of HPT perturbation by thyroid-disrupting chemicals (TDCs) on the whole organism. This project examined negative feedback con...

Thyroid-specific questions on work ability showed known-groups validity among Danes with thyroid diseases.

PubMed

Nexo, Mette Andersen; Watt, Torquil; Bonnema, Steen Joop; Hegedüs, Laszlo; Rasmussen, Åse Krogh; Feldt-Rasmussen, Ulla; Bjorner, Jakob Bue

2015-07-01

We aimed to identify the best approach to work ability assessment in patients with thyroid disease by evaluating the factor structure, measurement equivalence, known-groups validity, and predictive validity of a broad set of work ability items. Based on the literature and interviews with thyroid patients, 24 work ability items were selected from previous questionnaires, revised, or developed anew. Items were tested among 632 patients with thyroid disease (non-toxic goiter, toxic nodular goiter, Graves' disease (with or without orbitopathy), autoimmune hypothyroidism, and other thyroid diseases), 391 of which had participated in a study 5 years previously. Responses to select items were compared to general population data. We used confirmatory factor analyses for categorical data, logistic regression analyses and tests of differential item function, and head-to-head comparisons of relative validity in distinguishing known groups. Although all work ability items loaded on a common factor, the optimal factor solution included five factors: role physical, role emotional, thyroid-specific limitations, work limitations (without disease attribution), and work performance. The scale on thyroid-specific limitations showed the most power in distinguishing clinical groups and time since diagnosis. A global single item proved useful for comparisons with the general population, and a thyroid-specific item predicted labor market exclusion within the next 5 years (OR 5.0, 95 % CI 2.7-9.1). Items on work limitations with attribution to thyroid disease were most effective in detecting impact on work ability and showed good predictive validity. Generic work ability items remain useful for general population comparisons.

Diagnostic value of contrast-enhanced ultrasound in thyroid nodules with calcification.

PubMed

Jiang, Jue; Shang, Xu; Wang, Hua; Xu, Yong-Bo; Gao, Ya; Zhou, Qi

2015-03-01

The aim of this study was to investigate the diagnostic values of conventional ultrasound and contrast-enhanced ultrasound (CEUS) in benign and malignant thyroid nodules with calcification. Conventional ultrasound and CEUS were performed in 122 patients with thyroid nodules with calcification. The thyroid nodules were characterized as benign or malignant by pathological diagnosis. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accordance rate of the two imaging methods were determined. The area under the receiver operating characteristics curve (AUC) was used to assess the diagnostic values of the two imaging methods. In 122 cases of thyroid nodules with calcification, 73 benign nodules and 49 malignant nodules were verified by pathological diagnosis. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accordance rate of conventional ultrasound were 50%, 77%, 59%, 69%, and 66%, respectively, and those of CEUS were 90%, 92%, 88%, 93%, and 91%, respectively. There were significant differences between the two imaging methods. AUCs of conventional ultrasound and CEUS were 0.628 ± 0.052 and 0.908 ± 0.031, suggesting low and high diagnostic values, respectively. CEUS has high diagnostic values, being significantly greater than those of conventional ultrasound, in differential diagnosis of benign and malignant thyroid nodules with calcification. Copyright © 2014. Published by Elsevier Taiwan.

A predictive mathematical model for the calculation of the final mass of Graves' disease thyroids treated with 131I

NASA Astrophysics Data System (ADS)

Traino, Antonio C.; Di Martino, Fabio; Grosso, Mariano; Monzani, Fabio; Dardano, Angela; Caraccio, Nadia; Mariani, Giuliano; Lazzeri, Mauro

2005-05-01

Substantial reductions in thyroid volume (up to 70-80%) after radioiodine therapy of Graves' hyperthyroidism are common and have been reported in the literature. A relationship between thyroid volume reduction and outcome of 131I therapy of Graves' disease has been reported by some authors. This important result could be used to decide individually the optimal radioiodine activity A0 (MBq) to administer to the patient, but a predictive model relating the change in gland volume to A0 is required. Recently, a mathematical model of thyroid mass reduction during the clearance phase (30-35 days) after 131I administration to patients with Graves' disease has been published and used as the basis for prescribing the therapeutic thyroid absorbed dose. It is well known that the thyroid volume reduction goes on until 1 year after therapy. In this paper, a mathematical model to predict the final mass of Graves' diseased thyroids submitted to 131I therapy is presented. This model represents a tentative explanation of what occurs macroscopically after the end of the clearance phase of radioiodine in the gland (the so-called second-order effects). It is shown that the final thyroid mass depends on its basal mass, on the radiation dose absorbed by the gland and on a constant value α typical of thyroid tissue. α has been evaluated based on a set of measurements made in 15 reference patients affected by Graves' disease and submitted to 131I therapy. A predictive equation for the calculation of the final mass of thyroid is presented. It is based on macroscopic parameters measurable after a diagnostic 131I capsule administration (0.37-1.85 MBq), before giving the therapy. The final mass calculated using this equation is compared to the final mass of thyroid measured 1 year after therapy administration in 22 Graves' diseased patients. The final masses calculated and measured 1 year after therapy are in fairly good agreement (R = 0.81). The possibility, for the physician, to decide a therapeutic activity based on the desired decrease of thyroid mass instead of on a fixed thyroid absorbed dose could be a new opportunity to cure Graves' disease.

Age impact on autoimmune thyroid disease in females

NASA Astrophysics Data System (ADS)

Stoian, Dana; Craciunescu, Mihalea; Timar, Romulus; Schiller, Adalbert; Pater, Liana; Craina, Marius

2013-10-01

Thyroid autoimmune disease, a widespread phenomenon in female population, impairs thyroid function during pregnancy. Identifying cases, which will develop hypothyroidism during pregnancy, is crucial in the follow-up process. The study group comprised 108 females, with ages between 20-40 years; with known inactive autoimmune thyroid disease, before pregnancy that became pregnant in the study follow-up period. They were monitored by means of clinical, hormonal and immunological assays. Supplemental therapy with thyroid hormones was used, where needed. Maternal age and level of anti-thyroid antibodies were used to predict thyroid functional impairment.

Thyroid Cancer Risk Assessment Tool

Cancer.gov

The R package thyroid implements a risk prediction model developed by NCI researchers to calculate the absolute risk of developing a second primary thyroid cancer (SPTC) in individuals who were diagnosed with a cancer during their childhood.

The predictive value of MRI in detecting thyroid gland invasion in patients with advanced laryngeal or hypopharyngeal carcinoma.

PubMed

Lin, Peiliang; Huang, Xiaoming; Zheng, Chushan; Cai, Qian; Guan, Zhong; Liang, Faya; Zheng, Yiqing

2017-01-01

The aim of this study was to evaluate the predictive value of magnetic resonance imaging (MRI) in detecting thyroid gland invasion (TGI) in patients with advanced laryngeal or hypopharyngeal carcinoma. In a retrospective chart review, 41 patients with advanced laryngeal or hypopharyngeal carcinoma underwent MRI scan before total laryngectomy and ipsilateral or bilateral thyroidectomy during the past 5 years. The MRI findings were compared with the postoperative pathological results. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Among the 41 patients, 3 had thyroid gland invasion in postoperative pathological results. MRI correctly predicted the absence of TGI in 37 of 38 patients and TGI in all 3 patients. The sensitivity, specificity, PPV, and NPV of MRI were 100.0, 97.4, 75.0, and 100 %, respectively, with the diagnostic accuracy of 97.6 %. In consideration of the high negative predictive value of MRI, it may help surgeons selectively preserve thyroid gland in total laryngectomy and reduce the incidence of hypothyroidism and hypoparathyroidism postoperatively.

Efficacy of preoperative neck ultrasound in the detection of cervical lymph node metastasis from thyroid cancer.

PubMed

Hwang, Harry S; Orloff, Lisa A

2011-03-01

This study was performed to assess the diagnostic accuracy of surgeon-performed preoperative neck ultrasound (US) in the detection of both central and lateral cervical lymph node metastases from thyroid cancer. Prospective cohort study. Data for all patients with thyroid cancers and follicular thyroid lesions who were evaluated by means of preoperative neck US were reviewed. The cervical lymph nodes were assessed for suspicion of metastasis based on US characteristics. The diagnostic accuracy of US was determined according to whether histologically confirmed cancer was present in surgical cervical lymph node specimens. The sensitivity and specificity of US in predicting papillary thyroid carcinoma (PTC) metastasis in the central neck were 30.0% and 86.8%, respectively. The sensitivity and specificity of US in predicting metastasis in the lateral neck were 93.8% and 80.0%, respectively. A subset of patients underwent US followed by revision neck dissection for PTC, and the sensitivity and specificity of US in predicting metastasis in the lateral neck were 100% and 100%, respectively. Preoperative neck US is a valuable tool in assessing patients with thyroid cancers. The highly sensitive and specific nature of US in predicting cervical lymph node metastasis in the lateral neck, especially in the setting of recurrent disease, can provide reliable information to assist in surgical management. Although US for central compartment lymphadenopathy in the presence of the thyroid gland is less sensitive and specific than US for the lateral neck, it still provides useful information that can be obtained at the same time the primary thyroid pathology is assessed. Copyright © 2010 The American Laryngological, Rhinological, and Otological Society, Inc.

PREDICTION OF RELAPSE FROM HYPERTHYROIDISM FOLLOWING ANTITHYROID MEDICATION WITHDRAWAL USING TECHNETIUM THYROID UPTAKE SCANNING.

PubMed

Nakhjavani, Manouchehr; Abdollahi, Soraya; Farzanefar, Saeed; Abousaidi, Mohammadtagi; Esteghamati, Alireza; Naseri, Maryam; Eftekhari, Mohamad; Abbasi, Mehrshad

2017-04-02

Technetium thyroid uptake (TTU) is not inhibited by antithyroid drugs (ATD) and reflects the degree of thyroid stimulation. We intended to predict the relapse rate from hyperthyroidism based on TTU measurement. Out of 44 initially enrolled subjects, 38 patients aged 41.6 ± 14.6 with Graves disease (duration: 84 ± 78 months) completed the study. TTU was performed with 40-second imaging of the neck and mediastinum 20 minutes after injection of 1 mCi technetium-99m pertechnetate. TTU was measured as the percentage of the count of activity accumulated in the thyroidal region minus the mediastinal background uptake to the count of 1 mCi technetium-99m under the same acquisition conditions. Then methimazole was stopped and patients were followed. The optimal TTU cutoff value for Graves relapse prediction was calculated using Youden's J statistic. Hyperthyroidism relapsed in 11 (28.9%) patients 122 ± 96 (range: 15-290) days post-ATD withdrawal. The subjects in remission were followed for 209 ± 81 days (range: 88-390). TTU was significantly higher in patients with forthcoming relapse (12.0 ± 8.0 vs. 3.9 ± 2.0, P = .007). The difference was significant after adjustment for age, sex, history of previous relapse, disease duration, and thyroid-stimulating hormone (TSH) levels before withdrawal. The area under the receiver operative characteristic (ROC) curve was 0.87. The optimal TTU cutoff value for classification of subjects with relapse and remission was 8.7 with sensitivity, specificity, and positive and negative predictive value of 73%, 100%, 100%, and 90%, respectively (odds ratio [OR] = 10.0; 95% confidence interval [CI]: 3.4-29.3). TTU evaluation in hyperthyroid patients receiving antithyroid medication is an accurate and practical method for predicting relapse after ATD withdrawal. ATD = antithyroid drugs RIU = radio-iodine uptake TSH = thyroid-stimulating hormone TSI = thyroid-stimulating immunoglobulin TTU = technetium thyroid uptake.

Neoadjuvant chemotherapy prior to radical cystectomy for muscle-invasive bladder cancer with variant histology.

PubMed

Vetterlein, Malte W; Wankowicz, Stephanie A M; Seisen, Thomas; Lander, Richard; Löppenberg, Björn; Chun, Felix K-H; Menon, Mani; Sun, Maxine; Barletta, Justine A; Choueiri, Toni K; Bellmunt, Joaquim; Trinh, Quoc-Dien; Preston, Mark A

2017-11-15

Neoadjuvant chemotherapy in pure urothelial bladder cancer provides a significant survival benefit. However, to the authors' knowledge, it is unknown whether this benefit persists in histological variants. The objective of the current study was to assess the effect of neoadjuvant chemotherapy on the probability of non-organ-confined disease and overall survival after radical cystectomy (RC) in patients with histological variants. Querying the National Cancer Data Base, the authors identified 2018 patients with histological variants who were undergoing RC for bladder cancer between 2003 and 2012. Variants were categorized as micropapillary or sarcomatoid differentiation, squamous cell carcinoma, adenocarcinoma, neuroendocrine tumors, and other histology. Logistic regression models estimated the odds of non-organ-confined disease at the time of RC for each histological variant, stratified by the receipt of neoadjuvant chemotherapy. Cox regression models were used to examine the effect of neoadjuvant chemotherapy on overall mortality in each variant subgroup. Patients with neuroendocrine tumors (odds ratio [OR], 0.16; 95% confidence interval [95% CI], 0.08-0.32 [P<.001]), micropapillary differentiation (OR, 0.30; 95% CI, 0.10-0.95 [P=.041]), sarcomatoid urothelial carcinoma (OR, 0.40; 95% CI, 0.17-0.94 [P=.035]), and adenocarcinoma (OR, 0.24; 95% CI, 0.06-0.91 [P=.035]) were less likely to harbor non-organ-confined disease at the time of RC when treated with neoadjuvant chemotherapy. An overall survival benefit for neoadjuvant chemotherapy was only found in patients with neuroendocrine tumors (hazard ratio, 0.49; 95% CI, 0.33-0.74 [P=.001]). Patients with neuroendocrine tumors benefit from neoadjuvant chemotherapy, as evidenced by better overall survival and lower rates of non-organ-confined disease at the time of RC. For tumors with micropapillary differentiation, sarcomatoid differentiation, or adenocarcinoma, neoadjuvant chemotherapy decreased the frequency of non-organ-confined disease at the time of RC. However, this favorable effect did not translate into a statistically significant overall survival benefit for these patients, potentially due to the aggressive tumor biology. Cancer 2017;123:4346-55. © 2017 American Cancer Society. © 2017 American Cancer Society.

Web-based thyroid imaging reporting and data system: Malignancy risk of atypia of undetermined significance or follicular lesion of undetermined significance thyroid nodules calculated by a combination of ultrasonography features and biopsy results.

PubMed

Choi, Young Jun; Baek, Jung Hwan; Shin, Jung Hee; Shim, Woo Hyun; Kim, Seon-Ok; Lee, Won-Hong; Song, Dong Eun; Kim, Tae Yong; Chung, Ki-Wook; Lee, Jeong Hyun

2018-05-13

The purpose of this study was to construct a web-based predictive model using ultrasound characteristics and subcategorized biopsy results for thyroid nodules of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) to stratify the risk of malignancy. Data included 672 thyroid nodules from 656 patients from a historical cohort. We analyzed ultrasound images of thyroid nodules and biopsy results according to nuclear atypia and architectural atypia. Multivariate logistic regression analysis was performed to predict whether nodules were diagnosed as malignant or benign. The ultrasound features, including spiculated margin, marked hypoechogenicity, calcifications, biopsy results, and cytologic atypia, showed significant differences between groups. A 13-point risk scoring system was developed, and the area under the curve (AUC) of the receiver operating characteristic (ROC) curve of the development and validation sets were 0.837 and 0.830, respectively (http://www.gap.kr/thyroidnodule_b3.php). We devised a web-based predictive model using the combined information of ultrasound characteristics and biopsy results for AUS/FLUS thyroid nodules to stratify the malignant risk. © 2018 Wiley Periodicals, Inc.

Thyroid paraganglioma. Report of 3 cases and description of an immunohistochemical profile useful in the differential diagnosis with medullary thyroid carcinoma, based on complementary DNA array results.

PubMed

Castelblanco, Esmeralda; Gallel, Pilar; Ros, Susana; Gatius, Sonia; Valls, Joan; De-Cubas, Aguirre A; Maliszewska, Agnieszka; Yebra-Pimentel, M Teresa; Menarguez, Javier; Gamallo, Carlos; Opocher, Giuseppe; Robledo, Mercedes; Matias-Guiu, Xavier

2012-07-01

Thyroid paraganglioma is a rare disorder that sometimes poses problems in differential diagnosis with medullary thyroid carcinoma. So far, differential diagnosis is solved with the help of some markers that are frequently expressed in medullary thyroid carcinoma (thyroid transcription factor 1, calcitonin, and carcinoembryonic antigen). However, some of these markers are not absolutely specific of medullary thyroid carcinoma and may be expressed in other tumors. Here we report 3 new cases of thyroid paraganglioma and describe our strategy to design a diagnostic immunohistochemical battery. First, we performed a comparative analysis of the expression profile of head and neck paragangliomas and medullary thyroid carcinoma, obtained after complementary DNA array analysis of 2 series of fresh-frozen samples of paragangliomas and medullary thyroid carcinoma, respectively. Seven biomarkers showing differential expression were selected (nicotinamide adenine dinucleotide dehydrogenase 1 alpha subcomplex, 4-like 2, NDUFA4L2; cytochrome c oxidase subunit IV isoform 2; vesicular monoamine transporter 2; calcitonin gene-related protein/calcitonin; carcinoembryonic antigen; and thyroid transcription factor 1) for immunohistochemical analysis. Two tissue microarrays were constructed from 2 different series of paraffin-embedded samples of paragangliomas and medullary thyroid carcinoma. We provide a classifying rule for differential diagnosis that combines negativity or low staining for calcitonin gene-related protein (histologic score, <10) or calcitonin (histologic score, <50) together with positivity of any of NADH dehydrogenase 1 alpha subcomplex, 4-like 2; cytochrome c oxidase subunit IV isoform 2; or vesicular monoamine transporter 2 to predict paragangliomas, showing a prediction error of 0%. Finally, the immunohistochemical battery was checked in paraffin-embedded blocks from 4 examples of thyroid paraganglioma (1 previously reported case and 3 new cases), showing also a prediction error of 0%. Our results suggest that the comparative expression profile, obtained by complementary DNA arrays, seems to be a good tool to design immunohistochemical batteries used in differential diagnosis. Copyright © 2012 Elsevier Inc. All rights reserved.

Need of tetraiodothyronine supplemental therapy in pregnant women

NASA Astrophysics Data System (ADS)

Stoian, Dana; Craciunescu, Mihalea; Timar, Romulus; Schiller, Adalbert; Pater, Liana; Craina, Marius

2013-10-01

Thyroid hormones are essential for fetal development. Normal thyroid function in pregnant women adjusts by itself in cases of pregnancy, phenomenon that is deficient in cases of previous maternal thyroid disease. The study group was represented by 120 females, with reproductive age, with known thyroid disease, that had a up to delivery pregnancy. Thyroid ultrasound parameters and functional parameters were follow-up during the 9-month of gestation. The study proposes a mathematical model of predicting the need and the amount of tetraiodothyronine treatment in pregnant women with prevalent thyroid disease.

Incorporating thyroid markers in Down syndrome screening protocols.

PubMed

Dhaifalah, Ishraq; Salek, Tomas; Langova, Dagmar; Cuckle, Howard

2017-05-01

The article aimed to assess the benefit of incorporating maternal serum thyroid disease marker levels (thyroid-stimulating hormone and free thyroxine) into first trimester Down syndrome screening protocols. Statistical modelling was used to predict performance with and without the thyroid markers. Two protocols were considered: the combined test and the contingent cell-free DNA (cfDNA) test, where 15-40% women are selected for cfDNA because of increased risk based on combined test results. Published parameters were used for the combined test, cfDNA and the Down syndrome means for thyroid-stimulating hormone and free thyroxine; other parameters were derived from a series of 5230 women screened for both thyroid disease and Down syndrome. Combined test: For a fixed 85% detection rate, the predicted false positive rate was reduced from 5.3% to 3.6% with the addition of the thyroid markers. Contingent cfDNA test: For a fixed 95% detection rate, the proportion of women selected for cfDNA was reduced from 25.6% to 20.2%. When screening simultaneously for maternal thyroid disease and Down syndrome, thyroid marker levels should be used in the calculation of Down syndrome risk. The benefit is modest but can be achieved with no additional cost. © 2017 John Wiley & Sons, Ltd. © 2017 John Wiley & Sons, Ltd.

Optimizing treatment for children and adolescents with papillary thyroid carcinoma in post-Chernobyl exposed region: The roles of lymph node dissections in the central and lateral neck compartments.

PubMed

Fridman, Mikhail; Krasko, Olga; Lam, Alfred King-Yin

2018-06-01

There is lack of data to predict lymph node metastases in pediatric thyroid cancer. The aims are to study (1) the factors affecting the lymph node metastases in children and adolescence with papillary thyroid carcinoma in region exposed to radiation and (2) to evaluate the predictive significance of these factors for lateral compartment lymphadenectomy. Five hundred and nine patients with papillary thyroid carcinoma underwent total thyroidectomy and lymph nodes resection (central and lateral compartments of the neck) surgery during the period of 1991-2010 in Belarus were recruited. The factors related to lymph node metastases were studied in these patients. In the patients with papillary thyroid carcinoma, increase number of cancer-positive lymph nodes in the central neck compartment were associated with a risk to develop lateral nodal disease as well as bilateral nodal disease. Futhermore, positive lateral compartment nodal metastases are associated with age and gender of the patients, tumour size, minimal extra-thyroidal extension, solid architectonic, extensive desmoplasia in carcinoma, presence of psammoma bodies, extensive involvement of the thyroid and metastatic ratio index revealed after examination of the central cervical chain lymph nodes. The presence of nodal disease, degree of lymph node involvement and the distribution of lymph node metastases significantly increase the recurrence rates of patients with papillary thyroid carcinoma. To conclude, the lymph nodes metastases in young patients with papillary thyroid carcinoma in post-Chernobyl exposed region are common and the pattern could be predicted by many clinical and pathological factors. Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Epithelial borderline ovarian tumor: Diagnosis and treatment strategy.

PubMed

Ushijima, Kimio; Kawano, Kouichiro; Tsuda, Naotake; Nishio, Shin; Terada, Atsumu; Kato, Hiroyuki; Tasaki, Kazuto; Matsukuma, Ken

2015-05-01

Epithelial borderline ovarian tumors (BOT) are distinctive from benign tumors and carcinoma. They occur in younger women more often than carcinoma, and there is some difficulty making correct diagnosis of BOT. Two subtypes of BOT, serous and mucinous borderline tumor have different characteristics and very different clinical behavior. Serous borderline tumor (SBT) with micropapillary pattern shows more incidence of extra ovarian disease and often coexists with invasive implant. SBT with micropapillary pattern in advanced stage has showed a worse prognosis than typical SBT. Huge mucinous borderline tumors have histologic heterogeneity, and the accuracy of frozen section diagnosis is relatively low. Extensive sampling is required to reach a correct pathological diagnosis. Mucinous adenoma (intestinal type) also runs the risk of recurrence after cystectomy, or intraoperative rupture of cyst. Laparoscopic procedure for BOT has not increased the risk of recurrence. Fertility preserving procedures are generally accepted, except in advanced stage SBT with invasive implants. Only cystectomy shows a significant risk of recurrence. Re-staging surgery and full staging surgery is not necessary for all BOT. We should not attempt to treat them uniformly, by the single diagnosis of "borderline tumor". It depends on histologic type. Close communication with the pathologist is necessary to gain more detail and ask more pathological samples in order to make the optimal treatment strategy for each individual patients.

Utility of Quantitative Parameters from Single-Photon Emission Computed Tomography/Computed Tomography in Patients with Destructive Thyroiditis.

PubMed

Kim, Ji-Young; Kim, Ji Hyun; Moon, Jae Hoon; Kim, Kyoung Min; Oh, Tae Jung; Lee, Dong-Hwa; So, Young; Lee, Won Woo

2018-01-01

Quantitative parameters from Tc-99m pertechnetate single-photon emission computed tomography/computed tomography (SPECT/CT) are emerging as novel diagnostic markers for functional thyroid diseases. We intended to assess the utility of SPECT/CT parameters in patients with destructive thyroiditis. Thirty-five destructive thyroiditis patients (7 males and 28 females; mean age, 47.3 ± 13.0 years) and 20 euthyroid patients (6 males and 14 females; mean age, 45.0 ± 14.8 years) who underwent Tc-99m pertechnetate quantitative SPECT/CT were retrospectively enrolled. Quantitative parameters from the SPECT/CT (%uptake, standardized uptake value [SUV], thyroid volume, and functional thyroid mass [SUVmean × thyroid volume]) and thyroid hormone levels were investigated to assess correlations and predict the prognosis for destructive thyroiditis. The occurrence of hypothyroidism was the outcome for prognosis. All the SPECT/CT quantitative parameters were significantly lower in the 35 destructive thyroiditis patients compared to the 20 euthyroid patients using the same SPECT/CT scanner and protocol ( p < 0.001 for all parameters). T3 and free T4 did not correlate with any SPECT/CT parameters, but thyroid-stimulating hormone (TSH) significantly correlated with %uptake ( p = 0.004), SUVmean ( p < 0.001), SUVmax ( p = 0.002), and functional thyroid mass ( p < 0.001). Of the 35 destructive thyroiditis patients, 16 progressed to hypothyroidism. On univariate and multivariate analyses, only T3 levels were associated with the later occurrence of hypothyroidism ( p = 0.002, exp(β) = 1.022, 95% confidence interval: 1.008 - 1.035). Novel quantitative SPECT/CT parameters could discriminate patients with destructive thyroiditis from euthyroid patients, suggesting the robustness of the quantitative SPECT/CT approach. However, disease progression of destructive thyroiditis could not be predicted using the parameters, as these only correlated with TSH, but not with T3, the sole predictor of the later occurrence of hypothyroidism.

Utility of Quantitative Parameters from Single-Photon Emission Computed Tomography/Computed Tomography in Patients with Destructive Thyroiditis

PubMed Central

Kim, Ji-Young; Kim, Ji Hyun; Moon, Jae Hoon; Kim, Kyoung Min; Oh, Tae Jung; Lee, Dong-Hwa; So, Young

2018-01-01

Objective Quantitative parameters from Tc-99m pertechnetate single-photon emission computed tomography/computed tomography (SPECT/CT) are emerging as novel diagnostic markers for functional thyroid diseases. We intended to assess the utility of SPECT/CT parameters in patients with destructive thyroiditis. Materials and Methods Thirty-five destructive thyroiditis patients (7 males and 28 females; mean age, 47.3 ± 13.0 years) and 20 euthyroid patients (6 males and 14 females; mean age, 45.0 ± 14.8 years) who underwent Tc-99m pertechnetate quantitative SPECT/CT were retrospectively enrolled. Quantitative parameters from the SPECT/CT (%uptake, standardized uptake value [SUV], thyroid volume, and functional thyroid mass [SUVmean × thyroid volume]) and thyroid hormone levels were investigated to assess correlations and predict the prognosis for destructive thyroiditis. The occurrence of hypothyroidism was the outcome for prognosis. Results All the SPECT/CT quantitative parameters were significantly lower in the 35 destructive thyroiditis patients compared to the 20 euthyroid patients using the same SPECT/CT scanner and protocol (p < 0.001 for all parameters). T3 and free T4 did not correlate with any SPECT/CT parameters, but thyroid-stimulating hormone (TSH) significantly correlated with %uptake (p = 0.004), SUVmean (p < 0.001), SUVmax (p = 0.002), and functional thyroid mass (p < 0.001). Of the 35 destructive thyroiditis patients, 16 progressed to hypothyroidism. On univariate and multivariate analyses, only T3 levels were associated with the later occurrence of hypothyroidism (p = 0.002, exp(β) = 1.022, 95% confidence interval: 1.008 – 1.035). Conclusion Novel quantitative SPECT/CT parameters could discriminate patients with destructive thyroiditis from euthyroid patients, suggesting the robustness of the quantitative SPECT/CT approach. However, disease progression of destructive thyroiditis could not be predicted using the parameters, as these only correlated with TSH, but not with T3, the sole predictor of the later occurrence of hypothyroidism. PMID:29713225

The role of nerve monitoring to predict postoperative recurrent laryngeal nerve function in thyroid and parathyroid surgery.

PubMed

Eid, Issam; Miller, Frank R; Rowan, Stephanie; Otto, Randal A

2013-10-01

To determine the role and efficacy of intraoperative recurrent laryngeal nerve (RLN) stimulation in the prediction of early and permanent postoperative nerve function in thyroid and parathyroid surgery. A retrospective review of thyroid and parathyroid surgeries was performed with calculation of sensitivity and specificity of the response of intraoperative stimulation for different pathological groups. Normal electromyography (EMG) response with 0.5 mAmp stimulation was considered a positive stimulation response with postoperative function determined by laryngoscopy. No EMG response at >1-2 mAmps was considered a negative response. The rates of early and permanent paralysis, as well as sensitivity, specificity, and positive and negative predictive values for postoperative nerve function were calculated for separate pathological groups. The number of nerves at risk analyzed was 909. The overall early and permanent paralysis rates were 3.1% and 1.2%, respectively, with the highest rate being for Grave's disease cases. The overall sensitivity was 98.4%. The specificity was lower at 62.5% but acceptable in thyroid carcinoma and Grave's disease patients. The majority of nerves with a positive stimulation result and postoperative paralysis on laryngoscopy recovered function in 3 to 12 weeks, showing positive stimulation to be a good predictor of eventual recovery. Stimulation of the RLN during thyroid and parathyroid surgery is a useful tool in predicting postoperative RLN function. The sensitivity of stimulation is high, showing positive stimulation to be an excellent predictor of normal nerve function. Negative stimulation is more predictive of paralysis in cases of thyroid carcinoma and Grave's disease. 2b. Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

Gene Expression in Developing Brain is Altered by Modest Reductions in Circulating Levels of Thyroid Hormone.

EPA Science Inventory

Disruption of thyroid hormone (TH) homeostasis is a known effect of environmental contaminants. Although animal models of developmental TH deficiency can predict the impact of severe insults to the thyroid system, the effects of moderate TH insufficiencies have not been adequatel...

Predictive Modeling of a Mixture of Thyroid Hormone Disrupting Chemicals that Affect Production and Clearance of Thyroxine

EPA Science Inventory

Thyroid hormone (TH) disrupting compounds interfere with both thyroidal and extrathyroidal mechanisms to decrease circulating thyroxine (T4). This research tested the hypothesis that serum T4 concentrations of rodents exposed to a mixture of both TH synthesis inhibitors (pesticid...

Gene Expression as a Biomarker of Effect of Thyroid Hormone Action in Developing Brain: Relation to Serum Hormones.

EPA Science Inventory

Disruption of thyroid hormone (TH) homeostasis is a known effect of environmental contaminants. Although animal models of developmental TH deficiency can predict the impact of severe insults to the thyroid system, the effects of moderate TH insufficiencies have proved more diffic...

Dietary Iodine Sufficiency and Moderate Insufficiency in the Lactating Mother and Nursing Infant: A Computational Perspective

PubMed Central

Fisher, W.; Wang, Jian; George, Nysia I.; Gearhart, Jeffery M.; McLanahan, Eva D.

2016-01-01

The Institute of Medicine recommends that lactating women ingest 290 μg iodide/d and a nursing infant, less than two years of age, 110 μg/d. The World Health Organization, United Nations Children’s Fund, and International Council for the Control of Iodine Deficiency Disorders recommend population maternal and infant urinary iodide concentrations ≥ 100 μg/L to ensure iodide sufficiency. For breast milk, researchers have proposed an iodide concentration range of 150–180 μg/L indicates iodide sufficiency for the mother and infant, however no national or international guidelines exist for breast milk iodine concentration. For the first time, a lactating woman and nursing infant biologically based model, from delivery to 90 days postpartum, was constructed to predict maternal and infant urinary iodide concentration, breast milk iodide concentration, the amount of iodide transferred in breast milk to the nursing infant each day and maternal and infant serum thyroid hormone kinetics. The maternal and infant models each consisted of three sub-models, iodide, thyroxine (T4), and triiodothyronine (T3). Using our model to simulate a maternal intake of 290 μg iodide/d, the average daily amount of iodide ingested by the nursing infant, after 4 days of life, gradually increased from 50 to 101 μg/day over 90 days postpartum. The predicted average lactating mother and infant urinary iodide concentrations were both in excess of 100 μg/L and the predicted average breast milk iodide concentration, 157 μg/L. The predicted serum thyroid hormones (T4, free T4 (fT4), and T3) in both the nursing infant and lactating mother were indicative of euthyroidism. The model was calibrated using serum thyroid hormone concentrations for lactating women from the United States and was successful in predicting serum T4 and fT4 levels (within a factor of two) for lactating women in other countries. T3 levels were adequately predicted. Infant serum thyroid hormone levels were adequately predicted for most data. For moderate iodide deficient conditions, where dietary iodide intake may range from 50 to 150 μg/d for the lactating mother, the model satisfactorily described the iodide measurements, although with some variation, in urine and breast milk. Predictions of serum thyroid hormones in moderately iodide deficient lactating women (50 μg/d) and nursing infants did not closely agree with mean reported serum thyroid hormone levels, however, predictions were usually within a factor of two. Excellent agreement between prediction and observation was obtained for a recent moderate iodide deficiency study in lactating women. Measurements included iodide levels in urine of infant and mother, iodide in breast milk, and serum thyroid hormone levels in infant and mother. A maternal iodide intake of 50 μg/d resulted in a predicted 29–32% reduction in serum T4 and fT4 in nursing infants, however the reduced serum levels of T4 and fT4 were within most of the published reference intervals for infant. This biologically based model is an important first step at integrating the rapid changes that occur in the thyroid system of the nursing newborn in order to predict adverse outcomes from exposure to thyroid acting chemicals, drugs, radioactive materials or iodine deficiency. PMID:26930410

Dietary Iodine Sufficiency and Moderate Insufficiency in the Lactating Mother and Nursing Infant: A Computational Perspective.

PubMed

Fisher, W; Wang, Jian; George, Nysia I; Gearhart, Jeffery M; McLanahan, Eva D

2016-01-01

The Institute of Medicine recommends that lactating women ingest 290 μg iodide/d and a nursing infant, less than two years of age, 110 μg/d. The World Health Organization, United Nations Children's Fund, and International Council for the Control of Iodine Deficiency Disorders recommend population maternal and infant urinary iodide concentrations ≥ 100 μg/L to ensure iodide sufficiency. For breast milk, researchers have proposed an iodide concentration range of 150-180 μg/L indicates iodide sufficiency for the mother and infant, however no national or international guidelines exist for breast milk iodine concentration. For the first time, a lactating woman and nursing infant biologically based model, from delivery to 90 days postpartum, was constructed to predict maternal and infant urinary iodide concentration, breast milk iodide concentration, the amount of iodide transferred in breast milk to the nursing infant each day and maternal and infant serum thyroid hormone kinetics. The maternal and infant models each consisted of three sub-models, iodide, thyroxine (T4), and triiodothyronine (T3). Using our model to simulate a maternal intake of 290 μg iodide/d, the average daily amount of iodide ingested by the nursing infant, after 4 days of life, gradually increased from 50 to 101 μg/day over 90 days postpartum. The predicted average lactating mother and infant urinary iodide concentrations were both in excess of 100 μg/L and the predicted average breast milk iodide concentration, 157 μg/L. The predicted serum thyroid hormones (T4, free T4 (fT4), and T3) in both the nursing infant and lactating mother were indicative of euthyroidism. The model was calibrated using serum thyroid hormone concentrations for lactating women from the United States and was successful in predicting serum T4 and fT4 levels (within a factor of two) for lactating women in other countries. T3 levels were adequately predicted. Infant serum thyroid hormone levels were adequately predicted for most data. For moderate iodide deficient conditions, where dietary iodide intake may range from 50 to 150 μg/d for the lactating mother, the model satisfactorily described the iodide measurements, although with some variation, in urine and breast milk. Predictions of serum thyroid hormones in moderately iodide deficient lactating women (50 μg/d) and nursing infants did not closely agree with mean reported serum thyroid hormone levels, however, predictions were usually within a factor of two. Excellent agreement between prediction and observation was obtained for a recent moderate iodide deficiency study in lactating women. Measurements included iodide levels in urine of infant and mother, iodide in breast milk, and serum thyroid hormone levels in infant and mother. A maternal iodide intake of 50 μg/d resulted in a predicted 29-32% reduction in serum T4 and fT4 in nursing infants, however the reduced serum levels of T4 and fT4 were within most of the published reference intervals for infant. This biologically based model is an important first step at integrating the rapid changes that occur in the thyroid system of the nursing newborn in order to predict adverse outcomes from exposure to thyroid acting chemicals, drugs, radioactive materials or iodine deficiency.

Thyroid-stimulation hormone-receptor antibodies as a predictor of thyrosuppressive drug therapy outcome in Graves' disease patients.

PubMed

Aleksić, Aleksandar Z; Aleksić, Željka; Manić, Saška; Mitov, Vladimir; Jolić, Aleksandar

2014-01-01

Graves' disease is autoimmune hyperthyroidism caused by pathological stimulation of thyroid-stimulation hormone-receptor antibodies. The decision on changing the therapy can be made on time by determining the prognostic factors of thyrosuppressive drug therapy outcome. The aim of the study was to determine the significance of thyroid-stimulation hormone-receptor antibodies level on the prediction of therapy outcome. The study was prospective and involved 106 drug-treated patients with newly diagnosed Graves' disease. Thyroid-stimulation hormone-receptor antibodies level was measured at the beginning of therapy, during therapy and 12 months after it had been introduced. No statistically significant difference in the level of thyroid-stimulation hormone-receptor antibodies was found at the beginning of disease and 12 months after the introduction of thyrosuppressive drug therapy among the patients who had been in remission and those who had not. Regardless of the outcome, thyroid-stimulation hormone-receptor antibodies level significantly decreased in all patients 12 months after the therapy had been introduced. The level of thyroid-stimulation hormone-receptor antibodies at the beginning of disease and 12 months after the introduction of therapy cannot predict the outcome of thyrosuppressive drug therapy.

The reliability of fine-needle aspiration biopsy in terms of malignancy in patients with Hashimoto thyroiditis.

PubMed

Kapan, Murat; Onder, Akin; Girgin, Sadullah; Ulger, Burak Veli; Firat, Ugur; Uslukaya, Omer; Oguz, Abdullah

2015-02-01

The aim of this study was to analyze the presence of malignancy in patients with Hashimoto's thyroiditis and to investigate the reliability of preoperative fine-needle aspiration biopsy (FNAB). The retrospective study included 44 patients who were operated on for nodular goiter between December 2010 and October 2011. The patients underwent thyroidectomy following a cytologic analysis plus FNAB. Hashimoto's thyroiditis was confirmed on histopathology in all patients. FNAB results were defined as benign in 14 (31.8%), suspicion for malignancy in 17 (38.6%), malignant in 9 (20.5%), and inadequate in 4 (9.1%). Following the thyroidectomy, presence of papillary thyroid carcinoma and follicular variant of papillary thyroid carcinoma were detected in 10 patients (22.7%) and 1 (2.3%) patient, respectively. The FNAB results were interpreted in terms of malignancy, which revealed the sensitivity as 80%; specificity, 40%; false positives, 69.2%; false negatives, 14.3%; positive predictive value, 31.8%; negative predictive value, 85.7%; and diagnostic accuracy, 50%. The coexistence of Hashimoto's thyroiditis with papillary thyroid carcinoma is quite common. The FNAB results for such cases are hard to evaluate, and they are likely to increase the number of false positives.

Accuracy of increased thyroid activity during pertechnetate scintigraphy by subcutaneous injection for diagnosing hyperthyroidism in cats.

PubMed

Page, Richard B; Scrivani, Peter V; Dykes, Nathan L; Erb, Hollis N; Hobbs, Jeff M

2006-01-01

Our purpose was to determine the accuracy of increased thyroid activity for diagnosing hyperthyroidism in cats suspected of having that disease during pertechnetate scintigraphy using subcutaneous rather than intravenous radioisotope administration. Increased thyroid activity was determined by two methods: the thyroid:salivary ratio (T:S) and visual inspection. These assessments were made on the ventral scintigram of the head and neck. Scintigraphy was performed by injecting sodium pertechnetate (111 MBq, SQ) in the right-dorsal-lumbar region; static-acquisition images were obtained 20 min after injection. We used 49 cats; 34 (69%) had hyperthyroidism based on serum-chemistry analysis. Using a Wilcoxon's rank-sum test, a significant difference (P < 0.0001) was detected in the T:S between cats with and without hyperthyroidism. Using a decision criterion of 2.0 for the T:S, the test accurately predicted hyperthyroidism in 32/34 cats (sensitivity, 94%; 95% confidence interval (CI), 85-100%) and correctly predicted that hyperthyroidism was absent in 15/15 cats (specificity, 100%; CI, 97-100%). Using visual inspection, the test accurately predicted hyperthyroidism in 34/34 cats (sensitivity, 100%; CI, 99-100%) and correctly predicted that hyperthyroidism was absent in 12/15 cats (specificity, 80%; CI, 56-100%). The positive and negative predictive values were high for a wide range of prevalence of hyperthyroidism. And, the test had excellent agreement within and between examiners. Therefore, detecting increased thyroid activity during pertechnetate scintigraphy by subcutaneous injection is an accurate and reproducible test for feline hyperthyroidism.

Notch3 expression correlates with thyroid cancer differentiation, induces apoptosis, and predicts disease prognosis.

PubMed

Somnay, Yash R; Yu, Xiao-Min; Lloyd, Ricardo V; Leverson, Glen; Aburjania, Zviadi; Jang, Samuel; Jaskula-Sztul, Renata; Chen, Herbert

2017-03-01

Thyroid tumorigenesis is characterized by a progressive loss of differentiation exhibited by a range of disease variants. The Notch receptor family (1-4) regulates developmental progression in both normal and cancerous tissues. This study sought to characterize the third Notch isoform (Notch3) across the various differentiated states of thyroid cancer, and determine its clinical impact. Notch3 expression was analyzed in a tissue microarray of normal and pathologic thyroid biopsies from 155 patients. The functional role of Notch3 was then investigated by upregulating its expression in a follicular thyroid cancer (FTC) cell line. Notch3 expression regressed across decreasingly differentiated, increasingly malignant thyroid specimens, correlated with clinicopathological attributes reflecting poor prognosis, and independently predicted survival following univariate and multivariate analyses. Overexpression of the active Notch3 intracellular domain (NICD3) in a gain-of-function FTC line led to functional activation of centromere-binding protein 1, while increasing thyroid-specific gene transcription. NICD3 induction also reduced tumor burden in vivo and initiated the intrinsic apoptotic cascade, alongside suppressing cyclin and B-cell lymphoma 2 family expression. Loss of Notch3 expression may be fundamental to the process of dedifferentiation that accompanies thyroid oncogenesis. Conversely, activation of Notch3 in thyroid cancer exerts an antiproliferative effect and restores elements of a differentiated phenotype. These findings provide preclinical rationale for evaluating Notch3 as a disease prognosticator and therapeutic target in advanced thyroid cancer. Cancer 2017;123:769-82. © 2016 American Cancer Society. © 2016 American Cancer Society.

Next-Generation Sequencing Identifies Gene Mutations That Are Predictive of Malignancy in Residual Needle Rinses Collected From Fine-Needle Aspirations of Thyroid Nodules.

PubMed

Fuller, Maren Y; Mody, Dina; Hull, April; Pepper, Kristi; Hendrickson, Heather; Olsen, Randall

2018-02-01

- Thyroid nodules have a prevalence of approximately 70% in adults. Fine-needle aspiration (FNA) is a minimally invasive, cost-effective, standard method to collect tissue from thyroid nodules for cytologic examination. However, approximately 15% of thyroid FNA specimens cannot be unambiguously diagnosed as benign or malignant. - To investigate whether clinically actionable data can be obtained using next-generation sequencing of residual needle rinse material. - A total of 24 residual needle rinse specimens with malignant (n = 6), indeterminate (n = 9), or benign (n = 9) thyroid FNA diagnoses were analyzed in our clinical molecular diagnostics laboratory using next-generation sequencing assays designed to detect gene mutations and translocations that commonly occur in thyroid cancer. Results were correlated with surgical diagnoses and clinical outcomes. - Interpretable data were generated from 23 of 24 residual needle rinse specimens. Consistent with its well-known role in thyroid malignancy, BRAF V600E mutations were detected in 4 malignant cases. An NRAS mutation was detected in 1 benign case. No mutations were detected from specimens with indeterminate diagnoses. - Our data demonstrate that residual thyroid FNA needle rinses are an adequate source of material for molecular diagnostic testing. Importantly, detection of a mutation implicated in thyroid malignancy was predictive of the final surgical diagnosis and clinical outcome. Our strategy to triage thyroid nodules with indeterminate cytology with molecular testing eliminates the need to perform additional FNA passes into dedicated media or to schedule additional invasive procedures. Further investigation with a larger sample size to confirm the clinical utility of our proposed strategy is underway.

Subclinical thyroid dysfunction and circulating thyroid hormones are not associated with bone turnover markers or incident hip fracture in older men.

PubMed

Siru, Ranita; Alfonso, Helman; Chubb, S A Paul; Golledge, Jonathan; Flicker, Leon; Yeap, Bu B

2018-04-14

Overt thyroid dysfunction is a risk factor for osteoporosis and fractures. Subclinical hyperthyroidism has also been associated with fracture. It remains unclear whether variation in thyroid hormones within the euthyroid range modulates bone health, particularly among older men. We assessed whether thyroid stimulating hormone (TSH) and free thyroxine (FT4) are associated with bone turnover markers (BTMs) and predict hip fracture risk in community-dwelling older men without known thyroid disease. Prospective cohort study. 4248 men aged 70-89 years. Baseline blood samples were assayed for TSH, FT4, total osteocalcin (TOC), undercarboxylated osteocalcin (ucOC), N-terminal propeptide of type I collagen (P1NP) and collagen type I C-terminal cross-linked telopeptide (CTX). Incidence of hip fracture events was ascertained to 2012. Associations of TSH and FT4 with BTMs were analysed at baseline using Pearson correlation coefficients, and with incident hip fracture using Cox proportional hazards regression. After excluding men with pre-existing thyroid or bone disease, there were 3, 338 men for analysis. Of these, 3, 117 were euthyroid, 135 had subclinical hypothyroidism and 86 had subclinical hyperthyroidism. Men with subclinical thyroid disease were older and those with subclinical hyperthyroidism had lower creatinine than the other groups. After multivariate analysis, there was no association found between FT4, TSH or subclinical thyroid dysfunction and BTMs at baseline. Neither subclinical thyroid dysfunction, TSH nor FT4 were predictive of incident hip fracture in our study population. In euthyroid older men, TSH and FT4 were not associated with BTMs or incident hip fracture. Our findings differ from those previously described in post-menopausal women. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Fine-Needle Aspiration, Touch Imprint, and Crush Preparation Cytology for Diagnosing Thyroid Malignancies in Thyroid Nodules.

PubMed

Ahmadinejad, Mojtaba; Aliepour, Asghar; Anbari, Khatereh; Kaviani, Mojhgan; Ganjizadeh, Hasan; Nadri, Sedigheh; Foroutani, Niloufar; Meysami, Masoumeh; Almasi, Vahid

2015-12-01

Several methods are used to evaluate the thyroid nodules. The aim of this study was to determine the sensitivity, specificity, false positive and negative rates, positive predictive value (PPV), and negative predictive value (NPV) of touch imprint, crush preparation, and fine-needle aspiration (FNA) methods. This cross-sectional study was done in Shohada-ye Ashayer University Hospital in Khorramabad. All the patients who underwent thyroid surgery due to thyroid nodules in this hospital between March and September 2011 were evaluated. The thyroid nodules of all the patients were evaluated by touch imprint, crush preparation, FNA, and permanent pathology methods. Finally, the results of the first three methods were compared with the result of permanent pathology method. The mean age of 104 patients who underwent thyroid surgery was 42.6 ± 11.9 years old. Based on permanent pathology, touch imprint, crush preparation, and FNA methods, 15.3, 6.25, 6.25, and 4.4 % of thyroid nodules were malignant, respectively. Sensitivity, specificity, false positive rate, false negative rate, PPV, and NPV of FNA biopsy were 62.5, 100, 0, 37.5, 100, and 95.3 %, respectively. Also, sensitivity, specificity, false positive rate, false negative rate, PPV, and NPV of touch imprint and crush preparation were equal and were 80, 100, 0, 20, 100, and 96.7 %, respectively. Using touch imprint and crush preparation in evaluation of thyroid nodules for rapid evaluation of these nodules in operating rooms seems to be logical, and it can prevent further surgeries.

Thyroid hypoechogenicity after methimazole withdrawal in Graves' disease: a useful index for predicting recurrence?

PubMed

Zingrillo, M; D'Aloiso, L; Ghiggi, M R; Di Cerbo, A; Chiodini, I; Torlontano, M; Liuzzi, A

1996-08-01

A characteristic thyroid ultrasonographic picture with diffuse or scattered low echogenicity has been described in Graves' disease (GD). Thyroid hypoechogenicity in GD at onset has been considered a prognostic index of relapse after medical treatment; moreover, thyroid hypoechogenicity is regularly observed in GD at the onset, but not in patients with 'burned-out' disease. The aim of this study was to evaluate the usefulness of thyroid hypoechogenicity changes in predicting GD relapse. Longitudinal prospective study of previously untreated patients with GD. Thirty-nine consecutive patients aged 10-72 years were treated with methimazole (MMI) for 12-24 months on a titration regimen. Evaluation of patients in remission or with relapse was done 12 and 24 months after MMI withdrawal. Thyroid ultrasonography and TSH receptor antibodies (TRAb) were evaluated in basal conditions and then one month after MMI withdrawal. Thyroid hypoechogenicity score (assessed by the same observer with the same equipment) was graded as: 0 absent; 1 mild; 2 moderate; 3 marked. At the withdrawal evaluation a score < 2 and a TRAb value < 10 U/l were considered as normal. Twelve and 24 months after withdrawal, there were 10 (25.6%) and 17 (44.7%) relapses, respectively. Neither thyroid hypoechogenicity score nor TRAb values evaluated in basal conditions, showed significant differences between patients remaining euthyroid and those who became again hyperthyroid. In the whole group, the thyroid hypoechogenicity score was significantly lower at the withdrawal than in basal conditions (1.1 +/- 1.1 vs 2 +/- 0.8; P < 0.0001); it was significantly lower in patients in remission (P < 0.001), but not in those who relapsed. The thyroid hypoechogenicity score at withdrawal was normal in 23/29 (79.3%) of patients still euthyroid and in 4/10 (40%) of those who relapsed up to the 12th month (P < 0.05); it was normal in 19/21 (90.4%) of patients still euthyroid and in 7/17 (41.2%) of those who relapsed up to the 24th month (P < 0.05). A normal thyroid hypoechogenicity score at withdrawal of MMI had a higher specificity (0.95) and sensitivity (0.59) with respect to TRAb values (0.86 and 0.53, respectively) for the prediction of the relapse of hyperthyroidism at the 24th month. Basal thyroid hypoechogenicity cannot be used as an index of relapse of GD. MMI treatment induces evident changes in thyroid hypoechogenicity, mainly in patients who subsequently go into remission. The absence or a low grade of thyroid hypoechogenicity after MMI treatment seems to be a favourable prognostic index of remission of hyperthyroidism in GD.

Predictive features associated with thyrotoxic storm and management.

PubMed

Bacuzzi, Alessandro; Dionigi, Gianlorenzo; Guzzetti, Luca; De Martino, Alessandro Ivan; Severgnini, Paolo; Cuffari, Salvatore

2017-10-01

Thyroid storm (TS) is an endocrine emergency characterized by rapid deterioration, associated with high mortality rate therefore rapid diagnosis and emergent treatment is mandatory. In the past, thyroid surgery was the most common cause of TS, but recent preoperative medication creates a euthyroid state before performing surgery. An active approach during perioperative period could determine an effective clinical treatment of this life-threating diseases. Recently, the Japan Thyroid Association and Japan Endocrine Society developed diagnostic criteria for TS focusing on premature and prompt diagnosis avoiding inopportune e useless drugs. This review analyses predictive features associated with thyrotoxic storm highlighting recent literature to optimize the patient quality of care.

A clinicopathologic prediction model for postoperative recurrence in stage Ia non-small cell lung cancer.

PubMed

Zhang, Yang; Sun, Yihua; Xiang, Jiaqing; Zhang, Yawei; Hu, Hong; Chen, Haiquan

2014-10-01

Controversy remains over the appropriate postoperative management for patients with stage Ia non-small cell lung cancer who underwent complete surgical resection as a result of a heterogeneous prognosis. We aimed to identify the predictive factors for recurrence in these patients to aid in the decision making. We reviewed 344 patients with stage Ia non-small cell lung cancer to analyze the associations between recurrence-free survival and the following clinicopathologic variables: age, gender, smoking history, family history, preoperative serum carcinoembryonic antigen level, type of surgical resection, tumor location, tumor histology, lymphovascular invasion, tumor differentiation, and pathologic T status. Cox multivariate survival analysis revealed that central tumor location (P=.019), stage T1b (P=.006), high histologic grade (including large cell carcinoma, solid predominant, micropapillary predominant, and invasive mucinous adenocarcinoma, P=.007), poor differentiation (P=.022), and lymphovascular invasion (P=.035) were independently associated with recurrence-free survival. A nomogram for predicting the probability of 3-year recurrence-free survival was developed using the 5 variables. This model shows good calibration, reasonable discrimination (concordance index=0.733), and small overfitting (2.6%) demonstrated by bootstrapping. We developed a clinicopathologic prediction model for postoperative recurrence in stage Ia non-small cell lung cancer. This model can help with the selection of appropriate postoperative therapeutic strategies for these patients. Copyright © 2014 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Organizational Changes to Thyroid Regulation in Alligator mississippiensis: Evidence for Predictive Adaptive Responses

PubMed Central

Boggs, Ashley S. P.; Lowers, Russell H.; Cloy-McCoy, Jessica A.; Guillette, Louis J.

2013-01-01

During embryonic development, organisms are sensitive to changes in thyroid hormone signaling which can reset the hypothalamic-pituitary-thyroid axis. It has been hypothesized that this developmental programming is a ‘predictive adaptive response’, a physiological adjustment in accordance with the embryonic environment that will best aid an individual's survival in a similar postnatal environment. When the embryonic environment is a poor predictor of the external environment, the developmental changes are no longer adaptive and can result in disease states. We predicted that endocrine disrupting chemicals (EDCs) and environmentally-based iodide imbalance could lead to developmental changes to the thyroid axis. To explore whether iodide or EDCs could alter developmental programming, we collected American alligator eggs from an estuarine environment with high iodide availability and elevated thyroid-specific EDCs, a freshwater environment contaminated with elevated agriculturally derived EDCs, and a reference freshwater environment. We then incubated them under identical conditions. We examined plasma thyroxine and triiodothyronine concentrations, thyroid gland histology, plasma inorganic iodide, and somatic growth at one week (before external nutrition) and ten months after hatching (on identical diets). Neonates from the estuarine environment were thyrotoxic, expressing follicular cell hyperplasia (p = 0.01) and elevated plasma triiodothyronine concentrations (p = 0.0006) closely tied to plasma iodide concentrations (p = 0.003). Neonates from the freshwater contaminated site were hypothyroid, expressing thyroid follicular cell hyperplasia (p = 0.01) and depressed plasma thyroxine concentrations (p = 0.008). Following a ten month growth period under identical conditions, thyroid histology (hyperplasia p = 0.04; colloid depletion p = 0.01) and somatic growth (body mass p<0.0001; length p = 0.02) remained altered among the contaminated sites. This work supports the hypothesis that embryonic EDC exposure or iodide imbalance could induce adult metabolic disease states, thereby stressing the need to consider the multiple environmental variables present during development. PMID:23383213

Development of multivariate NTCP models for radiation-induced hypothyroidism: a comparative analysis.

PubMed

Cella, Laura; Liuzzi, Raffaele; Conson, Manuel; D'Avino, Vittoria; Salvatore, Marco; Pacelli, Roberto

2012-12-27

Hypothyroidism is a frequent late side effect of radiation therapy of the cervical region. Purpose of this work is to develop multivariate normal tissue complication probability (NTCP) models for radiation-induced hypothyroidism (RHT) and to compare them with already existing NTCP models for RHT. Fifty-three patients treated with sequential chemo-radiotherapy for Hodgkin's lymphoma (HL) were retrospectively reviewed for RHT events. Clinical information along with thyroid gland dose distribution parameters were collected and their correlation to RHT was analyzed by Spearman's rank correlation coefficient (Rs). Multivariate logistic regression method using resampling methods (bootstrapping) was applied to select model order and parameters for NTCP modeling. Model performance was evaluated through the area under the receiver operating characteristic curve (AUC). Models were tested against external published data on RHT and compared with other published NTCP models. If we express the thyroid volume exceeding X Gy as a percentage (Vx(%)), a two-variable NTCP model including V30(%) and gender resulted to be the optimal predictive model for RHT (Rs = 0.615, p < 0.001. AUC = 0.87). Conversely, if absolute thyroid volume exceeding X Gy (Vx(cc)) was analyzed, an NTCP model based on 3 variables including V30(cc), thyroid gland volume and gender was selected as the most predictive model (Rs = 0.630, p < 0.001. AUC = 0.85). The three-variable model performs better when tested on an external cohort characterized by large inter-individuals variation in thyroid volumes (AUC = 0.914, 95% CI 0.760-0.984). A comparable performance was found between our model and that proposed in the literature based on thyroid gland mean dose and volume (p = 0.264). The absolute volume of thyroid gland exceeding 30 Gy in combination with thyroid gland volume and gender provide an NTCP model for RHT with improved prediction capability not only within our patient population but also in an external cohort.

[Alpha interferon induced hyperthyroidism: a case report and review of the literature].

PubMed

Maiga, I; Valdes-Socin, H; Thiry, A; Delwaide, J; Sidibe, A T; Beckers, A

2015-01-01

Treatment with alpha interferon in hepatitis C triggers a thyroid autoimmunity in a variable percentage of cases (2-8%). This complication raises some questions about its screening, the possibility to continue anti-viral therapy and thyroid treatment. Alpha interferon has an immunomodulatory effect on the thyroid, but also an inhibitory effect on thyroid hormone synthesis. This explains the occurrence of cases of thyroid dysfunction, which often remain undetected because of their latency. Factors predicting thyroid dysfunction with interferon use are: female sex, history of thyroid disease and previous autoimmunity. Several clinical aspects are encountered including hypothyroidism (the most frequent depending on the series) and hyperthyroidism related to Graves' disease. For their detection, a cooperation between general practionners, gastroenterologists and endocrinologists is mandatory thyroid function tests are requested before, during and after treatment,with alpha interferon. Therapeutic aspects of thyroid disorders range from simple monitoring to symptomatic treatment, such as thyroxine prescription in the presence of hypothyroidism. Antithyroid drugs radioactive iodine or thyroid surgery are used in cases of severe or persistent Graves' disease induced by alpha interferon.

Sonographic features of thyroid nodules that may help distinguish clinically atypical subacute thyroiditis from thyroid malignancy.

PubMed

Pan, Fu-shun; Wang, Wei; Wang, Yan; Xu, Ming; Liang, Jin-yu; Zheng, Yan-ling; Xie, Xiao-yan; Li, Xiao-xi

2015-04-01

The purpose of this study was to evaluate sonographic features for distinguishing clinically atypical subacute thyroiditis from malignant thyroid nodules. A total of 165 hypoechoic thyroid nodules without calcification in 135 patients with histologic diagnosis were included in this study. These nodules were classified into 2 groups: a thyroiditis group (55 nodules in 36 patients) and a malignancy group (110 nodules in 99 patients). The sonographic features of the groups were retrospectively reviewed. No significant differences were detected for the variables of marked echogenicity, a taller-than-wide shape, and mixed vascularity. However, a poorly defined margin was detected more frequently in the thyroiditis group than the malignancy group (P < .05); it yielded a high capability for differential diagnosis of atypical subacute thyroiditis, with sensitivity and specificity of 87.3% and 80.9%, respectively. Centripetal reduction echogenicity was observed exclusively in the thyroiditis group, with high specificity (100%) but low sensitivity (21.8%) for atypical subacute thyroiditis diagnosis. All of the thyroiditis nodules with a positive color signal showed noninternal vascularity (negative predictive value, 100%). There is a considerable overlap between the sonographic features of atypical subacute thyroiditis and thyroid malignancy. However, the margin, echogenicity, and vascularity type are helpful indicators for differential diagnosis of atypical subacute thyroiditis. © 2015 by the American Institute of Ultrasound in Medicine.

Competitive inhibition of thyroidal uptake of dietary iodide by perchlorate does not describe perturbations in rat serum total T4 and TSH.

PubMed

McLanahan, Eva D; Andersen, Melvin E; Campbell, Jerry L; Fisher, Jeffrey W

2009-05-01

Perchlorate (ClO4(-)) is an environmental contaminant known to disrupt the thyroid axis of many terrestrial and aquatic species. ClO4(-) competitively inhibits iodide uptake into the thyroid at the sodium/iodide symporter and disrupts hypothalamic-pituitary-thyroid (HPT) axis homeostasis in rodents. We evaluated the proposed mode of action for ClO4(-)-induced rat HPT axis perturbations using a biologically based dose-response (BBDR) model of the HPT axis coupled with a physiologically based pharmacokinetic model of ClO4(-). We configured a BBDR-HPT/ClO4(-) model to describe competitive inhibition of thyroidal uptake of dietary iodide by ClO4(-) and used it to simulate published adult rat drinking water studies. We compared model-predicted serum thyroid-stimulating hormone (TSH) and total thyroxine (TT4) concentrations with experimental observations reported in these ClO4(-) drinking water studies. The BBDR-HPT/ClO4(-) model failed to predict the ClO4(-)-induced onset of disturbances in the HPT axis. Using ClO4(-) inhibition of dietary iodide uptake into the thyroid, the model underpredicted both the rapid decrease in serum TT4 concentrations and the rise in serum TSH concentrations. Assuming only competitive inhibition of thyroidal uptake of dietary iodide, BBDR-HPT/ClO4(-) model calculations were inconsistent with the rapid decrease in serum TT4 and the corresponding increase in serum TSH. Availability of bound iodide in the thyroid gland governed the rate of hormone secretion from the thyroid. ClO4(-) is translocated into the thyroid gland, where it may act directly or indirectly on thyroid hormone synthesis/secretion in the rat. The rate of decline in serum TT4 in these studies after 1 day of treatment with ClO4(-) appeared consistent with a reduction in thyroid hormone production/secretion. This research demonstrates the utility of a biologically based model to evaluate a proposed mode of action for ClO4(-) in a complex biological process.

Inflammatory myofibroblastic tumors of the lung carrying a chimeric A2M-ALK gene: report of 2 infantile cases and review of the differential diagnosis of infantile pulmonary lesions.

PubMed

Tanaka, Mio; Kohashi, Kenichi; Kushitani, Kei; Yoshida, Misa; Kurihara, Sho; Kawashima, Masumi; Ueda, Yuka; Souzaki, Ryota; Kinoshita, Yoshiaki; Oda, Yoshinao; Takeshima, Yukio; Hiyama, Eiso; Taguchi, Tomoaki; Tanaka, Yukichi

2017-08-01

We report 2 infantile cases of pulmonary tumor carrying a chimeric A2M-ALK gene. A2M-ALK is a newly identified anaplastic lymphoma kinase (ALK)-related chimeric gene from a tumor diagnosed as fetal lung interstitial tumor (FLIT). FLIT is a recently recognized infantile pulmonary lesion defined as a mass-like lesion that morphologically resembles the fetal lung. Grossly, FLIT characteristically appears as a well-circumscribed spongy mass, whereas the tumors in these patients were solid and firm. Histologically, the tumors showed intrapulmonary lesions composed of densely proliferating polygonal or spindle-shaped mesenchymal cells with diffuse and dense infiltrations of inflammatory cells forming microcystic or micropapillary structures lined by thyroid transcription factor 1-positive pneumocytes, favoring inflammatory myofibroblastic tumor rather than FLIT. The proliferating cells were immunoreactive for ALK, and A2M-ALK was identified in both tumors with reverse-transcription polymerase chain reaction. The dense infiltration of inflammatory cells, immunoreactivity for ALK, and identification of an ALK-related chimeric gene suggested a diagnosis of inflammatory myofibroblastic tumor. Histologically, most reported FLITs show sparse inflammatory infiltrates and a relatively low density of interstitial cells in the septa, although prominent infiltration of inflammatory cells and high cellularity of interstitial cells are seen in some FLITs. The present cases suggest that ALK rearrangements, including the chimeric A2M-ALK gene, may be present in these infantile pulmonary lesions, especially those with inflammatory cell infiltration. We propose that these infantile pulmonary lesions containing a chimeric A2M-ALK gene be categorized as a specific type of inflammatory myofibroblastic tumor that develops exclusively in neonates and infants. Copyright © 2017 Elsevier Inc. All rights reserved.

ADM3, TFF3 and LGALS3 are discriminative molecular markers in fine-needle aspiration biopsies of benign and malignant thyroid tumours

PubMed Central

Karger, S; Krause, K; Gutknecht, M; Schierle, K; Graf, D; Steinert, F; Dralle, H; Führer, D

2012-01-01

Background: Previously, we reported a six-marker gene set, which allowed a molecular discrimination of benign and malignant thyroid tumours. Now, we evaluated these markers in fine-needle aspiration biopsies (FNAB) in a prospective, independent series of thyroid tumours with proven histological outcome. Methods: Quantitative RT–PCR was performed (ADM3, HGD1, LGALS3, PLAB, TFF3, TG) in the needle wash-out of 156 FNAB of follicular adenoma (FA), adenomatous nodules, follicular and papillary thyroid cancers (TC) and normal thyroid tissues (NT). Results: Significant expression differences were found for TFF3, HGD1, ADM3 and LGALS3 in FNAB of TC compared with benign thyroid nodules and NT. Using two-marker gene sets, a specific FNAB distinction of benign and malignant tumours was achieved with negative predictive values (NPV) up to 0.78 and positive predictive values (PPV) up to 0.84. Two FNAB marker gene combinations (ADM3/TFF3; ADM3/ACTB) allowed the distinction of FA and malignant follicular neoplasia with NPV up to 0.94 and PPV up to 0.86. Conclusion: We demonstrate that molecular FNAB diagnosis of benign and malignant thyroid tumours including follicular neoplasia is possible with recently identified marker gene combinations. We propose multi-centre FNAB studies on these markers to bring this promising diagnostic tool closer to clinical practice. PMID:22223087

American Thyroid Association Guidelines on the Management of Thyroid Nodules and Differentiated Thyroid Cancer Task Force Review and Recommendation on the Proposed Renaming of Encapsulated Follicular Variant Papillary Thyroid Carcinoma Without Invasion to Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features.

PubMed

Haugen, Bryan R; Sawka, Anna M; Alexander, Erik K; Bible, Keith C; Caturegli, Patrizio; Doherty, Gerard M; Mandel, Susan J; Morris, John C; Nassar, Aziza; Pacini, Furio; Schlumberger, Martin; Schuff, Kathryn; Sherman, Steven I; Somerset, Hilary; Sosa, Julie Ann; Steward, David L; Wartofsky, Leonard; Williams, Michelle D

2017-04-01

American Thyroid Association (ATA) leadership asked the ATA Thyroid Nodules and Differentiated Thyroid Cancer Guidelines Task Force to review, comment on, and make recommendations related to the suggested new classification of encapsulated follicular variant papillary thyroid carcinoma (eFVPTC) without capsular or vascular invasion to noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). The task force consists of members from the 2015 guidelines task force with the recusal of three members who were authors on the paper under review. Four pathologists and one endocrinologist were added for this specific review. The manuscript proposing the new classification and related literature were assessed. It is recommended that the histopathologic nomenclature for eFVPTC without invasion be reclassified as a NIFTP, given the excellent prognosis of this neoplastic variant. This is a weak recommendation based on moderate-quality evidence. It is also noted that prospective studies are needed to validate the observed patient outcomes (and test performance in predicting thyroid cancer outcomes), as well as implications on patients' psychosocial health and economics.

Adenocarcinoma predominant pattern subtyping and nuclear grading in cytology: Is there a role in prognostication of advanced pulmonary adenocarcinomas?

PubMed

Nambirajan, A; Kaur, H; Jangra, K; Kaur, K; Madan, K; Mathur, S R; Iyer, V K; Jain, D

2018-04-01

Primary lung adenocarcinomas (ADs) show varied architectural patterns, and pattern-based subtyping of ADs is currently recommended due to prognostic implications. Predicting AD patterns on cytology is challenging; however, cytological nuclear features appear to correlate with histological grade and survival in early stage lung ADs. The feasibility and value of AD pattern prediction and nuclear grading on cytology in advanced lung ADs is not known. We aimed to predict patterns and analyse nuclear features on cytology and evaluate their role in prognostication. One-hundred patients of Stage III/IV lung AD with available matched cytology and histology samples were included. Cyto-patterns based on cell arrangement patterns (flat sheets vs three-dimensional clusters vs papillae) and cyto-nuclear score based on nuclear features (size, shape, contour), nucleoli (macronucleoli vs prominent vs inconspicuous), and nuclear chromatin were determined, and correlated with predominant histological-pattern observed on the matched small biopsy and outcome. Higher cyto-nuclear scores were observed with high-grade histo-patterns (solid, micropapillary and cribriform), while the predicted cyto-patterns did not correspond to the predominant pattern on histology in 77% cases. Highest cyto-histo agreement was observed for solid pattern (72%). High grade histo-patterns and cyto-nuclear scores > 3 showed a trend towards inferior survival (not significant). Nuclear grade scoring on cytology is simple to perform, and is predictive of high grade patterns. Its inclusion in routine reporting of cytology samples of lung ADs may be valuable. © 2018 John Wiley & Sons Ltd.

The estimation of the thyroid volume before surgery--an important prerequisite for minimally invasive thyroidectomy.

PubMed

Ruggieri, M; Fumarola, A; Straniero, A; Maiuolo, A; Coletta, I; Veltri, A; Di Fiore, A; Trimboli, P; Gargiulo, P; Genderini, M; D'Armiento, M

2008-09-01

Actually, thyroid volume >25 ml, obtained by preoperative ultrasound evaluation, is a very important exclusion criteria for minimally invasive thyroidectomy. So far, among different imaging techniques, two-dimensional ultrasonography has become the more accepted method for the assessment of thyroid volume (US-TV). The aims of this study were: (1) to estimate the preoperative thyroid volume in patients undergoing minimally invasive total thyroidectomy using a mathematical formula and (2) to verify its validity by comparing it with the postsurgical TV (PS-TV). In 53 patients who underwent minimally invasive total thyroidectomy (from January 2003 to December 2007), US-TV, obtained by ellipsoid volume formula, was compared to PS-TV determined by the Archimedes' principle. A mathematical formula able to predict the TV from the US-TV was applied in 34 cases in the last 2 years. Mean US-TV (14.4 +/- 5.9 ml) was significantly lower than mean PS-TV (21.7 +/- 10.3 ml). This underestimation was related to gland multinodularity and/or nodular involvement of the isthmus. A mathematical formula to reduce US-TV underestimation and predict the real TV was developed using a linear model. Mean predicted TV (16.8 +/- 3.7 ml) perfectly matched mean PS-TV, underestimating PS-TV in 19% of cases. We verified the accuracy of this mathematical model in patients' eligibility for minimally invasive total thyroidectomy, and we demonstrated that a predicted TV <25 ml was confirmed post-surgery in 94% of cases. We demonstrated that using a linear model, it is possible to predict from US the PS-TV with high accuracy. In fact, the mean predicted TV perfectly matched the mean PS-TV in all cases. In particular, the percentage of cases in which the predicted TV perfectly matched the PS-TV increases from 23%, estimated by US, to 43%. Moreover, the percentage of TV underestimation was reduced from 77% to 19%, as well as the range of the disagreement from up to 200% to 80%. This study shows that two-dimensional US can provide the accurate estimation of thyroid volume but that it can be improved by a mathematical model. This may contribute to a more appropriate surgical management of thyroid diseases.

Evaluation of Serum Vascular Adhesion Protein-1 as a Potential Biomarker in Thyroid Cancer

PubMed Central

Zhao, Pengxin; Zhang, Kaili

2016-01-01

Vascular adhesion protein-1 (VAP-1) is a glycoprotein that mediates tissue-selective lymphocyte adhesion. The prognostic value of VAP-1 has been determined in gastric cancer. The aim of this study was to evaluate the changes and the predictive value of serum VAP-1 in patients with thyroid cancer. A total of 126 patients with thyroid nodules and 53 healthy controls participated in this study. The patients were further divided into subgroup 1 (69 cases with benign thyroid nodules) and subgroup 2 (57 cases with thyroid cancer). Serum VAP-1 was measured by time-resolved immunofluorometric assay. Diagnostic value of presurgical VAP-1 for thyroid cancer was conducted by receiver operating characteristic (ROC) curves. Serum levels of VAP-1 were significantly lower in thyroid cancer group than in healthy control and benign thyroid nodule groups. VAP-1 concentrations negatively correlated with serum thyroglobulin (Tg) levels in thyroid cancer patients (r = −0.81; p < 0.001). The optimum cut-off value of VAP-1 was 456.6 ng/mL with a 77.4% specificity and 66.7% sensitivity for thyroid cancer diagnosis. Serum VAP-1 decreased in thyroid cancer patients and VAP-1 could be a potential useful adjunct biomarker in the diagnosis of thyroid cancer. PMID:27446209

Clinical utility of RAS mutations in thyroid cancer: a blurred picture now emerging clearer.

PubMed

Xing, Mingzhao

2016-01-27

RAS mutations play an important role in thyroid tumorigenesis. Considerable effort has been made in the last decade to apply RAS mutations as molecular markers to the clinical management of thyroid nodules and thyroid cancer. Yet, for the low diagnostic sensitivities and specificities of RAS mutations, when used alone, and for their uncertain role in the clinical outcomes of thyroid cancer, it has been unclear how to appropriately use them to assist the management of thyroid nodules and thyroid cancer. Studies from recent years, now added from the Alexander group, have shed light on this issue, making a blurred clinical picture now emerge clearer-RAS mutations, when combined with other genetic markers, have high diagnostic negative predictive values for thyroid cancer; cytologically benign thyroid nodules, including those positive for RAS mutations, have long-term clinical stability when non-surgically managed; and differentiated thyroid cancers harboring RAS mutations alone have an excellent prognosis. This progress in understanding RAS mutations in thyroid cancer is showing a major impact on molecular-based practice in the management of thyroid cancer.Please see related research articles: http://dx.doi.org/10.1186/s12916-016-0554-1 and http://dx.doi.org/10.1186/s12916-015-0419-z.

WOMEN IN CANCER THEMATIC REVIEW: Thyroid-stimulating hormone in thyroid cancer: does it matter?

PubMed

Nieto, Hannah; Boelaert, Kristien

2016-11-01

Differentiated thyroid cancer is the most common endocrine malignancy and the incidence is increasing rapidly worldwide. Appropriate diagnosis and post-treatment monitoring of patients with thyroid tumours are critical. Fine needle aspiration cytology remains the gold standard for diagnosing thyroid cancer, and although there have been significant refinements to this technique, diagnostic surgery is often required for patients suspected to have malignancy. Serum thyroid-stimulating hormone (TSH) is higher in patients with malignant thyroid nodules than in those with benign disease, and TSH is proportionally increased in more aggressive tumours. Importantly, we have shown that the pre-operative serum TSH concentration independently predicts the presence of malignancy in subjects presenting with thyroid nodules. Establishing the use of TSH measurements in algorithms identifying high-risk thyroid nodules in routine clinical practice represents an exciting, cost-efficient and non-invasive approach to optimise thyroid cancer diagnosis. Binding of TSH to receptors on thyrocytes stimulates a number of growth promoting pathways both in normal and malignant thyroid cells, and TSH suppression with high doses of levothyroxine is routinely used after thyroidectomy to prevent cancer recurrence, especially in high-risk tumours. This review examines the relationship between serum TSH and thyroid cancer and reflects on the clinical potential of TSH measurements in diagnosis and disease monitoring. © 2016 Society for Endocrinology.

SYSTEMS APPROACH TO CHARACTERIZING AND PREDICTING THYROID TOXICITY

EPA Science Inventory

A systems approach is being undertaken in which in vivo and in vitro assays are integrated to understand the mechanisms of thyroid hormone mediated pathways controlling frog metamorphosis, and more generally the regulation and control of the HPT axis.

The Effects of Hashimoto Thyroiditis on Lymph Node Metastases in Unifocal and Multifocal Papillary Thyroid Carcinoma

PubMed Central

Zhu, Feng; Shen, Yi Bin; Li, Fu Qiang; Fang, Yun; Hu, Liang; Wu, Yi Jun

2016-01-01

Abstract The purpose of this study was to investigate the risk factors for central and lateral neck lymph node metastases in papillary thyroid carcinoma (PTC) and multifocal papillary thyroid carcinoma (MPTC), particularly when associated with Hashimoto thyroiditis (HT). A retrospective analysis of 763 consecutive patients who underwent total thyroidectomy with bilateral central neck dissection in the First Affiliated Hospital, College of Medicine, Zhejiang University between October 2011 and October 2014 was conducted. All patients had formal histological diagnoses of HT. Multivariable logistic regression analysis was performed to identify risk factors of neck lymph node metastases. Our study identified 277 PTC patients with HT and showed comparatively low rates of central lymph node metastases (CLNM) compared with the PTC patients without HT (37.2% versus 54.7%, P < 0.001). There were no statistically significant differences in lateral lymph node metastases (LLNM) (P = 0.656). Neck lymph node metastases were histologically proven in 127 (45.8%) patients with PTC with HT, including 103 CLNM and 24 LLNM. There were no significant differences in LLNM between the MPTC-associated HT and classic MPTC cases; however, a significantly reduced risk of CLNM was observed in the MPTC-associated HT compared with the MPTC cases (35.7% versus 72.4%, respectively, P < 0.001). In the multivariate analysis, HT was identified as an independent alleviating factor for CLNM in all PTC patients (odds ratio, 0.369; 95% confidence interval (CI), 0.261 to 0.521; P < 0.001) and in MPTC patients (odds ratio, 0.227; 95% CI, 0.126–0.406; P < 0.001). A cut-off of thyroid peroxidase antibody >140 IU/mL was established as the most sensitive and specific level for the prediction of MPTC based on receiver operating characteristic curve analyses. Thyroid peroxidase antibody, age, tumor size, and multifocality exhibited the ability to predict CLNM in PTC with HT patients with an area under the curve of 81.1% based on a multivariate model. Hashimoto thyroiditis was associated with increased prevalences of multifocality and capsular invasion. In contrast, HT was associated with a reduced risk of CLNM in PTC and MPTC patients, which indicated a potential protective effect. We found that the prognostic prediction model was applicable for predicting multifocality and CLNM in PTC patients with HT. PMID:26871795

The Effects of Hashimoto Thyroiditis on Lymph Node Metastases in Unifocal and Multifocal Papillary Thyroid Carcinoma: A Retrospective Chinese Cohort Study.

PubMed

Zhu, Feng; Shen, Yi Bin; Li, Fu Qiang; Fang, Yun; Hu, Liang; Wu, Yi Jun

2016-02-01

The purpose of this study was to investigate the risk factors for central and lateral neck lymph node metastases in papillary thyroid carcinoma (PTC) and multifocal papillary thyroid carcinoma (MPTC), particularly when associated with Hashimoto thyroiditis (HT).A retrospective analysis of 763 consecutive patients who underwent total thyroidectomy with bilateral central neck dissection in the First Affiliated Hospital, College of Medicine, Zhejiang University between October 2011 and October 2014 was conducted. All patients had formal histological diagnoses of HT. Multivariable logistic regression analysis was performed to identify risk factors of neck lymph node metastases.Our study identified 277 PTC patients with HT and showed comparatively low rates of central lymph node metastases (CLNM) compared with the PTC patients without HT (37.2% versus 54.7%, P < 0.001). There were no statistically significant differences in lateral lymph node metastases (LLNM) (P = 0.656). Neck lymph node metastases were histologically proven in 127 (45.8%) patients with PTC with HT, including 103 CLNM and 24 LLNM. There were no significant differences in LLNM between the MPTC-associated HT and classic MPTC cases; however, a significantly reduced risk of CLNM was observed in the MPTC-associated HT compared with the MPTC cases (35.7% versus 72.4%, respectively, P < 0.001). In the multivariate analysis, HT was identified as an independent alleviating factor for CLNM in all PTC patients (odds ratio, 0.369; 95% confidence interval (CI), 0.261 to 0.521; P < 0.001) and in MPTC patients (odds ratio, 0.227; 95% CI, 0.126-0.406; P < 0.001). A cut-off of thyroid peroxidase antibody >140 IU/mL was established as the most sensitive and specific level for the prediction of MPTC based on receiver operating characteristic curve analyses. Thyroid peroxidase antibody, age, tumor size, and multifocality exhibited the ability to predict CLNM in PTC with HT patients with an area under the curve of 81.1% based on a multivariate model.Hashimoto thyroiditis was associated with increased prevalences of multifocality and capsular invasion. In contrast, HT was associated with a reduced risk of CLNM in PTC and MPTC patients, which indicated a potential protective effect. We found that the prognostic prediction model was applicable for predicting multifocality and CLNM in PTC patients with HT.

Surgical perspective of T1799A BRAF mutation diagnostic value in papillary thyroid carcinoma.

PubMed

Brahma, Bayu; Yulian, Erwin Danil; Ramli, Muchlis; Setianingsih, Iswari; Gautama, Walta; Brahma, Putri; Sastroasmoro, Sudigdo; Harimurti, Kuntjoro

2013-01-01

Throughout Indonesia, thyroid cancer is one of the ten commonest malignancies, with papillary thyroid carcinoma (PTC) in our hospital accounting for about 60% of all thyroid nodules. Although fine needle aspiration biopsy (FNAB) is the most reliable diagnostic tool, some nodules are diagnosed as indeterminate and second surgery is common for PTC. The aim of this study was to establish the diagnostic value and feasibility of testing the BRAF T1799A mutation on FNA specimens for improving PTC diagnosis. This prospective study enrolled 95 patients with thyroid nodules and future surgery planned. Results of mutational status were compared with surgical pathology diagnosis. Of the 70 cases included in the final analysis, 62.8% were PTC and the prevalence of BRAF mutation was 38.6%. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for BRAF mutation analysis were 36%, 100%, 100% and 48%, respectively. With other data findings, nodules with "onset less than 5 year" and "hard consistency" were proven as diagnostic determinants for BRAF mutation with a probability of 62.5%. This mutation was also a significant risk factor for extra-capsular extension. Molecular analysis of the BRAF T1799A mutation in FNAB specimens has high specificity and positive predictive value for PTC. It could be used in the selective patients with clinical characteristics to facilitate PTC diagnosis and for guidance regarding extent of thyroidectomy.

Comparison and relationship of thyroid hormones, IL-6, IL-10 and albumin as mortality predictors in case-mix critically ill patients.

PubMed

Quispe E, Álvaro; Li, Xiang-Min; Yi, Hong

2016-05-01

To compare the ability of thyroid hormones, IL-6, IL-10, and albumin to predict mortality, and to assess their relationship in case-mix acute critically ill patients. APACHE II scores and serum thyroid hormones (FT3, FT4, and TSH), IL-6, IL-10, and albumin were obtained at EICU admission for 79 cases of mix acute critically ill patients without previous history of thyroid disease. Patients were followed for 28 days with patient's death as the primary outcome. All mean values were compared, correlations assessed with Pearson' test, and mortality prediction assessed by multivariate logistic regression and ROC. Non survivors were older, with higher APACHE II score (p=0.000), IL-6 (p<0.05), IL-10 (p=0.000) levels, and lower albumin (p=0.000) levels compared to survivors at 28 days. IL-6 and IL-10 had significant negative correlation with albumin (p=0.001) and FT3 (p ⩽ 0.05) respectively, while low albumin had a direct correlation with FT3 (p<0.05). In the mortality prediction assessment, IL-10, albumin and APACHE II were independent morality predictors and showed to have a good (0.70-0.79) AUC-ROC (p<0.05). Despite that the entire cohort showed low FT3 serum levels (p=0.000), there was not statistical difference between survivors and non-survivors; neither showed any significance as mortality predictor. IL-6 and IL-10 are correlated with Low FT3 and hypoalbuminemia. Thyroid hormones assessed at EICU admission did not have any predictive value in our study. And finally, high levels of IL-6 and IL-10 in conjunction with albumin could improve our ability to evaluate disease's severity and predict mortality in the critically ill patients. When use in combination with APACHE II scores, our model showed improved mortality prediction. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Novel Application of Quantitative Single-Photon Emission Computed Tomography/Computed Tomography to Predict Early Response to Methimazole in Graves' Disease

PubMed Central

Kim, Hyun Joo; Bang, Ji-In; Kim, Ji-Young; Moon, Jae Hoon; So, Young

2017-01-01

Objective Since Graves' disease (GD) is resistant to antithyroid drugs (ATDs), an accurate quantitative thyroid function measurement is required for the prediction of early responses to ATD. Quantitative parameters derived from the novel technology, single-photon emission computed tomography/computed tomography (SPECT/CT), were investigated for the prediction of achievement of euthyroidism after methimazole (MMI) treatment in GD. Materials and Methods A total of 36 GD patients (10 males, 26 females; mean age, 45.3 ± 13.8 years) were enrolled for this study, from April 2015 to January 2016. They underwent quantitative thyroid SPECT/CT 20 minutes post-injection of 99mTc-pertechnetate (5 mCi). Association between the time to biochemical euthyroidism after MMI treatment and %uptake, standardized uptake value (SUV), functional thyroid mass (SUVmean × thyroid volume) from the SPECT/CT, and clinical/biochemical variables, were investigated. Results GD patients had a significantly greater %uptake (6.9 ± 6.4%) than historical control euthyroid patients (n = 20, 0.8 ± 0.5%, p < 0.001) from the same quantitative SPECT/CT protocol. Euthyroidism was achieved in 14 patients at 156 ± 62 days post-MMI treatment, but 22 patients had still not achieved euthyroidism by the last follow-up time-point (208 ± 80 days). In the univariate Cox regression analysis, the initial MMI dose (p = 0.014), %uptake (p = 0.015), and functional thyroid mass (p = 0.016) were significant predictors of euthyroidism in response to MMI treatment. However, only %uptake remained significant in a multivariate Cox regression analysis (p = 0.034). A %uptake cutoff of 5.0% dichotomized the faster responding versus the slower responding GD patients (p = 0.006). Conclusion A novel parameter of thyroid %uptake from quantitative SPECT/CT is a predictive indicator of an early response to MMI in GD patients. PMID:28458607

Trends in white blood cell and platelet indices in a comparison of patients with papillary thyroid carcinoma and multinodular goiter do not permit differentiation between the conditions.

PubMed

Machairas, Nikolaos; Kostakis, Ioannis D; Prodromidou, Anastasia; Stamopoulos, Paraskevas; Feretis, Themistoklis; Garoufalia, Zoe; Damaskos, Christos; Tsourouflis, Gerasimos; Kouraklis, Gregory

2017-11-01

Carcinogenesis has been related to systematic inflammatory response. Our aim was to study white blood cell and platelet indices as markers of this inflammatory response in thyroid cancer and to associate them with various clinicopathological parameters. We included 228 patients who underwent thyroidectomy within a period of 54 months, 89 with papillary thyroid carcinoma and 139 with multinodular hyperplasia. We examined potential links between white blood cell and platelet indices on the one hand and the type thyroid pathology and various clinicopathological parameters on the other. No significant differences were detected between thyroid cancer and multinodular hyperplasia and no significant associations were detected with regard to lymphovascular invasion and tumor size. However, the mean platelet volume was higher in multifocal tumors, while the platelet count, plateletcrit, and platelet-to-lymphocyte ratio were increased in cases with extrathyroidal extension and in T3 tumors. Additionally, T3 tumors had lower platelet distribution width. These associations demonstrated low accuracy in predicting these pathological features, but they were found to provide a satisfying negative predictive value, with the exception of the mean platelet volume. White blood cell and platelet indices cannot assist in distinguishing benign goiter from thyroid cancer. However, they can provide information about tumor multifocality, extrathyroidal extension, and presence of a T3 tumor, and they may be used as a means to exclude these pathological characteristics, especially the last two, in papillary thyroid carcinoma.

Prognostic Classifier Based on Genome-Wide DNA Methylation Profiling in Well-Differentiated Thyroid Tumors.

PubMed

Bisarro Dos Reis, Mariana; Barros-Filho, Mateus Camargo; Marchi, Fábio Albuquerque; Beltrami, Caroline Moraes; Kuasne, Hellen; Pinto, Clóvis Antônio Lopes; Ambatipudi, Srikant; Herceg, Zdenko; Kowalski, Luiz Paulo; Rogatto, Silvia Regina

2017-11-01

Even though the majority of well-differentiated thyroid carcinoma (WDTC) is indolent, a number of cases display an aggressive behavior. Cumulative evidence suggests that the deregulation of DNA methylation has the potential to point out molecular markers associated with worse prognosis. To identify a prognostic epigenetic signature in thyroid cancer. Genome-wide DNA methylation assays (450k platform, Illumina) were performed in a cohort of 50 nonneoplastic thyroid tissues (NTs), 17 benign thyroid lesions (BTLs), and 74 thyroid carcinomas (60 papillary, 8 follicular, 2 Hürthle cell, 1 poorly differentiated, and 3 anaplastic). A prognostic classifier for WDTC was developed via diagonal linear discriminant analysis. The results were compared with The Cancer Genome Atlas (TCGA) database. A specific epigenetic profile was detected according to each histological subtype. BTLs and follicular carcinomas showed a greater number of methylated CpG in comparison with NTs, whereas hypomethylation was predominant in papillary and undifferentiated carcinomas. A prognostic classifier based on 21 DNA methylation probes was able to predict poor outcome in patients with WDTC (sensitivity 63%, specificity 92% for internal data; sensitivity 64%, specificity 88% for TCGA data). High-risk score based on the classifier was considered an independent factor of poor outcome (Cox regression, P < 0.001). The methylation profile of thyroid lesions exhibited a specific signature according to the histological subtype. A meaningful algorithm composed of 21 probes was capable of predicting the recurrence in WDTC. Copyright © 2017 Endocrine Society

NA cohort study of thyroid cancer and other thyroid diseases after the Chernobyl accident: cytohistopathologic correlation and accuracy of fine-needle aspiration biopsy in nodules detected during the first screening in Ukraine (1998-2000).

PubMed

Bozhok, Yuriy; Greenebaum, Ellen; Bogdanova, Tetyana I; McConnell, Robert J; Zelinskaya, Anna; Brenner, Alina V; Zurnadzhy, Lyudmyla Y; Zablotska, Lydia; Tronko, Mykola D; Hatch, Maureen

2009-04-25

The Ukrainian American Cohort Study was established to evaluate the risk of thyroid disorders in a group exposed as children and adolescents to 131I by the Chernobyl accident (arithmetic mean thyroid dose, 0.79 grays). Individuals are screened by palpation and ultrasound and are referred to surgery according to fine-needle aspiration biopsy (FNA). However, the accuracy of FNA cytology for detecting histopathologically confirmed malignancy after this level of internal exposure to radioiodines is unknown. During the first screening cycle (1998-2000), 13,243 individuals were examined, 356 individuals with thyroid nodules were referred for FNA, 288 individuals completed the procedure, 85 individuals were referred to surgery, 82 individuals underwent surgery, and preoperative cytology was available for review in 78 individuals. Cytologic interpretation for the nodule that resulted in surgical referral was correlated with final pathomorphology; discrepancies were reviewed retrospectively; and the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of FNA cytology were calculated. All 24 cytologic interpretations that were definite for papillary thyroid cancer (PTC) were confirmed histopathologically (PPV, 100%); and, of 11 cytologic interpretations that were suspicious for PTC, 10 were confirmed (PPV, 90.9%). Ten of 41 FNAs that were interpreted as either definite or suspect for follicular neoplasm were confirmed as malignant (PPV, 24.4%), including 2 follicular thyroid cancers and 8 PTCs (all but 1 of the follicular or mixed subtypes). Depending on whether a cytologic interpretation of follicular neoplasm was considered "positive" or "negative," the sensitivity was 100% and 77.3%, respectively; similarly, the respective specificity was 17.6% and 97.1%, the respective PPV was 61.1% and 97.1%, and the respective NPV was 100% and 76.7%. Among children and adolescents who were exposed to 131I after the Chernobyl accident and were evaluated 12 to 14 years later, thyroid cytology had a sensitivity and a predictive value similar to those reported in unexposed populations. (c) 2009 American Cancer Society.

Predictive factors for intraoperative excessive bleeding in Graves' disease.

PubMed

Yamanouchi, Kosho; Minami, Shigeki; Hayashida, Naomi; Sakimura, Chika; Kuroki, Tamotsu; Eguchi, Susumu

2015-01-01

In Graves' disease, because a thyroid tends to have extreme vascularity, the amount of intraoperative blood loss (AIOBL) becomes significant in some cases. We sought to elucidate the predictive factors of the AIOBL. A total of 197 patients underwent thyroidectomy for Graves' disease between 2002 and 2012. We evaluated clinical factors that would be potentially related to AIOBL retrospectively. The median period between disease onset and surgery was 16 months (range: 1-480 months). Conventional surgery was performed in 125 patients, whereas video-assisted surgery was performed in 72 patients. Subtotal and near-total/total thyroidectomies were performed in 137 patients and 60 patients, respectively. The median weight of the thyroid was 45 g (range: 7.3-480.0 g). Univariate analysis revealed that the strongest correlation of AIOBL was noted with the weight of thyroid (p < 0.001). Additionally, AIOBL was correlated positively with the period between disease onset and surgery (p < 0.001) and negatively with preoperative free T4 (p < 0.01). Multivariate analysis showed that only the weight of the thyroid was independently correlated with AIOBL (p < 0.001). Four patients (2.0%) needed blood transfusion, including two requiring autotransfusion, whose thyroids were all weighing in excess of 200 g. The amount of drainage during the initial 6 hours and days until drain removal was correlated positively with AIOBL (p < 0.001, each). Occurrences of postoperative complications, such as recurrent laryngeal nerve palsy or hypoparathyroidism, and postoperative hospital stay were not correlated with AIOBL. A huge goiter presented as a predictive factor for excessive bleeding during surgery for Graves' disease, and preparation for blood transfusion should be considered in cases where thyroids weigh more than 200 g. Copyright © 2014. Published by Elsevier Taiwan.

Reevaluation of the thyroidal radioactive iodine uptake test, with special reference to reversible primary hypothyroidism with elevated thyroid radioiodine uptake

DOE Office of Scientific and Technical Information (OSTI.GOV)

Okamura, K.; Sato, K.; Ikenoue, H.

The clinical significance of the thyroidal radioactive iodine uptake (RAIU) test was reevaluated in patients with various thyroid disorders. Compared with 262 normal subjects or 194 patients with euthyroid diffuse goiter with normal serum TSH levels, RAIU values were significantly higher in 100 patients with latent primary hypothyroidism (serum TSH, 5-40 mU/L). In 126 patients with overt primary hypothyroidism (serum TSH, greater than 40 mU/L), RAIU values were either extremely high (49 patients with reversible hypothyroidism and 10 patients with postpartum hypothyroidism) or low (67 patients with irreversible hypothyroidism). The increase in RAIU values in latent, or reversible overt hypothyroidismmore » was TSH dependent, and there was a good correlation between RAIU values and serum TSH levels (r = 0.6203; P less than 0.001). In overt primary hypothyroidism, spontaneous recovery of thyroid function during iodide restriction alone occurred in 52 of 53 patients with RAIU values above 35%, in only 7 of 23 patients with RAIU values between 10-35%, and in none of 50 patients with RAIU below 10%. Thus, recovery was predicted by high RAIU values (P less than 0.001; prediction rate, 91.4%). Goiter was found in about 80% of the patients with reversible hypothyroidism, compared with only 34% of the patients with irreversible hypothyroidism. Recovery of thyroid function during iodide restriction also occurred in 71% of the patients with latent hypothyroidism. However, RAIU measurements did not predict the prognosis of patients with latent hypothyroidism. We conclude that iodine-induced reversible hypothyroidism is common in our patient population, and RAIU measurements may be helpful in determining the prognosis of patients with overt primary hypothyroidism.« less

A Risk Score Model for Evaluation and Management of Patients with Thyroid Nodules.

PubMed

Zhang, Yongwen; Meng, Fanrong; Hong, Lianqing; Chu, Lanfang

2018-06-12

The study is aimed to establish a simplified and practical tool for analyzing thyroid nodules. A novel risk score model was designed, risk factors including patient history, patient characteristics, physical examination, symptoms of compression, thyroid function, ultrasonography (US) of thyroid and cervical lymph nodes were evaluated and classified into high risk factors, intermediate risk factors, and low risk factors. A total of 243 thyroid nodules in 162 patients were assessed with risk score system and Thyroid Imaging-Reporting and Data System (TI-RADS). The diagnostic performance of risk score system and TI-RADS was compared. The accuracy in the diagnosis of thyroid nodules was 89.3% for risk score system, 74.9% for TI-RADS respectively. The specificity, accuracy and positive predictive value (PPV) of risk score system were significantly higher than the TI-RADS system (χ 2 =26.287, 17.151, 11.983; p <0.05), statistically significant differences were not observed in the sensitivity and negative predictive value (NPV) between the risk score system and TI-RADS (χ 2 =1.276, 0.290; p>0.05). The area under the curve (AUC) for risk score diagnosis system was 0.963, standard error 0.014, 95% confidence interval (CI)=0.934-0.991, the AUC for TI-RADS diagnosis system was 0.912 with standard error 0.021, 95% CI=0.871-0.953, the AUC for risk score system was significantly different from that of TI-RADS (Z=2.02; p <0.05). Risk score model is a reliable, simplified and cost-effective diagnostic tool used in diagnosis of thyroid cancer. The higher the score is, the higher the risk of malignancy will be. © Georg Thieme Verlag KG Stuttgart · New York.

Management of the thyroid gland during laryngectomy.

PubMed

Li, S X; Polacco, M A; Gosselin, B J; Harrington, L X; Titus, A J; Paydarfar, J A

2017-08-01

This study aimed to: describe the incidence of thyroid gland involvement in advanced laryngeal cancer, analyse patterns of spread to the thyroid and elucidate predictors of thyroid involvement. A retrospective review was performed on patients who underwent laryngectomy from 1991 to 2015 as a primary or salvage treatment for squamous cell carcinoma of the larynx, hypopharynx or base of tongue. The incidence of thyroidectomy during total laryngectomy, type of thyroidectomy, incidence of gland involvement, route of spread, and positive predictors of spread were analysed and reported. A total of 188 patients fit the inclusion criteria. Of these, 125 (66 per cent) underwent thyroidectomy. The thyroid was involved in 10 of the 125 patients (8 per cent), 9 by direct extension and 1 by metastasis. Cartilage invasion was a predictor of thyroid gland involvement, with a positive predictive value of 26 per cent. There is a low incidence of thyroid gland involvement in laryngeal carcinoma. Most cases of gland involvement occurred by direct extension. Thyroidectomy during laryngectomy should be considered for advanced stage tumours with cartilage invasion.

A preliminary study of simple voice assessment in a routine clinical setting to predict vocal cord paralysis after thyroid or parathyroid surgery.

PubMed

Hanna, B C; Brooker, D S

2008-02-01

To determine if a simple assessment of vocal cord function performed in a routine clinical setting can predict vocal cord paralysis on laryngoscopy in patients following thyroid or parathyroid surgery. Prospective observational cohort study of patients undergoing thyroid or parathyroid surgery. Vocal cord function was assessed in terms of an abnormality of voice or cough reported by the patient or detected by the examiner. Laryngoscopy was performed by indirect mirror examination or fibreoptic nasopharyngolaryngoscopy. Examiners included otolaryngology consultants, registrars, senior house officers and a general practitioner with a special interest in otolaryngology. The patient was often examined by a different clinician before and after surgery. Eighty-six patients participated in the study between August 2003 and July 2004. Eleven had a change in their voice postoperatively and one patient had difficulty coughing. Six of these patients had a vocal cord paralysis. A further five apparently asymptomatic patients had a vocal cord paralysis. The positive predictive value of voice assessment for vocal cord paralysis was 55%. In a routine clinical setting where the assessment of vocal cord function is often reported by different clinicians of varying experience at each patient attendance, the assessment of a patient's voice following thyroid or parathyroid surgery is not adequately predictive of vocal cord paralysis on indirect laryngoscopy or fibreoptic nasopharyngolaryngoscopy. Further study is required to determine reasons for this.

A Concise Atlas of Thyroid Cancer Next-Generation Sequencing Panel ThyroSeq v.2

PubMed Central

Alsina, Jorge; Alsina, Raul; Gulec, Seza

2017-01-01

The next-generation sequencing technology allows high out-put genomic analysis. An innovative assay in thyroid cancer, ThyroSeq® was developed for targeted mutation detection by next generation sequencing technology in fine needle aspiration and tissue samples. ThyroSeq v.2 next generation sequencing panel offers simultaneous sequencing and detection in >1000 hotspots of 14 thyroid cancer-related genes and for 42 types of gene fusions known to occur in thyroid cancer. ThyroSeq is being increasingly used to further narrow the indeterminate category defined by cytology for thyroid nodules. From a surgical perspective, genomic profiling also provides prognostic and predictive information and closely relates to determination of surgical strategy. Both the genomic analysis technology and the informatics for the cancer genome data base are rapidly developing. In this paper, we have gathered existing information on the thyroid cancer-related genes involved in the initiation and progression of thyroid cancer. Our goal is to assemble a glossary for the current ThyroSeq genomic panel that can help elucidate the role genomics play in thyroid cancer oncogenesis. PMID:28117295

Efficiency of the Bethesda System for Thyroid Cytopathology.

PubMed

Mora-Guzmán, Ismael; Muñoz de Nova, José Luis; Marín-Campos, Cristina; Jiménez-Heffernan, José Antonio; Cuesta Pérez, Juan Julián; Lahera Vargas, Marcos; Torres Mínguez, Emma; Martín-Pérez, Elena

2018-03-28

Fine-needle aspiration biopsies are a key tool for preoperative assessment of thyroid nodules, and the Bethesda system is the preferred method to report cytological analysis. The purpose of this study is to assess the efficiency of the Bethesda system to identify the malignancy risk of thyroid nodules. Patients who underwent thyroid surgery between June 2010 and June 2017 were included. Samples were classified into 6categories according to rates of malignancy associated with each diagnostic category. In order to investigate the correlation between categories, a statistical analysis compared the categories with pathology reports. Diagnostic indicators were calculated as a screening test (categories IV, V, VI as true-positive) and as a method to identify malignancy (V, VI as true-positive). In a series of 522 patients, we found 184 (35.2%) malignant tumours, papillary carcinoma being the most prevalent with 155 cases (84.2%). Malignant rates for diagnostic categories were: I, 0%; II, 1.5%; III, 6.4%; IV, 31%; V, 86.5%; VI, 100%. A robust correlation was identified between categories on statistical analysis. For the «screening test» analysis, sensitivity was 98.9%, specificity 84.4%, positive predictive value 69.6%, negative predictive value 99.5%, and diagnostic accuracy 88.2%. Analysing the accuracy to detect malignancy, values were: sensitivity 98.6%, specificity 97.6%, positive predictive value 93.5%, negative predictive value 99.5%, diagnostic accuracy 97.9%. The Bethesda system is a clear and reliable approach to report thyroid cytology and therefore is an effective tool to identify malignancy risk and guide clinical management. Copyright © 2018 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

Does the thyroid-stimulating hormone measured concurrently with first trimester biochemical screening tests predict adverse pregnancy outcomes occurring after 20 weeks gestation?

PubMed

Ong, Gregory S Y; Hadlow, Narelle C; Brown, Suzanne J; Lim, Ee Mun; Walsh, John P

2014-12-01

Maternal hypothyroidism in early pregnancy is associated with adverse outcomes, but not consistently across studies. First trimester screening for chromosomal anomalies is routine in many centers and provides an opportunity to test thyroid function. To determine if thyroid function tests performed with first trimester screening predicts adverse pregnancy outcomes. A cohort study of 2411 women in Western Australia with singleton pregnancies attending first trimester screening between 9 and 14 weeks gestation. We evaluated the association between TSH, free T4, free T3, thyroid antibodies, free beta human chorionic gonadotrophin (β-hCG) and pregnancy associated plasma protein A (PAPP-A) with a composite of adverse pregnancy events as the primary outcome. Secondary outcomes included placenta previa, placental abruption, pre-eclampsia, pregnancy loss after 20 weeks gestation, threatened preterm labor, preterm birth, small size for gestational age, neonatal death, and birth defects. TSH exceeded the 97.5th percentile for the first trimester (2.15 mU/L) in 133 (5.5%) women, including 22 (1%) with TSH above the nonpregnant reference range (4 mU/L) and 5 (0.2%) above 10 mU/L. Adverse outcomes occurred in 327 women (15%). TSH and free T4 did not differ significantly between women with or without adverse pregnancy events. On the multivariate analysis, neither maternal TSH >2.15 mU/L nor TSH as a continuous variable predicted primary or secondary outcomes. Testing maternal TSH as part of first trimester screening does not predict adverse pregnancy outcomes. This may be because in the community setting, mainly mild abnormalities in thyroid function are detected.

Ensuring patient safety when implementing a new diagnostic pathway for thyroid nodules.

PubMed

Brimioulle, M; Al-Lami, A; Marzouk, S; Emerson, H; Balfour, A; Dhar, V; Nixon, I J

2018-05-01

Introduction The aim of this study was to determine whether ultrasound alone is sufficient to safely exclude malignancy in thyroid nodules in a district general hospital setting, to comply with the latest British Thyroid Association guidelines. Methods This retrospective study investigated the quality of ultrasound reporting and the correlation between ultrasound report and histology for individual thyroid nodules. Cases were selected from the thyroid multidisciplinary meeting and included all patients having undergone surgery for a thyroid malignancy in a one-year period. Results Forty-seven patients were included in the study. Ultrasound reports were reviewed and assessed, in which 21 clinicians were involved; 36% of scans included a summary of whether the nodule(s) overall appeared benign, equivocal, suspicious or malignant; 4% of reports included a U classification; 81% of reports commented on cervical lymph nodes. Ultrasound was compared with histology. The sensitivity of ultrasound in correctly identifying nodules requiring further investigation was of 56% and specificity was 81%. Positive predictive value was 81% and negative predictive value was 56%. Discussion These findings suggest that, in a district general hospital setting without a dedicated head and neck radiologist, using only ultrasound and limiting fine-needle aspiration cytology to identify suspicious nodules may not be safe, as a high number of nodules appearing benign on ultrasound may ultimately prove to be malignant.

Diagnosis and management of differentiated thyroid cancer using molecular biology.

PubMed

Witt, Robert L; Ferris, Robert L; Pribitkin, Edmund A; Sherman, Steven I; Steward, David L; Nikiforov, Yuri E

2013-04-01

To define molecular biology in clinical practice for diagnosis, surgical management, and prognostication of differentiated thyroid cancer. Ovid Medline 2006-2012 Manuscripts with clinical correlates. Papillary thyroid carcinomas harbor point mutations of the BRAF and RAS genes or RET/PTC rearrangements, all of which activate the mitogen-activated protein kinase pathway. These mutually exclusive mutations are found in 70% of PTC. BRAF mutation is found in 45% of papillary thyroid cancer and is highly specific. Follicular carcinomas are known to harbor RAS mutation or PAX8/PPARγ rearrangement. These mutations are also mutually exclusive and identified in 70% of follicular carcinomas. Molecular classifiers measure the expression of a large number of genes on a microarray chip providing a substantial negative predictive value pending further validation. 1) 20% to 30% of cytologically classified Follicular Neoplasms and Follicular Lesion of Undetermined Significance collectively are malignant on final pathology. Approximately 70% to 80% of thyroid lobectomies performed solely for diagnostic purposes are benign. Molecular alteration testing may reduce the number of unnecessary thyroid procedures, 2) may reduce the number of completion thyroidectomies, and 3) may lead to more individualized operative and postoperative management. Molecular testing for BRAF, RAS, RET/PTC, and PAX8/PPARγ for follicular lesion of undetermined significance and follicular neoplasm improve specificity, whereas molecular classifiers may add negative predictive value to fine needle aspiration diagnosis. Copyright © 2013 The American Laryngological, Rhinological, and Otological Society, Inc.

Thyroid Isthmus Length and Iodine Turnover as Predictors of Successful Radioactive Iodine Therapy in Patients with Graves' Disease

PubMed Central

Hwang, Sena; Han, Seunghee; Lee, Eun Jig

2017-01-01

Radioactive iodine (RAI) therapy is an effective treatment option for Graves' disease. However, predicting treatment failures after RAI therapy remains controversial. The objective of this study was to investigate the factors associated with the success rate of RAI therapy for treatment of Graves' hyperthyroidism. Thyroid functional outcome, pre-RAI ultrasonographic features, and clinical parameters were evaluated retrospectively in 98 patients followed up for at least 12 months after RAI (mean RAI dose was 11.7 ± 1.8 mCi). Hypothyroidism was achieved in 59 patients (60.2%), and euthyroidism in 16 patients (16.3%), while 23 patients (23.5%) remained hyperthyroid. Age, sex, body mass index, pre-RAI thyroid function, or thyroid-stimulating immunoglobulin levels were not associated with treatment outcome. Length of thyroid isthmus (p = 0.028) and 2- to 24-hour iodine uptake ratios (p = 0.002) were significantly associated with treatment failure, which was defined as a persistent hyperthyroid status after RAI therapy. Patients with a longer isthmus had a higher risk of remaining hyperthyroid, with a threshold for isthmus length of 5.2 mm, with a sensitivity of 69.6% and specificity of 70.3% for treatment success. Measuring the length of the thyroid isthmus can be a simple and useful way to predict RAI treatment outcome. PMID:29358949

Levator Muscle Enlargement in Thyroid Eye Disease-Related Upper Eyelid Retraction.

PubMed

Davies, Michael J; Dolman, Peter J

To identify levator palpebrae superioris enlargement in thyroid eye disease (TED)-related upper eyelid retraction (ULR). Retrospective case-control. Subjects included 50 consecutive patients with unilateral thyroid eye disease-related ULR ≥ 2 mm and no previous eyelid surgery. The contralateral side was used as control. Clinical information was recorded from charts. CT scans were assessed by investigators blinded to the clinical data. A prediction of retracted side was made based on CT scan appearance and on basis of measured levator palpebrae superioris cross-sectional area at 2 defined points. Statistical analysis determined correlation between levator palpebrae superioris size and presence of ULR. The study was approved by the institutional ethics committee. Side with ULR predicted from CT scan review in over 85% of cases. Mean cross-sectional area of levator palpebrae superioris on retracted side was significantly larger than nonretracted side at 2 separate sites. Levator palpebrae superioris area was larger on retracted side compared with nonretracted side in over 85% of subjects. More than 30% of subjects had no enlargement of other extraocular muscles. Only 6% of patients had enlargement of the ipsilateral inferior rectus muscle. Levator palpebrae superioris enlargement from inflammation or scar is a factor in thyroid eye disease-related ULR. Upper eyelid retraction can be predicted from CT scan appearance in over 85% of cases. Ipsilateral inferior rectus enlargement is rare. Levator palpebrae superioris is the most commonly targeted muscle in thyroid eye disease.

Thyroid sonography as an effective tool to discriminate between euthyroid sick and hypothyroid dogs.

PubMed

Reese, Sven; Breyer, Ulrike; Deeg, Cornelia; Kraft, Wilfried; Kaspers, Bernd

2005-01-01

The diagnosis of canine hypothyroidism and its differentiation from euthyroid sick syndrome still is a major diagnostic challenge. In this study, ultrasonography was shown to be an effective tool for the investigation of thyroid gland diseases. Healthy control dogs (n = 87), dogs with euthyroid sick syndrome (n = 26), thyroglobulin autoantibody-positive (TgAA-positive, n = 30) hypothyroid dogs, and TgAA-negative (n = 23) hypothyroid dogs were examined by thyroid ultrasonography. Maximal cross sectional area (MCSA), thyroid volume, and echogenicity were measured. Statistical analysis identified highly significant (P < .001) differences between euthyroid and hypothyroid dogs both in thyroid volume and in MCSA, whereas no significant differences in thyroid size were detected between healthy euthyroid dogs and dogs with euthyroid sick syndrome. In euthyroid and euthyroid sick dogs, parenchymal echotexture was homogeneous and hyperechoic, whereas relative thyroid echogenicity of both TgAA-positive and TgAA-negative hypothyroid dogs was significantly lower (P < .001). When using arbitrarily chosen cutoff values for relative thyroid volume, MCSA, and echogenicity, thyroid volume especially was found to have highly specific predictive value for canine hypothyroidism. In summary, the data reveal that thyroid sonography is an effective ancillary diagnostic tool to differentiate between canine hypothyroidism and euthyroid sick syndrome.

Combined effect of Hashimoto's thyroiditis and BRAF(V600E) mutation status on aggressiveness in papillary thyroid cancer.

PubMed

Kim, Su-jin; Myong, Jun Pyo; Jee, Hyeon-Gun; Chai, Young Jun; Choi, June Young; Min, Hye Sook; Lee, Kyu Eun; Youn, Yeo-Kyu

2016-01-01

The purpose of this study was to evaluate the association between Hashimoto's thyroiditis and BRAF(V600E) mutation status in patients with papillary thyroid cancer (PTC) and to determine their combined association with tumor aggressiveness in PTC. A total of 1780 patients with PTC who underwent surgery were enrolled in this study. Simple and multiple analyses were performed to determine the association between Hashimoto's thyroiditis and the BRAF(V600E) mutation in PTC. Hashimoto's thyroiditis was present in 11.5% of patients (204/1780) with PTC. Multiple logistic regressions showed that BRAF(V600E) (odds ratio [OR] = 0.493; 95% confidence interval [CI] = 0.360-0.678) and the female sex (OR = 7.146; 95% CI = 3.408-18.347) were independent factors associated with Hashimoto's thyroiditis in PTC. BRAF(V600E) mutation and the Hashimoto's thyroiditis-negative PTC group were associated with aggressive disease (OR = 3.069; 95% CI = 1.654-5.916). Hashimoto's thyroiditis was associated less frequently with BRAF(V600E) , and frequently with the female sex in patients with PTC. Hashimoto's thyroiditis and BRAF(V600E) status may help to predict clinical outcome of PTC. © 2015 Wiley Periodicals, Inc.

Nivolumab-induced thyroid dysfunction lacking antithyroid antibody is frequently evoked in Japanese patients with malignant melanoma.

PubMed

Yano, Seiichi; Ashida, Kenji; Nagata, Hiromi; Ohe, Kenji; Wada, Naoko; Takeichi, Yukina; Hanada, Yuki; Ibayashi, Yuta; Wang, Lixiang; Sakamoto, Shohei; Sakamoto, Ryuichi; Uchi, Hiroshi; Shiratsuchi, Motoaki; Furue, Masutaka; Nomura, Masatoshi; Ogawa, Yoshihiro

2018-06-08

Nivolumab, an anti-programmed cell death-1 monoclonal antibody, has improved the survival of patients with malignant melanoma. Despite its efficacy, nivolumab inconsistently induces thyroid dysfunction as an immune-related adverse event (irAE). This study aimed to evaluate nivolumab-induced thyroid dysfunction to determine the risks and mechanisms of thyroid irAEs. After excluding 10 patients, data of 24 patients with malignant melanoma (aged 17-85 years; 54% female) were retrospectively analyzed. Thyroid irAEs were observed in seven patients (29%). Three patients had hypothyroidism after preceding transient thyrotoxicosis, and the other four patients had hypothyroidism without thyrotoxicosis. Levothyroxine-Na replacement was required in three patients. Antithyroid antibody (ATA) titer was elevated in one of four assessable patients. The average (±SD) time to onset of thyroid irAE was 33.6 (±21.9) weeks. The administration period of nivolumab was longer in patients with thyroid irAEs than in those without thyroid irAEs (P < 0.01). There were no significant differences between patients with and without thyroid irAEs regarding age, sex, tumor stage, response to nivolumab therapy, baseline thyroid function, antithyroid peroxidase antibody (anti-TPO Ab) and antithyroglobulin antibody (anti-Tg Ab). Thyroid dysfunction was a common irAE of nivolumab in malignant melanoma. Neither anti-TPO Ab nor anti-Tg Ab was associated with the risk for nivolumab-induced thyroid dysfunction. A conventional ATA-independent mechanism might be involved in thyroid irAEs. Further studies are required to clarify the mechanism and identify the predictive factors of thyroid irAEs.

Modeling mixtures of thyroid gland function disruptors in a vertebrate alternative model, the zebrafish eleutheroembryo

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thienpont, Benedicte; Barata, Carlos; Raldúa, Demetrio, E-mail: drpqam@cid.csic.es

2013-06-01

Maternal thyroxine (T4) plays an essential role in fetal brain development, and even mild and transitory deficits in free-T4 in pregnant women can produce irreversible neurological effects in their offspring. Women of childbearing age are daily exposed to mixtures of chemicals disrupting the thyroid gland function (TGFDs) through the diet, drinking water, air and pharmaceuticals, which has raised the highest concern for the potential additive or synergic effects on the development of mild hypothyroxinemia during early pregnancy. Recently we demonstrated that zebrafish eleutheroembryos provide a suitable alternative model for screening chemicals impairing the thyroid hormone synthesis. The present study usedmore » the intrafollicular T4-content (IT4C) of zebrafish eleutheroembryos as integrative endpoint for testing the hypotheses that the effect of mixtures of TGFDs with a similar mode of action [inhibition of thyroid peroxidase (TPO)] was well predicted by a concentration addition concept (CA) model, whereas the response addition concept (RA) model predicted better the effect of dissimilarly acting binary mixtures of TGFDs [TPO-inhibitors and sodium-iodide symporter (NIS)-inhibitors]. However, CA model provided better prediction of joint effects than RA in five out of the six tested mixtures. The exception being the mixture MMI (TPO-inhibitor)-KClO{sub 4} (NIS-inhibitor) dosed at a fixed ratio of EC{sub 10} that provided similar CA and RA predictions and hence it was difficult to get any conclusive result. There results support the phenomenological similarity criterion stating that the concept of concentration addition could be extended to mixture constituents having common apical endpoints or common adverse outcomes. - Highlights: • Potential synergic or additive effect of mixtures of chemicals on thyroid function. • Zebrafish as alternative model for testing the effect of mixtures of goitrogens. • Concentration addition seems to predict better the effect of mixtures of goitrogens.« less

[Predictive value and sensibility of hospital discharge system (PMSI) compared to cancer registries for thyroïd cancer (1999-2000)].

PubMed

Carré, N; Uhry, Z; Velten, M; Trétarre, B; Schvartz, C; Molinié, F; Maarouf, N; Langlois, C; Grosclaude, P; Colonna, M

2006-09-01

Cancer registries have a complete recording of new cancer cases occurring among residents of a specific geographic area. In France, they cover only 13% of the population. For thyroid cancer, where incidence rate is highly variable according to the district conversely to mortality, national incidence estimates are not accurate. A nationwide database, such as hospital discharge system, could improve this estimate but its positive predictive value and sensibility should be evaluated. The positive predictive value and the sensitivity for thyroid cancer case ascertainment (ICD-10) of the national hospital discharge system in 1999 and 2000 were estimated using the cancer registries database of 10 French districts as gold standard. The linkage of the two databases required transmission of nominative information from the health facilities of the study. From the registries database, a logistic regression analysis was carried out to identify factors related to being missed by the hospital discharge system. Among the 973 standardized discharge charts selected from the hospital discharge system, 866 were considered as true positive cases, and 107 as false positive. Forty five of the latter group were prevalent cases. The predictive positive value was 89% (95% confidence interval (CI): 87-91%) and did not differ according to the district (p=0,80). According to the cancer registries, 322 thyroid cancer cases diagnosed in 1999 or 2000 were missed by the hospital discharge system. Thus, the sensitivity of this latter system was 73% (70-76%) and varied significantly from 62% to 85% across districts (p<0.001) and according to the type of health facility (p<0.01). Predictive positive value of the French hospital discharge system for ascertainment of thyroid cancer cases is high and stable across districts. Sensitivity is lower and varies significantly according to the type of health facility and across districts, which limits the interest of this database for a national estimate of thyroid cancer incidence rate.

Establishment and validation of the scoring system for preoperative prediction of central lymph node metastasis in papillary thyroid carcinoma.

PubMed

Liu, Wen; Cheng, Ruochuan; Ma, Yunhai; Wang, Dan; Su, Yanjun; Diao, Chang; Zhang, Jianming; Qian, Jun; Liu, Jin

2018-05-03

Early preoperative diagnosis of central lymph node metastasis (CNM) is crucial to improve survival rates among patients with papillary thyroid carcinoma (PTC). Here, we analyzed clinical data from 2862 PTC patients and developed a scoring system using multivariable logistic regression and testified by the validation group. The predictive diagnostic effectiveness of the scoring system was evaluated based on consistency, discrimination ability, and accuracy. The scoring system considered seven variables: gender, age, tumor size, microcalcification, resistance index >0.7, multiple nodular lesions, and extrathyroid extension. The area under the receiver operating characteristic curve (AUC) was 0.742, indicating a good discrimination. Using 5 points as a diagnostic threshold, the validation results for validation group had an AUC of 0.758, indicating good discrimination and consistency in the scoring system. The sensitivity of this predictive model for preoperative diagnosis of CNM was 4 times higher than a direct ultrasound diagnosis. These data indicate that the CNM prediction model would improve preoperative diagnostic sensitivity for CNM in patients with papillary thyroid carcinoma.

In vitro, ex vivo, and in vivo determination of thyroid hormone modulating activity of benzothiazoles

EPA Science Inventory

As in vitro assays are increasingly used to screen chemicals for their potential to produce endocrine disrupting adverse effects, it is important to understand their predictive capacity. The potential for a set of six benzothiazoles to affect endpoints related to thyroid hormone ...

Ultrasound-Based Risk Stratification for Malignancy in Thyroid Nodules: A Four-Tier Categorization System.

PubMed

Seo, Hyobin; Na, Dong Gyu; Kim, Ji-Hoon; Kim, Kyung Won; Yoon, Ji Won

2015-07-01

The purpose of this study was to stratify the malignancy risk of US features, with an emphasis on nodule echogenicity. A total of 1,058 nodules of 824 consecutive patients (236 malignant and 822 benign) were included in this study. Malignancy risk of each nodule was analyzed according to US features, with an emphasis on nodule echogenecity, and was stratified into 4-tier categories. In multivariate analysis, isoechogenicity, indistinct margin, non-solid internal content, and parallel orientation were predictive of benign nodules (P < 0.002), while hypoechogenicity, marked hypoechogenicity, spiculated/microlobulated margin, solid content, nonparallel orientation (taller than wide), microcalcification, and macrocalcification were predictive of malignancy (P ≤ 0.037). Although the presence of US features associated with malignancy was significantly predictive of malignancy in hypoechoic and markedly hypoechoic nodules (P ≤ 0.004), it was not associated with malignancy in isoechoic or hyperechoic nodules. Thyroid nodules could be stratified into four categories according to the malignancy risk: benign (risk 0%), probably benign (risk ≤ 5%), indeterminate (risk > 5 and < 50%), and suspicion of malignancy (risk > 50%). The US-based four-tier categorization system will be useful for predicting the risk of malignancy and decisions regarding FNA for thyroid nodules. • No US feature was predictive of malignancy in isoechoic nodules. • Isoechoic nodules without calcification can be included in the probably benign category. • We suggest a four-tier categorization stratified primarily by nodule echogenecity. • The four-tier categorization of thyroid nodules will be useful for FNA decisions.

ECM1 and TMPRSS4 Are Diagnostic Markers of Malignant Thyroid Neoplasms and Improve the Accuracy of Fine Needle Aspiration Biopsy

PubMed Central

Kebebew, Electron; Peng, Miao; Reiff, Emily; Duh, Quan-Yang; Clark, Orlo H.; McMillan, Alex

2005-01-01

Objective: The objective of this study was to determine whether genes that regulate cellular invasion and metastasis are differentially expressed and could serve as diagnostic markers of malignant thyroid nodules. Summary and Background Data: Patients whose thyroid nodules have indeterminate or suspicious cytologic features on fine needle aspiration (FNA) biopsy require thyroidectomy because of a 20% to 30% risk of thyroid cancer. Cell invasion and metastasis is a hallmark of malignant phenotype; therefore, genes that regulate these processes might be differentially expressed and could serve as diagnostic markers of malignancy. Methods: Differentially expressed genes (2-fold higher or lower) in malignant versus benign thyroid neoplasms were identified by extracellular matrix and adhesion molecule cDNA array analysis and confirmed by real-time quantitative polymerase chain reaction (PCR). The area under the receiver operating characteristic (AUC) curve was calculated to determine diagnostic accuracy of gene expression level cutoffs established by logistic regression analysis. Results: By cDNA array analysis, ADAMTS8, ECM1, MMP8, PLAU, SELP, and TMPRSS4 were upregulated, and by quantitative PCR, ECM1, SELP, and TMPRSS4 mRNA expression was higher in malignant (n = 57) than in benign (n = 38) thyroid neoplasms (P< 0.002). ECM1 and TMPRSS4 mRNA expression levels were independent predictors of a malignant thyroid neoplasm (P < 0.003). The AUC was 0.956 for ECM1 and 0.926 for TMPRSS4. Combining both markers improved their diagnostic use (AUC 0.985; sensitivity, 91.7%; specificity, 89.8%; positive predictive value, 85.7%; negative predictive value, 82.8%). ECM1 and TMPRSS4 expression analysis improved the diagnostic accuracy of FNA biopsy in 35 of 38 indeterminate or suspicious results. The level of ECM1 mRNA expression was higher in TNM stage I differentiated thyroid cancers than in stage II and III tumors (P ≤ 0.031). Conclusions: ECM1 and TMPRSS4 are excellent diagnostic markers of malignant thyroid nodules and may be used to improve the diagnostic accuracy of FNA biopsy. ECM1 is also a marker of the extent of disease in differentiated thyroid cancers. PMID:16135921

Papillary neoplasia of the breast: immunohistochemically defined myoepithelial cells in the diagnosis of benign and malignant papillary breast neoplasms.

PubMed

Raju, U B; Lee, M W; Zarbo, R J; Crissman, J D

1989-11-01

The presence or absence of myoepithelial cells (ME) has been considered as an important feature in the differential diagnosis of benign and malignant papillary lesions of the breast. We evaluated the distribution of myoepithelial cells in formalin-fixed paraffin-embedded tissue sections of 25 papillomas and 18 papillary carcinomas by ABC immunoperoxidase technique with antibodies to muscle actin (HHF-35) and high molecular weight (HMW) keratin (clone 34BE12, cytokeratins 1, 5, 10, and 14; reacting preferentially with ME cells) and an antiserum to S-100 protein. Also included in the study were eight cases of micropapillary ductal carcinoma in situ (DCIS) having a few fibrovascular cores and five peripheral papillomas with accompanying ductal carcinoma in situ or atypical hyperplasia. The antibodies to muscle actin were sensitive and relatively specific for ME cells of the breast and uniformly labeled ME cells in all 25 papillomas. ME cells were absent or extremely sparse in papillary carcinomas. They were present focally in some of the fibrovascular cores of the micropapillary DCIS, and a mixed pattern was observed in peripheral papillomas with areas of carcinoma. HMW keratin was variably expressed in ME cells in most cases with positive internal controls and was present in several normal ductal and papilloma epithelial cells but not in epithelial cells of papillary carcinomas. HMW keratin, although less specific for ME cells, was a useful adjunct because of its reactivity with ME cells as well as hyperplastic epithelial cells in papillomas, which resulted in a combined positive reaction.(ABSTRACT TRUNCATED AT 250 WORDS)

Elastographic techniques of thyroid gland: current status.

PubMed

Andrioli, Massimiliano; Persani, Luca

2014-08-01

Thyroid nodules are very common with malignancies accounting for about 5 %. Fine-needle biopsy is the most accurate test for thyroid cancer diagnosis. Elastography, a new technology directly evaluating the elastic property of the tissue, has been recently added to the diagnostic armamentarium of the endocrinologists as noninvasive predictor of thyroid malignancy. In this paper, we critically reviewed characteristics and applications of elastographic methods in thyroid gland. Elastographic techniques can be classified on the basis of the following: source-of-tissue compression (free-hand, carotid vibration, ultrasound pulses), processing time (real-time, off-line), stiffness expression (qualitative, semi-quantitative, or quantitative). Acoustic radiation force impulse and aixplorer shear wave are the newest and most promising quantitative elastographic methods. Primary application of elastography is the detection of nodular lesions suspicious for malignancy. Published data show a high sensitivity and negative predictive value of the technique. Insufficient data are available on the possible application of elastography in the differential diagnosis of indeterminate lesions and in thyroiditis. Elastography represents a noninvasive tool able to increase the performance of ultrasound in the selection of thyroid nodules at higher risk of malignancy. Some technical improvements and definition of more robust quantitative diagnostic criteria are required for assigning a definite role in the management of thyroid nodules and thyroiditis to elastography.

A TSHR-LH/CGR chimera that measures functional thyroid-stimulating autoantibodies (TSAb) can predict remission or recurrence in Graves' patients undergoing antithyroid drug (ATD) treatment.

PubMed

Giuliani, Cesidio; Cerrone, Dominique; Harii, Norikazu; Thornton, Mark; Kohn, Leonard D; Dagia, Nilesh M; Bucci, Ines; Carpentieri, Maria; Di Nenno, Barbara; Di Blasio, Andrea; Vitti, Paolo; Monaco, Fabrizio; Napolitano, Giorgio

2012-07-01

A functional thyroid-stimulating autoantibodies (TSAb) assay using a thyroid-stimulating hormone receptor chimera (Mc4) appears to be clinically more useful than the commonly used assay, a binding assay that measures all the antibodies binding to the thyroid-stimulating hormone receptor without functional discrimination, in diagnosing patient with Graves' disease (GD). The objective of the study was to investigate whether an Mc4 assay can predict relapse/remission of hyperthyroidism after antithyroid drug (ATD) treatment in patients with GD. An Mc4 assay was used to prospectively track TSAb activity in GD patients treated with ATD over a 5-yr period. GD patients from the Chieti University participated in this study. Interventions included the assessment of patients' sera using the Mc4 assay, the Mc4-derivative assay (Thyretain), and a human monoclonal thyroid-stimulating hormone receptor antibody, M22 assay. The Mc4 assay, a sensitive index of remission and recurrence, was used in this study. The TSAb levels significantly decreased only in the remitting group as evidenced by Mc4 assay values at the end of ATD (0.96 ± 1.47, 10.9 ± 26.6. and 24.7 ± 37.5 arbitrary units for the remitting, relapsing, and unsuspended therapy groups, respectively). Additional prognostic help was obtained by thyroid volume measurements at the end of treatment. Although not statistically significant, the Mc4 assay has a trend toward improved positive predictive value (95.4 vs. 84.2 or 87.5%), specificity (96.4 vs. 86.4 and 90.9%), and accuracy (87.3 vs. 83.3 and 80.9%) comparing the Mc4, Thyretain, and M22 assays, respectively. Thyretain has a trend toward improved negative predictive value (82.6 vs. 81.8 and 76.9%) and sensitivity (80 vs. 77.8 and 70%) comparing Thyretain, Mc4, and M22 assays, respectively. The Mc4 assay is a clinically useful index of remission and relapse in patients with GD. Larger studies are required to confirm these findings.

Role of imprint cytology in intra operative diagnosis of thyroid lesions.

PubMed

Anila, K R; Krishna, G

2014-07-01

Intra-operative imprint cytology is an important diagnostic modality in the diagnosis of thyroid lesions. A correct intra-operative diagnosis helps eliminate the need for second surgery. To study diagnostic accuracy of imprint cytology and to compare the imprint cytology results with that of the corresponding paraffin section diagnosis in thyroidectomy cases. This is a prospective study of 84 patients who have undergone thyroidectomies over a period of one year at the Department of Surgery, Thiruvananthapuram, Kerala, India. The intraoperative imprint cytology smears were stained by Papanicolaou method. The imprint cytology interpretation was later compared with the paraffin section diagnosis. Of the 84 patients using haematoxylin and eosin stained histopathology sections as the gold standard, the diagnostic sensitivity of imprint cytology was 75% and specificity was 100%. Positive predictive value was 100%. Negative predictive value was 98.74%. Imprint cytology has high sensitivity and specificity in diagnosing lesions of the thyroid. The problems faced were in diagnosing follicular carcinomas and differentiating low grade lymphoma from lymphocytic thyroiditis. Imprint cytology is a simple, reliable diagnostic technique. It has high sensitivity and specificity in intra-operative diagnosis of lesions of thyroid. In spite of the advent of newer diagnostic modalities like frozen sections, imprint cytology still holds its unique position in the current perspective.

Clinical Significance of Thyrotrophin Binding Inhibitor Immunoglobulins in Patients with Graves’ Disease and Various Types of Thyroiditis

PubMed Central

Lee, Chong Suk; Kim, Doo Man; Kim, Chong Soon; Yoo, Hyung Joon

1987-01-01

It is well known that thyrotrophin receptor antibodies are present in the sera of patients with autoimmune thyroid disease. There is now compelling evidence that the hyperthyroidism of Graves’ disease is due to antibodies to the thyrotrophin (TSH) receptor. The measurement of these antibodies is valuable in the diagnosis and monitoring of Graves’ disease and in predicting the outcome of treatment. In the present study, thyrotrophin binding inhibitor immunoglobulin (TBII) activites were measured by radioreceptor assay, according to the method of Shewring and Smith1), in 30 patients with Graves’ disease, 13 patients with Hashimoto’s thyroiditis, 20 patients with lymphocytic thyroiditis with spontaneously resolving hyperthyroidism (LT-SRH), 5 patients with postpartum thyroiditis, and 7 patients with subacute thyroiditis. The TBII activity results a mean of 3.0±3.0% in normal controls, 44.8±8.7% in Graves’ disease, 8.69±8.06% in Hashimoto’s thyroiditis, 7.63±2.32% in LT-SRH, 3.33±1.16% in postpartum thyroiditis, and 2.67±2.33% in subacute thyroiditis respectively. These clinical and laboratory findings show that TBII also plays a role in the pathogenesis of Graves’ disease. The levels of the TBII activties in Hashimoto’s thyroiditis and LT-SRH, suggest a pathognomic role similar to that of Graves’ disease in above mentioned two disease, but that TBII activity is not significant in postpartum or subacute thyroiditis. PMID:2908728

Clinical Features of Early and Late Postoperative Hypothyroidism After Lobectomy.

PubMed

Park, Suyeon; Jeon, Min Ji; Song, Eyun; Oh, Hye-Seon; Kim, Mijin; Kwon, Hyemi; Kim, Tae Yong; Hong, Suck Joon; Shong, Young Kee; Kim, Won Bae; Sung, Tae-Yon; Kim, Won Gu

2017-04-01

Lobectomy is preferred in thyroid cancer to decrease surgical complications and avoid lifelong thyroid-hormone replacement. However, postoperative hypothyroidism, requiring thyroid-hormone replacement, may occur. We aimed to identify the incidence and risk factors of postoperative hypothyroidism to develop a surveillance strategy after lobectomy for papillary thyroid microcarcinoma (PTMC). This historical cohort study involved 335 patients with PTMC treated by lobectomy. Postoperative thyroid functions were measured regularly, and patients were prescribed levothyroxine according to specific criteria. Patients not satisfying hormone-replacement criteria were closely followed up. Postoperative hypothyroidism occurred in 215 patients (64.2%) including 5 (1.5%) with overt hypothyroidism and 210 (62.7%) with subclinical hypothyroidism. Forty patients (11.9%) were required thyroid hormone replacement. One hundred nineteen patients (33.5%) experienced temporary hypothyroidism and spontaneously recovered to euthyroid state. High preoperative thyroid-stimulating hormone (TSH) was the most important factor predicting postoperative hypothyroidism and failure of recover from hypothyroidism (odds ratio [OR], 2.82 and 1.77; 95% confidence interval [CI], 2.07 to 3.95 and 1.22 to 2.63; P < 0.001 and 0.002, respectively). Of the 215 patients eventually developing postoperative hypothyroidism, 70 (32.6%) developed hypothyroidism after the first postoperative year. Postoperative 1-year TSH levels were able to differentiate patients developing late hypothyroidism or euthyroidism (OR, 2.29; 95% CI, 1.68 to 3.26; P < 0.001). Preoperative and postoperative TSH levels might be predictive for patients who develop postlobectomy hypothyroidism and identify those requiring long-term surveillance for hypothyroidism. Additionally, mild postoperative hypothyroidism cases should be followed up without immediate levothyroxine replacement with the expectation of spontaneous recovery. Copyright © 2017 by the Endocrine Society

Correlation of final evoked potential amplitudes on intraoperative electromyography of the recurrent laryngeal nerve with immediate postoperative vocal fold function after thyroid and parathyroid surgery.

PubMed

Genther, Dane J; Kandil, Emad H; Noureldine, Salem I; Tufano, Ralph P

2014-02-01

Thyroid and parathyroid surgery are among the most common operations in the United States. Recurrent laryngeal nerve (RLN) injury is an infrequent but potentially detrimental complication. To correlate the final evoked potential amplitudes on intraoperative electromyography (EMG) after stimulation of the RLN with immediate postoperative vocal fold function after thyroid and parathyroid surgery. Retrospective observational study at a tertiary academic medical center. We included 674 patients (with 1000 nerves at risk) undergoing thyroid or parathyroid surgery from July 1, 2008, through June 30, 2012. Thyroid and parathyroid surgery. The association of final evoked potential amplitudes on EMG after thyroid and parathyroid surgery with vocal fold function as determined by postoperative fiberoptic laryngoscopy. Three patients experienced permanent vocal fold paresis (VFP) secondary to intraoperative RLN transection. Of the remaining 997 RLNs at risk, 22 (2.2%) in 20 patients exhibited temporary VFP on fiberoptic laryngoscopy after extubation. Eighteen patients experienced unilateral temporary VFP, and 2 experienced bilateral VFP without the need for tracheostomy or reintubation. Of the 22 RLNs, postdissection EMG amplitudes were less than 200 µV (true-positive findings) in 21 and at least 200 µV (false-negative finding) in 1. Of the 975 RLNs (97.5%) with normal function, postdissection EMG amplitudes were at least 200 µV (true-negative findings) in 967 and less than 200 µV (false-positive findings) in 8. In regard to immediate postoperative VFP, sensitivity, specificity, positive and negative predictive values, and accuracy of postdissection EMG amplitudes of less than 200 µV were 95.5%, 99.2%, 72.4%, 99.9%, and 99.1%, respectively. Intraoperative nerve monitoring of the RLN with EMG provides real-time information regarding neurophysiologic function of the RLN and can predict immediate postoperative VFP reliably when a cutoff of 200 µV is used. The high negative predictive value means that the surgeon can presume with confidence that the RLN has not been injured in the presence of a potential of at least 200 µV. This information would be useful in patients for whom bilateral thyroid surgery is being considered.

An AOP-based alternative testing strategy to predict the impact of thyroid hormone disruption on swim bladder inflation in zebrafish

EPA Science Inventory

Within the field of chemical safety assessment, there is a desire to replace costly whole organism testing with more efficient and cost-effective alternatives based on in vitro test systems. Disruption of thyroid hormone signaling via inhibition of enzymes called deiodinases is o...

A SYSTEMS APPROACH TO CHARACTERIZING AND PREDICTING THYROID TOXICITY USING AN AMPHIBIAN MODEL

EPA Science Inventory

The EPA was recently mandated to evaluate the potential effects of chemicals on endocrine function and has identified Xenopus as a model organism to use as the basis for a thyroid disruption screening assay. The main objective of this work is to develop a hypothalamic-pituitary-t...

Thyroid Allostasis–Adaptive Responses of Thyrotropic Feedback Control to Conditions of Strain, Stress, and Developmental Programming

PubMed Central

Chatzitomaris, Apostolos; Hoermann, Rudolf; Midgley, John E.; Hering, Steffen; Urban, Aline; Dietrich, Barbara; Abood, Assjana; Klein, Harald H.; Dietrich, Johannes W.

2017-01-01

The hypothalamus–pituitary–thyroid feedback control is a dynamic, adaptive system. In situations of illness and deprivation of energy representing type 1 allostasis, the stress response operates to alter both its set point and peripheral transfer parameters. In contrast, type 2 allostatic load, typically effective in psychosocial stress, pregnancy, metabolic syndrome, and adaptation to cold, produces a nearly opposite phenotype of predictive plasticity. The non-thyroidal illness syndrome (NTIS) or thyroid allostasis in critical illness, tumors, uremia, and starvation (TACITUS), commonly observed in hospitalized patients, displays a historically well-studied pattern of allostatic thyroid response. This is characterized by decreased total and free thyroid hormone concentrations and varying levels of thyroid-stimulating hormone (TSH) ranging from decreased (in severe cases) to normal or even elevated (mainly in the recovery phase) TSH concentrations. An acute versus chronic stage (wasting syndrome) of TACITUS can be discerned. The two types differ in molecular mechanisms and prognosis. The acute adaptation of thyroid hormone metabolism to critical illness may prove beneficial to the organism, whereas the far more complex molecular alterations associated with chronic illness frequently lead to allostatic overload. The latter is associated with poor outcome, independently of the underlying disease. Adaptive responses of thyroid homeostasis extend to alterations in thyroid hormone concentrations during fetal life, periods of weight gain or loss, thermoregulation, physical exercise, and psychiatric diseases. The various forms of thyroid allostasis pose serious problems in differential diagnosis of thyroid disease. This review article provides an overview of physiological mechanisms as well as major diagnostic and therapeutic implications of thyroid allostasis under a variety of developmental and straining conditions. PMID:28775711

CIRCULATING THYROID-STIMULATING HORMONE RECEPTOR MESSENGER RNA AS A MARKER OF TUMOR AGGRESSIVENESS IN PATIENTS WITH PAPILLARY THYROID MICROCARCINOMA.

PubMed

Aliyev, Altay; Gupta, Manjula; Nasr, Christian; Hatipoglu, Betul; Milas, Mira; Siperstein, Allan; Berber, Eren

2015-07-01

We have previously shown that thyroid-stimulating hormone receptor messenger RNA (TSHR mRNA) is detectable in the peripheral blood of patients with papillary thyroid microcarcinoma (PTmC). The aim of this study was to analyze the utility of TSHR mRNA status as a marker of tumor aggressiveness in patients with PTmC. Preoperative TSHR mRNA values were obtained in 152 patients who underwent thyroidectomy and were found to have PTmC on final pathology. Clinical parameters were analyzed from an institutional review board-approved database using χ(2) and t tests. Preoperatively, TSHR mRNA was detected in the peripheral blood in 46% of patients, which was less than that for macroscopic papillary thyroid carcinoma (PTC) (80%) but higher than for benign thyroid disease (18%) (P<.001). The focus of cancer was larger in the TSHR mRNA-positive group compared to the negative group (0.41 vs. 0.30 cm, respectively, P = .015). The prevalence of tall-cell variant was higher in the TSHR mRNA positive group. The rates of lymph node (LN) metastasis (16% vs. 10%), multifocality (46% vs. 49%), and extra-thyroidal extension (10% vs. 5%) were similar between the TSHR mRNA-positive and-negative groups, respectively. In patients 45 years or older, rate of LN metastasis was higher in those who were TSHR mRNA positive (10%) versus negative (2%) (P = .039). TSHR mRNA positivity predicted a higher likelihood of radioactive iodine treatment (36% vs. 17%, P = .009) postoperatively. This study shows that TSHR mRNA, which is a marker of circulating thyroid cancer cells, is detectable in about half of patients with PTmC. The positivity of this marker predicts a higher likelihood of LN involvement in patients with PTmC who are 45 years or older.

[Study on the relationship between ultrasonographic features of papillary thyroid carcinoma and central cervical lymph node metastasis].

PubMed

Wang, X Q; Wei, W; Wei, X; Xu, Y; Wang, H L; Xing, X J; Zhang, S

2018-03-23

Objective: To investigate the correlation between ultrasonographic features of papillary thyroid carcinoma and central cervical lymph node metastasis. Methods: We retrospectively analyzed 486 patients with papillary thyroid carcinoma(PTC), pathologically confirmed after surgery in Tianjin Medical University Cancer Institute & Hospital. All patients were divided into central cervical lymph node metastasis group and non-metastasis group. No lateral cervical lymph node metastasis was found in preoperative ultrasonography and postoperative pathology. The characteristics of the ultrasound was observed and analyzed. Results: 297 out of 486 patients with papillary thyroid carcinomahad central metastasis, and the other 189 cases did not. Take pathology results as a standard, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy rate of preoperative ultrasound diagnosis in PTC patients with central cervical lymph node metastasis were 35.3%, 88.6%, 83.2%, 47.4%, 56.6%, respectively. Univariate analysis showed that multi-focus, taller-than-wide, diameter>1 cm, located in the lower pole, ill-defined margin, hypoechogenicity, micro-calcification, capsule invasion more than 1/4 perimeter of papillary thyroid carcinoma were significantly associated with central cervical lymph node metastasis (all P <0.05). Multivariate analysis showed that diameter>1 cm, micro-calcification, capsule invasion more than 1/4 perimeter of papillary thyroid carcinoma became independent risk factors of central cervical neck lymph node metastasis (all P <0.05). Conclusions: Preoperative description of ultrasonographical features has important value to assess central cervical lymph node metastasis in patients with papillary thyroid carcinoma. More information could be provided for clinical treatment. When the papillary thyroid carcinoma presented as diameter>1 cm, micro-calcification, and capsule invasion more than 1/4 perimeter of, there will be a greater risk of central cervical lymph node metastasis, and we shall suggest prophylactic central lymph cervical node dissection.

Testing prediction capabilities of an 131I terrestrial transport model by using measurements collected at the Hanford nuclear facility.

PubMed

Apostoaei, A Iulian

2005-05-01

A model describing transport of 131I in the environment was developed by SENES Oak Ridge, Inc., for assessment of radiation doses and excess lifetime risk from 131I atmospheric releases from Oak Ridge Reservation in Oak Ridge, Tennessee, and from Idaho National Engineering and Environmental Laboratory in southeast Idaho. This paper describes the results of an exercise designed to test the reliability of this model and to identify the main sources of uncertainty in doses and risks estimated by this model. The testing of the model was based on materials published by the International Atomic Energy Agency BIOMASS program, specifically environmental data collected after the release into atmosphere of 63 curies of 131I during 2-5 September 1963, after an accident at the Hanford PUREX Chemical Separations Plant, in Hanford, Washington. Measurements of activity in air, vegetation, and milk were collected in nine counties around Hanford during the first couple of months after the accident. The activity of 131I in the thyroid glands of two children was measured 47 d after the accident. The model developed by SENES Oak Ridge, Inc., was used to estimate concentrations of 131I in environmental media, thyroid doses for the general population, and the activity of 131I in thyroid glands of the two children. Predicted concentrations of 131I in pasture grass and milk and thyroid doses were compared with similar estimates produced by other modelers. The SENES model was also used to estimate excess lifetime risk of thyroid cancer due to the September 1963 releases of 131I from Hanford. The SENES model was first calibrated and then applied to all locations of interest around Hanford without fitting the model parameters to a given location. Predictions showed that the SENES model reproduces satisfactorily the time-dependent and the time-integrated measured concentrations in vegetation and milk, and provides reliable estimates of 131I activity in thyroids of children. SENES model generated concentrations of 131I closer to observed concentrations, as compared to the predictions produced with other models. The inter-model comparison showed that variation of thyroid doses among all participating models (SENES model included) was a factor of 3 for the general population, but a factor of 10 for the two studied children. As opposed to other models, SENES model allows a complete analysis of uncertainties in every predicted quantity, including estimated thyroid doses and risk of thyroid cancer. The uncertainties in the risk-per-unit-dose and the dose-per-unit-intake coefficients are major contributors to the uncertainty in the estimated lifetime risk and thyroid dose, respectively. The largest contributors to the uncertainty in the estimated concentration in milk are the feed-to-milk transfer factor (F(m)), the dry deposition velocity (V(d)), and the mass interception factor (r/Y)dry for the elemental form of iodine (I2). Exposure to the 1963 PUREX/Hanford accident produced low doses and risks for people living at the studied locations. The upper 97.5th percentile of the excess lifetime risk of thyroid cancer for the most extreme situations is about 10(-4). Measurements in pasture grass and milk at all locations around Hanford indicate a very low transfer of 131I from pasture to cow's milk (e.g., a feed-to-milk transfer coefficient, F(m), for commercial cows of about 0.0022 d L(-1)). These values are towards the low end of F(m) values measured elsewhere and they are low compared to the F(m) values used in other dose reconstruction studies, including the Hanford Environmental Dose Reconstruction.

Usefulness of Measuring Thyroid Stimulating Antibody at the Time of Antithyroid Drug Withdrawal for Predicting Relapse of Graves Disease.

PubMed

Kwon, Hyemi; Kim, Won Gu; Jang, Eun Kyung; Kim, Mijin; Park, Suyeon; Jeon, Min Ji; Kim, Tae Yong; Ryu, Jin Sook; Shong, Young Kee; Kim, Won Bae

2016-06-01

Hyperthyroidism relapse in Graves disease after antithyroid drug (ATD) withdrawal is common; however, measuring the thyrotropin receptor antibody (TRAb) at ATD withdrawal in order to predict outcomes is controversial. This study compared measurement of thyroid stimulatory antibody (TSAb) and thyrotropin-binding inhibitory immunoglobulin (TBII) at ATD withdrawal to predict relapse. This retrospective study enrolled patients with Graves disease who were treated with ATDs and whose serum thyroid-stimulating hormone levels were normal after receiving low-dose ATDs. ATD therapy was stopped irrespective of TRAb positivity after an additional 6 months of receiving the minimum dose of ATD therapy. Patients were followed using thyroid function tests and TSAb (TSAb group; n=35) or TBII (TBII group; n=39) every 3 to 6 months for 2 years after ATD withdrawal. Twenty-eight patients (38%) relapsed for a median follow-up of 21 months, and there were no differences in baseline clinical characteristics between groups. In the TSAb group, relapse was more common in patients with positive TSAb at ATD withdrawal (67%) than patients with negative TSAb (17%; P=0.007). Relapse-free survival was shorter in TSAb-positive patients. In the TBII group, there were no differences in the relapse rate and relapse-free survivals according to TBII positivity. For predicting Graves disease relapse, the sensitivity and specificity of TSAb were 63% and 83%, respectively, whereas those of TBII were 28% and 65%. TSAb at ATD withdrawal can predict the relapse of Graves hyperthyroidism, but TBII cannot. Measuring TSAb at ATD withdrawal can assist with clinical decisions making for patients with Graves disease.

Usefulness of Measuring Thyroid Stimulating Antibody at the Time of Antithyroid Drug Withdrawal for Predicting Relapse of Graves Disease

PubMed Central

Kwon, Hyemi; Jang, Eun Kyung; Kim, Mijin; Park, Suyeon; Jeon, Min Ji; Kim, Tae Yong; Ryu, Jin-Sook; Shong, Young Kee; Kim, Won Bae

2016-01-01

Background Hyperthyroidism relapse in Graves disease after antithyroid drug (ATD) withdrawal is common; however, measuring the thyrotropin receptor antibody (TRAb) at ATD withdrawal in order to predict outcomes is controversial. This study compared measurement of thyroid stimulatory antibody (TSAb) and thyrotropin-binding inhibitory immunoglobulin (TBII) at ATD withdrawal to predict relapse. Methods This retrospective study enrolled patients with Graves disease who were treated with ATDs and whose serum thyroid-stimulating hormone levels were normal after receiving low-dose ATDs. ATD therapy was stopped irrespective of TRAb positivity after an additional 6 months of receiving the minimum dose of ATD therapy. Patients were followed using thyroid function tests and TSAb (TSAb group; n=35) or TBII (TBII group; n=39) every 3 to 6 months for 2 years after ATD withdrawal. Results Twenty-eight patients (38%) relapsed for a median follow-up of 21 months, and there were no differences in baseline clinical characteristics between groups. In the TSAb group, relapse was more common in patients with positive TSAb at ATD withdrawal (67%) than patients with negative TSAb (17%; P=0.007). Relapse-free survival was shorter in TSAb-positive patients. In the TBII group, there were no differences in the relapse rate and relapse-free survivals according to TBII positivity. For predicting Graves disease relapse, the sensitivity and specificity of TSAb were 63% and 83%, respectively, whereas those of TBII were 28% and 65%. Conclusion TSAb at ATD withdrawal can predict the relapse of Graves hyperthyroidism, but TBII cannot. Measuring TSAb at ATD withdrawal can assist with clinical decisions making for patients with Graves disease. PMID:27118279

Relapse prediction in Graves´ disease: Towards mathematical modeling of clinical, immune and genetic markers.

PubMed

Langenstein, Christoph; Schork, Diana; Badenhoop, Klaus; Herrmann, Eva

2016-12-01

Graves' disease (GD) is an important and prevalent thyroid autoimmune disorder. Standard therapy for GD consists of antithyroid drugs (ATD) with treatment periods of around 12 months but relapse is frequent. Since predictors for relapse are difficult to identify the individual decision making for optimal treatment is often arbitrary. After reviewing the literature on this topic we summarize important factors involved in GD and with respect to their potential for relapse prediction from markers before and after treatment. This information was used to design a mathematical model integrating thyroid hormone parameters, thyroid size, antibody titers and a complex algorithm encompassing genetic predisposition, environmental exposures and current immune activity in order to arrive at a prognostic index for relapse risk after treatment. In the search for a tool to analyze and predict relapse in GD mathematical modeling is a promising approach. In analogy to mathematical modeling approaches in other diseases such as viral infections, we developed a differential equation model on the basis of published clinical trials in patients with GD. Although our model needs further evaluation to be applicable in a clinical context, it provides a perspective for an important contribution to a final statistical prediction model.

Psychosocial distress in patients with thyroid cancer.

PubMed

Buchmann, Luke; Ashby, Shaelene; Cannon, Richard B; Hunt, Jason P

2015-04-01

The purpose of this study is to evaluate levels of psychosocial distress in thyroid cancer patients. An analysis of factors contributing to levels of distress is included. Individual retrospective cohort study. Head and neck cancer clinic at the Huntsman Cancer Institute. A total of 118 newly diagnosed thyroid cancer patients were included in the study. Univariate and multivariate analyses evaluated levels of and factors contributing to distress. Almost half (43.3%) of patients had significant distress. Those with self-reported psychiatric history, use of antidepressant medication, and history of radiation treatment had higher levels of distress. On multivariate analysis, patient endorsement of emotional issues predicted a higher distress level. Thyroid cancer patients have high distress levels. Identification of thyroid cancer patients with high distress levels is important to offer additional support during cancer therapy. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.

Pioglitazone Induces a Proadipogenic Antitumor Response in Mice with PAX8-PPARγ Fusion Protein Thyroid Carcinoma

PubMed Central

Dobson, Melissa E.; Diallo-Krou, Ericka; Grachtchouk, Vladimir; Yu, Jingcheng; Colby, Lesley A.; Wilkinson, John E.; Giordano, Thomas J.

2011-01-01

Approximately 35% of follicular thyroid carcinomas harbor a chromosomal translocation that results in expression of a paired box gene 8-peroxisome proliferator-activated receptor γ gene (PPARγ) fusion protein (PPFP). To better understand the oncogenic role of PPFP and its relationship to endogenous PPARγ, we generated a transgenic mouse model that combines Cre-dependent PPFP expression (PPFP;Cre) with homozygous deletion of floxed Pten (PtenFF;Cre), both thyroid specific. Although neither PPFP;Cre nor PtenFF;Cre mice develop thyroid tumors, the combined PPFP;PtenFF;Cre mice develop metastatic thyroid cancer, consistent with patient data that PPFP is occasionally found in benign thyroid adenomas and that PPFP carcinomas have increased phosphorylated AKT/protein kinase B. We then tested the effects of the PPARγ agonist pioglitazone in our mouse model. Pioglitazone had no effect on PtenFF;Cre mouse thyroids. However, the thyroids in pioglitazone-fed PPFP;PtenFF;Cre mice decreased 7-fold in size, and metastatic disease was prevented. Remarkably, pioglitazone caused an adipogenic response in the PPFP;PtenFF;Cre thyroids characterized by lipid accumulation and the induction of a broad array of adipocyte PPARγ target genes. These data indicate that, in the presence of pioglitazone, PPFP has PPARγ-like activity that results in trans-differentiation of thyroid carcinoma cells into adipocyte-like cells. Furthermore, the data predict that pioglitazone will be therapeutic in patients with PPFP-positive carcinomas. PMID:21952241

Thyroid Hypoplasia in Congenital Hypothyroidism Associated with Thyroid Peroxidase Mutations.

PubMed

Stoupa, Athanasia; Chaabane, Rim; Guériouz, Manelle; Raynaud-Ravni, Catherine; Nitschke, Patrick; Bole-Feyset, Christine; Mnif, Mouna; Ammar Keskes, Leila; Hachicha, Mongia; Belguith, Neila; Polak, Michel; Carré, Aurore

2018-05-23

Primary congenital hypothyroidism (CH) affects about 1:3000 newborns worldwide and is mainly caused by defects in thyroid gland development (thyroid dysgenesis, TD) or hormone synthesis. A genetic cause is identified in less than 10% of TD patients. Our aim was to identify novel candidate genes in patients with TD using next-generation sequencing tools. We used whole exome sequencing (WES) to study two families, a consanguineous Tunisian family (one child with severe thyroid hypoplasia) and a French family (two newborn siblings, with a thyroid in situ that was not enlarged on ultrasound at diagnosis). Variants in candidate genes were filtered according to type of variation, frequency in public and in-house databases, in silico prediction tools, and inheritance mode. We unexpectedly identified three different variants of the thyroid peroxidase (TPO) gene. A homozygous missense mutation (c.875C>T, p.S292F) was found in the Tunisian patient with severe thyroid hypoplasia. The two French siblings were compound heterozygotes (c.387delC/c.2578G>A, p.N129Kfs*80/p.G860R) for TPO mutations. All three mutations have been previously described in patients with goitrous CH. In our patients treatment was initiated immediately after diagnosis and the effect, if any, of TSH stimulation of these thyroids remains unclear. We report the first cases of thyroid hypoplasia at diagnosis during neonatal period in patients with CH and TPO mutations. These cases highlight the importance of screening for TPO mutations not only in goitrous CH, but also in thyroids of normal or small size, and they broaden the clinical spectrum of described phenotypes.

An AOP-based alternative testing strategy to predict the impact of thyroid hormone disruption on swim bladder inflation in zebrafish (poster)

EPA Science Inventory

Within the field of chemical safety assessment, there is a desire to replace costly whole organism testing with more efficient and cost-effective alternatives based on in vitro test systems. Disruption of thyroid hormone signaling via inhibition of enzymes called deiodinases is o...

Comparison of in vitro and ex vivo thyroid hormone synthesis inhibition results and in vivo outcomes for a series of benzothiazoles

EPA Science Inventory

Assessing how in vitro data may be used to predict adverse effects in vivo is critical as efforts are advanced to incorporate in vitro assays into a risk assessment framework. Within the context of a thyroid hormone (TH) synthesis inhibition adverse outcome pathway (AOP), in vitr...

[On-site fine-needle aspiration cytology of thyroid nodules. Quality assurance of the Bethesda System for Reporting Thyroid Cytopathology (2008)].

PubMed

Bak, Mihály; Péter, Ilona; Nyári, Tibor; Simon, Péter; Újlaky, Mátyás; Boér, András; Kásler, Miklós

2015-10-11

The methods available for the diagnosis of thyroid nodules include physical examination, imaging, laboratory and fine-needle aspiration cytology tests. The aim of this study was to determine the quality assurance of fine-needle aspiration cytology of thyroid nodules. Cytology results were rated to 6 categories according to the Bethesda System for Reporting Thyroid Cytopathology (2008) (I. nondiagnostic; II. benign; III. atypia of undetermined significance; IV. follicular neoplasia; V. suspicious for malignancy; VI. malignant). All cytology reports were compared with the final histology diagnosis. A total of 1384 patient with thyroid nodule underwent fine-needle aspiration biopsy cytology. Smears were classified I. inadequate in 214 (15.9%); II. benign 986; III. atypical 56; IV. follicular neoplasm 41; V. suspicious for malignancy 18; VI. malignant 33 cases. Two hundred and twenty seven (16.8%) of the cases were operated and histologically verified. The positive predictive value in the benign category was 98.25% and in the malignant 88.46%. The sensitivity of the follicular neoplasm was 66.67%. The results suggest that fine-needle aspiration cytology of thyroid nodules using the Bethesda System for Reporting Thyroid Cytopathology has a high diagnostic accuracy. The auditing values of the results meet the proposed threshold values.

Breaking Tolerance to Thyroid Antigens: Changing Concepts in Thyroid Autoimmunity

PubMed Central

Rapoport, Basil

2014-01-01

Thyroid autoimmunity involves loss of tolerance to thyroid proteins in genetically susceptible individuals in association with environmental factors. In central tolerance, intrathymic autoantigen presentation deletes immature T cells with high affinity for autoantigen-derived peptides. Regulatory T cells provide an alternative mechanism to silence autoimmune T cells in the periphery. The TSH receptor (TSHR), thyroid peroxidase (TPO), and thyroglobulin (Tg) have unusual properties (“immunogenicity”) that contribute to breaking tolerance, including size, abundance, membrane association, glycosylation, and polymorphisms. Insight into loss of tolerance to thyroid proteins comes from spontaneous and induced animal models: 1) intrathymic expression controls self-tolerance to the TSHR, not TPO or Tg; 2) regulatory T cells are not involved in TSHR self-tolerance and instead control the balance between Graves' disease and thyroiditis; 3) breaking TSHR tolerance involves contributions from major histocompatibility complex molecules (humans and induced mouse models), TSHR polymorphism(s) (humans), and alternative splicing (mice); 4) loss of tolerance to Tg before TPO indicates that greater Tg immunogenicity vs TPO dominates central tolerance expectations; 5) tolerance is induced by thyroid autoantigen administration before autoimmunity is established; 6) interferon-α therapy for hepatitis C infection enhances thyroid autoimmunity in patients with intact immunity; Graves' disease developing after T-cell depletion reflects reconstitution autoimmunity; and 7) most environmental factors (including excess iodine) “reveal,” but do not induce, thyroid autoimmunity. Micro-organisms likely exert their effects via bystander stimulation. Finally, no single mechanism explains the loss of tolerance to thyroid proteins. The goal of inducing self-tolerance to prevent autoimmune thyroid disease will require accurate prediction of at-risk individuals together with an antigen-specific, not blanket, therapeutic approach. PMID:24091783

A prospective cohort study on radiation-induced hypothyroidism: development of an NTCP model.

PubMed

Boomsma, Marjolein J; Bijl, Hendrik P; Christianen, Miranda E M C; Beetz, Ivo; Chouvalova, Olga; Steenbakkers, Roel J H M; van der Laan, Bernard F A M; Wolffenbuttel, Bruce H R; Oosting, Sjoukje F; Schilstra, Cornelis; Langendijk, Johannes A

2012-11-01

To establish a multivariate normal tissue complication probability (NTCP) model for radiation-induced hypothyroidism. The thyroid-stimulating hormone (TSH) level of 105 patients treated with (chemo-) radiation therapy for head-and-neck cancer was prospectively measured during a median follow-up of 2.5 years. Hypothyroidism was defined as elevated serum TSH with decreased or normal free thyroxin (T4). A multivariate logistic regression model with bootstrapping was used to determine the most important prognostic variables for radiation-induced hypothyroidism. Thirty-five patients (33%) developed primary hypothyroidism within 2 years after radiation therapy. An NTCP model based on 2 variables, including the mean thyroid gland dose and the thyroid gland volume, was most predictive for radiation-induced hypothyroidism. NTCP values increased with higher mean thyroid gland dose (odds ratio [OR]: 1.064/Gy) and decreased with higher thyroid gland volume (OR: 0.826/cm(3)). Model performance was good with an area under the curve (AUC) of 0.85. This is the first prospective study resulting in an NTCP model for radiation-induced hypothyroidism. The probability of hypothyroidism rises with increasing dose to the thyroid gland, whereas it reduces with increasing thyroid gland volume. Copyright © 2012 Elsevier Inc. All rights reserved.

Diagnosis of hyperfunctional thyroid nodules: impact of US-elastography.

PubMed

Ruhlmann, M; Stebner, V; Görges, R; Farahati, J; Simon, D; Bockisch, A; Rosenbaum-Krumme, S; Nagarajah, J

2014-01-01

Several studies described the ultrasound based real-time elastography (USE) having a high sensitivity, specificity and negative predictive value in the diagnosis of suspicious thyroid nodules. Recently published studies called these results into question. Until now the usefulness of USE in the diagnosis of scintigraphically hyperfunctional thyroid nodules is not examined. This study included 135 hyperfunctional thyroid nodules of 102 consecutive patients. The following attributes of the nodules were analyzed: stiffness with the USE using scores of Rago or Asteria and ultrasound criteria using TIRADS. 94 of the examined thyroid nodules (70%) were rated as hard (suspicious for malignancy) and 41 nodules (30%) as soft (not suspicious) with a specificity of 30%. The scoring systems of Rago and Asteria showed no significant difference. Applying the TIRADS criteria 44 nodules (33%) have a higher risk for malignancy (33 nodules TIRADS 4a, 11 nodules TIRADS 4b). Combining USE and TIRADS 32 nodules (24%) are categorized as suspicious (intersection of hard nodules that are categorized as TIRADS 4a or 4b). Ultrasound based real-time elastography cannot identify scintigraphically hyperfunctional thyroid nodules as benign nodules reliably. Its accuracy in the assessment of at least "hot" thyroid nodules is to be questioned.

Diagnostic accuracy of [99mTc]Tc-Sestamibi in the assessment of thyroid nodules

PubMed Central

Yordanova, Anna; Mahjoob, Soha; Lingohr, Philipp; Kalff, Jörg; Türler, Andreas; Palmedo, Holger; Biersack, Hans-Jürgen; Kristiansen, Glen; Farahati, Jamshid; Essler, Markus; Ahmadzadehfar, Hojjat

2017-01-01

[99mTc]Tc-Sestamibi (MIBI) is an increasingly used tool for evaluation of thyroid nodules. However, there is a lack of evidence about the accuracy of this method in the European population. The aim of this study was to assess the utility of MIBI for the differentiation of thyroid nodules in a large cohort. 161 patients underwent MIBI, followed by a thyroidectomy. We used a dual phase MIBI protocol. Interpretation of the images included a scoring system from 0 (absent) to 3 (increased); this was to provide a scale for the uptake of the thyroid nodule in comparison to the paranodular tissue. Additionally, we evaluated the tracer uptake trend in late images compared to early images. We used the final histopathology as the reference standard. Scores 0-1 in early images, scores 0-2 in late images, and an absence of increasing uptake in the thyroid nodule in late images, showed the best predictive values to exclude malignancy, respectively (negative predictive value (NPV) 89%). Highest sensitivity (91%) for malignant nodules was evident in early images with a score 1-3. Highest specificity (91%) was obtained when the negative was defined as an absence of uptake-increase, in the late images. This study confirms that the most valuable feature of MIBI is the high NPV. Thus, with the appropriate interpretation method, high sensitivity and specificity, and moderate PPV can be obtained. PMID:29212258

Diagnostic accuracy of [99mTc]Tc-Sestamibi in the assessment of thyroid nodules.

PubMed

Yordanova, Anna; Mahjoob, Soha; Lingohr, Philipp; Kalff, Jörg; Türler, Andreas; Palmedo, Holger; Biersack, Hans-Jürgen; Kristiansen, Glen; Farahati, Jamshid; Essler, Markus; Ahmadzadehfar, Hojjat

2017-11-07

[ 99m Tc]Tc-Sestamibi (MIBI) is an increasingly used tool for evaluation of thyroid nodules. However, there is a lack of evidence about the accuracy of this method in the European population. The aim of this study was to assess the utility of MIBI for the differentiation of thyroid nodules in a large cohort. 161 patients underwent MIBI, followed by a thyroidectomy. We used a dual phase MIBI protocol. Interpretation of the images included a scoring system from 0 (absent) to 3 (increased); this was to provide a scale for the uptake of the thyroid nodule in comparison to the paranodular tissue. Additionally, we evaluated the tracer uptake trend in late images compared to early images. We used the final histopathology as the reference standard. Scores 0-1 in early images, scores 0-2 in late images, and an absence of increasing uptake in the thyroid nodule in late images, showed the best predictive values to exclude malignancy, respectively (negative predictive value (NPV) 89%). Highest sensitivity (91%) for malignant nodules was evident in early images with a score 1-3. Highest specificity (91%) was obtained when the negative was defined as an absence of uptake-increase, in the late images. This study confirms that the most valuable feature of MIBI is the high NPV. Thus, with the appropriate interpretation method, high sensitivity and specificity, and moderate PPV can be obtained.

Molecular genetic markers for thyroid FNAB. Established assays and future perspective.

PubMed

Musholt, Thomas J; Musholt, P B

2015-01-01

Thyroid nodules > 1 cm are observed in about 12% of unselected adult employees aged 18-65 years screened by ultrasound scan (40). While intensive ultrasound screening leads to early detection of thyroid diseases, the determination of benign or malignant behaviour remains uncertain and may trigger anxieties in many patients and their physicians. A considerable number of thyroid resections are consecutively performed due to suspicion of malignancy in the detected nodes. Fine needle aspiration biopsy (FNAB) has been recommended for the assessment of thyroid nodules to facilitate detection of thyroid carcinomas but also to rule out malignancy and thereby avoid unnecessary thyroid resections. However, cytology results are dependent on experience of the respective cytologist and unfortunately inconclusive in many cases. Molecular genetic markers are already used nowadays to enhance sensitivity and specificity of FNAB cytology in some centers in Germany. The most clinically relevant molecular genetic markers as pre-operative diagnostic tools and the clinical implications for the intraoperative and postoperative management were reviewed. Molecular genetic markers predominantly focus on the preoperative detection of thyroid malignancies rather than the exclusion of thyroid carcinomas. While some centers routinely assess FNABs, other centers concentrate on FNABs with cytology results of follicular neoplasia or suspicion of thyroid carcinoma. Predominantly mutations of BRAF, RET/PTC, RAS, and PAX8/PPARγ or expression of miRNAs are analyzed. However, only the detection of BRAF mutations predicts the presence of (papillary) thyroid malignancy with almost 98% probability, indicating necessity of oncologic thyroid resections irrespective of the cytology result. Other genetic alterations are associated with thyroid malignancy with varying frequency and achieve less impact on the clinical management. Molecular genetic analysis of FNABs is increasingly performed in Germany. Standardization, quality controls, and validation of various methods need to be implemented in the near future to be able to compare the results. With increasing knowledge about the impact of genetic alterations on the prognosis of thyroid carcinomas, recommendations have to be defined that may lead to individually optimized treatment strategies.

EVALUATION OF QUANTITATIVE THYROID SCINTIGRAPHY FOR DIAGNOSIS AND STAGING OF DISEASE SEVERITY IN CATS WITH HYPERTHYROIDISM: COMPARISON OF THE PERCENT THYROIDAL UPTAKE OF PERTECHNETATE TO THYROID-TO-SALIVARY RATIO AND THYROID-TO-BACKGROUND RATIOS.

PubMed

Peterson, Mark E; Guterl, Jade N; Rishniw, Mark; Broome, Michael R

2016-07-01

Thyroid scintigraphy is commonly used for evaluation of cats with hyperthyroidism, with the thyroid-to-salivary ratio (T/S) being the most common method to quantify the degree of thyroid activity and disease. Calculation of thyroid-to-background ratios (T/B) or percent thyroidal uptake of (99m) TcO(-) 4 (TcTU) has only been reported in a few studies. The purpose of this prospective, cross-sectional study was to evaluate a number of quantitative scintigraphic indices as diagnostic tests for hyperthyroidism, including the T/S, three different T/B, TcTU, and estimated thyroid volume. Of 524 cats referred to our clinic for evaluation of suspected hyperthyroidism, the diagnosis was confirmed (n = 504) or excluded (n = 20) based on results of a serum thyroid panel consisting of thyroxine (T4 ), triiodothyronine (T3 ), free T4 (fT4 ), and thyroid-stimulating hormone (TSH) concentrations. In the hyperthyroid cats, median values for TcTU, T/S, and three T/B ratios were all significantly higher (P < 0.001) than values in euthyroid suspect cats or clinically normal cats. All scintigraphic parameters were relatively sensitive and specific as diagnostic tests for hyperthyroidism, but the T/S ratio had the highest test accuracy. The T/S ratio correlated strongly with the TcTU (r = 0.85). However, the TcTU had a higher and more significant correlation (P < 0.01) with serum T4 (r = 0.76 vs. 0.64), T3 (r = 0.77 vs. 0.64), and estimated thyroid volume (r = 0.62 vs. 0.38). Overall, calculation of TcTU is an accurate diagnostic test, but also appears to be the best parameter to predict the functional volume and metabolic activity of the feline adenomatous thyroid gland. © 2016 American College of Veterinary Radiology.

[Thyroid cancer in patients with Grave's Disease].

PubMed

Mssrouri, R; Benamr, S; Essadel, A; Mdaghri, J; Mohammadine, El H; Lahlou, M-K; Taghy, A; Belmahi, A; Chad, B

2008-01-01

To evaluate the incidence of thyroid carcinoma in patients operated on for Graves' disease, to identify criteria which may predict malignancy, and to develop a practical approach to determine the extensiveness of thyroidectomy. Retrospective study of all patients who underwent thyroidectomy for Graves' disease between 1995 and 2005. 547 patients underwent subtotal thyroidectomy for Graves' disease during this period. Post-operative pathology examination revealed six cases of thyroid cancer (1.1%). All six cases had differentiated thyroid carcinoma (papillary carcinoma in 3 cases, follicular carcinoma in 2 cases and papillo-follicular carcinoma in 1 case). The indication for initial thyroidectomy was a palpable thyroid nodule in 3 cases (50%), failure of medical treatment for Grave's disease in 2 cases (33%), and signs of goiter compression in 1 case (17%). Five patients underwent re-operative total thyroidectomy. This study shows that while malignancy in Grave's disease is uncommon, the presence of thyroid nodule(s) in patients with Grave's disease may be considered as an indication for radical surgery. The most adequate radical surgery in this situation is to perform a total thyroidectomy.

Validation of the modified 4-tiered categorization system through comparison with the 5-tiered categorization system of the 2015 American Thyroid Association guidelines for classifying small thyroid nodules on ultrasound.

PubMed

Lee, Ji Hye; Han, Kyunghwa; Kim, Eun-Kyung; Moon, Hee Jung; Yoon, Jung Hyun; Park, Vivian Y; Kwak, Jin Young

2017-11-01

The purpose of this study was to validate the modified 4-tiered categorization system and to compare stratification of malignancy risk in small thyroid nodules with the 2015 American Thyroid Association (ATA) management guidelines. From January 2015 to December 2015, 737 thyroid nodules measured ≥ 1 cm and <2 cm were included in this study. Each nodule was assigned a category with the ultrasonographic patterns described by the 2015 ATA guidelines. On univariate analysis, there was no difference of malignancy risk between low suspicion and very low suspicion nodules (P = .584). Therefore, we suggested a modified 4-tiered categorization, which combines very low suspicion and low suspicion nodules into the "revised low suspicion" category. Specificity, positive predictive value (PPV) and accuracy were higher with the modified 4-tiered categorization system (P < .001 for all). The modified 4-tiered categorization system allows more efficient management with better diagnostic performance than the 2015 ATA categorization system in small thyroid nodules. © 2017 Wiley Periodicals, Inc.

Lattice-based model of ductal carcinoma in situ suggests rules for breast cancer progression to an invasive state.

PubMed

Boghaert, Eline; Radisky, Derek C; Nelson, Celeste M

2014-12-01

Ductal carcinoma in situ (DCIS) is a heterogeneous group of non-invasive lesions of the breast that result from abnormal proliferation of mammary epithelial cells. Pathologists characterize DCIS by four tissue morphologies (micropapillary, cribriform, solid, and comedo), but the underlying mechanisms that distinguish the development and progression of these morphologies are not well understood. Here we explored the conditions leading to the emergence of the different morphologies of DCIS using a two-dimensional multi-cell lattice-based model that incorporates cell proliferation, apoptosis, necrosis, adhesion, and contractility. We found that the relative rates of cell proliferation and apoptosis governed which of the four morphologies emerged. High proliferation and low apoptosis favored the emergence of solid and comedo morphologies. In contrast, low proliferation and high apoptosis led to the micropapillary morphology, whereas high proliferation and high apoptosis led to the cribriform morphology. The natural progression between morphologies cannot be investigated in vivo since lesions are usually surgically removed upon detection; however, our model suggests probable transitions between these morphologies during breast cancer progression. Importantly, cribriform and comedo appear to be the ultimate morphologies of DCIS. Motivated by previous experimental studies demonstrating that tumor cells behave differently depending on where they are located within the mammary duct in vivo or in engineered tissues, we examined the effects of tissue geometry on the progression of DCIS. In agreement with our previous experimental work, we found that cells are more likely to invade from the end of ducts and that this preferential invasion is regulated by cell adhesion and contractility. This model provides additional insight into tumor cell behavior and allows the exploration of phenotypic transitions not easily monitored in vivo.

Clinical risk stratification in patients with surgically resectable micropapillary bladder cancer.

PubMed

Fernández, Mario I; Williams, Stephen B; Willis, Daniel L; Slack, Rebecca S; Dickstein, Rian J; Parikh, Sahil; Chiong, Edmund; Siefker-Radtke, Arlene O; Guo, Charles C; Czerniak, Bogdan A; McConkey, David J; Shah, Jay B; Pisters, Louis L; Grossman, H Barton; Dinney, Colin P N; Kamat, Ashish M

2017-05-01

To analyse survival in patients with clinically localised, surgically resectable micropapillary bladder cancer (MPBC) undergoing radical cystectomy (RC) with and without neoadjuvant chemotherapy (NAC) and develop risk strata based on outcome data. A review of our database identified 103 patients with surgically resectable (≤cT4acN0 cM0) MPBC who underwent RC. Survival estimates were calculated using Kaplan-Meier method and compared using log-rank tests. Classification and regression tree (CART) analysis was performed to identify risk groups for survival. For the entire cohort, estimated 5-year overall survival and disease-specific survival (DSS) rates were 52% and 58%, respectively. CART analysis identified three risk subgroups: low-risk: cT1, no hydronephrosis; high-risk: ≥cT2, no hydronephrosis; and highest-risk: cTany with tumour-associated hydronephrosis. The 5-year DSS for the low-, high-, and highest-risk groups were 92%, 51%, and 17%, respectively (P < 0.001). Patients down-staged at RC

Hyperthyroidism in patients with ischaemic heart disease after iodine load induced by coronary angiography: Long-term follow-up and influence of baseline thyroid functional status.

PubMed

Bonelli, Nadia; Rossetto, Ruth; Castagno, Davide; Anselmino, Matteo; Vignolo, Francesca; Parasiliti Caprino, Mirko; Gaita, Fiorenzo; Ghigo, Ezio; Garberoglio, Roberto; Grimaldi, Roberto; Maccario, Mauro

2018-02-01

To study the effect of a iodine load on thyroid function of patients with ischaemic heart disease (IHD) and the long-term influence of unknown subclinical hyperthyroidism. Subclinical hyperthyroidism is considered an independent risk factors for cardiovascular morbidity of patients with IHD. They routinely undergo coronary angiography with iodine contrast media (ICM) which may induce or even worsen hyperthyroidism. A cross-sectional study followed by a longitudinal study on patients with subclinical hyperthyroidism. 810 consecutive IHD outpatients without known thyroid diseases or treatment with drugs influencing thyroid activity undergoing elective coronary angiography. We evaluated thyroid function either before and 1 month after ICM; patients with thyrotoxicosis at baseline or after ICM were then followed up for 1 year. 58 patients had hyperthyroidism at baseline (HB, 7.2%), independently associated to FT4 levels, thyroid nodules and family history of thyroid diseases. After ICM, the prevalence of hyperthyroidism was 81 (10%). Hyperthyroidism after ICM was positively predicted by baseline fT4 levels, thyroid nodules, age over 60, male gender, family history of thyroid diseases. Three months after ICM, 34 patients (4.2%) still showed hyperthyroidism (22 from HB, 13 treated with methimazole). One year after ICM, hyperthyroidism was still present in 20 patients (2.5%, all from HB, 13 treated). The prevalence of spontaneous subclinical hyperthyroidism in IHD is surprisingly elevated and is further increased by iodine load, particularly in patients with thyroid nodules and familial history of thyroid diseases, persisting in a not negligible number of them even after one year. © 2017 John Wiley & Sons Ltd.

Prospective Observation of 5-Year Clinical Course of Subclinical Hypothyroidism in Korean Population

PubMed Central

Park, Woo Ri; Oh, Tae Keun

2013-01-01

Subclinical hypothyroidism (SCH) is a common clinical condition, whereas it's natural course has not been identified distinctly. We evaluated the natural history of 169 SCH patients over 5-yr and the prognostic factors including thyroid autoantibodies and thyroid ultrasonographic (USG) findings related to develop overt hypothyroidism. After 5 yr, 47.3% of patients showed normalization of TSH, while 36.7% of patients remained persistence of high level of TSH, and overt hypothyroidism developed in 11.2% of patients. There were painless thyroiditis (2.9%) and hyperthyroidism (1.7%) during 5 yr follow-up. The thyroid nodule was seen in 48.6% of patients. Most of patients had 1 to 2 nodules whereas only 3% of patients with thyroid nodule had more than 6 nodules. Overt hypothyroidism patients had more heterogenous echogenecity in USG compared to patients with normalization or persistent SCH (76.5% vs 50.0% vs 35.0%, P = 0.048) and higher prevalence positive anti-thyroid peroxidase (anti-TPO Ab) and anti-thyroglobulin antibody (anti-Tg Ab) and titer of anti-TPO Ab than other two groups. The cut off values for prediction of overt hypothyroidism were TSH > 7.45 µIU/mL, free T4 < 1.09 ng/dL and Anti-TPO Ab > 560 IU/mL. SCH has various courses and initial TSH, free T4, presence of thyroid autoantibody, titer of thyroid autoantibody; and thyroid USG findings can serve as a prognostic factor for progression of overt hypothyroidism. These parameters suggest consideration to initiate thyroid hormone treatment in SCH. PMID:24265525

Thyroid Radiation Dose and Other Risk Factors of Thyroid Carcinoma Following Childhood Cancer.

PubMed

de Vathaire, Florent; Haddy, Nadia; Allodji, Rodrigue S; Hawkins, Mike; Guibout, Catherine; El-Fayech, Chiraz; Teinturier, Cécile; Oberlin, Odile; Pacquement, Hélène; Diop, Fara; Kalhouche, Amar; Benadjaoud, Mohamedamine; Winter, David; Jackson, Angela; Bezin Mai-Quynh, Giao; Benabdennebi, Aymen; Llanas, Damien; Veres, Cristina; Munzer, Martine; Nguyen, Tan Dat; Bondiau, Pierre-Yves; Berchery, Delphine; Laprie, Anne; Deutsch, Eric; Lefkopoulos, Dimitri; Schlumberger, Martin; Diallo, Ibrahima; Rubino, Carole

2015-11-01

Thyroid carcinoma is a frequent complication of childhood cancer radiotherapy. The dose response to thyroid radiation dose is now well established, but the potential modifier effect of other factors requires additional investigation. This study aimed to investigate the role of potential modifiers of the dose response. We followed a cohort of 4338 5-year survivors of solid childhood cancer treated before 1986 over an average of 27 years. The dose received by the thyroid gland and some other anatomical sites during radiotherapy was estimated after reconstruction of the actual conditions in which irradiation was delivered. Fifty-five patients developed thyroid carcinoma. The risk of thyroid carcinoma increased with a radiation dose to the thyroid of up to two tenths of Gy, then leveled off for higher doses. When taking into account the thyroid radiation dose, a surgical or radiological splenectomy (>20 Gy to the spleen) increased thyroid cancer risk (relative risk [RR] = 2.3; 95% confidence interval [CI], 1.3-4.0), high radiation doses (>5 Gy) to pituitary gland lowered this risk (RR = 0.2; 95% CI, 0.1-0.6). Patients who received nitrosourea chemotherapy had a 6.6-fold (95% CI, 2.5-15.7) higher risk than those who did not. The excess RR per Gy of radiation to the thyroid was 4.7 (95% CI, 1.7-22.6). It was 7.6 (95% CI, 1.6-33.3) if body mass index at time of interview was equal or higher than 25 kg/m(2), and 4.1 (95% CI, 0.9-17.7) if not (P for interaction = .1). Predicting thyroid cancer risk following childhood cancer radiation therapy probably requires the assessment of more than just the radiation dose to the thyroid. Chemotherapy, splenectomy, radiation dose to pituitary gland, and obesity also play a role.

An age-specific biokinetic model for iodine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leggett, Richard Wayne

This study reviews age-specific biokinetic data for iodine in humans and extends to pre-adult ages the baseline parameter values of the author’s previously published model for systemic iodine in adult humans. Compared with the ICRP’s current age-specific model for iodine introduced in Publication 56 (1989), the present model provides a more detailed description of the behavior of iodine in the human body; predicts greater cumulative (integrated) activity in the thyroid for short-lived isotopes of iodine; predicts similar cumulative activity in the thyroid for isotopes with half-time greater than a few hours; and, for most iodine isotopes, predicts much greater cumulativemore » activity in salivary glands, stomach wall, liver, and kidneys.« less

An age-specific biokinetic model for iodine

DOE PAGES

Leggett, Richard Wayne

2017-10-26

This study reviews age-specific biokinetic data for iodine in humans and extends to pre-adult ages the baseline parameter values of the author’s previously published model for systemic iodine in adult humans. Compared with the ICRP’s current age-specific model for iodine introduced in Publication 56 (1989), the present model provides a more detailed description of the behavior of iodine in the human body; predicts greater cumulative (integrated) activity in the thyroid for short-lived isotopes of iodine; predicts similar cumulative activity in the thyroid for isotopes with half-time greater than a few hours; and, for most iodine isotopes, predicts much greater cumulativemore » activity in salivary glands, stomach wall, liver, and kidneys.« less

Thyroid V50 Highly Predictive of Hypothyroidism in Head-and-Neck Cancer Patients Treated With Intensity-modulated Radiotherapy (IMRT).

PubMed

Sachdev, Sean; Refaat, Tamer; Bacchus, Ian D; Sathiaseelan, Vythialinga; Mittal, Bharat B

2017-08-01

Radiation-induced hypothyroidism affects a significant number of patients with head-and-neck squamous cell cancer (HNSCC). We examined detailed dosimetric and clinical parameters to better determine the risk of hypothyroidism in euthyroid HNSCC patients treated with intensity-modulated radiation therapy (IMRT). From 2006 to 2010, 75 clinically euthyroid patients with HNSCC were treated with sequential IMRT. The cohort included 59 men and 16 females with a median age of 55 years (range, 30 to 89 y) who were treated to a median dose of 70 Gy (range, 60 to 75 Gy) with concurrent chemotherapy in nearly all (95%) cases. Detailed thyroid dosimetric parameters including maximum dose, mean dose, and other parameters (eg, V50-percent volume receiving at least 50 Gy) were obtained. Freedom from hypothyroidism was evaluated using the Kaplan-Meier method. Univariate and multivariate analyses were conducted using Cox regression. After a median follow-up period of 50 months, 25 patients (33%) became hypothyroid. On univariate analysis, thyroid V50 was highly correlated with developing hypothyroidism (P=0.035). Other dosimetric paramaters including mean thyroid dose (P=0.11) and maximum thyroid dose (P=0.39) did not reach statistical significance. On multivariate analysis incorporating patient, tumor, and treatment variables, V50 remained highly statistically significant (P=0.037). Regardless of other factors, for V50>60%, the odds ratio of developing hypothyroidism was 6.76 (P=0.002). In HNSCC patients treated with IMRT, thyroid V50 highly predicts the risk of developing hypothyroidism. V50>60% puts patients at a significantly higher risk of becoming hypothyroid. This can be a useful dose constraint to consider during treatment planning.

Can technical characteristics predict clinical performance in PET/CT imaging? A correlation study for thyroid cancer diagnosis

NASA Astrophysics Data System (ADS)

Kallergi, Maria; Menychtas, Dimitrios; Georgakopoulos, Alexandros; Pianou, Nikoletta; Metaxas, Marinos; Chatziioannou, Sofia

2013-03-01

The purpose of this study was to determine whether image characteristics could be used to predict the outcome of ROC studies in PET/CT imaging. Patients suspected for recurrent thyroid cancer underwent a standard whole body (WB) examination and an additional high-resolution head-and-neck (HN) F18-FDG PET/CT scan. The value of the latter was determined with an ROC study, the results of which showed that the WB+HN combination was better than WB alone for thyroid cancer detection and diagnosis. Following the ROC experiment, the WB and HN images of confirmed benign or malignant thyroid disease were analyzed and first and second order textural features were determined. Features included minimum, mean, and maximum intensity, as well as contrast in regions of interest encircling the thyroid lesions. Lesion size and standard uptake values (SUV) were also determined. Bivariate analysis was applied to determine relationships between WB and HN features and between observer ROC responses and the various feature values. The two sets showed significant associations in the values of SUV, contrast, and lesion size. They were completely different when the intensities were considered; no relationship was found between the WB minimum, maximum, and mean ROI values and their HN counterparts. SUV and contrast were the strongest predictors of ROC performance on PET/CT examinations of thyroid cancer. The high resolution HN images seem to enhance these relationships but without a single dramatic effect as was projected from the ROC results. A combination of features from both WB and HN datasets may possibly be a more robust predictor of ROC performance.

Diagnostic accuracy of circulating thyrotropin receptor messenger RNA combined with neck ultrasonography in patients with Bethesda III-V thyroid cytology.

PubMed

Aliyev, Altay; Patel, Jinesh; Brainard, Jennifer; Gupta, Manjula; Nasr, Christian; Hatipoglu, Betul; Siperstein, Allan; Berber, Eren

2016-01-01

The aim of this study was to analyze the usefulness of thyrotropin receptor messenger RNA (TSHR-mRNA) combined with neck ultrasonography (US) in the management of thyroid nodules with Bethesda III-V cytology. Cytology slides of patients with a preoperative fine needle aspiration (FNA) and TSHR-mRNA who underwent thyroidectomy between 2002 and 2011 were recategorized based on the Bethesda classification. Results of thyroid FNA, TSHR-mRNA, and US were compared with the final pathology. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. There were 12 patients with Bethesda III, 112 with Bethesda IV, and 58 with Bethesda V cytology. The sensitivity of TSHR-mRNA in predicting cancer was 33%, 65%, and 79 %, and specificity was 67%, 66%, and 71%, for Bethesda III, IV, and V categories, respectively. For the same categories, the PPV of TSHR-mRNA was 25%, 33%, and 79%, respectively; whereas the NPV was 75%, 88%, and 71%, respectively. The addition of neck US to TSHR-mRNA increased the NPV to 100% for Bethesda III, and 86%, for Bethesda IV, and 82% for Bethesda V disease. This study documents the potential usefulness of TSHR-mRNA for thyroid nodules with Bethesda III-V FNA categories. TSHR-mRNA may be used to exclude Bethesda IV disease. A large sample analysis is needed to determine its accuracy for Bethesda category III nodules. Copyright © 2016 Elsevier Inc. All rights reserved.

Norepinephrine and thyroxine are predictors of fat mass gain in humans with cold-induced brown adipose tissue activation.

PubMed

Begaye, Brittany; Piaggi, Paolo; Thearle, Marie S; Haskie, Kaitlyn; Walter, Mary; Schlögl, Mathias; Bonfiglio, Susan; Krakoff, Jonathan; Vinales, Karyne L

2018-05-16

In healthy adults with detectable cold-induced brown fat activation (CIBA), the relationships between sympathetic nervous system (SNS) or thyroid activity during energy balance (EBL) with CIBA and body composition change are undetermined. To investigate the relationships between CIBA and thermoneutral catecholamines and thyroid hormones measured during EBL and to determine if CIBA, catecholamines, or thyroid hormones predict body composition changes. Twelve healthy volunteers (7M/5F) with positive CIBA (>2 standardized uptake value (g/mL)) had 24-h energy expenditure (24hEE) assessed during EBL via whole-room indirect calorimetry while residing on a clinical research unit. Positron-emission tomography/computed tomography scans were performed after exposure to 16°C for 2h to quantify CIBA. CIBA, 24hEE during EBL and thermoneutrality with concomitant measurement of urinary catecholamines and plasma free T3 (fT3) and free t4 (fT4). Body composition at baseline and six months by DXA. Lower urinary norepinephrine and fT4 were associated with higher CIBA (r = ‒0.65, p = 0.03 and r = ‒0.75, p<0.01, respectively), but CIBA was not associated with 24hEE at thermoneutrality (p=0.77). Lower CIBA (β = ̶̶ 3.5 kg/SUV, p<0.01) predicted fat mass gain; whereas, higher urinary norepinephrine and fT4 predicted future fat mass gain at 6 months (β = 3.0 kg per two-fold difference in norepinephrine, p=0.03; β = 1.2 kg per 0.1 ng/dL difference in fT4, p=0.03, respectively). Lower SNS and free thyroid measurements at baseline indicate a greater capacity for CIBA, which may be predictive against fat mass gain.

A 10-Gene Classifier for Indeterminate Thyroid Nodules: Development and Multicenter Accuracy Study

PubMed Central

González, Hernán E.; Martínez, José R.; Vargas-Salas, Sergio; Solar, Antonieta; Veliz, Loreto; Cruz, Francisco; Arias, Tatiana; Loyola, Soledad; Horvath, Eleonora; Tala, Hernán; Traipe, Eufrosina; Meneses, Manuel; Marín, Luis; Wohllk, Nelson; Diaz, René E.; Véliz, Jesús; Pineda, Pedro; Arroyo, Patricia; Mena, Natalia; Bracamonte, Milagros; Miranda, Giovanna; Bruce, Elsa

2017-01-01

Background: In most of the world, diagnostic surgery remains the most frequent approach for indeterminate thyroid cytology. Although several molecular tests are available for testing in centralized commercial laboratories in the United States, there are no available kits for local laboratory testing. The aim of this study was to develop a prototype in vitro diagnostic (IVD) gene classifier for the further characterization of nodules with an indeterminate thyroid cytology. Methods: In a first stage, the expression of 18 genes was determined by quantitative polymerase chain reaction (qPCR) in a broad histopathological spectrum of 114 fresh-tissue biopsies. Expression data were used to train several classifiers by supervised machine learning approaches. Classifiers were tested in an independent set of 139 samples. In a second stage, the best classifier was chosen as a model to develop a multiplexed-qPCR IVD prototype assay, which was tested in a prospective multicenter cohort of fine-needle aspiration biopsies. Results: In tissue biopsies, the best classifier, using only 10 genes, reached an optimal and consistent performance in the ninefold cross-validated testing set (sensitivity 93% and specificity 81%). In the multicenter cohort of fine-needle aspiration biopsy samples, the 10-gene signature, built into a multiplexed-qPCR IVD prototype, showed an area under the curve of 0.97, a positive predictive value of 78%, and a negative predictive value of 98%. By Bayes' theorem, the IVD prototype is expected to achieve a positive predictive value of 64–82% and a negative predictive value of 97–99% in patients with a cancer prevalence range of 20–40%. Conclusions: A new multiplexed-qPCR IVD prototype is reported that accurately classifies thyroid nodules and may provide a future solution suitable for local reference laboratory testing. PMID:28521616

Cell division cycle 45 promotes papillary thyroid cancer progression via regulating cell cycle.

PubMed

Sun, Jing; Shi, Run; Zhao, Sha; Li, Xiaona; Lu, Shan; Bu, Hemei; Ma, Xianghua

2017-05-01

Cell division cycle 45 was reported to be overexpressed in some cancer-derived cell lines and was predicted to be a candidate oncogene in cervical cancer. However, the clinical and biological significance of cell division cycle 45 in papillary thyroid cancer has never been investigated. We determined the expression level and clinical significance of cell division cycle 45 using The Cancer Genome Atlas, quantitative real-time polymerase chain reaction, and immunohistochemistry. A great upregulation of cell division cycle 45 was observed in papillary thyroid cancer tissues compared with adjacent normal tissues. Furthermore, overexpression of cell division cycle 45 positively correlates with more advanced clinical characteristics. Silence of cell division cycle 45 suppressed proliferation of papillary thyroid cancer cells via G1-phase arrest and inducing apoptosis. The oncogenic activity of cell division cycle 45 was also confirmed in vivo. In conclusion, cell division cycle 45 may serve as a novel biomarker and a potential therapeutic target for papillary thyroid cancer.

Subclinical Hypothyroidism: A Prospective Observational Study from Southern India.

PubMed

Sridhar, Mathrubootham; Mahadevan, Shriraam; Vishwanathan, Latha; Subbarayan, Anbezhil

2018-03-15

To assess the natural history and progression of subclinical hypothyroidism and to study factors which help predict evolution of subclinical hypothyroidism into overt hypothyroidism. Longitudinal study in 40 children (2-16 yrs) presenting with subclinical hypothyroidism in a tertiary care unit in Chennai, India. Patients showing evidence of overt hypothyroidism or thyroid stimulating hormone ≥15 mIU/mL during follow-up were started on thyroxine. Others were followed up with 3-monthly thyroid function tests up to one year. At the end of our study period 3 (7.5%) were overtly hypothyroid, 16 (40%) remained as subclinical hypothyroid, and 21 (52.5%) became euthyroid. Evidence of auto- immunity at baseline was a significant (P<0.05) risk factor for progression to overt hypothyroidism. Subclinical hypothyroidism in children, with thyroid stimulating hormone upto 15 mIU/L and irrespective of thyroid autoimmunity, needs only periodic clinical and biochemical follow up. Thyroid autoimmunity may point to an increased probability of progression to overt hypothyroidism.

Autoimmune Abnormalities of Postpartum Thyroid Diseases

PubMed Central

Di Bari, Flavia; Granese, Roberta; Le Donne, Maria; Vita, Roberto; Benvenga, Salvatore

2017-01-01

The year following parturition is a critical time for the de novo appearance or exacerbation of autoimmune diseases, including autoimmune thyroid disease. The vast majority of postpartum thyroid disease consists of postpartum thyroiditis (PPT) and the minority by Graves’ disease and non-autoimmune thyroiditis. PPT has a worldwide prevalence ranging from 1 to 22% and averaging 5% based on a review published in 2012. Several factors confer risk for the development of PPT. Typically, the clinical course of PPT is characterized by three phases: thyrotoxic, hypothyroid, and euthyroid phase. Approximately half of PPT women will have permanent hypothyroidism. The best humoral marker for predictivity, already during the first trimester of gestation, is considered positivity for thyroperoxidase autoantibodies (TPOAb), though only one-third to half of such TPOAb-positive pregnant women will develop PPT. Nutraceuticals (such as selenium) or omega-3-fatty acid supplements seem to have a role in prevention of PPT. In a recent study on pregnant women with stable dietary habits, we found that the fish consumers had lower rates of positivity (and lower serum levels) of both TPOAb and thyroglobulin Ab compared to meat eaters. Finally, we remind the reader of other diseases that can be observed in the postpartum period, either autoimmune or non-autoimmune, thyroid or non-thyroid. PMID:28751877

Relationship between negative mental adjustment to cancer and distress in thyroid cancer patients.

PubMed

Seok, Jeong-Ho; Choi, Won-Jung; Lee, Yong Sang; Park, Cheong Soo; Oh, Young-Ja; Kim, Jong-Sun; Chang, Hang-Seok

2013-05-01

Previous studies have reported that over a third of cancer patients experience significant psychological distress with diagnosis and treatment of cancer. Mental adjustment to cancer as well as other biologic and demographic factors may be associated with their distress. We investigated the relationship between mental adjustment and distress in patients with thyroid cancer prior to thyroidectomy. One hundred and fifty-two thyroid cancer patients were included in the final analysis. After global distress levels were screened with a distress thermometer, patients were evaluated concerning mental adjustment to cancer, as well as demographic and cancer-related characteristics. A thyroid function test was also performed. Regression analysis was performed to discern significant factors associated with distress in thyroid cancer patients. Our regression model was significant and explained 38.5% of the total variance in distress of this patient group. Anxious-preoccupation and helpless-hopeless factors on the mental adjustment to cancer scale were significantly associated with distress in thyroid cancer patients. Negative emotional response to cancer diagnosis may be associated with distress in thyroid cancer patients awaiting thyroidectomy. Screening of mental coping strategies at the beginning of cancer treatment may predict psychological distress in cancer patients. Further studies on the efficacy of psychiatric intervention during cancer treatment may be needed for patients showing maladaptive psychological responses to cancer.

DIAGNOSIS OF ENDOCRINE DISEASE: High-yield thyroid fine-needle aspiration cytology: an update focused on ancillary techniques improving its accuracy.

PubMed

Bongiovanni, M; Trimboli, P; Rossi, E D; Fadda, G; Nobile, A; Giovanella, L

2016-02-01

Thyroid fine-needle aspiration (FNA) cytology is a fast growing field. One of the most developing areas is represented by molecular tests applied to cytological material. Patients that could benefit the most from these tests are those that have been diagnosed as 'indeterminate' on FNA. They could be better stratified in terms of malignancy risk and thus oriented with more confidence to the appropriate management. Taking in to consideration the need to improve and keep high the yield of thyroid FNA, professionals from various fields (i.e. molecular biologists, endocrinologists, nuclear medicine physicians and radiologists) are refining and fine-tuning their diagnostic instruments. In particular, all these developments aim at increasing the negative predictive value of FNA to improve the selection of patients for diagnostic surgery. These advances involve terminology, the application of next-generation sequencing to thyroid FNA, the use of immunocyto- and histo-chemistry, the development of new sampling techniques and the increasing use of nuclear medicine as well as molecular imaging in the management of patients with a thyroid nodule. Herein, we review the recent advances in thyroid FNA cytology that could be of interest to the 'thyroid-care' community, with particular focus on the indeterminate diagnostic category. © 2016 European Society of Endocrinology.

[Prediction of occult carcinoma in contralateral nodules based on the ultrasonic features of unilateral papillary thyroid carcinoma].

PubMed

Yang, L M; Li, Q; Zhao, B W; Lyu, J G; Xu, H S; Xu, L L; Li, S Y; Gao, L; Zhu, J

2017-04-07

Objective: To investigate the occurrence of occult carcinoma in contralateral lobes based on the ultrasonic features of unilateral papillary thyroid carcinoma. Methods: The study included 202 consecutives cases of unilateral papillary thyroid carcinoma with benign nodules in the contralateral lobe identified by preoperative ultrasound or fine-needle aspiration from June 2014 to December 2015. All patients received total thyroidectomies, and with postoperative pathological examination they were divided into two groups, one including 60 cases with positive occult cancer and another one consisting of 142 cases with negative occult cancer. Univariate and multivariate analyses were performed to analyze the sonographic features of unilateral papillary thyroid carcinoma relevant to the occurrence of occult carcinoma in the contralateral nodules. Results: Univariate analysis indicated occult carcinoma in the contralateral lobes was associated with Hashimoto's thyroiditis(χ(2)=3.955, P =0.047), unclear border (χ(2)=4.375, P =0.036)and multifocality in the ipsilateral(χ(2)=7.375, P =0.007), but not with tumors maximum size, location, A/T, shape, internal structure, internal echo, acoustic halo, calcification, capsular invasion and blood flow signal in the lobe with carcinoma on another side. Multivariate analysis showed unclear border ( OR =2.727, P =0.010) and multifocality in the ipsilateral( OR =2.807, P =0.005)of carcinoma were independent predictive factor for contralateral occult PTC. Conclusions: Unclear border and multifocality of PTC in the ipsilateral were closely relevant to the occurrence of occult carcinoma in the contralateral nodules.

Thyroid hormones and changes in body weight and metabolic parameters in response to weight loss diets: the POUNDS LOST trial.

PubMed

Liu, G; Liang, L; Bray, G A; Qi, L; Hu, F B; Rood, J; Sacks, F M; Sun, Q

2017-06-01

The role of thyroid hormones in diet-induced weight loss and subsequent weight regain is largely unknown. To examine the associations between thyroid hormones and changes in body weight and resting metabolic rate (RMR) in a diet-induced weight loss setting. Data analysis was conducted among 569 overweight and obese participants aged 30-70 years with normal thyroid function participating in the 2-year Prevention of Obesity Using Novel Dietary Strategies (POUNDS) LOST randomized clinical trial. Changes in body weight and RMR were assessed during the 2-year intervention. Thyroid hormones (free triiodothyronine (T3), free thyroxine (T4), total T3, total T4 and thyroid-stimulating hormone (TSH)), anthropometric measurements and biochemical parameters were assessed at baseline, 6 months and 24 months. Participants lost an average of 6.6 kg of body weight during the first 6 months and subsequently regained an average of 2.7 kg of body weight over the remaining period from 6 to 24 months. Baseline free T3 and total T3 were positively associated, whereas free T4 was inversely associated, with baseline body weight, body mass index and RMR. Total T4 and TSH were not associated with these parameters. Higher baseline free T3 and free T4 levels were significantly associated with a greater weight loss during the first 6 months (P<0.05) after multivariate adjustments including dietary intervention groups and baseline body weight. Comparing extreme tertiles, the multivariate-adjusted weight loss±s.e. was -3.87±0.9 vs -5.39±0.9 kg for free T3 (P trend =0.02) and -4.09±0.9 vs -5.88±0.9 kg for free T4 (P trend =0.004). The thyroid hormones did not predict weight regain in 6-24 months. A similar pattern of associations was also observed between baseline thyroid hormones and changes in RMR. In addition, changes in free T3 and total T3 levels were positively associated with changes in body weight, RMR, body fat mass, blood pressure, glucose, insulin, triglycerides and leptin at 6 months and 24 months (all P<0.05). In this diet-induced weight loss setting, higher baseline free T3 and free T4 predicted more weight loss, but not weight regain among overweight and obese adults with normal thyroid function. These findings reveal a novel role of thyroid hormones in body weight regulation and may help identify individuals more responsive to weight loss diets.

Qualitative and Semiquantitative Elastography for the Diagnosis of Intermediate Suspicious Thyroid Nodules Based on the 2015 American Thyroid Association Guidelines.

PubMed

Yang, Bo Ra; Kim, Eun-Kyung; Moon, Hee Jung; Yoon, Jung Hyun; Park, Vivian Y; Kwak, Jin Young

2018-04-01

To evaluate qualitative and semiquantitative elastography for the diagnosis of intermediate suspicious thyroid nodules based on the 2015 American Thyroid Association (ATA) guidelines. Through a retrospective search of our institutional database, 746 solid thyroid nodules found on grayscale ultrasonography, strain elastography, and ultrasound-guided fine-needle aspiration between June and November 2009 were collected. Among them, 80 nodules from 80 patients with an intermediate suspicion of malignancy based on the 2015 ATA guidelines that were 10 mm or larger were recruited as the final study nodules. Elastographic findings were categorized according to the criteria of Rago et al (J Clin Endocrinol Metab 2007; 92:2917-2922) and Asteria et al (Thyroid 2008; 18:523-531), and strain ratio values were calculated and recorded. The independent 2-sample t test and χ 2 test (or Fisher exact test) were used to evaluate differences in clinical parameters between benign and malignant thyroid nodules. All variables were compared by univariate and multivariate logistic regression analyses, and odds ratios with 95% confidence intervals were calculated. Of the 80 nodules, 6 (7.5%) were malignant, and 74 (92.5%) were benign. No significant differences were observed in age, sex, nodule size, elasticity score, and strain ratio between benign and malignant nodules. No variables significantly predicted thyroid malignancy on the univariate analysis. On the multivariate logistic regression analysis, there were no independent variables associated with thyroid malignancy, including the elasticity score and strain ratio (all P > .05). Elastographic analysis using the elasticity score and strain ratio has limited ability to characterize the benignity or malignancy of thyroid nodules with an intermediate suspicion of malignancy based on the 2015 ATA guidelines. © 2017 by the American Institute of Ultrasound in Medicine.

Computer-aided diagnostic system for detection of Hashimoto thyroiditis on ultrasound images from a Polish population.

PubMed

Acharya, U Rajendra; Sree, S Vinitha; Krishnan, M Muthu Rama; Molinari, Filippo; Zieleźnik, Witold; Bardales, Ricardo H; Witkowska, Agnieszka; Suri, Jasjit S

2014-02-01

Computer-aided diagnostic (CAD) techniques aid physicians in better diagnosis of diseases by extracting objective and accurate diagnostic information from medical data. Hashimoto thyroiditis is the most common type of inflammation of the thyroid gland. The inflammation changes the structure of the thyroid tissue, and these changes are reflected as echogenic changes on ultrasound images. In this work, we propose a novel CAD system (a class of systems called ThyroScan) that extracts textural features from a thyroid sonogram and uses them to aid in the detection of Hashimoto thyroiditis. In this paradigm, we extracted grayscale features based on stationary wavelet transform from 232 normal and 294 Hashimoto thyroiditis-affected thyroid ultrasound images obtained from a Polish population. Significant features were selected using a Student t test. The resulting feature vectors were used to build and evaluate the following 4 classifiers using a 10-fold stratified cross-validation technique: support vector machine, decision tree, fuzzy classifier, and K-nearest neighbor. Using 7 significant features that characterized the textural changes in the images, the fuzzy classifier had the highest classification accuracy of 84.6%, sensitivity of 82.8%, specificity of 87.0%, and a positive predictive value of 88.9%. The proposed ThyroScan CAD system uses novel features to noninvasively detect the presence of Hashimoto thyroiditis on ultrasound images. Compared to manual interpretations of ultrasound images, the CAD system offers a more objective interpretation of the nature of the thyroid. The preliminary results presented in this work indicate the possibility of using such a CAD system in a clinical setting after evaluating it with larger databases in multicenter clinical trials.

Computed Tomography Density Change in the Thyroid Gland Before and After Radiation Therapy.

PubMed

Ishibashi, Naoya; Maebayashi, Toshiya; Aizawa, Takuya; Sakaguchi, Masakuni; Okada, Masahiro; Matsushita, Junichi

2018-01-01

Hypothyroidism is an established adverse effect of radiation therapy for head and neck cancer, and computed tomography (CT) density of the thyroid gland is lower in hypothyroid than euthyroid individuals. No previous studies have evaluated changes in CT densities of the thyroid gland caused by radiation therapy. The aim was to investigate the relationship between the change in CT density of the thyroid gland before and after radiation therapy for head and neck cancer and hypothyroidism. This retrospective study analyzed data of 24 patients treated by radiation therapy for head and neck cancers. After dosimetric analysis of received radiation therapy, a Picture Archiving and Communication System was used to manually contour the thyroid on pre-treatment CT images to enable determination of mean thyroid gland CT densities and received radiation doses. Pre- and post-treatment thyroid function was assessed on the basis of serum TSH concentrations. Multivariate and univariate analyses were used to determine what clinical factors are associated with post-radiation therapy decrease in CT density of the thyroid and Pearson's χ 2 test was used to assess correlations between these densities and TSH concentrations. Mean CT densities of the thyroid gland decreased from before to after radiation therapy in 73.9% of our patients (median decrease 16.8 HU). Serum TSH concentrations were significantly higher in patients with greater then median decreases in CT density than in those with lesser or no decreases. Post-radiation therapy hypothyroidism may be predicted by significant decreases in CT density of the thyroid gland. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

The role of postoperative Tc-99m pertechnetate scintigraphy in estimation of remnant mass and prediction of successful ablation in patients with differentiated thyroid cancer.

PubMed

Ozdemir, Didem; Cuhaci, Fatma N; Ozdemir, Elif; Aydin, Cevdet; Ersoy, Reyhan; Turkolmez, Seyda; Cakir, Bekir

2016-06-01

Surgery and radioactive iodine (RAI) ablation constitute the mainstay of the treatment of differentiated thyroid carcinoma (DTC). In this study, we aimed to evaluate the diagnostic value of postoperative early Tc-99m pertechnetate scanning to detect remnant thyroid tissue and predict ablation success. DTC patients evaluated with postoperative Tc-99m pertechnetate scintigraphy and treated with RAI between January 2007 and December 2014 were recruited. The results of Tc-99m pertechnetate scanning were compared with therapeutic I-131 whole-body scanning (TxWBS) and diagnostic I-131 whole-body scanning (DxWBS) performed 6-9 months after RAI. There were 154 (21.5%) male and 563 (78.5%) female patients, with a mean age of 49.11±12.35 years. Postoperative Tc-99m pertechnetate scanning was positive in 499 patients (69.6%) and negative in 218 (30.4%) patients. There were 673 (93.9%) patients with a positive TxWBS scan and 44 (6.1%) patients with negative TxWBS scan. Considering TxWBS as the standard test, sensitivity, specificity, positive predictive value, and negative predictive value of Tc-99m pertechnetate scanning were 72.2, 70.5, 97.4, and 14.2%, respectively. DxWBS was positive in 57 (9.0%) and negative in 564 (91%) patients. Ablation dose was higher and preablation thyroglobulin was lower in patients with negative DxWBS (P=0.001 and 0.04, respectively). Overall, 171 (92.9%) of 184 patients with negative Tc-99m pertechnetate had negative DxWBS. Postoperative Tc-99m pertechnetate scintigraphy has a high positive predictive value to detect remnant tissue in patients with DTC. Although negative Tc-99m pertechnetate scanning does not indicate removal of all thyroid tissue, it is related to successful ablation in more than 90% of patients.

Assessment of the Role of Different Imaging Modalities with Emphasis on Fdg Pet/Ct in the Management of Well Differentiated Thyroid Cancer (WDTC).

PubMed

Kendi A, Tuba Karagulle; Mudalegundi, Shwetha; Switchenko, Jeffrey; Lee, Daniel; Halkar, Raghuveer; Chen, Amy Y

2016-01-01

Positron emission tomography/computed tomography is suggested to have a role in detection of iodine negative recurrence in well differentiated thyroid cancer. The aim of this study is to identify role of different imaging modalities in the management of well differentiated thyroid cancer. We reviewed 900 well differentiated thyroid cancer patients after post-thyroidectomy who underwent recombinant human thyroid stimulating hormone stimulated Sodium Iodide I 131 imaging. Out of 900 patients, 74 had positron emission tomography/computed tomography. Multivariate analysis was performed by controlling positron emission tomography/computed tomography, Sodium Iodide I 131 scan, neck ultrasonography, age, sex, primary tumor size, stage, histology, thyroglobulin. Patients were grouped according to results of Sodium Iodide I 131 scan and positron emission tomography/computed tomography. Positron emission tomography/computed tomography was positive in 23 of 74 patients. The sensitivity for positron emission tomography was 11/11(100%), the specificity was 51/63 (81.0%), the positive predictive value was 11/23 (47.8%), and the negative predictive value was 51/51 (100%). The sensitivity for the neck ultrasonography was 4/8 (50%), the specificity was 53/60 (88.3%), positive predictive value was 4/11 (36.4%), and negative predictive value was 53/57 (93.0%). 50% of patients who had Sodium Iodide I 131 negative scan and positive positron emission tomography/computed tomography had a change in management. Thirty-six percent with positive neck ultrasonography had a change in management. Out of 11 recurrences, 6 had distant metastatic disease, and 5/11 had regional nodal disease. Neck ultrasonography showed nodal metastasis in 4/5 (80%). Positron emission tomography/computed tomography altered management in the presence of a high thyroglobulin level and a negative Sodium Iodide I 131 scan. Neck ultrasonography should be the first line of imaging with rising thyroglobulin levels. Positron emission tomography/computed tomography should be considered for cases with high thyroglobulin levels and normal neck ultrasonography to look for distant metastatic disease.

Evaluating for a geospatial relationship between radon levels and thyroid cancer in Pennsylvania.

PubMed

Goyal, Neerav; Camacho, Fabian; Mangano, Joseph; Goldenberg, David

2015-01-01

To determine whether there is an association between radon levels and the rise in incidence of thyroid cancer in Pennsylvania. Epidemiological study of the state of Pennsylvania. We used information from the Pennsylvania Cancer Registry and the Pennsylvania Department of Energy. From the registry, information regarding thyroid incidence by county and zip code was recorded. Information regarding radon levels per county was recorded from the state. Poisson regression models were fit predicting county-level thyroid incidence and change as a function of radon/lagged radon levels. To account for measurement error in the radon levels, a Bayesian Model extending the Poisson models was fit. Geospatial clustering analysis was also performed. No association was noted between cumulative radon levels and thyroid incidence. In the Poisson modeling, no significant association was noted between county radon level and thyroid cancer incidence (P = .23). Looking for a lag between the radon level and its effect, no significant effect was seen with a lag of 0 to 6 years between exposure and effect (P = .063 to P = .59). The Bayesian models also failed to show a statistically significant association. A cluster of high thyroid cancer incidence was found in western Pennsylvania. Through a variety of models, no association was elicited between annual radon levels recorded in Pennsylvania and the rising incidence of thyroid cancer. However, a cluster of thyroid cancer incidence was found in western Pennsylvania. Further studies may be helpful in looking for other exposures or associations. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

Increased sensitivity of thyroid hormone-mediated signaling despite prolonged fasting.

PubMed

Martinez, Bridget; Scheibner, Michael; Soñanez-Organis, José G; Jaques, John T; Crocker, Daniel E; Ortiz, Rudy M

2017-10-01

Thyroid hormones (TH) can increase cellular metabolism. Food deprivation in mammals is typically associated with reduced thyroid gland responsiveness, in an effort to suppress cellular metabolism and abate starvation. However, in prolonged-fasted, elephant seal pups, cellular TH-mediated proteins are up-regulated and TH levels are maintained with fasting duration. The function and contribution of the thyroid gland to this apparent paradox is unknown and physiologically perplexing. Here we show that the thyroid gland remains responsive during prolonged food deprivation, and that its function and production of TH increase with fasting duration in elephant seals. We discovered that our modeled plasma TH data in response to exogenous thyroid stimulating hormone predicted cellular signaling, which was corroborated independently by the enzyme expression data. The data suggest that the regulation and function of the thyroid gland in the northern elephant seal is atypical for a fasted animal, and can be better described as, "adaptive fasting". Furthermore, the modeling data help substantiate the in vivo responses measured, providing unique insight on hormone clearance, production rates, and thyroid gland responsiveness. Because these unique endocrine responses occur simultaneously with a nearly strict reliance on the oxidation of lipid, these findings provide an intriguing model to better understand the TH-mediated reliance on lipid metabolism that is not otherwise present in morbidly obese humans. When coupled with cellular, tissue-specific responses, these data provide a more integrated assessment of thyroidal status that can be extrapolated for many fasting/food deprived mammals. Copyright © 2017 Elsevier Inc. All rights reserved.

Predictive Factors of Nivolumab-induced Hypothyroidism in Patients with Non-small Cell Lung Cancer.

PubMed

Maekura, Toshiya; Naito, Maiko; Tahara, Masahiro; Ikegami, Naoya; Kimura, Yohei; Sonobe, Shoko; Kobayashi, Takehiko; Tsuji, Taisuke; Minomo, Shojiro; Tamiya, Akihiro; Atagi, Shinji

2017-01-01

Although immune checkpoint inhibitors play an important role in the therapy of lung cancer, they are associated with various immune-related adverse events and predictive factors of them are unclear. In this study, we investigated predictive factors of nivolumab-induced hypothyroidism which is one of the adverse events in patients with lung cancer. Patients with non-small-cell lung cancer who were administered nivolumab at our hospital between December 2015 and May 2016 were retrospectively enrolled. The thyroid-stimulating hormone, free triiodothyronine, free thyroxine, thyroid peroxidase (TPO) antibody, and thyroglobulin antibody levels of each patient were analyzed. Of the 64 patients enrolled, 5 (7.8%) developed hypothyroidism after treatment with nivolumab. The TPO and thyroglobulin antibodies were significantly positive in patients who developed primary hypothyroidism. TPO and thyroglobulin antibody levels at baseline may be predictive of hypothyroidism. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Validation of 131I ecological transfer models and thyroid dose assessments using Chernobyl fallout data from the Plavsk district, Russia

PubMed Central

Zvonova, I.; Krajewski, P.; Berkovsky, V.; Ammann, M.; Duffa, C.; Filistovic, V.; Homma, T.; Kanyar, B.; Nedveckaite, T.; Simon, S.L.; Vlasov, O.; Webbe-Wood, D.

2009-01-01

Within the project “Environmental Modelling for Radiation Safety” (EMRAS) organized by the IAEA in 2003 experimental data of 131I measurements following the Chernobyl accident in the Plavsk district of Tula region, Russia were used to validate the calculations of some radioecological transfer models. Nine models participated in the inter-comparison. Levels of 137Cs soil contamination in all the settlements and 131I/137Cs isotopic ratios in the depositions in some locations were used as the main input information. 370 measurements of 131I content in thyroid of townspeople and villagers, and 90 measurements of 131I concentration in milk were used for validation of the model predictions. A remarkable improvement in models performance comparing with previous inter-comparison exercise was demonstrated. Predictions of the various models were within a factor of three relative to the observations, discrepancies between the estimates of average doses to thyroid produced by most participant not exceeded a factor of ten. PMID:19783331

Tumor classification in well-differentiated thyroid carcinoma and sentinel lymph node biopsy outcomes: a direct correlation.

PubMed

Maniakas, Anastasios; Forest, Veronique-Isabelle; Jozaghi, Yelda; Saliba, Joe; Hier, Michael P; Mlynarek, Alex; Tamilia, Michael; Payne, Richard J

2014-04-01

Predicting locoregional metastasis in well-differentiated thyroid carcinoma (WDTC) is a challenge for thyroid cancer surgeons. Sentinel lymph node biopsy (SLNB) has been shown to be an effective predictive tool. To our knowledge, primary tumor (T) classification has yet to be studied with regard to SLNB. We hypothesized that larger primary tumors would correlate with the rate of malignancy in SLNBs. A retrospective chart review was conducted on patients operated for WDTC at the McGill Thyroid Cancer Center over a 36-month period. Patients who underwent a total thyroidectomy and SLNB for WDTC were included in this study. A total of 311 patients were included and separated into two groups (236 negative and 75 positive SLNBs). Among patients with negative SLNBs, 65% had T1 primary tumors, 17% T2, 16% T3, and 2% T4, whereas 18% of patients with positive SLNBs had T1 primary tumors, 5% T2, 45% T3, and 32% T4 (p<0.001). Patients under the age of 45 years had a higher rate of positive SLNs (36% in those <45 years vs. 17% in those ≥ 45 years; p<0.001). Age (<45 years) and higher T category were found to be associated with a higher rate of positive SLNBs.

In vitro perturbations of targets in cancer hallmark processes predict rodent chemical carcinogenesis.

PubMed

Kleinstreuer, Nicole C; Dix, David J; Houck, Keith A; Kavlock, Robert J; Knudsen, Thomas B; Martin, Matthew T; Paul, Katie B; Reif, David M; Crofton, Kevin M; Hamilton, Kerry; Hunter, Ronald; Shah, Imran; Judson, Richard S

2013-01-01

Thousands of untested chemicals in the environment require efficient characterization of carcinogenic potential in humans. A proposed solution is rapid testing of chemicals using in vitro high-throughput screening (HTS) assays for targets in pathways linked to disease processes to build models for priority setting and further testing. We describe a model for predicting rodent carcinogenicity based on HTS data from 292 chemicals tested in 672 assays mapping to 455 genes. All data come from the EPA ToxCast project. The model was trained on a subset of 232 chemicals with in vivo rodent carcinogenicity data in the Toxicity Reference Database (ToxRefDB). Individual HTS assays strongly associated with rodent cancers in ToxRefDB were linked to genes, pathways, and hallmark processes documented to be involved in tumor biology and cancer progression. Rodent liver cancer endpoints were linked to well-documented pathways such as peroxisome proliferator-activated receptor signaling and TP53 and novel targets such as PDE5A and PLAUR. Cancer hallmark genes associated with rodent thyroid tumors were found to be linked to human thyroid tumors and autoimmune thyroid disease. A model was developed in which these genes/pathways function as hypothetical enhancers or promoters of rat thyroid tumors, acting secondary to the key initiating event of thyroid hormone disruption. A simple scoring function was generated to identify chemicals with significant in vitro evidence that was predictive of in vivo carcinogenicity in different rat tissues and organs. This scoring function was applied to an external test set of 33 compounds with carcinogenicity classifications from the EPA's Office of Pesticide Programs and successfully (p = 0.024) differentiated between chemicals classified as "possible"/"probable"/"likely" carcinogens and those designated as "not likely" or with "evidence of noncarcinogenicity." This model represents a chemical carcinogenicity prioritization tool supporting targeted testing and functional validation of cancer pathways.

Breast-Milk Iodine Concentrations, Iodine Status, and Thyroid Function of Breastfed Infants Aged 2-4 Months and Their Mothers Residing in a South African Township.

PubMed

Osei, Jennifer; Andersson, Maria; Reijden, Olivia van der; Dold, Susanne; Smuts, Cornelius M; Baumgartner, Jeannine

2016-12-01

Lactating women and their infants are susceptible to iodine deficiency and iodine excess. In South Africa, no data exist on the iodine status and thyroid function of these vulnerable groups. In a cross-sectional study, urinary iodine concentrations (UIC), thyroid function, and breast-milk iodine concentrations (BMIC) were assessed in 100 lactating women from a South African township and their 2-4-month-old breastfed infants. Potential predictors of UIC, thyroid function, and BMIC, including household salt iodine concentrations (SIC) and maternal sodium excretion, were also investigated. The median (25th-75th percentile) UIC was 373 (202-627) μg/L in infants and 118 (67-179) μg/L in mothers. Median household SIC was 44 (27-63) ppm. Household SIC and maternal urinary sodium excretion predicted UIC of lactating mothers. Median BMIC was 179 (126-269) μg/L. Age of infants, SIC, and maternal UIC predicted BMIC. In turn, infant age and BMIC predicted UIC of infants. Forty-two percent of SIC values were within the South African recommended salt iodine fortification level at production of 35-65 ppm, whilst 21% of SIC were >65 ppm. Thyroid-stimulating hormone, total thyroxine, and thyroglobulin concentrations in the dried whole blood spot specimens from the infants were 1.3 (0.8-1.9) mU/L, 128±33 mmol/L, and 77.1 (56.3-105.7) μg/L, respectively, and did not correlate with infant UIC or BMIC. Our results suggest that the salt fortification program in South Africa provides adequate iodine to lactating women and indirectly to their infants via breast milk. However, monitoring of salt iodine content of the mandatory salt iodization program in South Africa is important to avoid over-iodization of salt.

The predictive value of dominant nodules and the management of indeterminate group in multinodular goiter.

PubMed

Acıoğlu, Engin; Yiğit, Özgür; Seden, Nihal; Huq, Gülben Erdem

2012-01-01

The objectives of this study were to determine the predictive value of dominant nodules (DNs) in multinodular goiters (MNGs), and to stratify the risk of malignancy within the indeterminate category. The study design was retrospective study of patients with MNG. A total of 140 patients were reviewed. Fine needle aspiration biopsy (FNAB) findings for all DNs were categorized into four groups: (1) benign, (2) positive or suspicious for malignancy, (3) indeterminate, and (4) non-diagnostic. All FNAB specimens of the indeterminate group were also evaluated for the presence of Hurthle cell metaplasia and were categorized according to the presence of cytological atypia. Cytohistological comparison was then performed. Mean number and diameter of the DNs were 1.45 and 25.6 mm, respectively. Based on final histopathology, 22.14% of the patients had thyroid malignancy and 74.2% of thyroid carcinomas were located in DNs. The number of DNs was significantly larger in malignant thyroid glands than in benign ones. In total, 22.6% of the indeterminate FNABs were malignant. FNABs of the indeterminate group that included atypical cells had a statistically significant higher incidence of malignancy. The presence of Hurthle cells was not statistically different in malignant and benign nodules upon final histological diagnosis. In conclusion, FNAB of only DNs in MNG could determine thyroid malignancy in 75% of patients. The DN number might be required for the predictive value of malignancy. A subclassification of the indeterminate group, based on the presence or absence of cytological atypia, is necessary to better assess the risk of malignancy.

Sunitinib-induced hypothyroidism predicts progression-free survival in metastatic renal cell carcinoma patients.

PubMed

Buda-Nowak, Anna; Kucharz, Jakub; Dumnicka, Paulina; Kuzniewski, Marek; Herman, Roman Maria; Zygulska, Aneta L; Kusnierz-Cabala, Beata

2017-04-01

Sunitinib is a tyrosine kinase inhibitor (TKI) used in treatment of metastatic renal cell carcinoma (mRCC), gastrointestinal stromal tumors and pancreatic neuroendocrine tumors. One of the most common side effects related to sunitinib is hypothyroidism. Recent trials suggest correlation between the incidence of hypothyroidism and treatment outcome in patients treated with TKI. This study evaluates whether development of hypothyroidism is a predictive marker of progression-free survival (PFS) in patients with mRCC treated with sunitinib. Twenty-seven patients diagnosed with clear cell mRCC, after nephrectomy and in 'good' or 'intermediate' MSKCC risk prognostic group, were included in the study. All patients received sunitinib as a first-line treatment on a standard schedule (initial dose 50 mg/day, 4 weeks on, 2 weeks off). The thyroid-stimulating hormone serum levels were obtained at the baseline and every 12 weeks of treatment. In statistic analyses, we used Kaplan-Meier method for assessment of progression-free survival; for comparison of survival, we used log-rank test. In our study, the incidence of hypothyroidism was 44%. The patients who had developed hypothyroidism had better median PFS to patients with normal thyroid function 28,3 months [95% (CI) 20.4-36.2 months] versus 9.8 months (6.4-13.1 months). In survival analysis, we perceive that thyroid dysfunction is a predictive factor of a progression-free survival (PFS). In the unified group of patients, the development of hypothyroidism during treatment with sunitinib is a positive marker for PFS. During that treatment, thyroid function should be evaluated regularly.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Willemin, Marie-Emilie; Lumen, Annie, E-mail: Anni

Thyroid homeostasis can be disturbed due to thiocyanate exposure from the diet or tobacco smoke. Thiocyanate inhibits both thyroidal uptake of iodide, via the sodium-iodide symporter (NIS), and thyroid hormone (TH) synthesis in the thyroid, via thyroid peroxidase (TPO), but the mode of action of thiocyanate is poorly quantified in the literature. The characterization of the link between intra-thyroidal thiocyanate concentrations and dose of exposure is crucial for assessing the risk of thyroid perturbations due to thiocyanate exposure. We developed a PBPK model for thiocyanate that describes its kinetics in the whole-body up to daily doses of 0.15 mmol/kg, withmore » a mechanistic description of the thyroidal kinetics including NIS, passive diffusion, and TPO. The model was calibrated in a Bayesian framework using published studies in rats. Goodness-of-fit was satisfactory, especially for intra-thyroidal thiocyanate concentrations. Thiocyanate kinetic processes were quantified in vivo, including the metabolic clearance by TPO. The passive diffusion rate was found to be greater than NIS-mediated uptake rate. The model captured the dose-dependent kinetics of thiocyanate after acute and chronic exposures. Model behavior was evaluated using a Morris screening test. The distribution of thiocyanate into the thyroid was found to be determined primarily by the partition coefficient, followed by NIS and passive diffusion; the impact of the latter two mechanisms appears to increase at very low doses. Extrapolation to humans resulted in good predictions of thiocyanate kinetics during chronic exposure. The developed PBPK model can be used in risk assessment to quantify dose-response effects of thiocyanate on TH. - Highlights: • A PBPK model of thiocyanate (SCN{sup −}) was calibrated in rats in a Bayesian framework. • The intra-thyroidal kinetics of thiocyanate including NIS and TPO was modeled. • Passive diffusion rate for SCN{sup −} seemed to be greater than the NIS-mediated uptake. • The dose-dependent kinetics of SCN{sup −} was captured after an acute and chronic exposure. • The PBPK model of thiocyanate was successfully extrapolated to humans.« less

Thyroid hormone levels in the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex.

PubMed Central

Tang, W W; Kaptein, E M

1989-01-01

Hypothalamic-pituitary dysfunction and thyroid gland cytomegalovirus inclusions have been described in patients with the acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC). We evaluated 80 patients with AIDS or ARC for the frequency of hypothalamic-pituitary or thyroid gland failure and altered serum thyroid hormone levels due to nonthyroidal disorders. One patient had subclinical hypothyroidism. Of these patients, 60% had low free triiodothyronine (T3) index values and 4% had low free thyroxine (T4) indexes; none of the latter had hypothalamic-pituitary or thyroid gland failure, since all serum cortisol values were greater than or equal to 552 nmol per liter (greater than or equal to 20 micrograms per dl) and all thyrotropin levels were less than or equal to 3 mU per liter (less than or equal to 3 microU per ml), respectively. Those who died had lower total T4 and T3, free T3 index, and albumin levels than those discharged from hospital. Serum total T4 and T3 levels correlated with albumin levels and total T3 with serum sodium levels. Serum total T3 levels best predicted the outcome of the hospital stay (accuracy = 82%). Thus, abnormal serum thyroid hormone levels in AIDS or ARC patients are most frequently due to nonthyroidal disorders, but hypothalamic-pituitary or thyroid gland failure may occur. PMID:2618039

Incidence of Subclinical Hypothyroidism and Hypothyroidism in Early Pregnancy.

PubMed

Akram, Frida Hosseini; Johansson, Bengt; Möllerström, Gunnar; Landgren, Britt-Marie; Stavreus-Evers, Anneli; Skjöldebrand-Sparre, Lottie

2017-11-01

Untreated and subclinical hypothyroidism (SCH) has been associated with adverse pregnancy complications such as increased risk of miscarriage, hypertension, preeclampsia, and preterm delivery. However, in Sweden, screening for thyroid dysfunction during pregnancy is only recommended for women with a high risk of thyroid disease. Therefore, the aim of this study was to determine the incidence of clinical and SCH in women in the first trimester of pregnancy. In this prospective study, 1298 pregnant women were divided into three groups: one unselected general screening group (n = 611), one low-risk group comprising women without risk factors for thyroid disorder (n = 511), and one high-risk group comprising women with an inheritance or suspicion of thyroid disease or undergoing treatment for thyroid disease (n = 88). Serum was obtained up to gestational week 13, and thyrotropin (TSH) was analyzed. The incidences of thyroid dysfunction in the three screening groups were 9.8% in the general screening group, 9.6% in the low-risk group, and 10.2%, p = 0.948, in the high-risk group. In the women with known hypothyroidism on levothyroxine treatment, 50.6% had serum TSH levels above 2.0 mIU/L. High-risk screening is not useful in predicting which women are at risk of thyroid disease in early pregnancy since ∼10% of women with SCH or hypothyroidism could not be diagnosed in this way.

Heritability analysis of IgG4 antibodies in autoimmune thyroid disease.

PubMed

Outschoorn, I M; Talor, M V; Burek, C L; Hoffman, W H; Rose, N R

2014-08-01

A study of IgG4 autoantibody levels in juvenile thyroid disease patients showed evidence of heritability using the ROMP screening method. These levels increased with time despite the fact that total IgG antibody decreased with time. Evidence of heritability was demonstrated only in patients with high titers of autoantibodies to both thyroglobulin (Tg) and thyroperoxidase (TPO) unlike family members who may show high titers of one or the other and be asymptomatic at the time of sampling. Since high and low IgG4 levels give different heritability plots, these findings may represent a more severe fibrotic form of thyroiditis with a distinct genetic background. Hence a simple predictive approach is offered by this screening tool for the disease in patients and family members which may be helpful in the future to identify IgG4-related thyroiditis early in the course of disease without the requirement for biopsy.

Kcne2 deletion uncovers its crucial role in thyroid hormone biosynthesis

PubMed Central

Roepke, Torsten K.; King, Elizabeth C.; Reyna-Neyra, Andrea; Paroder, Monika; Purtell, Kerry; Koba, Wade; Fine, Eugene; Lerner, Daniel J.; Carrasco, Nancy; Abbott, Geoffrey W.

2009-01-01

Thyroid dysfunction affects 1–4% of the population worldwide, causing defects including neurodevelopmental disorders, dwarfism and cardiac arrhythmia. Here, we show that KCNQ1 and KCNE2 form a TSH-stimulated, constitutively-active, thyrocyte K+ channel required for normal thyroid hormone biosynthesis. Targeted disruption of Kcne2 impaired thyroid iodide accumulation up to 8-fold, impaired maternal milk ejection and halved milk T4 content, causing hypothyroidism, 50% reduced litter size, dwarfism, alopecia, goiter, and cardiac abnormalities including hypertrophy, fibrosis, and reduced fractional shortening. The alopecia, dwarfism and cardiac abnormalities were alleviated by T3/T4 administration to pups, by supplementing dams with T4 pre- and postpartum, or by pre-weaning surrogacy with Kcne2+/+ dams; conversely these symptoms were elicited in Kcne2+/+ pups by surrogacy with Kcne2−/− dams. The data identify a critical thyrocyte K+ channel, provide a possible novel therapeutic avenue for thyroid disorders, and predict an endocrine component to some previously-identified KCNE2- and KCNQ1-linked human cardiac arrhythmias. PMID:19767733

Thyrotropin receptor autoantibodies and early miscarriages in patients with Hashimoto thyroiditis: a case-control study.

PubMed

Toulis, Konstantinos A; Goulis, Dimitrios G; Tsolakidou, Konstantina; Hilidis, Ilias; Fragkos, Marios; Polyzos, Stergios A; Gerofotis, Antonios; Kita, Marina; Bili, Helen; Vavilis, Dimitrios; Daniilidis, Michail; Tarlatzis, Basil C; Papadimas, Ioannis

2013-08-01

We have previously hypothesized that early miscarriage in women with Hashimoto thyroiditis might be the result of a cross-reactivity process, in which blocking autoantibodies against thyrotropin receptor (TSHr-Ab) antagonize hCG action on its receptor on the corpus luteum. To test this hypothesis from the clinical perspective, we investigated the presence of TSHr-Ab in Hashimoto thyroiditis patients with apparently unexplained, first-trimester recurrent miscarriages compared to that in Hashimoto thyroiditis patients with documented normal fertility. A total of 86 subjects (43 cases and 43 age-matched controls) were finally included in a case-control study. No difference in the prevalence of TSHr-Ab positivity was detected between cases and controls (Fisher's exact test, p value = 1.00). In patients with recurrent miscarriages, TSHr-Ab concentrations did not predict the number of miscarriages (univariate linear regression, p value = 0.08). These results were robust in sensitivity analyses, including only cases with full investigation or those with three or more miscarriages. We conclude that no role could be advocated for TSHr-Ab in the aetiology of recurrent miscarriages in women with Hashimoto thyroiditis.

Influence of lake trophic structure on iodine-131 accumulation and subsequent cumulative radiation dose to trout thyroids.

PubMed

Martinez, Nicole E; Johnson, Thomas E; Pinder, John E

2014-05-01

Iodine-131 is a major component of the atmospheric releases following reactor accidents, and the passage of (131)I through food chains from grass to human thyroids has been extensively studied. By comparison, the fate and effects of (131)I deposition onto lakes and other aquatic systems have been less studied. In this study we: (1) reanalyze 1960s data from experimental releases of (131)I into two small lakes; (2) compare the effects of differences in lake trophic structures on the accumulation of (131)I by fish; (3) relate concentrations in fish and fish tissues to that in the water column using empirically estimated uptake (L kg(-1) d(-1)) and loss (d(-1)) parameters; and (4) show that the largest concentrations in the thyroids of trout (Oncorhynchus mykiss) may occur from 8 to 32 days after initial release. Iodine-131 concentration in trout thyroids at 30-days post release may be >1000 times that in the water. Estimates of cumulative radiation dose (mGy) to thyroids computed using an anatomically-appropriate model of trout thyroid structure within the Monte Carlo N-particle modeling software predicted cumulative thyroid doses that increased approximately linearly after the first 8 days and resulted in 32-day cumulative thyroid doses that ranged from 6 mGy g(-1) to 18 mGy g(-1) per 1 Bq mL(-1) of initial (131)I in the water depending upon fish size. The majority of this dose is due to beta emissions, and the dose varies with positions in the thyroid tissue. Copyright © 2013 Elsevier Ltd. All rights reserved.

Cytological Evaluation of Thyroid Lesions by Nuclear Morphology and Nuclear Morphometry.

PubMed

Yashaswini, R; Suresh, T N; Sagayaraj, A

2017-01-01

Fine needle aspiration (FNA) of the thyroid gland is an effective diagnostic method. The Bethesda system for reporting thyroid cytopathology classifies them into six categories and gives implied risk for malignancy and management protocol in each category. Though the system gives specific criteria, diagnostic dilemma still exists. Using nuclear morphometry, we can quantify the number of parameters, such as those related to nuclear size and shape. The evaluation of nuclear morphometry is not well established in thyroid cytology. To classify thyroid lesions on fine needle aspiration cytology (FNAC) using Bethesda system and to evaluate the significance of nuclear parameters in improving the prediction of thyroid malignancy. In the present study, 120 FNAC cases of thyroid lesions with histological diagnosis were included. Computerized nuclear morphometry was done on 81 cases which had confirmed cytohistological correlation, using Aperio computer software. One hundred nuclei from each case were outlined and eight nuclear parameters were analyzed. In the present study, thyroid lesions were common in female with M: F ratio of 1:5 and most commonly in 40-60 yrs. Under Bethesda system, 73 (60.83%) were category II; 14 (11.6%) were category III, 3 (2.5%) were category IV, 8 (6.6%) were category V, and 22 (18.3%) were category VI, which were malignant on histopathological correlation. Sensitivity, specificity, and diagnostic accuracy of Bethesda reporting system are 62.5, 84.38, and 74.16%, respectively. Minimal nuclear diameter, maximal nuclear diameter, nuclear perimeter, and nuclear area were higher in malignant group compared to nonneoplastic and benign group. The Bethesda system is a useful standardized system of reporting thyroid cytopathology. It gives implied risk of malignancy. Nuclear morphometry by computerized image analysis can be utilized as an additional diagnostic tool.

In vitro pituitary and thyroid cell proliferation assays and their relevance as alternatives to animal testing.

PubMed

Jomaa, Barae; Aarts, Jac M M J G; de Haan, Laura H J; Peijnenburg, Ad A C M; Bovee, Toine F H; Murk, Albertinka J; Rietjens, Ivonne M C M

2013-01-01

This study investigates the in vitro effect of eleven thyroid-active compounds known to affect pituitary and/or thyroid weights in vivo, using the proliferation of GH3 rat pituitary cells in the so-called "T-screen," and of FRTL-5 rat thyroid cells in a newly developed test denoted "TSH-screen" to gain insight into the relative value of these in vitro proliferation tests for an integrated testing strategy (ITS) for thyroid activity. Pituitary cell proliferation in the T-screen was stimulated by three out of eleven tested compounds, namely thyrotropin releasing hormone (TRH), triiodothyronine (T3) and thyroxine (T4). Of these three compounds, only T4 causes an increase in relative pituitary weight, and thus T4 was the only compound for which the effect in the in vitro assay correlated with a reported in vivo effect. As to the newly developed TSH-screen, two compounds had an effect, namely, thyroid-stimulating hormone (TSH) induced and T4 antagonized FRTL-5 cell proliferation. These effects correlated with in vivo changes induced by these compounds on thyroid weight. Altogether, the results indicate that most of the selected compounds affect pituitary and thyroid weights by modes of action different from a direct thyroid hormone receptor (THR) or TSH receptor (TSHR)-mediated effect, and point to the need for additional in vitro tests for an ITS. Additional analysis of the T-screen revealed a positive correlation between the THR-mediated effects of the tested compounds in vitro and their effects on relative heart weight in vivo, suggesting that the T-screen may directly predict this THR-mediated in vivo adverse effect.

Delphian node metastasis in head and neck cancers--oracle or myth?

PubMed

Iyer, N Gopalakrishna; Shaha, Ashok R; Ferlito, Alfio; Thomas Robbins, K; Medina, Jesus E; Silver, Carl E; Rinaldo, Alessandra; Takes, Robert P; Suárez, Carlos; Rodrigo, Juan P; Bradley, Patrick J; Werner, Jochen A

2010-09-15

Delphian node (DN) refers to the pre-laryngeal or pre-cricoid nodal tissue often identified during laryngeal or thyroid surgery. The original nomenclature is based on the assumption that metastasis to this node was predictive of aggressive disease and poor outcome for patients. In this article, we review the existing literature on the topic to determine the significance of DN metastasis in laryngeal, hypopharyngeal and thyroid cancers. (c) 2010 Wiley-Liss, Inc.

Etiological evaluation of primary congenital hypothyroidism cases.

PubMed

Bezen, Diğdem; Dilek, Emine; Torun, Neşe; Tütüncüler, Filiz

2017-06-01

Primary congenital hypothyroidism is frequently seen endocrine disorder and one of the preventable cause of mental retardation. Aim of study was to evaluate the frequency of permanent/transient hypothyrodism, and to detect underlying reason to identfy any marker which carries potential to discriminate permanent/transient form. Forty eight cases older than 3 years of age, diagnosed as primary congenital hypothyroidism and started thyroxin therapy in newborn-period, and followed up between January 2007-June 2013 were included in the study. Thyroid hormon levels were evaluated and thyroid ultrasonography was performed in cases who are at the end of their 3 years of age, after 6 weeks of thyroxine free period. Thyroid sintigraphy was performed if serum thyroid-stimulating hormone was high (≥ 5 mIU/mL) and perchlorate discharge test was performed if uptake was normal or increased on sintigraphy. Cases with thyroid-stimulating hormone levels ≥ 5 mIU/mL were defined as permanent primary congenital hypothyroidism group and as transient primary congenital hypothyroidism group with normal thyroid hormones during 6 months. The mean age was 3.8±0.7 years. Mean diagnosis age was 16.6±6.5 days and 14 cases (29.2%) were diagnosed by screening program of Ministry of Health. There were 23 cases (14F, 9M) in permanent primary congenital hypothyroidism group and 12 (52.2%) of them were dysgenesis (8 hypoplasia, 4 ectopia), and 11 (47.8%) dyshormonogenesis. In transient primary congenital hypothyroidism group, there were 25 cases (17M, 8F). The mean thyroid-stimulating hormone levels at diagnosis were similar in two groups. The mean thyroxin dose in permanent primary congenital hypothyroidism group was significantly higher than transient group at the time of thyroxin cessation (2.1±0.7, 1.5±0.5 mg/kg/d, respectively, p=0.004). Thyroxin dose ≥1.6 mcg/kg/d was 72% sensitive and 69.6% specific for predicting permenant primary congenital hypothyroidism. Transient primary congenital hypothyroidism is more frequent than expected and found often in males in the primary congenital hypothyroidism cases, started thyroxin therapy in neonatal period. While fT4, thyroid-stimulating hormone, Tg levels at diagnosis do not predict transient/permenant primary congenital hypothyroidism, thyroxin dose before the therapy cessation at the age of 3 may make the distinction between transient/permenant primary congenital hypothyroidism.

GAUGING THE EXTENT OF THYROIDECTOMY FOR INDETERMINATE THYROID NODULES: AN ONCOLOGIC PERSPECTIVE.

PubMed

Schneider, David F; Cherney Stafford, Linda M; Brys, Nicole; Greenberg, Caprice C; Balentine, Courtney J; Elfenbein, Dawn M; Pitt, Susan C

2017-04-02

Increasing emphasis is being placed on appropriateness of care and avoidance of over- and under-treatment. Indeterminate thyroid nodules (ITNs) present a particular risk for this problem because cancer found via diagnostic lobectomy (DL) often requires a completion thyroidectomy (CT). However, initial total thyroidectomy (TT) for benign ITN results in lifelong thyroid hormone replacement. We sought to measure the accuracy and factors associated with the extent of initial thyroidectomy for ITN. We queried a single institution thyroid surgery database for all adult patients undergoing an initial operation for ITN. Multivariate logistic regression identified factors associated with either oncologic under- or overtreatment at initial operation. There were 639 patients with ITN. The median age was 52 (range, 18 to 93) years, 78.4% were female, and final pathology revealed a cancer >1 cm in 24.7%. The most common cytology was follicular neoplasm (45.1%) followed by Hürthle cell neoplasm (20.2%). CT or initial oncologic undertreatment was required in 58 patients (9.3%). Excluding those with goiters, 19.0% were treated with TT for benign final pathology. Multivariate analysis failed to identify any factor that independently predicted the need for CT. Female gender was associated with TT in benign disease (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.0 to 4.5; P = .05). Age >45 years predicted correct initial use of DL (OR, 2.6; 95% CI, 1.2 to 5.7; P = .02). Suspicious for papillary thyroid carcinoma (OR, 5.7; 95% CI, 2.1 to 15.3; P<.01) and frozen section (OR, 9.7; 95% CI, 2.5 to 38.6; P<.01) were associated with oncologically appropriate initial TT. The highest frequency of CT occurred in patients with follicular lesion of undetermined significance (11.6%). TT for benign final pathology occurred most frequently in patients with a Hürthle cell neoplasm (24.8%). In patients with ITN, nearly 30% received an inappropriate extent of initial thyroidectomy from an oncologic standpoint. Tools to pre-operatively identify both benign and malignant disease can assist in the complex decision making to gauge the proper extent of initial surgery for ITN. ATA = American Thyroid Association AUS = atypia of undetermined significance CI = confidence interval CT = completion thyroidectomy FLUS = follicular lesion of undetermined significance ITN = indeterminate thyroid nodule OR = odds ratio PTC = papillary thyroid carcinoma TT = total thyroidectomy.

NFE2-Related Transcription Factor 2 Coordinates Antioxidant Defense with Thyroglobulin Production and Iodination in the Thyroid Gland.

PubMed

Ziros, Panos G; Habeos, Ioannis G; Chartoumpekis, Dionysios V; Ntalampyra, Eleni; Somm, Emmanuel; Renaud, Cédric O; Bongiovanni, Massimo; Trougakos, Ioannis P; Yamamoto, Masayuki; Kensler, Thomas W; Santisteban, Pilar; Carrasco, Nancy; Ris-Stalpers, Carrie; Amendola, Elena; Liao, Xiao-Hui; Rossich, Luciano; Thomasz, Lisa; Juvenal, Guillermo J; Refetoff, Samuel; Sykiotis, Gerasimos P

2018-06-01

The thyroid gland has a special relationship with oxidative stress. While generation of oxidative substances is part of normal iodide metabolism during thyroid hormone synthesis, the gland must also defend itself against excessive oxidation in order to maintain normal function. Antioxidant and detoxification enzymes aid thyroid cells to maintain homeostasis by ameliorating oxidative insults, including during exposure to excess iodide, but the factors that coordinate their expression with the cellular redox status are not known. The antioxidant response system comprising the ubiquitously expressed NFE2-related transcription factor 2 (Nrf2) and its redox-sensitive cytoplasmic inhibitor Kelch-like ECH-associated protein 1 (Keap1) defends tissues against oxidative stress, thereby protecting against pathologies that relate to DNA, protein, and/or lipid oxidative damage. Thus, it was hypothesized that Nrf2 should also have important roles in maintaining thyroid homeostasis. Ubiquitous and thyroid-specific male C57BL6J Nrf2 knockout (Nrf2-KO) mice were studied. Plasma and thyroids were harvested for evaluation of thyroid function tests by radioimmunoassays and of gene and protein expression by real-time polymerase chain reaction and immunoblotting, respectively. Nrf2-KO and Keap1-KO clones of the PCCL3 rat thyroid follicular cell line were generated using CRISPR/Cas9 technology and were used for gene and protein expression studies. Software-predicted Nrf2 binding sites on the thyroglobulin enhancer were validated by site-directed in vitro mutagenesis and chromatin immunoprecipitation. The study shows that Nrf2 mediates antioxidant transcriptional responses in thyroid cells and protects the thyroid from oxidation induced by iodide overload. Surprisingly, it was also found that Nrf2 has a dramatic impact on both the basal abundance and the thyrotropin-inducible intrathyroidal abundance of thyroglobulin (Tg), the precursor protein of thyroid hormones. This effect is mediated by cell-autonomous regulation of Tg gene expression by Nrf2 via its direct binding to two evolutionarily conserved antioxidant response elements in an upstream enhancer. Yet, despite upregulating Tg levels, Nrf2 limits Tg iodination both under basal conditions and in response to excess iodide. Nrf2 exerts pleiotropic roles in the thyroid gland to couple cell stress defense mechanisms to iodide metabolism and the thyroid hormone synthesis machinery, both under basal conditions and in response to excess iodide.

Interstitial laser photocoagulation for benign thyroid nodules: time to treat large nodules.

PubMed

Amabile, Gerardo; Rotondi, Mario; Pirali, Barbara; Dionisio, Rosa; Agozzino, Lucio; Lanza, Michele; Buonanno, Luciano; Di Filippo, Bruno; Fonte, Rodolfo; Chiovato, Luca

2011-09-01

Interstitial laser photocoagulation (ILP) is a new therapeutic option for the ablation of non-functioning and hyper-functioning benign thyroid nodules. Amelioration of the ablation procedure currently allows treating large nodules. Aim of this study was to evaluate the therapeutic efficacy of ILP, performed according to a modified protocol of ablation, in patients with large functioning and non-functioning thyroid nodules and to identify the best parameters for predicting successful outcome in hyperthyroid patients. Fifty-one patients with non-functioning thyroid nodules (group 1) and 26 patients with hyperfunctioning thyroid nodules (group 2) were enrolled. All patients had a nodular volume ≥40 ml. Patients were addressed to 1-3 cycles of ILP. A cycle consisted of three ILP sessions, each lasting 5-10 minutes repeated at an interval of 1 month. After each cycle of ILP patients underwent thyroid evaluation. A nodule volume reduction, expressed as percentage of the basal volume, significantly occurred in both groups (F = 190.4; P < 0.0001 for group 1 and F = 100.2; P < 0.0001 for group 2). Receiver-operator-characteristic (ROC) curves were constructed for: (i) percentage of volume reduction; (ii) difference in nodule volume; (iii) total amount of energy delivered expressed in Joule. ROC curves identified the percentage of volume reduction as the best parameter predicting a normalized serum TSH (area under the curve 0.962; P < 0.0001). Intraoperative complications consisted in: (i) mild pain occurring in five (6.5%) patients, (ii) vasovagal reaction in two (2.6%) patients, (iii) fever within 24 hours from ILP in five (6.5%) patients. No major complications including persistent pain, laringeal nerve dysfunction, hypoparathyroidism, pseudocystic transformation, and/or neck fascitis were observed. ILP represents a valid alternative to surgery also for large benign thyroid nodules, both in terms of nodule size reduction and cure of hyperthyroidism (87% of cured patients after the last ILP cycle). ILP should not be limited to patients refusing or being ineligible for surgery and/or radioiodine. Copyright © 2011 Wiley-Liss, Inc.

Thyroid V30 Predicts Radiation-Induced Hypothyroidism in Patients Treated With Sequential Chemo-Radiotherapy for Hodgkin's Lymphoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cella, Laura; Department of Diagnostic Imaging and Radiation Oncology, Federico II University School of Medicine, Naples; Conson, Manuel

Purpose: Hypothyroidism (HT) is a frequent late side effect of Hodgkin's lymphoma (HL) therapy. The purpose of this study is to determine dose-volume constraints that correlate with functional impairment of the thyroid gland in HL patients treated with three-dimensional radiotherapy. Methods and Materials: A total of 61 consecutive patients undergoing antiblastic chemotherapy and involved field radiation treatment (median dose, 32 Gy; range, 30-36 Gy) for HL were retrospectively considered. Their median age was 28 years (range, 14-70 years). Blood levels of thyroid-stimulating hormone (TSH), free triiodo-thyronine (FT3), free thyroxine (FT4), and thyroglobulin antibody (ATG) were recorded basally and at differentmore » times after the end of therapy. For the thyroid gland, normal tissue complication probability (NTCP), dosimetric parameters, and the percentage of thyroid volume exceeding 10, 20, and 30 Gy (V10, V20, and V30) were calculated in all patients. To evaluate clinical and dosimetric factors possibly associated with HT, univariate and multivariate logistic regression analyses were performed. Results: Eight of 61 (13.1%) patients had HT before treatment and were excluded from further evaluation. At a median follow-up of 32 months (range, 6-99 months), 41.5% (22/53) of patients developed HT after treatment. Univariate analyses showed that all dosimetric factors were associated with HT (p < 0.05). On multivariate analysis, the thyroid V30 value was the single independent predictor associated with HT (p = 0.001). This parameter divided the patients into low- vs. high-risk groups: if V30 was {<=} 62.5%, the risk of developing HT was 11.5%, and if V30 was >62.5%, the risk was 70.8% (p < 0.0001). A Cox regression curve stratified by two levels of V30 value was created (odds ratio, 12.6). Conclusions: The thyroid V30 predicts the risk of developing HT after sequential chemo-radiotherapy and defines a useful constraint to consider for more accurate HL treatment planning.« less

THYROSIM App for Education and Research Predicts Potential Health Risks of Over-the-Counter Thyroid Supplements.

PubMed

Han, Simon X; Eisenberg, Marisa; Larsen, P Reed; DiStefano, Joseph

2016-04-01

Computer simulation tools for education and research are making increasingly effective use of the Internet and personal devices. To facilitate these activities in endocrinology and metabolism, a mechanistically based simulator of human thyroid hormone and thyrotropin (TSH) regulation dynamics was developed and further validated, and it was implemented as a facile and freely accessible web-based and personal device application: the THYROSIM app. This study elucidates and demonstrates its utility in a research context by exploring key physiological effects of over-the-counter thyroid supplements. THYROSIM has a simple and intuitive user interface for teaching and conducting simulated "what-if" experiments. User-selectable "experimental" test-input dosages (oral, intravenous pulses, intravenous infusions) are represented by animated graphical icons integrated with a cartoon of the hypothalamic-pituitary-thyroid axis. Simulations of familiar triiodothyronine (T3), thyroxine (T4), and TSH temporal dynamic responses to these exogenous stimuli are reported graphically, along with normal ranges on the same single interface page; and multiple sets of simulated experimental results are superimposable to facilitate comparative analyses. This study shows that THYROSIM accurately reproduces a wide range of published clinical study data reporting hormonal kinetic responses to large and small oral hormone challenges. Simulation examples of partial thyroidectomies and malabsorption illustrate typical usage by optionally changing thyroid gland secretion and/or gut absorption rates--expressed as percentages of normal--as well as additions of oral hormone dosing, all directly on the interface, and visualizing the kinetic responses to these challenges. Classroom and patient education usage--with public health implications--is illustrated by predictive simulated responses to nonprescription thyroid health supplements analyzed previously for T3 and T4 content. Notably, it was found that T3 in supplements has potentially more serious pathophysiological effects than does T4--concomitant with low-normal TSH levels. Some preparations contain enough T3 to generate thyrotoxic conditions, with supernormal serum T3-spiking and subnormal serum T4 and TSH levels and, in some cases, with normal or low-normal range TSH levels due to thyroidal axis negative feedback. These results suggest that appropriate regulation of these products is needed.

Thyroid Hormones and Changes in Body Weight and Metabolic Parameters in Response to Weight-Loss Diets: The POUNDS LOST Trial

PubMed Central

Liu, Gang; Liang, Liming; Bray, George A.; Qi, Lu; Hu, Frank B.; Rood, Jennifer; Sacks, Frank M.; Sun, Qi

2017-01-01

Background The role of thyroid hormones in diet-induced weight loss and subsequent weight regain is largely unknown. Objectives To examine the associations between thyroid hormones and changes in body weight and resting metabolic rate (RMR) in a diet-induced weight-loss setting. Subjects/Methods Data analysis was conducted among 569 overweight and obese participants aged 30–70 years with normal thyroid function participating in the 2-year POUNDS LOST randomized clinical trial. Changes in body weight and RMR were assessed during the 2-year intervention. Thyroid hormones (free triiodothyronine [T3], free thyroxine [T4], total T3, total T4, and thyroid stimulating hormone [TSH]), anthropometric measurements, and biochemical parameters were assessed at baseline, 6 months, and 24 months. Results Participants lost an average of 6.6 kg of body weight during the first 6 months and subsequently regained an average of 2.7 kg of body weight over the remaining period from 6–24 months. Baseline free T3 and total T3 were positively associated, whereas free T4 was inversely associated, with baseline body weight, body mass index, and RMR. Total T4 and TSH were not associated with these parameters. Higher baseline free T3 and free T4 levels were significantly associated with a greater weight loss during the first 6 months (P<0.05) after multivariate adjustments including dietary intervention groups and baseline body weight. Comparing extreme tertiles, the multivariate-adjusted weight loss ± standard error was −3.87±0.9 vs −5.39±0.9 kg for free T3 (P trend=0.02) and −4.09±0.9 vs −5.88±0.9 kg for free T4 (P trend=0.004). The thyroid hormones did not predict weight regain in 6–24 months. A similar pattern of associations was also observed between baseline thyroid hormones and changes in RMR. In addition, changes in free T3 and total T3 levels were positively associated with changes in body weight, RMR, body fat mass, blood pressure, glucose, insulin, triglycerides, and leptin at 6 months and 24 months (all P<0.05). Conclusions In this diet-induced weight-loss setting, higher baseline free T3 and free T4 predicted more weight loss, but not weight regain among overweight and obese adults with normal thyroid function. These findings reveal a novel role of thyroid hormones in body weight regulation and may help identify individuals more responsive to weight-loss diets. PMID:28138133

Serum Anti-TPO and TPO Gene Polymorphism as a Predictive Factor for Hidden Autoimmune Thyroiditis in Patient with Bronchial Asthma and Allergic Rhinitis.

PubMed

El Shabrawy, Reham M; Atta, Amal H; Rashad, Nearmeen M

2016-01-01

Thyroid peroxidase (TPO) is the key enzyme in the biosynthesis of thyroid hormones T3 and T4. Autoimmune thyroiditis is a common disorder affecting 10% of population worldwide. A key feature of autoimmune thyroiditis is the presence of anti TPO antibodies, and some mutation of the TPO gene. Association between autoimmune thyroiditis and other autoimmune disorders has been reported but little is known about association with allergic diseases. In this study, we aimed to evaluate frequency of hidden autoimmune thyroiditis among allergic patient and examine possible relationship between anti-TPO levels and polymorphism at the TPO gene A2173/C exon 12 and different types of allergens. The study included 50 adult Egyptian patients with allergic rhinitis and /or bronchial asthma and 50 controls. For each subject, thyroid stimulating hormone (TSH), thyroxin 4 (T4) and Triiodothyronine (T3) hormones were measured. Anti-thyroid peroxidase (anti-TPO) level was detected by ELISA; and TPO gene polymorphism 2173A>C exon 12 was analyzed using restriction fragment length polymorphism (RFLP). Skin prick test was done to assess allergic response in patients. Serum levels of T3, T4 and TSH did not show any statistical significant difference between patients and groups. However, mean serum anti-TPO level was statistically higher in patients than controls, and correlated positively with body mass index, age, diastolic blood pressure, suggesting higher prevalence of hidden autoimmune thyroiditis in allergic patients than in control group. 2173A>C Genotyping revealed that the frequency of C allele is increased in the patient group. C allele represents a risk factor with odds ratio of 2.37 (1.035-5.44) and a significant P value <0.05. It is concluded that TPO 2173A>C polymorphism may be considered as a risk factor for developing autoimmune thyroiditis in patients with allergic rhinitis and asthma and that these patients should regularly be checked for hidden thyroiditis. Copyright© by the Egyptian Association of Immunologists.

The threshold of hypothyroidism after radiation therapy for head and neck cancer: a retrospective analysis of 116 cases

PubMed Central

Fujiwara, Masayuki; Kamikonya, Norihiko; Odawara, Soichi; Suzuki, Hitomi; Niwa, Yasue; Takada, Yasuhiro; Doi, Hiroshi; Terada, Tomonori; Uwa, Nobuhiro; Sagawa, Kosuke; Hirota, Shozo

2015-01-01

The purpose of the present study was to determine the risk factors for developing thyroid disorders based on a dose–volume histograms (DVHs) analysis. Data from a total of 116 consecutive patients undergoing 3D conformal radiation therapy for head and neck cancers was retrospectively evaluated. Radiation therapy was performed between April 2007 and December 2010. There were 108 males and 8 females included in the study. The median follow-up term was 24 months (range, 1–62 months). The thyroid function was evaluated by measuring thyroid-stimulating hormone (TSH) and free thyroxine (FT4) levels. The mean thyroid dose, and the volume of thyroid gland spared from doses ≥10, 20, 30 and 40 Gy (VS10, VS20, VS30 and VS40) were calculated for all patients. The thyroid dose and volume were calculated by the radiotherapy planning system (RTPS). The cumulative incidences of hypothyroidism were 21.1% and 36.4% at one year and two years, respectively, after the end of radiation therapy. In the DVH analyses, the patients who received a mean thyroid dose <30 Gy had a significantly lower incidence of hypothyroidism. The univariate analyses showed that the VS10, VS20, VS30 and VS40 were associated with the risk of hypothyroidism. Hypothyroidism was a relatively common type of late radiation-induced toxicity. A mean thyroid dose of 30 Gy may be a useful threshold for predicting the development of hypothyroidism after radiation therapy for head and neck cancers. PMID:25818629

Clinico-pathological Correlation of Thyroid Nodule Ultrasound and Cytology Using the TIRADS and Bethesda Classifications.

PubMed

Singaporewalla, R M; Hwee, J; Lang, T U; Desai, V

2017-07-01

Clinico-pathological correlation of thyroid nodules is not routinely performed as until recently there was no objective classification system for reporting thyroid nodules on ultrasound. We compared the Thyroid Imaging Reporting and Data System (TIRADS) of classifying thyroid nodules on ultrasound with the findings on fine-needle aspiration cytology (FNAC) reported using the Bethesda System. A retrospective analysis of 100 consecutive cases over 1 year (Jan-Dec 2015) was performed comparing single-surgeon-performed bedside thyroid nodule ultrasound findings based on the TIRADS classification to the FNAC report based on the Bethesda Classification. TIRADS 1 (normal thyroid gland) and biopsy-proven malignancy referred by other clinicians were excluded. Benign-appearing nodules were reported as TIRADS 2 and 3. Indeterminate or suspected follicular lesions were reported as TIRADS 4, and malignant-appearing nodules were classified as TIRADS 5 during surgeon-performed bedside ultrasound. All the nodules were subjected to ultrasound-guided FNAC, and TIRADS findings were compared to Bethesda FNAC Classification. Of the 100 cases, 74 were considered benign or probably benign, 20 were suspicious for malignancy, and 6 were indeterminate on ultrasound. Overall concordance rate with FNAC was 83% with sensitivity and specificity of 70.6 and 90.4%, respectively. The negative predictive value was 93.8%. It is essential for clinicians performing bedside ultrasound thyroid and guided FNAC to document their sonographic impression of the nodule in an objective fashion using the TIRADS classification and correlate with the gold standard cytology to improve their learning curve and audit their results.

Computational modeling of the amphibian thyroid axis ...

EPA Pesticide Factsheets

In vitro screening of chemicals for bioactivity together with computational modeling are beginning to replace animal toxicity testing in support of chemical risk assessment. To facilitate this transition, an amphibian thyroid axis model has been developed to describe thyroid homeostasis during Xenopus laevis pro-metamorphosis. The model simulates the dynamic relationships of normal thyroid biology throughout this critical period of amphibian development and includes molecular initiating events (MIEs) for thyroid axis disruption to allow in silico simulations of hormone levels following chemical perturbations. One MIE that has been formally described using the adverse outcome pathway (AOP) framework is thyroperoxidase (TPO) inhibition. The goal of this study was to refine the model parameters and validate model predictions by generating dose-response and time-course biochemical data following exposure to three TPO inhibitors, methimazole, 6-propylthiouracil and 2-mercaptobenzothiazole. Key model variables including gland and blood thyroid hormone (TH) levels were compared to empirical values measured in biological samples at 2, 4, 7 and 10 days following initiation of exposure at Nieuwkoop and Faber (NF) stage 54 (onset of pro-metamorphosis). The secondary objective of these studies was to relate depleted blood TH levels to delayed metamorphosis, the adverse apical outcome. Delayed metamorphosis was evaluated by continuing exposure with a subset of larvae until a

A Prospective Cohort Study on Radiation-induced Hypothyroidism: Development of an NTCP Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boomsma, Marjolein J.; Bijl, Hendrik P.; Christianen, Miranda E.M.C.

Purpose: To establish a multivariate normal tissue complication probability (NTCP) model for radiation-induced hypothyroidism. Methods and Materials: The thyroid-stimulating hormone (TSH) level of 105 patients treated with (chemo-) radiation therapy for head-and-neck cancer was prospectively measured during a median follow-up of 2.5 years. Hypothyroidism was defined as elevated serum TSH with decreased or normal free thyroxin (T4). A multivariate logistic regression model with bootstrapping was used to determine the most important prognostic variables for radiation-induced hypothyroidism. Results: Thirty-five patients (33%) developed primary hypothyroidism within 2 years after radiation therapy. An NTCP model based on 2 variables, including the mean thyroidmore » gland dose and the thyroid gland volume, was most predictive for radiation-induced hypothyroidism. NTCP values increased with higher mean thyroid gland dose (odds ratio [OR]: 1.064/Gy) and decreased with higher thyroid gland volume (OR: 0.826/cm{sup 3}). Model performance was good with an area under the curve (AUC) of 0.85. Conclusions: This is the first prospective study resulting in an NTCP model for radiation-induced hypothyroidism. The probability of hypothyroidism rises with increasing dose to the thyroid gland, whereas it reduces with increasing thyroid gland volume.« less

A case of ovarian enterobiasis

PubMed Central

Hong, Sung-Tae; Chai, Jong-Yil; Kim, Young Tak; Kim, Mi Kyung; Kim, Kyu Rae

2002-01-01

A 36-year old Korean woman consulted a clinic for a regular gynecological examination, and a mass was noticed in her pelvis. She was referred to the Asan Medical Center, Seoul where transvaginal ultrasonography confirmed a pelvic mass exceeding 10 cm in diameter. She received total abdominal hysterectomy and bilateral salpingoophorectomy, and a borderline serous neoplasm with micropapillary features involving the left ovary and right ovarian serosa was histopathologically confirmed. In addition, a section of a nematode with numerous eggs was found in the parenchyma of the left ovary. The worm had degenerated but the eggs were well-preserved and were identified as those of Enterobius vermicularis. She is an incidentally recognized case of ovarian enterobiasis. PMID:12325444

Marginal iodide deficiency and thyroid function: dose-response analysis for quantitative pharmacokinetic modeling.

PubMed

Gilbert, M E; McLanahan, E D; Hedge, J; Crofton, K M; Fisher, J W; Valentín-Blasini, L; Blount, B C

2011-04-28

Severe iodine deficiency (ID) results in adverse health outcomes and remains a benchmark for understanding the effects of developmental hypothyroidism. The implications of marginal ID, however, remain less well known. The current study examined the relationship between graded levels of ID in rats and serum thyroid hormones, thyroid iodine content, and urinary iodide excretion. The goals of this study were to provide parametric and dose-response information for development of a quantitative model of the thyroid axis. Female Long Evans rats were fed casein-based diets containing varying iodine (I) concentrations for 8 weeks. Diets were created by adding 975, 200, 125, 25, or 0 μg/kg I to the base diet (~25 μg I/kg chow) to produce 5 nominal I levels, ranging from excess (basal+added I, Treatment 1: 1000 μg I/kg chow) to deficient (Treatment 5: 25 μg I/kg chow). Food intake and body weight were monitored throughout and on 2 consecutive days each week over the 8-week exposure period, animals were placed in metabolism cages to capture urine. Food, water intake, and body weight gain did not differ among treatment groups. Serum T4 was dose-dependently reduced relative to Treatment 1 with significant declines (19 and 48%) at the two lowest I groups, and no significant changes in serum T3 or TSH were detected. Increases in thyroid weight and decreases in thyroidal and urinary iodide content were observed as a function of decreasing I in the diet. Data were compared with predictions from a recently published biologically based dose-response (BBDR) model for ID. Relative to model predictions, female Long Evans rats under the conditions of this study appeared more resilient to low I intake. These results challenge existing models and provide essential information for development of quantitative BBDR models for ID during pregnancy and lactation. Published by Elsevier Ireland Ltd.

Radioiodine therapy in Graves' disease based on tissue-absorbed dose calculations: effect of pre-treatment thyroid volume on clinical outcome.

PubMed

Reinhardt, Michael J; Brink, Ingo; Joe, Alexius Y; Von Mallek, Dirk; Ezziddin, Samer; Palmedo, Holger; Krause, Thomas M

2002-09-01

This study was performed with three aims. The first was to analyse the effectiveness of radioiodine therapy in Graves' disease patients with and without goitres under conditions of mild iodine deficiency using several tissue-absorbed doses. The second aim was to detect further parameters which might be predictive for treatment outcome. Finally, we wished to determine the deviation of the therapeutically achieved dose from that intended. Activities of 185-2,220 MBq radioiodine were calculated by means of Marinelli's formula to deliver doses of 150, 200 or 300 Gy to the thyroids of 224 patients with Graves' disease and goitres up to 130 ml in volume. Control of hyperthyroidism, change in thyroid volume and thyrotropin-receptor antibodies were evaluated 15+/-9 months after treatment for each dose. The results were further evaluated with respect to pre-treatment parameters which might be predictive for therapy outcome. Thyroidal radioiodine uptake was measured every day during therapy to determine the therapeutically achieved target dose and its coefficient of variation. There was a significant dose dependency in therapeutic outcome: frequency of hypothyroidism increased from 27.4% after 150 Gy to 67.7% after 300 Gy, while the frequency of persistent hyperthyroidism decreased from 27.4% after 150 Gy to 8.1% after 300 Gy. Patients who became hypothyroid had a maximum thyroid volume of 42 ml and received a target dose of 256+/-80 Gy. The coefficient of variation for the achieved target dose ranged between 27.7% for 150 Gy and 17.8% for 300 Gy. When analysing further factors which might influence therapeutic outcome, only pre-treatment thyroid volume showed a significant relationship to the result of treatment. It is concluded that a target dose of 250 Gy is essential to achieve hypothyroidism within 1 year after radioiodine therapy in Graves' disease patients with goitres up to 40 ml in volume. Patients with larger goitres might need higher doses.

Delayed risk stratification, to include the response to initial treatment (surgery and radioiodine ablation), has better outcome predictivity in differentiated thyroid cancer patients.

PubMed

Castagna, Maria Grazia; Maino, Fabio; Cipri, Claudia; Belardini, Valentina; Theodoropoulou, Alexandra; Cevenini, Gabriele; Pacini, Furio

2011-09-01

After initial treatment, differentiated thyroid cancer (DTC) patients are stratified as low and high risk based on clinical/pathological features. Recently, a risk stratification based on additional clinical data accumulated during follow-up has been proposed. To evaluate the predictive value of delayed risk stratification (DRS) obtained at the time of the first diagnostic control (8-12 months after initial treatment). We reviewed 512 patients with DTC whose risk assessment was initially defined according to the American (ATA) and European Thyroid Association (ETA) guidelines. At the time of the first control, 8-12 months after initial treatment, patients were re-stratified according to their clinical status: DRS. Using DRS, about 50% of ATA/ETA intermediate/high-risk patients moved to DRS low-risk category, while about 10% of ATA/ETA low-risk patients moved to DRS high-risk category. The ability of the DRS to predict the final outcome was superior to that of ATA and ETA. Positive and negative predictive values for both ATA (39.2 and 90.6% respectively) and ETA (38.4 and 91.3% respectively) were significantly lower than that observed with the DRS (72.8 and 96.3% respectively, P<0.05). The observed variance in predicting final outcome was 25.4% for ATA, 19.1% for ETA, and 62.1% for DRS. Delaying the risk stratification of DTC patients at a time when the response to surgery and radioiodine ablation is evident allows to better define individual risk and to better modulate the subsequent follow-up.

Combined 3D-QSAR, molecular docking and molecular dynamics study on thyroid hormone activity of hydroxylated polybrominated diphenyl ethers to thyroid receptors β

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Xiaolin; Ye, Li; Wang, Xiaoxiang

2012-12-15

Several recent reports suggested that hydroxylated polybrominated diphenyl ethers (HO-PBDEs) may disturb thyroid hormone homeostasis. To illuminate the structural features for thyroid hormone activity of HO-PBDEs and the binding mode between HO-PBDEs and thyroid hormone receptor (TR), the hormone activity of a series of HO-PBDEs to thyroid receptors β was studied based on the combination of 3D-QSAR, molecular docking, and molecular dynamics (MD) methods. The ligand- and receptor-based 3D-QSAR models were obtained using Comparative Molecular Similarity Index Analysis (CoMSIA) method. The optimum CoMSIA model with region focusing yielded satisfactory statistical results: leave-one-out cross-validation correlation coefficient (q{sup 2}) was 0.571 andmore » non-cross-validation correlation coefficient (r{sup 2}) was 0.951. Furthermore, the results of internal validation such as bootstrapping, leave-many-out cross-validation, and progressive scrambling as well as external validation indicated the rationality and good predictive ability of the best model. In addition, molecular docking elucidated the conformations of compounds and key amino acid residues at the docking pocket, MD simulation further determined the binding process and validated the rationality of docking results. -- Highlights: ► The thyroid hormone activities of HO-PBDEs were studied by 3D-QSAR. ► The binding modes between HO-PBDEs and TRβ were explored. ► 3D-QSAR, molecular docking, and molecular dynamics (MD) methods were performed.« less

Histogram Analysis of Diffusion Weighted Imaging at 3T is Useful for Prediction of Lymphatic Metastatic Spread, Proliferative Activity, and Cellularity in Thyroid Cancer.

PubMed

Schob, Stefan; Meyer, Hans Jonas; Dieckow, Julia; Pervinder, Bhogal; Pazaitis, Nikolaos; Höhn, Anne Kathrin; Garnov, Nikita; Horvath-Rizea, Diana; Hoffmann, Karl-Titus; Surov, Alexey

2017-04-12

Pre-surgical diffusion weighted imaging (DWI) is increasingly important in the context of thyroid cancer for identification of the optimal treatment strategy. It has exemplarily been shown that DWI at 3T can distinguish undifferentiated from well-differentiated thyroid carcinoma, which has decisive implications for the magnitude of surgery. This study used DWI histogram analysis of whole tumor apparent diffusion coefficient (ADC) maps. The primary aim was to discriminate thyroid carcinomas which had already gained the capacity to metastasize lymphatically from those not yet being able to spread via the lymphatic system. The secondary aim was to reflect prognostically important tumor-biological features like cellularity and proliferative activity with ADC histogram analysis. Fifteen patients with follicular-cell derived thyroid cancer were enrolled. Lymph node status, extent of infiltration of surrounding tissue, and Ki-67 and p53 expression were assessed in these patients. DWI was obtained in a 3T system using b values of 0, 400, and 800 s/mm². Whole tumor ADC volumes were analyzed using a histogram-based approach. Several ADC parameters showed significant correlations with immunohistopathological parameters. Most importantly, ADC histogram skewness and ADC histogram kurtosis were able to differentiate between nodal negative and nodal positive thyroid carcinoma. histogram analysis of whole ADC tumor volumes has the potential to provide valuable information on tumor biology in thyroid carcinoma. However, further studies are warranted.

Histogram Analysis of Diffusion Weighted Imaging at 3T is Useful for Prediction of Lymphatic Metastatic Spread, Proliferative Activity, and Cellularity in Thyroid Cancer

PubMed Central

Schob, Stefan; Meyer, Hans Jonas; Dieckow, Julia; Pervinder, Bhogal; Pazaitis, Nikolaos; Höhn, Anne Kathrin; Garnov, Nikita; Horvath-Rizea, Diana; Hoffmann, Karl-Titus; Surov, Alexey

2017-01-01

Pre-surgical diffusion weighted imaging (DWI) is increasingly important in the context of thyroid cancer for identification of the optimal treatment strategy. It has exemplarily been shown that DWI at 3T can distinguish undifferentiated from well-differentiated thyroid carcinoma, which has decisive implications for the magnitude of surgery. This study used DWI histogram analysis of whole tumor apparent diffusion coefficient (ADC) maps. The primary aim was to discriminate thyroid carcinomas which had already gained the capacity to metastasize lymphatically from those not yet being able to spread via the lymphatic system. The secondary aim was to reflect prognostically important tumor-biological features like cellularity and proliferative activity with ADC histogram analysis. Fifteen patients with follicular-cell derived thyroid cancer were enrolled. Lymph node status, extent of infiltration of surrounding tissue, and Ki-67 and p53 expression were assessed in these patients. DWI was obtained in a 3T system using b values of 0, 400, and 800 s/mm2. Whole tumor ADC volumes were analyzed using a histogram-based approach. Several ADC parameters showed significant correlations with immunohistopathological parameters. Most importantly, ADC histogram skewness and ADC histogram kurtosis were able to differentiate between nodal negative and nodal positive thyroid carcinoma. Conclusions: histogram analysis of whole ADC tumor volumes has the potential to provide valuable information on tumor biology in thyroid carcinoma. However, further studies are warranted. PMID:28417929

Methylation Markers for Early Detection and Differentiation of Follicular Thyroid Cancer Subtypes

PubMed Central

Stephen, Josena K.; Chen, Kang Mei; Merritt, Jason; Chitale, Dhananjay; Divine, George; Worsham, Maria J.

2016-01-01

Thyroid cancer has the fastest rising incidence rates and is the fifth most common cancer in women. There are four main types of which the papillary and follicular types together account for >90%, followed by medullary cancers (3%−5%) and anaplastic carcinomas (<3%). For individuals who present with early stage disease of papillary and follicular cancers, there are no accurate markers to predict whether they will develop metastatic or recurrent disease. Our immediate goal is to molecularly differentiate follicular cancer subtypes for enhanced classification. Promoter methylation status of genes with reported associations in thyroid cancer (CASP8, CDKN2A, DAPK1, ESR1, NIS, RASSF1 and TIMP3) were examined in a cohort of follicular thyroid cancers comprising of 26 Hurthle and 27 Classic subtypes utilizing quantitative methylation-specific PCR. RASSF1 was differentially methylated in Classic tumor tissue compared to Hurthle (p<0.001). Methylation of RASSF1 pointed to racial group differences between African Americans and Caucasian Americans (p=0.05). Extra thyroidal extension was found to be associated with DAPK1 (p=0.014) and ESR1 (p=0.036) methylation. Late stage disease was associated with older age (p<0.001) and methylation of DAPK1 (p=0.034) and ESR1 (p=0.035). The methylation status of RASSF1, DAPK1 and ESR1 suggests the utility of methylation markers to molecularly differentiate thyroid cancer subtypes for enhanced classification and early detection of thyroid cancer. PMID:27158284

Free triiodothyronine/free thyroxine ratio rather than thyrotropin is more associated with metabolic parameters in healthy euthyroid adult subjects.

PubMed

Park, So Young; Park, Se Eun; Jung, Sang Won; Jin, Hyun Seok; Park, Ie Byung; Ahn, Song Vogue; Lee, Sihoon

2017-07-01

The interrelation between TSH, thyroid hormones and metabolic parameters is complex and has not been confirmed. This study aimed to determine the association of TSH and thyroid hormones in euthyroid subjects and the relationship between thyroid function and metabolic risk factors. Furthermore, this study examined whether thyroid function has predictive power for metabolic syndrome. This is a cross-sectional study that included subjects in a medical health check-up programme at a single institution. The study included 132 346 participants (66 991 men and 65 355 women) aged over 18 years who had TSH, free T4 (FT4) and free T3 (FT3) levels within the institutional reference ranges. Thyrotropin, FT4, FT3 and metabolic parameters including height, weight, waist circumference, blood pressure, serum levels of total cholesterol, triglyceride, high-density lipoprotein cholesterol, insulin and glucose were measured. There was a positive association between FT3/FT4 ratio and TSH in both men and women after adjusting for age, body mass index, smoking status and menopausal status (in women). The FT3/FT4 ratio and TSH were positively associated with risk of metabolic syndrome parameters including insulin resistance. The FT3/FT4 ratio had a greater predictive power than TSH for metabolic syndrome in both men and women. Thyrotropin levels were positively associated with FT3/FT4 ratio within the euthyroid range. The higher FT3/FT4 ratio is associated with increased risk of metabolic syndrome parameters and insulin resistance. FT3/FT4 ratio has a better predictive power for metabolic syndrome than TSH. © 2017 John Wiley & Sons Ltd.

Patterns of Interferon-Alpha–Induced Thyroid Dysfunction Vary with Ethnicity, Sex, Smoking Status, and Pretreatment Thyrotropin in an International Cohort of Patients Treated for Hepatitis C

PubMed Central

Ghazarian, Sharon R.; Rosen, Antony; Ladenson, Paul W.

2013-01-01

Background Interferon-alpha (IFNα)–induced thyroid dysfunction occurs in up to 20% of patients undergoing therapy for hepatitis C. The diversity of thyroid disease presentations suggests that several different pathological mechanisms are involved, such as autoimmunity and direct toxicity. Elucidating the relationships between risk factors and disease phenotype provides insight into the mechanisms of disease pathophysiology. Methods We studied 869 euthyroid patients from the ACHIEVE 2/3 trial, a randomized international clinical trial comparing pegylated-IFNα2a weekly or albumin-IFNα2b every 2 weeks for up to 24 weeks in patients with hepatitis C, genotype 2 or 3, from 136 centers. The study population was 60% male and 55% white. Serum thyrotropin (TSH) and free thyroxine were measured before therapy, monthly during treatment from week 8, and at 4- and 12-week follow-up visits. Results Overall, 181 (20.8%) participants had at least one abnormal TSH during the study. Low TSH occurred in 71 (8.2%), of whom 30 (3.5%) had a suppressed TSH below 0.1 mU/L. Hypothyroidism occurred in 53 patients (6.1%), with peak TSH above 10 mU/L in 12 patients (1.4%). Fifty-seven patients had a biphasic thyroiditis (6.6%), with extreme values for the nadir and/or peak TSH in all but one. Medical therapy was given to one thyrotoxic patient, four hypothyroid patients, and 26 biphasic thyroiditis patients. Multivariate logistic regression analysis demonstrated that biphasic thyroiditis is associated with being female and higher pretreatment serum TSH, whereas being Asian or a current smoker decreased the risk of thyroiditis. Hypo- and hyperthyroidism are most strongly predicted by the pretreatment TSH. Conclusions Biphasic thyroiditis accounted for the majority (58%) of clinically relevant IFNα-induced thyroid dysfunction. We confirmed our recent findings in a related cohort that female sex is a risk factor for thyroiditis but not hypothyroidism. Further, in this large multiethnic study, the risk of thyroiditis is dramatically increased, specifically for white women. Smoking was found to be protective of thyroiditis. These results support closer monitoring of women and those with a serum TSH at the extremes of the normal range during therapy so that prompt intervention can mitigate the consequences of thyroid dysfunction associated with IFNα treatment. PMID:23517287

Predicted Risk of Radiation-Induced Cancers After Involved Field and Involved Node Radiotherapy With or Without Intensity Modulation for Early-Stage Hodgkin Lymphoma in Female Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weber, Damien C., E-mail: damien.weber@unige.ch; Johanson, Safora; Peguret, Nicolas

2011-10-01

Purpose: To assess the excess relative risk (ERR) of radiation-induced cancers (RIC) in female patients with Hodgkin lymphoma (HL) female patients treated with conformal (3DCRT), intensity modulated (IMRT), or volumetric modulated arc (RA) radiation therapy. Methods and Materials: Plans for 10 early-stage HL female patients were computed for 3DCRT, IMRT, and RA with involved field RT (IFRT) and involvednode RT (INRT) radiation fields. Organs at risk dose--volume histograms were computed and inter-compared for IFRT vs. INRT and 3DCRT vs. IMRT/RA, respectively. The ERR for cancer induction in breasts, lungs, and thyroid was estimated using both linear and nonlinear models. Results:more » The mean estimated ERR for breast, lung, and thyroid were significantly lower (p < 0.01) with INRT than with IFRT planning, regardless of the radiation delivery technique used, assuming a linear dose-risk relationship. We found that using the nonlinear model, the mean ERR values were significantly (p < 0.01) increased with IMRT or RA compared to those with 3DCRT planning for the breast, lung, and thyroid, using an IFRT paradigm. After INRT planning, IMRT or RA increased the risk of RIC for lung and thyroid only. Conclusions: In this comparative planning study, using a nonlinear dose--risk model, IMRT or RA increased the estimated risk of RIC for breast, lung, and thyroid for HL female patients. This study also suggests that INRT planning, compared to IFRT planning, may reduce the ERR of RIC when risk is predicted using a linear model. Observing the opposite effect, with a nonlinear model, however, questions the validity of these biologically parameterized models.« less

Ultrasound guided FNA of thyroid performed by cytopathologists enhances Bethesda diagnostic value.

PubMed

Wu, Maoxin; Choi, YoonSun; Zhang, Zesong; Si, Quisheng; Salem, Fadi; Szporn, Arnold; Zhang, David; Burstein, David; Teng, Marita; Miles, Brett A; Genden, Eric

2016-10-01

Ultrasound (US) guided fine needle aspiration (FNA) biopsy of thyroid are examined and reported by cytopathologists based usually on The Bethesda System for Reporting Thyroid Cytopathology (BTC) regardless of the procedure's performers. This study is designed to determine whether there is any performer-dependent difference. Six hundred and fifty-one thyroid US-FNAs in correlation with surgical follow-up (SFU) were studied. The statistical analysis was performed using the surgical pathology diagnosis as the gold standard. Among the 283 cases performed by cytopathologists, there were 8 (2.8%) nondiagnostic (BTC I), 197 (69.6%) benign (BTC II), 31 (11%) atypical (BTC III), 14 (5%) suspicious for follicular neoplasm (BTC IV), 12 (4.2%) suspicious for malignancy (BTC V), and 21 (7.4%) positive for malignancy (BTC VI), and there were 55 (19.4%) cases with SFU. The 368 cases performed by others showed 76 (21%) BTC I, 238 (65%) BTC II, 26 (7%) BTC III, 10 (3%) BTC IV, 9 (2.5%) BTC V 5, and 9 (2.5%) BTC VI, and there were 26 (7%) cases with SFU. The cytopathologist group achieved better sensitivity (91.3 vs.78%); slightly better specificity (83.3 vs. 82%); better positive predictive value (87.5 vs. 70%); similar negative predictive value (88.2 vs. 88%); and better overall accuracy (87.8 vs. 81%) compared with the non-cytopathologist group. Overall the difference for all statistical values is significant different (P = 0.041). US-FNA performed by cytopathologists showed a lower unsatisfactory rate and significantly better overall statistical values. Cytopathologists may play an important role in thyroid patient care. Diagn. Cytopathol. 2016;44:787-791. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

How radiologic/clinicopathologic features relate to compressive symptoms in benign thyroid disease.

PubMed

Siegel, Bianca; Ow, Thomas J; Abraham, Suzanne S; Loftus, Patricia A; Tassler, Andrew B; Smith, Richard V; Schiff, Bradley A

2017-04-01

To identify compressive symptomatology in a patient cohort with benign thyroid disease who underwent thyroidectomy. To determine radiographic/clinicopathologic features related to and predictive of a compressive outcome. Retrospective cohort study. Medical records of 232 patients with benign thyroid disease on fine needle aspiration who underwent thyroidectomy from 2009 to 2012 at an academic medical center were reviewed. Data collection and analyses involved subjects' demographics, compressive symptoms, preoperative airway encroachment, intubation complications, specimen weight, and final pathologic diagnosis. Subjects were ages 14 to 86 years (mean: 52.4 years). Ninety-six subjects (41.4%) reported compressive symptomatology of dysphagia (n =74; 32%), dyspnea (n = 39; 17%), and hoarseness (n = 24; 10%). Ninety-seven (42.2%) had preoperative airway encroachment. Dyspnea was significantly related to tracheal compression, tracheal deviation, and substernal extension. Dysphagia was related to tracheal compression and tracheal deviation. Compressive symptoms and preoperative airway encroachment were not related to intubation complications. Final pathologic diagnosis was not related to compressive symptoms, whereas specimen weight was significantly related to dyspnea and dysphagia. Final pathology revealed 74 subjects (32%) with malignant lesions. Malignant and benign nodular subject groups differed significantly in substernal extension, gland weight, tracheal deviation, and dyspnea. Logit modeling for dyspnea was significant for tracheal compression as a predictor for the likelihood of dyspnea. Dyspnea was closely related to preoperative airway encroachment and most indicative of a clinically relevant thyroid in our cohort with benign thyroid disease. Tracheal compression was found to have predictive value for the likelihood of a dyspneic outcome. 4. Laryngoscope, 127:993-997, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Age as a predictor of recurrent hypothyroidism in patients with post-partum thyroid dysfunction.

PubMed

Azizi, F

2004-12-01

The long term effect of post-partum thyroid dysfunction (PPTD) is not well established. This study was conducted to evaluate the outcome of permanent hypothyroidism and factors predictive of thyroid dysfunction in a large cohort of women with PPTD. In 164 women, treated with levothyroxine for moderate and severe post- partum hypothyroidism, the treatment was discontinued and subjects were followed-up for the recurrence of hypothyroidism. Factors such as thyroid function tests, tyroid peroxidase antibodies (TPOAb) titers, multiparity, history of autoimmune disorders, smoking habits, use of oral contraceptives, family history of thyroid disease, goiter size and age at active phase of PPTD were assessed. Seventy-one post-partum women without PPTD were considered as control group. One hundred forty-eight women (90%) returned for follow-up, and 93 subjects (63%) developed hypothyroidism with a median of 2 months after T4 withdrawal. Of factors predicting recurrence of hypothyroidism, only age, and serum TSH and T3 concentrations at the time of occurrence of PPTD entered the model in multiple stepwise regression analysis. Hypothyroidism occurred earlier and more frequently in women aged 30 and over, as compared to younger ones (p < 0.01), hazard ratio 1.69. In 55 euthyroid subjects with history of PPTD, serum TSH was significantly increased as compared to the control group (3.0 +/- 1.6 vs 0.8 +/- 0.5 mU/l, p < 0.001). These data, representing the largest cohort of women with PPTD who have been followed, show that a significant proportion of women with moderate and severe PPTD, in particular those aged 30 yr and over, develop recurrent hypothyroidism. Proper follow-up of all women with PPTD, the older ones in particular, is recommended.

Invasive micropapillary carcinoma of the breast overexpresses MUC4 and is associated with poor outcome to adjuvant trastuzumab in HER2-positive breast cancer.

PubMed

Mercogliano, María F; Inurrigarro, Gloria; De Martino, Mara; Venturutti, Leandro; Rivas, Martín A; Cordo-Russo, Rosalía; Proietti, Cecilia J; Fernández, Elmer A; Frahm, Isabel; Barchuk, Sabrina; Allemand, Daniel H; Figurelli, Silvina; Deza, Ernesto Gil; Ares, Sandra; Gercovich, Felipe G; Cortese, Eduardo; Amasino, Matías; Guzmán, Pablo; Roa, Juan C; Elizalde, Patricia V; Schillaci, Roxana

2017-12-28

Invasive micropapillary carcinoma of the breast (IMPC) is a histological tumor variant that occurs with low frequency characterized by an inside-out formation of tumor clusters with a pseudopapillary arrangement. IMPC is an aggressive tumor with poor clinical outcome. In addition, this histological subtype usually expresses human epidermal growth factor receptor 2 (HER2) which also correlates with a more aggressive tumor. In this work we studied the clinical significance of IMPC in HER2-positive breast cancer patients treated with adjuvant trastuzumab. We also analyzed mucin 4 (MUC4) expression as a novel biomarker to identify IMPC. We retrospectively studied 86 HER2-positive breast cancer patients treated with trastuzumab and chemotherapy in the adjuvant setting. We explored the association of the IMPC component with clinicopathological parameters at diagnosis and its prognostic value. We compared MUC4 expression in IMPC with respect to other histological breast cancer subtypes by immunohistochemistry. IMPC, either as a pure entity or associated with invasive ductal carcinoma (IDC), was present in 18.6% of HER2-positive cases. It was positively correlated with estrogen receptor expression and tumor size and inversely correlated with patient's age. Disease-free survival was significantly lower in patients with IMPC (hazard ratio = 2.6; 95%, confidence interval 1.1-6.1, P = 0.0340). MUC4, a glycoprotein associated with metastasis, was strongly expressed in all IMPC cases tested. IMPC appeared as the histological breast cancer subtype with the highest MUC4 expression compared to IDC, lobular and mucinous carcinoma. In HER2-positive breast cancer, the presence of IMPC should be carefully examined. As it is often not informed, because it is relatively difficult to identify or altogether overlooked, we propose MUC4 expression as a useful biomarker to highlight IMPC presence. Patients with MUC4-positive tumors with IMPC component should be more frequently monitored and/or receive additional therapies.

Invasive micropapillary carcinoma of the breast has a better long-term survival than invasive ductal carcinoma of the breast in spite of its aggressive clinical presentations: a comparison based on large population database and case-control analysis.

PubMed

Chen, Hongliang; Wu, Kejin; Wang, Maoli; Wang, Fuwen; Zhang, Mingdi; Zhang, Peng

2017-12-01

There are controversies in the comparison of overall survival between invasive micropapillary carcinoma of the breast (IMPC) and invasive ductal carcinoma (IDC). The objective of this study was to compare the long-term survival outcome between non-metastatic IMPC and IDC. The Surveillance, Epidemiology, and End Results database was searched to identify women with non-metastatic IMPC and IDC diagnosed between 2001 and 2013. Comparisons of patient and tumor characteristics were performed using Pearson's chi-square. The propensity score matching method was applied with each IMPC matched to one IDC. Breast cancer-specific survival (BCSS) and overall survival (OS) were estimated using the Kaplan-Meier product limit method and compared across groups using the log-rank statistic. Multivariate analysis was performed through Cox models. IMPC was presented with aggressive clinical presentations such as larger tumor, more positive lymph nodes, and more advanced stage compared with IDC. A higher rate of estrogen receptor (ER)/progesterone receptor (PR) positivity was also observed in IMPC. With a median follow-up of 64 months, IMPC had a better BCSS (P = 0.031) and OS (P = 0.012) compared with IDC. In a case-control analysis IMPC was still an independent favorable prognostic factor for BCSS (HR = 0.410, P < 0.001, 95% CI: 0.293-0.572) and OS (HR = 0.497, P < 0.001, 95% CI: 0.387-0.637). In subgroup analysis, IMPC always showed a better survival outcome compared with IDC except in AJCC stage I and histologic grade I disease. IMPC has a better long-term survival outcome compared with IDC in spite of its highly aggressive clinical presentation. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

The threshold of hypothyroidism after radiation therapy for head and neck cancer: a retrospective analysis of 116 cases.

PubMed

Fujiwara, Masayuki; Kamikonya, Norihiko; Odawara, Soichi; Suzuki, Hitomi; Niwa, Yasue; Takada, Yasuhiro; Doi, Hiroshi; Terada, Tomonori; Uwa, Nobuhiro; Sagawa, Kosuke; Hirota, Shozo

2015-05-01

The purpose of the present study was to determine the risk factors for developing thyroid disorders based on a dose-volume histograms (DVHs) analysis. Data from a total of 116 consecutive patients undergoing 3D conformal radiation therapy for head and neck cancers was retrospectively evaluated. Radiation therapy was performed between April 2007 and December 2010. There were 108 males and 8 females included in the study. The median follow-up term was 24 months (range, 1-62 months). The thyroid function was evaluated by measuring thyroid-stimulating hormone (TSH) and free thyroxine (FT4) levels. The mean thyroid dose, and the volume of thyroid gland spared from doses ≥10, 20, 30 and 40 Gy (VS10, VS20, VS30 and VS40) were calculated for all patients. The thyroid dose and volume were calculated by the radiotherapy planning system (RTPS). The cumulative incidences of hypothyroidism were 21.1% and 36.4% at one year and two years, respectively, after the end of radiation therapy. In the DVH analyses, the patients who received a mean thyroid dose <30 Gy had a significantly lower incidence of hypothyroidism. The univariate analyses showed that the VS10, VS20, VS30 and VS40 were associated with the risk of hypothyroidism. Hypothyroidism was a relatively common type of late radiation-induced toxicity. A mean thyroid dose of 30 Gy may be a useful threshold for predicting the development of hypothyroidism after radiation therapy for head and neck cancers. © The Author 2015. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Risk Stratification of Neck Lesions Detected Sonographically During the Follow-Up of Differentiated Thyroid Cancer.

PubMed

Lamartina, Livia; Grani, Giorgio; Biffoni, Marco; Giacomelli, Laura; Costante, Giuseppe; Lupo, Stefania; Maranghi, Marianna; Plasmati, Katia; Sponziello, Marialuisa; Trulli, Fabiana; Verrienti, Antonella; Filetti, Sebastiano; Durante, Cosimo

2016-08-01

The European Thyroid Association (ETA) has classified posttreatment cervical ultrasound findings in thyroid cancer patients based on their association with disease persistence/recurrence. The objective of the study was to assess this classification's ability to predict the growth and persistence of such lesions during active posttreatment surveillance of patients with differentiated thyroid cancer (DTC). This was a retrospective, observational study. The study was conducted at a thyroid cancer center in a large Italian teaching hospital. Center referrals (2005-2014) were reviewed and patients selected with pathologically-confirmed DTC; total thyroidectomy, with or without neck dissection and/or radioiodine remnant ablation; abnormal findings on two or more consecutive posttreatment neck sonograms; and subsequent follow-up consisting of active surveillance. Baseline ultrasound abnormalities (thyroid bed masses, lymph nodes) were classified according to the ETA system. Patients were divided into group S (those with one or more lesions classified as suspicious) and group I (indeterminate lesions only). We recorded baseline and follow-up clinical data through June 30, 2015. The main outcomes were patients with growth (>3 mm, largest diameter) of one or more lesions during follow-up and patients with one or more persistent lesions at the final visit. The cohort included 58 of the 637 DTC cases screened (9%). A total of 113 lesions were followed up (18 thyroid bed masses, 95 lymph nodes). During surveillance (median 3.7 y), group I had significantly lower rates than group S of lesion growth (8% vs 36%, P = .01) and persistence (64% vs 97%, P = .014). The median time to scan normalization was 2.9 years. The ETA's evidence-based classification of sonographically detected neck abnormalities can help identify papillary thyroid cancer patients eligible for more relaxed follow-up.

Hypothalamic-pituitary-thyroid system activity during lithium augmentation therapy in patients with unipolar major depression

PubMed Central

Bschor, Tom; Baethge, Christopher; Adli, Mazda; Lewitzka, Ute; Eichmann, Uta; Bauer, Michael

2003-01-01

Objective Lithium augmentation is an established strategy in the treatment of refractory depression, but little is known about predictors of response and its mode of action. There is increasing evidence that low thyroid function indices within the normal range are associated with a poorer treatment response to antidepressants, but previous studies on the hypothalamic-pituitary-thyroid (HPT) system during lithium augmentation provide inconclusive results and have methodological limitations. This study aimed at exploring the role of thyroid function in lithium augmentation and used a prospective design that included a homogeneous sample of inpatients with unipolar major depressive disorder. Methods In 24 euthyroid patients with a major depressive episode who had not responded to antidepressant monotherapy of at least 4 weeks, we measured serum thyroid-stimulating hormone (TSH), total triiodothyronine (T3) and total thyroxine (T4) before (baseline) and during lithium augmentation therapy (follow-up). The time point of the endocrinological follow-up depended on the status of response, which was assessed weekly with the Hamilton Depression Rating Scale, 17-item version (HDRS17). Responders were reassessed immediately after response was determined, and non-responders after 4 weeks of lithium augmentation. Results There was a statistically significant change in thyroid system activity during lithium augmentation, with an increase of TSH levels and a decrease of peripheral T3 and T4 levels. However, there were no differences in any of the HPT hormones between responders and non-responders at baseline or at follow-up. Conclusions The decrease of thyroid system activity during lithium treatment reflects the well-established “antithyroid” properties of lithium. However, it appears that thyroid status does not predict response to lithium augmentation in euthyroid patients before treatment. PMID:12790161

A new standardized data collection system for interdisciplinary thyroid cancer management: Thyroid COBRA.

PubMed

Tagliaferri, Luca; Gobitti, Carlo; Colloca, Giuseppe Ferdinando; Boldrini, Luca; Farina, Eleonora; Furlan, Carlo; Paiar, Fabiola; Vianello, Federica; Basso, Michela; Cerizza, Lorenzo; Monari, Fabio; Simontacchi, Gabriele; Gambacorta, Maria Antonietta; Lenkowicz, Jacopo; Dinapoli, Nicola; Lanzotti, Vito; Mazzarotto, Renzo; Russi, Elvio; Mangoni, Monica

2018-07-01

The big data approach offers a powerful alternative to Evidence-based medicine. This approach could guide cancer management thanks to machine learning application to large-scale data. Aim of the Thyroid CoBRA (Consortium for Brachytherapy Data Analysis) project is to develop a standardized web data collection system, focused on thyroid cancer. The Metabolic Radiotherapy Working Group of Italian Association of Radiation Oncology (AIRO) endorsed the implementation of a consortium directed to thyroid cancer management and data collection. The agreement conditions, the ontology of the collected data and the related software services were defined by a multicentre ad hoc working-group (WG). Six Italian cancer centres were firstly started the project, defined and signed the Thyroid COBRA consortium agreement. Three data set tiers were identified: Registry, Procedures and Research. The COBRA-Storage System (C-SS) appeared to be not time-consuming and to be privacy respecting, as data can be extracted directly from the single centre's storage platforms through a secured connection that ensures reliable encryption of sensible data. Automatic data archiving could be directly performed from Image Hospital Storage System or the Radiotherapy Treatment Planning Systems. The C-SS architecture will allow "Cloud storage way" or "distributed learning" approaches for predictive model definition and further clinical decision support tools development. The development of the Thyroid COBRA data Storage System C-SS through a multicentre consortium approach appeared to be a feasible tool in the setup of complex and privacy saving data sharing system oriented to the management of thyroid cancer and in the near future every cancer type. Copyright © 2018 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Cutoff value of thyroid uptake of (99m)Tc-pertechnetate to discriminate between Graves' disease and painless thyroiditis: a single center retrospective study.

PubMed

Uchida, Toyoyoshi; Suzuki, Ruriko; Kasai, Takatoshi; Onose, Hiroyuki; Komiya, Koji; Goto, Hiromasa; Takeno, Kageumi; Ishii, Shinya; Sato, Junko; Honda, Akira; Kawano, Yui; Himuro, Miwa; Yamada, Emiko; Yamada, Tetsu; Watada, Hirotaka

2016-01-01

Thyroid uptake of (99m)Tc-pertechnetate is a useful way to determine the cause of thyrotoxicosis. In daily clinical practice, (99m)Tc-pertechnetate uptake is used to discriminate between Graves' disease and painless thyroiditis when clinical information is not enough to make the distinction. However, since the optimal cutoff value of (99m)Tc-pertechnetate uptake has not yet been elucidated, our aim was to determine this value. We recruited patients with thyrotoxicosis in whom (99m)Tc-pertechnetate uptake was measured in clinical settings between 2009 and 2013. Three experienced endocrinologists (who were blinded to the value of (99m)Tc-pertechnetate uptake and initial treatment) diagnosed the cause of thyrotoxicosis based on thyrotropin, free triiodothyronine, free thyroxine, and thyrotropin receptor antibody levels, and by ultrasound findings and using images of thyroid uptake of (99m)Tc-pertechnetate without the actual values. Ninety-four patients diagnosed as having Graves' disease or painless thyroiditis were finally included. According to the diagnosis, the optimal cutoff value of (99m)Tc-pertechnetate uptake was determined by receiver operating characteristics analysis. A cutoff value of 1.0% provided optimal sensitivity and specificity of 96.6% and 97.1%, respectively. Then, its validity was confirmed in 78 patients with confirmed Graves' disease or painless thyroiditis diagnosed at another institute. Applying this cutoff value to the patients with thyrotoxicosis revealed positive and negative predictive values for Graves' disease of 100% and 88.9%, respectively. In conclusion, a cutoff value for (99m)Tc-pertechnetate uptake of 1.0% was useful to discriminate between Graves' disease and painless thyroiditis.

Effect of Hashimoto thyroiditis on low-dose radioactive-iodine remnant ablation.

PubMed

Kwon, Hyungju; Choi, June Young; Moon, Jae Hoon; Park, Hyo Jin; Lee, Won Woo; Lee, Kyu Eun

2016-04-01

Radioactive-iodine remnant ablation is an integral part of the papillary thyroid carcinoma (PTC) treatment. Although a minimum dose is usually recommended, there is controversy as to whether the low-dose (1100 MBq) radioactive-iodine remnant ablation is adequate for selected patients. A retrospective cohort study was conducted on 691 patients. Patients with no remnant thyroid on the follow-up whole body scan and low stimulated thyroglobulin (sTg) level (<2.0 ng/mL) were deemed as successful treatment cases. Initial low-dose radioactive-iodine remnant ablation was successful in 431 patients (62.3%). Multivariate analysis demonstrated a negative correlation between successful radioactive-iodine remnant ablation and coexisting Hashimoto thyroiditis based on histopathology diagnosis (odds ratio [OR] = 3.23; p < .001) as well as elevated preablation sTg (OR = 1.24; p < .001). Our data suggest that coexisting Hashimoto thyroiditis and elevated sTg are negative predictive factors for successful low-dose radioactive-iodine remnant ablation treatment. An appropriate risk-adjusted approach may improve the efficacy of radioactive-iodine remnant ablation treatment. © 2015 Wiley Periodicals, Inc. Head Neck 38: E730-E735, 2016. © 2015 Wiley Periodicals, Inc.

Preoperative vocal cord paralysis and its association with malignant thyroid disease and other pathological features.

PubMed

Kay-Rivest, Emily; Mitmaker, Elliot; Payne, Richard J; Hier, Michael P; Mlynarek, Alex M; Young, Jonathan; Forest, Véronique-Isabelle

2015-09-11

Vocal cord paralysis (VCP) is found in both benign and malignant thyroid disease. This study was performed to determine if the presence of preoperative VCP predicts malignancy. A retrospective analysis was performed on a cohort of 1923 consecutive patients undergoing thyroid surgery. The incidence of preoperative VCP was recorded. Patient and nodule characteristics were correlated with final pathology. 1.3% of our cohort was found to have preoperative VCP. Malignant pathology was discovered in 76% of patients with preoperative VCP. Among these patients, 72% had a left sided paralysis. 10.5% of patients with preoperative VCP had perineural invasion (PNI) on final pathology, compared to 1.1% of patients with normal VC function. Preoperative VCP appears to be a strong, though not an absolute, indicator of malignancy. Most VCP were on the left side. Assessing for preoperative VCP is crucial in all patients who need thyroid surgery, as even benign nodules can be accompanied by preoperative vocal cord paralysis.

[The relation between the low T3 syndrome in the clinical course of myocardial infarction and heart failure].

PubMed

Frączek, Magdalena Maria; Gackowski, Andrzej; Przybylik-Mazurek, Elwira; Nessler, Jadwiga

2016-06-01

It has been proven that either excess or deficiency of thyroid hormones has harmful influence on the cardiovascular system function. On the other hand, severe systemic conditions like myocardial infarction or severe heart failure may affect thyroid hormones secretion and their peripheral conversion, leading to low T3 syndrome. Amongst many mechanisms causing T4 to T3 conversion disturbances, important role plays decreased activity of D1 deiodinase and increased activity of D3 deiodinase. The animal research confirmed that thyroid hormones influence cardiomiocytes phenotype and morphology. They inhibit inflammation, apoptosis and cardiac remodelling after myocardial infarction. It was also proven that free triiodothyronine similarly to brain natriuretic peptide predict long-term prognosis in chronic and acute heart failure patients. Potential influence of low T3 syndrome on the course of myocardial infarction and heart failure may have significant impact on the future research on individualization of myocardial infarction and heart failure treatment depending on patient's thyroid status. © 2016 MEDPRESS.

Factors Associated With Mortality of Thyroid Storm: Analysis Using a National Inpatient Database in Japan.

PubMed

Ono, Yosuke; Ono, Sachiko; Yasunaga, Hideo; Matsui, Hiroki; Fushimi, Kiyohide; Tanaka, Yuji

2016-02-01

Thyroid storm is a life-threatening and emergent manifestation of thyrotoxicosis. However, predictive features associated with fatal outcomes in this crisis have not been clearly defined because of its rarity. The objective of this study was to investigate the associations of patient characteristics, treatments, and comorbidities with in-hospital mortality. We conducted a retrospective observational study of patients diagnosed with thyroid storm using a national inpatient database in Japan from April 1, 2011 to March 31, 2014. Of approximately 21 million inpatients in the database, we identified 1324 patients diagnosed with thyroid storm. The mean (standard deviation) age was 47 (18) years, and 943 (71.3%) patients were female. The overall in-hospital mortality was 10.1%. The number of patients was highest in the summer season. The most common comorbidity at admission was cardiovascular diseases (46.6%). Multivariable logistic regression analyses showed that higher mortality was significantly associated with older age (≥60 years), central nervous system dysfunction at admission, nonuse of antithyroid drugs and β-blockade, and requirement for mechanical ventilation and therapeutic plasma exchange combined with hemodialysis. The present study identified clinical features associated with mortality of thyroid storm using large-scale data. Physicians should pay special attention to older patients with thyrotoxicosis and coexisting central nervous system dysfunction. Future prospective studies are needed to clarify treatment options that could improve the survival outcomes of thyroid storm.

Factors Associated With Mortality of Thyroid Storm

PubMed Central

Ono, Yosuke; Ono, Sachiko; Yasunaga, Hideo; Matsui, Hiroki; Fushimi, Kiyohide; Tanaka, Yuji

2016-01-01

Abstract Thyroid storm is a life-threatening and emergent manifestation of thyrotoxicosis. However, predictive features associated with fatal outcomes in this crisis have not been clearly defined because of its rarity. The objective of this study was to investigate the associations of patient characteristics, treatments, and comorbidities with in-hospital mortality. We conducted a retrospective observational study of patients diagnosed with thyroid storm using a national inpatient database in Japan from April 1, 2011 to March 31, 2014. Of approximately 21 million inpatients in the database, we identified 1324 patients diagnosed with thyroid storm. The mean (standard deviation) age was 47 (18) years, and 943 (71.3%) patients were female. The overall in-hospital mortality was 10.1%. The number of patients was highest in the summer season. The most common comorbidity at admission was cardiovascular diseases (46.6%). Multivariable logistic regression analyses showed that higher mortality was significantly associated with older age (≥60 years), central nervous system dysfunction at admission, nonuse of antithyroid drugs and β-blockade, and requirement for mechanical ventilation and therapeutic plasma exchange combined with hemodialysis. The present study identified clinical features associated with mortality of thyroid storm using large-scale data. Physicians should pay special attention to older patients with thyrotoxicosis and coexisting central nervous system dysfunction. Future prospective studies are needed to clarify treatment options that could improve the survival outcomes of thyroid storm. PMID:26886648

Estimation of iodine nutrition and thyroid function status in late-gestation pregnant women in the United States: Development and application of a population-based pregnancy model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lumen, A., E-mail: Annie.Lumen@fda.hhs.gov

Previously, a deterministic biologically-based dose-response (BBDR) pregnancy model was developed to evaluate moderate thyroid axis disturbances with and without thyroid-active chemical exposure in a near-term pregnant woman and fetus. In the current study, the existing BBDR model was adapted to include a wider functional range of iodine nutrition, including more severe iodine deficiency conditions, and to incorporate empirically the effects of homeostatic mechanisms. The extended model was further developed into a population-based model and was constructed using a Monte Carlo-based probabilistic framework. In order to characterize total (T4) and free (fT4) thyroxine levels for a given iodine status at themore » population-level, the distribution of iodine intake for late-gestation pregnant women in the U.S was reconstructed using various reverse dosimetry methods and available biomonitoring data. The range of median (mean) iodine intake values resulting from three different methods of reverse dosimetry tested was 196.5–219.9 μg of iodine/day (228.2–392.9 μg of iodine/day). There was minimal variation in model-predicted maternal serum T4 and ft4 thyroxine levels from use of the three reconstructed distributions of iodine intake; the range of geometric mean for T4 and fT4, was 138–151.7 nmol/L and 7.9–8.7 pmol/L, respectively. The average value of the ratio of the 97.5th percentile to the 2.5th percentile equaled 3.1 and agreed well with similar estimates from recent observations in third-trimester pregnant women in the U.S. In addition, the reconstructed distributions of iodine intake allowed us to estimate nutrient inadequacy for late-gestation pregnant women in the U.S. via the probability approach. The prevalence of iodine inadequacy for third-trimester pregnant women in the U.S. was estimated to be between 21% and 44%. Taken together, the current work provides an improved tool for evaluating iodine nutritional status and the corresponding thyroid function status in pregnant women in the U.S. This model enables future assessments of the relevant risk of thyroid hormone level perturbations due to exposure to thyroid-active chemicals at the population-level. - Highlights: • A population-based thyroid function model for pregnant women was developed. • The model was used specifically study the late-gestation pregnant women in the U.S. • The prevalence of iodine inadequacy was estimated in the sub-population studied. • Developed model well predicts trimester-specific thyroid hormone reference ranges. • The model can be further used to study thyroid perturbations at a population level.« less

Accuracy of two simple methods for estimation of thyroidal {sup 131}I kinetics for dosimetry-based treatment of Graves' disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Traino, A. C.; Xhafa, B.; Sezione di Fisica Medica, U.O. Fisica Sanitaria, Azienda Ospedaliero-Universitaria Pisana, via Roma n. 67, Pisa 56125

2009-04-15

One of the major challenges to the more widespread use of individualized, dosimetry-based radioiodine treatment of Graves' disease is the development of a reasonably fast, simple, and cost-effective method to measure thyroidal {sup 131}I kinetics in patients. Even though the fixed activity administration method does not optimize the therapy, giving often too high or too low a dose to the gland, it provides effective treatment for almost 80% of patients without consuming excessive time and resources. In this article two simple methods for the evaluation of the kinetics of {sup 131}I in the thyroid gland are presented and discussed. Themore » first is based on two measurements 4 and 24 h after a diagnostic {sup 131}I administration and the second on one measurement 4 h after such an administration and a linear correlation between this measurement and the maximum uptake in the thyroid. The thyroid absorbed dose calculated by each of the two methods is compared to that calculated by a more complete {sup 131}I kinetics evaluation, based on seven thyroid uptake measurements for 35 patients at various times after the therapy administration. There are differences in the thyroid absorbed doses between those derived by each of the two simpler methods and the ''reference'' value (derived by more complete uptake measurements following the therapeutic {sup 131}I administration), with 20% median and 40% 90-percentile differences for the first method (i.e., based on two thyroid uptake measurements at 4 and 24 h after {sup 131}I administration) and 25% median and 45% 90-percentile differences for the second method (i.e., based on one measurement at 4 h post-administration). Predictably, although relatively fast and convenient, neither of these simpler methods appears to be as accurate as thyroid dose estimates based on more complete kinetic data.« less

Glomerular filtration rate is associated with free triiodothyronine in euthyroid subjects: Comparison between various equations to estimate renal function and creatinine clearance.

PubMed

Anderson, Josephine L C; Gruppen, Eke G; van Tienhoven-Wind, Lynnda; Eisenga, Michele F; de Vries, Hanne; Gansevoort, Ron T; Bakker, Stephan J L; Dullaart, Robin P F

2018-02-01

Effects of variations in thyroid function within the euthyroid range on renal function are unclear. Cystatin C-based equations to estimate glomerular filtration rate (GFR) are currently advocated for mortality and renal risk prediction. However, the applicability of cystatin C-based equations is discouraged in patients with overt thyroid dysfunction, since serum cystatin C and creatinine levels are oppositely affected by thyroid dysfunction. Here, we compared relationships of thyroid stimulating hormone (TSH), free thyroxine (FT4) and free triiodothyronine (FT3) with various measures of kidney function in euthyroid subjects. Relationships of eGFR, based on creatinine (eGFRcrea), cystatin C (eGFRcysC), creatinine+cystatin C combined (eGFRcrea-cysC) and creatinine clearance (CrCl) with TSH, FT4 and FT3 were determined in 2180 euthyroid subjects (TSH, FT4 and FT3 all within the reference range; anti-thyroid peroxidase autoantibodies negative) who did not use thyroid hormones, anti-thyroid drugs, amiodarone or lithium carbonate. In multivariable models including TSH, FT3 and FT4 together, eGFRcrea, eGFRcysC and eGFRcrea-cysC and CrCl were all positively related to FT3 (P≤0.001), translating into a 2.61 to 2.83mL/min/1.73m 2 increase in eGFR measures and a 3.92mL/min increase in CrCl per 1pmol/L increment in FT3. These relationships with FT3 remained taking account of relevant covariates. In euthyroid subjects renal function is associated with thyroid function status, especially by serum FT3, irrespective of the eGFR equation applied. In the euthyroid state, cystatin C-based eGFR equations are appropriate to assess the relationship of renal function with variation in thyroid function status. Copyright © 2017 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Etiological evaluation of primary congenital hypothyroidism cases

PubMed Central

Bezen, Diğdem; Dilek, Emine; Torun, Neşe; Tütüncüler, Filiz

2017-01-01

Aim Primary congenital hypothyroidism is frequently seen endocrine disorder and one of the preventable cause of mental retardation. Aim of study was to evaluate the frequency of permanent/transient hypothyrodism, and to detect underlying reason to identfy any marker which carries potential to discriminate permanent/transient form. Material and Methods Forty eight cases older than 3 years of age, diagnosed as primary congenital hypothyroidism and started thyroxin therapy in newborn-period, and followed up between January 2007–June 2013 were included in the study. Thyroid hormon levels were evaluated and thyroid ultrasonography was performed in cases who are at the end of their 3 years of age, after 6 weeks of thyroxine free period. Thyroid sintigraphy was performed if serum thyroid-stimulating hormone was high (≥ 5 mIU/mL) and perchlorate discharge test was performed if uptake was normal or increased on sintigraphy. Cases with thyroid-stimulating hormone levels ≥ 5 mIU/mL were defined as permanent primary congenital hypothyroidism group and as transient primary congenital hypothyroidism group with normal thyroid hormones during 6 months. Results The mean age was 3.8±0.7 years. Mean diagnosis age was 16.6±6.5 days and 14 cases (29.2%) were diagnosed by screening program of Ministry of Health. There were 23 cases (14F, 9M) in permanent primary congenital hypothyroidism group and 12 (52.2%) of them were dysgenesis (8 hypoplasia, 4 ectopia), and 11 (47.8%) dyshormonogenesis. In transient primary congenital hypothyroidism group, there were 25 cases (17M, 8F). The mean thyroid-stimulating hormone levels at diagnosis were similar in two groups. The mean thyroxin dose in permanent primary congenital hypothyroidism group was significantly higher than transient group at the time of thyroxin cessation (2.1±0.7, 1.5±0.5 mg/kg/d, respectively, p=0.004). Thyroxin dose ≥1.6 mcg/kg/d was 72% sensitive and 69.6% specific for predicting permenant primary congenital hypothyroidism. Conclusions Transient primary congenital hypothyroidism is more frequent than expected and found often in males in the primary congenital hypothyroidism cases, started thyroxin therapy in neonatal period. While fT4, thyroid-stimulating hormone, Tg levels at diagnosis do not predict transient/permenant primary congenital hypothyroidism, thyroxin dose before the therapy cessation at the age of 3 may make the distinction between transient/permenant primary congenital hypothyroidism. PMID:28747839

Association between Decreased Serum Parathyroid Hormone after Total Thyroidectomy and Persistent Hypoparathyroidism

PubMed Central

Wang, Jian-Biao; Sun, Hai-Li; Song, Chun-Yi; Gao, Li

2015-01-01

Background Postoperative hypocalcemia caused by hypoparathyroidism is one of the most common morbidities of total thyroidectomy. The aim of this study was to analyze the kinetics and factors affecting PTH levels after total thyroidectomy and central neck dissection (CND). Material/Methods We performed a retrospective study in 438 consecutive patients who underwent total thyroidectomy between January 2007 and December 2010. No patient had a history of thyroid or neck surgery. PTH and calcium levels were recorded 1 day before the operation, during the first 5 days, and during follow-up (2 weeks and 2, 6, and 12 months). Results PTH levels declined to 41.90% of its initial value on the first day after the operation. After surgery, PTH was correlated positively with calcium and inversely with phosphate levels from postoperative day 1 to 14. Based on clinical observation, using a PTH threshold of <7 ng/L on postoperative day 1 was predictive of persistent hypoparathyroidism, with sensitivity and negative predictive value 100%, but poor specificity (70.19%). CND increased the risk of transient hypoparathyroidism compared with total thyroidectomy alone. Patients with thyroiditis had an increased risk of permanent hypoparathyroidism compared with those without thyroiditis. Iatrogenic removal of the parathyroid glands increased the risk of permanent hypoparathyroidism compared with those without iatrogenic parathyroidectomy. Conclusions PTH declined on the first day after thyroidectomy. PTH levels <7 ng/L on the first day after surgery might be associated with persistent hypoparathyroidism. CND, thyroiditis, and iatrogenic parathyroidectomy increased the risk of hypoparathyroidism. PMID:25923249

Preoperative Molecular Markers in Thyroid Nodules.

PubMed

Sahli, Zeyad T; Smith, Philip W; Umbricht, Christopher B; Zeiger, Martha A

2018-01-01

The need for distinguishing benign from malignant thyroid nodules has led to the pursuit of differentiating molecular markers. The most common molecular tests in clinical use are Afirma ® Gene Expression Classifier (GEC) and Thyroseq ® V2. Despite the rapidly developing field of molecular markers, several limitations exist. These challenges include the recent introduction of the histopathological diagnosis "Non-Invasive Follicular Thyroid neoplasm with Papillary-like nuclear features", the correlation of genetic mutations within both benign and malignant pathologic diagnoses, the lack of follow-up of molecular marker negative nodules, and the cost-effectiveness of molecular markers. In this manuscript, we review the current published literature surrounding the diagnostic value of Afirma ® GEC and Thyroseq ® V2. Among Afirma ® GEC studies, sensitivity (Se), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV) ranged from 75 to 100%, 5 to 53%, 13 to 100%, and 20 to 100%, respectively. Among Thyroseq ® V2 studies, Se, Sp, PPV, and NPV ranged from 40 to 100%, 56 to 93%, 13 to 90%, and 48 to 97%, respectively. We also discuss current challenges to Afirma ® GEC and Thyroseq ® V2 utility and clinical application, and preview the future directions of these rapidly developing technologies.

Predictors of Malignancy in Patients with Cytologically Suspicious Thyroid Nodules

PubMed Central

Espiritu, Rachel P.; Bahn, Rebecca S.; Henry, Michael R.; Gharib, Hossein; Caraballo, Pedro J.; Morris, John C.

2011-01-01

Background Fine needle aspiration (FNA), although very reliable for cytologically benign and malignant thyroid nodules, has much lower predictive value in the case of suspicious or indeterminate nodules. We aimed to identify clinical predictors of malignancy in the subset of patients with suspicious FNA cytology. Methods We reviewed the electronic medical records of 462 patients who had FNA of thyroid nodules at our institution with a suspicious cytological diagnosis, and underwent surgery at Mayo Clinic between January 2004 and September 2008. Demographic data including age, gender, history of exposure to radiation and use of thyroid hormone was collected. The presence of single versus multiple nodules by ultrasonography, nodule size, and serum thyroid-stimulating harmone (TSH) level before thyroid surgery were recorded. Analysis of the latter was limited to patients not taking thyroid hormone or antithyroid drugs at the time of FNA. Results Of the 462 patients, 327 had lesions suspicious for follicular neoplasm (S-FN) or Hürthle cell neoplasm (S-HCN), 125 had cytology suspicious for papillary carcinoma (S-PC) and 10 had a variety of other suspicious lesions (medullary cancer, lymphoma and atypical). Malignancy rate for suspicious neoplastic lesions (FN+HCN) was ∼15%, whereas malignancy rate for lesions S-PC was 77%. Neither age, serum TSH level, or history of radiation exposure were associated with increased malignancy risk. The presence of multiple nodules (41.1% vs. 26.4%, p=0.0014) or smaller nodule size (2.6±1.8 cm vs. 2.9±1.6 cm, p=0.008) was associated with higher malignancy risk. In patients with cytology suspicious for neoplasm (FN, HCN) malignancy risk was higher in those receiving thyroid hormone therapy than in nonthyroid hormone users (37.7% vs. 16.5%, p=0.0004; odds ratio: 3.1), although serum TSH values did not differ significantly between thyroid hormone users and nonusers. Conclusion In patients with cytologically suspicious thyroid nodules, the presence of multiple nodules or smaller nodule size was associated with increased risk of malignancy. In addition, our study demonstrates for the first time, an increased risk of malignancy in patients with nodules suspicious for neoplasm who are taking thyroid hormone therapy. The reason for this association is unknown. PMID:22007937

Thyroid disorders associated with pregnancy: etiology, diagnosis, and management.

PubMed

Lazarus, John H

2005-01-01

Pregnancy has an effect on thyroid economy with significant changes in iodine metabolism, serum thyroid binding proteins, and the development of maternal goiter especially in iodine-deficient areas. Pregnancy is also accompanied by immunologic changes, mainly characterized by a shift from a T helper-1 (Th1) lymphocyte to a Th2 lymphocyte state. Thyroid peroxidase antibodies are present in 10% of women at 14 weeks' gestation, and are associated with (i) an increased pregnancy failure (i.e. abortion), (ii) an increased incidence of gestational thyroid dysfunction, and (iii) a predisposition to postpartum thyroiditis. Thyroid function should be measured in women with severe hyperemesis gravidarum but not in every patient with nausea and vomiting during pregnancy. Graves hyperthyroidism during pregnancy is best managed with propylthiouracil administered throughout gestation. Thyroid-stimulating hormone-receptor antibody measurements at 36 weeks' gestation are predictive of transient neonatal hyperthyroidism, and should be checked even in previously treated patients receiving thyroxine. Postpartum exacerbation of hyperthyroidism is common, and should be evaluated in women with Graves disease not on treatment. Radioiodine therapy in pregnancy is absolutely contraindicated. Hypothyroidism (including subclinical hypothyroidism) occurs in about 2.5% of pregnancies, and may lead to obstetric and neonatal complications as well as being a cause of infertility. During the last few decades, evidence has been presented to underpin the critical importance of adequate fetal thyroid hormone levels in order to ensure normal central and peripheral nervous system maturation. In iodine-deficient and iodine-sufficient areas, low maternal circulating thyroxine levels have been associated with a significant decrement in child IQ and development. These data suggest the advisability of further evaluation for a screening program early in pregnancy to identify women with hypothyroxinemia, and the initiation of prompt treatment for its correction. Hypothyroidism in pregnancy is treated with a larger dose of thyroxine than in the nonpregnant state. Postpartum thyroid dysfunction (PPTD) occurs in 50% of women found to have thyroid peroxidase antibodies in early pregnancy. The hypothyroid phase of PPTD is symptomatic and requires thyroxine therapy. A high incidence (25-30%) of permanent hypothyroidism has been noted in these women. Women having transient PPTD with hypothyroidism should be monitored frequently, as there is a 50% chance of these patients developing hypothyroidism during the next 7 years.

Coexistence of chronic lymphocytic thyroiditis with papillary thyroid carcinoma: clinical manifestation and prognostic outcome.

PubMed

Jeong, Jun Soo; Kim, Hyun Ki; Lee, Cho-Rok; Park, Seulkee; Park, Jae Hyun; Kang, Sang-Wook; Jeong, Jong Ju; Nam, Kee-Hyun; Chung, Woong Youn; Park, Cheong Soo

2012-08-01

The study aimed to identify the clinical characteristics of coexisting chronic lymphocytic thyroiditis (CLT) in papillary thyroid carcinoma (PTC) and to evaluate the influence on prognosis. A total of 1,357 patients who underwent thyroid surgery for PTC were included. The clinicopathological characteristics were identified. Patients who underwent total thyroidectomy (n = 597) were studied to evaluate the influence of coexistent CLT on prognosis. Among the total 1,357 patients, 359 (26.5%) had coexistent CLT. In the CLT group, the prevalence of females was higher than in the control group without CLT (P < 0.001). Mean tumor size and mean age in the patients with CLT were smaller than without CLT (P = 0.040, P = 0.047, respectively). Extrathyroidal extension in the patients with CLT was significantly lower than without CLT (P = 0.016). Among the subset of 597 patients, disease-free survival rate in the patients with CLT was significantly higher than without CLT (P = 0.042). However, the multivariate analysis did not reveal a negative association between CLT coexistence and recurrence. Patients with CLT display a greater female preponderance, smaller size, younger and lower extrathyroidal extension. CLT is not a significant independent negative predictive factor for recurrence, although presence of CLT indicates a reduced risk of recurrence.

Coexistence of Chronic Lymphocytic Thyroiditis with Papillary Thyroid Carcinoma: Clinical Manifestation and Prognostic Outcome

PubMed Central

Jeong, Jun Soo; Kim, Hyun Ki; Lee, Cho-Rok; Park, Seulkee; Park, Jae Hyun; Kang, Sang-Wook; Nam, Kee-Hyun; Chung, Woong Youn; Park, Cheong Soo

2012-01-01

The study aimed to identify the clinical characteristics of coexisting chronic lymphocytic thyroiditis (CLT) in papillary thyroid carcinoma (PTC) and to evaluate the influence on prognosis. A total of 1,357 patients who underwent thyroid surgery for PTC were included. The clinicopathological characteristics were identified. Patients who underwent total thyroidectomy (n = 597) were studied to evaluate the influence of coexistent CLT on prognosis. Among the total 1,357 patients, 359 (26.5%) had coexistent CLT. In the CLT group, the prevalence of females was higher than in the control group without CLT (P < 0.001). Mean tumor size and mean age in the patients with CLT were smaller than without CLT (P = 0.040, P = 0.047, respectively). Extrathyroidal extension in the patients with CLT was significantly lower than without CLT (P = 0.016). Among the subset of 597 patients, disease-free survival rate in the patients with CLT was significantly higher than without CLT (P = 0.042). However, the multivariate analysis did not reveal a negative association between CLT coexistence and recurrence. Patients with CLT display a greater female preponderance, smaller size, younger and lower extrathyroidal extension. CLT is not a significant independent negative predictive factor for recurrence, although presence of CLT indicates a reduced risk of recurrence. PMID:22876054

Thyroid Function Variations Within the Reference Range Do Not Affect Quality of Life, Mood, or Cognitive Function in Community-Dwelling Older Men.

PubMed

Samuels, Mary H; Kaimal, Rajani; Waring, Avantika; Fink, Howard A; Yaffe, Kristine; Hoffman, Andrew R; Orwoll, Eric; Bauer, Douglas

2016-09-01

Variations in thyroid function within the laboratory reference range have been associated with a number of clinical outcomes. However, quality of life, mood, and cognitive function have not been extensively studied, and it is not clear whether mild variations in thyroid function have major effects on these neurocognitive outcomes. Data were analyzed from the Osteoporotic Fractures in Men (MrOS) Study, a cohort of community-dwelling men aged 65 years and older in the United States. A total of 539 participants who were not taking thyroid medications and had age-adjusted TSH levels within the reference range underwent detailed testing of quality of life, mood, and cognitive function at baseline. The same quality of life, mood, and cognitive outcomes were measured again in 193 of the men after a mean follow-up of 6 years. Outcomes were analyzed using thyrotropin (TSH) and free thyroxine (FT4) levels as continuous independent variables, adjusting for relevant covariates. At baseline, there were no associations between TSH or FT4 levels and measures of quality of life, mood, or cognition in the 539 euthyroid men. Baseline thyroid function did not predict changes in these outcomes over a mean of 6 years in the 193 men in the longitudinal analysis. Variations in thyroid function within the age-adjusted laboratory reference range are not associated with variations in quality of life, mood, or cognitive function in community-dwelling older men.

Assessing risk of thyroid cancer using resonance-frequency based electrical impedance measurements

NASA Astrophysics Data System (ADS)

Zheng, Bin; Tublin, Mitchell E.; Lederman, Dror; Klym, Amy H.; Brown, Erica D.; Gur, David

2011-03-01

The incidence of thyroid cancer has risen faster than many malignancies and has nearly doubled in the USA over the past 30 years. Palpable nodules and subclinical nodules detected by imaging are found in a large percentage of the USA population. Most of these (.>95%) are fortunately benign. This vast reservoir of nodules makes the detection and diagnosis of thyroid cancer a diagnostic dilemma. Ultrasound guided Fine Needle Aspiration Biopsy (FNAB) is excellent for triaging patients but up to 25% of FNABs are inconclusive. As a result, definitive diagnosis is often only possible with a diagnostic lobectomy; many thousands of these are performed in the USA annually for ultimately benign disease. It would be extremely beneficial if we could develop a non-invasive procedure that could assist the diagnostician in reliably predicting the likelihood of malignancy of otherwise indeterminate thyroid nodules, thereby reducing the number of these "exploratory/diagnostic" lobectomies performed under general anesthesia. Electrical Impedance Spectroscopy (EIS) was considered as a possible approach to address this problem. However, the diagnostic accuracy of EIS is too low for routine clinical use to date. In our group, we developed a substantially modified technology termed Resonance-frequency Electrical Impedance Spectroscopy (REIS), which yields usable information for classifying risk of having breast abnormalities. We preliminarily applied REIS to measure signals on participants having thyroid nodules aiming to assess whether we can assist in improving diagnosis of indeterminate thyroid nodules. In this study we present a new multi-probe based REIS device specifically designed for the assessment of indeterminate thyroid nodules. Our preliminary assessment presented here demonstrates the feasibility of using this proposed REIS device in a busy tertiary care center.

Urinary metabolomics reveals glycemic and coffee associated signatures of thyroid function in two population-based cohorts

PubMed Central

Friedrich, Nele; Pietzner, Maik; Cannet, Claire; Thuesen, Betina H.; Hansen, Torben; Wallaschofski, Henri; Grarup, Niels; Skaaby, Tea; Budde, Kathrin; Pedersen, Oluf; Nauck, Matthias; Linneberg, Allan

2017-01-01

Background Triiodothyronine (T3) and thyroxine (T4) as the main secretion products of the thyroid affect nearly every human tissue and are involved in a broad range of processes ranging from energy expenditure and lipid metabolism to glucose homeostasis. Metabolomics studies outside the focus of clinical manifest thyroid diseases are rare. The aim of the present investigation was to analyze the cross-sectional and longitudinal associations of urinary metabolites with serum free T4 (FT4) and thyroid-stimulating hormone (TSH). Methods Urine Metabolites of participants of the population-based studies Inter99 (n = 5620) and Health2006/Health2008 (n = 3788) were analyzed by 1H-NMR spectroscopy. Linear or mixed linear models were used to detect associations between urine metabolites and thyroid function. Results Cross-sectional analyses revealed positive relations of alanine, trigonelline and lactic acid with FT4 and negative relations of dimethylamine, glucose, glycine and lactic acid with log(TSH). In longitudinal analyses, lower levels of alanine, dimethylamine, glycine, lactic acid and N,N-dimethylglycine were linked to a higher decline in FT4 levels over time, whereas higher trigonelline levels were related to a higher FT4 decline. Moreover, the risk of hypothyroidism was higher in subjects with high baseline trigonelline or low lactic acid, alanine or glycine values. Conclusion The detected associations mainly emphasize the important role of thyroid hormones in glucose homeostasis. In addition, the predictive character of these metabolites might argue for a potential feedback of the metabolic state on thyroid function. Besides known metabolic consequences of TH, the link to the urine excretion of trigonelline, a marker of coffee consumption, represents a novel finding of this study and given the ubiquitous consumption of coffee requires further research. PMID:28253303

Thyroid surgery--the Tan Tock Seng Hospital otolaryngology experience.

PubMed

Lee, J C Y; Siow, J K

2002-03-01

Central to the management of a patient with a thyroid nodule is the evaluation of the risk of malignancy. Postoperative morbidity, though rare, remains a concern because of its impact on the quality of the life of the patient. A retrospective audit of 91 consecutive patients who underwent thyroid surgery for thyroid nodules, at the Department of Otolaryngology, Tan Tock Seng Hospital, between January 1995 and December 2000. The sensitivity and specificity of fine-needle aspiration cytology (FNAC) were 60% and 100%, respectively. The sensitivity and specificity of intraoperative frozen section examination was 82% and 100%, respectively. Sixty-four patients experienced no postoperative morbidity. Of the 27 patients with postoperative morbidity, only 1 was permanent. The incidence of transient and permanent biochemical hypocalcaemia was 44% and 0%, respectively. Nodal dissection performed together with total thyroidectomy increased the incidence of postoperative hypocalcaemia (P < 0.05). The number of parathyroid glands preserved in situ did not predict for postoperative hypocalcaemia. The incidence of transient and permanent recurrent laryngeal nerve (RLN) palsy was 10.3% and 1.1% (8.2% and 0.9% of nerves at risk), respectively. Tracheo-oesophageal groove clearance performed together with thyroid lobectomy did not increase the incidence of postoperative RLN palsy (P > 0.05). The median hospital stay was 3 days for benign thyroid disease, 4.5 and 16 days for malignant disease with tracheo-oesophageal groove clearance only and with neck dissection, respectively. The combination of clinical examination and FNAC remains the mainstay in selecting patients for surgery. Frozen section examination is an important intraoperative diagnostic adjunct to decide the extent of surgery. With proper surgical training and experience, thyroid surgery for malignancy can be undertaken with minimum postoperative morbidity and a short hospital stay.

Type of fish consumed and thyroid autoimmunity in pregnancy and postpartum.

PubMed

Benvenga, Salvatore; Vigo, Maria Teresa; Metro, Daniela; Granese, Roberta; Vita, Roberto; Le Donne, Maria

2016-04-01

Fish consumption or supplementation with omega-3 fatty acids was reported to cure and/or prevent autoimmune and nonautoimmune disorders. Serum positivity for thyroid autoantibodies is a predictive marker of postpartum thyroiditis and postpartum depression. We hypothesized that stable consumption of the omega-3-rich oily fish was associated with a more favorable profile of serum thyroid antibodies throughout pregnancy and early postpartum compared with stable consumption of swordfish, a predator that concentrates pollutants. We prospectively measured serum thyroglobulin antibodies and thyroperoxidase antibodies in pregnancy (first, second trimesters) and postpartum (day 4), in 236 thyroid disease-free, nonsmoker Caucasian women with stable dietary habits. We did not measure thyroid autoantibodies prior to pregnancy. Women were divided into groups A (n = 48; swordfish), B (n = 52; oily fish), C (n = 68; swordfish + other fish, not necessarily oily fish), and D (n = 68; fish other than swordfish and oily fish). Major endpoints were positivity rates and serum concentrations of the two autoantibodies. We resorted to previous studies for the estimated content of fatty acids and microelements in the consumed fish. Positivity rates and serum concentrations of both antibodies were the greatest in group A and the lowest in group B (P < 0.001 and P < 0.05 to < 0.001, respectively). Relationship between monthly fish consumption and serum concentrations of either antibody was direct in group A but inverse in group B. The estimated content of omega-3 fatty acids in fish consumed by group B was the greatest (P < 0.001 vs. any other group). These data reinforce recommendations that pregnant women should avoid consuming swordfish and indicate consumption of oily fish as a favorable alternative. Because thyroid autoantibodies are markers of autoimmune-related postpartum problems, our data suggest a dietary prophylaxis of such problems.

Development of a microRNA-based molecular assay for the detection of papillary thyroid carcinoma in aspiration biopsy samples.

PubMed

Mazeh, Haggi; Mizrahi, Ido; Halle, David; Ilyayev, Nadia; Stojadinovic, Alexander; Trink, Barry; Mitrani-Rosenbaum, Stella; Roistacher, Marina; Ariel, Ilana; Eid, Ahmed; Freund, Herbert R; Nissan, Aviram

2011-02-01

Although thyroid nodules are common and diagnosed in over 5% of the adult population, only 5% harbor malignancy. Patients with clinically suspicious thyroid nodules need to undergo fine-needle aspiration biopsy (FNAB). The main limitation of FNAB remains indeterminate cytopathology. Only 20%-30% of the indeterminate nodules harbor malignancy, and therefore up to 80% of patients undergo unnecessary thyroidectomy. The aim of this study was to identify and validate a panel of microRNAs (miRNAs) that could serve as a platform for an FNAB-based diagnostic for thyroid neoplasms. The study population included 27 consecutive patients undergoing total thyroidectomy for FNAB-based papillary thyroid cancer (n = 20) and benign disorders (n = 7). Aspiration biopsy was performed from the index lesion and from the opposite lobe normal tissue in all study patients at the time of operation. RNA was extracted from all aspiration biopsy samples. Quantitative polymerase chain reaction on a panel of previously selected miRNAs was performed. Polymerase chain reaction results were compared with final histopathology. miRNA from tumor tissues was amplified using the highest value of each miRNA expression in normal tissue as a threshold for malignancy detection. Diagnostic characteristics were most favorable for mir-221 in differentiating benign from malignant thyroid pathology. mir-221 was overexpressed in 19 patients (p < 0.0001) with a sensitive yield of 95%. Specificity, negative and positive predictive value, and accuracy of the miRNA panel were 100%, 96%, 100%, and 98%, respectively. miRNA quantification for differential diagnosis of thyroid neoplasms within aspiration biopsy samples is feasible and may improve the accuracy of FNAB cytology.

Value of CT added to ultrasonography for the diagnosis of lymph node metastasis in patients with thyroid cancer.

PubMed

Lee, Younghen; Kim, Ji-Hoon; Baek, Jung Hwan; Jung, So Lyung; Park, Sun-Won; Kim, Jinna; Yun, Tae Jin; Ha, Eun Ju; Lee, Kyu Eun; Kwon, Soon Young; Yang, Kyung-Sook; Na, Dong Gyu

2018-05-13

The benefit of CT for the diagnosis of lymph node metastasis in patients with thyroid cancer is still unclear. Three hundred fifty-one patients with thyroid cancers from 7 hospitals were prospectively enrolled in order to compare diagnostic performance between a combination of ultrasound and CT (ultrasound/CT) and ultrasound alone for prediction of lymph node metastasis and to calculate patient-based benefits of CT added to ultrasound. Of 801 pathologically proven neck levels, ultrasound/CT showed higher sensitivities in both central and lateral compartments and improved accuracy in the lateral compartment compared to ultrasound alone. In the retropharyngeal/superior mediastinal compartment, although CT could detect lymph node metastasis an ultrasound could not. Patient-based benefit was demonstrated in 13.1% of patients (46/351), and was higher in patients with cancers >1 cm than cancers ≤1 cm. In patients with thyroid cancer, CT improved surgical planning by enhancing the sensitivity for lymph node metastasis and by detecting lymph node metastasis that was overlooked with ultrasound alone. © 2018 Wiley Periodicals, Inc.

Significance of expression of suppressor of cytokine signaling proteins: Suppressor of cytokine signaling-1, suppressor of cytokine signaling-2, and suppressor of cytokine signaling-3 in papillary thyroid cancer.

PubMed

Kobawala, Toral Pundrik; Trivedi, Trupti I; Gajjar, Kinjal Kevin; Patel, Girish H; Ghosh, Nandita R

2017-01-01

Uncontrolled cytokine signal transduction largely associated with oncogene activation, can have disastrous biological consequences. The suppressor of cytokine signaling (SOCS) proteins represent one of the mechanisms by which this rampant signaling can be dissipated. Thus, we aimed to study the expression of SOCS-1, SOCS-2, and SOCS-3 in patients having benign thyroid disease and papillary thyroid cancer. SOCS protein expression was studied in 45 patients with benign thyroid disease and in 83 papillary thyroid cancer patients by immunohistochemistry and their association with clinicopathological characteristics and overall survival in cancer patients were analyzed using SPSS software. Expressions of SOCS proteins were significantly higher in papillary thyroid cancer than in patients having benign disease. SOCS-1 expression was predominantly higher in males (P = 0.004), unilateral tumors (P = 0.030), and noninflammatory conditions (P = 0.028). SOCS-1 expression was also able to predict poor overall survival in subgroup of papillary thyroid cancer patients having larger tumor size (P = 0.013) and advanced stage disease (P = 0.033). Expression of SOCS-2 significantly correlated with tumor size (P = 0.017), extrathyroidal extension (P = 0.000), residual disease (P = 0.043), and treatment (P = 0.007), while preponderance of SOCS-3 expression was observed in males (P = 0.030) and in patients having extrathyroidal extension (P = 0.011) and absence of metastasis (P = 0.032). Expression of the studied SOCS proteins may be a consequence of activation of Janus kinase-signal transducers and activators of transcription and other pathways supporting growth and survival of cancer cells that are sustained by several cytokines. Thus, SOCS-1, SOCS-2, and SOCS-3 proteins may directly or indirectly, have important roles in development and pathogenesis of papillary thyroid cancer.

Validation of American Thyroid Association Ultrasound Risk Assessment of Thyroid Nodules Selected for Ultrasound Fine-Needle Aspiration.

PubMed

Tang, Alice L; Falciglia, Mercedes; Yang, Huaitao; Mark, Jonathan R; Steward, David L

2017-08-01

The aim of this study was to validate the American Thyroid Association (ATA) sonographic risk assessment of thyroid nodules. The ATA sonographic risk assessment was prospectively applied to 206 thyroid nodules selected for ultrasound-guided fine-needle aspiration (US-FNA), and analyzed with The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC), as well as surgical pathology for the subset undergoing surgical excision. The analysis included 206 thyroid nodules averaging 2.4 cm (range 1-7 cm; standard error of the mean 0.07). Using the ATA US pattern risk assessment, nodules were classified as high (4%), intermediate (31%), low (38%), and very low (26%) risk of malignancy. Nodule size was inversely correlated with sonographic risk assessment, as lower risk nodules were larger on average (p < 0.0001). Malignancy rates determined by cytology/surgical pathology were high 100%, intermediate 11%, low 8%, and very low 2%, which were closely aligned with ATA malignancy risk estimates (high 70-90%, intermediate 10-20%, low 5-10%, and very low 3%). ATA US pattern risk assessment also appropriately predicted the proportion of nodules classified as malignant or suspicious for malignancy through TBSRTC classification-high (77%), intermediate (6%), low (1%), and very low 0%-as well as benign TBSRTC classification-high (0%), intermediate (47%), low (61%), and very low (70%) (p < 0.0001). Malignancy rates of surgically excised, cytologically indeterminate nodules followed ATA sonographic risk stratification (high 100%, intermediate 21%, low 17%, and very low 12%; p = 0.003). This prospective study supports the new ATA sonographic pattern risk assessment for selection of thyroid nodules for US-FNA based upon TBSRTC and surgical pathology results. In the setting of indeterminate cytopathology, nodules categorized as atypia of undetermined significance/follicular lesion of undetermined significance with ATA high-risk sonographic patterns have a high likelihood of being malignant.

Five months' follow-up of patients with and without iodine-positive lymph node metastases of thyroid carcinoma as disclosed by (131)I-SPECT/CT at the first radioablation.

PubMed

Schmidt, Daniela; Linke, Rainer; Uder, Michael; Kuwert, Torsten

2010-04-01

In differentiated thyroid carcinoma (DTC), (131)I-SPECT/CT is more accurate in identifying radioiodine-positive lymph node metastases (LNM) than planar whole-body scans (WBS). The purpose of this study was to investigate the value of (131)I-SPECT/CT performed at the first radioablation to predict the occurrence and/or persistence of cervical radioiodine-positive LNM 5 months later. The study included 81 DTC patients that had had SPECT/ spiral CT after radioablation of thyroid remnants after thyroidectomy. The patients were re-examined 5 months later using (131)I-WBS performed at TSH stimulation. In addition, SPECT/CT of the neck was performed in patients with iodine-positive cervical foci to distinguish between thyroid remnant and LNM. The outcome variable of the study was the detection or exclusion of iodine-positive cervical LNM. Of 61 patients without a SPECT/CT diagnosis of (131)I-positive LNM at radioablation, 60 had no (131)I-positive LNM at follow-up. In the remaining patient of this group, a new radioiodine-positive LNM was detected. In 17 of 20 patients with a SPECT/CT diagnosis of (131)I-positive LNM (n = 19) or an indeterminate lesion (n = 1) at first radioablation, no (131)I-positive LNM were detected 5 months later. Radioiodine-positive LNM persisted in three patients of this group. (131)I-SPECT/CT has a high negative predictive value with regard to the occurrence of radioiodine-positive cervical LNM 5 months after initial therapy. The majority of iodine-positive LNM diagnosed by SPECT/CT at radioablation disappear within 5 months. These findings motivate further research into the value of (131)I-SPECT/CT of the neck for predicting recurrence and planning surgical reintervention in DTC.

Novel and Practical Scoring Systems for the Diagnosis of Thyroid Nodules

PubMed Central

Wei, Ying; Zhou, Xinrong; Liu, Siyue; Wang, Hong; Liu, Limin; Liu, Renze; Kang, Jinsong; Hong, Kai; Wang, Daowen; Yuan, Gang

2016-01-01

Objective The clinical management of patients with thyroid nodules that are biopsied by fine-needle aspiration cytology and yield indeterminate results remains unsettled. The BRAF V600E mutation has dubious diagnostic value due to its low sensitivity. Novel strategies are urgently needed to distinguish thyroid malignancies from thyroid nodules. Design This prospective study included 504 thyroid nodules diagnosed by ultrasonography from 468 patients, and fine-needle aspiration cytology was performed under ultrasound guidance. Cytology and molecular analysis, including BRAF V600E, RET/PTC1 and RET/PTC3, were conducted simultaneously. The cytology, ultrasonography results, and mutational status were gathered and analyzed together. Predictive scoring systems were designed using a combination of diagnostic parameters for ultrasonography, cytology and genetic analysis. The utility of the scoring systems was analyzed and compared to detection using the individual methods alone or combined. Result The sensitivity of scoring systema (ultrasonography, cytology, BRAF V600E, RET/PTC) was nearly identical to that of scoring systemb (ultrasonography, cytology, BRAF V600E); these were 91.0% and 90.2%, respectively. These sensitivities were significantly higher than those obtained using FNAC, genetic analysis and US alone or combined; their sensitivities were 63.9%, 70.7% and 87.2%, respectively. Scoring systemc (ultrasonography, cytology) was slightly inferior to the former two scoring systems but still had relatively high sensitivity and specificity (80.5% and 95.1%, respectively), which were significantly superior to those of single cytology, ultrasonography or genetic analysis. In nodules with uncertainty cytology, scoring systema, scoring systemb and scoring systemc could elevate the malignancy detection rates to 69.7%, 69.7% and 63.6%, respectively. Conclusion These three scoring systems were quick for clinicians to master and could provide quantified information to predict the probability of malignant nodules. Scoring systemb is recommended for improving the detection rate among nodules of uncertain cytology. PMID:27654865

Molecular Testing for miRNA, mRNA, and DNA on Fine-Needle Aspiration Improves the Preoperative Diagnosis of Thyroid Nodules With Indeterminate Cytology.

PubMed

Labourier, Emmanuel; Shifrin, Alexander; Busseniers, Anne E; Lupo, Mark A; Manganelli, Monique L; Andruss, Bernard; Wylie, Dennis; Beaudenon-Huibregtse, Sylvie

2015-07-01

Molecular testing for oncogenic mutations or gene expression in fine-needle aspirations (FNAs) from thyroid nodules with indeterminate cytology identifies a subset of benign or malignant lesions with high predictive value. This study aimed to evaluate a novel diagnostic algorithm combining mutation detection and miRNA expression to improve the diagnostic yield of molecular cytology. Surgical specimens and preoperative FNAs (n = 638) were tested for 17 validated gene alterations using the miRInform Thyroid test and with a 10-miRNA gene expression classifier generating positive (malignant) or negative (benign) results. Cross-sectional sampling of thyroid nodules with atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) or follicular neoplasm/suspicious for a follicular neoplasm (FN/SFN) cytology (n = 109) was conducted at 12 endocrinology centers across the United States. Qualitative molecular results were compared with surgical histopathology to determine diagnostic performance and model clinical effect. Mutations were detected in 69% of nodules with malignant outcome. Among mutation-negative specimens, miRNA testing correctly identified 64% of malignant cases and 98% of benign cases. The diagnostic sensitivity and specificity of the combined algorithm was 89% (95% confidence interval [CI], 73-97%) and 85% (95% CI, 75-92%), respectively. At 32% cancer prevalence, 61% of the molecular results were benign with a negative predictive value of 94% (95% CI, 85-98%). Independently of variations in cancer prevalence, the test increased the yield of true benign results by 65% relative to mRNA-based gene expression classification and decreased the rate of avoidable diagnostic surgeries by 69%. Multiplatform testing for DNA, mRNA, and miRNA can accurately classify benign and malignant thyroid nodules, increase the diagnostic yield of molecular cytology, and further improve the preoperative risk-based management of benign nodules with AUS/FLUS or FN/SFN cytology.

Diffuse thyroid 18F-FDG uptake after R-CHOP therapy predicts favorable outcome in patients with DLBCL.

PubMed

Song, Moo-Kon; Chung, Joo-Seop; Kim, Seong-Jang; Kim, Sang-Soo; Shin, Ho-Jin

2015-06-01

Therapy-induced autoimmunity may mediate the destruction of cancer cells. Previous studies have demonstrated that presence of autoimmune thyroid disorder is associated with favorable outcome in patients with solid cancer. Patients with diffuse large B cell lymphoma (DLBCL) who achieved complete response on positron emission tomography/computed tomography (PET/CT) after rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy were enrolled in this study. The patients with and without diffuse thyroid uptake (DTU) were classified by PET/CT. A total of 270 patients were enrolled in this study. DTU related to autoimmune thyroiditis was present in 61 patients. The median time to DTU detection was 5.7 months (range, 0-21.3 months). High International Prognostic Index (IPI) score (progression-free survival [PFS], p = 0.001; overall survival [OS], p = 0.008), bulky mass ≥10 cm (PFS, p = 0.001; OS, p = 0.001), bone marrow involvement (PFS, p < 0.001; OS, p = 0.001), and DTU after R-CHOP therapy (PFS, p < 0.001; OS, p = 0.001) were significantly associated with PFS and OS. High IPI score (PFS, p = 0.003; OS, p = 0.014), BM involvement (PFS, p = 0.009; OS, p = 0.039), and DTU after R-CHOP therapy (PFS, p = 0.002; OS, p = 0.002) were independently associated with PFS and OS. DTU after R-CHOP therapy independently predicted favorable outcomes in patients with DLBCL.

RISK FACTORS FOR NONREMISSION AND PROGRESSION-FREE SURVIVAL AFTER I-131 THERAPY IN PATIENTS WITH LUNG METASTASIS FROM DIFFERENTIATED THYROID CANCER: A SINGLE-INSTITUTE, RETROSPECTIVE ANALYSIS IN SOUTHERN CHINA.

PubMed

Chen, Pan; Feng, Hui-Juan; Ouyang, Wei; Wu, Ju-Qing; Wang, Jing; Sun, Yun-Gang; Xian, Jia-Lang; Huang, Liu-Hua

2016-09-01

Prognostic factors related to progression-free survival (PFS) have not received much attention in the literature regarding iodine-131 ((131)I) therapy for patients with differentiated thyroid cancer and lung metastases. We sought to explore the factors associated with PFS and nonremission in a group of patients with differentiated thyroid cancer and pulmonary metastases at initial diagnosis and to investigate the impact of (131)I therapy on pulmonary function and peripheral blood counts in the same cohort of patients. The medical records of 1,050 patients with differentiated thyroid cancer treated at the Zhujiang Hospital of Southern Medical University from January 2006 to January 2015 were retrospectively reviewed. Among them, 107 patients fulfilled the inclusion criteria. Multivariate Cox regression analysis indicated that age ≥45 years and (131)I nonavidity were independent risk factors for disease progression. Multivariate logistic regression analysis revealed that pulmonary nodule size ≥1 cm and (131)I nonavidity were the strongest risk factors predicting nonremission. Varying cumulative (131)I dosage had no association with posttreatment pulmonary function or peripheral blood cell counts. Similar to earlier studies, our results confirm that (131)I nonavidity was associated with an increased risk of disease progression and greater odds of nonremission. In addition, patients with differentiated thyroid cancer and lung metastases with pulmonary nodules ≥1 cm had a reduced likelihood of achieving remission. Furthermore, special attention is needed when monitoring patients over 45 years at a higher risk of disease progression. CI = confidence interval DTC = differentiated thyroid cancer (18)F-FDG = fluoro-18 fluorodeoxyglucose FEF = forced expiratory flow FTC = follicular thyroid cancer FVC = forced vital capacity GR = granulocytes Hb = hemoglobin HR = hazard ratio (131)I = iodine-131 LN = lymph node OR = odds ratio OS = overall survival PET/CT = positive positron emission tomography/computed tomography PFS = progression-free survival PT = partial thyroidectomy PTC = papillary thyroid cancer RAI = radioactive iodine RBC = red blood cell Tg = thyroglobulin TgAb = thyroglobulin antibody TSH = thyroid-stimulating hormone TT = total thyroidectomy WBC = white blood cells WBS = whole body scan.

Role of Virtual Touch Tissue Quantification in Hashimoto's Thyroiditis.

PubMed

Lin, Zi-Mei; Wang, Yao; Liu, Chun-Mei; Yan, Cao-Xin; Huang, Pin-Tong

2018-06-01

We investigated the role of the virtual touch tissue quantification (VTQ) technique in diagnosing Hashimoto's thyroiditis (HT) and in distinguishing various HT-related thyroid dysfunctions. Two hundred HT patients and 100 healthy volunteers (the control group) were enrolled. The diagnostic performance of VTQ in predicting HT was calculated as the area under the receiver operating characteristic curve (A Z ). The HT patients were further classified into three subgroups on the basis of serologic tests of thyroid function: hyperthyroidism, euthyroidism and hypothyroidism. Comparisons of shear wave velocity (SWV) between three subgroups were evaluated by analysis of variance. The mean SWV of the control group was significantly lower than that of the HT group (1.93 ± 0.33 m/s vs. 2.32 ± 0.49 m/s, p <0.001). A z was 0.734 with a cut-off value of 1.86 m/s for performance of SWV in distinguishing between HT and a healthy thyroid; the sensitivity and specificity were 82.5% and 50.0%, respectively. Mean SWV values in the three HT subgroups (hyperthyroidism [2.07 ± 0.37 cm/s] vs. euthyroidism [2.20 ± 0.40 cm/s] vs. hypothyroidism [2.49 ± 0.46 cm/s]) were significantly different (p <0.05). Our results suggest that VTQ is a promising technique for assessing HT and HT-related thyroid dysfunction. Copyright © 2018 World Federation for Ultrasound in Medicine and Biology. Published by Elsevier Inc. All rights reserved.

Follicular neoplasms of the thyroid: importance of clinical and cytological correlation.

PubMed

Granados-García, Martín; Cortés-Flores, Ana Olivia; del Carmen González-Ramírez, Imelda; Cano-Valdez, Ana María; Flores-Hernández, Lorena; Aguilar-Ponce, José Luis

2010-01-01

Thyroid cancer presents as nodules. Thyroid nodules are frequent, but only 5-30% are malignant. Fine needle aspiration biopsy (FNAB) is useful for initial evaluation; nevertheless, malignancy is uncertain when follicular neoplasm is reported. Some factors can be associated with malignancy. Therefore, we analyzed our follicular neoplasms in order to identify those factors associated with a higher risk of malignancy. We analyzed the clinical files of consecutive patients with cytological diagnoses of follicular neoplasm. From 1,005 cases of thyroid nodules, 121 were follicular neoplasms according to cytology. Of these, 75 were surgically treated. Definitive report showed 45 benign (60%) and 30 malignant (40%) cases. Benign cases included 29 goiters, 11 follicular adenomas, and 5 cases of thyroiditis. Malignant cases were comprised of 12 papillary carcinomas, 4 follicular carcinomas, 3 papillary carcinomas-follicular variant, 1 lymphoma, 1 teratoma, 5 medullary carcinomas, 2 insular carcinomas, 1 anaplastic carcinoma and 1 metastatic breast carcinoma. Tumor size of benign lesions was 3.43 ± 2.04 cm, and 4.67 ± 2.78 (p = 0.049) for malignant lesions. Age was 46.95 ± 15.39 years for benign lesions and 48.67 ± 17.28 for malignant lesions (p = 0.66). Fifty percent of males showed malignancy vs. 37.7% of females (p < 0.005). Our results suggest that size and gender, but not age, are associated with cytological pattern. Ultrasonographic characteristics may be useful discriminating patients with a higher risk of malignancy. FNAB is a useful tool for initial evaluation of thyroid nodules, but clinical evaluation can enhance predictive value.

[Neonatal hyperthyroidism in a premature infant born to a mother with Grave's disease].

PubMed

Nicaise, C; Gire, C; Brémond, V; Minodier, P; Soula, F; d'Ercole, C; Palix, C

2000-05-01

Neonatal thyrotoxicosis is most commonly due to transplacental transfer of maternal thyroid-stimulating hormone receptor antibodies (TRAb). Bioassay of thyrotropin receptor antibodies may help to determine the risk for neonatal hyperthyroidism. Thyrotoxicosis developed in a premature infant born to a mother with Graves' disease, with a low level of TRAb by bioassay. The infant was treated with carbimazole for two months, until TRAb had disappeared. Bioassay TRAb is not always reliable for predicting the development of neonatal hyperthyroidism in infants born to mothers with Graves' disease. Thyroid function should be measured in all these neonates.

[Fine-needle aspiration (FNA) of the thyroid gland : Analysis of discrepancies between cytological and histological diagnoses].

PubMed

Dalquen, P; Rashed, B; Hinsch, A; Issa, R; Clauditz, T; Luebke, A; Lüttges, J; Saeger, W; Bohuslavizki, K H

2016-09-01

Diagnostic problems of thyroid cytology are frequently discussed, but relevance and causes of discrepant cytological and histological diagnoses are rarely studied in detail. Investigation of causes and relevance of discrepant diagnoses. The analysis includes 297 patients who had thyroid resection after prior fine needle aspiration (FNA) and is based on the cytological and histological reports. In special cases, cytological and histological specimens were re-examined. Malignant tumors were found in 45 patients (15.1 %). In 5 patients the cytological diagnosis was "false negative". Three of these 5 tumors were papillary carcinomas (PTC) of ≤10 mm, one an obviously nonmalignant papillary proliferation of the thyroidal epithelium and one a malignant lymphoma complicating autoimmune thyreoiditis (AIT). In 11 of the 35 patients with a FNA diagnosis "suspicious of malignancy" or "malignant," 1 AIT, 4 goiter nodules, and 6 adenomas were diagnosed histologically. However, since distinct nuclear atypia was found in three of five false positive diagnoses, there still remains doubt in their benignity. Carcinomas of ≤10 mm incidentally detected in the resected thyroid tissue may not be relevant to the patient and do not reduce the high negative predictive value of FNA. The final diagnosis on the resected tissue should include the cytological findings. Discrepant findings should be commented in the report to the clinician.

The Profile of Heparanase Expression Distinguishes Differentiated Thyroid Carcinoma from Benign Neoplasms

PubMed Central

Matos, Leandro Luongo; Suarez, Eloah Rabello; Theodoro, Thérèse Rachell; Trufelli, Damila Cristina; Melo, Carina Mucciolo; Garcia, Larissa Ferraz; Oliveira, Olivia Capela Grimaldi; Matos, Maria Graciela Luongo; Kanda, Jossi Ledo; Nader, Helena Bonciani; Martins, João Roberto Maciel; Pinhal, Maria Aparecida Silva

2015-01-01

Introduction The search for a specific marker that could help to distinguish between differentiated thyroid carcinoma and benign lesions remains elusive in clinical practice. Heparanase (HPSE) is an endo-beta-glucoronidase implicated in the process of tumor invasion, and the heparanase-2 (HPSE2) modulates HPSE activity. The aim of this study was to evaluate the role of heparanases in the development and differential diagnosis of follicular pattern thyroid lesions. Methods HPSE and HPSE2 expression by qRT-PCR, immunohistochemistry evaluation, western blot analysis and HPSE enzymatic activity were evaluated. Results The expression of heparanases by qRT-PCR showed an increase of HPSE2 in thyroid carcinoma (P = 0.001). HPSE activity was found to be higher in the malignant neoplasms than in the benign tumors (P<0.0001). On Western blot analysis, HPSE2 isoforms were detected only in malignant tumors. The immunohistochemical assay allowed us to establish a distinct pattern for malignant and benign tumors. Carcinomas showed a typical combination of positive labeling for neoplastic cells and negative immunostaining in colloid, when compared to benign tumors (P<0.0001). The proposed diagnostic test presents sensitivity and negative predictive value of around 100%, showing itself to be an accurate test for distinguishing between malignant and benign lesions. Conclusions This study shows, for the first time, a distinct profile of HPSE expression in thyroid carcinoma suggesting its role in carcinogenesis. PMID:26488476

Identification of Novel Genetic Loci Associated with Thyroid Peroxidase Antibodies and Clinical Thyroid Disease

PubMed Central

Teumer, Alexander; Brown, Suzanne J.; Jensen, Richard A.; Rawal, Rajesh; Roef, Greet L.; Plantinga, Theo S.; Vermeulen, Sita H.; Lahti, Jari; Simmonds, Matthew J.; Husemoen, Lise Lotte N.; Freathy, Rachel M.; Shields, Beverley M.; Pietzner, Diana; Nagy, Rebecca; Broer, Linda; Chaker, Layal; Korevaar, Tim I. M.; Plia, Maria Grazia; Sala, Cinzia; Völker, Uwe; Richards, J. Brent; Sweep, Fred C.; Gieger, Christian; Corre, Tanguy; Kajantie, Eero; Thuesen, Betina; Taes, Youri E.; Visser, W. Edward; Hattersley, Andrew T.; Kratzsch, Jürgen; Hamilton, Alexander; Li, Wei; Homuth, Georg; Lobina, Monia; Mariotti, Stefano; Soranzo, Nicole; Cocca, Massimiliano; Nauck, Matthias; Spielhagen, Christin; Ross, Alec; Arnold, Alice; van de Bunt, Martijn; Liyanarachchi, Sandya; Heier, Margit; Grabe, Hans Jörgen; Masciullo, Corrado; Galesloot, Tessel E.; Lim, Ee M.; Reischl, Eva; Leedman, Peter J.; Lai, Sandra; Delitala, Alessandro; Bremner, Alexandra P.; Philips, David I. W.; Beilby, John P.; Mulas, Antonella; Vocale, Matteo; Abecasis, Goncalo; Forsen, Tom; James, Alan; Widen, Elisabeth; Hui, Jennie; Prokisch, Holger; Rietzschel, Ernst E.; Palotie, Aarno; Feddema, Peter; Fletcher, Stephen J.; Schramm, Katharina; Rotter, Jerome I.; Kluttig, Alexander; Radke, Dörte; Traglia, Michela; Surdulescu, Gabriela L.; He, Huiling; Franklyn, Jayne A.; Tiller, Daniel; Vaidya, Bijay; de Meyer, Tim; Jørgensen, Torben; Eriksson, Johan G.; O'Leary, Peter C.; Wichmann, Eric; Hermus, Ad R.; Psaty, Bruce M.; Ittermann, Till; Hofman, Albert; Bosi, Emanuele; Schlessinger, David; Wallaschofski, Henri; Pirastu, Nicola; Aulchenko, Yurii S.; de la Chapelle, Albert; Netea-Maier, Romana T.; Gough, Stephen C. L.; Meyer zu Schwabedissen, Henriette; Frayling, Timothy M.; Kaufman, Jean-Marc; Linneberg, Allan; Räikkönen, Katri; Smit, Johannes W. A.; Kiemeney, Lambertus A.; Rivadeneira, Fernando; Uitterlinden, André G.; Walsh, John P.; Meisinger, Christa; den Heijer, Martin; Visser, Theo J.; Spector, Timothy D.; Wilson, Scott G.; Völzke, Henry; Cappola, Anne; Toniolo, Daniela; Sanna, Serena; Naitza, Silvia; Peeters, Robin P.

2014-01-01

Autoimmune thyroid diseases (AITD) are common, affecting 2-5% of the general population. Individuals with positive thyroid peroxidase antibodies (TPOAbs) have an increased risk of autoimmune hypothyroidism (Hashimoto's thyroiditis), as well as autoimmune hyperthyroidism (Graves' disease). As the possible causative genes of TPOAbs and AITD remain largely unknown, we performed GWAS meta-analyses in 18,297 individuals for TPOAb-positivity (1769 TPOAb-positives and 16,528 TPOAb-negatives) and in 12,353 individuals for TPOAb serum levels, with replication in 8,990 individuals. Significant associations (P<5×10−8) were detected at TPO-rs11675434, ATXN2-rs653178, and BACH2-rs10944479 for TPOAb-positivity, and at TPO-rs11675434, MAGI3-rs1230666, and KALRN-rs2010099 for TPOAb levels. Individual and combined effects (genetic risk scores) of these variants on (subclinical) hypo- and hyperthyroidism, goiter and thyroid cancer were studied. Individuals with a high genetic risk score had, besides an increased risk of TPOAb-positivity (OR: 2.18, 95% CI 1.68–2.81, P = 8.1×10−8), a higher risk of increased thyroid-stimulating hormone levels (OR: 1.51, 95% CI 1.26–1.82, P = 2.9×10−6), as well as a decreased risk of goiter (OR: 0.77, 95% CI 0.66–0.89, P = 6.5×10−4). The MAGI3 and BACH2 variants were associated with an increased risk of hyperthyroidism, which was replicated in an independent cohort of patients with Graves' disease (OR: 1.37, 95% CI 1.22–1.54, P = 1.2×10−7 and OR: 1.25, 95% CI 1.12–1.39, P = 6.2×10−5). The MAGI3 variant was also associated with an increased risk of hypothyroidism (OR: 1.57, 95% CI 1.18–2.10, P = 1.9×10−3). This first GWAS meta-analysis for TPOAbs identified five newly associated loci, three of which were also associated with clinical thyroid disease. With these markers we identified a large subgroup in the general population with a substantially increased risk of TPOAbs. The results provide insight into why individuals with thyroid autoimmunity do or do not eventually develop thyroid disease, and these markers may therefore predict which TPOAb-positives are particularly at risk of developing clinical thyroid dysfunction. PMID:24586183

Prediction of infarct severity from triiodothyronine levels in patients with ST-elevation myocardial infarction.

PubMed

Kim, Dong Hun; Choi, Dong-Hyun; Kim, Hyun-Wook; Choi, Seo-Won; Kim, Bo-Bae; Chung, Joong-Wha; Koh, Young-Youp; Chang, Kyong-Sig; Hong, Soon-Pyo

2014-07-01

The aim of the present study was to evaluate the relationship between thyroid hormone levels and infarct severity in patients with ST-elevation myocardial infarction (STEMI). We retrospectively reviewed thyroid hormone levels, infarct severity, and the extent of transmurality in 40 STEMI patients evaluated via contrast-enhanced cardiac magnetic resonance imaging. The high triiodothyronine (T3) group (≥ 68.3 ng/dL) exhibited a significantly higher extent of transmural involvement (late transmural enhancement > 75% after administration of gadolinium contrast agent) than did the low T3 group (60% vs. 15%; p = 0.003). However, no significant difference was evident between the high- and low-thyroid-stimulating hormone/free thyroxine (FT4) groups. When the T3 cutoff level was set to 68.3 ng/dL using a receiver operating characteristic curve, the sensitivity was 80% and the specificity 68% in terms of differentiating between those with and without transmural involvement. Upon logistic regression analysis, high T3 level was an independent predictor of transmural involvement after adjustment for the presence of diabetes mellitus (DM) and the use of glycoprotein IIb/IIIa inhibitors (odds ratio, 40.62; 95% confidence interval, 3.29 to 502; p = 0.004). The T3 level predicted transmural involvement that was independent of glycoprotein IIb/IIIa inhibitor use and DM positivity.

How to manage thyroid nodules with two consecutive non-diagnostic results on ultrasonography-guided fine-needle aspiration.

PubMed

Moon, Hee Jung; Kwak, Jin Young; Choi, Yoon Seong; Kim, Eun-Kyung

2012-03-01

The aim of this study was to investigate the factors for considering surgery on thyroid nodules that had non-diagnostic results on two consecutive cytology examinations. A total of 104 thyroid nodules with two consecutive non-diagnostic cytology examinations in 104 patients were investigated. Nodules with one or more suspicious ultrasonography (US) features of marked hypoechogenicity, a not well defined margin, microcalcifications, or a taller-than-wide shape were assessed as sonographically suspicious. Those without any suspicious features were assessed as sonographically benign. The clinicopathologic characteristics of patients and US features of the nodules were compared according to malignancy and benignity. The odds ratio for predicting malignancy was calculated. Altogether, 12 nodules were malignant, and 92 were benign. Age, sex, nodule size, and solidness were not associated with malignancy (P = 0.73, 0.92, 0.48, and 0.73, respectively). The malignancy rate of sonographically suspicious nodules was 25.7%, higher than the 4.3% of sonographically benign nodules (P = 0.002). The odds ratio of sonographically suspicious nodules for predicting malignancy was 16.01 (95% confidence interval 2.36-108.54, P = 0.005). Based on sonographic features, surgery can be performed selectively on nodules with two consecutive non-diagnostic cytology results.

Thyroid cartilage invasion in laryngeal and hypopharyngeal squamous cell carcinoma treated with total laryngectomy.

PubMed

Koopmann, Mario; Weiss, Daniel; Steiger, Matthias; Elges, Sandra; Rudack, Claudia; Stenner, Markus

2016-11-01

The objective of this study is to analyze the accuracy of computed tomography in detecting malignant thyroid cartilage invasion. In a retrospective chart review, 120 patients with carcinoma of the larynx and hypopharynx underwent computed tomography before total laryngectomy. These data were compared with the histological specimens. Multidetector computed tomography (MDCT) scan had a positive predictive value (PPV) of 76 % and a negative predictive value (NPV) of 69 %. The specificity of MDCT was 89 % and sensitivity was 46 %. Comparison between radiologic suspected cartilage invasion and histologic results showed a significant correlation (p < 0.02). We found no significant impact of cartilage invasion concerning survival rates (5-year overall survival p = 0.683; 5-year disease-free survival p = 0.711). Preoperative CT scan is an important instrument in detecting neoplastic cartilage invasion.

Heritability of levels of autoantibodies to thyroid antigens using the method of plotting regression of offspring on midparent (ROMP).

PubMed

Outschoorn, Ingrid M; Hoffman, William H; Rose, Noel R; Burek, C Lynne

2007-07-01

Only a few methods can be applied in a simple manner to estimate the genetic control of autoimmunity in humans. Here we examined the heritability of autoantibodies to two thyroid antigens; thyroglobulin (Tg) and thyroperoxidase (TPO, formerly known as thyroid microsomal antigen), using methods of regression of offspring on mid-parental values (ROMP). With the data sets available, affected and unaffected siblings were compared by this rapid screening method using results determined by hemagglutination (HA). The presence of both types of autoantibodies showed positive heritability in patients with Graves' thyrotoxicosis (TT), but it was not observed in chronic lymphocytic or Hashimoto's thyroiditis (CLT) patients. Since these assays have been extensively used over the years by most diagnostic and research laboratories, they should provide some insight as to which quantifiable parameters may be usefully accumulated to help select groups of patients and their families for further genetic study. ROMP may also be useful to determine the sequential appearance of different types of antibody in predicting disease onset in other family members, and in distinguishing maternal and paternal effects on imprinting. The method may be extended to study epitope spreading and other measures of disease progression.

Solid papillary carcinoma with reverse polarity of the breast harbors specific morphologic, immunohistochemical and molecular profile in comparison with other benign or malignant papillary lesions of the breast: a comparative study of 9 additional cases.

PubMed

Alsadoun, Nadjla; MacGrogan, Gaëtan; Truntzer, Caroline; Lacroix-Triki, Magali; Bedgedjian, Isabelle; Koeb, Marie-Hélène; El Alam, Elsy; Medioni, Dan; Parent, Michel; Wuithier, Pascal; Robert, Isabelle; Boidot, Romain; Arnould, Laurent

2018-05-21

Solid papillary carcinoma with reverse polarity is a rare breast cancer of favorable prognosis that can be difficult to diagnose. We report here nine additional cases of this tumor, and we describe its morphologic, immunohistochemical and molecular profile in comparison to other types of papillary and micropapillary lesions of the breast that are intraductal papilloma with usual ductal hyperplasia, encapsulated papillary carcinoma, solid papillary carcinoma and invasive micropapillary carcinoma. We studied nine cases of this special papillary tumor and six of each other types mentioned above. We found that solid papillary carcinoma with reverse polarity harbor specific morphologic features as cuboid or tall cells with abundant eosinophilic cytoplasms located at the basal pole giving the impression of reverse nuclear polarity. Nuclei were sometimes grooved. Immunohistochemistry demonstrated the lack of myoepithelial cells, as in encapsulated papillary carcinoma and solid papillary carcinoma, questioning their invasive nature. Seven of nine solid papillary carcinoma with reverse polarity showed a low Ki67 proliferative index (Ki67 <5%). They showed expression of CK5/6 as in intraductal papilloma with usual ductal hyperplasia. They showed expression of calretinin and a low or lack of hormonal receptor (HR) expression that were not observed in other breast tumors studied. By whole-exome analysis, seven of nine solid papillary carcinomas with reverse polarity (78%) harbored a hotspot mutation in IDH2 (R172) that was totally absent in other groups. Six of nine tumors (67%) also harbored PRUNE2 mutation, including the two IDH2 wild-type cases. We also demonstrated for the first time in this breast tumor, immunostaining with a specific antibody IDH1/2 mutant R132/R172 (7/9) that can highlight IDH2 mutation. Moreover, transcriptomic analysis showed that proteoglycan pathway was significantly enriched. Our findings support the fact that solid papillary carcinoma with reverse polarity is a singular breast neoplasm that can be distinguished from other papillary breast tumors.

Strain ratio ultrasound elastography increases the accuracy of colour-Doppler ultrasound in the evaluation of Thy-3 nodules. A bi-centre university experience.

PubMed

Cantisani, Vito; Maceroni, Piero; D'Andrea, Vito; Patrizi, Gregorio; Di Segni, Mattia; De Vito, Corrado; Grazhdani, Hektor; Isidori, Andrea M; Giannetta, Elisa; Redler, Adriano; Frattaroli, Fabrizio; Giacomelli, Laura; Di Rocco, Giorgio; Catalano, Carlo; D'Ambrosio, Ferdinando

2016-05-01

To assess whether ultrasound elastography (USE) with strain ratio increases diagnostic accuracy of Doppler ultrasound in further characterisation of cytologically Thy3 thyroid nodules. In two different university diagnostic centres, 315 patients with indeterminate cytology (Thy3) in thyroid nodules aspirates were prospectively evaluated with Doppler ultrasound and strain ratio USE before surgery. Ultrasonographic features were analysed separately and together as ultrasound score, to assess sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). Receiver operating characteristic (ROC) curves to identify optimal cut-off value of the strain ratio were also provided. Diagnosis on a surgical specimen was considered the standard of reference. Higher strain ratio values were found in malignant nodules, with an optimum strain ratio cut-off of 2.09 at ROC analysis. USE with strain ratio showed 90.6% sensitivity, 93% specificity, 82.8% PPV, 96.4% NPV, while US score yielded a sensitivity of 52.9%, specificity of 84.3%, PPV 55.6% and NPV 82.9%. The diagnostic gain with strain ratio was statistically significant as proved by ROC areas, which was 0.9182 for strain ratio and 0.6864 for US score. USE with strain ratio should be considered a useful additional tool to colour-Doppler US, since it improves characterisation of thyroid nodules with indeterminate cytology. • Strain ratio measurements improve differentiation of thyroid nodules with indeterminate cytology • Elastography with strain ratio is more reliable than ultrasound features and ultrasound score • Strain ratio may help to better select patients with Thy 3 nodules candidate for surgery.

Approximate distribution of dose among foetal organs for radioiodine uptake via placenta transfer

NASA Astrophysics Data System (ADS)

Millard, R. K.; Saunders, M.; Palmer, A. M.; Preece, A. W.

2001-11-01

Absorbed radiation doses to internal foetal organs were calculated according to the medical internal radiation dose (MIRD) technique in this study. Anthropomorphic phantoms of the pregnant female as in MIRDOSE3 enabled estimation of absorbed dose to the whole foetus at two stages of gestation. Some foetal organ self-doses could have been estimated by invoking simple spherical models for thyroid, liver, etc, but we investigated the use of the MIRDOSE3 new-born phantom as a surrogate for the stage 3 foetus, scaled to be compatible with total foetal body mean absorbed dose/cumulated activity. We illustrate the method for obtaining approximate dose distribution in the foetus near term following intake of 1 MBq of 123I, 124I, 125I or 131I as sodium iodide by the mother using in vivo biodistribution data examples from a good model of placenta transfer. Doses to the foetal thyroid of up to 1.85 Gy MBq-1 were predicted from the 131I uptake data. Activity in the foetal thyroid was the largest contributor to absorbed dose in the foetal body, brain, heart and thymus. Average total doses to the whole foetus ranged from 0.16 to 1.2 mGy MBq-1 for stages 1 and 3 of pregnancy using the MIRDOSE3 program, and were considerably higher than those predicted from the maternal contributions alone. Doses to the foetal thymus and stomach were similar, around 2-3 mGy MBq-1. Some foetal organ doses from the radioiodides were ten times higher than to the corresponding organs of the mother, and up to 100 times higher to the thyroid. The fraction of activity uptakes in foetal organs were distributed similarly to the maternal ones.

Efficacy and Safety of Radiofrequency Ablation for Benign Thyroid Nodules: A Prospective Multicenter Study

PubMed Central

Jung, So Lyung; Lee, Jeong Hyun; Shong, Young Kee; Sung, Jin Yong; Kim, Kyu Sun; Lee, Ducky; Kim, Ji-hoon; Baek, Seon Mi; Sim, Jung Suk; Na, Dong Gyu

2018-01-01

Objective To assess the efficacy and safety of thyroid radiofrequency (RF) ablation for benign thyroid nodules by trained radiologists according to a unified protocol in a multi-center study. Materials and Methods From 2010 to 2011, 345 nodules from 345 patients (M:F = 43:302; mean age ± SD = 46.0 ± 12.7 years, range = 15–79) who met eligibility criteria were enrolled from five institutions. At pre-ablation, the mean volume was 14.2 ± 13.2 mL (1.1–80.8 mL). For 12 months or longer after treatment, 276 lesions, consisting of 248 solid and 28 predominantly cystic nodules, were followed. All operators performed RF ablation with a cool-tip RF system and two standard techniques (a transisthmic approach and the moving-shot technique). Volume reduction at 12 months after RF ablation (the primary outcome), therapeutic success, improvement of symptoms as well as of cosmetic problems, and complications were evaluated. Multiple linear regression analysis was applied to identify factors that were independently predictive of volume reduction. Results The mean volume reduction at 12 months was 80.3% (n = 276) and at the 24-, 36-, 48-, and 60-month follow-ups 84.3% (n = 198), 89.2% (n = 128), 91.9% (n = 57), and 95.3% (n = 6), respectively. Our therapeutic success was 97.8%. Both mean symptom and cosmetic scores showed significant improvements (p < 0.001). The rate of major complications was 1.0% (3/276). Solidity and applied energy were independent factors that predicted volume reduction. Conclusion Radiofrequency ablation performed by trained radiologists from multiple institutions using a unified protocol and similar devices was effective and safe for treating benign thyroid nodules. PMID:29354014

The BRAFT1799A mutation is not associated with occult contralateral carcinoma in patients with unilateral papillary thyroid microcarcinoma.

PubMed

Wan, Han-Feng; Zhang, Bin; Yan, Dan-Gui; Xu, Zhen-Gang

2015-01-01

The phenomenon of occult carcinoma maybe observed in patients with clinically unilateral papillary thyroid microcarcinoma (PTMC). Although many studies have reported that the BRAFT1799A mutation is associated with aggressive PTMC, the relationship between BRAFT1799A mutation and occult carcinoma is unclear. The aim of this study was to investigate the risk factors, including BRAFT1799A mutation, for occult contralateral carcinoma in clinically unilateral PTMC accompanied by benign nodules in the contralateral lobe. From January 2011 to December 2013,we prospectively enrolled 89 consecutive PTMC patients with clinically unilateral carcinoma accompanied by benign nodules in the contralateral lobe who received a total thyroidectomy and cervical lymph node dissection. BRAFT1799A mutation was tested by pyrosequencing on postoperative paraffin specimens. The frequency and predictive factors for occult contralateral carcinoma were analyzed with respect to the following variables: age, gender, family history, tumor size, presence of Hashimoto thyroiditis, extrathyroidal extension, central lymph node metastasis, multifocality of primary tumor, or BRAFT1799A mutation. A total of 36 patients (40.4%) had occult PTMC in the contralateral lobe. The median diameter of the occult tumors was 0.33±0.21 cm. The BRAFT1799A mutation was found in 38 cases (42.7%). According to the univariate analysis, there were no significant differences between the presence of occult contralateral carcinoma and age, gender, family history, tumor size, presence of Hashimoto thyroiditis, extrathyroidal extension, central lymph node metastasis, multifocality of primary tumor, or BRAFT1799A mutation. Using current methods, it is difficult to preoperatively identify patients with PTMC, and further research is needed to determine predictive factors for the presence of occult contralateral carcinoma in patients with unilateral PTMC.

Combined value of Virtual Touch tissue quantification and conventional sonographic features for differentiating benign and malignant thyroid nodules smaller than 10 mm.

PubMed

Zhang, Huiping; Shi, Qiusheng; Gu, Jiying; Jiang, Luying; Bai, Min; Liu, Long; Wu, Ying; Du, Lianfang

2014-02-01

This study aimed to investigate the value of sonographic features including Virtual Touch tissue quantification (VTQ; Siemens Medical Solutions, Mountain View, CA) for differentiating benign and malignant thyroid nodules smaller than 10 mm. Seventy-one thyroid nodules smaller than 10 mm with pathologic diagnoses were included in this study. The conventional sonographic features and quantitative elasticity features (VTQ) were observed and compared between benign and malignant nodules. There were 39 benign and 32 malignant nodules according to histopathologic examination. When compared with benign nodules, malignant nodules were more frequently taller than wide, poorly defined, and markedly hypoechoic (P < .05). Color Doppler sonographic features were not significantly different between benign and malignant nodules. The VTQ value for malignant nodules (mean ± SD 3.260 ± 0.725 m/s) was significantly higher than that of benign ones (2.108 ± 0.455 m/s; P < .001). The cutoff point for the differential diagnosis was 2.910 m/s, with sensitivity, specificity, a positive predictive value, a negative predictive value, and diagnostic accuracy of 71.9%, 100%, 100%, 81.2%, and 87.3% respectively. Logistic regression analysis showed that a taller-than-wide shape, a poorly defined boundary, marked hypoechogenicity, and a VTQ value greater than 2.910 m/s were independent risk factors for malignancy, with odds ratios of 69.366, 41.864, 5.945, and 64.991. The combination of VTQ with a taller-than-wide shape had the highest sensitivity and specificity of 90.6% and 97.4%. The shape, margin, echogenicity, and VTQ value are useful sonographic criteria for differentiating benign and malignant thyroid nodules smaller than 10 mm. When VTQ was combined with B-mode sonographic features, the sensitivity was improved significantly.

Predictive value of tracer studies for /sup 131/I treatment in hyperthyroid cats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Broome, M.R.; Turrel, J.M.; Hays, M.T.

In 76 cats with hyperthyroidism, peak thyroidal radioiodine (/sup 131/I) uptakes and effective half-lives were determined after administration of tracer and therapeutic activities of /sup 131/I. In 6 additional hyperthyroid cats, only peak thyroidal uptakes after administration of tracer and therapeutic activities of /sup 131/I were determined. Good correlation was found between peak thyroidal uptakes of tracer and therapeutic /sup 131/I; however, only fair correlation was observed between effective half-lives. In 79% of the cats, the effective half-life for therapeutic /sup 131/I was longer than that for tracer /sup 131/I. After administration of therapeutic activity of /sup 131/I, monoexponential andmore » biphasic decay curves were observed in 51 and 16 cats, respectively. Using therapeutic kinetic data, radiation doses to the thyroid gland were calculated retrospectively on the basis of 2 methods for determining the activity of /sup 131/I administered: (1) actual administration of tracer-compensated activity and (2) hypothetic administration of uniform activity (3 mCi). Because of the good predictive ability of tracer kinetic data for the therapeutic kinetic data, the tracer-compensated radiation doses came significantly (P = 0.008) closer to the therapeutic goal than did the uniform-activity doses. In addition, the use of tracer kinetic information reduced the extent of the tendency for consistently high uniform-activity doses. A manual method for acquiring tracer kinetic data was developed and was an acceptable alternative to computerized techniques. Adoption of this method gives individuals and institutions with limited finances the opportunity to characterize the iodine kinetics in cats before proceeding with administration of therapeutic activities of /sup 131/I.« less

Pesticides in mixture disrupt metabolic regulation: in silico and in vivo analysis of cumulative toxicity of mancozeb and imidacloprid on body weight of mice.

PubMed

Bhaskar, Rakesh; Mohanty, Banalata

2014-09-01

Pesticides acting as endocrine disrupting chemicals disrupt the homeostasis of body metabolism. The present study elucidated that the low dose coexposure of thyroid disrupting dithiocarbamate fungicide mancozeb (MCZ) and neonicotinoid insecticide imidacloprid (IMI) during lactation increased the risk of body weight gain in mice later in life. Body weight gain has been linked to pesticide-induced hypothyroidism and hyperprolactinemia and alteration of lipid profiles. In vivo results were substantiated with in silico molecular docking (MD) analysis that predicted the binding affinity of pesticides with thyroid hormone receptors (TRα and TRβ) and peroxisome proliferator activated receptor gamma (PPARγ), the major nuclear receptors of peripheral fat metabolism. Binding potency of MCZ and IMI was compared with that of T3, and its antagonist ethylene thiourea (ETU) as well as PPARγ agonist (rosiglitazone) and antagonist (HL005). MD simulation predicted that both MCZ and IMI may compete with T3 for binding with TRs. Imidazole group of IMI formed hydrogen bonds with TRs like that of ETU. MCZ may compete with rosiglitazone and HL005 for PPARγ, but IMI showed no affinity. Thus while both MCZ and IMI could disrupt the TRs functioning, MCZ alone may affect PPARγ. Coexposure of pesticides decreased the plasma thyroid hormones and increased the cholesterol and triglyceride. Individual pesticide exposure in low dose might not exert the threshold response to affect the receptors signaling further to cause hormonal/metabolic impairment. Thus, cumulative response of the mixture of thyroid disrupting pesticides can disrupt metabolic regulation through several pathways and contribute to gain in body weight. Copyright © 2014 Elsevier Inc. All rights reserved.

The utility of radioiodine uptake and thyroid scintigraphy in the diagnosis and management of hyperthyroidism.

PubMed

Okosieme, O E; Chan, D; Price, S A; Lazarus, J H; Premawardhana, L D K E

2010-01-01

The value and practice of thyroid radionuclide imaging in the diagnosis and management of hyperthyroidism is unsettled. Our objectives were to determine the influence of thyroid uptake and scintigraphy on the diagnosis of hyperthyroidism and the prediction of outcome following radioiodine therapy. We reviewed records and scintigraphic studies on 881 hyperthyroid patients carried out between 2000 and 2007. The agreement between the clinical and scintigraphic diagnosis was evaluated by kappa statistics. We determined the relationship between 4-h (123)I uptake and the outcome of (131)I treatment in 626 patients. A multiple logistic regression model was used to determine variables influencing treatment outcome in 1 year. The diagnostic categories were Graves' disease (GD, n = 383), toxic multinodular goitre (n = 253), solitary toxic nodule (n = 164) and Graves' disease coexisting with nodules (n = 81). The mean age of the patients was 58 +/- 17, (M:F 160:721). There was good agreement between clinical and scintigraph diagnosis (K = 0.60, 95% CI 0.57-0.64, P < 0.001); and they were correctly matched in 74%; mismatched in 6% and indeterminate in 20% of patients. Treatment outcome was not associated with scintigraph diagnosis (P = 0.98) or radioiodine uptake at 4 h (P = 0.2). The use of antithyroid medications before treatment predicted treatment failure (odds ratio 2.0, 95% CI 1.2-3.6, P = 0.01). Thyroid scintigraphy and uptake studies did not influence diagnosis or treatment outcomes in most cases of hyperthyroidism. Our findings in this retrospective study do not justify their routine use. Selective scanning will reduce cost and exposure to radioisotopes without compromising diagnostic accuracy or treatment outcomes.

Age, tumor size, and in-office ultrasonography are predictive parameters of malignancy in follicular neoplasms of the thyroid.

PubMed

Paramo, Juan C; Mesko, Thomas

2008-01-01

To identify clinical predictors of malignancy in patients with intraoperative frozen-section diagnosis of follicular neoplasm of the thyroid. We performed a retrospective cross-sectional study of 71 patients with intraoperative frozen-section diagnosis of follicular neoplasm who underwent thyroidectomy between January 1992 and December 2000. Age, sex, tumor size, and in-office ultrasonography characteristics of the lesions were assessed. These clinical factors were compared between cases that had benign definitive pathologic findings and those that were found to be carcinomas on permanent sections. Nine (13%) of the 71 follicular neoplasms were found to be carcinomas after definitive pathologic evaluation. The incidence of malignancy was 13% (2/16) in men and 13% (7/55) in women (P>.5). Patients younger than 45 years had a 27% (8/30) incidence of malignancy compared with 2% (1/41) in patients 45 years or older (P<.01). Of tumors smaller than 4 cm, 7% (4/55) were ultimately diagnosed as carcinomas compared with 31% (5/16) of those 4 cm or larger (P = .05). When the in-office ultrasonography findings were interpreted as benign, only 7% (3/46) of cases were malignant compared with 40% (4/10) when the ultrasonography findings were suspicious (P = .02). Age and tumor size are predictive parameters of malignancy in follicular neoplasm of the thyroid. Suspicious ultrasonography findings also have an important predictive role. Total thyroidectomy is reasonable in patients with follicular neoplasm on frozen section if they are young (<45 years old), with large (>4 cm) tumors or if there are suspicious findings on in-office ultrasonography.

Prospective evaluation of intra-operative quick parathyroid hormone assay as an early predictor of post thyroidectomy hypocalcaemia.

PubMed

Reddy, Ashwini C; Chand, Gyan; Sabaretnam, M; Mishra, Anjali; Agarwal, Gaurav; Agarwal, Amit; Verma, A K; Mishra, S K

2016-10-01

Hypocalcaemia following total thyroidectomy is a major contributing factor in delayed hospital discharge and dissuading surgeons from day care thyroidectomy. We prospectively evaluated the utility of Intra-operative serum quick parathyroid hormone level measurement twenty minutes after total thyroidectomy in predicting post-operative hypocalcemia. Prospective longitudinal study which included patients undergoing total thyroidectomy for benign or malignant thyroid disorders at SGPGIMS, Lucknow, India from November 2013 to February 2015. Patients who received calcium prophylaxis were excluded from the study. Intraoperative serum quick PTH level measurements were done twenty minutes after resection of thyroid. Serum calcium levels were estimated preoperatively and on three consecutive post operative days. Calcium supplementation was started in patients with symptomatic hypocalcemia. The study included 100 patients with a mean age of 41 years, range 17-72 years. 48 patients had Euthyroid multinodular goitre, 10 patients grave's disease and 42 patients had differentiated thyroid cancer. Total thyroidectomy was performed in 88 patients, total thyroidectomy with lymph node dissection in 12 patients. Post-operatively 23% patients experienced symptomatic hypocalcemia. The IOPTH level of 9 pmol/L, twenty minutes after total thyroidectomy, had the highest sensitivity and specificity of 92% and 83% respectively in predicting post-operative hypocalcemia. Parathyroid hormone assay twenty minutes after thyroidectomy is an accurate and reliable means of predicting clinically relevant hypocalcemia. Patients with PTH values greater than 9 pmol/L twenty minutes after thyroidectomy, can be safely discharged on the same postoperative day as the probability of life threatening hypocalcemia is unlikely. Copyright © 2016. Published by Elsevier Ltd.

Variation of normal tissue complication probability (NTCP) estimates of radiation-induced hypothyroidism in relation to changes in delineation of the thyroid gland.

PubMed

Rønjom, Marianne F; Brink, Carsten; Lorenzen, Ebbe L; Hegedüs, Laszlo; Johansen, Jørgen

2015-01-01

To examine the variations of risk-estimates of radiation-induced hypothyroidism (HT) from our previously developed normal tissue complication probability (NTCP) model in patients with head and neck squamous cell carcinoma (HNSCC) in relation to variability of delineation of the thyroid gland. In a previous study for development of an NTCP model for HT, the thyroid gland was delineated in 246 treatment plans of patients with HNSCC. Fifty of these plans were randomly chosen for re-delineation for a study of the intra- and inter-observer variability of thyroid volume, Dmean and estimated risk of HT. Bland-Altman plots were used for assessment of the systematic (mean) and random [standard deviation (SD)] variability of the three parameters, and a method for displaying the spatial variation in delineation differences was developed. Intra-observer variability resulted in a mean difference in thyroid volume and Dmean of 0.4 cm(3) (SD ± 1.6) and -0.5 Gy (SD ± 1.0), respectively, and 0.3 cm(3) (SD ± 1.8) and 0.0 Gy (SD ± 1.3) for inter-observer variability. The corresponding mean differences of NTCP values for radiation-induced HT due to intra- and inter-observer variations were insignificantly small, -0.4% (SD ± 6.0) and -0.7% (SD ± 4.8), respectively, but as the SDs show, for some patients the difference in estimated NTCP was large. For the entire study population, the variation in predicted risk of radiation-induced HT in head and neck cancer was small and our NTCP model was robust against observer variations in delineation of the thyroid gland. However, for the individual patient, there may be large differences in estimated risk which calls for precise delineation of the thyroid gland to obtain correct dose and NTCP estimates for optimized treatment planning in the individual patient.

Thyroid peroxidase antibodies during early gestation and the subsequent risk of first-onset postpartum depression: A prospective cohort study.

PubMed

Wesseloo, Richard; Kamperman, Astrid M; Bergink, Veerle; Pop, Victor J M

2018-01-01

During the postpartum period, women are at risk for the new onset of both auto-immune thyroid disorders and depression. The presence of thyroid peroxidase antibodies (TPO-ab) during early gestation is predictive for postpartum auto-immune thyroid dysfunction. The aim of this study was to investigate the association between TPO-ab status during early gestation and first-onset postpartum depression. Prospective cohort study (n = 1075) with follow-up during pregnancy up to one year postpartum. Thyroid function and TPO-ab status were measured during early gestation. Depressive symptomatology was assessed during each trimester and at four time points postpartum with the Edinburgh Depression Scale (EDS). Women with antenatal depression were not eligible for inclusion. Self-reported postpartum depression was defined with an EDS cut-off of ≥ 13. The cumulative incidence of self-reported first-onset depression in the first postpartum year was 6.3%. A positive TPO-ab status was associated with an increased risk for self-reported first-onset depression at four months postpartum (adjusted OR 3.8; 95% CI 1.3-11.6), but not at other postpartum time points. Prevalence rates of self-reported postpartum depression declined after four months postpartum in the TPO-ab positive group, but remained constant in the TPO-ab negative group. Depression was defined with a self-rating questionnaire (EDS). Women with an increased TPO-ab titer during early gestation are at increased risk for self-reported first-onset depression. The longitudinal pattern of self-reported postpartum depression in the TPO-ab positive group was similar to the typical course of postpartum TPO-ab titers changes. This suggests overlap in the etiology of first-onset postpartum depression and auto-immune thyroid dysfunction. Thyroid function should be evaluated in women with first-onset postpartum depression. Copyright © 2017 Elsevier B.V. All rights reserved.

Hypothyroid Symptoms Fail to Predict Thyroid Insufficiency in Old People: A Population-Based Case-Control Study.

PubMed

Carlé, Allan; Pedersen, Inge Bülow; Knudsen, Nils; Perrild, Hans; Ovesen, Lars; Andersen, Stig; Laurberg, Peter

2016-10-01

Clinic-based studies have indicated that older hypothyroid patients may present only few symptoms. In this population-based study of hypothyroidism, we investigated how the power of symptom presence predicts overt hypothyroidism in both young and older subjects. We identified patients newly diagnosed with overt autoimmune hypothyroidism in a population (n = 140, median thyroid-stimulating hormone, 54.5; 95% confidence interval [CI], 28.3-94.8; median total T4, 37; 95% CI, 18-52) and individually matched each patient with 4 controls free of thyroid disease (n = 560). Participants filled out questionnaires concerning the presence and duration of symptoms. We compared the usefulness of hypothyroidism-associated symptoms in predicting overt hypothyroidism in different age groups (young: <50 years, middle age: 50-59 years, old: ≥60 years) also taking various confounders into account. In young hypothyroid patients, all 13 hypothyroidism-associated symptoms studied were more prevalent than in their matched controls, whereas only 3 of those (tiredness, shortness of breath, and wheezing) were more prevalent in old patients. The mean numbers of symptoms presented at disease onset were 6.2, 5.0, and 3.6 at the ages of 0 to 49 years, 50 to 59 years, and 60+ years, respectively. In young versus old people with 0 to 1 symptoms, the odds ratio for being hypothyroid was 0.04 (95% CI, 0.007-0.18) versus 0.34 (95% CI, 0.15-0.78) (reference all other groups). In young versus old subjects reporting ≥4 symptoms, the odds ratio for being hypothyroid was 16.4 (95% CI, 6.96-40.0) versus 2.22 (95% CI, 1.001-4.90). Receiver operating characteristic analyses revealed that the symptom score was an excellent tool for predicting hypothyroidism in young men (area under the receiver operating characteristic curve, 0.91; 95% CI, 0.82-0.998), whereas it was poor in evaluating older women (area under the receiver operating characteristic curve, 0.64; 95% CI, 0.54-0.75). Hypothyroid symptom score is a good discriminating tool to identify hypothyroidism in young patients but fails to identify hypothyroidism in the elderly. Thus, thyroid function should be tested on wide indications in old age. Copyright © 2016 Elsevier Inc. All rights reserved.

Radioiodine: the classic theranostic agent.

PubMed

Silberstein, Edward B

2012-05-01

Radioiodine has the distinction of being the first theranostic agent in our armamentarium. Millennia were required to discover that the agent in orally administered seaweed and its extracts, which had been shown to cure neck swelling due to thyromegaly, was iodine, first demonstrated to be a new element in 1813. Treatment of goiter with iodine began at once, but its prophylactic value to prevent a common form of goiter took another century. After Enrico Fermi produced the first radioiodine, (128)I, in 1934, active experimentation in the United States and France delineated the crucial role of iodine in thyroid metabolism and disease. (130)I and (131)I were first employed to treat thyrotoxicosis by 1941, and thyroid cancer in 1943. After World War II, (131)I became widely available at a reasonable price for diagnostic testing and therapy. The rectilinear scanner of Cassen and Curtis (Science 1949;110:94-95), and a dedicated gamma camera invented by Anger (Nature 1952;170:200-201), finally permitted the diagnostic imaging of thyroid disease, with (131)I again the radioisotope of choice, although there were short-lived attempts to employ (125)I and (132)I for this purpose. (123)I was first produced in 1949 but did not become widely available until about 1982, 10 years after a production technique eliminated high-energy (124)I contamination. I continues to be the radioiodine of choice for the diagnosis of benign thyroid disease, whereas (123)I and (131)I are employed in the staging and detection of functioning thyroid cancer. (124)I, a positron emitter, can produce excellent anatomically correlated images employing positron emission tomography/computed tomography equipment and has the potential to enhance heretofore imperfect dosimetric studies in determining the appropriate administered activity to ablate/treat thyroid cancer. Issues of acceptable measuring error in thyroid cancer dosimetry and the role in (131)I therapy of tumor heterogeneity, tumor hypoxia, and kinetics must be overcome, and long-term outcome studies following (131)I given based on this new dosimetry must be completed before the nuclear medicine community will be able to predictably cure our thyroid cancer patients with this technology. Copyright © 2012 Elsevier Inc. All rights reserved.

Comparison of transcriptomic signature of post-Chernobyl and postradiotherapy thyroid tumors.

PubMed

Ory, Catherine; Ugolin, Nicolas; Hofman, Paul; Schlumberger, Martin; Likhtarev, Illya A; Chevillard, Sylvie

2013-11-01

We previously identified two highly discriminating and predictive radiation-induced transcriptomic signatures by comparing series of sporadic and postradiotherapy thyroid tumors (322-gene signature), and by reanalyzing a previously published data set of sporadic and post-Chernobyl thyroid tumors (106-gene signature). The aim of the present work was (i) to compare the two signatures in terms of gene expression deregulations and molecular features/pathways, and (ii) to test the capacity of the postradiotherapy signature in classifying the post-Chernobyl series of tumors and reciprocally of the post-Chernobyl signature in classifying the postradiotherapy-induced tumors. We now explored if postradiotherapy and post-Chernobyl papillary thyroid carcinomas (PTC) display common molecular features by comparing molecular pathways deregulated in the two tumor series, and tested the potential of gene subsets of the postradiotherapy signature to classify the post-Chernobyl series (14 sporadic and 12 post-Chernobyl PTC), and reciprocally of gene subsets of the post-Chernobyl signature to classify the postradiotherapy series (15 sporadic and 12 postradiotherapy PTC), by using conventional principal component analysis. We found that the five genes common to the two signatures classified the learning/training tumors (used to search these signatures) of both the postradiotherapy (seven PTC) and the post-Chernobyl (six PTC) thyroid tumor series as compared with the sporadic tumors (seven sporadic PTC in each series). Importantly, these five genes were also effective for classifying independent series of postradiotherapy (five PTC) and post-Chernobyl (six PTC) tumors compared to independent series of sporadic tumors (eight PTC and six PTC respectively; testing tumors). Moreover, part of each postradiotherapy (32 genes) and post-Chernobyl signature (16 genes) cross-classified the respective series of thyroid tumors. Finally, several molecular pathways deregulated in post-Chernobyl tumors matched those found to be deregulated in postradiotherapy tumors. Overall, our data suggest that thyroid tumors that developed following either external exposure or internal (131)I contamination shared common molecular features, related to DNA repair, oxidative and endoplasmic reticulum stresses, allowing their classification as radiation-induced tumors in comparison with sporadic counterparts, independently of doses and dose rates, which suggests there may be a "general" radiation-induced signature of thyroid tumors.

A single nucleotide polymorphism associated with isolated cleft lip and palate, thyroid cancer and hypothyroidism alters the activity of an oral epithelium and thyroid enhancer near FOXE1

PubMed Central

Lidral, Andrew C.; Liu, Huan; Bullard, Steven A.; Bonde, Greg; Machida, Junichiro; Visel, Axel; Uribe, Lina M. Moreno; Li, Xiao; Amendt, Brad; Cornell, Robert A.

2015-01-01

Three common diseases, isolated cleft lip and cleft palate (CLP), hypothyroidism and thyroid cancer all map to the FOXE1 locus, but causative variants have yet to be identified. In patients with CLP, the frequency of coding mutations in FOXE1 fails to account for the risk attributable to this locus, suggesting that the common risk alleles reside in nearby regulatory elements. Using a combination of zebrafish and mouse transgenesis, we screened 15 conserved non-coding sequences for enhancer activity, identifying three that regulate expression in a tissue specific pattern consistent with endogenous foxe1 expression. These three, located −82.4, −67.7 and +22.6 kb from the FOXE1 start codon, are all active in the oral epithelium or branchial arches. The −67.7 and +22.6 kb elements are also active in the developing heart, and the −67.7 kb element uniquely directs expression in the developing thyroid. Within the −67.7 kb element is the SNP rs7850258 that is associated with all three diseases. Quantitative reporter assays in oral epithelial and thyroid cell lines show that the rs7850258 allele (G) associated with CLP and hypothyroidism has significantly greater enhancer activity than the allele associated with thyroid cancer (A). Moreover, consistent with predicted transcription factor binding differences, the −67.7 kb element containing rs7850258 allele G is significantly more responsive to both MYC and ARNT than allele A. By demonstrating that this common non-coding variant alters FOXE1 expression, we have identified at least in part the functional basis for the genetic risk of these seemingly disparate disorders. PMID:25652407

Differentiation between malignant and benign thyroid nodules and stratification of papillary thyroid cancer with aggressive histological features: Whole-lesion diffusion-weighted imaging histogram analysis.

PubMed

Hao, Yonghong; Pan, Chu; Chen, WeiWei; Li, Tao; Zhu, WenZhen; Qi, JianPin

2016-12-01

To explore the usefulness of whole-lesion histogram analysis of apparent diffusion coefficient (ADC) derived from reduced field-of-view (r-FOV) diffusion-weighted imaging (DWI) in differentiating malignant and benign thyroid nodules and stratifying papillary thyroid cancer (PTC) with aggressive histological features. This Institutional Review Board-approved, retrospective study included 93 patients with 101 pathologically proven thyroid nodules. All patients underwent preoperative r-FOV DWI at 3T. The whole-lesion ADC assessments were performed for each patient. Histogram-derived ADC parameters between different subgroups (pathologic type, extrathyroidal extension, lymph node metastasis) were compared. Receiver operating characteristic curve analysis was used to determine optimal histogram parameters in differentiating benign and malignant nodules and predicting aggressiveness of PTC. Mean ADC, median ADC, 5 th percentile ADC, 25 th percentile ADC, 75 th percentile ADC, 95 th percentile ADC (all P < 0.001), and kurtosis (P = 0.001) were significantly lower in malignant thyroid nodules, and mean ADC achieved the highest AUC (0.919) with a cutoff value of 1842.78 × 10 -6 mm 2 /s in differentiating malignant and benign nodules. Compared to the PTCs without extrathyroidal extension, PTCs with extrathyroidal extension showed significantly lower median ADC, 5 th percentile ADC, and 25 th percentile ADC. The 5 th percentile ADC achieved the highest AUC (0.757) with cutoff value of 911.5 × 10 -6 mm 2 /s for differentiating between PTCs with and without extrathyroidal extension. Whole-lesion ADC histogram analysis might help to differentiate malignant nodules from benign ones and show the PTCs with extrathyroidal extension. J. Magn. Reson. Imaging 2016;44:1546-1555. © 2016 International Society for Magnetic Resonance in Medicine.

Thyroid gland invasion in advanced squamous cell carcinoma of the larynx and hypopharynx.

PubMed

Mangussi-Gomes, João; Danelon-Leonhardt, Fernando; Moussalem, Guilherme Figner; Ahumada, Nicolas Galat; Oliveira, Cleydson Lucena; Hojaij, Flávio Carneiro

Squamous cell carcinoma of the larynx and hypopharynx has the potential to invade the thyroid gland. Despite this risk, the proposition of either partial or total thyroidectomy as part of the surgical treatment of all such cases remains controversial. To evaluate the frequency of invasion of the thyroid gland in patients with advanced laryngeal or hypopharyngeal squamous cell carcinoma submitted to total laryngectomy or pharyngolaryngectomy and thyroidectomy; to determine whether clinic-pathological characteristics can predict glandular involvement. A retrospective case series with chart review, from January 1998 to July 2013, was undertaken in a tertiary care university medical center. An inception cohort of 83 patients with larynx/hypopharynx squamous cell carcinoma was considered. All patients had advanced stage disease (clinically T3-T4) and underwent total laryngectomy or total pharyngolaryngectomy in association with thyroidectomy. Adjuvant therapy was indicated when tumor or neck conditions required. Frequency of thyroid cartilage invasion was calculated; univariate and multivariate analysis of demographic, clinical and pathological characteristics associated with cartilage invasion were performed. The overall frequency of invasion of the thyroid gland was 18.1%. Glandular involvement was associated with invasion of the following structures: anterior commissure (odds ratio=5.13; 95% confidence interval 1.07-24.5), subglottis (odds ratio=12.44; 95% confidence interval 1.55-100.00) and cricoid cartilage (odds ratio=15.95; 95% confidence interval 4.23-60.11). Invasion of the thyroid gland is uncommon in the context of laryngopharyngeal squamous cell carcinoma. Clinical and pathological features such as invasion of the anterior commissure, subglottis and cricoid cartilage are more associated with glandular invasion. Copyright © 2017 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

Insulin resistance, diabetes mellitus and thyroid dysfunction in patients with palmoplantar pustulosis: a case-controlled study.

PubMed

Ataş, Hatice; Gönül, Müzeyyen

2017-06-01

Palmoplantar pustulosis (PPP) is a chronic pustular inflammatory skin disease; however, its pathogenesis is not well understood. Several factors, such as genetics, tobacco use and autoimmune issues, may contribute to this disease. This research was conducted to investigate the relationships between insulin resistance, thyroid disease and PPP. Thirty-three patients with PPP and 27 age- and gender-matched controls were analysed for their smoking histories, thyroid function tests, anti-thyroid peroxidase antibody (anti-TPO) levels, fasting glucose, fasting insulin levels and the homeostatic model assessment (HOMA) index for insulin resistance. We found significant differences between the PPP and control groups according to their tobacco use and anti-TPO levels ( p = 0.009 and p = 0.009, respectively). The proportion of tobacco use was 90% in the PPP patients and 63% in the controls. Gender and tobacco use were predictive risk factors for PPP in the multivariate analysis ( OR = 141.7, p < 0.0001 and OR = 147.6, p = 0.006, respectively). An anti-TPO level > 35 U/ml and the presence of a thyroid abnormality were independent risk factors in the univariate, but not the multivariate analysis ( OR = 4.2, p = 0.025 and OR = 5.4, p = 0.004, respectively). A moderate correlation between the gender and anti-TPO level was found ( r = 0.361, p = 0.039); however, the fasting glucose, insulin and HOMA index were not significant between the PPP and control groups. Female gender and smoking were the most important risk factors for PPP; however, the increase in the anti-TPO level may be related to the predominance of females afflicted with this disease. Additional studies are necessary to clarify the relationships between PPP, thyroid disease and diabetes mellitus.

Thyroid antibody status, subclinical hypothyroidism, and the risk of coronary heart disease: an individual participant data analysis.

PubMed

Collet, Tinh-Hai; Bauer, Douglas C; Cappola, Anne R; Asvold, Bjørn O; Weiler, Stefan; Vittinghoff, Eric; Gussekloo, Jacobijn; Bremner, Alexandra; den Elzen, Wendy P J; Maciel, Rui M B; Vanderpump, Mark P J; Cornuz, Jacques; Dörr, Marcus; Wallaschofski, Henri; Newman, Anne B; Sgarbi, José A; Razvi, Salman; Völzke, Henry; Walsh, John P; Aujesky, Drahomir; Rodondi, Nicolas

2014-09-01

Subclinical hypothyroidism has been associated with increased risk of coronary heart disease (CHD), particularly with thyrotropin levels of 10.0 mIU/L or greater. The measurement of thyroid antibodies helps predict the progression to overt hypothyroidism, but it is unclear whether thyroid autoimmunity independently affects CHD risk. The objective of the study was to compare the CHD risk of subclinical hypothyroidism with and without thyroid peroxidase antibodies (TPOAbs). A MEDLINE and EMBASE search from 1950 to 2011 was conducted for prospective cohorts, reporting baseline thyroid function, antibodies, and CHD outcomes. Individual data of 38 274 participants from six cohorts for CHD mortality followed up for 460 333 person-years and 33 394 participants from four cohorts for CHD events. Among 38 274 adults (median age 55 y, 63% women), 1691 (4.4%) had subclinical hypothyroidism, of whom 775 (45.8%) had positive TPOAbs. During follow-up, 1436 participants died of CHD and 3285 had CHD events. Compared with euthyroid individuals, age- and gender-adjusted risks of CHD mortality in subclinical hypothyroidism were similar among individuals with and without TPOAbs [hazard ratio (HR) 1.15, 95% confidence interval (CI) 0.87-1.53 vs HR 1.26, CI 1.01-1.58, P for interaction = .62], as were risks of CHD events (HR 1.16, CI 0.87-1.56 vs HR 1.26, CI 1.02-1.56, P for interaction = .65). Risks of CHD mortality and events increased with higher thyrotropin, but within each stratum, risks did not differ by TPOAb status. CHD risk associated with subclinical hypothyroidism did not differ by TPOAb status, suggesting that biomarkers of thyroid autoimmunity do not add independent prognostic information for CHD outcomes.

Investigation of the impact of thyroid surgery on vocal tract steadiness.

PubMed

Timon, Conrad I; Hirani, Shashi P; Epstein, Ruth; Rafferty, Mark A

2010-09-01

Subjective nonspecific upper aerodigestive symptoms are not uncommon after thyroid surgery. These are postulated to be related to injury of an extrinsic perithyroid nerve plexus that innervates the muscles of the supraglottic and glottic larynx. This plexus is thought to receive contributing branches from both the recurrent and superior laryngeal nerves. The technique of linear predictive coding was used to estimate the F(2) values from a sustained vowel /a/ in patients before and 48 hours after thyroid or parathyroid surgery. These patients were controlled against a matched pair undergoing surgery without any theoretical effect on the supraglottic musculature. In total, 12 patients were recruited into each group. Each patient had the formant frequency fluctuation (FFF) and the formant frequency fluctuation ratio (FFFR) calculated for F(1) and F(2). Mixed analysis of variance (ANOVA) for all acoustic parameters revealed that the chiF(2)FF showed a significant "time" main effect (F(1,22)=7.196, P=0.014, partial eta(2)=0.246) and a significant "time by group interaction" effect (F(1,22)=8.036, P=0.010, eta(p)(2)=0.268), with changes over time for the thyroid group but not for the controls. Similarly, mean chiF(2)FFR showed a similar significant "time" main effect (F(1,22)=6.488, P=0.018, eta(p)(2)=0.228) and a "time by group interaction" effect (F(1,22)=7.134, P=0.014, eta(p)(2)=0.245). This work suggests that thyroid surgery produces a significant reduction in vocal tract stability in contrast to the controls. This noninvasive measurement offers a potential instrument to investigate the functional implications of any disturbance that thyroid surgery may have on pharyngeal innervations. 2010 The Voice Foundation. Published by Mosby, Inc. All rights reserved.

Short-chain chlorinated paraffins (SCCPs) induced thyroid disruption by enhancement of hepatic thyroid hormone influx and degradation in male Sprague Dawley rats.

PubMed

Gong, Yufeng; Zhang, Haijun; Geng, Ningbo; Xing, Liguo; Fan, Jingfeng; Luo, Yun; Song, Xiaoyao; Ren, Xiaoqian; Wang, Feidi; Chen, Jiping

2018-06-01

Short-chain chlorinated paraffins (SCCPs) are known to disturb thyroid hormone (TH) homeostasis in rodents. However, the mechanism remains to be fully characterized. In this study, male Sprague Dawley rats received SCCPs (0, 1, 10, or 100mg/kg/day) via gavage once a day for consecutive 28days. Plasma and hepatic TH concentrations, thyrocyte structure, as well as thyroid and hepatic mRNA and protein levels of genes associated with TH homeostasis were examined. Moreover, we performed molecular docking to predict interactions between constitutive androstane receptor (CAR), a key regulator in xenobiotic-induced TH metabolism, with different SCCP molecules. Exposure to SCCPs significantly decreased the circulating free thyroxine (T 4 ) and triiodothyronine (T 3 ) levels, but increased thyroid-stimulating hormone (TSH) levels by a feedback mechanism. Decreased hepatic T 4 and increased hepatic T 3 levels were also seen after 100mg/kg/day SCCPs exposure. SCCPs didn't show any significant effects on the expression of thyroid TH synthesis genes or thyrocyte structure. However, stimulation effects were observed for mRNA and protein levels of hepatic uridine diphosphoglucuronosyl transferase (UGT) 1A1 and organic anion transporter 2, suggesting an accelerated TH metabolism in rat liver. The increased cytochrome P450 2B1 but not 1A1 mRNA and protein levels indicated that the CAR signaling was activated by SCCPs exposure. According to docking analysis, SCCPs form hydrophobic interactions with CAR and the binding affinity shows dependency on chlorine content. Overall, our data showed that CAR implicated enhancement of hepatic TH influx and degradation could be the main cause for SCCPs induced TH deficiency in male rats. Copyright © 2017 Elsevier B.V. All rights reserved.

A molecular computational model improves the preoperative diagnosis of thyroid nodules

PubMed Central

2012-01-01

Background Thyroid nodules with indeterminate cytological features on fine needle aspiration (FNA) cytology have a 20% risk of thyroid cancer. The aim of the current study was to determine the diagnostic utility of an 8-gene assay to distinguish benign from malignant thyroid neoplasm. Methods The mRNA expression level of 9 genes (KIT, SYNGR2, C21orf4, Hs.296031, DDI2, CDH1, LSM7, TC1, NATH) was analysed by quantitative PCR (q-PCR) in 93 FNA cytological samples. To evaluate the diagnostic utility of all the genes analysed, we assessed the area under the curve (AUC) for each gene individually and in combination. BRAF exon 15 status was determined by pyrosequencing. An 8-gene computational model (Neural Network Bayesian Classifier) was built and a multiple-variable analysis was then performed to assess the correlation between the markers. Results The AUC for each significant marker ranged between 0.625 and 0.900, thus all the significant markers, alone and in combination, can be used to distinguish between malignant and benign FNA samples. The classifier made up of KIT, CDH1, LSM7, C21orf4, DDI2, TC1, Hs.296031 and BRAF had a predictive power of 88.8%. It proved to be useful for risk stratification of the most critical cytological group of the indeterminate lesions for which there is the greatest need of accurate diagnostic markers. Conclusion The genetic classification obtained with this model is highly accurate at differentiating malignant from benign thyroid lesions and might be a useful adjunct in the preoperative management of patients with thyroid nodules. PMID:22958914

Assessment of cellularity, genomic DNA yields, and technical platforms for BRAF mutational testing in thyroid fine-needle aspirate samples.

PubMed

Dyhdalo, Kathryn; Macnamara, Stephen; Brainard, Jennifer; Underwood, Dawn; Tubbs, Raymond; Yang, Bin

2014-02-01

BRAF mutation V600E (substitution Val600Glu) is a molecular signature for papillary thyroid carcinoma (PTC). Testing for BRAF mutation is clinically useful in providing prognostic prediction and facilitating accurate diagnosis of PTC in thyroid fine-needle aspirate (FNA) samples. This study assessed the correlation of cellularity with DNA yield and compared 2 technical platforms with different sensitivities in detection of BRAF mutation in cytologic specimens. Cellularity was evaluated based on groups of 10+ cells on a ThinPrep slide: 1+ (1-5 groups), 2+ (6-10 groups), 3+ (11-20 groups), and 4+ (> 20 groups). Genomic DNA was extracted from residual materials of thyroid FNAs after cytologic diagnosis. Approximately 49% of thyroid FNA samples had low cellularity (1-2+). DNA yield is proportionate with increased cellularity and increased nearly 4-fold from 1+ to 4+ cellularity in cytologic samples. When applied to BRAF mutational assay, using a cutoff of 6 groups of follicular cells with 10+ cells per group, 96.7% of cases yielded enough DNA for at least one testing for BRAF mutation. Five specimens (11.6%) with lower cellularity did not yield sufficient DNA for duplicate testing. Comparison of Sanger sequencing to allele-specific polymerase chain reaction methods shows the latter confers better sensitivity in detection of BRAF mutation, especially in limited cytologic specimens with a lower percentage of malignant cells. This study demonstrates that by using 6 groups of 10+ follicular cells as a cutoff, nearly 97% of thyroid FNA samples contain enough DNA for BRAF mutational assay. Careful selection of a molecular testing system with high sensitivity facilitates the successful conduction of molecular testing in limited cytologic specimens. Cancer (Cancer Cytopathol) 2014;122:114-22 © 2013 American Cancer Society. © 2013 American Cancer Society.

The Bethesda system for reporting thyroid cytopathology: An experience of 1,382 cases in a community practice setting with the implication for risk of neoplasm and risk of malignancy.

PubMed

Wu, Howard Her-Juing; Rose, Crystal; Elsheikh, Tarik M

2012-05-01

The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) has provided a set of uniform diagnostic terminology including benign (B), atypia of undetermined significance (AUS), follicular neoplasm (FN), suspicious for malignancy (SM), malignancy (M), and nondiagnostic (ND) for the interpretation of thyroid fine-needle aspiration (FNA). We applied this terminology on our 1,382 thyroid aspirates in a community practice setting, which included 539 cases of B (39%), 376 cases of AUS (27.2%), 116 cases of FN (8.4%), 37 cases of malignant (2.7%), 36 cases of SM (2.6%), and 278 cases of ND (20.1%). Two hundred twenty-one cases (16%) of thyroid FNA had corresponding follow-up thyroidectomies. Each diagnostic category represented a unique association with risk of malignancy and risk of neoplasm. Based on histologic follow-up, the risk of neoplasm (including benign and malignant neoplasm) was B 14%, AUS 44%, FN 67%, SM 77%, and M 100% and the risk of malignancy was B 3%, AUS 6%, FN 22%, SM 56%, and M 100%. The classification and follow-up recommendation of TBSRTC are appropriate for each category. Both B and AUS are low-risk lesions with low probability of malignancy. FN predicts a higher rate for neoplasm but an intermediate rate for malignancy while SM carries a high risk for malignancy. Copyright © 2011 Wiley-Liss, Inc.

Neck circumference correlates with tumor size and lateral lymph node metastasis in men with small papillary thyroid carcinoma.

PubMed

Kim, Mi Ra; Kim, Sang Soo; Huh, Jung Eun; Lee, Byung Joo; Lee, Jin Choon; Jeon, Yun Kyung; Kim, Bo Hyun; Kim, Seong Jang; Wang, Soo Geun; Kim, Yong Ki; Kim, In Joo

2013-01-01

Obesity is correlated with numerous diseases, including thyroid cancer, but the clinical significance of obesity with regard to the clinical characteristics of thyroid cancer remains unclear. Neck circumference is an index of upper-body adipose tissue distribution. In total, 401 patients with papillary thyroid carcinoma (PTC) measuring ≤ 2 cm were included. Neck circumference was measured horizontally at the level just below the thyroid cartilage on preoperative neck computed tomographic images. Neck circumference correlated significantly with tumor size in men (p = 0.001) but not in women (p = 0.930). Body mass index (BMI) did not significantly correlate with tumor size in either sex. Neck circumference was significantly larger in men with lateral lymph node (LN) metastasis than in those without (p = 0.004). Neck circumference and BMI did not differ significantly in women according to other factors such as tumor size, multifocality, extrathyroid extension, and LN metastasis. Tumor size and the prevalence of lateral LN metastasis in men tended to increase in the middle/large neck circumference subgroup compared with those in the low neck circumference subgroup. Multivariate logistic regression analysis revealed that neck circumference (p = 0.009) was a predictor for the presence of lateral LN metastasis in men. BMI was not a predictive factor for lateral LN involvement in either sex. Neck circumference, an indicator of central or visceral obesity but not BMI, may be associated with some prognostic factors in men with small PTC.

Lack of HER-2 gene amplification and association with pathological and clinical characteristics of differentiated thyroid cancer.

PubMed

Mdah, Wahid; Mzalbat, Raneen; Gilbey, Peter; Stein, Moshe; Sharabi, Adi; Zidan, Jamal

2014-11-01

Human epidermal growth factor receptor 2 (HER-2) is a well recognized prognostic and predictive factor in breast cancer. However, the role of HER-2 in thyroid cancer remains controversial. The aim of this study was to evaluate HER-2 expression in differentiated thyroid cancer (DTC) and determine whether there is an association with other clinical and pathological characteristics. A total of 69 patients with DTC were investigated, 58 of whom had papillary and 11 follicular carcinomas. HER-2 was detected by immunohistochemical examination on sections from formalin-fixed, paraffin-embedded tumor tissues. Tumors with HER-2 expression classed as +1 and +2 were retested with chromogenic in situ hybridization. Clinicopathological data were retrieved from the hospital records of the patients. HER-2 overexpression was found in 4 (6.9%) of the 58 patients with papillary carcinoma, whereas there was no HER-2 overexpression in any of the 11 cases of follicular carcinoma. There was no association of HER-2 expression with tumor size, pathological grade and cervical lymph node metastasis. In conclusion, there were no HER-2 positive cases of follicular carcinoma and the incidence of HER-2 overexpression in papillary carcinoma was very low. Thus, HER-2 cannot be used routinely as a prognostic or predictive factor in DTC. The expression of other epidermal growth factor receptors in DTC merits further investigation.

The nightmare of indeterminate follicular proliferations: when liquid-based cytology and ancillary techniques are not a moon landing but a realistic plan.

PubMed

Rossi, Esther Diana; Fadda, Guido; Schmitt, Fernando

2014-01-01

Thyroid nodules are a common finding in the general population, including both nonneoplastic and neoplastic entities. Fine-needle aspiration cytology (FNAC) is the first tool for evaluating thyroid nodules. In spite of its high diagnostic accuracy, 25% of nodules result in the category of follicular neoplasms (FN), with varying risk of malignancy and different management strategies. The use of ancillary techniques is reshaping the practice of FNAC. These tools can significantly empower the morphological diagnosis and prognosis of thyroid nodules, allowing a more accurate prediction of the nature of the lesion. Several studies have underlined the role of single or multiple testing for the category of FN as strong indicators of cancer. Every cytological preparation can be used for the application of ancillary techniques but the introduction of liquid-based cytology (LBC) might facilitate the application. Our experience involving an immunocytochemical panel made up of HBME-1 and galectin-3 pointed to an 81% overall diagnostic accuracy in discriminating between low and high risk of malignancy in FN. The application of these techniques on LBC represents an adjunct to the morphological evaluation of FN. They represent a critical and challenging, but also a feasible, tool in the preoperative diagnoses, allowing specific prognostic and predictive details regardless of the cytological preparation. © 2014 S. Karger AG, Basel.

Prediction of infarct severity from triiodothyronine levels in patients with ST-elevation myocardial infarction

PubMed Central

Kim, Dong Hun; Kim, Hyun-Wook; Choi, Seo-Won; Kim, Bo-Bae; Chung, Joong-Wha; Koh, Young-Youp; Chang, Kyong-Sig; Hong, Soon-Pyo

2014-01-01

Background/Aims The aim of the present study was to evaluate the relationship between thyroid hormone levels and infarct severity in patients with ST-elevation myocardial infarction (STEMI). Methods We retrospectively reviewed thyroid hormone levels, infarct severity, and the extent of transmurality in 40 STEMI patients evaluated via contrast-enhanced cardiac magnetic resonance imaging. Results The high triiodothyronine (T3) group (≥ 68.3 ng/dL) exhibited a significantly higher extent of transmural involvement (late transmural enhancement > 75% after administration of gadolinium contrast agent) than did the low T3 group (60% vs. 15%; p = 0.003). However, no significant difference was evident between the high- and low-thyroid-stimulating hormone/free thyroxine (FT4) groups. When the T3 cutoff level was set to 68.3 ng/dL using a receiver operating characteristic curve, the sensitivity was 80% and the specificity 68% in terms of differentiating between those with and without transmural involvement. Upon logistic regression analysis, high T3 level was an independent predictor of transmural involvement after adjustment for the presence of diabetes mellitus (DM) and the use of glycoprotein IIb/IIIa inhibitors (odds ratio, 40.62; 95% confidence interval, 3.29 to 502; p = 0.004). Conclusions The T3 level predicted transmural involvement that was independent of glycoprotein IIb/IIIa inhibitor use and DM positivity. PMID:25045293

ANIMAL PHYSIOLOGY. Exceptionally low daily energy expenditure in the bamboo-eating giant panda.

PubMed

Nie, Yonggang; Speakman, John R; Wu, Qi; Zhang, Chenglin; Hu, Yibo; Xia, Maohua; Yan, Li; Hambly, Catherine; Wang, Lu; Wei, Wei; Zhang, Jinguo; Wei, Fuwen

2015-07-10

The carnivoran giant panda has a specialized bamboo diet, to which its alimentary tract is poorly adapted. Measurements of daily energy expenditure across five captive and three wild pandas averaged 5.2 megajoules (MJ)/day, only 37.7% of the predicted value (13.8 MJ/day). For the wild pandas, the mean was 6.2 MJ/day, or 45% of the mammalian expectation. Pandas achieve this exceptionally low expenditure in part by reduced sizes of several vital organs and low physical activity. In addition, circulating levels of thyroid hormones thyroxine (T4) and triiodothyronine (T3) averaged 46.9 and 64%, respectively, of the levels expected for a eutherian mammal of comparable size. A giant panda-unique mutation in the DUOX2 gene, critical for thyroid hormone synthesis, might explain these low thyroid hormone levels. A combination of morphological, behavioral, physiological, and genetic adaptations, leading to low energy expenditure, likely enables giant pandas to survive on a bamboo diet. Copyright © 2015, American Association for the Advancement of Science.

Spatiotemporal Co-existence of Female Thyroid and Breast Cancers in Hangzhou, China

NASA Astrophysics Data System (ADS)

Fei, Xufeng; Christakos, George; Lou, Zhaohan; Ren, Yanjun; Liu, Qingmin; Wu, Jiaping

2016-06-01

Thyroid and breast cancers (TC, BC) are common female malignant tumors worldwide. Studies suggest that TC patients have a higher BC risk, and vice versa. However, it has not been investigated quantitatively if there is an association between the space-time TC and BC incidence distributions at the population level. This work aims to answer this question. 5358 TC and 8784 BC (female) cases were diagnosed in Hangzhou (China, 2008-2012). Pearson and Spearman rank correlation coefficients of the TC and BC incidences were high, and their patterns were geographically similar. The spatiotemporal co-existence of TC and BC distributions was investigated using the integrative disease predictability (IDP) criterion: if TC-BC association is part of the disease mapping knowledge bases, it should yield improved space-time incidence predictions. Improved TC (BC) incidence predictions were generated when integrating both TC and BC data than when using only TC (BC) data. IDP consistently demonstrated the spatiotemporal co-existence of TC and BC distributions throughout Hangzhou (2008-2012), which means that when the population experiences high incidences of one kind of cancer attention should be paid to the other kind of cancer too. The strength of TC-BC association was measured by the IDP coefficients and incidence prediction accuracy.

Spatiotemporal Co-existence of Female Thyroid and Breast Cancers in Hangzhou, China

PubMed Central

Fei, Xufeng; Christakos, George; Lou, Zhaohan; Ren, Yanjun; Liu, Qingmin; Wu, Jiaping

2016-01-01

Thyroid and breast cancers (TC, BC) are common female malignant tumors worldwide. Studies suggest that TC patients have a higher BC risk, and vice versa. However, it has not been investigated quantitatively if there is an association between the space-time TC and BC incidence distributions at the population level. This work aims to answer this question. 5358 TC and 8784 BC (female) cases were diagnosed in Hangzhou (China, 2008–2012). Pearson and Spearman rank correlation coefficients of the TC and BC incidences were high, and their patterns were geographically similar. The spatiotemporal co-existence of TC and BC distributions was investigated using the integrative disease predictability (IDP) criterion: if TC-BC association is part of the disease mapping knowledge bases, it should yield improved space-time incidence predictions. Improved TC (BC) incidence predictions were generated when integrating both TC and BC data than when using only TC (BC) data. IDP consistently demonstrated the spatiotemporal co-existence of TC and BC distributions throughout Hangzhou (2008–2012), which means that when the population experiences high incidences of one kind of cancer attention should be paid to the other kind of cancer too. The strength of TC-BC association was measured by the IDP coefficients and incidence prediction accuracy. PMID:27341638

Recent advances in managing differentiated thyroid cancer.

PubMed

Lamartina, Livia; Grani, Giorgio; Durante, Cosimo; Filetti, Sebastiano

2018-01-01

The main clinical challenge in the management of thyroid cancer is to avoid over-treatment and over-diagnosis in patients with lower-risk disease while promptly identifying those patients with more advanced or high-risk disease requiring aggressive treatment. In recent years, novel clinical and molecular data have emerged, allowing the development of new staging systems, predictive and prognostic tools, and treatment approaches. There has been a notable shift toward more conservative management of low- and intermediate-risk patients, characterized by less extensive surgery, more selective use of radioisotopes (for both diagnostic and therapeutic purposes), and less intensive follow-up. Furthermore, the histologic classification; tumor, node, and metastasis (TNM) staging; and American Thyroid Association risk stratification systems have been refined, and this has increased the number of patients in the low- and intermediate-risk categories. There is now a need for new, prospective data to clarify how these changing practices will impact long-term outcomes of patients with thyroid cancer, and new follow-up strategies and biomarkers are still under investigation. On the other hand, patients with more advanced or high-risk disease have a broader portfolio of options in terms of treatments and therapeutic agents, including multitarget tyrosine kinase inhibitors, more selective BRAF or MEK inhibitors, combination therapies, and immunotherapy.

Multiple metals predict prolactin and thyrotropin (TSH) levels in men

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meeker, John D., E-mail: meekerj@umich.edu; Rossano, Mary G.; Protas, Bridget

2009-10-15

Exposure to a number of metals can affect neuroendocrine and thyroid signaling, which can result in adverse effects on development, behavior, metabolism, reproduction, and other functions. The present study assessed the relationship between metal concentrations in blood and serum prolactin (PRL) and thyrotropin (TSH) levels, markers of dopaminergic, and thyroid function, respectively, among men participating in a study of environmental influences on male reproductive health. Blood samples from 219 men were analyzed for concentrations of 11 metals and serum levels of PRL and TSH. In multiple linear regression models adjusted for age, BMI and smoking, PRL was inversely associated withmore » arsenic, cadmium, copper, lead, manganese, molybdenum, and zinc, but positively associated with chromium. Several of these associations (Cd, Pb, Mo) are consistent with limited studies in humans or animals, and a number of the relationships (Cr, Cu, Pb, Mo) remained when additionally considering multiple metals in the model. Lead and copper were associated with non-monotonic decrease in TSH, while arsenic was associated with a dose-dependent increase in TSH. For arsenic these findings were consistent with recent experimental studies where arsenic inhibited enzymes involved in thyroid hormone synthesis and signaling. More research is needed for a better understanding of the role of metals in neuroendocrine and thyroid function and related health implications.« less

Thyroid peroxidase antibody positivity and triiodothyronine levels are associated with pediatric Graves' ophthalmopathy.

PubMed

Lee, Jung Hyun; Park, So Hyun; Koh, Dae Gyun; Suh, Byung Kyu

2014-05-01

Graves' ophthalmopathy (GO) occurs commonly in children with Graves' disease (GD). However, there are limited studies on the clinical manifestations and thyroid autoantibodies in pediatric GO. The aim of this study was to investigate the prevalence and risk factors of GO in childhood GD. Clinical and biochemical data from children and adolescents with GD were retrospectively reviewed. Eighty patients under 19 years of age were included in the present study. We compared the clinical and biochemical differences between patients with and without GO. Thirty-nine percent of the patients had GO, and 81% of the GO patients were females. Of these, two patients showed unilateral GO. Triiodothyronine (T3) levels were higher in GO patients than in those without GO. Anti-thyroglobulin antibody and thyroid stimulating hormone receptor antibody titers were not significantly different between the two groups. Anti-thyroid peroxidase antibody (TPO Ab) positivity was 68% in the patients with GO and only 47% in the patients without GO. In multivariate regression analysis, high T3 levels and TPO Ab positivity were related to the presence of GO. In children and adolescents with GD, TPO Ab positivity and high T3 levels could act as predictive factors for the presence of GO.

Association of allelic loss on 1q, 4p, 7q, 9p, 9q, and 16q with postoperative death in papillary thyroid carcinoma.

PubMed

Kitamura, Y; Shimizu, K; Tanaka, S; Ito, K; Emi, M

2000-05-01

Papillary thyroid carcinomas, most of which are characterized by slow growth and good prognosis, account for the majority of thyroid carcinomas. To provide appropriate postoperative management, it is important to classify them by prediction of their prognosis. To find genetic markers associated with poor prognosis, allelic loss at all 39 nonacrocentric chromosome arms was compared in 24 deceased cases and 45 age-, sex-, stage-, and type-matched survived cases. Allelic loss was examined in primary tumors from both groups using highly polymorphic microsatellite markers on 39 nonacrocentric autosomal arms. Age at diagnosis, sex, stage, and types of tumors were matched between the two groups. No recurrent tumor was used for DNA analysis. Mean fractional allelic loss in the deceased and survived cases was 0.10+/-0.08 and 0.03+/-0.05 (P < 0.001). The survived cases showed marginal frequencies of allelic loss throughout all chromosome arms except 22q. The deceased cases showed frequent allelic losses on chromosomes 1q (37%), 4p (21%), 7q (20%), 9p (36%), 9q (31%), and 16q (29%), with significant difference (P < 0.05). These chromosome regions may include tumor suppressor genes whose inactivation is associated with aggressive phenotypes of papillary thyroid carcinoma.

Sunitinib in Treating Patients With Thyroid Cancer That Did Not Respond to Iodine I 131 and Cannot Be Removed by Surgery

ClinicalTrials.gov

2017-08-18

Recurrent Thyroid Gland Carcinoma; Stage III Thyroid Gland Follicular Carcinoma; Stage III Thyroid Gland Medullary Carcinoma; Stage IV Thyroid Gland Follicular Carcinoma; Stage IV Thyroid Gland Medullary Carcinoma; Stage IV Thyroid Gland Papillary Carcinoma; Stage IVA Thyroid Gland Follicular Carcinoma; Stage IVA Thyroid Gland Medullary Carcinoma; Stage IVA Thyroid Gland Papillary Carcinoma; Stage IVB Thyroid Gland Follicular Carcinoma; Stage IVB Thyroid Gland Medullary Carcinoma; Stage IVB Thyroid Gland Papillary Carcinoma; Stage IVC Thyroid Gland Follicular Carcinoma; Stage IVC Thyroid Gland Medullary Carcinoma; Stage IVC Thyroid Gland Papillary Carcinoma; Thyroid Gland Oncocytic Follicular Carcinoma

Lowered quality of life in mood disorders is associated with increased neuro-oxidative stress and basal thyroid-stimulating hormone levels and use of anticonvulsant mood stabilizers.

PubMed

Nunes, Caroline Sampaio; Maes, Michael; Roomruangwong, Chutima; Moraes, Juliana Brum; Bonifacio, Kamila Landucci; Vargas, Heber Odebrecht; Barbosa, Decio Sabbatini; Anderson, George; de Melo, Luiz Gustavo Piccoli; Drozdstoj, Stoyanov; Moreira, Estefania; Carvalho, André F; Nunes, Sandra Odebrecht Vargas

2018-04-17

Major affective disorders including bipolar disorder (BD) and major depressive disorder (MDD) are associated with impaired health-related quality of life (HRQoL). Oxidative stress and subtle thyroid abnormalities may play a pathophysiological role in both disorders. Thus, the current study was performed to examine whether neuro-oxidative biomarkers and thyroid-stimulating hormone (TSH) levels could predict HRQoL in BD and MDD. This cross-sectional study enrolled 68 BD and 37 MDD patients and 66 healthy controls. The World Health Organization (WHO) QoL-BREF scale was used to assess 4 QoL subdomains. Peripheral blood malondialdehyde (MDA), advanced oxidation protein products, paraoxonaxe/CMPAase activity, a composite index of nitro-oxidative stress, and basal TSH were measured. In the total WHOQoL score, 17.3% of the variance was explained by increased advanced oxidation protein products and TSH levels and lowered CMPAase activity and male gender. Physical HRQoL (14.4%) was associated with increased MDA and TSH levels and lowered CMPAase activity. Social relations HRQoL (17.4%) was predicted by higher nitro-oxidative index and TSH values, while mental and environment HRQoL were independently predicted by CMPAase activity. Finally, 73.0% of the variance in total HRQoL was explained by severity of depressive symptoms, use of anticonvulsants, lower income, early lifetime emotional neglect, MDA levels, the presence of mood disorders, and suicidal ideation. These data show that lowered HRQoL in major affective disorders could at least in part result from the effects of lipid peroxidation, protein oxidation, lowered antioxidant enzyme activities, and higher levels of TSH. © 2018 John Wiley & Sons, Ltd.

A novel thyroid function index associated with opposite therapeutic outcomes in advanced hepatocellular carcinoma patients receiving chemotherapy or sorafenib.

PubMed

Chu, Yu-De; Lin, Kwang-Huei; Huang, Ya-Hui; Lin, Chen-Chun; Hung, Chien-Fu; Yeh, Ta-Sen; Lee, Wei-Chen; Yeh, Chau-Ting

2018-05-21

A sustained proportion of advanced hepatocellular carcinoma (HCC) patients worldwide received either chemotherapy or sorafenib. However, to date, effective and convenient biomarkers to predict their therapeutic outcomes remained elusive. Hypothyroidism was associated with favorable anticancer treatment outcomes in several advanced cancers. Here, we aimed to investigate the potential of using thyroid-stimulating hormone (TSH) and free T4 (FT4) levels as biomarkers to predict clinical outcomes in HCC patients receiving chemotherapy or sorafenib. Total 123 advanced HCC patients at Barcelona Clinical Liver Cancer Stage C were included. They were separated into two cohorts, one treated by sorafenib (n = 62) and the other by chemotherapy (n = 61). Clinical data including TSH and FT4 were retrieved and correlated with treatment outcomes. Because of restriction in local insurance policy, the baseline liver function reserve was better in patients receiving sorafenib. Therefore, the two cohorts were analyzed separately. The results showed that a higher (> median) TSH × FT4 value was independently associated with favorable time-to-tumor progression (P = 0.006) and overall survival (P = 0.002) if chemotherapy was provided; whereas it was associated with unfavorable time-to-tumor progression (P = 0.017) and overall survival (P = 0.001) if sorafenib was administrated. These opposite associations remained valid when patients with Child-Pugh class A liver function from either cohort were included for analysis. A novel thyroid function index, TSH × FT4, significantly predicted opposite clinical outcomes in advanced HCC patients receiving sorafenib or chemotherapy treatment. © 2018 John Wiley & Sons Australia, Ltd.

Superiority of delayed risk stratification in differentiated thyroid cancer after total thyroidectomy and radioactive iodine ablation.

PubMed

Hong, Chae Moon; Lee, Won Kee; Jeong, Shin Young; Lee, Sang-Woo; Ahn, Byeong-Cheol; Lee, Jaetae

2014-11-01

The aim of this study was to validate the effectiveness of delayed risk stratification (DRS) in predicting structural progression and compare the predictive value of American Thyroid Association (ATA) risk stratification with that of DRS in patients with differentiated thyroid cancer (DTC). A total of 398 patients with DTC who underwent surgery followed by radioactive iodine ablation were enrolled. Patients were categorized as having excellent response, acceptable response, biochemical incomplete response, or structural incomplete response at 8-15 months' evaluation after radioactive iodine ablation for DRS. Effectiveness of DRS was evaluated according to structural progression-free survival (PFS; median follow-up, 10.7 years). A total of 229 patients (57.5%) were classified as having excellent response, 78 (19.6%) as having acceptable response, 62 (15.6%) as having biochemical incomplete response, and 29 patients (7.3%) as having structural incomplete response. After DRS, 60.2% of intermediate-risk patients and 20.5% of high-risk patients were shifted to the excellent response category. Sixty-nine patients (17.3%) showed structural progression. DRS showed statistical difference in PFS (hazard ratio, 4.268; 95% confidence interval, 3.258-5.477; P<0.001). In multivariate analysis of ATA risk stratification and DRS, DRS was significantly associated with PFS (hazard ratio, 4.383; 95% confidence interval, 3.250-5.912; P<0.001), but ATA risk stratification was not. There was no significant difference in deviances between the use of DRS alone and the use of both DRS and ATA risk stratification (χ=0.103, d.f.=1, P=0.748). DRS is superior to ATA risk stratification in predicting structural disease progression for DTC patients.

Low T3 syndrome as a predictor of poor prognosis in chronic lymphocytic leukemia.

PubMed

Gao, Rui; Chen, Rui-Ze; Xia, Yi; Liang, Jin-Hua; Wang, Li; Zhu, Hua-Yuan; Zhu Wu, Jia-; Fan, Lei; Li, Jian-Yong; Yang, Tao; Xu, Wei

2018-02-19

Low triiodothyronine (T3) state is associated with poor prognosis in critical acute and prolonged illness. However, the information on thyroid dysfunction and cancer is limited. The aim of our study was to evaluate the prognostic value of low T3 syndrome in chronic lymphocytic leukemia (CLL). Two hundred and fifty-eight patients with detailed thyroid hormone profile at CLL diagnosis were enrolled. Low T3 syndrome was defined by low free T3 (FT3) level accompanied by normal-to-low free tetraiodothyronine (FT4) and thyroid-stimulating hormone (TSH) levels. A propensity score-matched method was performed to balance the baseline characteristics. Multivariate Cox regression analyses screened the independent prognostic factors related to time-to-first-treatment (TTFT) and cancer-specific survival (CSS). Area under the curve (AUC) assessed the predictive accuracy of CLL-International Prognostic Index (IPI) together with low T3 syndrome. The results showed that 37 (14.34%) patients had low T3 syndrome, which was significantly associated with unfavorable TTFT and CSS in the propensity-matched cohort, and it was an independent prognostic indicator for both TTFT and CSS. Serum FT3 level was positively related to protein metabolism and anemia, and inversely related to inflammatory state. Patients with only low FT3 demonstrated better survival than those with synchronously low FT3 and FT4, while those with synchronously low FT3, FT4 and TSH had the worst clinical outcome. Low T3 syndrome together with CLL-IPI had larger AUCs compared with CLL-IPI alone in TTFT and CSS prediction. In conclusion, low T3 syndrome may be a good candidate for predicting prognosis in future clinical practice of CLL. © 2018 UICC.

Lenvatinib and Pembrolizumab in DTC

ClinicalTrials.gov

2018-05-21

Columnar Cell Variant Thyroid Gland Papillary Carcinoma; Follicular Variant Thyroid Gland Papillary Carcinoma; Poorly Differentiated Thyroid Gland Carcinoma; Recurrent Thyroid Gland Carcinoma; Stage III Differentiated Thyroid Gland Carcinoma AJCC v7; Stage III Thyroid Gland Follicular Carcinoma AJCC v7; Stage III Thyroid Gland Papillary Carcinoma AJCC v7; Stage IV Thyroid Gland Follicular Carcinoma AJCC v7; Stage IV Thyroid Gland Papillary Carcinoma AJCC v7; Stage IVA Differentiated Thyroid Gland Carcinoma AJCC v7; Stage IVA Thyroid Gland Follicular Carcinoma AJCC v7; Stage IVA Thyroid Gland Papillary Carcinoma AJCC v7; Stage IVB Differentiated Thyroid Gland Carcinoma AJCC v7; Stage IVB Thyroid Gland Follicular Carcinoma AJCC v7; Stage IVB Thyroid Gland Papillary Carcinoma AJCC v7; Stage IVC Differentiated Thyroid Gland Carcinoma AJCC v7; Stage IVC Thyroid Gland Follicular Carcinoma AJCC v7; Stage IVC Thyroid Gland Papillary Carcinoma AJCC v7; Tall Cell Variant Thyroid Gland Papillary Carcinoma; Thyroid Gland Oncocytic Follicular Carcinoma

Imaging of thyrotoxicosis.

PubMed

Sipos, Jennifer A; Kahaly, George J

2012-09-01

The diagnostic algorithm for patients with Graves' disease frequently involves the use of thyroid autoantibody testing and radioisotope scanning (full text available online: http://education.amjmed.com/pp1/248). However, ultrasound has myriad uses in the evaluation of patients with hyperthyroidism. The purpose of this paper is to review the medical literature outlining the important role that ultrasonography (US) can play in the diagnosis and management of patients with hyperthyroidism. We will make a case for the use of ultrasonography in the initial evaluation of all patients with thyrotoxicosis. This review will delineate the advantages of ultrasonography compared to nuclear medicine imaging in determining the etiology of the hyperthyroidism. The role of sonography in predicting remission and relapse of Graves' disease will also be examined. Finally, this paper will detail the importance of ultrasonography in the workup of hyperthyroidism during pregnancy. We will also outline its utility for predicting fetal thyroid dysfunction in maternal Graves' disease without the need for cordocentesis and its attendant complications. Copyright © 2012. Published by Elsevier Inc.

Incidence rate of symptomatic painless thyroiditis presenting with thyrotoxicosis in Denmark as evaluated by consecutive thyroid scintigraphies.

PubMed

Schwartz, Frederik; Bergmann, Natasha; Zerahn, Bo; Faber, Jens

2013-04-01

Painless thyroiditis (PT) is a transient kind of thyrotoxicosis, with lack of uptake on a thyroid scintigraphy in a non-tender thyroid gland, elevated anti-TPO antibodies, no fever, no history of increased iodine intake, and a normal sedimentation rate. The prevalence of PT varies hugely in the literature. To establish the incidence rate of PT in Denmark as well as to describe the phenotype of PT in more detail. Tc-99m pertechnetate scintigraphies were performed over a period of 9.75 years on 6022 consecutive patients (2349 had a thyrotoxic episode), and were divided into high or normal (5528), reduced (300) or lack of uptake (194). Patient records were evaluated: 292 with reduced, and 186 with lack of uptake. As a control measure, 230 consecutive thyrotoxic patients were also analyzed. Based on scintigraphies, 12 patients had PT, 10 with lack of uptake and two with reduced, corresponding to an incidence rate of 0.49/100,000 person years. It was predicted, that only one patient among the newly diagnosed consecutive thyrotoxic cohort had PT. This patient was identified. The prevalence of PT among thyrotoxic patients was 0.51% as evaluated by scintigraphy, and 0.43% among the biochemically thyrotoxic patient cohort. Twenty-five percent had more than one thyrotoxic episode, 75% had at least one subsequent hypothyroid episode, and 33% developed permanent hypothyroidism. PT presenting with symptomatic thyrotoxicosis is an extremely rare disease in Denmark. Symptomatic PT presents most often with no uptake on a Tc-99m pertechnetate scintigraphy. Clinical follow-up is essential.

Identification of occult tumors by whole-specimen mapping in solitary papillary thyroid carcinoma.

PubMed

Park, Seog Yun; Jung, Yuh-S; Ryu, Chang Hwan; Lee, Chang Yoon; Lee, You Jin; Lee, Eun Kyung; Kim, Seok-Ki; Kim, Tae Sung; Kim, Tae Hyun; Jang, Jeyun; Park, Daeyoon; Dong, Seung Myung; Kang, Jae-Goo; Lee, Jin Soo; Ryu, Junsun

2015-08-01

We undertook this study to estimate an accurate incidence and spread patterns of occult papillary thyroid carcinoma (PTC) in patients with a preoperative diagnosis of solitary PTC by using whole-specimen mapping of all specimens after a total thyroidectomy. Enrolled prospectively in this whole-thyroid mapping study are 82 consecutive patients who underwent a total thyroidectomy under a preoperative diagnosis of solitary PTC. All thyroidectomy specimens were serially sectioned in 2 mm thickness and whole-thyroid mapping was carried out for additional foci of occult PTC. The frequencies of occult lesions detected in the whole and contralateral lobe were determined, and clinicopathologic factors associated with multifocality were assessed. Whole-thyroid mapping revealed 66 occult PTC lesions missed by preoperative ultrasound in 37 (45.1%) of the 82 patients. The great majority (92.5%) of the occult PTC was smaller than 3 mm in size and 25 patients (30.5%) had contralateral lesions. We found that the male sex was an independent predictor of multifocality (odds ratio (OR), 3.00; 95% CI, 1.11-8.14), adjusting for preoperative findings. Analysis with pathologic parameters showed that the male sex (OR, 5.03; 95% CI, 1.68-15.08) and extrathyroidal extensions (OR, 3.03; 95% CI, 1.03-8.95) were associated with multifocal PTC. However, none of the clinicopathologic factors evaluated predicted contralateral PTC. Our study demonstrates the diagnostic limitations of ultrasound for the detection of multifocal PTC and the need to consider the possibility of occult lesions in the management of solitary PTC, especially in male patients. © 2015 Society for Endocrinology.

Iodine I-131 With or Without Selumetinib in Treating Patients With Recurrent or Metastatic Thyroid Cancer

ClinicalTrials.gov

2018-05-15

Metastatic Thyroid Gland Carcinoma; Poorly Differentiated Thyroid Gland Carcinoma; Recurrent Thyroid Gland Carcinoma; Stage IV Thyroid Gland Follicular Carcinoma; Stage IV Thyroid Gland Papillary Carcinoma; Stage IVA Thyroid Gland Follicular Carcinoma; Stage IVA Thyroid Gland Papillary Carcinoma; Stage IVB Thyroid Gland Follicular Carcinoma; Stage IVB Thyroid Gland Papillary Carcinoma; Stage IVC Thyroid Gland Follicular Carcinoma; Stage IVC Thyroid Gland Papillary Carcinoma

Hypocalcaemia following total thyroidectomy: An analysis of 806 patients.

PubMed

Nair, C Gopalakrishnan; Babu, Misha J C; Menon, Riju; Jacob, Pradeep

2013-03-01

Permanent hypocalcaemia following thyroidectomy causes considerable morbidity. This prospective observational study aims to define the factors likely to predict hypocalcaemia following total thyroidectomy. Patients who were subjected to total thyroidectomy during January 2005 to December 2009 were followed up for a minimum period of 1 year. Efficacy of an intraoperative parathyroid hormone assay to predict hypocalcaemia was validated. Overall incidence of hypocalcaemia was 23.6% (n = 190) and that of permanent hypocalcaemia was 1.61% (n = 13). Onset was delayed up to 3(rd) postoperative day in 13 patients. Hypocalcaemia was significantly associated with thyroidectomy for Grave's Disease (P = 0.001), Hashimoto's thyroiditis (P = 0.003), and with incidental parathyroidectomy (P = 0.006). The intraoperative assay of parathyroid hormone showed low sensitivity (0.5) and satisfactory specificity (0.9) in predicting hypocalcemia. Hypocalcemia could manifest late in the immediate postoperative period and this may explain latent hypocalcemia. High incidence of hypocalcaemia noted in Grave's Disease could be due to the autoimmunity since same feature was noted associated with Hashimoto's thyroiditis and the incidence of hypocalcaemia was not high in the subgroup with toxic nodular goiter. The incidence of hypocalcemia was not affected by age or sex.

Hypocalcaemia following total thyroidectomy: An analysis of 806 patients

PubMed Central

Nair, C. Gopalakrishnan; Babu, Misha J. C.; Menon, Riju; Jacob, Pradeep

2013-01-01

Background: Permanent hypocalcaemia following thyroidectomy causes considerable morbidity. This prospective observational study aims to define the factors likely to predict hypocalcaemia following total thyroidectomy. Materials and Methods: Patients who were subjected to total thyroidectomy during January 2005 to December 2009 were followed up for a minimum period of 1 year. Efficacy of an intraoperative parathyroid hormone assay to predict hypocalcaemia was validated. Results: Overall incidence of hypocalcaemia was 23.6% (n = 190) and that of permanent hypocalcaemia was 1.61% (n = 13). Onset was delayed up to 3rd postoperative day in 13 patients. Hypocalcaemia was significantly associated with thyroidectomy for Grave's Disease (P = 0.001), Hashimoto's thyroiditis (P = 0.003), and with incidental parathyroidectomy (P = 0.006). The intraoperative assay of parathyroid hormone showed low sensitivity (0.5) and satisfactory specificity (0.9) in predicting hypocalcemia. Conclusion: Hypocalcemia could manifest late in the immediate postoperative period and this may explain latent hypocalcemia. High incidence of hypocalcaemia noted in Grave's Disease could be due to the autoimmunity since same feature was noted associated with Hashimoto's thyroiditis and the incidence of hypocalcaemia was not high in the subgroup with toxic nodular goiter. The incidence of hypocalcemia was not affected by age or sex. PMID:23776907

Thyrotropin suppression and disease progression in patients with differentiated thyroid cancer: results from the National Thyroid Cancer Treatment Cooperative Registry.

PubMed

Cooper, D S; Specker, B; Ho, M; Sperling, M; Ladenson, P W; Ross, D S; Ain, K B; Bigos, S T; Brierley, J D; Haugen, B R; Klein, I; Robbins, J; Sherman, S I; Taylor, T; Maxon, H R

1998-09-01

The ideal therapy for differentiated thyroid cancer is uncertain. Although thyroid hormone treatment is pivotal, the degree of thyrotropin (TSH) suppression that is required to prevent recurrences has not been studied in detail. We have examined the relation of TSH suppression to baseline disease characteristics and to the likelihood of disease progression in a cohort of thyroid cancer patients who have been followed in a multicenter thyroid cancer registry that was established in 1986. The present study describes 617 patients with papillary and 66 patients with follicular thyroid cancer followed annually for a median of 4.5 years (range 1-8.6 years). Cancer staging was assessed using a staging scheme developed and validated by the registry. Cancer status was defined as no residual disease; progressive disease at any follow-up time; or death from thyroid cancer. A mean TSH score was calculated for each patient by averaging all available TSH determinations, where 1 = undetectable TSH; 2 = subnormal TSH; 3 = normal TSH; and 4 = elevated TSH. Patients were also grouped by their TSH scores: group 1: mean TSH score 1.0-1.99; group 2: mean TSH score 2.0-2.99; group 3: mean TSH score 3.0-4.0. The degree of TSH suppression did not differ between papillary and follicular thyroid cancer patients. However, TSH suppression was greater in papillary cancer patients who were initially classified as being at higher risk for recurrence. This was not the case for follicular cancer patients, where TSH suppression was similar for all patients. For all stages of papillary cancer, a Cox proportional hazards model showed that disease stage, patient age, and radioiodine therapy all predicted disease progression, but TSH score category did not. However, TSH score category was an independent predictor of disease progression in high risk patients (p = 0.03), but was no longer significant when radioiodine therapy was included in the model (p = 0.09). There were too few patients with follicular cancer for multivariate analysis. These data suggest that physicians use greater degrees of TSH suppression in higher risk papillary cancer patients. Our data do not support the concept that greater degrees of TSH suppression are required to prevent disease progression in low-risk patients, but this possibility remains in high-risk patients. Additional studies with more patients and longer follow-up may provide the answer to this important question.

Predictors of Hypothyroidism in Hodgkin Lymphoma Survivors After Intensity Modulated Versus 3-Dimensional Radiation Therapy.

PubMed

Pinnix, Chelsea C; Cella, Laura; Andraos, Therese Y; Ayoub, Zeina; Milgrom, Sarah A; Gunther, Jillian; Thosani, Sonali; Wogan, Christine; Conson, Manuel; D'Avino, Vittoria; Oki, Yasuhiro; Fanale, Michelle; Lee, Hun J; Neelapu, Sattva; Fayad, Luis; Hagemeister, Frederick; Rodriguez, M Alma; Nastoupil, Loretta J; Nieto, Yago; Qiao, Wei; Pacelli, Roberto; Dabaja, Bouthaina

2018-03-14

To identify predictors of hypothyroidism after chemoradiation therapy for Hodgkin lymphoma (HL) and to compare outcomes after intensity modulated radiation therapy (IMRT) with those after 3-dimensional (3D) conformal radiation therapy (CRT). Ninety patients who underwent involved-site IMRT in 2009 through 2014 were evaluated for treatment-induced hypothyroidism, defined as elevated thyroid-stimulating hormone or decreased free thyroxine levels (or both). Receiver operating characteristic curve analysis identified individuals at low versus high risk based on dosimetric variables. Dosimetric cutoff points were verified with an external data set of 50 patients who underwent 3D-CRT. In the IMRT group, most patients (75 [83%]) had stage II HL, and the median prescribed dose was 30.6 Gy; in the 3D-CRT group, 32 patients (64%) had stage II HL, and the median prescribed dose was 32.0 Gy. No differences were found in the proportions of patients with bilateral (P = .982) or unilateral (P = .074) neck involvement between the 2 groups. Hypothyroidism rates were marginally higher in the IMRT group, with estimated 3-year rates of freedom from hypothyroidism of 56.1% in the 3D-CRT group and 40% in the IMRT group (P = .057). Univariate analysis showed that smaller thyroid volume and higher thyroid dose were associated with hypothyroidism in both groups (P < .05). In the IMRT group, the percentage of the thyroid gland volume receiving ≥25 Gy (V25) and the absolute volume of the thyroid gland spared from 25 Gy (VS25Gy) were the strongest predictors of hypothyroidism (P = .001 and P < .001, respectively). Cutoff points of 63.5% (V25) and 2.2 mL (VS25Gy) classified patients as high risk (80%-82%) or low risk (37%-44%) (P < .001). Use of a thyroid avoidance structure reduced the incidence of hypothyroidism (P < .05) in the IMRT group. The percentage of the thyroid receiving 25 Gy and the volume of the thyroid spared from 25 Gy predicted the risk of hypothyroidism after either IMRT or 3D-CRT for HL. IMRT may confer a higher risk than 3D-CRT unless a treatment avoidance structure is used during planning. Copyright © 2018 Elsevier Inc. All rights reserved.

A meta-analysis of inferior thyroid artery variations in different human ethnic groups and their clinical implications.

PubMed

Toni, Roberto; Casa, Claudia Della; Castorina, Sergio; Roti, Elio; Ceda, Gianpaolo; Valenti, Giorgio

2005-09-01

We have recently found ethnic differences in superior thyroid artery (STA) variational anatomy. Therefore, we now focus on the inferior thyroid artery (ITA). In particular, we analyze whether presence, numerical variations and site of origin of ITA are influenced by ethnic group and gender, whether and which neck side has the largest arterial caliber, whether differences occur between the presence of ITA and STA, to which extent a non-selective thyroid angiography is effective in visualizing ITA, also in comparison to STA, and which clinical value this information may have in selected pathologies of the thyroid, parathyroid and larynx. A meta-analysis has been performed, including 33 library- and Medline-selected publications on Caucasoids (European and non-European) and East Asians, and a set of original data on European Caucasoids. A total of 6285 Caucasoid and 847 East Asian items, comprising half bodies and arteries, were analyzed. After testing the homogeneity of the available data sources in relation to the anatomical variables under study we calculated a cumulative value for each selected anatomical parameter and evaluated differences using non-parametric statistics. The effectiveness of non-selective thyroid angiography was determined using sensitivity, specificity, positive and negative predictive values. The ITA was more frequently absent in East Asians than in Caucasoids, and respectively either more or less frequently arising from thyrocervical and subclavian arteries, in East Asians versus Caucasoids. In contrast, the ITA was less frequently present both in Caucasoids and East Asians than the STA. In addition, the ITA was more frequently present on the right than on the left side in both ethnic groups, but no neck side predominated in size of arterial caliber in European Caucasoids. Finally, the ITA was more frequently present in East Asian males than females, and the effectiveness of a non-selective thyroid angiography showed higher numbers for ITA than STA in Caucasoids. Statistically significant variations occur in some ITA parameters between Caucasoids and East Asians, and in its presence with respect to STA, within each ethnic group. These differences, together with a sexual dimorphic presence of ITA in East Asians and high effectiveness of its visualization by non-selective angiography in European Caucasoids, may represent an evidence-based supply of anatomical information for analysis in selected pathologies of the thyroid, parathyroid and larynx.

Oncocytic follicular nodules of the thyroid with or without chronic lymphocytic thyroiditis: An institutional experience.

PubMed

Canberk, Sule; Griffin, A Carruth; Goyal, Abha; Wang, He; Montone, Kathleen; Livolsi, Virginia; Baloch, Zubair

2013-01-01

Oncocytic follicular (OF) cells can be a prominent component of fine needle aspiration (FNA) specimens from neoplasms (adenomas and carcinomas) and nodules arising in multinodular goiter and chronic lymphocytic thyroiditis (CLT). Because OF cells can be present in non-neoplastic and neoplastic thyroid lesions it can be challenging to differentiate between these two in FNA specimens. The aims of this study were to determine the risk of malignancy in cases diagnosed as either oncocytic follicular neoplasm (OFN) or hyperplastic/adenomatoid nodule with OF on FNA and to identify clinicopathologic features that may help in predicting malignancy in such cases, especially the presence or absence of CLT. We retrospectively searched the computerized laboratory information system at our institution between 1998 and 2009 for thyroid US guided FNA specimens in which the term "oncocytic/oncocytes" was mentioned in the final cytopathologic diagnosis. A total of 340 cases were selected for this study. The following data points were collected: Patient demographics, site of thyroid biopsy, size of lesion, FNA diagnosis, histopathologic follow-up and presence of CLT. Surgical pathology follow-up (SPFU) was available in 269 (79%) cases. Two hundred and sixty patients were females and 80 males (average age 53 years). The lesion size was <3.0 cm in 241 (71%) and ≥ 3.0 cm in 99 (29%) cases. Cytologic diagnoses included: Follicular neoplasm with oncocytic features (FNOF) 321 and suggestive of FNOF 19 cases; a secondary cytologic diagnosis of CLT was made in 20 cases. SPFU was available in 269 (79%) cases; it was benign in 213 (213/267 = 79%) and malignant in 56 (56/269 = 21%) cases. The background thyroid showed CLT in 67 (25%) cases; 24% (48/196) neoplasms occurred with versus 76% (147/196) without CLT. The rate of malignancy was lower in nodules measuring less than 3.0 cm as compared to those equal or greater than 3.0 cm in size (17% vs. 28% respectively). The presence of CLT did not significantly alter the rate of malignancy in both FNA and surgical pathology specimens. Based on this study, nodule size and not CLT appears to be an important clinicopathologic features in the management of thyroid FNA specimens diagnosed as OFN.

Assessing the relationship between perfluoroalkyl substances, thyroid hormones and binding proteins in pregnant women; a longitudinal mixed effects approach.

PubMed

Berg, Vivian; Nøst, Therese Haugdahl; Hansen, Solrunn; Elverland, Astrid; Veyhe, Anna-Sofía; Jorde, Rolf; Odland, Jon Øyvind; Sandanger, Torkjel Manning

2015-04-01

The mechanisms involved in thyroid homeostasis are complex, and perfluoroalkyl substances (PFASs) have been indicated to interfere at several levels in this endocrine system. Disruption of the maternal thyroid homeostasis during early pregnancy is of particular concern, where subclinical changes in maternal thyroid hormones (THs) may affect embryonic and foetal development. The present study investigated associations between THs, thyroid binding proteins (TH-BPs) and PFAS concentrations in pregnant women from Northern Norway. Women participating in The Northern Norway Mother-and-Child contaminant Cohort Study (MISA) donated a blood sample at three visits related to their pregnancy and postpartum period (during the second trimester, 3 days and 6 weeks after delivery) in the period 2007-2009. Participants were assigned to quartiles according to PFAS concentrations during the second trimester and mixed effects linear models were used to investigate potential associations between PFASs and repeated measurements of THs, TH-BPs, thyroxin binding capacity and thyroid peroxidase antibodies (anti-TPOs). Women within the highest perfluorooctane sulfonate (PFOS) quartile had 24% higher mean concentrations of thyroid stimulating hormone (TSH) compared to the first quartile at all sampling points. Women within the highest quartiles of perfluorodecanoate (PFDA) had 4% lower mean concentrations of triiodothyronine (T3) and women within the highest quartile of perfluoroundecanoate (PFUnDA) had 3% lower mean concentrations of free triiodothyronine (FT3). Further, the difference in concentrations and the changes between three time points were the same for the PFAS quartiles. Thyroxin binding capacity was associated with all the THs and TH-BPs, and was selected as a holistic adjustment for individual changes in TH homeostasis during pregnancy. Finally, adjusting for maternal iodine status did not influence the model predictions. Findings in the present study suggest modifications of TH homeostasis by PFASs in a background exposed maternal population. The variation in levels of THs between PFAS quartiles was within normal reference ranges and may not be of clinical significance in the pregnant woman. However, subtle individual changes in maternal THs may have significant consequences for foetal health. Copyright © 2015 Elsevier Ltd. All rights reserved.

Spectrum of the Breast Lesions With Increased 18F-FDG Uptake on PET/CT

PubMed Central

Dong, Aisheng; Wang, Yang; Lu, Jianping; Zuo, Changjing

2016-01-01

Abstract Interpretation of 18F-FDG PET/CT studies in breast is challenging owing to nonspecific FDG uptake in various benign and malignant conditions. Benign conditions include breast changes in pregnancy and lactation, gynecomastia, mastitis, fat necrosis, fibroadenoma, intraductal papilloma, and atypical ductal hyperplasia. Among malignancies, invasive ductal carcinoma and invasive lobular carcinoma are common histological types of breast carcinoma. Rarely, other unusual histological types of breast carcinomas (eg, intraductal papillary carcinoma, invasive micropapillary carcinoma, medullary carcinoma, mucinous carcinoma, and metaplastic carcinoma), lymphoma, and metastasis can be the causes. Knowledge of a wide spectrum of hypermetabolic breast lesions on FDG PET/CT is essential in accurate reading of FDG PET/CT. The purpose of this atlas article is to demonstrate features of various breast lesions encountered at our institution, both benign and malignant, which can result in hypermetabolism on FDG PET/CT imaging. PMID:26975010

Cediranib Maleate With or Without Lenalidomide in Treating Patients With Thyroid Cancer

ClinicalTrials.gov

2018-05-23

Recurrent Thyroid Gland Carcinoma; Stage I Thyroid Gland Follicular Carcinoma AJCC v7; Stage I Thyroid Gland Papillary Carcinoma AJCC v7; Stage II Thyroid Gland Follicular Carcinoma AJCC v7; Stage II Thyroid Gland Papillary Carcinoma AJCC v7; Stage III Thyroid Gland Follicular Carcinoma AJCC v7; Stage III Thyroid Gland Papillary Carcinoma AJCC v7; Stage IV Thyroid Gland Follicular Carcinoma AJCC v7; Stage IV Thyroid Gland Papillary Carcinoma AJCC v7; Stage IVA Thyroid Gland Follicular Carcinoma AJCC v7; Stage IVA Thyroid Gland Papillary Carcinoma AJCC v7; Stage IVB Thyroid Gland Follicular Carcinoma AJCC v7; Stage IVB Thyroid Gland Papillary Carcinoma AJCC v7; Stage IVC Thyroid Gland Follicular Carcinoma AJCC v7; Stage IVC Thyroid Gland Papillary Carcinoma AJCC v7

Recurrent Silent Thyroiditis as a Sequela of Postpartum Thyroiditis

PubMed Central

Kim, Paul

2014-01-01

Thyroiditis encompasses a group of disorders characterized by thyroid inflammation. Though clinically indistinguishable from silent thyroiditis, postpartum thyroiditis occurs in women within 12 months after delivery. Recurrent postpartum thyroiditis in subsequent pregnancies is common, but recurrent silent thyroiditis is rare. We reported a case of patient with recurrent episodes of thyroiditis, unrelated to pregnancy, after an episode of postpartum thyroiditis. It is of interest that postpartum thyroiditis and silent thyroiditis could occur closely to each other; however, the link between these disorders is not well established. This report is to remind physicians of the possibility of recurrent silent thyroiditis in women with a history of postpartum thyroiditis. PMID:24987536

Decitabine in Treating Patients With Metastatic Papillary Thyroid Cancer or Follicular Thyroid Cancer Unresponsive to Iodine I 131

ClinicalTrials.gov

2014-08-20

Recurrent Thyroid Cancer; Stage IVA Follicular Thyroid Cancer; Stage IVA Papillary Thyroid Cancer; Stage IVB Follicular Thyroid Cancer; Stage IVB Papillary Thyroid Cancer; Stage IVC Follicular Thyroid Cancer; Stage IVC Papillary Thyroid Cancer

Gallium-67 uptake by the thyroid associated with progressive systemic sclerosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sjoberg, R.J.; Blue, P.W.; Kidd, G.S.

1989-01-01

Although thyroidal uptake of gallium-67 has been described in several thyroid disorders, gallium-67 scanning is not commonly used in the evaluation of thyroid disease. Thyroidal gallium-67 uptake has been reported to occur frequently with subacute thyroiditis, anaplastic thyroid carcinoma, and thyroid lymphoma, and occasionally with Hashimoto's thyroiditis and follicular thyroid carcinoma. A patient is described with progressive systemic sclerosis who, while being scanned for possible active pulmonary involvement, was found incidentally to have abnormal gallium-67 uptake only in the thyroid gland. Fine needle aspiration cytology of the thyroid revealed Hashimoto's thyroiditis. Although Hashimoto's thyroiditis occurs with increased frequency in patientsmore » with progressive systemic sclerosis, thyroidal uptake of gallium-67 associated with progressive systemic sclerosis has not, to our knowledge, been previously described. Since aggressive thyroid malignancies frequently are imaged by gallium-67 scintigraphy, fine needle aspiration cytology of the thyroid often is essential in the evaluation of thyroidal gallium-67 uptake.« less

Pazopanib Hydrochloride in Treating Patients With Advanced Thyroid Cancer

ClinicalTrials.gov

2018-05-08

Recurrent Thyroid Gland Carcinoma; Stage III Differentiated Thyroid Gland Carcinoma AJCC v7; Stage III Thyroid Gland Medullary Carcinoma AJCC v7; Stage IVA Differentiated Thyroid Gland Carcinoma AJCC v7; Stage IVA Thyroid Gland Medullary Carcinoma AJCC v7; Stage IVA Thyroid Gland Undifferentiated (Anaplastic) Carcinoma AJCC v7; Stage IVB Differentiated Thyroid Gland Carcinoma AJCC v7; Stage IVB Thyroid Gland Medullary Carcinoma AJCC v7; Stage IVB Thyroid Gland Undifferentiated (Anaplastic) Carcinoma AJCC v7; Stage IVC Differentiated Thyroid Gland Carcinoma AJCC v7; Stage IVC Thyroid Gland Medullary Carcinoma AJCC v7; Stage IVC Thyroid Gland Undifferentiated (Anaplastic) Carcinoma AJCC v7; Thyroglobulin Antibody Negative; Thyroid Gland Undifferentiated (Anaplastic) Carcinoma

MicroRNA-142-5p contributes to Hashimoto's thyroiditis by targeting CLDN1.

PubMed

Zhu, Jin; Zhang, Yuehua; Zhang, Weichen; Zhang, Wei; Fan, Linni; Wang, Lu; Liu, Yixiong; Liu, Shasha; Guo, Ying; Wang, Yingmei; Yi, Jun; Yan, Qingguo; Wang, Zhe; Huang, Gaosheng

2016-06-08

MicroRNAs have the potential as diagnostic biomarkers and therapeutic targets in autoimmune diseases. However, very limited studies have evaluated the expression of microRNA profile in thyroid gland related to Hashimoto's thyroiditis (HT). MicroRNA microarray expression profiling was performed and validated by quantitative RT-PCR. The expression pattern of miR-142-5p was detected using locked nucleic acid-in situ hybridization. The target gene was predicted and validated using miRNA targets prediction database, gene expression analysis, quantitative RT-PCR, western blot, and luciferase assay. The potential mechanisms of miR-142-5p were studied using immunohistochemistry, immunofluorescence, and quantitative assay of thyrocyte permeability. Thirty-nine microRNAs were differentially expressed in HT (Fold change ≥2, P < 0.05) and miR-142-5p, miR-142-3p, and miR-146a were only high expression in HT thyroid gland (P < 0.001). miR-142-5p, which was expressed at high levels in injured follicular epithelial cells, was also detected in HT patient serum and positively correlated with thyroglobulin antibody (r ≥ 0.6, P < 0.05). Furthermore, luciferase assay demonstrated CLDN1 was the direct target gene of miR-142-5p (P < 0.05), and Immunohistochemical staining showed a reverse expression patterns with miR-142-5p and CLDN1. Overexpression of miR-142-5p in thyrocytes resulted in reducing of the expression of claudin-1 both in mRNA and protein level (P = 0.032 and P = 0.009 respectively) and increasing the permeability of thyrocytes monolayer (P < 0.01). Our findings indicate a previously unrecognized mechanism that miR-142-5p, targeting CLDN1, plays an important role in HT pathogenesis.

Hyperfunctioning parathyroid tumours in patients with thyroid nodules. Sensitivity and positive predictive value of high-resolution ultrasonography and 99mTc-sestamibi scintigraphy.

PubMed

Lumachi, F; Marzola, M C; Zucchetta, P; Tregnaghi, A; Cecchin, D; Bui, F

2003-09-01

A series of 112 consecutive patients with primary hyperparathyroidism who underwent both high-resolution neck ultrasonography (US) and 99mTc-sestamibi/99mTc-pertechnetate subtraction scintigraphy (SS) prior to successful parathyroidectomy was reviewed. There were 29 (25.9%) men and 83 (74.1%) women, with a median age of 58 years (range 13-78 years). Patients were divided into two groups, according to the preoperative US findings: group A (87 patients, 77.7%) without thyroid diseases, and group B (25 patients, 22.3%) with either multinodular goitre or a solitary nontoxic thyroid nodule. In group B patients partial or total thyroidectomy was also performed, according to the intraoperative findings and frozen-section examination results. Final histopathology showed 99 (88.4%) solitary parathyroid (PT) adenomas and 3 (2.7%) PT carcinomas, while 10 (8.9%) patients had a multiglandular disease. The sensitivity and positive predictive value (PPV) were (group A vs group B) 79.8% vs 70.8% (P=0.25) and 95.7% vs 94.4% (P=0.58) for US, and 83.3% vs 87.0% (P=0.47) and 95.9% vs 90.9% (P=0.32) for SS respectively. Better but similar (P=not significant) results were obtained in patients with solitary PT tumours: 81.5% vs 77.8% (US) and 85.0 vs 94.1% (SS) sensitivity; 97.1% vs 93.3% (US) and 95.8% vs 88.9% (SS) PPV. Overall, the combination of US and SS was 92.9% sensitive (group A=93.1%, group B=92.0%; P=0.55), and the PPV reached 100% in each group. In conclusion, in patients with primary hyperparathyroidism the results of both US and SS are independent of coexistent thyroid disease, especially in patients with solitary PT tumours.

[18F]DOPA PET/ceCT in diagnosis and staging of primary medullary thyroid carcinoma prior to surgery.

PubMed

Rasul, Sazan; Hartenbach, Sabrina; Rebhan, Katharina; Göllner, Adelina; Karanikas, Georgios; Mayerhoefer, Marius; Mazal, Peter; Hacker, Marcus; Hartenbach, Markus

2018-05-15

Medullary thyroid carcinoma (MTC) is characterized by a high rate of metastasis. In this study we evaluated the ability of [ 18 F]DOPA PET/ceCT to stage MTC in patients with suspicious thyroid nodules and pathologically elevated serum calcitonin (Ctn) levels prior to total thyroidectomy and lymph node (LN) dissection. A group of 32 patients with sonographically suspicious thyroid nodules and pathologically elevated basal Ctn (bCtn) and stimulated Ctn (sCtn) levels underwent DOPA PET/ceCT prior to surgery. Postoperative histology served as the standard of reference for ultrasonography and DOPA PET/ceCT region-based LN staging. Univariate and multivariate regression analyses as well as receiver operating characteristic analysis were used to evaluate the correlations between preoperative and histological parameters and postoperative tumour persistence or relapse. Primary MTC was histologically verified in all patients. Of the 32 patients, 28 showed increased DOPA decarboxylase activity in the primary tumour (sensitivity 88%, mean SUVmax 10.5). Undetected tumours were exclusively staged pT1a. The sensitivities of DOPA PET in the detection of central and lateral metastatic neck LN were 53% and 73%, in contrast to 20% and 39%, respectively, for neck ultrasonography. Preoperative bCtn and carcinoembryonic antigen levels as well as cN1b status and the number of involved neck regions on DOPA PET/ceCT were predictive of postoperative tumour persistence/relapse in the univariate regression analysis (P < 0.05). Only DOPA PET/ceCT cN1b status remained significant in the multivariate analysis (P = 0.016, relative risk 4.02). This study revealed that DOPA PET/ceCT has high sensitivity in the detection of primary MTC and superior sensitivity in the detection of LN metastases compared to ultrasonography. DOPA PET/ceCT identification of N1b status predicts postoperative tumour persistence. Thus, implementation of a DOPA-guided LN dissection might improve surgical success.

Thyroid Antibody Status, Subclinical Hypothyroidism, and the Risk of Coronary Heart Disease: An Individual Participant Data Analysis

PubMed Central

Collet, Tinh-Hai; Bauer, Douglas C.; Cappola, Anne R.; Åsvold, Bjørn O.; Weiler, Stefan; Vittinghoff, Eric; Gussekloo, Jacobijn; Bremner, Alexandra; den Elzen, Wendy P. J.; Maciel, Rui M. B.; Vanderpump, Mark P. J.; Cornuz, Jacques; Dörr, Marcus; Wallaschofski, Henri; Newman, Anne B.; Sgarbi, José A.; Razvi, Salman; Völzke, Henry; Walsh, John P.; Aujesky, Drahomir

2014-01-01

Context: Subclinical hypothyroidism has been associated with increased risk of coronary heart disease (CHD), particularly with thyrotropin levels of 10.0 mIU/L or greater. The measurement of thyroid antibodies helps predict the progression to overt hypothyroidism, but it is unclear whether thyroid autoimmunity independently affects CHD risk. Objective: The objective of the study was to compare the CHD risk of subclinical hypothyroidism with and without thyroid peroxidase antibodies (TPOAbs). Data Sources and Study Selection: A MEDLINE and EMBASE search from 1950 to 2011 was conducted for prospective cohorts, reporting baseline thyroid function, antibodies, and CHD outcomes. Data Extraction: Individual data of 38 274 participants from six cohorts for CHD mortality followed up for 460 333 person-years and 33 394 participants from four cohorts for CHD events. Data Synthesis: Among 38 274 adults (median age 55 y, 63% women), 1691 (4.4%) had subclinical hypothyroidism, of whom 775 (45.8%) had positive TPOAbs. During follow-up, 1436 participants died of CHD and 3285 had CHD events. Compared with euthyroid individuals, age- and gender-adjusted risks of CHD mortality in subclinical hypothyroidism were similar among individuals with and without TPOAbs [hazard ratio (HR) 1.15, 95% confidence interval (CI) 0.87–1.53 vs HR 1.26, CI 1.01–1.58, P for interaction = .62], as were risks of CHD events (HR 1.16, CI 0.87–1.56 vs HR 1.26, CI 1.02–1.56, P for interaction = .65). Risks of CHD mortality and events increased with higher thyrotropin, but within each stratum, risks did not differ by TPOAb status. Conclusions: CHD risk associated with subclinical hypothyroidism did not differ by TPOAb status, suggesting that biomarkers of thyroid autoimmunity do not add independent prognostic information for CHD outcomes. PMID:24915118

Prevalence of c.2268dup and detection of two novel alterations, c.670_672del and c.1186C>T, in the TPO gene in a cohort of Malaysian–Chinese with thyroid dyshormonogenesis

PubMed Central

Lee, Ching Chin; Harun, Fatimah; Jalaludin, Muhammad Yazid; Heh, Choon Han; Othman, Rozana; Junit, Sarni Mat

2015-01-01

Objectives The c.2268dup mutation in the thyroid peroxidase (TPO) gene is the most common TPO alteration reported in Taiwanese patients with thyroid dyshormonogenesis. The ancestors of these patients are believed to originate from the southern province of China. Our previous study showed that this mutation leads to reduced abundance of the TPO protein and loss of TPO enzyme activity in a Malaysian–Chinese family with goitrous hypothyroidism. The aim of our study was to provide further data on the incidence of the c.2268dup mutation in a cohort of Malaysian–Chinese and its possible phenotypic effects. Setting Cohort study. Participants Twelve biologically unrelated Malaysian–Chinese patients with congenital hypothyroidism were recruited in this study. All patients showed high thyrotropin and low free thyroxine levels at the time of diagnosis with proven presence of a thyroid gland. Primary outcome measure Screening of the c.2268dup mutation in the TPO gene in all patients was carried out using a PCR–direct DNA sequencing method. Secondary outcome measure Further screening for mutations in other exonic regions of the TPO gene was carried out if the patient was a carrier of the c.2268dup mutation. Results The c.2268dup mutation was detected in 4 of the 12 patients. Apart from the c.2268dup and a previously documented mutation (c.2647C>T), two novel TPO alterations, c.670_672del and c.1186C>T, were also detected in our patients. In silico analyses predicted that the novel alterations affect the structure/function of the TPO protein. Conclusions The c.2268dup mutation was detected in approximately one-third of the Malaysian–Chinese patients with thyroid dyshormonogenesis. The detection of the novel c.670_672del and c.1186C>T alterations expand the mutation spectrum of TPO associated with thyroid dyshormonogenesis. PMID:25564141

Inability of recombinant human thyrotropin to predict the evolution from subclinical hypothyroidism to overt disease. A pilot study.

PubMed

Zafon, C; Rodríguez, B; Montoro, J B; Cabo, D; Mesa, J

2012-01-01

The use of recombinant human TSH (rhTSH) is indicated to evaluate thyroid carcinoma patients. In recent years, some authors have reported that rhTSH could serve as a dynamic test of thyroid reserve. The aim of the present study was to determine whether or not rhTSH can predict the evolution from subclinical hypothyroidism (SH) to overt hypothyroidism. Twenty-one women who met the diagnostic criteria of SH were enrolled. All patients received a single dose of rhTSH (0.1 mg). Basal blood samples for TSH, free T4 (fT4), thyroglobulin (Tg), and anti-thyoperoxidase and anti-Tg antibodies were obtained before and 1 day after rhTSH administration. All patients were followed for 2 yr, and blood samples were obtained every 6 months. Twenty-four hours after rhTSH administration, the TSH level increased to >20 mU/l in 14 patients; the serum peak TSH levels remained <10 mU/l in only 5 patients. On follow-up, 7 women (33%) required L-T4 replacement therapy for overt hypothyroidism or a persistent TSH level >10 mlU/l. None of the parameters analyzed differed significantly between patients who developed overt hypothyroidism from those who had persistent SH. The response of thyroid function tests to a single low dose of rhTSH is not useful in identifying those patients with SH who will develop overt hypothyroidism over a 2-yr period.

Tc-99m imaging in thyroidectomized differentiated thyroid cancer patients immediately before I-131 treatment.

PubMed

Tsai, Chi-Jung; Cheng, Cheng-Yi; Shen, Daniel Hueng-Yuan; Kuo, Shou Jen; Wang, Lien-Yen; Lee, Chiang-Hsuan; Wang, Jhi-Joung; Chang, Ming-Che; Huang, Wen-Sheng

2016-02-01

The aim of this study was to evaluate the clinical role of technetium-99m pertechnetate (Tc-99m) imaging in thyroidectomized differentiated thyroid cancer patients immediately before radioiodine-131 (I-131) treatment (Tx). Eighty-six consecutive post-total-thyroidectomy patients (15 men, 71 women; mean age: 46.8 years) with pathologically diagnosed differentiated thyroid cancer were retrospectively studied. Tc-99m imaging immediately before I-131 Tx using both patient-based and lesion-based measurements were analyzed and were further compared with those of post-Tx I-131 whole-body scans. For patients with unequivocally positive Tc-99m uptake, the sensitivity was 77% (patient-based) and 59% (site-based). The positive predictive value (PPV) was 100% for both patient-based and site-based measurements. If equivocal Tc-99m uptake was counted as positive, the sensitivity was 83 and 67%, and the PPV was 100 and 99% for patient-based and site-based measurements, respectively. (a) To increase sensitivity yet maintaining high PPV, equivocal Tc-99m uptake should be considered a positive finding. (b) The nearly 100% PPV of Tc-99m imaging immediately before I-131 Tx for remnant detection suggests that Tc-99m imaging not only serves as an alternative to low-dose I-131 scanning in the low-risk post-thyroidectomy patients but also provides a clue for the subsequent I-131 therapeutic dosage and even for the outcome prediction.

Evaluation of hypothesized adverse outcome pathway linking thyroid peroxidase inhibition to fish early life stage toxicity

EPA Science Inventory

There is an interest in developing alternatives to the fish early-life stage (FELS) test (OECD test guideline 210), for predicting adverse outcomes (e.g., impacts on growth and survival) using less resource-intensive methods. Development and characterization of adverse outcome pa...

Initial investigation of a hypothesized link between thyroid peroxidase inhibition and fish early-life stage toxicity

EPA Science Inventory

There is an interest in developing alternatives to the fish early-life stage (FELS) test (OECD test guideline 210), for predicting adverse outcomes (e.g., impacts on growth and survival) using less resource-intensive methods. Development and characterization of adverse outcome pa...

IN VITRO TO IN VIVO SCREENING OF THYROID HORMONE RECEPTOR DISRUPTING CHEMICALS

EPA Science Inventory

Upon completion of these studies, we will have established the predictive value of the GH3.TRE-LUC cell line to detect chemicals that can impact TH regulated gene expression and TH regulated developmental events in vivo. These studies have excellent potential to discover new c...

Ultrasound-based clinical prediction rule model for detecting papillary thyroid cancer in cervical lymph nodes: A pilot study.

PubMed

Patel, Nayana U; McKinney, Kristin; Kreidler, Sarah M; Bieker, Teresa M; Russ, Paul; Roberts, Katherine; Glueck, Deborah H; Albuja-Cruz, Maria; Klopper, Joshua; Haugen, Bryan R

2016-01-01

To identify sonographic features of cervical lymph nodes (LNs) that are associated with papillary thyroid cancer (PTC) and to develop a prediction model for classifying nodes as metastatic or benign. This retrospective study included the records of postthyroidectomy patients with PTC who had undergone cervical ultrasound and LN biopsy. LN location, size, shape, hilum, echopattern, Doppler flow, and microcalcifications were assessed. Model selection was used to identify features associated with malignant LNs and to build a predictive, binary-outcome, generalized linear mixed model. A cross-validated receiver operating characteristic analysis was conducted to assess the accuracy of the model for classifying metastatic nodes. We analyzed records from 71 LNs (23 metastatic) in 44 patients (16 with PTC). The predictive model included a nonhomogeneous echopattern (odds ratio [OR], 5.73; 95% confidence interval [CI], 1.07-30.74; p = 0.04), microcalcifications (OR, 4.91; 95% CI, 0.91-26.54; p = 0.06), and volume (OR, 2.57; 95% CI, 0.66-9.99; p = 0.16) as predictors. The model had an area under the curve of 0.74 (95% CI, 0.60-0.85), sensitivity of 65% (95% CI, 50% to 78%), and specificity of 85% (95% CI, 73% to 94%) at the Youden optimal cut point of 0.38. Nonhomogeneous echopattern, microcalcifications, and node volume were predictive of malignant LNs in patients with PTC. A larger sample is needed to validate this model. © 2015 Wiley Periodicals, Inc.

Cloning and characterization of a type 3 iodothyronine deiodinase (D3) in the liver of the chondrichtyan Chiloscyllium punctatum.

PubMed

Martínez, Lidia Mayorga; Orozco, Aurea; Villalobos, Patricia; Valverde-R, Carlos

2008-05-01

Thyroid hormone bioactivity is finely regulated at the cellular level by the peripheral iodothyronine deiodinases (D). The study of thyroid function in fish has been restricted mainly to teleosts, whereas the study and characterization of Ds have been overlooked in chondrichthyes. Here we report the cloning and operational characterization of both the native and the recombinant hepatic type 3 iodothyronine deiodinase in the tropical shark Chiloscyllium punctatum. Native and recombinant sD3 show identical catalytic activities: a strong preference for T3-inner-ring deiodination, a requirement for a high concentration of DTT, a sequential reaction mechanism, and resistance to PTU inhibition. The cloned cDNA contains 1298 nucleotides [excluding the poly(A) tail] and encodes a predicted protein of 259 amino acids. The triplet TGA coding for selenocysteine (Sec) is at position 123. The consensus selenocysteine insertion sequence (SECIS) was identified 228 bp upstream of the poly(A) tail and corresponds to form 2. The deduced amino acid sequence was 77% and 72% identical to other D3 cDNAs in fishes and other vertebrates, respectively. As in the case of other piscivore teleost species, shark expresses hepatic D3 through adulthood. This characteristic may be associated with the alimentary strategy in which the protection from an exogenous overload of thyroid hormones could be of physiological importance for thyroidal homeostasis.

Long-term vemurafenib treatment drives inhibitor resistance through a spontaneous KRAS G12D mutation in a BRAF V600E papillary thyroid carcinoma model

PubMed Central

Danysh, Brian P.; Rieger, Erin Y.; Sinha, Deepankar K.; Evers, Caitlin V.; Cote, Gilbert J.; Cabanillas, Maria E.; Hofmann, Marie-Claude

2016-01-01

The BRAF V600E mutation is commonly observed in papillary thyroid cancer (PTC) and predominantly activates the MAPK pathway. Presence of BRAF V600E predicts increasing risk of recurrence and higher mortality rate, and treatment options for such patients are limited. Vemurafenib, a BRAF V600E inhibitor, is initially effective, but cells inevitably develop alternative mechanisms of pathway activation. Mechanisms of primary resistance have been described in short-term cultures of PTC cells; however, mechanisms of acquired resistance have not. In the present study, we investigated possible adaptive mechanisms of BRAF V600E inhibitor resistance in KTC1 thyroid cancer cells following long-term vemurafenib exposure. We found that a subpopulation of KTC1 cells acquired resistance to vemurafenib following 5 months of treatment with the inhibitor. Resistance coincided with the spontaneous acquisition of a KRAS G12D activating mutation. Increases in activated AKT, ERK1/2, and EGFR were observed in these cells. In addition, the resistant cells were less sensitive to combinations of vemurafenib and MEK1 inhibitor or AKT inhibitor. These results support the KRAS G12D mutation as a genetic mechanism of spontaneously acquired secondary BRAF inhibitor resistance in BRAF V600E thyroid cancer cells. PMID:27127178

Role of Ultrasound in Predicting Tumor Invasiveness in Follicular Variant of Papillary Thyroid Carcinoma.

PubMed

Hahn, Soo Yeon; Shin, Jung Hee; Oh, Young Lyun; Kim, Tae Hyuk; Lim, Yaeji; Choi, Ji Soo

2017-09-01

Follicular variant of papillary thyroid carcinoma (FVPTC) is traditionally divided into infiltrative and encapsulated types. Adding to this classification, noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) represents a reclassification of a subset of cases (encapsulated tumors without lymphovascular or capsular invasion). The purpose of this study was to assess the role of ultrasound (US) in predicting tumor invasiveness in FVPTC. From January 2014 to May 2016, preoperative US examinations were performed on 151 patients with 152 FVPTCs who underwent surgery. Based on a pathologic analysis, the FVPTCs were categorized into three groups: NIFTP, invasive encapsulated FVPTC (iE-FVPTC), or infiltrative FVPTC (I-FVPTC). Each nodule was categorized based on the US pattern according to the Korean Thyroid Imaging Reporting and Data System (K-TIRADS) and the American Thyroid Association (ATA) guidelines. The correlation between tumor invasiveness and the K-TIRADS or ATA category was investigated using Spearman's rank correlation coefficient. Among the 152 FVPTCs, there were 48 (31.6%) NIFTPs, 60 (39.5%) iE-FVPTCs, and 44 (28.9%) I-FVPTCs. US characteristics of the FVPTCs differed significantly according to tumor invasiveness (p ≤ 0.030). Tumor invasiveness showed a significant positive correlation with K-TIRADS (tumors of all sizes: r = 0.591, p < 0.001; tumors ≥1.0 cm: r = 0.427, p < 0.001) and ATA categories (tumors of all sizes: r = 0.532, p < 0.001; tumors ≥1.0 cm: r = 0.466, p < 0.001). According to both K-TIRADS and ATA guidelines for all-sized tumors, the most common subtype was NIFTP in low-suspicion nodules (52.6% and 51.6%), iE-FVPTC in intermediate-suspicion nodules (52.7% and 54.2%), and I-FVPTC in high-suspicion nodules (82.5% and 69.4%). After surgery, lymph node metastases were confirmed in two (4.2%) NIFTP cases, three (5.0%) iE-FVPTC cases, and eight (18.2%) I-FVPTC cases (p = 0.001). The results of the BRAF mutation analysis were not significantly different between the groups (p = 0.507). Increasing tumor invasiveness from NIFTP to iE-FVPTC to I-FVPTC is positively correlated with the level of suspicion on US using both K-TIRADS and ATA guidelines.

Autoantibody heritability in thyroiditis: IgG subclass contributions.

PubMed

Outschoorn, Ingrid M; Talor, Monica V; Hoffman, William H; Rowley, Merrill J; Mackay, Ian R; Rose, Noel R; Burek, C Lynne

2011-05-01

Using a simple screening technique called regression of offspring on mid-parent (ROMP) to examine the role of IgG subclasses in affected and unaffected siblings of children and adolescents with autoimmune thyroid disease and their parents, both total-restricted and subclass-restricted autoantibodies to thyroglobulin (Tg) were assayed quantitatively for each of the IgG subclasses. There was a significant correlation of anti-Tg titer of probands with parental titers in thyrotoxicosis (TT), (R(2) = 0.569, p = 0.001), but not in chronic lymphocytic thyroiditis. The most striking correlation was in TT patients of African-American ancestry, (R(2) = 0.9863, p = 0.0007). Additional insight is provided by examining the contributions of the IgG subclasses individually, particularly those whose concentrations appear not to have direct influence on the total IgG titers. Thus, using small numbers of patients, and assaying the IgG subclass distributions, as well as any other immunoglobulin isotypes that are significantly altered in autoantibody assays, ROMP can be performed rapidly to ascertain which quantifiable parameters may be usefully extended to predict disease onset and progression.

The effect of oxidative stress on the progression of Hashimoto's thyroiditis.

PubMed

Ates, Ihsan; Arikan, Mehmet Fettah; Altay, Mustafa; Yilmaz, Fatma Meric; Yilmaz, Nisbet; Berker, Dilek; Guler, Serdar

2017-11-29

We aimed to investigate the effects of oxidative stress in the pathogenesis and progression of Hashimoto's thyroiditis (HT). Forty euthyroid and 40 subclinical hypothyroid patients older than 18 years and not yet had received treatment were enrolled in the study. In the 9 months follow-up, 14 of the HT patients developed overt hypothyroidism. The mean total oxidant status (TOS) and oxidative stress index (OSI) were higher in patients who developed overt hypothyroidism than those who did not (p < .001). And no significant difference was found between the two groups in terms of paraoxanase-1 and arylesterase (p > .05). Multivariable Cox regression model showed thyroid stimulating hormone level (HR = 1.348, p < .001), free-thyroxine level (HR = 0.481, p = .017) and OSI ratio (HR = 2.349, p < .001) to be independent predictors of development of overt hypothyroidism. OSI level, being over 2.96 with 92.9% sensitivity and 62.5% specificity, predicts the risk of hypothyroidism. Oxidative stress may be an effective risk factor in the development of overt hypothyroidism in HT.

Trametinib in Increasing Tumoral Iodine Incorporation in Patients With Recurrent or Metastatic Thyroid Cancer

ClinicalTrials.gov

2018-04-18

BRAF Gene Mutation; Poorly Differentiated Thyroid Gland Carcinoma; RAS Family Gene Mutation; Recurrent Thyroid Gland Carcinoma; Stage IV Thyroid Gland Follicular Carcinoma AJCC v7; Stage IV Thyroid Gland Papillary Carcinoma AJCC v7; Stage IVA Thyroid Gland Follicular Carcinoma AJCC v7; Stage IVA Thyroid Gland Papillary Carcinoma AJCC v7; Stage IVB Thyroid Gland Follicular Carcinoma AJCC v7; Stage IVB Thyroid Gland Papillary Carcinoma AJCC v7; Stage IVC Thyroid Gland Follicular Carcinoma AJCC v7; Stage IVC Thyroid Gland Papillary Carcinoma AJCC v7

Painless giant cell thyroiditis diagnosed by fine needle aspiration and associated with intense thyroidal uptake of gallium

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sanders, L.R.; Moreno, A.J.; Pittman, D.L.

1986-05-01

A 52-year-old woman presented with fever, goiter, and no evidence of pain or tenderness in the thyroid. A diagnosis of silent thyroiditis was made after obtaining evidence of biochemical thyrotoxicosis, intense gallium-67 citrate thyroidal localization, and cytologic thyroiditis. Fine needle aspiration biopsy of the thyroid revealed numerous giant cells in all areas of the thyroid, typical of subacute thyroiditis. This is believed to be the first time painless thyroiditis is reported with the classic cytologic feature of painful subacute thyroiditis.

Painless thyroiditis associated to thyroid carcinoma: role of initial ultrasonography evaluation.

PubMed

Valentini, Raisa Bressan; Macedo, Bruno Mussoi de; Izquierdo, Rogério Friedrich; Meyer, Erika Laurini Souza

2016-04-01

Even though it is a rare event, most associations of thyroid carcinoma with subacute thyroiditis described in the literature are related to its granulomatous form (Quervain's thyroiditis). We present a patient with subacute lymphocytic thyroiditis (painless thyroiditis) and papillary thyroid cancer that was first suspected in an initial ultrasound evaluation. A 30-year old female patient who was referred to the emergency room due to hyperthyroidism symptoms was diagnosed with painless thyroiditis established by physical examination and laboratory findings. With the presence of a palpable painless thyroid nodule an ultrasound was prescribed and the images revealed a suspicious thyroid nodule, microcalcification focus in the heterogeneous thyroid parenquima and cervical lymphadenopathy. Fine needle aspiration biopsy was taken from this nodule; cytology was assessed for compatibility with papillary thyroid carcinoma. Postsurgical pathology evaluation showed a multicentric papillary carcinoma and lymphocytic infiltration. Subacute thyroiditis, regardless of type, may produce transitory ultrasound changes that obscure the coexistence of papillary carcinoma. Due to this, initial thyroid ultrasound evaluation should be delayed until clinical recovery. We recommended a thyroid ultrasound exam for initial evaluation of painless thyroiditis, particularly in patients with palpable thyroid nodule. Further cytological examination is recommended in cases presenting with suspect thyroid nodule and/or non-nodular hypoechoic (> 1 cm) or heterogeneous areas with microcalcification focus.

Assessment of the value of quantitative thyroid scintigraphy for determination of thyroid function in dogs.

PubMed

Shiel, R E; Pinilla, M; McAllister, H; Mooney, C T

2012-05-01

To assess the value of thyroid scintigraphy to determine thyroid status in dogs with hypothyroidism and various non-thyroidal illnesses. Thyroid hormone concentrations were measured and quantitative thyroid scintigraphy performed in 21 dogs with clinical and/or clinicopathological features consistent with hypothyroidism. In 14 dogs with technetium thyroidal uptake values consistent with euthyroidism, further investigations supported non-thyroidal illness. In five dogs with technetium thyroidal uptake values within the hypothyroid range, primary hypothyroidism was confirmed as the only disease in four. The remaining dog had pituitary-dependent hyperadrenocorticism. Two dogs had technetium thyroidal uptake values in the non-diagnostic range. One dog had iodothyronine concentrations indicative of euthyroidism. In the other, a dog receiving glucocorticoid therapy, all iodothyronine concentrations were decreased. Markedly asymmetric technetium thyroidal uptake was present in two dogs. All iodothyronine concentrations were within reference interval but canine thyroid stimulating hormone concentration was elevated in one. Non-thyroidal illness was identified in both cases. In dogs, technetium thyroidal uptake is a useful test to determine thyroid function. However, values may be non-diagnostic, asymmetric uptake can occur and excess glucocorticoids may variably suppress technetium thyroidal uptake and/or thyroid hormone concentrations. Further studies are necessary to evaluate quantitative thyroid scintigraphy as a gold standard method for determining canine thyroid function. © 2012 British Small Animal Veterinary Association.

Thyroiditis: an integrated approach.

PubMed

Sweeney, Lori B; Stewart, Christopher; Gaitonde, David Y

2014-09-15

Thyroiditis is a general term that encompasses several clinical disorders characterized by inflammation of the thyroid gland. The most common is Hashimoto thyroiditis; patients typically present with a nontender goiter, hypothyroidism, and an elevated thyroid peroxidase antibody level. Treatment with levothyroxine ameliorates the hypothyroidism and may reduce goiter size. Postpartum thyroiditis is transient or persistent thyroid dysfunction that occurs within one year of childbirth, miscarriage, or medical abortion. Release of preformed thyroid hormone into the bloodstream may result in hyperthyroidism. This may be followed by transient or permanent hypothyroidism as a result of depletion of thyroid hormone stores and destruction of thyroid hormone-producing cells. Patients should be monitored for changes in thyroid function. Beta blockers can treat symptoms in the initial hyperthyroid phase; in the subsequent hypothyroid phase, levothyroxine should be considered in women with a serum thyroid-stimulating hormone level greater than 10 mIU per L, or in women with a thyroid-stimulating hormone level of 4 to 10 mIU per L who are symptomatic or desire fertility. Subacute thyroiditis is a transient thyrotoxic state characterized by anterior neck pain, suppressed thyroid-stimulating hormone, and low radioactive iodine uptake on thyroid scanning. Many cases of subacute thyroiditis follow an upper respiratory viral illness, which is thought to trigger an inflammatory destruction of thyroid follicles. In most cases, the thyroid gland spontaneously resumes normal thyroid hormone production after several months. Treatment with high-dose acetylsalicylic acid or nonsteroidal anti-inflammatory drugs is directed toward relief of thyroid pain.

Clinicopathological correlations of Bcl-xL and Bax expression in differentiated thyroid carcinoma.

PubMed

Martínez-Brocca, M Asunción; Castilla, Carolina; Navarro, Elena; Amaya, M José; Travado, Paulino; Japón, Miguel A; Sáez, Carmen

2008-02-01

The Bcl-2 family proteins are essential mediators in the apoptotic process. Our aim was to investigate whether anti-apoptotic Bcl-xL and pro-apoptotic Bax were over-expressed in a large series of differentiated thyroid carcinomas (DTC) and to study their association with tumour presentation at diagnosis and prognosis. We examined the immunohistochemical expression of Bcl-xL and Bax in benign nodular thyroid disease (BNTD) and DTC and their association with clinicopathological parameters. Thyroid tissue samples were collected from an unselected series of patients undergoing surgical resection for DTC (n = 74) or BNTD (n = 15). Among DTC cases, expression of Bcl-xL was found to be high in 43.2% and low or absent in 56.8%. Expression of Bax was high in 75.7% and low or absent in 24.3%. Non-neoplastic thyroid tissue was largely unstained for both proteins. Among BNTD cases, expression of Bcl-xL was high in 13.3% and low or absent in 86.6%. Expression of Bax was high in 14.3% and low or absent in 86.6%. A significant association was found between Bcl-xL expression and the presence of high-risk histological subtype (P < 0.05), and regional lymph node (P < 0.01) and distant metastases (P < 0.01). The association between high Bcl-xL expression levels and a longer time of persistent disease after radioiodine ablation was also significant (P < 0.01). Bcl-xL expression was confirmed as an independent prognostic factor for persistent disease in DTC (relative risk, 2.5; 95% confidence interval, 1.1-5.9; P < 0.05). Immunohistochemical expression of Bcl-xL might be a valuable tool in the prediction of tumour aggressiveness in DTC.

Multifocality and Bilaterality of Papillary Thyroid Microcarcinoma

PubMed Central

So, Yoon Kyoung; Kim, Myung Woo

2015-01-01

Objectives Papillary thyroid carcinomas frequently occur as two or more separate foci within the thyroid gland (18%-87%). However, those multifocal tumors are easy to be undetected by preoperative radiologic evaluations, which lead to remnant disease after initial surgery. We aimed to study the incidence of multifocal papillary thyroid microcarcinomas (PTMCs), diagnostic accuracy of preoperative radiologic evaluation, predictive factors, and the chance of bilateral tumors. Methods Two hundred and seventy-seven patients with PTMC were included in this study. All patients underwent total thyroidectomy as an initial treatment. Medical records, pathologic reports, and radiological reports were reviewed for analysis. Results Multifocal PTMCs were detected in 100 of 277 patients (36.1%). The mean number of tumors in each patient was 1.6±1.1, ranging from 1 to 10. The additional tumor foci were significantly smaller (0.32±0.18 cm) than the primary tumors (0.63±0.22 cm) (P<0.001). There was no significant relationship between primary tumor size and the presence of contralateral tumors. With more tumors detected in one lobe, there was greater chance of contralateral tumors; 18.8% with single tumor focus, 30.2% with 2 tumor foci, and 46.2% with 3 or more tumor foci in one lobe. Sensitivity of preoperative sonography was 42.7% for multifocal tumors and 49.0% for bilateral tumors. With multivariate analysis, nodular hyperplasia was the only significant factor for multifocal tumors. Conclusion In cases of PTMCs, the incidence of multifocal tumors is high. However, additional tumor foci are too small to be diagnosed preoperatively, especially under the recent guidelines on radiologic screening tests for papillary thyroid carcinoma. Multifocal PTMCs have high risk of bilateral tumors, necessitating more extensive surgery or more thorough follow-up. PMID:26045918

Hashimoto's thyroiditis predicts outcome in intrathyroidal papillary thyroid cancer.

PubMed

Marotta, Vincenzo; Sciammarella, Concetta; Chiofalo, Maria Grazia; Gambardella, Claudio; Bellevicine, Claudio; Grasso, Marica; Conzo, Giovanni; Docimo, Giovanni; Botti, Gerardo; Losito, Simona; Troncone, Giancarlo; De Palma, Maurizio; Giacomelli, Laura; Pezzullo, Luciano; Colao, Annamaria; Faggiano, Antongiulio

2017-09-01

Hashimoto's thyroiditis (HT) seems to have favourable prognostic impact on papillary thyroid cancer (PTC), but data were obtained analysing all disease stages. Given that HT-related microenvironment involves solely the thyroid, we aimed to assess the relationship between HT, as detected through pathological assessment, and outcome in intrathyroidal PTC. This was a multicentre, retrospective, observational study including 301 PTC with no evidence of extrathyroidal disease. Primary study endpoint was the rate of clinical remission. Auxiliary endpoint was recurrence-free survival (RFS). HT was detected in 42.5% of the cohort and was associated to female gender, smaller tumour size, lower rate of aggressive PTC variants and less frequent post-surgery radio-iodine administration. HT showed relationship with significantly higher rate of clinical remission ( P  < 0.001, OR 4, 95% CI 1.78-8.94). PTCs with concomitant HT had significantly longer RFS, as compared with non-HT tumours ( P  = 0.004). After adjustment for other parameters affecting disease outcome at univariate analysis (age at diagnosis, histology, tumour size and multifocality), prognostic effect of HT remained significant ( P  = 0.006, OR 3.28, 95% CI 1.39-7.72). To verify whether HT could optimise the identification of PTCs with unfavourable outcome, we assessed the accuracy of 'non-HT status' as negative prognostic marker, demonstrating poor capability of identifying patients not maintaining clinical remission until final follow-up (probability of no clinical remission in PTCs without HT: 21.05%, 95% CI 15.20-27.93). In conclusion, our data show that HT represents an independent prognostic parameter in intrathyroidal PTC, but cannot improve prognostic specificity. © 2017 Society for Endocrinology.

Utility of shear wave elastography to detect papillary thyroid carcinoma in thyroid nodules: efficacy of the standard deviation elasticity.

PubMed

Kim, Hye Jeong; Kwak, Mi Kyung; Choi, In Ho; Jin, So-Young; Park, Hyeong Kyu; Byun, Dong Won; Suh, Kyoil; Yoo, Myung Hi

2018-02-23

The aim of this study was to address the role of the elasticity index as a possible predictive marker for detecting papillary thyroid carcinoma (PTC) and quantitatively assess shear wave elastography (SWE) as a tool for differentiating PTC from benign thyroid nodules. One hundred and nineteen patients with thyroid nodules undergoing SWE before ultrasound-guided fine needle aspiration and core needle biopsy were analyzed. The mean (EMean), minimum (EMin), maximum (EMax), and standard deviation (ESD) of SWE elasticity indices were measured. Among 105 nodules, 14 were PTC and 91 were benign. The EMean, EMin, and EMax values were significantly higher in PTCs than benign nodules (EMean 37.4 in PTC vs. 23.7 in benign nodules, p = 0.005; EMin 27.9 vs. 17.8, p = 0.034; EMax 46.7 vs. 31.5, p < 0.001). The EMean, EMin, and EMax were significantly associated with PTC with diagnostic odds ratios varying from 6.74 to 9.91, high specificities (86.4%, 86.4%, and 88.1%, respectively), and positive likelihood ratios (4.21, 3.69, and 4.82, respectively). The ESD values were significantly higher in PTC than in benign nodules (6.3 vs. 2.6, p < 0.001). ESD had the highest specificity (96.6%) when applied with a cut-off value of 6.5 kPa. It had a positive likelihood ratio of 14.75 and a diagnostic odds ratio of 28.50. The shear elasticity index of ESD, with higher likelihood ratios for PTC, will probably identify nodules that have a high potential for malignancy. It may help to identify and select malignant nodules, while reducing unnecessary fine needle aspiration and core needle biopsies of benign nodules.

Serum thyroid stimulating hormone, total and free T4 during the neonatal period: Establishing regional reference intervals

PubMed Central

Sheikhbahaei, Sara; Mahdaviani, Behnaz; Abdollahi, Alireza; Nayeri, Fatemeh

2014-01-01

Context: Congenital hypothyroidism (CH), the most common etiology of preventable mental retardation in children, is estimated to be more prevalent among Asian population. Aims: Since thyroid function tests (TFTs) varied among different ages and geographical regions, in this study, the neonatal thyroid reference intervals in a healthy neonatal population is determined for the first time in Iran. Settings and Design: A cross-sectional study performed on 246 healthy term newborns aged between 2 days and 1 month. Materials and Methods: Blood samples were obtained by venipuncture from all subjects. The median, 2.5th, 5th, 95th, and 97.5th percentile of serum thyroid-stimulating hormone (TSH), as well as the total and free T4 were assessed among different age groups. Statistical Analysis Used: Predictive Analytics Software (PASW Statistics 18) was used for the analysis. Results: Serum TSH, total and free T4 concentration peaked in 5th to 7th days of life, continued over 2 weeks, then decreased and started reaching to adult reference range. A significant negative correlation between age and serum concentration of TSH (P = 0.02), total T4 (P = 0.01) and free T4 (P = 0.01) was found. Conclusion: This study yielded fairly different values for TFTs compared compared values found in other countries and also different from values reported for laboratory kits we used. These differences were assumed to be due to variations in ethnicity, age, and laboratory methods used. Due to the lack of international standardization, conducting multicenter studies helps in making a more precise evaluation of thyroid status in neonates. PMID:24701428

Cytomorphological Spectrum of Thyroiditis: A Review of 110 Cases

PubMed Central

Nair, Rahul; Gambhir, Anushree; Kaur, Supreet; Pandey, Aditi; Shetty, Abhinav; Naragude, Piyusha

2018-01-01

Introduction Different types of thyroiditis may share some parallel clinical and biochemical features. Timely intervention can significantly reduce morbidity and mortality. Aim Aim of this study is to find the frequency of various thyroiditis, study the cytomorphological features and correlate with clinical findings including radiological findings, thyroid function test, and anti-thyroid peroxidase antibodies (Anti-TPO antibodies). Materials and Methods The study included consecutive 110 cases of thyroiditis. Detailed cytomorphological features were studied and correlated with ultrasonography findings, thyroid function test, anti-thyroid peroxidase antibodies (anti-TPO) and histopathological features where thyroidectomy specimens were received for histopathological examination. Results The majority were Hashimoto's thyroiditis (n = 100) and females (n = 103). Other forms of thyroiditis were Hashimoto's thyroiditis with colloid goiter (n = 5), De Quervain's thyroiditis (n = 3), and one case each of postpartum thyroiditis and Hashimoto's thyroiditis with associated malignancy. The majority of patients were in the age group of 21–40 (n = 70) and the majority (n = 73) had diffuse enlargement of thyroid. The majority of patients were hypothyroid (n = 52). The serum anti-TPO antibodies were elevated in 47 patients out of 71 patients. In the 48 patients who underwent ultrasonography, 38 were diagnosed as having thyroiditis. The most consistent cytomorphological features seen in fine-needle aspiration smears of Hashimoto's thyroiditis were increased background lymphocytes, lymphocytic infiltration of thyroid follicular cell clusters, and Hurthle cells. Conclusion The diagnostic cytological features in Hashimoto's thyroiditis are increased background lymphocytes, lymphocytic infiltration of thyroid follicular cell clusters, and Hurthle cells. FNAC remains the “Gold Standard” for diagnosing Hashimoto's thyroiditis. Clinical history, thyroid function, and biochemical parameters are the key for diagnosis of other forms of thyroiditis. PMID:29686830

[Non-autoimmune thyroiditis].

PubMed

Rizzo, Leonardo F L; Mana, Daniela L; Bruno, Oscar D

2014-01-01

The term thyroiditis comprises a group of thyroid diseases characterized by the presence of inflammation, including autoimmune and non-autoimmune entities. It may manifest as an acute illness with severe thyroid pain (subacute thyroiditis and infectious thyroiditis), and conditions in which the inflammation is not clinically evident evolving without pain and presenting primarily thyroid dysfunction and/or goiter (drug-induced thyroiditis and Riedel thyroiditis). The aim of this review is to provide an updated approach on non-autoimmune thyroiditis and its clinical, diagnostic and therapeutic aspects.

Ultrasonography of Various Thyroid Diseases in Children and Adolescents: A Pictorial Essay

PubMed Central

Lee, Eun Hye; Jeong, Sun Hye; Park, Jisang; Lee, Heon

2015-01-01

Thyroid imaging is indicated to evaluate congenital hypothyroidism during newborn screening or in cases of a palpable thyroid mass in children and adolescents. This pictorial essay reviews the ultrasonography (US) of thyroid diseases in children and adolescents, including normal thyroid gland development, imaging features of congenital thyroid disorders (dysgenesis, [aplasia, ectopy, hypoplasia], dyshormonogenesis, transient hypothyroidism, thyroglossal duct cyst), diffuse thyroid disease (Grave's disease, Hashimoto's thyroiditis, and suppurative thyroiditis), and thyroid nodules. The primary imaging modalities for evaluating thyroid diseases are US and radionuclide scintigraphy. Additionally, US can be used to guide aspiration of detected nodules. PMID:25741204

Development of a functional thyroid model based on an organoid culture system.

PubMed

Saito, Yoshiyuki; Onishi, Nobuyuki; Takami, Hiroshi; Seishima, Ryo; Inoue, Hiroyoshi; Hirata, Yuki; Kameyama, Kaori; Tsuchihashi, Kenji; Sugihara, Eiji; Uchino, Shinya; Ito, Koichi; Kawakubo, Hirofumi; Takeuchi, Hiroya; Kitagawa, Yuko; Saya, Hideyuki; Nagano, Osamu

2018-03-04

The low turnover rate of thyroid follicular cells and the lack of a long-term thyroid cell culture system have hampered studies of thyroid carcinogenesis. We have now established a thyroid organoid culture system that supports thyroid cell proliferation in vitro. The established mouse thyroid organoids performed thyroid functions including thyroglobulin synthesis, iodide uptake, and the production and release of thyroid hormone. Furthermore, transplantation of the organoids into recipient mice resulted in the formation of normal thyroid-like tissue capable of iodide uptake and thyroglobulin production in vivo. Finally, forced expression of oncogenic NRAS (NRAS Q61R ) in thyroid organoids established from p53 knockout mice and transplantation of the manipulated organoids into mouse recipients generated a model of poorly differentiated thyroid cancer. Our findings suggest that this newly developed thyroid organoid culture system is a potential research tool for the study of thyroid physiology and pathology including thyroid cancer. Copyright © 2018 Elsevier Inc. All rights reserved.

Iodine I 131 and Pazopanib Hydrochloride in Treating Patients With Recurrent and/or Metastatic Thyroid Cancer Previously Treated With Iodine I 131 That Cannot Be Removed By Surgery

ClinicalTrials.gov

2015-11-04

Recurrent Thyroid Cancer; Stage IVA Follicular Thyroid Cancer; Stage IVA Papillary Thyroid Cancer; Stage IVB Follicular Thyroid Cancer; Stage IVB Papillary Thyroid Cancer; Stage IVC Follicular Thyroid Cancer; Stage IVC Papillary Thyroid Cancer

Impact of lymphocytic thyroiditis on incidence of pathological incidental thyroid carcinoma.

PubMed

Farrell, Eric; Heffron, Cynthia; Murphy, Matthew; O'Leary, Gerard; Sheahan, Patrick

2017-01-01

The purpose of this study was to investigate the impact of lymphocytic thyroiditis on incidence of incidental thyroid cancers. We conducted a retrospective review of 713 consecutive patients who underwent thyroidectomies. Incidental thyroid cancer was defined as an unexpected cancer discovered on pathological examination outside the index nodule undergoing preoperative cytology. We excluded 65 cases because of preoperative diagnosis of thyroid cancer, and 68 because of nonincidental cancer within the index nodule. Among the remaining 580 cases, there were 43 cases (7.4%) of incidental thyroid cancers. Incidental thyroid cancers were significantly associated with moderate/severe lymphocytic thyroiditis (relative risk = 2.5; p = .03). Sixteen of 56 patients with moderate/severe lymphocytic thyroiditis had Graves' disease, none of whom had incidental thyroid cancer. The risk of incidental thyroid cancer associated with moderate/severe lymphocytic thyroiditis was significantly higher in non-Graves' than patients with Graves' disease (p = .05). The risk of incidental thyroid cancer is significantly increased in patients with moderate/severe lymphocytic thyroiditis. Moderate/severe lymphocytic thyroiditis associated with Graves' disease seems to have a lower risk of incidental thyroid cancer. © 2016 Wiley Periodicals, Inc. Head Neck 39: 122-127, 2017. © 2016 Wiley Periodicals, Inc.

Submandibular ectopic thyroid with normally located thyroid gland.

PubMed

Yılmaz, Mahmut Sinan; Aytürk, Semra; Güven, Mehmet; Dilek, Fatma Hüsniye

2014-01-01

Ectopic thyroid is a rare developmental anomaly of the thyroid gland which is defined as the presence of thyroid tissue at a site other than the pretracheal area. Nearly 1 to 3% of all ectopic thyroids are located in the lateral neck. Simultaneous submandibular ectopic thyroid tissue presenting with a functional orthotopic thyroid gland is extremely rare. In this article, we report a 37-year-old female case admitted to our clinic with a complaint of swollen neck in whom ultrasonography revealed submandibular ectopic thyroid tissue presenting with an orthotopic thyroid gland.

Thyroid and parathyroid imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sandler, M.P.; Patton, J.A.; Partain, C.L.

1986-01-01

This book describes the numerous modalities currently used in the diagnosis and treatment of both thyroid and parathyroid disorders. Each modality is fully explained and then evaluated in terms of benefits and limitations in the clinical context. Contents: Production and Quality Control of Radiopharmaceutics Used for Diagnosis and Therapy in Thyroid and Parathyroid Disorders. Basic Physics. Nuclear Instrumentation. Radioimmunoassay: Thyroid Function Tests. Quality Control. Embryology, Anatomy, Physiology, and Thyroid Function Studies. Scintigraphic Thyroid Imaging. Neonatal and Pediatric Thyroid Imaging. Radioiodine Thyroid Uptake Measurement. Radioiodine Treatment of Thyroid Disorders. Radiation Dosimetry of Diagnostic Procedures. Radiation Safety Procedures for High-Level I-131 Therapies.more » X-Ray Fluorescent Scanning. Thyroid Sonography. Computed Tomography in Thyroid Disease. Magnetic Resonance Imaging in Thyroid Disease. Parathyroid Imaging.« less

Increased Prevalence of Chronic Lymphocytic Thyroiditis in Korean Patients with Papillary Thyroid Cancer

PubMed Central

Oh, Chang-Mo; Park, Sohee; Lee, Joo Young; Won, Young-Joo; Shin, Aesun; Kong, Hyun-Joo; Choi, Kui-Sun; Lee, You Jin; Chung, Ki- Wook; Jung, Kyu-Won

2014-01-01

Background In recent years, some reports have suggested that papillary thyroid cancers are more frequently associated with lymphocytic thyroiditis or Hashimoto's thyroiditis. This study investigated a potential increase in the prevalence of chronic lymphocytic thyroiditis among papillary thyroid cancer patients. Materials and Methods We used national epidemiological survey data on thyroid cancer patients diagnosed in 1999, 2005, and 2008. A retrospective medical record survey was conducted by representative sampling of a national cancer incidence database. The analysis included 5,378 papillary thyroid cancer patients aged 20–79 years. We calculated the age-standardized prevalence and age-adjusted prevalence ratios using a binomial regression model with a log link for the prevalence of chronic lymphocytic thyroiditis among papillary thyroid cancer patients by sex for each year. Results The prevalence of chronic lymphocytic thyroiditis among papillary thyroid cancer patients was 4.0% and 12.8% for men and women in 1999, 6.5% and 24.6% in 2005, and 10.7% and 27.6% in 2008, respectively. Between 1999 and 2008, the age-standardized prevalence of chronic lymphocytic thyroiditis increased 4.1-fold in male patients and 2.0-fold in female patients with papillary thyroid cancer. The prevalence of other thyroid diseases, however, did not increase in either gender. Conclusions Among Korean papillary thyroid cancer patients, the prevalence of chronic lymphocytic thyroiditis increased between 1999 and 2008, whereas the prevalence of other thyroid disorders did not change. PMID:24927027

Physiological and psychosocial factors that predict HIV-related fatigue.

PubMed

Barroso, Julie; Hammill, Bradley G; Leserman, Jane; Salahuddin, Naima; Harmon, James L; Pence, Brian Wells

2010-12-01

Fatigue is one of the most common and debilitating symptoms experienced by HIV-infected people. We report the results of our longitudinal analysis of physiological and psychosocial factors that were thought to predict changes in HIV-related fatigue in 128 participants over a 1-year period, in an effort to sort out the complex interplay among a comprehensive set of physiological and psychosocial variables. Physiological measures included hepatic function (aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transpeptidase, alkaline phosphatase, total bilirubin, hepatitis C status), thyroid function (thyroid stimulating hormone, thyroxine), HIV viral load, immunologic function (CD4, CD8, CD4/CD8 ratio, CD16, CD8CD38), gonadal function (testosterone, dehydroepiandrosterone), hematologic function (hemoglobin, hematocrit, serum erythropoietin), and cellular injury (lactic acid). Psychosocial measures included childhood and adult trauma, anxiety, depression, social support, stressful life events, and post-traumatic stress disorder (PTSD). Unemployment, not being on antiretroviral therapy, having fewer years since HIV diagnosis, more childhood trauma, more stressful life events, less social support, and more psychological distress (e.g., PTSD, anxiety and depression) put HIV-infected persons at risk for greater fatigue intensity and fatigue-related impairment in functioning during 1-year follow-up. Physiological variables did not predict greater fatigue. Stressful life events had both direct and indirect effects on fatigue.

Physiological and Psychosocial Factors that Predict HIV-Related Fatigue

PubMed Central

Hammill, Bradley G.; Leserman, Jane; Salahuddin, Naima; Harmon, James L.; Pence, Brian Wells

2010-01-01

Fatigue is one of the most common and debilitating symptoms experienced by HIV-infected people. We report the results of our longitudinal analysis of physiological and psychosocial factors that were thought to predict changes in HIV-related fatigue in 128 participants over a 1-year period, in an effort to sort out the complex interplay among a comprehensive set of physiological and psychosocial variables. Physiological measures included hepatic function (aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transpeptidase, alkaline phosphatase, total bilirubin, hepatitis C status), thyroid function (thyroid stimulating hormone, thyroxine), HIV viral load, immunologic function (CD4, CD8, CD4/CD8 ratio, CD16, CD8CD38), gonadal function (testosterone, dehydroepiandrosterone), hematologic function (hemoglobin, hematocrit, serum erythropoietin), and cellular injury (lactic acid). Psychosocial measures included childhood and adult trauma, anxiety, depression, social support, stressful life events, and post-traumatic stress disorder (PTSD). Unemployment, not being on antiretroviral therapy, having fewer years since HIV diagnosis, more childhood trauma, more stressful life events, less social support, and more psychological distress (e.g., PTSD, anxiety and depression) put HIV-infected persons at risk for greater fatigue intensity and fatigue-related impairment in functioning during 1-year follow-up. Physiological variables did not predict greater fatigue. Stressful life events had both direct and indirect effects on fatigue. PMID:20352317

[Characteristics of thyroid carcinoma in Grave's disease Hashimoto's thyroiditis and nodular goiter].

PubMed

Filipović, A; Paunović, I

2003-01-01

The biology of thyroid cancer represents a spectrum of behavior ranging from well-differentiated lesions with an excellent prognosis to anaplastic carcinoma, which is almost fatal. For this reason, it is important that clinicians have methods at their disposal to asses the characteristics of patient's thyroid malignancy. In this work we discuss the behavior of differentiated thyroid cancer in associated diseases of thyroid as: Graves' disease, chronic lymphocytic thyroiditis--Hashimoto and nodular goiter. This is retrospectively reviewing of 50 patients treated for differentiated thyroid carcinoma at Department of surgery, Clinical Centre of Montenegro in Podgorica from 1998 until 2003. We evaluated occurrence, as well as the role of this diseases in patients with thyroid cancer. We found a more favorable course of thyroid cancer in the presence of chronic lymphocytic thyroiditis and nodular goiter, a contrary Graves' disease. In associated diseases of thyroid, a significantly greater proportion of patients with thyroid cancer, have modular goiter.

IL-1β a potential factor for discriminating between thyroid carcinoma and atrophic thyroiditis.

PubMed

Kammoun-Krichen, Maha; Bougacha-Elleuch, Noura; Mnif, Mouna; Bougacha, Fadia; Charffedine, Ilhem; Rebuffat, Sandra; Rebai, Ahmed; Glasson, Emilie; Abid, Mohamed; Ayadi, Fatma; Péraldi-Roux, Sylvie; Ayadi, Hammadi

2012-01-01

Interactions between cytokines and others soluble factors (hormones, antibodies...) can play an important role in the development of thyroid pathogenesis. The purpose of the present study was to examine the possible correlation between serum cytokine concentrations, thyroid hormones (FT4 and TSH) and auto-antibodies (Tg and TPO), and their usefulness in discriminating between different thyroid conditions. In this study, we investigated serum from 115 patients affected with a variety of thyroid conditions (44 Graves' disease, 17 Hashimoto's thyroiditis, 11 atrophic thyroiditis, 28 thyroid nodular goitre and 15 papillary thyroid cancer), and 30 controls. Levels of 17 cytokines in serum samples were measured simultaneously using a multiplexed human cytokine assay. Thyroid hormones and auto-antibodies were measured using ELISA. Our study showed that IL-1β serum concentrations allow the discrimination between atrophic thyroiditis and papillary thyroid cancer groups (p = 0.027).

A Pathway Approach to Predicting Thyroid Hormone Disrupting Activity of Chemicals Using in vitro, ex vivo and in vivo Assays

EPA Science Inventory

The potential for commercial and industrial chemicals that may be released into the environment to have endocrine disrupting activity is of concern for human health and wildlife. Most initial endocrine disruptor research has focused on estrogen- or androgen-mediated pathways. In ...

Cross-species extrapolation of toxicity information using the Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS) tool

EPA Science Inventory

In the United States, the Endocrine Disruptor Screening Program (EDSP) was established to identify chemicals that may lead to adverse effects via perturbation of the endocrine system (i.e., estrogen, androgen, and thyroid hormone systems). In the mid-1990s the EDSP adopted a two ...

Develop a Systems Approach to Characterizing and Predicting Thyroid Toxicity using an Amphibian Model

EPA Science Inventory

This research makes use of in vitro and in vivo approaches to understand and discriminate the compensatory and toxicological responses of the highly regulated HPT system. Development of an initial systems model will be based on the current understanding of the HPT axis and the co...

Thyroid Fine Needle Aspiration Biopsies in Children: Study of Cytological-Histological Correlation and Immunostaining with Thyroid Peroxidase Monoclonal Antibodies

PubMed Central

Hoperia, Victoria; Larin, Alexander; Jensen, Kirk; Bauer, Andrew; Vasko, Vasily

2010-01-01

Context. There is limited data comparing results of fine needle aspiration biopsies (FNABs) to histological diagnosis in children. Design. FNABs were performed in 707 children and cytological results were compared to histology in 165 cases. The usefulness of immunostaining with anti-TPO monoclonal antibodies (MoAb47) on FNAB samples was examined in 54 operated patients. Results. Among unsatisfactory, benign, suspicious, and malignant FNAB, the histological diagnoses were benign in 12/12 (100%), 69/70 (98.5%), 40/50 (80.0%), and 0/33 (0%), respectively. After surgery, malignancy was established in 44/165 (26.6%) cases. The sensitivity, specificity, and positive and negative predictive values were 95.4%, 55.8%, 61.7%, and 95% with standard FNAB; and 100%, 75%, 73.3, and 100% with MoAb47. Among suspicious FNAB, positive MoAb47 staining was a reliable marker for exclusion of malignancy. Conclusion. Benign and malignant FNAB accurately predict histological diagnosis. In suspicious FNAB, MoAb47 immunostaining may be a useful adjunct to standard cytology. PMID:20652042

Histopathologic study of the so called 'palpation thyroiditis'.

PubMed Central

Hwang, T. S.; Park, S. H.

1988-01-01

We have reviewed 1066 thyroid lesions and compared the relative incidence of the so called 'palpation thyroiditis' between autoimmune thyroiditis and normal thyroid parenchyme surrounding the nodular thyroid lesion and also discussed the pathogenesis of palpation thyroiditis. The typical histopathologic features of 'palpation thyroiditis' were seen in 275 cases among 467 adenomatous goiters and in none of the autoimmune thyroiditis. We here in this paper suggest that the so called 'palpation thyroiditis' is not merely a secondary phenomenon to mechanical follicular damage by vigorous palpation, but this lesion more likely develops in conditions where certain types of physiologic alteration has occurred in follicular basement membrane, just like a pathogenesis of subacute granulomatous thyroiditis. PMID:3079564

[Thyroiditis].

PubMed

Buffet, Camille; Groussin, Lionel

2013-02-01

The diagnosis of thyroiditis encompasses a broad spectrum of thyroid disorders. Analysis of signs and symptoms, biochemical changes, neck ultrasound characteristics and radioactive iodine uptake values allows an accurate diagnosis. Recent studies of the whole genome have helped to identify many susceptibility genes for autoimmune thyroiditis. However, none of these genes contribute to a significant increase in risk of developing this thyroiditis. Clinical awareness of the characteristic presentations of exceptional thyroiditis (acute suppurative thyroiditis, Riedel's thyroiditis) is an important issue. Selenium administration seems to be beneficial for reducing the incidence of thyroiditis. Finally, certain drug-induced thyroiditis remains a therapeutic challenge for the physician.

Coexistence of papillary thyroid cancer and Hashimoto thyroiditis in children: report of 3 cases.

PubMed

Koibuchi, Harumi; Omoto, Kiyoka; Fukushima, Noriyoshi; Toyotsuji, Tomonori; Taniguchi, Nobuyuki; Kawano, Mikihiko

2014-07-01

This report documents 3 pediatric papillary thyroid carcinoma cases with associated Hashimoto thyroiditis. In all 3 cases, hypoechoic nodules accompanied by multiple echogenic spots were noted on sonography of the thyroid. Hashimoto thyroiditis was suspected on the basis of positive thyroid autoantibody test results and pathologic examinations of thyroidectomy specimens, which revealed chronic thyroiditis with lymphocytic infiltration as the background of papillary thyroid carcinoma development. The potential for papillary carcinoma development warrants close follow-up, and meticulous sonographic examinations must be performed in children with Hashimoto thyroiditis. © 2014 by the American Institute of Ultrasound in Medicine.

Predictive and prognostic value of 18F-DOPA PET/CT in patients affected by recurrent medullary carcinoma of the thyroid.

PubMed

Caobelli, Federico; Chiaravalloti, Agostino; Evangelista, Laura; Saladini, Giorgio; Schillaci, Orazio; Vadrucci, Manuela; Scalorbi, Federica; Donner, Davide; Alongi, Pierpaolo

2018-01-01

Medullary thyroid carcinoma (MTC) is a malignancy accounting for about 5-8% of thyroid cancers. Serum calcitonin and carcinoembryonic antigen (CEA) levels are widely used to monitor disease progression. However, prognostic factors able to predict outcomes are highly desirable. We, therefore, aimed to assess the prognostic role of 18 F-DOPA PET/CT in patients with recurrent MTC. 60 patients (mean age 64 ± 13 years, range 44-82) with recurrent MTC were eligible from a multicenter database. All patients underwent a restaging 18 F-DOPA PET/CT, performed at least 6 months after surgery. CEA/calcitonin levels, local recurrences, nodal involvement and metastases at PET/CT were recorded. SUVmax, SUVmean (also normalized to mediastinal uptake) and metabolic tumor volume were automatically calculated for each lesion, by placing a volume of interest around the lesion with 40% of peak activity as threshold for the automatic contouring. The patients were clinically and radiologically followed up for 21 ± 11 months. Rate of progression-free survival (PFS), disease-specific survival (DSS) and incremental prognostic value of 18 F-DOPA PET/CT over conventional imaging modalities were assessed by Kaplan-Meier curves and Log-Rank test. Cox regression univariate and multivariate analyses were performed for assessing predictors of prognosis. 18 F-DOPA PET/CT showed abnormal findings in 27 patients (45%) and resulted unremarkable in 33 (55%). PFS was significantly longer in patients with an unremarkable PET/CT scan (p = 0.018). Similarly, an unremarkable PET/CT study was associated with a significantly longer DSS (p = 0.04). 18 F-DOPA PET/CT added prognostic value over other imaging modalities both for PFS and for DSS (p < 0.001 and p = 0.012, respectively). Neither semiquantitative PET parameters nor clinical or laboratory data were predictive of a worse PFS and DSS in patients with recurrent MTC. 18 F-DOPA PET/CT scan has an important prognostic value in predicting disease progression and mortality rate.

Is visual assessment of thyroid attenuation on unenhanced CT of the chest useful for detecting hypothyroidism?

PubMed

Maldjian, P D; Chen, T

2016-11-01

To determine if visual assessment of the attenuation of morphologically normal appearing thyroid glands on unenhanced computed tomography (CT) of the chest is useful for identifying patients with decreased thyroid function. This was a retrospective study of 765 patients who underwent both unenhanced CT of the chest and thyroid function tests performed within 1 year of the CT examination. Attenuation of the thyroid gland was visually assessed in each patient relative to the attenuation of the surrounding muscles to categorise the gland as "low attenuation" (attenuation similar to surrounding muscles) or "high attenuation" (attenuation greater than surrounding muscles). Thyroid attenuation was quantitatively measured in each case to determine the validity of the visual assessment. Results of thyroid function tests were used to classify thyroid function as hypothyroid, euthyroid, or hyperthyroid. Data were analysed to determine the relationship between visual assessment of thyroid attenuation and status of thyroid function. Thyroid glands of low attenuation were present in 4.2% (32/765) of the patients. Nearly half (47%) of the patients with low-attenuation thyroids had hypofunctioning thyroid glands. Compared to patients with high-attenuation thyroids, patients with low-attenuation thyroids were significantly more likely to have decreased thyroid function (clinical and subclinical hypothyroidism) and significantly less likely to be euthyroid (p<0.0001). Quantitative measurement of thyroid attenuation confirmed the validity of the visual assessment. Low attenuation of an otherwise normal-appearing thyroid gland on unenhanced CT of the chest is strongly associated with decreased thyroid function. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Thyroid Hormone Receptor α Mutation Causes a Severe and Thyroxine-Resistant Skeletal Dysplasia in Female Mice

PubMed Central

Bassett, J. H. Duncan; Boyde, Alan; Zikmund, Tomas; Evans, Holly; Croucher, Peter I.; Zhu, Xuguang; Park, Jeong Won

2014-01-01

A new genetic disorder has been identified that results from mutation of THRA, encoding thyroid hormone receptor α1 (TRα1). Affected children have a high serum T3:T4 ratio and variable degrees of intellectual deficit and constipation but exhibit a consistently severe skeletal dysplasia. In an attempt to improve developmental delay and alleviate symptoms of hypothyroidism, patients are receiving varying doses and durations of T4 treatment, but responses have been inconsistent so far. Thra1PV/+ mice express a similar potent dominant-negative mutant TRα1 to affected individuals, and thus represent an excellent disease model. We hypothesized that Thra1PV/+ mice could be used to predict the skeletal outcome of human THRA mutations and determine whether prolonged treatment with a supraphysiological dose of T4 ameliorates the skeletal abnormalities. Adult female Thra1PV/+ mice had short stature, grossly abnormal bone morphology but normal bone strength despite high bone mass. Although T4 treatment suppressed TSH secretion, it had no effect on skeletal maturation, linear growth, or bone mineralization, thus demonstrating profound tissue resistance to thyroid hormone. Despite this, prolonged T4 treatment abnormally increased bone stiffness and strength, suggesting the potential for detrimental consequences in the long term. Our studies establish that TRα1 has an essential role in the developing and adult skeleton and predict that patients with different THRA mutations will display variable responses to T4 treatment, which depend on the severity of the causative mutation. PMID:24914936

Proposed algorithm for management of patients with thyroid nodules/focal lesions, based on ultrasound (US) and fine-needle aspiration biopsy (FNAB); our own experience

PubMed Central

2013-01-01

Background The standard management in patients with thyroid nodules is to assess the risk of malignancy, based on cytological examination. On the other hand, there are thyroid patterns of ultrasound (US) image, associated with an increased risk of malignancy. The aim of our study was to create a diagnostic algorithm that would employ both data from US examination (expressed by a total score, according to our scoring system) and FNAB results, classified according to Bethesda system (The Bethesda System for Reporting Thyroid Cytopathology - TBSRTC categories). Material and methods 100 thyroid cancer foci (94 papillary carcinomas, 4 medullary carcinomas, 2 undifferentiated carcinomas) and 100 benign focal lesions were selected during postoperative histopathological examination of thyroid glands excised during surgery from 111 patients. The corresponding US images of each lesion – performed in the course of preoperative diagnostics – were evaluated for the presence of seven (7) different features in US image, suggesting a malignant character of lesion, viz. vascularity, i.e., the increased central intranodular blood flows, microcalcifications, “taller-than-wide” orientation, solid composition, hypoechogenicity, irregular margin and either absence of peripheral halo or the presence of outer shell of uneven thickness, surrounding the lesion. The sensitivity, specificity, positive predictive values, negative predictive values and odds ratios for each US feature were calculated. Results In US image of the analyzed cancer foci, we obtained the following values of odds ratio for each of the above mentioned features suggesting malignancy: “taller-than-wide” orientation - odds ratio - 301.0, microcalcifications - 24.67, increased intranodular vascularity - 20.44, hypoechogenicity - 18.61, irregular margins - 7.81, absence of halo - 5.88, and solid composition - 4.16. Taking into account our own experience and the present data, in juxtaposition with the opinions of other authors, we propose a division of US features into 3 groups of different prognostic importance, expressed by a total score calculated based on our scoring system. Accordingly, microcalcifications, “taller-than-wide” orientation, the increased intranodular vascularity, and hypoechogenicity constitute one group - each of the features in this group is awarded 1 point. In turn, the characteristics of minor prognostic importance, such as irregular margin, absence of halo, solid composition, and large size (a diameter longer than 3.0 cm) - are associated with the granting 0.5 points each. The most important prognostic features – a rapid growth (enlargement) of nodules/focal lesions and a presence of pathologically altered lymph nodes are associated with the granting 3 points for each. Our scoring system can be applied in order to better assessment of thyroid US patterns in whole. In patients with a total score ranging from 0 < 4 points there is US pattern of a low risk of malignancy, with ≥ 4 < 7 points - intermediate risk, and in patients with a score ≥ 7 points – a high risk in question. Conclusion Complementary use of our scoring system and FNAB TBSRTC categories can help to make optimal clinical decisions as regards the selection of treatment strategy. PMID:23601166

Proposed algorithm for management of patients with thyroid nodules/focal lesions, based on ultrasound (US) and fine-needle aspiration biopsy (FNAB); our own experience.

PubMed

Adamczewski, Zbigniew; Lewiński, Andrzej

2013-01-01

The standard management in patients with thyroid nodules is to assess the risk of malignancy, based on cytological examination. On the other hand, there are thyroid patterns of ultrasound (US) image, associated with an increased risk of malignancy. The aim of our study was to create a diagnostic algorithm that would employ both data from US examination (expressed by a total score, according to our scoring system) and FNAB results, classified according to Bethesda system (The Bethesda System for Reporting Thyroid Cytopathology - TBSRTC categories). 100 thyroid cancer foci (94 papillary carcinomas, 4 medullary carcinomas, 2 undifferentiated carcinomas) and 100 benign focal lesions were selected during postoperative histopathological examination of thyroid glands excised during surgery from 111 patients. The corresponding US images of each lesion - performed in the course of preoperative diagnostics - were evaluated for the presence of seven (7) different features in US image, suggesting a malignant character of lesion, viz. vascularity, i.e., the increased central intranodular blood flows, microcalcifications, "taller-than-wide" orientation, solid composition, hypoechogenicity, irregular margin and either absence of peripheral halo or the presence of outer shell of uneven thickness, surrounding the lesion. The sensitivity, specificity, positive predictive values, negative predictive values and odds ratios for each US feature were calculated. IN US IMAGE OF THE ANALYZED CANCER FOCI, WE OBTAINED THE FOLLOWING VALUES OF ODDS RATIO FOR EACH OF THE ABOVE MENTIONED FEATURES SUGGESTING MALIGNANCY: "taller-than-wide" orientation - odds ratio - 301.0, microcalcifications - 24.67, increased intranodular vascularity - 20.44, hypoechogenicity - 18.61, irregular margins - 7.81, absence of halo - 5.88, and solid composition - 4.16. Taking into account our own experience and the present data, in juxtaposition with the opinions of other authors, we propose a division of US features into 3 groups of different prognostic importance, expressed by a total score calculated based on our scoring system. Accordingly, microcalcifications, "taller-than-wide" orientation, the increased intranodular vascularity, and hypoechogenicity constitute one group - each of the features in this group is awarded 1 point. In turn, the characteristics of minor prognostic importance, such as irregular margin, absence of halo, solid composition, and large size (a diameter longer than 3.0 cm) - are associated with the granting 0.5 points each. The most important prognostic features - a rapid growth (enlargement) of nodules/focal lesions and a presence of pathologically altered lymph nodes are associated with the granting 3 points for each. Our scoring system can be applied in order to better assessment of thyroid US patterns in whole. In patients with a total score ranging from 0 < 4 points there is US pattern of a low risk of malignancy, with ≥ 4 < 7 points - intermediate risk, and in patients with a score ≥ 7 points - a high risk in question. Complementary use of our scoring system and FNAB TBSRTC categories can help to make optimal clinical decisions as regards the selection of treatment strategy.

Thyroid cell lines in research on goitrogenesis.

PubMed

Gerber, H; Peter, H J; Asmis, L; Studer, H

1991-12-01

Thyroid cell lines have contributed a lot to the understanding of goitrogenesis. The cell lines mostly used in thyroid research are briefly discussed, namely the rat thyroid cell lines FRTL and FRTL-5, the porcine thyroid cell lines PORTHOS and ARTHOS, The sheep thyroid cell lines OVNIS 5H and 6H, the cat thyroid cell lines PETCAT 1 to 4 and ROMCAT, and the human thyroid cell lines FTC-133 and HTh 74. Chinese hamster ovary (CHO) cells and COS-7 cells, stably transfected with TSH receptor cDNA and expressing a functional TSH receptor, are discussed as examples for non-thyroidal cells, transfected with thyroid genes.

Thyroid Echography-induced Thyroid Storm and Exacerbation of Acute Heart Failure.

PubMed

Nakabayashi, Keisuke; Nakazawa, Naomi; Suzuki, Toshiaki; Asano, Ryotaro; Saito, Hideki; Nomura, Hidekimi; Isomura, Daichi; Okada, Hisayuki; Sugiura, Ryo; Oka, Toshiaki

2016-01-01

Hyperthyroidism and thyroid storm affect cardiac circulation in some conditions. Several factors including trauma can induce thyroid storms. We herein describe the case of a 57-year-old woman who experienced a thyroid storm and exacerbation of acute heart failure on thyroid echography. She initially demonstrated a good clinical course after medical rate control for atrial fibrillation; however, thyroid echography for evaluating hyperthyroidism led to a thyroid storm and she collapsed. A multidisciplinary approach stabilized her thyroid hormone levels and hemodynamics. Thus, the medical staff should be prepared for a deterioration in the patient's condition during thyroid echography in heart failure patients with hyperthyroidism.

Shear-Wave Elastography for the Preoperative Risk Stratification of Follicular-patterned Lesions of the Thyroid: Diagnostic Accuracy and Optimal Measurement Plane.

PubMed

Samir, Anthony E; Dhyani, Manish; Anvari, Arash; Prescott, Jason; Halpern, Elkan F; Faquin, William C; Stephen, Antonia

2015-11-01

To evaluate the diagnostic accuracy of shear-wave elastography (SWE) for the diagnosis of malignancy in follicular lesions and to identify the optimal SWE measurement plane. The institutional review board approved this HIPAA-compliant, single-institution, prospective pilot study. Subjects scheduled for surgery after a previous fine-needle aspiration report of "atypia of undetermined significance" or "follicular lesion of undetermined significance," "suspicion for follicular neoplasm," or "suspicion for Hurthle cell neoplasm," were enrolled after obtaining informed consent. Subjects underwent conventional ultrasonography (US), Doppler evaluation, and SWE preoperatively, and their predictive value for thyroid malignancy was evaluated relative to the reference standard of surgical pathologic findings. Thirty-five patients (12 men, 23 women) with a mean age of 55 years (range, 23-85 years) and a fine-needle aspiration diagnosis of atypia of undetermined significance or follicular lesion of undetermined significance (n = 16), suspicion for follicular neoplasm (n = 14), and suspicion for Hurthle cell neoplasm (n = 5) were enrolled in the study. Male sex was a statistically significant (P = .02) predictor of malignancy, but age was not. No sonographic morphologic parameter, including nodule size, microcalcification, macrocalcification, halo sign, taller than wide dimension, or hypoechogenicity, was associated with malignancy. Similarly, no Doppler feature, including intranodular vascularity, pulsatility index, resistive index, or peak-systolic velocity, was associated with malignancy. Higher median SWE tissue Young modulus estimates from the transverse insonation plane were associated with malignancy, yielding an area under the receiver operating characteristic curve of 0.81 (95% confidence interval: 0.62, 1.00) for differentiation of malignant from benign nodules. At a cutoff value of 22.3 kPa, sensitivity, specificity, positive predictive value, and negative predictive value of 82%, 88%, 75%, and 91%, respectively, were observed. This prospective pilot study indicates that SWE may be a valuable tool in preoperative malignancy risk assessment of follicular-patterned thyroid nodules. © RSNA, 2015

Ability of the rhTSH stimulation test to predict relapse in patients with differentiated thyroid carcinoma, after long-term follow-up

PubMed Central

MARCELINO, MAFALDA; LOPES, ANA FILIPA; MADUREIRA, DEOLINDA; FERREIRA, TERESA C.; LIMBERT, EDWARD; LEITE, VALERIANO

2015-01-01

The analysis of serum thyroglobulin (Tg) following thyroid-stimulating hormone (TSH) stimulation (sTg) has been recommended in the follow-up of differentiated thyroid carcinoma (DTC) patients, however, its routine use remains controversial. The aim of the current study was to evaluate the accuracy of sTg testing following recombinant human (rh) TSH stimulation in DTC patients, with a follow-up of 12.4 years. Retrospective studies were conducted of 125 DTC patients, who underwent rhTSH stimulation testing between 1999 and 2002. The exclusion criteria were: Patients with anti-Tg antibodies, Tg levels >1 ng/ml under TSH suppression and the absence of radioactive iodine (RAI) ablation therapy following surgery. In total, 49 patients were included in the study and all had been previously treated with total or near total thyroidectomy (with or without central neck dissection) and RAI, postoperatively. The Tg functional sensitivity was 1.0 ng/ml. The follow-up for patients was performed annually. During the median follow-up of 12.4 years after the rhTSH stimulation test, nine patients exhibited recurrence (18.4%). Of the nine patients, six exhibited sTg levels >2 ng/ml (positive result) and three exhibited levels <2 ng/ml (negative result). Relapse occurred at a mean of 5.9 years following the rhTSH stimulation test. The positive predictive value and negative predictive value (NPV) of positive sTg were 50 and 91.9%, respectively, with a sensitivity of 66.6% and a specificity of 85.0%. The rhTSH-stimulated Tg levels have a high NPV, allowing the identification of the patients who are free of the tumour. These results are consistent with the previously published data; however, to the best of our knowledge, this is the study with the longest follow-up duration after rhTSH stimulation. PMID:25663898

Selumetinib in Treating Patients With Papillary Thyroid Cancer That Did Not Respond to Radioactive Iodine

ClinicalTrials.gov

2016-12-02

Recurrent Thyroid Gland Carcinoma; Stage I Thyroid Gland Papillary Carcinoma; Stage II Thyroid Gland Papillary Carcinoma; Stage III Thyroid Gland Papillary Carcinoma; Stage IV Thyroid Gland Papillary Carcinoma

Thyroid Cancer Screening in South Korea Increases Detection of Papillary Cancers with No Impact on Other Subtypes or Thyroid Cancer Mortality.

PubMed

Ahn, Hyeong Sik; Kim, Hyun Jung; Kim, Kyoung Hoon; Lee, Young Sung; Han, Seung Jin; Kim, Yuri; Ko, Min Ji; Brito, Juan P

2016-11-01

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. 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. Between 2008 and 2010, the incidence of thyroid cancer was 64.1 per 100,000 individuals: the incidence in females was 107.3 and in males was 21.1. There was a strong positive correlation between regional thyroid cancer screening and regional thyroid cancer incidence (r = 0.77, [95% confidence interval 0.70-0.82]). The magnitude of correlation was higher for females (r = 0.88 [CI 0.83-0.92]) than in males (r = 0.76 [CI 0.67-0.84]) in any age group. Thyroid screening was only associated with increased detection of papillary thyroid cancer (r = 0.74 [CI 0.59-0.88]); and not associated with mortality (r = -0.08 [CI -0.59-0.63]) due to thyroid cancer. 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 thyroid cancer, particularly among females. Thyroid cancer screening, however, was only associated with the increase of one tumor histology, papillary thyroid cancer, and it did not have any association with thyroid cancer mortality. The extent to which opportunistic thyroid cancer screening is converting thousands of asymptomatic persons to cancer patients without any known benefit to them needs to be examined carefully.

Thyroid lymphoma: diagnostic pitfalls on pre-operative ago-biopsy.

PubMed

Antonino, Antonio; Rosato, Andrea; Barbato, Filomena; De Dominicis, Gianfranco; De Palma, Maurizio

2013-01-01

Thyroid cancer has the highest prevalence of all endocrine malignancies. Malignancy can be of thyroid or non-thyroid origin. Sarcomas and primary thyroid lymphomas (PTL) are rare and surgery is treatment of choice in the former but not in latter. To describe thyroid lymphomas histological types of thyroid cancer found in a reference center. Medical chart review from admitted patients diagnosed with thyroid cancer in the period from january 2007 to june 2012. Demographic, diagnostic, therapeutic and histopathological information were collected. 1604 records of patients admitted with thyroid disease were reviewed. Among 307 thyroid cancer, the cases diagnosed with rare tumors were: 10 cases of anaplastic carcinoma (3.5%), followed by 4 cases of medullary carcinoma (1.3%), 1 cases of teratoma (0.03%), 2 cases of lymphoma (0.06%). The most frequent clinical presentation was a palpable thyroid nodule. All patients with lymphoma died. Thyroid lymphomas are uncommon and tend to worse outcomes.

A predictive data-driven framework for endocrine prioritization: a triazole fungicide case study.

PubMed

Paul Friedman, Katie; Papineni, Sabitha; Marty, M Sue; Yi, Kun Don; Goetz, Amber K; Rasoulpour, Reza J; Kwiatkowski, Pat; Wolf, Douglas C; Blacker, Ann M; Peffer, Richard C

2016-10-01

The US Environmental Protection Agency Endocrine Disruptor Screening Program (EDSP) is a tiered screening approach to determine the potential for a chemical to interact with estrogen, androgen, or thyroid hormone systems and/or perturb steroidogenesis. Use of high-throughput screening (HTS) to predict hazard and exposure is shifting the EDSP approach to (1) prioritization of chemicals for further screening; and (2) targeted use of EDSP Tier 1 assays to inform specific data needs. In this work, toxicology data for three triazole fungicides (triadimefon, propiconazole, and myclobutanil) were evaluated, including HTS results, EDSP Tier 1 screening (and other scientifically relevant information), and EPA guideline mammalian toxicology study data. The endocrine-related bioactivity predictions from HTS and information that satisfied the EDSP Tier 1 requirements were qualitatively concordant. Current limitations in the available HTS battery for thyroid and steroidogenesis pathways were mitigated by inclusion of guideline toxicology studies in this analysis. Similar margins (3-5 orders of magnitude) were observed between HTS-predicted human bioactivity and exposure values and between in vivo mammalian bioactivity and EPA chronic human exposure estimates for these products' registered uses. Combined HTS hazard and human exposure predictions suggest low priority for higher-tiered endocrine testing of these triazoles. Comparison with the mammalian toxicology database indicated that this HTS-based prioritization would have been protective for any potential in vivo effects that form the basis of current risk assessment for these chemicals. This example demonstrates an effective, human health protective roadmap for EDSP evaluation of pesticide active ingredients via prioritization using HTS and guideline toxicology information.

A predictive data-driven framework for endocrine prioritization: a triazole fungicide case study

PubMed Central

Paul Friedman, Katie; Papineni, Sabitha; Marty, M. Sue; Yi, Kun Don; Goetz, Amber K.; Rasoulpour, Reza J.; Kwiatkowski, Pat; Wolf, Douglas C.; Blacker, Ann M.; Peffer, Richard C.

2016-01-01

Abstract The US Environmental Protection Agency Endocrine Disruptor Screening Program (EDSP) is a tiered screening approach to determine the potential for a chemical to interact with estrogen, androgen, or thyroid hormone systems and/or perturb steroidogenesis. Use of high-throughput screening (HTS) to predict hazard and exposure is shifting the EDSP approach to (1) prioritization of chemicals for further screening; and (2) targeted use of EDSP Tier 1 assays to inform specific data needs. In this work, toxicology data for three triazole fungicides (triadimefon, propiconazole, and myclobutanil) were evaluated, including HTS results, EDSP Tier 1 screening (and other scientifically relevant information), and EPA guideline mammalian toxicology study data. The endocrine-related bioactivity predictions from HTS and information that satisfied the EDSP Tier 1 requirements were qualitatively concordant. Current limitations in the available HTS battery for thyroid and steroidogenesis pathways were mitigated by inclusion of guideline toxicology studies in this analysis. Similar margins (3–5 orders of magnitude) were observed between HTS-predicted human bioactivity and exposure values and between in vivo mammalian bioactivity and EPA chronic human exposure estimates for these products’ registered uses. Combined HTS hazard and human exposure predictions suggest low priority for higher-tiered endocrine testing of these triazoles. Comparison with the mammalian toxicology database indicated that this HTS-based prioritization would have been protective for any potential in vivo effects that form the basis of current risk assessment for these chemicals. This example demonstrates an effective, human health protective roadmap for EDSP evaluation of pesticide active ingredients via prioritization using HTS and guideline toxicology information. PMID:27347635

Hashimoto's thyroiditis following Graves' disease.

PubMed

Umar, Husaini; Muallima, Nur; Adam, John M F; Sanusi, Harsinen

2010-01-01

Both Graves' disease and chronic thyroiditis (Hashimoto's thyroiditis) are autoimmune diseases of thyroid gland. Graves' disease is caused by stimulation of TSH receptor located on the thyroid gland by an antibody, which is known as TSH receptor antibody (TRAb). Furthermore, this may lead to hyperplasia and hyperfunction of the thyroid gland. On the contrary, the cause of Hashimoto's thyroiditis is thought due to a TSH stimulation-blocking antibody (TSBAb) which blocks the action of TSH hormone and subsequently brings damage and atrophy to thyroid gland. Approximately 15-20% of patients with Graves' disease had been reported to have spontaneous hypothyroidism resulting from the chronic thyroiditis (Hashimoto's disease). Pathogenesis for chronic thyroiditis following anti-thyroid drug treatment in patients with Graves' disease remains unclear. It has been estimated that chronic thyroiditis or Hashimoto's disease, which occurs following the Graves' disease episode is due to extended immune response in Graves' disease. It includes the immune response to endogenous thyroid antigens, i.e. thyroid peroxidase and thyroglobulin, which may enhance lymphocyte infiltration and finally causes Hashimoto's thyroiditis. We report four cases of chronic thyroiditis (Hashimoto's disease) in patients who have been previously diagnosed with Graves' hyperthyroidism. In three cases, Hashimoto's thyroiditis occurs in 7 to 25 years after the treatment of Grave's disease; while the other case has it only after few months of Grave's disease treatment. The diagnosis of Hashimoto's disease (chronic thyroiditis) was based on clinical manifestation, high TSHs level, positive thyroid peroxidase antibody and thyroglobulin antibody, and supported by positive results of fine needle aspiration biopsy. Moreover, the result of histopathological test has also confirmed the diagnosis in two cases. All cases have been successfully treated by levothyroxine treatment.

Quantitative single-photon emission computed tomography/computed tomography for technetium pertechnetate thyroid uptake measurement

PubMed Central

Lee, Hyunjong; Kim, Ji Hyun; Kang, Yeon-koo; Moon, Jae Hoon; So, Young; Lee, Won Woo

2016-01-01

Abstract Objectives: Technetium pertechnetate (99mTcO4) is a radioactive tracer used to assess thyroid function by thyroid uptake system (TUS). However, the TUS often fails to deliver accurate measurements of the percent of thyroid uptake (%thyroid uptake) of 99mTcO4. Here, we investigated the usefulness of quantitative single-photon emission computed tomography/computed tomography (SPECT/CT) after injection of 99mTcO4 in detecting thyroid function abnormalities. Materials and methods: We retrospectively reviewed data from 50 patients (male:female = 15:35; age, 46.2 ± 16.3 years; 17 Graves disease, 13 thyroiditis, and 20 euthyroid). All patients underwent 99mTcO4 quantitative SPECT/CT (185 MBq = 5 mCi), which yielded %thyroid uptake and standardized uptake value (SUV). Twenty-one (10 Graves disease and 11 thyroiditis) of the 50 patients also underwent conventional %thyroid uptake measurements using a TUS. Results: Quantitative SPECT/CT parameters (%thyroid uptake, SUVmean, and SUVmax) were the highest in Graves disease, second highest in euthyroid, and lowest in thyroiditis (P < 0.0001, Kruskal–Wallis test). TUS significantly overestimated the %thyroid uptake compared with SPECT/CT (P < 0.0001, paired t test) because other 99mTcO4 sources in addition to thyroid, such as salivary glands and saliva, contributed to the %thyroid uptake result by TUS, whereas %thyroid uptake, SUVmean and SUVmax from the SPECT/CT were associated with the functional status of thyroid. Conclusions: Quantitative SPECT/CT is more accurate than conventional TUS for measuring 99mTcO4 %thyroid uptake. Quantitative measurements using SPECT/CT may facilitate more accurate assessment of thyroid tracer uptake. PMID:27399139

Intraoperative neural monitoring in thyroid surgery: lessons learned from animal studies

PubMed Central

Randolph, Gregory W.; Lu, I-Cheng; Chang, Pi-Ying; Chen, Yi-Ting; Hun, Pao-Chu; Lin, Yi-Chu; Dionigi, Gianlorenzo; Chiang, Feng-Yu

2016-01-01

Recurrent laryngeal nerve (RLN) injury remains a significant morbidity associated with thyroid and parathyroid surgery. In the past decade, surgeons have increasingly used intraoperative neural monitoring (IONM) as an adjunct technique for localizing and identifying the RLN, detecting RLN injury, and predicting the outcome of vocal cord function. In recent years, many animal studies have investigated common pitfalls and new applications of IONM. For example, the use of IONM technology in animal models has proven valuable in studies of the electrophysiology of RLN injury. The advent of animal studies has substantially improved understanding of IONM technology. Lessons learned from animal studies have immediate clinical applications in establishing reliable strategies for preventing intraoperative RLN injury. This article gives an overview of the research progress on IONM-relevant animal models. PMID:27867861

MiR-221, a potential prognostic biomarker for recurrence in papillary thyroid cancer.

PubMed

Dai, Lei; Wang, Yaozong; Chen, Liangliang; Zheng, Jueru; Li, Jianjun; Wu, Xianjiang

2017-01-07

Many studies have reported several transcriptionally deregulated microRNAs (miRNAs) in papillary thyroid cancer (PTC) tissue in comparison with benign thyroid nodules and normal thyroid tissues. However, the correlation between miRNA expressions and PTC recurrence still remains unclear. The PTC patients who scheduled to undergo total thyroidectomy by the same surgical team in Ningbo NO.2 Hospital from March 1998 to March 2008 were enrolled in this study. The clinical and pathological characteristics of each patient were recorded in detail. The selected miRNA expressions were detected using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Potential predictive factors for cancer recurrence were evaluated by univariate and multivariate Cox proportional hazard analysis. A total of 78 patients were enrolled with 49 females at a mean age of 45.8 years. Enrolled patients were divided into two groups: nonrecurrent group (n = 54) and recurrent group (n = 24). The results from the univariate Cox proportional hazard analysis revealed that primary tumor size, TNM stage, extrathyroid extension, miR-221, and miR-222 expressions were significantly associated with PTC recurrence (P < 0.05). The tissue expression of miR-221 was the only independent risk factor for PTC recurrence (HR 1.41; 95%CI 1.14-1.95, P = 0.007) by multiple Cox proportional hazard analysis. This study identified the potential role of miR-221 as a prognostic biomarker for the recurrence in PTC.

Computerized cytometry and wavelet analysis of follicular lesions for detecting malignancy: A pilot study in thyroid cytology.

PubMed

Gilshtein, Hayim; Mekel, Michal; Malkin, Leonid; Ben-Izhak, Ofer; Sabo, Edmond

2017-01-01

The cytologic diagnosis of indeterminate lesions of the thyroid involves much uncertainty, and the final diagnosis often requires operative resection. Computerized cytomorphometry and wavelets analysis were examined to evaluate their ability to better discriminate between benign and malignant lesions based on cytology slides. Cytologic reports from patients who underwent thyroid operation in a single, tertiary referral center were retrieved. Patients with Bethesda III and IV lesions were divided according to their final histopathology. Cytomorphometry and wavelet analysis were performed on the digitized images of the cytology slides. Cytology slides of 40 patients were analyzed. Seven patients had a histologic diagnosis of follicular malignancy, 13 had follicular adenomas, and 20 had a benign goiter. Computerized cytomorphometry with a combination of descriptors of nuclear size, shape, and texture was able to predict quantitatively adenoma versus malignancy within the indeterminate group with 95% accuracy. An automated wavelets analysis with a neural network algorithm reached an accuracy of 96% in identifying correctly malignant vs. benign lesions based on cytology. Computerized analysis of cytology slides seems to be more accurate in defining indeterminate thyroid lesions compared with conventional cytologic analysis, which is based on visual characteristics on cytology as well as the expertise of the cytologist. This pilot study needs to be validated with a greater number of samples. Providing a successful validation, we believe that such methods carry promise for better patient treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

The relationship between chronic lymphocytic thyroiditis and central neck lymph node metastasis in North American patients with papillary thyroid carcinoma.

PubMed

Jara, Sebastian M; Carson, Kathryn A; Pai, Sara I; Agrawal, Nishant; Richmon, Jeremy D; Prescott, Jason D; Dackiw, Alan; Zeiger, Martha A; Bishop, Justin A; Tufano, Ralph P

2013-12-01

Several studies have reported that concurrent chronic lymphocytic thyroiditis (CLT) with papillary thyroid carcinoma (PTC) is associated with improved prognosis of the PTC, including decreased lymph node metastasis. We sought to assess the incidence of central nodal metastasis (CNM) in patients with PTC and concurrent CLT. We studied 495 consecutive patients who underwent thyroidectomy with nodal excision for PTC. Pathology reports identified the presence of CLT and the extent of CNM. There were 226 patients (46%) with CLT and 220 (44%) with CNM. Patients with CLT were more often female (88% vs. 71%; P < .001) and had a younger median age (43 vs. 47 years; P = .03), a lesser incidence of CNM (35% vs. 52.4%; P < .001), and a greater incidence of pT1a (40% vs. 25%; P < .001) and pT1b (38% vs. 29%; P < .001) tumors. Multivariate analysis showed that the presence of CLT was associated with a 39% decreased odds of CNM after adjusting for age, gender, tumor size, PTC histopathologic subtype, and presence of lymphovascular invasion (odds ratio, 0.61; 95% confidence interval, 0.38-0.99; P = .046). Predicted probability modeling showed that all females with CLT and no suspicious nodal findings on ultrasonography had a 9-11% risk of CNM with pT1a tumors. Female patients of all ages with CLT and small PTCs have the least incidence of CNM. Copyright © 2013 Mosby, Inc. All rights reserved.

Thyroid Autoimmunity: Role of Anti-thyroid Antibodies in Thyroid and Extra-Thyroidal Diseases

PubMed Central

Fröhlich, Eleonore; Wahl, Richard

2017-01-01

Autoimmune diseases have a high prevalence in the population, and autoimmune thyroid disease (AITD) is one of the most common representatives. Thyroid autoantibodies are not only frequently detected in patients with AITD but also in subjects without manifest thyroid dysfunction. The high prevalence raises questions regarding a potential role in extra-thyroidal diseases. This review summarizes the etiology and mechanism of AITD and addresses prevalence of antibodies against thyroid peroxidase, thyroid-stimulating hormone receptor (TSHR), and anti-thyroglobulin and their action outside the thyroid. The main issues limiting the reliability of the conclusions drawn here include problems with different specificities and sensitivities of the antibody detection assays employed, as well as potential confounding effects of altered thyroid hormone levels, and lack of prospective studies. In addition to the well-known effects of TSHR antibodies on fibroblasts in Graves’ disease (GD), studies speculate on a role of anti-thyroid antibodies in cancer. All antibodies may have a tumor-promoting role in breast cancer carcinogenesis despite anti-thyroid peroxidase antibodies having a positive prognostic effect in patients with overt disease. Cross-reactivity with lactoperoxidase leading to induction of chronic inflammation might promote breast cancer, while anti-thyroid antibodies in manifest breast cancer might be an indication for a more active immune system. A better general health condition in older women with anti-thyroid peroxidase antibodies might support this hypothesis. The different actions of the anti-thyroid antibodies correspond to differences in cellular location of the antigens, titers of the circulating antibodies, duration of antibody exposure, and immunological mechanisms in GD and Hashimoto’s thyroiditis. PMID:28536577

Role of color Doppler in differentiation of Graves' disease and thyroiditis in thyrotoxicosis

PubMed Central

Donkol, Ragab Hani; Nada, Aml Mohamed; Boughattas, Sami

2013-01-01

AIM: To evaluate the role of thyroid blood flow assessment by color-flow Doppler ultrasonography in the differential diagnosis of thyrotoxicosis and compare it to technetium pertechnetate thyroid scanning. METHODS: Twenty-six patients with thyrotoxicosis were included in the study. Clinical history was taken and physical examination and thyroid function tests were performed for all patients. Thyroid autoantibodies were measured. The thyroid glands of all patients were evaluated by gray scale ultrasonography for size, shape and echotexture. Color-flow Doppler ultrasonography of the thyroid tissue was performed and spectral flow analysis of both inferior thyroid arteries was assessed. Technetium99 pertechnetate scanning of the thyroid gland was done for all patients. According to thyroid scintigraphy, the patients were divided into two groups: 18 cases with Graves’ disease and 8 cases with Hashimoto’s thyroiditis. All patients had suppressed thyrotropin. The diagnosis of Graves’ disease and Hashimoto’s thyroiditis was supported by the clinical picture and follow up of patients. RESULTS: Peak systolic velocities of the inferior thyroid arteries were significantly higher in patients with Graves’ disease than in patients with thyroiditis (P = 0.004 in the right inferior thyroid artery and P = 0.001 in left inferior thyroid artery). Color-flow Doppler ultrasonography parameters demonstrated a sensitivity of 88.9% and a specificity of 87.5% in the differential diagnosis of thyrotoxicosis. CONCLUSION: Color Doppler flow of the inferior thyroid artery can be used in the differential diagnosis of thyrotoxicosis, especially when there is a contraindication of thyroid scintigraphy by radioactive material in some patients. PMID:23671754

Aflibercept in Treating Patients With Recurrent and/or Metastatic Thyroid Cancer That Did Not Respond to Radioactive Iodine Therapy

ClinicalTrials.gov

2017-01-24

Recurrent Thyroid Gland Carcinoma; Stage III Thyroid Gland Follicular Carcinoma; Stage III Thyroid Gland Papillary Carcinoma; Stage IV Thyroid Gland Follicular Carcinoma; Stage IV Thyroid Gland Papillary Carcinoma

Endosonographic examination of thyroid gland among patients with nonthyroid cancers.

PubMed

Alkhatib, Amer A; Mahayni, Abdulah A; Chawki, Ghaleb R; Yoder, Leon; Elkhatib, Fateh A; Al-Haddad, Mohammad

2016-01-01

There is limited endosonographic literature regarding thyroid gland pathology, which is frequently visualized during upper endoscopic ultrasound (EUS). Our objective was to assess the prevalence of benign and malignant thyroid lesions encountered during routine upper EUS within a cancer center setting. The data were prospectively collected and retrospectively analyzed. All upper EUS procedures performed between October 2012 and July 2014 were reviewed at a large referral cancer center. Data collected included patient demographics, preexisting thyroid conditions, thyroid gland dimensions, the presence or absence of thyroid lesions, and EUS morphology of lesions if present, and interventions performed to characterize thyroid lesions and pathology results when applicable. Two hundred and forty-five EUS procedures were reviewed. Of these, 100 cases reported a detailed endosonographic examination of the thyroid gland. Most of the thyroid glands were endosonographically visualized when the tip of the scope was at 18 cm from the incisors. Twelve cases showed thyroid lesions, out of which three previously undiagnosed thyroid cancers were visualized during EUS (two primary papillary thyroid cancers and one anaplastic thyroid cancer). Transesophageal EUS-guided fine needle aspiration of thyroid lesions was feasible when the lesion was in the inferior portion of the thyroid gland, and the tip of the scope was at 18 cm or more from the incisors. Routine EUS examination may detect unexpected thyroid lesions including malignant ones. We encourage endosonographers to screen the visualized portions of the thyroid gland during routine withdrawal of the echoendoscope.

Glucagon Like Peptide-1 Receptor Expression in the Human Thyroid Gland

PubMed Central

Gier, Belinda; Butler, Peter C.; Lai, Chi K.; Kirakossian, David; DeNicola, Matthew M.

2012-01-01

Background: Glucagon like peptide-1 (GLP-1) mimetic therapy induces medullary thyroid neoplasia in rodents. We sought to establish whether C cells in human medullary thyroid carcinoma, C cell hyperplasia, and normal human thyroid express the GLP-1 receptor. Methods: Thyroid tissue samples with medullary thyroid carcinoma (n = 12), C cell hyperplasia (n = 9), papillary thyroid carcinoma (n = 17), and normal human thyroid (n = 15) were evaluated by immunofluorescence for expression of calcitonin and GLP-1 receptors. Results: Coincident immunoreactivity for calcitonin and GLP-1 receptor was consistently observed in both medullary thyroid carcinoma and C cell hyperplasia. GLP-1 receptor immunoreactivity was also detected in 18% of papillary thyroid carcinoma (three of 17 cases). Within normal human thyroid tissue, GLP-1 receptor immunoreactivity was found in five of 15 of the examined cases in about 35% of the total C cells assessed. Conclusions: In humans, neoplastic and hyperplastic lesions of thyroid C cells express the GLP-1 receptor. GLP-1 receptor expression is detected in 18% papillary thyroid carcinomas and in C cells in 33% of control thyroid lobes. The consequence of long-term pharmacologically increased GLP-1 signaling on these GLP-1 receptor-expressing cells in the thyroid gland in humans remains unknown, but appropriately powered prospective studies to exclude an increase in medullary or papillary carcinomas of the thyroid are warranted. PMID:22031513

Thyroid Diseases

MedlinePlus

... beats. All of these activities are your body's metabolism. Thyroid problems include Goiter - enlargement of the thyroid gland Hyperthyroidism - when your thyroid gland makes more thyroid hormones ...

Prediction of Neonatal Hyperthyroidism.

PubMed

Banigé, Maïa; Polak, Michel; Luton, Dominique

2018-06-01

To assess whether it is possible to identify the neonatal predictors of neonatal hyperthyroidism at the presymptomatic stage of the disease. This retrospective multicenter study in 10 maternity units was based on the medical records of all patients monitored for a pregnancy between January 1, 2007, and January 1, 2014. Among 280 000 births, 2288 medical records of women with thyroid dysfunction were selected and screened. Of these, 415 women had Graves disease and were positive for thyrotropin receptor antibody during pregnancy, and were included. A thyroid-stimulating hormone (TSH) level of less than 0.90 mIU/L between days 3 and 7 of life predicted neonatal hyperthyroidism with a sensitivity 78% (95% CI, 74%-82%) and a and specificity of 99% (95% CI, 98%-100%), a positive predictive value of 90% (95% CI, 87%-93%), a negative predictive value of 98% (95% CI, 97%-99%), and an area under the receiver operating characteristic curve of 0.99 (95% CI, 0.97-1.0). A thyrotropin receptor antibody (TRAb) elimination time was calculated using the equation: 7.28 + 2.88 × log() + 11.62 log(TRAb 2 ). All newborns with a TSH level of less than 0.90 mIU/L should be examined by a pediatrician. Using TSH, it is possible to screen for neonatal hypothyroidism and for neonatal hyperthyroidism with a TSH cutoff of 0.90 mIU/L, and this shows the relevance of our study in terms of public health. Copyright © 2018 Elsevier Inc. All rights reserved.

Likelihood ratio-based differentiation of nodular Hashimoto thyroiditis and papillary thyroid carcinoma in patients with sonographically evident diffuse hashimoto thyroiditis: preliminary study.

PubMed

Wang, Liang; Xia, Yu; Jiang, Yu-Xin; Dai, Qing; Li, Xiao-Yi

2012-11-01

To assess the efficacy of sonography for discriminating nodular Hashimoto thyroiditis from papillary thyroid carcinoma in patients with sonographically evident diffuse Hashimoto thyroiditis. This study included 20 patients with 24 surgically confirmed Hashimoto thyroiditis nodules and 40 patients with 40 papillary thyroid carcinoma nodules; all had sonographically evident diffuse Hashimoto thyroiditis. A retrospective review of the sonograms was performed, and significant benign and malignant sonographic features were selected by univariate and multivariate analyses. The combined likelihood ratio was calculated as the product of each feature's likelihood ratio for papillary thyroid carcinoma. We compared the abilities of the original sonographic features and combined likelihood ratios in diagnosing nodular Hashimoto thyroiditis and papillary thyroid carcinoma by their sensitivity, specificity, and Youden index. The diagnostic capabilities of the sonographic features varied greatly, with Youden indices ranging from 0.175 to 0.700. Compared with single features, combinations of features were unable to improve the Youden indices effectively because the sensitivity and specificity usually changed in opposite directions. For combined likelihood ratios, however, the sensitivity improved greatly without an obvious reduction in specificity, which resulted in the maximum Youden index (0.825). With a combined likelihood ratio greater than 7.00 as the diagnostic criterion for papillary thyroid carcinoma, sensitivity reached 82.5%, whereas specificity remained at 100.0%. With a combined likelihood ratio less than 1.00 for nodular Hashimoto thyroiditis, sensitivity and specificity were 90.0% and 92.5%, respectively. Several sonographic features of nodular Hashimoto thyroiditis and papillary thyroid carcinoma in a background of diffuse Hashimoto thyroiditis were significantly different. The combined likelihood ratio may be superior to original sonographic features for discrimination of nodular Hashimoto thyroiditis from papillary thyroid carcinoma; therefore, it is a promising risk index for thyroid nodules and warrants further investigation.

Synthetic gene network restoring endogenous pituitary–thyroid feedback control in experimental Graves’ disease

PubMed Central

Saxena, Pratik; Charpin-El Hamri, Ghislaine; Folcher, Marc; Zulewski, Henryk; Fussenegger, Martin

2016-01-01

Graves’ disease is an autoimmune disorder that causes hyperthyroidism because of autoantibodies that bind to the thyroid-stimulating hormone receptor (TSHR) on the thyroid gland, triggering thyroid hormone release. The physiological control of thyroid hormone homeostasis by the feedback loops involving the hypothalamus–pituitary–thyroid axis is disrupted by these stimulating autoantibodies. To reset the endogenous thyrotrophic feedback control, we designed a synthetic mammalian gene circuit that maintains thyroid hormone homeostasis by monitoring thyroid hormone levels and coordinating the expression of a thyroid-stimulating hormone receptor antagonist (TSHAntag), which competitively inhibits the binding of thyroid-stimulating hormone or the human autoantibody to TSHR. This synthetic control device consists of a synthetic thyroid-sensing receptor (TSR), a yeast Gal4 protein/human thyroid receptor-α fusion, which reversibly triggers expression of the TSHAntag gene from TSR-dependent promoters. In hyperthyroid mice, this synthetic circuit sensed pathological thyroid hormone levels and restored the thyrotrophic feedback control of the hypothalamus–pituitary–thyroid axis to euthyroid hormone levels. Therapeutic plug and play gene circuits that restore physiological feedback control in metabolic disorders foster advanced gene- and cell-based therapies. PMID:26787873

Prevalence of c.2268dup and detection of two novel alterations, c.670_672del and c.1186C>T, in the TPO gene in a cohort of Malaysian-Chinese with thyroid dyshormonogenesis.

PubMed

Lee, Ching Chin; Harun, Fatimah; Jalaludin, Muhammad Yazid; Heh, Choon Han; Othman, Rozana; Junit, Sarni Mat

2015-01-05

The c.2268dup mutation in the thyroid peroxidase (TPO) gene is the most common TPO alteration reported in Taiwanese patients with thyroid dyshormonogenesis. The ancestors of these patients are believed to originate from the southern province of China. Our previous study showed that this mutation leads to reduced abundance of the TPO protein and loss of TPO enzyme activity in a Malaysian-Chinese family with goitrous hypothyroidism. The aim of our study was to provide further data on the incidence of the c.2268dup mutation in a cohort of Malaysian-Chinese and its possible phenotypic effects. Cohort study. Twelve biologically unrelated Malaysian-Chinese patients with congenital hypothyroidism were recruited in this study. All patients showed high thyrotropin and low free thyroxine levels at the time of diagnosis with proven presence of a thyroid gland. Screening of the c.2268dup mutation in the TPO gene in all patients was carried out using a PCR-direct DNA sequencing method. Further screening for mutations in other exonic regions of the TPO gene was carried out if the patient was a carrier of the c.2268dup mutation. The c.2268dup mutation was detected in 4 of the 12 patients. Apart from the c.2268dup and a previously documented mutation (c.2647C>T), two novel TPO alterations, c.670_672del and c.1186C>T, were also detected in our patients. In silico analyses predicted that the novel alterations affect the structure/function of the TPO protein. The c.2268dup mutation was detected in approximately one-third of the Malaysian-Chinese patients with thyroid dyshormonogenesis. The detection of the novel c.670_672del and c.1186C>T alterations expand the mutation spectrum of TPO associated with thyroid dyshormonogenesis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Effectiveness of thyroid gland shielding in dental CBCT using a paediatric anthropomorphic phantom

PubMed Central

Davies, J; Horner, K; Theodorakou, C

2015-01-01

Objectives: The purpose of the study is to evaluate the effectiveness of thyroid shielding in dental CBCT examinations using a paediatric anthropomorphic phantom. Methods: An ATOM® 706-C anthropomorphic phantom (Computerized Imaging Reference Systems Inc., Norfolk, VA) representing a 10-year-old child was loaded with six thermoluminescent dosemeters positioned at the level of the thyroid gland. Absorbed doses to the thyroid were measured for five commercially available thyroid shields using a large field of view (FOV). Results: A statistically significant thyroid gland dose reduction was found using thyroid shielding for paediatric CBCT examinations for a large FOV. In addition, a statistically significant difference in thyroid gland doses was found depending on the position of the thyroid gland. There was little difference in the effectiveness of thyroid shielding when using a lead vs a lead-equivalent thyroid shield. Similar dose reduction was found using 0.25- and 0.50-mm lead-equivalent thyroid shields. Conclusions: Thyroid shields are to be recommended when undertaking large FOV CBCT examinations on young patients. PMID:25411710

Benign Thyroid Diseases and Risk of Thyroid Cancer: A Nationwide Cohort Study.

PubMed

Kitahara, Cari M; K Rmendiné Farkas, Dóra; Jørgensen, Jens Otto L; Cronin-Fenton, Deirdre; Sørensen, Henrik Toft

2018-06-01

Thyroid nodules, adenomas, and goiter have consistently been associated with thyroid cancer risk. Few studies have assessed whether thyroid dysfunction and thyroid autoimmunity influence this risk. To examine thyroid cancer risk after diagnoses of a wide range of benign thyroid conditions. Hospital and cancer registry linkage cohort study for the years 1978 to 2013. Nationwide (Denmark). Patients diagnosed with hyperthyroidism (n = 85,169), hypothyroidism (n = 63,143), thyroiditis (n = 12,532), nontoxic nodular goiter (n = 65,782), simple goiter (n = 11,582), other/unspecified goiter (n = 21,953), or adenoma (n = 6,481) among 8,258,807 residents of Denmark during the study period. We computed standardized incidence ratios (SIRs) for differentiated thyroid cancer, excluding the first 12 months of follow-up after benign thyroid disease diagnosis. SIRs were significantly elevated for all benign thyroid diseases apart from hypothyroidism. SIRs were higher for men than women and in the earlier follow-up periods. Elevated SIRs were observed for localized and regional/distant thyroid cancer. After excluding the first 10 years of follow-up, hyperthyroidism [n = 27 thyroid cancer cases; SIR = 2.00; 95% confidence interval (CI): 1.32 to 2.92], nontoxic nodular goiter (n = 83; SIR = 4.91; 95% CI: 3.91 to 6.09), simple goiter (n = 8; SIR = 4.33; 95% CI: 1.87 to 8.53), other/unspecified goiter (n = 20; SIR = 3.94; 95% CI: 2.40 to 6.08), and adenoma (n = 9; SIR = 6.02; 95% CI: 2.76 to 11.5) remained positively associated with thyroid cancer risk. We found an unexpected increased risk of differentiated thyroid cancer, including regional/distant disease, following diagnosis of hyperthyroidism and thyroiditis that could not be solely attributed to increased medical surveillance. Hypothyroidism was less clearly associated with thyroid cancer risk.

Insulin resistance is associated with larger thyroid volume in adults with type 1 diabetes independently from presence of thyroid autoimmunity.

PubMed

Rogowicz-Frontczak, Anita; Pilacinski, Stanislaw; Chwialkowska, Anna Teresa; Naskret, Dariusz; Zozulinska-Ziolkiewicz, Dorota

2018-04-19

To investigate the effect of insulin resistance (IR) on thyroid function, thyroid autoimmunity (AIT) and thyroid volume in type 1 diabetes (T1DM). 100 consecutive patients with T1DM aged 29 (±6) years with diabetes duration 13 (±6) years were included. Exclusion criteria were: history of thyroid disease, current treatment with L-thyroxin or anti-thyroid drugs. Evaluation of thyroid stimulating hormone (TSH), free thyroid hormones and anti-thyroid antibodies was performed. Thyroid volume was measured by ultrasonography. IR was assessed using the estimated glucose disposal rate (eGDR) formula. In the study group 22% of subjects had insulin resistance defined as eGDR lower or equal to 7.5 mg/kg/min. The prevalence of thyroid autoimmunity (positivity for ATPO or ATg or TRAb) in the study group was 37%. There were no significant differences in the concentration of TSH, FT3, FT4, the prevalence of AIT and hypothyroidism between IR and insulin sensitive (IS) group. Mean (±SD) thyroid volume was 15.6 (±6.2) mL in patients with IR and 11.7 (±4.7) mL in IS subjects (p = .002). Thyroid volume correlated inversely with eGDR (r = -0.35, p < .001). In a multivariate linear regression model the association between thyroid volume and eGDR was independent of sex, age, duration of diabetes, daily insulin dose, BMI, cigarette smoking, TSH value and presence of thyroid autoimmunity (beta: -0.29, p = .012). Insulin resisance is associated with larger thyroid volume in patients with type 1 diabetes independently of sex, body mass index, TSH value and presence of autoimmune thyroid disease.

Cytomorphologic spectrum of lymphocytic thyroiditis and correlation between cytological grading and biochemical parameters

PubMed Central

Anila, KR; Nayak, Nileena; Jayasree, K

2016-01-01

Introduction: Chronic lymphocytic thyroiditis [Hashimoto thyroiditis (HT)] is a common thyroid lesion diagnosed on fine-needle aspiration cytology (FNAC). Apart from FNAC, various other parameters, such as clinical features, ultrasonographic findings, antithyroid antibody levels, hormone profiles, and radionuclide thyroid scan, are also taken into consideration in making a diagnosis of HT. Aims: To grade lymphocytic thyroiditis based on the cytomorphology and to correlate the cytological grades with the levels of antithyroid peroxidase antibody (ATPO), antithyroglobulin antibody (ATG), and thyroid stimulating hormone (TSH). Materials and Methods: During a period of one and half years, 1,667 cases underwent FNAC of thyroid at our tertiary care center. Of these, 128 cases had cytological evidence of lymphocytic thyroiditis. Out of these, in 60 cases the levels of ATPO, ATG, and TSH were known. The cytological grades of lymphocytic thyroiditis in these cases were correlated with these parameters. Results: Out of the 60 cases, 55 were females. Age ranged from 5 years to 70 years, with majority of patients in third decade. Diffuse enlargement of thyroid was the commonest presentation. However, 14 cases presented with nodular disease. Majority of the patients had grade 1 thyroiditis (27 cases), followed by grade 2 thyroiditis (22 cases). Cytomorphology was diagnostic of thyroiditis in all 60 cases. ATPO was elevated in 57 cases and ATG was elevated in 40 cases. Elevated level of TSH was seen in only 18 cases. In 39 cases, TSH value was normal. There was no correlation between the cytological grades of thyroiditis and the levels of antithyroid antibodies and TSH. Conclusion: Lymphocytic infiltration of thyroid follicles is pathognomonic of lymphocytic thyroiditis. Positivity for antithyroid antibodies is strongly associated with HT but no correlation was observed between the grades of thyroiditis and the levels of ATPO, ATG, and TSH. PMID:27756987

[Screening of benign and malignant thyroid nodules in 5 196 physical examination population].

PubMed

Li, M H; Liu, J T

2018-02-23

Objective: To investigate the distribution characteristics of thyroid nodules and thyroid cancer in physical examination population in Tianjin, and report the outcome of ultrasonography in detection of thyroid nodules. Methods: Enrolled all of physical examination population in our hospital from Jan 1, 2014 to Dec 31, 2014 as our study subjects then the thyroid gland lesions were screened by ultrasound diagnostic technique. The risk assessment of benign and malignant thyroid nodules was assessed by ultrasonography and thyroid imaging reporting and data system (TI-RADS), and the individuals were followed up for 1 year. Results: Among the 5 196 cases, the patients with thyroid nodules was 2 068 cases (39.80%). The thyroid nodules was 35.04% in male and 44.78% in female subjects, lower in females than in male cases ( P <0.001). 18 cases of thyroid cancer patients were detected (0.35%). The thyroid cancer rate were 0.34% and 0.36% in male and female respectively ( P >0.05). Thyroid nodules increased with age, but the thyroid cancer patients were mainly concentrated in the 30 to 39 years old group and 50 to 59 years old group. All of the thyroid cancer patients underwent surgical treatment, better differentiation thyroid papillary carcinoma (17 cases) in major, most were early stage cancer and micro-cancer, possessing relatively low risk of recurrence. The sensitivity, specificity and accuracy of ultrasonography and TI-RADS diagnosis of thyroid cancer was 72.22%, 98.94% and 98.85%. Conclusions: The detection rate of thyroid nodules in our population is close to 40%, and there are differences between sexes and ages. Ultrasonography and TI-RADS association is an efficient method to detect the nodules in thyroid.

Thyroiditis

MedlinePlus

... 12-18 months, 20% possibility of permanent hypothyroidism. Post partum thyroiditis Anti-thyroid antibodies, autoimmune disease Thyrotoxicosis followed by hypothyroidism. Thyroid function tests, thyroid antibody tests, radioactive iodine uptake (contraindicated if ...

Graves' disease: diagnostic and therapeutic challenges (multimedia activity).

PubMed

Kahaly, George J; Grebe, Stefan K G; Lupo, Mark A; McDonald, Nicole; Sipos, Jennifer A

2011-06-01

Graves' disease is the most common cause of hyperthyroidism in the United States. Graves' disease occurs more often in women with a female:male ratio of 5:1 and a population prevalence of 1% to 2%. A genetic determinant to the susceptibility to Graves' disease is suspected because of familial clustering of the disease, a high sibling recurrence risk, the familial occurrence of thyroid autoantibodies, and the 30% concordance in disease status between identical twins. Graves' disease is an autoimmune thyroid disorder characterized by the infiltration of immune effector cells and thyroid antigen-specific T cells into the thyroid and thyroid-stimulating hormone receptor expressing tissues, with the production of autoantibodies to well-defined thyroidal antigens, such as thyroid peroxidase, thyroglobulin, and the thyroid-stimulating hormone receptor. The thyroid-stimulating hormone receptor is central to the regulation of thyroid growth and function. Stimulatory autoantibodies in Graves' disease activate the thyroid-stimulating hormone receptor leading to thyroid hyperplasia and unregulated thyroid hormone production and secretion. Below-normal levels of baseline serum thyroid-stimulating hormone receptor, normal to elevated serum levels of T4, elevated serum levels of T3 and thyroid-stimulating hormone receptor autoantibodies, and a diffusely enlarged, heterogeneous, hypervascular (increased Doppler flow) thyroid gland confirm diagnosis of Graves' disease (available at: http://supplements.amjmed.com/2010/hyperthyroid/faculty.php). This Resource Center is also available through the website of The American Journal of Medicine (www.amjmed.com). Click on the “Thyroid/Graves' Disease” link in the “Resource Centers” section, found on the right side of the Journal homepage. Copyright © 2011 Elsevier Inc. All rights reserved.

21 CFR 866.5870 - Thyroid autoantibody immunological test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... (enlargement of the thyroid gland with protrusion of the eyeballs), and cancer of the thyroid. (b... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Thyroid autoantibody immunological test system....5870 Thyroid autoantibody immunological test system. (a) Identification. A thyroid autoantibody...

21 CFR 866.5870 - Thyroid autoantibody immunological test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... (enlargement of the thyroid gland with protrusion of the eyeballs), and cancer of the thyroid. (b... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Thyroid autoantibody immunological test system....5870 Thyroid autoantibody immunological test system. (a) Identification. A thyroid autoantibody...

21 CFR 866.5870 - Thyroid autoantibody immunological test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... (enlargement of the thyroid gland with protrusion of the eyeballs), and cancer of the thyroid. (b... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Thyroid autoantibody immunological test system....5870 Thyroid autoantibody immunological test system. (a) Identification. A thyroid autoantibody...

21 CFR 866.5870 - Thyroid autoantibody immunological test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... (enlargement of the thyroid gland with protrusion of the eyeballs), and cancer of the thyroid. (b... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Thyroid autoantibody immunological test system....5870 Thyroid autoantibody immunological test system. (a) Identification. A thyroid autoantibody...

Differential expression of connexin 43 in human autoimmune thyroid disease.

PubMed

Jiang, Xiao-Yan; Feng, Xiao-Hong; Li, Guo-Yan; Zhao, Qian; Yin, Hui-Qing

2010-05-01

Gap junctions provide a pathway for cell-to-cell communication. Reduced thyroid epithelial cell-cell communication has been reported in some animal models of autoimmune thyroid disease. In order to assess whether this change was similar to human autoimmune thyroid disease, we identified some connexin proteins and their corresponding mRNA in human thyroid gland. The aim of our study was to explore the expression of connexin 43 (Cx43) in the thyroid gland from normal and diseased human thyroid tissue by immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR). The expression levels of Cx43 in Grave's disease were significantly increased in comparison with those of normal thyroid tissue. There was a significant decrease in expression of Cx43 in Hashimoto's thyroiditis, compared with normal thyroid tissue. These data indicate that changes of Cx43 expression in human autoimmune thyroid disease were associated with variations in thyroid function and hormone secretion. 2009 Elsevier GmbH. All rights reserved.

[Hashimoto's thyroiditis(chronic thyroiditis), IgG4-related thyroiditis].

PubMed

Itoh, Mitsuyasu

2012-11-01

Hashimoto's thyroiditis emerges in patients who have genetic preponderance such as SNPs of CTLA-4 and risk factors such as excess intake of iodine, pregnancy or postpartum period, and smoking. Such risk factors also affect the entire clinical course. One of the major outcomes in Hashimoto's thyroiditis appears to be increased in cardio-vascular risks through subclinical hypothyroidism and concomitant metabolic syndrome, but in most cases, treatment with L-T4 has little effects on cardio-vascular benefit or quality of life. The pregnant women also have risks for obstetric complications and postpartum thyroid dysfunction. The women who have anti-TPO antibodies, type 1 diabetes, or previous history of post-partum thyroid dysfunction are recommended to be measured their TSH. It is noteworthy that Hashimoto's thyroiditis is sometimes complicated with encephalopathy, papillary carcinoma, or IgG4-related thyroiditis. IgG4-related thyroiditis is partly similar but partly discerned from a variant of Hashimoto's thyroiditis. The pathogenetic roles of this variant on autoimmune-based thyroiditis remain unclear.

A misdiagnosed Riedel's thyroiditis successfully treated by thyroidectomy and tamoxifen.

PubMed

Wang, Chih-Jung; Wu, Ta-Jen; Lee, Chung-Ta; Huang, Shih-Ming

2012-12-01

Riedel's thyroiditis, known as invasive fibrous thyroiditis, is a very rare form of chronic thyroiditis. It is hard to make the diagnosis without surgical biopsy. We present a case of Riedel's thyroiditis in a 52-year-old female with past history of Hashimoto's thyroiditis. She suffered from bilateral neck pain, which radiated to both lower jaws. The erythrocyte sedimentation rate was 125 mm/hour. Subacute thyroiditis superimposed on Hashimoto's thyroiditis was diagnosed and treated with steroid. However the response was poor and she had a history of severe peptic ulcer. To avoid inducing the peptic ulcer by steroid, she received bilateral subtotal thyroidectomy. During surgery, the thyroid had severe adhesion to surrounding soft tissue and the pathology showed Riedel's thyroiditis. The neck pain improved after thyroidectomy. Tamoxifen has been given for 8 months and the size of remnant thyroid decreased to 8 mm. We concluded that combined thyroidectomy and tamoxifen successfully cured a patient with Riedel's thyroiditis. Copyright © 2012. Published by Elsevier B.V.

Differentiated thyroid carcinoma with functional autonomy.

PubMed

Yaturu, Subhashini; Fowler, Marjorie R

2002-01-01

To present a case of papillary carcinoma in an autonomously hyperfunctioning thyroid nodule. We chronicle the clinical and laboratory findings in a patient with a painless neck mass, with a particular focus on the pathologic findings after surgical removal of the right thyroid lobe. A 39-year-old woman had an enlarging nodule of the right thyroid lobe. Results of thyroid function tests suggested subclinical hyperthyroidism. Two months later, the patient complained of increasing swelling in the neck (but still had no symptoms suggestive of hyperthyroidism). Thus, resection of the right thyroid lobe was performed. Pathologic analysis disclosed low-grade papillary thyroid carcinoma within the nodule, with a small rim of compressed inactive-appearing thyroid tissue surrounding the nodule. Subsequently, she underwent total thyroidectomy and follow-up care for thyroid carcinoma. Although solitary hyperfunctioning nodules of the thyroid gland are usually considered benign, the current case suggests that the diagnosis of autonomous thyroid nodules does not preclude thyroid carcinoma in a functioning nodule.

Thyroid cancer - medullary carcinoma

MedlinePlus

Thyroid - medullary carcinoma; Cancer - thyroid (medullary carcinoma); MTC; Thyroid nodule - medullary ... in children and adults. Unlike other types of thyroid cancer, MTC is less likely to be caused by ...

Recent developments in the investigation of thyroid regulation and thyroid carcinogenesis.

PubMed Central

Hard, G C

1998-01-01

This review covers new mechanistic information spanning the past 10 years relevant to normal and abnormal thyroid growth and function that may assist in the risk assessment of chemicals inducing thyroid follicular cell neoplasia. Recent studies have shown that thyroid regulation occurs via a complex interactive network mediated through several different messenger systems. Increased thyroid-stimulating hormone (TSH) levels activate the signal transduction pathways to stimulate growth and differentiation of the follicular cell. The important role of TSH in growth as well as in function helps to explain how disruptions in the thyroid-pituitary axis may influence thyroid neoplasia in rodents. New investigations that couple mechanistic studies with information from animal cancer bioassays (e. g., sulfamethazine studies) confirm the linkage between prolonged disruption of the thyroid-pituitary axis and thyroid neoplasia. New initiation/promotion studies in rodents also support the concept that chronic stimulation of the thyroid induced by goitrogens can result in thyroid tumors. Some of these studies confirm previous suggestions regarding the importance of chemically induced thyroid peroxidase inhibition and the inhibition of 3,3',5, 5'-tetraiodothyronine (T4, thyroxine) deiodinases on disruption of the thyroid-pituitary axis leading to thyroid neoplasia. Some comparative physiologic and mechanistic data highlight certain differences between rodents and humans that could be expected to confer an increased vulnerability of rodents to chronic hypersecretion of TSH. New data from epidemiologic and molecular genetic studies in humans contribute further to an understanding of thyroid neoplasia. Acute exposure to ionizing radiation, especially in childhood, remains the only verified cause of thyroid carcinogenesis in humans. Iodine deficiency studies as a whole remain inconclusive, even though several new studies in humans examine the role of dietary iodine deficiency in thyroid cancer. Specific alterations in gene expression have been identified in human thyroid neoplasia, linked to tumor phenotype, and thus oncogene activation and tumor-suppressor gene inactivation may also be factors in the development and progression of thyroid cancer in humans. An analysis by the U.S. EPA Risk Assessment Forum, prepared as a draft report in 1988 and completed in 1997, focused on the use of a threshold for risk assessment of thyroid follicular tumors. New studies, involving several chemicals, provide further support that there will be no antithyroid activity until critical intracellular concentrations are reached. Thus, for chemically induced thyroid neoplasia linked to disruptions in the thyroid-pituitary axis, a practical threshold for thyroid cancer would be expected. More information on thyroid autoregulation, the role of oncogene mutations and growth factors, and studies directly linking persistently high TSH levels with the sequential cellular development of thyroid follicular cell neoplasia would provide further confirmation. PMID:9681969

Application of the ToxMiner Database: Network Analysis of Linkage between ToxCast Phase I Chemicals and Thyroid Related Disease Outcomes

EPA Science Inventory

The US EPA ToxCast program is using in vitro HTS (High-Throughput Screening) methods to profile and model bioactivity of environmental chemicals. The main goals of the ToxCast program are to generate predictive signatures of toxicity, and ultimately provide rapid and cost-effecti...

Thyroid consequences of the Chernobyl nuclear accident.

PubMed

Pacini, F; Vorontsova, T; Molinaro, E; Shavrova, E; Agate, L; Kuchinskaya, E; Elisei, R; Demidchik, E P; Pinchera, A

1999-12-01

It is well recognized that the use of external irradiation of the head and neck to treat patients with various non-thyroid disorders increases their risk of developing papillary thyroid carcinoma years after radiation exposure. An increased risk of thyroid cancer has also been reported in survivors of the atomic bombs in Japan, as well as in Marshall Island residents exposed to radiation during the testing of hydrogen bombs. More recently, exposure to radioactive fallout as a result of the Chernobyl nuclear reactor accident has clearly caused an enormous increase in the incidence of childhood thyroid carcinoma in Belarus, Ukraine, and, to a lesser extent, in the Russian Federation, starting in 1990. When clinical and epidemiological features of thyroid carcinomas diagnosed in Belarus after the Chernobyl accident are compared with those of naturally occurring thyroid carcinomas in patients of the same age group in Italy and France, it becomes apparent that the post-Chernobyl thyroid carcinomas were much less influenced by gender, virtually always papillary (solid and follicular variants), more aggressive at presentation and more frequently associated with thyroid autoimmunity. Gene mutations involving the RET proto-oncogene, and less frequently TRK, have been shown to be causative events specific for papillary cancer. RET activation was found in nearly 70% of the patients who developed papillary thyroid carcinomas following the Chernobyl accident. In addition to thyroid cancer, radiation-induced thyroid diseases include benign thyroid nodules, hypothyroidism and autoimmune thyroiditis, with or without thyroid insufficiency, as observed in populations after environmental exposure to radioisotopes of iodine and in the survivors of atomic bomb explosions. On this basis, the authors evaluated thyroid autoimmune phenomena in normal children exposed to radiation after the Chernobyl accident. The results demonstrated an increased prevalence of circulating thyroid antibodies not associated with significant thyroid dysfunction. This finding is consistent with the short period of follow-up, but it is highly likely that these children will develop clinical thyroid autoimmune diseases in the future. Therefore, screening programmes for this at-risk population should focus, not only on the detection of thyroid nodules and cancer, but also on the development of thyroid autoimmune diseases.

Endocrinological side-effects of immune checkpoint inhibitors.

PubMed

Torino, Francesco; Corsello, Salvatore M; Salvatori, Roberto

2016-07-01

Three mAbs targeting immune checkpoint proteins are available for the treatment of patients with melanoma, lung, and kidney cancer, and their use will likely expand in the future to additional tumor types. We here update the literature on the incidence and pathophysiology of endocrine toxicities induced by these agents, and discuss management guidance. Immune checkpoint inhibition may trigger autoimmune syndromes involving different organs, including several endocrine glands (pituitary, thyroid, adrenals, and endocrine pancreas). Hypophysitis is more frequently associated with ipilimumab, whereas the incidence of thyroid dysfunction is higher with nivolumab/pembrolizumab. Primary adrenal insufficiency can rarely occur with either treatment. Autoimmune diabetes is very rare. As hypophysitis and adrenalitis may be life-threatening, endocrinological evaluation is essential particularly in patients developing fatigue and other symptoms consistent with adrenal insufficiency. Corticosteroids should be promptly used when hypophysitis-induced adrenal insufficiency or adrenalitis are diagnosed, but not in thyroiditis or diabetes. No impact of corticosteroids on the efficacy/activity of immune checkpoint-inhibiting drugs is reported. Hormonal deficiencies are often permanent. In absence of predicting factors, accurate information to patients provided by the oncology care team is essential for early diagnosis and to limit the consequences of checkpoint inhibition-related endocrine toxicity.

Clinical Consequences of Mutations in Thyroid Hormone Receptor-α1

PubMed Central

van Mullem, Alies A.; Visser, Theo J.; Peeters, Robin P.

2014-01-01

Thyroid hormone (TH) exerts its biological activity via the TH receptors TRα1 and TRβ1/2, which are encoded by the THRA and THRB genes. The first patients with mutations in THRB were identified decades ago. These patients had a clinical syndrome of resistance to TH associated with high serum TH and nonsuppressed thyroid-stimulating hormone levels. Until recently, no patients with mutations in THRA had been identified. In an attempt to predict the clinical phenotype of such patients, different TRα1 mutant mouse models have been generated. These mice have a variable phenotype depending on the location and severity of the mutation. Recently, the first humans with mutations in THRA were identified. Their phenotype consists of relatively low serum T4 and high serum T3 levels (and thus an elevated T3/T4 ratio), growth retardation, delayed mental and bone development, and constipation. While, in retrospect, certain features present in humans can also be found in mouse models, the first humans carrying a defect in TRα1 were not suspected of having a THRA gene mutation initially. The current review focuses on the clinical consequences of TRα1 mutations. PMID:24847461

Increases in thyroid nodule fine-needle aspirations, operations, and diagnoses of thyroid cancer in the United States.

PubMed

Sosa, Julie Ann; Hanna, John W; Robinson, Karen A; Lanman, Richard B

2013-12-01

To provide population-based estimates of trends in thyroid nodule fine-needle aspirations (FNA) and operative volumes, we used multiple claims databases to quantify rates of these procedures and their association with the increasing incidence of thyroid cancer in the United States. Private and public insurance claims databases were used to estimate procedure volumes from 2006 to 2011. Rates of FNA and thyroid operations related to thyroid nodules were defined by CPT4 codes associated with International Classification of Diseases, Ninth Revision Clinical Modification codes for nontoxic uni- or multinodular goiter and thyroid neoplasms. Use of thyroid FNA more than doubled during the 5-year study period (16% annual growth). The number of thyroid operations performed for thyroid nodules increased by 31%. Total thyroidectomies increased by 12% per year, whereas lobectomies increased only 1% per year. In 2011, total thyroidectomies accounted for more than half (56%) of the operations for thyroid neoplasms in the United States. Thyroid operations became increasingly (62%) outpatient procedures. Thyroid FNA and operative procedures have increased rapidly in the United States, with an associated increase in the incidence of thyroid cancer. The more substantial increase in number of total versus partial thyroid resections suggests that patients undergoing thyroid operation are perceived to have a greater risk of cancer as determined by preoperative assessments, but this trend could also increase detection of incidental microcarcinomas. Copyright © 2013 Mosby, Inc. All rights reserved.

Risk of thyroid cancer in patients with thyroiditis: a population-based cohort study.

PubMed

Liu, Chien-Liang; Cheng, Shih-Ping; Lin, Hui-Wen; Lai, Yuen-Liang

2014-03-01

The causative relationship between autoimmune thyroiditis and thyroid cancer remains a controversial issue. The aim of this population-based study was to investigate the risk of thyroid cancer in patients with thyroiditis. From the Longitudinal Health Insurance Database 2005 (LHID2005) of Taiwan, we identified adult patients newly diagnosed with thyroiditis between 2004 and 2009 (n = 1,654). The comparison cohort (n = 8,270) included five randomly selected age- and sex-matched controls for each patient in the study cohort. All patients were followed up from the date of cohort entry until they developed thyroid cancer or to the end of 2010. Multivariate Cox regression was used to assess the risk of developing thyroid cancer. A total of 1,000 bootstrap replicates were created for internal validation. A total of 35 patients developed thyroid cancer during the study period, of whom 24 were from the thyroiditis cohort and 11 were from the comparison cohort (incidence 353 and 22 per 100,000 person-years, respectively). After adjusting for potential confounding factors, the hazard ratio (HR) for thyroid cancer in patients with thyroiditis was 13.24 (95 % CI 6.40-27.39). Excluding cancers occurring within 1 year of follow-up, the HR remained significantly increased (6.64; 95 % CI 2.35-18.75). Hypothyroidism was not an independent factor associated with the occurrence of thyroid cancer. We found an increased risk for the development of thyroid cancer after a diagnosis of thyroiditis, independent of comorbidities.

Unilateral occurrence of five different thyroid arteries-a need of terminological systematization: a case report.

PubMed

Lovasova, Kvetuse; Kachlik, David; Santa, Marian; Kluchova, Darina

2017-08-01

This article highlights an unusual and unilateral variation in the blood supply to the inferior portion of the thyroid gland observed on the right lobe during anatomy dissection course. The rare variation of the occurrence of two anomalous arteries: the middle thyroid artery and the aberrant accessory inferior thyroid artery, and one uncommon variant, the thyroid ima artery, was detected in an adult female cadaver. The two generally constant arteries, the superior thyroid artery and the inferior thyroid artery, have been found in their usual anatomical location. Both the middle thyroid artery and aberrant accessory inferior thyroid artery arose from the right common carotid artery. The middle thyroid artery coursed as a very short branch ventromedially to enter the inferior lateral portion of the right lobe of the thyroid gland. It was at the same level, in which the inferior thyroid artery reached the lateral border of the thyroid gland. The aberrant accessory inferior thyroid artery originated similarly, from the ventromedial surface of the right common carotid artery and passed to supply the inferior pole of the right lobe. The thyroid ima artery was found to arise from the brachiocephalic trunk, entering the isthmus of the thyroid gland. Information about the embryological background might be helpful to clarify why such a type of variation occurs. It is necessary to understand the possible existence of this anomaly, to carry out successful radical neck dissection and to minimize the risk of postoperative complications in patients.

Evaluation of clinical hypothyroidism risk due to irradiation of thyroid and pituitary glands in radiotherapy of nasopharyngeal cancer patients.

PubMed

Lin, Zhixiong; Wang, Xiaoyan; Xie, Wenjia; Yang, Zhining; Che, Kaijun; Wu, Vincent W C

2013-12-01

Radiation-induced thyroid dysfunction after radiotherapy for nasopharyngeal cancer (NPC) has been reported. This study investigated the radiation effects of the thyroid and pituitary glands on thyroid function after radiotherapy for NPC. Sixty-five NPC patients treated with radiotherapy were recruited. Baseline thyroid hormone levels comprising free triiodothyronine (fT3), free thyroxine (fT4) and thyroid-stimulating hormone (TSH) were taken before treatment and at 3, 6, 12 and 18 months. A seven-beam intensity-modulated radiotherapy plan was generated for each patient. Thyroid and pituitary gland dose volume histograms were generated, dividing the patients into four groups: high (>50 Gy) thyroid and pituitary doses (HTHP group); high thyroid and low pituitary doses (HTLP group); low thyroid and high pituitary doses; and low thyroid and pituitary doses. Incidence of hypothyroidism was analysed. Twenty-two (34%) and 17 patients (26%) received high mean thyroid and pituitary doses, respectively. At 18 months, 23.1% of patients manifested various types of hypothyroidism. The HTHP group showed the highest incidence (83.3%) of hypothyroidism, followed by the HTLP group (50%). NPC patients with high thyroid and pituitary gland doses carried the highest risk of abnormal thyroid physiology. The dose to the thyroid was more influential than the pituitary dose at 18 months after radiotherapy, and therefore more attention should be given to the thyroid gland in radiotherapy planning. © 2013 The Royal Australian and New Zealand College of Radiologists.

Thyroid Radiofrequency Ablation: Updates on Innovative Devices and Techniques

PubMed Central

Park, Hye Sun; Park, Auh Whan; Chung, Sae Rom; Choi, Young Jun; Lee, Jeong Hyun

2017-01-01

Radiofrequency ablation (RFA) is a well-known, effective, and safe method for treating benign thyroid nodules and recurrent thyroid cancers. Thyroid-dedicated devices and basic techniques for thyroid RFA were introduced by the Korean Society of Thyroid Radiology (KSThR) in 2012. Thyroid RFA has now been adopted worldwide, with subsequent advances in devices and techniques. To optimize the treatment efficacy and patient safety, understanding the basic and advanced RFA techniques and selecting the optimal treatment strategy are critical. The goal of this review is to therefore provide updates and analysis of current devices and advanced techniques for RFA treatment of benign thyroid nodules and recurrent thyroid cancers. PMID:28670156

Co-occurrence of papillary thyroid carcinoma and mucosa-associated lymphoid tissue lymphoma in a patient with long-standing hashimoto thyroiditis.

PubMed

Nam, Yoon Jeong; Kim, Bo Hyun; Lee, Seong Keun; Jeon, Yun Kyung; Kim, Sang Soo; Jung, Woo Jin; Kahng, Dong Hwahn; Kim, In Ju

2013-12-01

Papillary thyroid carcinoma (PTC) is a common affliction of the thyroid gland, accounting for 70% to 80% of all thyroid cancers, whereas mucosa-associated lymphoid tissue (MALT) lymphoma of the thyroid gland is uncommon. The simultaneous occurrence of both malignancies is extremely rare. We report the case of a patient with both PTC and MALT lymphoma in the setting of Hashimoto thyroiditis. An 81-year-old female patient was first admitted with goiter and hoarseness, which was attributed to an ultrasonographic thyroid nodule. Subsequent fine-needle aspirate, interpreted as suspicious of papillary thyroid cancer, prompted total thyroidectomy. MALT lymphoma was an incidental postsurgical finding, coexisting with PTC in the setting of Hashimoto thyroiditis. Although the development of MALT lymphoma is very rare, patients with longstanding Hashimoto thyroiditis should undergo careful surveillance for both malignancies.

Co-Occurrence of Papillary Thyroid Carcinoma and Mucosa-Associated Lymphoid Tissue Lymphoma in a Patient with Long-Standing Hashimoto Thyroiditis

PubMed Central

Nam, Yoon Jeong; Lee, Seong Keun; Jeon, Yun Kyung; Kim, Sang Soo; Jung, Woo Jin; Kahng, Dong Hwahn; Kim, In Ju

2013-01-01

Papillary thyroid carcinoma (PTC) is a common affliction of the thyroid gland, accounting for 70% to 80% of all thyroid cancers, whereas mucosa-associated lymphoid tissue (MALT) lymphoma of the thyroid gland is uncommon. The simultaneous occurrence of both malignancies is extremely rare. We report the case of a patient with both PTC and MALT lymphoma in the setting of Hashimoto thyroiditis. An 81-year-old female patient was first admitted with goiter and hoarseness, which was attributed to an ultrasonographic thyroid nodule. Subsequent fine-needle aspirate, interpreted as suspicious of papillary thyroid cancer, prompted total thyroidectomy. MALT lymphoma was an incidental postsurgical finding, coexisting with PTC in the setting of Hashimoto thyroiditis. Although the development of MALT lymphoma is very rare, patients with longstanding Hashimoto thyroiditis should undergo careful surveillance for both malignancies. PMID:24396701

Sorafenib induced thyroiditis in two patients with hepatocellular carcinoma.

PubMed

van Doorn, Leni; Eskens, Ferry A L M; Visser, Theo J; van der Lugt, Aad; Mathijssen, Ron H J; Peeters, Robin P

2011-02-01

Sorafenib is a multi-targeted tyrosine kinase inhibitor licensed for the treatment of hepatocellular carcinoma and renal cell carcinoma. Thyroid function test abnormalities have been reported for different tyrosine kinase inhibitors, but only limited data on thyroid function test abnormalities related to sorafenib are available, demonstrating the occurrence of hypothyroidism in patients treated with sorafenib. We describe two patients who developed temporary hyperthyroidism during the course of sorafenib treatment, which was followed by overt and subclinical hypothyroidism, respectively. Thyroid ultrasonography showed an atrophic thyroid gland in patient 1 , and signs of thyroiditis in patient 2 . Detailed reassessment of thyroid volumes on routinely performed computerized tomography scans showed a gradual decrease in thyroid volume during sorafenib treatment in one patient, suggesting progressive thyroid destruction. This case report describes in detail and for the first time two cases of sorafenib-induced thyroiditis. We assume that this sorafenib-induced destructive thyroiditis is an important cause of sorafenib-induced hypothyroidism.

Benign Thyroid Conditions Associated with Increased Risk of Thyroid Cancer Later in Life

Cancer.gov

In a new study from the National Cancer Institute and Aarhus University Hospital in Denmark, researchers report an association between diagnosis of hyperthyroidism and thyroiditis (inflammation of the thyroid gland), two benign thyroid conditions, and increased risk of differentiated thyroid cancer.

Influence of presence/absence of thyroid gland on the cutoff value for thyroglobulin in lymph-node aspiration to detect metastatic papillary thyroid carcinoma.

PubMed

Zhao, Huan; Wang, Yong; Wang, Min-Jie; Zhang, Zhi-Hui; Wang, Hai-Rui; Zhang, Bing; Guo, Hui-Qin

2017-04-28

Thyroglobulin measurement with fine-needle aspiration (Tg-FNA) is a sensitive method for detecting metastatic papillary thyroid carcinoma (PTC). However, the diagnostic threshold is not well established and the influence of the thyroid gland on the cutoff value is also controversial. In this study, patients were classified into two groups according to the presence or absence of thyroid tissue, to determine an appropriate cutoff value for clinical practice. Patients with a history of thyroid nodules or surgery for PTC and with enlarged cervical lymph nodes on an FNA examination were enrolled for Tg-FNA detection. One hundred ninety-six lymph nodes (189 patients) were included: 100 from preoperative patients, 49 from patients treated with partial thyroid ablation, and 47 from patients with total thyroid ablation. In 149 lymph nodes from patient with thyroids, the cutoff value for Tg-FNA was 55.99 ng/mL (sensitivity, 95.1%; specificity, 100%), whereas in 47 lymph nodes from patients without a thyroid, it was 9.71 ng/mL (sensitivity, 96.7%; specificity, 100%). Thus, the cutoff value for Tg-FNA was higher in patients with thyroids than in patients without thyroids. The cutoff value for Tg-FNA is influenced by residual thyroid tissue, and a higher cutoff value is recommended for patients with thyroids than for patients without thyroids.

Dual ectopic thyroid associated with thyroid hemiagenesis.

PubMed

Nakamura, Shigenori; Masuda, Teruyuki; Ishimori, Masatoshi

2018-01-01

We report a case of a 15-year-old girl with a midline neck mass that was first noted 2 or 3 years previously. She had been treated with levothyroxine (L-T4) for congenital hypothyroidism until 11 years of age. Ultrasonography revealed an atrophic right thyroid (1.0 × 1.6 × 2.6 cm in size) and a mass (2.3 × 1.0 × 3.5 cm in size) in the upper part of the neck. No left lobe of the thyroid was detected. On further evaluation, Tc-99m pertechnetate thyroid scintigraphy and CT showed ectopic thyroid tissue in the lingual region and infrahyoid region. Thus, she was diagnosed as having dual ectopic thyroid and thyroid hemiagenesis. The atrophic right thyroid was thought be non-functional. Treatment with L-T4 was started to reduce the size of the dual ectopic thyroid tissue. This may be the first reported case of dual ectopic thyroid associated with hemiagenesis detected only by ultrasonography. Ultrasonography can confirm the presence or absence of orthotopic thyroid tissue in patients with ectopic thyroid.The cause of congenital hypothyroidism should be examined.Clinical manifestation of ectopic thyroid may appear when the treatment with L-T4 is discontinued.Annual follow-up is needed in all children when their thyroid hormone replacement is stopped.

[Clinical features of myasthenia gravis with thyroid disease with 106 patients].

PubMed

Meng, Chao; Jing, Yun; Li, Ran; Zhang, Xiaojun; Wang, Jiawei

2016-03-22

To report the presentation, clinical course and prognosis of myasthenia gravis (MG) with thyroid disease. Retrospective data analysis was conducted.Between 2004 and 2013, we reviewed a total of 106 patients with MG. We analyzed the clinical features, the relationship between the thyroid function, antibodies and the clinical course, prognosis. (1) In our study, 20/106 (18.87%) patients were thyroid function-abnormal, 37/106 (34.91) were thyroglobulin antibodies (TGAb) and/or thyroid microsomal antibody (TMAb)-positive, and abnormality was observed in 46 (43.40%) of the thyroid gland. Thyroid antibody positive rate was higher than abnormal thyroid function rate, and the difference was significant (P=0.036). (2) The thyroid stimulating hormone (TSH) level ((2.9±4.0) mIU/L) of ocular MG was higher than the level ((1.5±1.1) mIU/L) of generalized MG (P=0.01). (3) The transformation time of 52 ocular type to generalized type was longer in higher antibody group than in normal group (P=0.04). And there were no significant differences between the elevated TSH type and the normal TSH type, the abnormal thyroid function type and normal thyroid function type, the abnormal thyroid type and the normal thyroid type. (4) Comparing the TSH level, total antibody level, TGAb, and TMAb level between the ease group and the unease group in the course of 1 year, 2 years, 5 years, there were no significant differences (all P>0.05). MG is often companied with thyroid abnormalities. MG patients are more susceptible to hashimoto thyroiditis and other autoimmune thyroid diseases. Ocular type patients are more likely to suffer from thyroid function decrease than the generalized type. MG patients with hashimoto thyroiditis and other autoimmune thyroid diseases are more sensitive to respond to therapy means like glucocorticoid therapy, and the short-term prognosis is relatively good. There are no significant correlations between the MG remission rate and TSH level, total antibody level, TGAb and TMAb level.

Thyroid dysfunction and thyroid autoimmunity in euthyroid women in achieving fertility.

PubMed

Medenica, S; Nedeljkovic, O; Radojevic, N; Stojkovic, M; Trbojevic, B; Pajovic, B

2015-01-01

Thyroid disease is the second most common endocrine condition in women of childbearing age. Thyroid hormones are involved in control of menstrual cycle and in achieving fertility affecting the actions of follicle-stimulating hormone and luteinizing hormone on steroid biosynthesis by specific triiodothyronine sites on oocytes; therefore, affect all aspects of reproduction. It remains controversial if pregnant women should be screened for thyroid dysfunction. Purpose of this review was to examine recent studies on the assessment of thyroid dysfunction in pregnancy, its treatment and newly perspective of thyroid autoimmunity in pregnant euthyroid women in achieving fertility. An electronic search was conducted using the internet medical databases: Medline/PubMed, EMBASE, EBSCO, and the Cochrane library. Thyroid gland faces great challenge in pregnancy when many hormonal changes occur. Precondition for normal follicular development and ovulation is pulsate gonadothropin realizing hormone secretion. Thyroid dysfunction in pregnancy is classified as forms of hypothyroidism (positivity of thyroid autoantibody, isolated hypothyroidism, and subclinical or overt hypothyroidism), hyperthyroidism, and autoimmune disease, but also thyroid nodules and cancer, iodine insufficiency and postpartum thyroiditis. These conditions can cause adverse effects on mother and fetus including pregnancy loss, gestational hypertension, or pre-eclampsia, pre-term delivery, low birth weight, placental abruption and postpartum hemorrhage. There is an evidence that thyroid autoimmunity, in thyroid dysfunction adversely affects conception and pregnancy outcomes, but it is unclear what impact has isolated eumetabolic thyroid autoimmunity in achieving fertility, especially in women undergoing in vitro fertilization. Treatment of euthyroid pregnant women with positive thyroid peroxides antibodies is still controverse, but not few studies show that levothyroxine substitution is able to lower the chance of miscarriage and premature delivery. Further randomized trials are needed to expand our knowledge of physiologic changes in thyroid function during the pregnancy and to reveal mechanisms by which thyroid autoimmunity in euthyroid women affect fertility, especially the success of assisted reproductive technology in achieving the same and validity of levothyroxine administration in thyroid autoimmunity positive women.

Significant role of serum CRP in differentiating inflammatory from non-inflammatory causes of thyrotoxicosis

PubMed Central

Baruah, Manash P.; Bhattacharya, Bhaskar

2012-01-01

Background: C-reactive protein (CRP), which is a marker of inflammation, has not been widely studied in inflammatory thyroid disorders particularly in sub-acute thyroiditis (SAT). Aim: This study was aimed to find the significance of CRP level rise in patients with SAT and compare that to the rise in erythrocyte sedimentation rate (ESR), a gold standard laboratory parameter in establishing the diagnosis of SAT. Materials and Methods: Serum CRP levels were measured at initial presentation in 28 subjects with SAT(12 male, 16 female, age (Mean +SD) 37.96 ±8.5 years),and 19 patients with Graves’ disease (2 male, 17 female, age [Mean +SD] 36.8 ±16.5 years) as controls. Erythrocyte sedimentation rate (ESR) was measured in all 28 patients with SAT by Westergrens’ method. Either Tc99 nucleotide thyroid scan or high resolution ultrasonography (HR-USG) was performed to differentiate SAT from Graves’ disease.Fine needle aspiration cytology (FNAC) of thyroid was performed selected patients. Results: Serum CRP level was high in 61% of SAT patients but in none of the Graves′patients. Mean (SEM) (90%CI) serum CRP level (mg/L) was also significantly higher (P <0.0004) in the SAT group [27.55 (5.76) (15.72-39.38)], than in the Graves’ group [4.09 (0.12) (3.81-4.36)]. The sensitivity of serum CRP was 73.33%, specificity 53.85%, positive predictive value (PPV) 64.71%, and negative predictive value (NPV) 63.64% as compared to the sensitivity (53.57%), specificity (15.38%), PPV (57.69 %), and NPV (13.33%) of ESR. Conclusion: There is significantly higher rise in serum CRP level in patients with SAT is compared to patients with Graves’ disease. It correlates well with the rise in ESR. Such findings of this pilot study highlight the scope of using serum CRP as a diagnostic marker of SAT specially in situations when it may be confused with Graves’ disease, another common cause of thyrotoxicosis. It is logical to carry out studies to find a particular cut-off for serum CRP which can serve as an objective parameter for grading the inflammation in patients with SAT. PMID:23226645

Significant role of serum CRP in differentiating inflammatory from non-inflammatory causes of thyrotoxicosis.

PubMed

Baruah, Manash P; Bhattacharya, Bhaskar

2012-11-01

C-reactive protein (CRP), which is a marker of inflammation, has not been widely studied in inflammatory thyroid disorders particularly in sub-acute thyroiditis (SAT). This study was aimed to find the significance of CRP level rise in patients with SAT and compare that to the rise in erythrocyte sedimentation rate (ESR), a gold standard laboratory parameter in establishing the diagnosis of SAT. Serum CRP levels were measured at initial presentation in 28 subjects with SAT(12 male, 16 female, age (Mean +SD) 37.96 ±8.5 years),and 19 patients with Graves' disease (2 male, 17 female, age [Mean +SD] 36.8 ±16.5 years) as controls. Erythrocyte sedimentation rate (ESR) was measured in all 28 patients with SAT by Westergrens' method. Either Tc(99) nucleotide thyroid scan or high resolution ultrasonography (HR-USG) was performed to differentiate SAT from Graves' disease.Fine needle aspiration cytology (FNAC) of thyroid was performed selected patients. Serum CRP level was high in 61% of SAT patients but in none of the Graves'patients. Mean (SEM) (90%CI) serum CRP level (mg/L) was also significantly higher (P <0.0004) in the SAT group [27.55 (5.76) (15.72-39.38)], than in the Graves' group [4.09 (0.12) (3.81-4.36)]. The sensitivity of serum CRP was 73.33%, specificity 53.85%, positive predictive value (PPV) 64.71%, and negative predictive value (NPV) 63.64% as compared to the sensitivity (53.57%), specificity (15.38%), PPV (57.69 %), and NPV (13.33%) of ESR. There is significantly higher rise in serum CRP level in patients with SAT is compared to patients with Graves' disease. It correlates well with the rise in ESR. Such findings of this pilot study highlight the scope of using serum CRP as a diagnostic marker of SAT specially in situations when it may be confused with Graves' disease, another common cause of thyrotoxicosis. It is logical to carry out studies to find a particular cut-off for serum CRP which can serve as an objective parameter for grading the inflammation in patients with SAT.

Thyroid Tests

MedlinePlus

... calories and how fast your heart beats. Thyroid tests check how well your thyroid is working. They ... thyroid diseases such as hyperthyroidism and hypothyroidism. Thyroid tests include blood tests and imaging tests. Blood tests ...

[Riedel thyroiditis: two cases report].

PubMed

Zhou, Rongjin; Wang, Junguo

2014-10-01

Riedel thyroiditis is a benign disease, which is often self-limited. Examinations, such as CT and histologic diagnosis can distinguish it from malignant neoplasms and hashimoto's thyroiditis. Riedel thyroiditis is an uncommon form of chronic thyroiditis in which the thyroid gland is replaced by fibrous tissue. It can be cured by surgery and medicine.

Thyroid gland disorder emergencies: thyroid storm and myxedema coma.

PubMed

Hampton, Jessica

2013-01-01

Although thyroid dysfunction will develop in more than 12% of the US population during their lifetimes, true thyroid emergencies are rare. Thyroid storm and myxedema coma are endocrine emergencies resulting from thyroid hormone dysregulation, usually coupled with an acute illness as a precipitant. Careful assessment of risk and rapid action, once danger is identified, are essential for limiting morbidity and mortality related to thyroid storm and myxedema coma. This article reviews which patients are at risk, explains thyroid storm and myxedema coma, and describes pharmacological treatment and supportive cares.

Development of the thyroid gland.

PubMed

Nilsson, Mikael; Fagman, Henrik

2017-06-15

Thyroid hormones are crucial for organismal development and homeostasis. In humans, untreated congenital hypothyroidism due to thyroid agenesis inevitably leads to cretinism, which comprises irreversible brain dysfunction and dwarfism. Elucidating how the thyroid gland - the only source of thyroid hormones in the body - develops is thus key for understanding and treating thyroid dysgenesis, and for generating thyroid cells in vitro that might be used for cell-based therapies. Here, we review the principal mechanisms involved in thyroid organogenesis and functional differentiation, highlighting how the thyroid forerunner evolved from the endostyle in protochordates to the endocrine gland found in vertebrates. New findings on the specification and fate decisions of thyroid progenitors, and the morphogenesis of precursor cells into hormone-producing follicular units, are also discussed. © 2017. Published by The Company of Biologists Ltd.

Overview of the 2015 American Thyroid Association guidelines for managing thyroid nodules and differentiated thyroid cancer.

PubMed

Matti, Bashar; Cohen-Hallaleh, Ruben

2016-09-09

The last few years have witnessed numerous publications addressing the management of thyroid nodules and differentiated thyroid cancers. The purpose of this review is to provide a simplified summary of the newly released guidelines by the American Thyroid Association. A systematic approach has been recommended to evaluate a thyroid nodule through clinical assessment, measurement of serum Thyroid Stimulating Hormone, neck ultrasonography and Fine Needle Aspiration where appropriate. This is followed by cytology analysis using the Bethesda scoring system to detect malignancy. Once diagnosed, thyroid cancers need to be staged and risk stratification needs to be applied to develop further treatment plans. Lastly, several recommendations have been presented to assure proper follow-up and support for thyroid cancer patients regardless of the treatment received.

[Sub-acute thyroiditis in a patient on immunosuppressive treatment].

PubMed

D'Amico, Giovanna; Di Crescenzo, Vincenzo; Caleo, Alessia; Garzi, Alfredo; Vitale, Mario

2013-01-01

Sub-acute thyroiditis or De Quervain's thyroiditis is a viral, inflammatory disease which causes the serum release of thyroidal hormones and hyperthyroidism. The pathogenesis of thyroid follicle damage is unclear because the exclusive viral action or a concomitant autoimmune component, determined by the lymphoid infiltrate remain to be assessed. We describe the case of a patient under immunosuppressive treatment, who developed sub-acute thyroiditis with hormone release and hyperthyroidism. The patient, while was under immunosuppressive treatment for kidney transplant, exhibited a clinical picture and hormonal profile of hyperthyroidism. Thyroid scintiscan exhibited an extremely low uptake. Fine-needle cytologic diagnosis was granulomatous sub-acute thyroiditis (De Quervain's thyroiditis). This case suggests the primary or even exclusive role of the viral infection in hormone release and hyperthyroidism in sub-acute thyroiditis, excluding an autoimmune component.

The thyroid axis in ageing.

PubMed

Leitol, Holger; Behrends, Jens; Brabant, Georg

2002-01-01

The hypothalmo-pituitary thyroid axis, among various endocrine systems, undergoes physiological alterations associated with the ageing process. Directly age-related changes have to be distinguished from indirect modifications which are caused by simultaneous thyroidal or non-thyroidal illness or other physiological or pathophysiological states whose incidence increases with age. In summary, direct changes of the hypothalmo-pituitary-thyroid axis seem to be subtle and suggestive of a decreased hypothalamic stimulation of thyroid function. In parallel, disease-specific alterations such as the development of thyroid autonomy or changes in energy intake or sleep lead to pronounced alterations of thyroid function with age which may dominate the underlying ageing of the hypothalmo-pituitary thyroid axis itself. The following article attempts to delineate some aspects of the interplay of the regulation of thyroid function and the ageing process.

Gene expression profiles reveal that DCN, DIO1, and DIO2 are underexpressed in benign and malignant thyroid tumors.

PubMed

Arnaldi, L A T; Borra, R C; Maciel, R M B; Cerutti, J M

2005-03-01

To investigate the molecular events involved in the pathogenesis and/or progression of thyroid tumors, we compared the gene expression profiles of three thyroid carcinoma cell lines, which represent major tumor subtypes of thyroid cancer and normal thyroid tissue. Using cDNA array methodology, we investigated the expression of 1807 open reading frame expressed sequence tags (ORESTES), selected from head and neck tumor libraries generated through the Brazilian Human Cancer Project-LICR/FAPESP. We found that 505 transcripts were differentially expressed in the thyroid carcinoma cell lines. Using a more stringent criterion, transcripts underexpressed or overexpressed more than fivefold in 1 of 3 or 3 of 3 carcinoma cell lines, a list of 55 ESTs were detected. Five candidate genes were further validated by quantitative polymerase chain reaction (qPCR) in an independent set of 52 thyroid tumors and 22 matched normal thyroid tissues. DCN was found underexpressed in a high percentage of the follicular thyroid adenomas, follicular thyroid carcinomas, and follicular variant of papillary thyroid carcinomas. DIO1 and DIO2 were underexpressed in nearly all papillary thyroid carcinomas. These genes not only could help to better define a tumor signature for thyroid tumors, but may, in part, also become useful as potential targets for thyroid tumor treatment.

Thyroid Surgery

MedlinePlus

... thyroid surgery, requiring treatment with thyroid hormone (see Hypothyroidism brochure ). This is especially true if you had ... Disease Graves’ Eye Disease Hashimoto’s Thyroiditis Hyperthyroidism (Overactive) Hypothyroidism (Underactive) Iodine Deficiency Low Iodine Diet Medullary Thyroid ...

Diagnosis and Treatment of Patients with Thyroid Cancer

PubMed Central

Nguyen, Quang T.; Lee, Eun Joo; Huang, Melinda Gingman; Park, Young In; Khullar, Aashish; Plodkowski, Raymond A.

2015-01-01

Background Thyroid cancer is the most common malignancy of the endocrine system, representing 3.8% of all new cancer cases in the United States and is the ninth most common cancer overall. The American Cancer Society estimates that 62,450 people in the United States will be diagnosed with thyroid cancer in 2015, and 1950 deaths will result from the disease. Objective To review the current approach to the diagnosis and treatment of patients with thyroid cancer. Discussion Over the past 3 decades, there has been a dramatic increase in the number of people diagnosed with thyroid cancer, which may be attributable to the wide use of imaging studies, including ultrasounds, computed tomography, magnetic resonance imaging, and positron emission tomography scans that incidentally detect thyroid nodules. Thyroid cancer is divided into several main types, with papillary thyroid cancer being the most common. The treatment options for patients with thyroid cancer include the surgical removal of the entire thyroid gland (total thyroidectomy), radioactive iodine therapy, and molecular-targeted therapies with tyrosine kinase inhibitors. This article summarizes the diagnosis and treatment of thyroid cancer, with recommendations from the American Thyroid Association regarding thyroid nodules and differentiated thyroid cancer. Recently approved drugs and treatment trends are also explored. Conclusion The prognosis and treatment of thyroid cancer depend on the tumor type and its stage at the time of diagnosis. Many thyroid cancers remain stable, microscopic, and indolent. The increasing treatment options for patients with thyroid cancer, including therapies that were recently approved by the US Food and Drug Administration, have kept the mortality rate from this malignancy low, despite the increase in its incidence. Early diagnosis and appropriate treatment can improve prognosis and reduce mortality. PMID:25964831

Incidence of Thyroid-Related Adverse Events in Melanoma Patients Treated With Pembrolizumab

PubMed Central

Jansen, Yanina; Schreuer, Max; Everaert, Hendrik; Velkeniers, Brigitte; Neyns, Bart; Bravenboer, Bert

2016-01-01

Context: Immune checkpoint blockade is associated with endocrine-related adverse events. Thyroid dysfunction during pembrolizumab therapy, an anti-programmed cell death 1 (PD-1) receptor monoclonal antibody, remains to be fully characterized. Objective: To assess the incidence and characteristics of pembrolizumab-associated thyroid dysfunction. Design and Setting: Thyroid function was monitored prospectively in melanoma patients who initiated pembrolizumab within an expanded access program at a referral oncology center. 18Fluorodeoxyglucose uptake on positron emission tomography/computed tomography (18FDG-PET/CT) was reviewed in cases compatible with inflammatory thyroiditis. Patients: Ninety-nine patients with advanced melanoma (age, 26.3–93.6 years; 63.6% females) who received at least one administration of pembrolizumab. Main Outcome Measures: Patient characteristics, thyroid function (TSH, free T4), thyroid autoantibodies, and 18FDG-PET/CT. Results: Eighteen adverse events of thyroid dysfunction were observed in 17 patients. Thyrotoxicosis occurred in 12 patients, of which nine evolved to hypothyroidism. Isolated hypothyroidism was present in six patients. Levothyroxine therapy was required in 10 of 15 hypothyroid patients. Thyroid autoantibodies were elevated during thyroid dysfunction in four of 10 cases. Diffuse increased 18FDG uptake by the thyroid gland was observed in all seven thyrotoxic patients who progressed to hypothyroidism. Conclusions: Thyroid dysfunction is common in melanoma patients treated with pembrolizumab. Hypothyroidism and thyrotoxicosis related to inflammatory thyroiditis are the most frequent presentations. Serial measurements of thyroid function tests are indicated during anti-PD-1 monoclonal antibody therapy. Thyrotoxicosis compatible with inflammatory thyroiditis was associated with diffuse increased 18FDG uptake by the thyroid gland. The prospective role of thyroid autoantibodies should be further investigated, together with the histopathological correlates. PMID:27571185

Diffuse sclerosing variant of thyroid carcinoma presenting as Hashimoto thyroiditis: a case report.

PubMed

Vukasović, Anamarija; Kuna, Sanja Kusacić; Ostović, Karmen Trutin; Prgomet, Drago; Banek, Tomislav

2012-11-01

The aim of report is to present a case of a rare diffuse sclerosing variant of a papillary thyroid carcinoma. A 15-year old girl referred for ultrasound examination because of painless thyroid swelling lasting 10 days before. An ultrasound of the neck showed diffusely changed thyroid parenchyma, without nodes, looking as lymphocytic thyroiditis Hashimoto at first, but with snow-storm appearance, predominantly in the right lobe. Positive thyroid peroxidase antibodies (TPO-AT) also suggested Hashimoto thyroiditis. Repeated US-FNAB (fine needle-aspiration biopsy) of the right lobe revealed diffuse sclerosing variant of papillary thyroid carcinoma and patient underwent total thyreoidectomy. Patohistologic finding confirmed diffuse sclerosing variant of a papillary thyroid carcinoma in the both thyroid lobes and several metastatic lymph nodes. Two months later patient recived radioablative therapy with 3700 MBq (100 mCi) of 1-131 followed by levothyroxine replacement. At the moment, patient is without evidence of local or distant metastases and next regular control is scheduled in 6 months. In conclusion, a diffuse sclerosing variant is rare form of papillary thyroid carcinoma that echographically looks similar to Hashimoto thyroiditis and sometimes could be easily overlooked.

Recent Advances in the Classification of Low-grade Papillary-like Thyroid Neoplasms and Aggressive Papillary Thyroid Carcinomas: Evolution of Diagnostic Criteria.

PubMed

Guo, Zhenying; Ge, Minghua; Chu, Ying-Hsia; Asioli, Sofia; Lloyd, Ricardo V

2018-07-01

Papillary thyroid carcinomas account for ∼80% of well-differentiated thyroid tumors. During the past decade, several new variants of papillary-like thyroid neoplasms and papillary thyroid carcinomas have been recognized. Some of these neoplasms that were previously classified as malignant have been reclassified as low-grade neoplasms, as the diagnostic criteria have evolved. Similarly, some of the papillary thyroid carcinomas that were previously classified as conventional or classic papillary thyroid carcinomas have now been recognized as more aggressive variants of papillary thyroid carcinomas. Recognizing these differences becomes more important for the proper medical, surgical, and radiotherapeutic management of patients with these neoplasms.

TSH Receptor Function Is Required for Normal Thyroid Differentiation in Zebrafish

PubMed Central

Opitz, Robert; Maquet, Emilie; Zoenen, Maxime; Dadhich, Rajesh

2011-01-01

TSH is the primary physiological regulator of thyroid gland function. The effects of TSH on thyroid cells are mediated via activation of its membrane receptor [TSH receptor (TSHR)]. In this study, we examined functional thyroid differentiation in zebrafish and characterized the role of TSHR signaling during thyroid organogenesis. Cloning of a cDNA encoding zebrafish Tshr showed conservation of primary structure and functional properties between zebrafish and mammalian TSHR. In situ hybridization confirmed that the thyroid is the major site of tshr expression during zebrafish development. In addition, we identified tpo, iyd, duox, and duoxa as novel thyroid differentiation markers in zebrafish. Temporal analyses of differentiation marker expression demonstrated the induction of an early thyroid differentiation program along with thyroid budding, followed by a delayed onset of duox and duoxa expression coincident with thyroid hormone synthesis. Furthermore, comparative analyses in mouse and zebrafish revealed for the first time a thyroid-enriched expression of cell death regulators of the B-cell lymphoma 2 family during early thyroid morphogenesis. Knockdown of tshr function by morpholino microinjection into embryos did not affect early thyroid morphogenesis but caused defects in later functional differentiation. The thyroid phenotype observed in tshr morphants at later stages comprised a reduction in number and size of functional follicles, down-regulation of differentiation markers, as well as reduced thyroid transcription factor expression. A comparison of our results with phenotypes observed in mouse models of defective TSHR and cAMP signaling highlights the value of zebrafish as a model to enhance the understanding of functional differentiation in the vertebrate thyroid. PMID:21737742

Single photon emission computed tomography imaging for temporal dynamics of thyroidal and salivary radionuclide accumulation in 17-allyamino-17-demothoxygeldanamycin-treated thyroid cancer mouse model

PubMed Central

Liu, Yu-Yu; Brandt, Michael P; Shen, Daniel H; Kloos, Richard T; Zhang, Xiaoli; Jhiang, Sissy M

2014-01-01

Selective iodide uptake and prolonged iodine retention in the thyroid is the basis for targeted radioiodine therapy for thyroid cancer patients; however, salivary gland dysfunction is the most frequent nonthyroidal complications. In this study, we have used noninvasive single photon emission computed tomography functional imaging to quantify the temporal dynamics of thyroidal and salivary radioiodine accumulation in mice. At 60 min post radionuclide injection, radionuclide accumulation in the salivary gland was generally higher than that in thyroid due to much larger volume of the salivary gland. However, radionuclide accumulation per anatomic unit in the salivary gland was lower than that in thyroid and was comparable among mice of different age and gender. Differently, radionuclide accumulation per anatomic unit in thyroid varied greatly among mice. The extent of thyroidal radioiodine accumulation stimulated by a single dose of exogenous bovine TSH (bTSH) in triiodothyronine (T3)-supplemented mice was much less than that in mice received neither bTSH nor T3 (nontreated mice), suggesting that the duration of elevated serum TSH level is important to maximize thyroidal radioiodine accumulation. Furthermore, the extent and duration of radioiodine accumulation stimulated by bTSH was less in the thyroids of the thyroid-targeted RET/PTC1 (thyroglobulin (Tg)-PTC1) mice bearing thyroid tumors compared with the thyroids in wild-type (WT) mice. Finally, the effect of 17-allyamino-17-demothoxygeldanamycin on increasing thyroidal, but not salivary, radioiodine accumulation was validated in both WT mice and Tg-PTC1 preclinical thyroid cancer mouse model. PMID:20943721

Persistent Graves' hyperthyroidism despite rapid negative conversion of thyroid-stimulating hormone-binding inhibitory immunoglobulin assay results: a case report.

PubMed

Ohara, Nobumasa; Kaneko, Masanori; Kitazawa, Masaru; Uemura, Yasuyuki; Minagawa, Shinichi; Miyakoshi, Masashi; Kaneko, Kenzo; Kamoi, Kyuzi

2017-02-06

Graves' disease is an autoimmune thyroid disorder characterized by hyperthyroidism, and patients exhibit thyroid-stimulating hormone receptor antibody. The major methods of measuring circulating thyroid-stimulating hormone receptor antibody include the thyroid-stimulating hormone-binding inhibitory immunoglobulin assays. Although the diagnostic accuracy of these assays has been improved, a minority of patients with Graves' disease test negative even on second-generation and third-generation thyroid-stimulating hormone-binding inhibitory immunoglobulins. We report a rare case of a thyroid-stimulating hormone-binding inhibitory immunoglobulin-positive patient with Graves' disease who showed rapid lowering of thyroid-stimulating hormone-binding inhibitory immunoglobulin levels following administration of the anti-thyroid drug thiamazole, but still experienced Graves' hyperthyroidism. A 45-year-old Japanese man presented with severe hyperthyroidism (serum free triiodothyronine >25.0 pg/mL; reference range 1.7 to 3.7 pg/mL) and tested weakly positive for thyroid-stimulating hormone-binding inhibitory immunoglobulins on second-generation tests (2.1 IU/L; reference range <1.0 IU/L). Within 9 months of treatment with oral thiamazole (30 mg/day), his thyroid-stimulating hormone-binding inhibitory immunoglobulin titers had normalized, but he experienced sustained hyperthyroidism for more than 8 years, requiring 15 mg/day of thiamazole to correct. During that period, he tested negative on all first-generation, second-generation, and third-generation thyroid-stimulating hormone-binding inhibitory immunoglobulin assays, but thyroid scintigraphy revealed diffuse and increased uptake, and thyroid ultrasound and color flow Doppler imaging showed typical findings of Graves' hyperthyroidism. The possible explanations for serial changes in the thyroid-stimulating hormone-binding inhibitory immunoglobulin results in our patient include the presence of thyroid-stimulating hormone receptor antibody, which is bioactive but less reactive on thyroid-stimulating hormone-binding inhibitory immunoglobulin assays, or the effect of reduced levels of circulating thyroid-stimulating hormone receptor antibody upon improvement of thyroid autoimmunity with thiamazole treatment. Physicians should keep in mind that patients with Graves' disease may show thyroid-stimulating hormone-binding inhibitory immunoglobulin assay results that do not reflect the severity of Graves' disease or indicate the outcome of the disease, and that active Graves' disease may persist even after negative results on thyroid-stimulating hormone-binding inhibitory immunoglobulin assays. Timely performance of thyroid function tests in combination with sensitive imaging tests, including thyroid ultrasound and scintigraphy, are necessary to evaluate the severity of Graves' disease and treatment efficacy.

Pediatric Thyroid Cancer

MedlinePlus

... Marketplace Find an ENT Doctor Near You Pediatric Thyroid Cancer Pediatric Thyroid Cancer Patient Health Information News media ... and neck issues, should be consulted. Types of thyroid cancer in children: Papillary : This form of thyroid cancer ...

[Atypical subacute thyroiditis in combination with Grave's disease:Diagnostic difficulties in a case report].

PubMed

Koutouridou, Emmanouela; Planck, Tereza; Uddman, Erik; Lantz, Mikael

2018-04-13

Subacute thyroiditis is a common inflammatory disorder of the thyroid gland, possibly of viral etiology, that typically presents with neck pain, fever and tenderness on palpation of the thyroid gland. Graves' disease is an autoimmune thyroid disorder caused by stimulation of the thyroid gland by thyrotropin receptor antibodies (TRAb). The development of Graves´ disease and subacute thyroiditis simultaneously is an uncommon condition and only a few cases have been reported. In this article we present a case of a 46-year old woman diagnosed with Graves´ disease who was started on thiamazole and weeks later developed high fever. Several differential diagnoses were considered such as infection, lymphoma and vasculitis due to thiamazole. Finally, the fine needle aspiration of the thyroid gland displayed histopathological features of subacute thyroiditis. Remarkably, our patient did not have neck pain or tenderness on palpation of the thyroid gland and overall the clinical presentation of subacute thyroiditis was atypical. Thus, subacute thyroiditis may be considered as a potential cause of fever of unknown origin.

Acute thyrotoxicosis secondary to destructive thyroiditis associated with cardiac catheterization contrast dye.

PubMed

Calvi, Laura; Daniels, Gilbert H

2011-04-01

Thyrotoxicosis caused by destructive thyroiditis is self-limited and results from the subacute release of preformed thyroid hormone. Common etiologies include painful subacute thyroiditis and silent (painless) subacute thyroiditis (including postpartum thyroiditis, amiodarone-associated destructive thyroiditis, and lithium-associated thyroiditis). Thyrotoxicosis commonly evolves slowly over a matter of weeks. We report a unique case of severe thyrotoxicosis caused by acute- onset painful destructive thyroiditis in a patient who received large amounts of nonionic contrast dye Hexabrix® for cardiac catheterization. The results of thyroid function and physical examination were normal before the catheterization. The acute onset of severe thyroid pain, rapid increase in serum Free Thyroxine Index, and thyroglobulin concentrations with a triiodothyronine to free thyroxine index ratio of < 20 to 1 were compatible with an acute onset destructive thyroiditis, likely related to direct toxicity from the iodinated contrast material. In light of the large number of patients who receive these contrast agents during cardiac catheterization, clinicians should be advised of this potentially serious complication, particularly in the setting of unstable cardiac disease.

Papillary thyroid carcinoma in an autonomous hyperfunctioning thyroid nodule: case report and review of the literature.

PubMed

Tfayli, Hala M; Teot, Lisa A; Indyk, Justin A; Witchel, Selma Feldman

2010-09-01

Whereas thyroid nodules are less common among children than among adults, the anxiety generated by the finding of a thyroid nodule is high because 20% of nodules found in children contain thyroid cancer. Discovery of a nodule in the context of hyperthyroidism is usually comforting due to the presumption that the nodule represents a benign toxic adenoma. An 11-year-old girl presented with heavy menses, fatigue, and a right thyroid mass. Laboratory evaluation revealed elevated triiodothyronine and undetectable thyroid-stimulating hormone. Thyroid ultrasonography revealed a 3.5 cm nonhomogenous nodule, and scintigraphy was consistent with an autonomous hyper-functioning nodule. Fine-needle aspiration biopsy could not rule out malignancy, and patient underwent right hemithyroidectomy and isthmusectomy. Pathology was consistent with papillary thyroid carcinoma. We report the discovery of papillary thyroid carcinoma in an autonomously hyperfunctioning nodule in an 11-year-old girl. Detection of an autonomously functioning thyroid nodule in children and adolescents does not exclude the possibility of thyroid carcinoma and warrants careful evaluation and appropriate therapy.

Papillary Thyroid Carcinoma in an Autonomous Hyperfunctioning Thyroid Nodule: Case Report and Review of the Literature

PubMed Central

Tfayli, Hala M.; Teot, Lisa A.; Indyk, Justin A.

2010-01-01

Background Whereas thyroid nodules are less common among children than among adults, the anxiety generated by the finding of a thyroid nodule is high because 20% of nodules found in children contain thyroid cancer. Discovery of a nodule in the context of hyperthyroidism is usually comforting due to the presumption that the nodule represents a benign toxic adenoma. Summary An 11-year-old girl presented with heavy menses, fatigue, and a right thyroid mass. Laboratory evaluation revealed elevated triiodothyronine and undetectable thyroid-stimulating hormone. Thyroid ultrasonography revealed a 3.5 cm nonhomogenous nodule, and scintigraphy was consistent with an autonomous hyper-functioning nodule. Fine-needle aspiration biopsy could not rule out malignancy, and patient underwent right hemithyroidectomy and isthmusectomy. Pathology was consistent with papillary thyroid carcinoma. Conclusions We report the discovery of papillary thyroid carcinoma in an autonomously hyperfunctioning nodule in an 11-year-old girl. Detection of an autonomously functioning thyroid nodule in children and adolescents does not exclude the possibility of thyroid carcinoma and warrants careful evaluation and appropriate therapy. PMID:20718686

[Rare differential diagnosis of hyperthyroidism].

PubMed

Besemer, Britta; Müssig, Karsten

2016-06-01

A 54-year-old female patient is admitted for evaluation of her thyroid function after two cycles of ipilimumab therapy. The decision for the anti-cytotoxic-T-lymphocyte-antigen-4-therapy (anti-CTLA-4) was made two months earlier because of malignant melanoma with pulmonary metastases. The patient was euthyroid before initiation of treatment and without known thyroid disease. The laboratory reveals thyrotoxicosis with elevated anti-thyroid peroxidase and anti-thyroglobulin antibody levels. The anti-thyroid stimulating hormone receptor antibody levels are within the normal range. Thyroid ultrasound shows a normal-sized, inhomogenous, hypoechogenic thyroid gland, consistent with autoimmune thyroiditis. Diagnosis of hyperthyroidism due to ipilimumab-induced autoimmune thyroiditis is made. The patient does not receive any thyroid-specific medication, with regular control of the thyroid hormone levels. When the patient becomes euthyroid, the ipilimumab therapy is continued. Three weeks later, the patient develops hypothyroidism and a supplementation with L-thyroxine is initiated. An anti-CTLA-4 therapy may cause thyroid dysfunction. Therefore, before initiation and in the course of the treatment, regular controls of the thyroid hormone levels are required. © Georg Thieme Verlag KG Stuttgart · New York.

Generalized Resistance to Thyroid Hormone Associated with a Mutation in the Ligand-Binding Domain of the Human Thyroid Hormone Receptor β

NASA Astrophysics Data System (ADS)

Sakurai, Akihiro; Takeda, Kyoko; Ain, Kenneth; Ceccarelli, Paola; Nakai, Akira; Seino, Susumu; Bell, Graeme I.; Refetoff, Samuel; Degroot, Leslie J.

1989-11-01

The syndrome of generalized resistance to thyroid hormone is characterized by elevated circulating levels of thyroid hormone in the presence of an overall eumetabolic state and failure to respond normally to triiodothyronine. We have evaluated a family with inherited generalized resistance to thyroid hormone for abnormalities in the thyroid hormone nuclear receptors. A single guanine --> cytosine replacement in the codon for amino acid 340 resulted in a glycine --> arginine substitution in the hormone-binding domain of one of two alleles of the patient's thyroid hormone nuclear receptor β gene. In vitro translation products of this mutant human thyroid hormone nuclear receptor β gene did not bind triiodothyronine. Thus, generalized resistance to thyroid hormone can result from expression of an abnormal thyroid hormone nuclear receptor molecule.

Thyroid nodules and thyroid autoimmunity in the context of environmental pollution.

PubMed

Benvenga, Salvatore; Antonelli, Alessandro; Vita, Roberto

2015-12-01

Evidence suggests that in most industrialized countries autoimmune disorders, including chronic lymphocytic thyroiditis, are increasing. This increase parallels the one regarding differentiated thyroid cancer, the increment of which is mainly due to the papillary histotype. A number of studies have pointed to an association between chronic lymphocytic thyroiditis and differentiated thyroid cancer. The upward trend of these two thyroid diseases is sustained by certain environmental factors, such as polluting substances acting as endocrine disrupting chemicals. Herein we will review the experimental and clinical literature that highlights the effects of environmental and occupational exposure to polluting chemicals in the development of autoimmune thyroid disease or differentiated thyroid cancer. Stakeholders, starting from policymarkers, should become more sensitive to the consequences for the thyroid resulting from exposure to EDC. Indeed, the economic burden resulting from such consequences has not been quantified thus far.

[Clinico-pathological features of papillary thyroid cancer coexistent with Hashimoto's thyroiditis].

PubMed

Molnár, Sarolta; Győry, Ferenc; Nagy, Endre; Méhes, Gábor; Molnár, Csaba

2017-02-01

Former studies suggest the frequent coexistence of Hashimoto's thyreoditis with papillary thyroid cancer, frequently featured by multifocal carcinogenesis but lower clinical stages compared to thyroid cancers lacking thyroiditis. We examined the clinico-pathological correlations between Hashimoto's thyroditis and papillary thyroid cancer in our region in the North-Eastern part of Hungary. We included a total of 230 patients with papillary thyroid cancer who underwent thyroid surgery at the Surgical Department of the University of Debrecen. Patients' sex, age, multifocality of thyroid cancer and clinical stage were evaluated. Cases included 40 patients (17.4%) with (4 male, 36 female) and 190 (82.6%) patients without HT (44 male, 146 female). Hashimoto's thyroiditis related thyroid cancer was almost exclusively associated with the papillary histological type. Multifocality of papillary cancer was significantly more frequent with coexisting Hashimoto's thyroiditis (16/40; 40.0%) compared to cases uninvolved (45/190; 23.7%; p = 0.034). In contrast, lymph node metastasis was significantly less frequent among patients with Hashimoto's thyroiditis (4 pN1 [36.4%]; 7 pN0 [63.6%]) then without it (34 pN1 [82.9%]; 7 pN0 [17.1%]; p = 0.002). Higher frequency and multifocality of papillary thyroid cancer might be the consequence of preexisting Hashimoto's thyroiditis to be considered as a preneoplastic stimulus supporting carcinogenesis, though the exact pathomechanism of this correlation is not clear yet. Orv. Hetil., 2017, 158(5), 178-182.

Morphological, diagnostic and surgical features of ectopic thyroid gland: a review of literature.

PubMed

Guerra, Germano; Cinelli, Mariapia; Mesolella, Massimo; Tafuri, Domenico; Rocca, Aldo; Amato, Bruno; Rengo, Sandro; Testa, Domenico

2014-01-01

Ectopic thyroid tissue remains a rare developmental abnormality involving defective or aberrant embryogenesis of the thyroid gland during its passage from the floor of the primitive foregut to its usual final position in pre-tracheal region of the neck. Its specific prevalence accounts about 1 case per 100.000-300.000 persons and one in 4.000-8.000 patients with thyroid disease show this condition. The cause of this defect is not fully known. Despite genetic factors have been associated with thyroid gland morphogenesis and differentiation, just recently some mutation has been associated with human thyroid ectopy. Lingual region in the most common site of thyroid ectopy but ectopic thyroid tissue were found in other head and neck locations. Nevertheless, aberrant ectopic thyroid tissue has been found in other places distant from the neck region. Ectopic tissue is affected by different pathological changes that occur in the normal eutopic thyroid. Patients may present insidiously or as an emergency. Diagnostic management of thyroid ectopy is performed by radionuclide thyroid imaging, ultrasonography, CT scan, MRI, biopsy and thyroid function tests. Asymptomatic euthyroid patients with ectopic thyroid do not usually require therapy but are kept under observation. For those with symptoms, treatment depends on size of the gland, nature of symptoms, thyroid function status and histological findings. Surgical excision is often required as treatment for this condition. Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

Transition between morule-like and solid components may occur in solid-predominant adenocarcinoma of the lung: report of 2 cases with EGFR and KRAS mutations.

PubMed

Tajima, Shogo; Koda, Kenji

2015-01-01

A limited number of pulmonary adenocarcinoma cases with morule-like components have been described to date, and the most frequent histological subtype is papillary-predominant adenocarcinoma. Occasionally, this type of adenocarcinoma is associated with solid-predominant adenocarcinoma. EGFR mutations are predominant in adenocarcinoma with morule-like components, followed by ALK rearrangements. Herein, we present 2 cases of solid-predominant adenocarcinoma with morule-like components harboring either an EGFR or KRAS mutation. This KRAS-mutant case is the first to be associated with morule-like components, to the best of our knowledge. Both cases showed transition between micropapillary and morule-like components. Transition between morule-like and solid components was also observed in both cases. Although a few cases of solid-predominant adenocarcinoma have been shown to harbor morule-like components, this type of transition has not been previously well described. We surmised that the solid components of some EGFR-mutant adenocarcinomas might be derived from morule-like components.

Thyroid disease in pustulosis palmoplantaris.

PubMed

Agner, T; Sindrup, J H; Høier-Madsen, M; Hegedüs, L

1989-10-01

An increased frequency of thyroid autoantibodies has been reported in patients with palmar and plantar pustulosis (PPP). This study was undertaken to determine the frequency and type of thyroid disease in 32 patients with this disease compared with a control group. Thyroid disease was demonstrated in 53% of the patients with PPP as compared to 16% in the matched control group. Fourteen patients with PPP had an enlarged thyroid and in six there were thyroid autoantibodies. There appears to be an increased incidence of goitre and thyroid autoantibodies in PPP with a decrease in the level of the thyroid hormones.

[Poorly differentiated thyroid carcinomas: new therapeutic considerations].

PubMed

Graf, Hans

2005-10-01

For most differentiated thyroid carcinomas, as papillary and follicular carcinomas, following total thyroidectomy and 131I therapy for thyroid remnant ablation, treatment with thyroid hormones to suppress TSH levels will reduce the growth of any remaining thyroid cancer cells, and thyroid cell-specific radiation therapy will either cure or control the disease. Thyroid carcinomas are considered poorly differentiated when they start to lose such functions as iodine uptake and thyrotropin-dependence for growth and production of thyroid proteins like NIS, thyroglobulin and desiodases. One of the greatest challenges in the management of patients with follicular cell-derived thyroid cancer is the treatment of tumors that progressed despite surgery, (131)I and T4 suppression of TSH. With the better knowledge of the abnormal molecular signaling in thyroid cancer cells, actually known targeted cancer therapies, directed against molecules involved in neoplastic transformation, are being used. As the critical molecular requirements for tumor initiation, maintenance and progression are identified, combination therapies with targeted agents acting on each of them will improve the treatment of poorly differentiated thyroid carcinoma.

Expression and clinical significance of connective tissue growth factor in thyroid carcinomas.

PubMed

Wang, Guimin; Zhang, Wei; Meng, Wei; Liu, Jia; Wang, Peisong; Lin, Shan; Xu, Liyan; Li, Enmin; Chen, Guang

2013-08-01

To examine expression of the connective tissue growth factor (CTGF) gene in human thyroid cancer and establish whether a correlation exists between the presence of CTGF protein and clinicopathological parameters of the disease. CTGF protein expression was investigated retrospectively by immunohistochemical analysis of CTGF protein levels in thyroid tumour tissue. Associations between immunohistochemical score and several clinicopathological parameters were examined. In total, 131 thyroid tissue specimens were included. High levels of CTGF protein were observed in papillary thyroid carcinoma tissue; benign thyroid tumour tissue scored negatively for CTGF protein. In papillary thyroid carcinoma, there was a significant relationship between high CTGF protein levels and Union for International Cancer Control disease stage III-IV, and presence of lymph node metastasis. In papillary thyroid carcinomas, CTGF protein levels were not significantly associated with sex or age. These findings suggest that the CTGF protein level is increased in papillary thyroid carcinoma cells compared with benign thyroid tumours. CTGF expression might play a role in the development of malignant tumours in the thyroid.

Diffuse Thyroid Metastasis From Lung Cancer Mimicking Thyroiditis on 99mTc-Pertechnetate Scintigraphy.

PubMed

Gao, Rui; Gao, Shan; Feng, Jinteng; Wang, Yuanbo; Zhang, Guangjian

2017-09-01

Possible thyroiditis was suspected in a 56-year-old man who initially presented sore throat because laboratory examinations revealed decreased serum thyroid hormone and the Tc-pertechnetate scintigraphy showed no tracer uptake by the thyroid gland. However, subsequent examination demonstrated that the absence of pertechnetate activity in the thyroid was due to complete replacement of thyroid gland by the metastasis from lung adenocarcinoma, which was unknown at the initial presentation.

The role of thyroid hormone in trophoblast function, early pregnancy maintenance, and fetal neurodevelopment.

PubMed

Ohara, Noriyuki; Tsujino, Taro; Maruo, Takeshi

2004-11-01

To review the literature on the roles of thyroid hormone in trophoblast function, early pregnancy maintenance, and fetal neurodevelopment. MEDLINE was searched for English-language papers published from 1971 to 2003, using the key words "brain," "hypothyroidism," "placenta," "pregnancy," "threatened abortion," "thyroid hormone," "thyroid hormone receptor," "thyroid hormone replacement therapy," "thyroid hormone-responsive gene," and "trophoblast." Transplacental transfer of thyroid hormone occurs before the onset of fetal thyroid hormone secretion. Thyroid hormone receptors and iodothyronine deiodinases are present in the placenta and the fetal central nervous system early in pregnancy, and thyroid hormone plays a crucial role both in trophoblast function and fetal neurodevelopment. Maternal hypothyroxinemia is associated with a high rate of spontaneous abortion and long-term neuropsychological deficits in children born of hypothyroid mothers. Maternal iodine deficiency also causes a wide spectrum of neuropsychological disorders in children, ranging from subclinical deficits in cognitive motor and auditory functions to hypothyroid-induced cognitive impairment in infants. However, these conditions are preventable when iodine supplementation is initiated before the second trimester. Although thyroid hormone replacement therapy is effective for reducing the adverse effects complicated by maternal hypothyroidism, the appropriate dose of thyroid hormone is mandatory in protecting the early stage of pregnancy. Close monitoring of maternal thyroid hormone status and ensuring adequate maternal thyroid hormone levels in early pregnancy are of great importance to prevent miscarriage and neuropsychological deficits in infants.

Thyroid Cancer—Health Professional Version

Cancer.gov

There are four types of thyroid cancer. These are papillary, follicular, medullary, and anaplastic thyroid cancer. Papillary is the most common type of thyroid cancer. Find evidence-based information on thyroid cancer treatment, screening, research, genetics, and statistics.

Neurotoxicity of Thyroid Disrupting Contaminants

EPA Science Inventory

Thyroid hormones playa critical role in the normal development ofthe mammalian brain. Thyroid disrupting chemicals (TDCs) are environmental contaminants that alter the structure or function ofthe thyroid gland, alter regulatory enzymes associated with thyroid hormone (TH) homeost...

Development of a normal tissue complication probability (NTCP) model for radiation-induced hypothyroidism in nasopharyngeal carcinoma patients.

PubMed

Luo, Ren; Wu, Vincent W C; He, Binghui; Gao, Xiaoying; Xu, Zhenxi; Wang, Dandan; Yang, Zhining; Li, Mei; Lin, Zhixiong

2018-05-18

The objectives of this study were to build a normal tissue complication probability (NTCP) model of radiation-induced hypothyroidism (RHT) for nasopharyngeal carcinoma (NPC) patients and to compare it with other four published NTCP models to evaluate its efficacy. Medical notes of 174 NPC patients after radiotherapy were reviewed. Biochemical hypothyroidism was defined as an elevated level of serum thyroid-stimulating hormone (TSH) value with a normal or decreased level of serum free thyroxine (fT4) after radiotherapy. Logistic regression with leave-one-out cross-validation was performed to establish the NTCP model. Model performance was evaluated and compared by the area under the receiver operating characteristic curve (AUC) in our NPC cohort. With a median follow-up of 24 months, 39 (22.4%) patients developed biochemical hypothyroidism. Gender, chemotherapy, the percentage thyroid volume receiving more than 50 Gy (V 50 ), and the maximum dose of the pituitary (P max ) were identified as the most predictive factors for RHT. A NTCP model based on these four parameters were developed. The model comparison was made in our NPC cohort and our NTCP model performed better in RHT prediction than the other four models. This study developed a four-variable NTCP model for biochemical hypothyroidism in NPC patients post-radiotherapy. Our NTCP model for RHT presents a high prediction capability. This is a retrospective study without registration.

Combining micro-RNA and protein sequencing to detect robust biomarkers for Graves' disease and orbitopathy.

PubMed

Zhang, Lei; Masetti, Giulia; Colucci, Giuseppe; Salvi, Mario; Covelli, Danila; Eckstein, Anja; Kaiser, Ulrike; Draman, Mohd Shazli; Muller, Ilaria; Ludgate, Marian; Lucini, Luigi; Biscarini, Filippo

2018-05-30

Graves' Disease (GD) is an autoimmune condition in which thyroid-stimulating antibodies (TRAB) mimic thyroid-stimulating hormone function causing hyperthyroidism. 5% of GD patients develop inflammatory Graves' orbitopathy (GO) characterized by proptosis and attendant sight problems. A major challenge is to identify which GD patients are most likely to develop GO and has relied on TRAB measurement. We screened sera/plasma from 14 GD, 19 GO and 13 healthy controls using high-throughput proteomics and miRNA sequencing (Illumina's HiSeq2000 and Agilent-6550 Funnel quadrupole-time-of-flight mass spectrometry) to identify potential biomarkers for diagnosis or prognosis evaluation. Euclidean distances and differential expression (DE) based on miRNA and protein quantification were analysed by multidimensional scaling (MDS) and multinomial regression respectively. We detected 3025 miRNAs and 1886 proteins and MDS revealed good separation of the 3 groups. Biomarkers were identified by combined DE and Lasso-penalized predictive models; accuracy of predictions was 0.86 (±0:18), and 5 miRNA and 20 proteins were found including Zonulin, Alpha-2 macroglobulin, Beta-2 glycoprotein 1 and Fibronectin. Functional analysis identified relevant metabolic pathways, including hippo signaling, bacterial invasion of epithelial cells and mRNA surveillance. Proteomic and miRNA analyses, combined with robust bioinformatics, identified circulating biomarkers applicable to diagnose GD, predict GO disease status and optimize patient management.

Preoperative vitamin D deficiency and postoperative hypocalcemia in thyroid cancer patients undergoing total thyroidectomy plus central compartment neck dissection

PubMed Central

Wang, Xiaofei; Zhu, Jingqiang; Liu, Feng; Gong, Yanping; Li, Zhihui

2017-01-01

Background There appears to be a lack of consensus whether preoperative vitamin D deficiency (VDD) increases the risk of postoperative hypocalcemia and decreases the accuracy of postoperative parathyroid hormone (PTH) in predicting hypocalcemia in thyroid cancer patients undergoing total thyroidectomy (TT) plus central compartment neck dissection (CCND). This study aims to address these issues. Method All consecutive thyroid cancer patients who underwent TT plus CCND were retrospectively reviewed through a prospectively collected database between October 2015 and April 2016 in a tertiary referral hospital. The multivariate analysis was performed to identify the significant predictors for hypocalcemia. Receiver operator characteristic curve (ROC) was created and the area under the ROC was used to evaluate the predictive accuracy of postoperative PTH and compared between patients with or without VDD. Results A total of 186 patients were included. The incidence of VDD was 73.7% (137 patients). The incidence of biochemical and symptomatic hypocalcemia was similar in patients with or without VDD (P = 0.304 and 0.657, respectively). Multivariate analysis showed that only postoperative PTH was an independent predictor of symptomatic hypocalcemia (OR = 8.05, 95%CI = 3.99-16.22; P = 0.000). The area under the ROC was similar between patients with preoperative vitamin D level < 20 and ≥20 ng/mL (0.809 versus 0.845, P = 0.592). Conclusion VDD was not a significant risk factor for hypocalcemia following TT+CCND, and did not affect the accuracy of postoperative PTH as a predictor of postoperative hypocalcemia. Thus, routine preoperative screening for vitamin D seems to be unnecessary. PMID:29100453

Frequent cellular phone use modifies hypothalamic-pituitary-adrenal axis response to a cellular phone call after mental stress in healthy children and adolescents: A pilot study.

PubMed

Geronikolou, Styliani A; Chamakou, Aikaterini; Mantzou, Aimilia; Chrousos, George; KanakaGantenbein, Christina

2015-12-01

The hypothalamic-pituitary-adrenal (HPA) axis is the main "gate-keeper" of the organism's response to every somatic or mental stress. This prospective study aims to investigate the HPA-axis response to a cellular phone call exposure after mental stress in healthy children and adolescents and to assess the possible predictive role of baseline endocrine markers to this response. Two groups of healthy school-age children aged 11-14 (12.5±1.5) years were included in the study, the one comprising those who are occasional users of a cellular phone (Group A) while the second those who do regularly use one (Group B). Blood samples were obtained from all participants at 8.00 am after a 12-hour overnight fasting for thyroid hormone, glucose, insulin, and cortisol levels determination. The participants performed the Trier Social Stress Test for Children (TSST-C) (5 minoral task followed by 5 min arithmetic task). Salivary cortisol samples were obtained at baseline, 10' and 20' min after the TSST-C and 10' and 20' after a 5 minute cellular phone call. Significant changes in the salivary cortisol levels were noted between 10' and 20' mins after the cellular phone call with different responses between the two groups. Baseline thyroid hormone levels seem to predict the cortisol response to mental stress mainly in group A, while HOMA had no impact on salivary cortisol response at any phase of the test, in either group. HPA axis response to cellular phone after mental stress in children and adolescents follow a different pattern in frequent users than in occasional users that seems to be influenced by the baseline thyroid hormone levels. Copyright © 2015 Elsevier B.V. All rights reserved.

Both thyroid hormone levels and resting metabolic rate decrease in African striped mice when food availability decreases.

PubMed

Rimbach, Rebecca; Pillay, Neville; Schradin, Carsten

2017-03-01

In response to variation in food availability and ambient temperature ( T a ), many animals show seasonal adaptations in their physiology. Laboratory studies showed that thyroid hormones are involved in the regulation of metabolism, and their regulatory function is especially important when the energy balance of an individual is compromised. However, little is known about the relationship between thyroid hormones and metabolism in free-living animals and animals inhabiting seasonal environments. Here, we studied seasonal changes in triiodothyronine (T 3 ) levels, resting metabolic rate (RMR) and two physiological markers of energy balance (blood glucose and ketone bodies) in 61 free-living African striped mice ( Rhabdomys pumilio ) that live in an semi-arid environment with food shortage during the dry season. We predicted a positive relationship between T 3 levels and RMR. Further, we predicted higher T 3 levels, blood glucose levels and RMR, but lower ketone body concentrations, during the moist season when food availability is high compared with summer when food availability is low. RMR and T 3 levels were negatively related in the moist season but not in the dry season. Both RMR and T 3 levels were higher in the moist than in the dry season, and T 3 levels increased with increasing food availability. In the dry season, blood glucose levels were lower but ketone body concentrations were higher, indicating a change in substrate use. Seasonal adjustments in RMR and T 3 levels permit a reduction of energy expenditure when food is scarce, and reflect an adaptive response to reduced food availability in the dry season. © 2017. Published by The Company of Biologists Ltd.

Comparison of the Seventh and Eighth Editions of the American Joint Committee on Cancer/Union for International Cancer Control Tumor-Node-Metastasis Staging System for Differentiated Thyroid Cancer.

PubMed

Kim, Mijin; Kim, Won Gu; Oh, Hye-Seon; Park, Suyeon; Kwon, Hyemi; Song, Dong Eun; Kim, Tae Yong; Shong, Young Kee; Kim, Won Bae; Sung, Tae-Yon; Jeon, Min Ji

2017-09-01

To evaluate the efficacy and prognostic validity for disease-specific survival (DSS) of the eighth edition American Joint Committee on Cancer/Union for International Cancer Control tumor-node-metastasis (TNM) staging system (TNM-8) compared to the seventh edition (TNM-7) in patients with differentiated thyroid carcinoma (DTC). The seventh and eighth editions of the TNM staging system were applied to 1613 DTC patients who underwent thyroid surgery between 1996 and 2003. The proportion of variation explained and Harrell's c-index were evaluated to compare the predictive capability of DSS. The mean age of the patients was 44.7 years, and the median follow-up period was 11.2 years. When TNM-8 was applied, 63% of T3 and 3% of N1b DTCs were downgraded to T1/T2 and N1a, respectively. About 38% of patients were downstaged according to TNM-8. The 10-year DSS rates in TNM-7 stages I, II, III, and IV were 99.7%, 98.2%, 98.8%, and 83.2%, respectively. Those in TNM-8 stages I, II, III, and IV were 99.6%, 95.4%, 72.3%, and 48.6%, respectively. The proportion of variation explained values of TNM-7 and TNM-8 were 6.0% and 7.0%, respectively. The Harrell's c-index of TNM-7 was 0.86 and that of TNM-8 was 0.88. A significant number of patients were reclassified to lower stages with the application of TNM-8 compared to TNM-7. Applying TNM-8 could improve the accuracy of the staging system for predicting DSS in patients with DTC.

False-negative BRAF V600E mutation results on fine-needle aspiration cytology of papillary thyroid carcinoma.

PubMed

Paek, Se Hyun; Kim, Byung Seup; Kang, Kyung Ho; Kim, Hee Sung

2017-11-13

The BRAF V600E mutation is highly specific for papillary thyroid carcinoma (PTC). A test for this mutation can increase the diagnostic accuracy of fine-needle aspiration cytology (FNAC), but a considerably high false-negative rate for the BRAF V600E mutation on FNAC has been reported. In this study, we investigated the risk factors associated with false-negative BRAF V600E mutation results on FNAC. BRAF V600E mutation results of 221 PTC nodules between December 2011 and June 2013 were retrospectively reviewed. BRAF V600E mutation results on both preoperative FNAC and postoperative formalin-fixed, paraffin-embedded (FFPE) samples were compared. We investigated the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of BRAF V600E mutation results on FNAC. And, we identified the risk factors associated with false-negative results. Of 221 PTC nodules, 150 (67.9%) on FNAC and 185 (83.7%) on FFPE samples were BRAF V600E mutation positive. The sensitivity, specificity, PPV, and NPV for BRAF V600E mutation testing with FNAC were 80.5, 97.2, 99.3, and 49.3%, respectively. Thirty-six (16.3%) BRAF V600E mutation-negative nodules on FNAC were mutation positive on FFPE sample analysis. Risk factors for these false-negative results were age, indeterminate FNAC results (nondiagnostic, atypia of undetermined significance (AUS), and findings suspicious for PTC), and PTC subtype. False-negative rate of BRAF mutation testing with FNAC for thyroid nodules is increased in cases of old age, indeterminate FNAC pathology results, and certain PTC subtypes. Therapeutic surgery can be considered for these cases. A well-designed prospective study with informed consent of patients will be essential for more informative results.

Decreased expression of hsa_circ_0137287 predicts aggressive clinicopathologic characteristics in papillary thyroid carcinoma.

PubMed

Lan, Xiabin; Cao, Jun; Xu, Jiajie; Chen, Chao; Zheng, Chuanming; Wang, Jiafeng; Zhu, Xuhang; Zhu, Xin; Ge, Minghua

2018-05-22

Circular RNA (circRNA) is a new type of noncoding RNA that can serve as ideal biomarkers. Evidence has showed that circRNAs play an important role in carcinogenesis and cancer development. However, little is known about the diagnostic value of circRNAs in papillary thyroid carcinoma (PTC) as well as their associations with clinicopathologic characteristics of patients with PTC. The expression levels of hsa_circ_0137287 were detected in 120 PTC and 60 adjacent noncancerous thyroid tissues by quantitative real-time polymerase chain reaction. The relationships between the expression of hsa_circ_0137287 in PTC and the clinicopathologic factors were analyzed. Finally, receiver operating characteristic (ROC) curves were generated to assess the diagnostic value of hsa_circ_0137287 as a biomarker for PTC. The expression of hsa_circ_0137287 was significantly downregulated in PTC tissues compared with adjacent noncancerous tissues (P < .0001). Downregulation of hsa_circ_0137287 correlated with aggressive clinicopathologic characteristics of PTC such as extrathyroidal extension (P < .001), lymph node metastasis (P = .022), advanced T stage (P < .001) and larger tumor size (P < .001). The ROC curves revealed that hsa_circ_0137287 had a potential diagnostic value in predicting malignancy, extrathyroidal extension and lymph node metastasis. The area under curves were 0.8973 (95% CI = 0.8452-0.9494, P < .0001), 0.6885 (95%CI = 0.5908-0.7862, P = .0009), and 0.6691(95%CI = 0.5641-0.7742, P = .0034), respectively. Our findings suggest that hsa_circ_0137287 may serve as a novel biomarker for PTC. © 2018 Wiley Periodicals, Inc.

Day 3 thyroglobulin ≤ 1 ng/ml after recombinant human TSH just prior to radioactive iodine is predictive of low risk for persistent/recurrent disease in patients with papillary thyroid carcinoma.

PubMed

Rosario, Pedro W; Siman, Thássio Leonardo; Calsolari, Maria R

2015-05-01

We evaluated the negative predictive value (NPV) of thyroglobulin obtained 24 h after the second recombinant human TSH (rhTSH) ampoule (Tg-D3), before ablation with (131)I, for persistent/recurrent disease (PRD) in low/intermediate risk patients with papillary thyroid carcinoma. One hundred and one patients with Tg-D3 ≤ 1 ng/ml without anti-Tg antibodies (TgAb) were selected. Post-therapy whole-body scanning was negative for metastases in 98 (97 %) patients, and three patients showed discrete ectopic cervical uptake, but no corresponding disease was detected by neck ultrasound or computed tomography. One year after ablation, 98 (97 %) patients were free of the disease. Three patients had stimulated Tg >1 ng/ml, but no metastases were detected by the imaging methods. During follow-up (median 50 months), tumor recurrence was observed in only one patient. Thus, the NPV of Tg-D3 ≤ 1 ng/ml for PRD was 99 %. Among the 101 patients with Tg-D3 ≤ 1 ng/ml, Tg obtained 48 h after ablation (Tg-D5) continued to be ≤ 1 ng/ml in 56, and 45 had Tg-D5 >1 ng/ml. None of these 45 patients had PRD. In conclusion, Tg-D3 ≤ 1 ng/ml had a high NPV for PRD in patients without TgAb or known persistent disease and who are not at high risk. In these patients, Tg-D5 >1 ng/ml is more likely to reflect actinic damage to the remnant thyroid tissue rather than persistence of significant normal or tumor tissue.

Somatostatin receptor scintigraphy using 99mTc-EDDA/HYNIC-TOC in patients with medullary thyroid carcinoma.

PubMed

Czepczyński, Rafał; Parisella, Maria Gemma; Kosowicz, Jerzy; Mikołajczak, Renata; Ziemnicka, Katarzyna; Gryczyńska, Maria; Sowiński, Jerzy; Signore, Alberto

2007-10-01

Several new somatostatin analogues have been developed for the diagnosis and therapy of different tumours. Since somatostatin receptors are often over-expressed in medullary thyroid carcinoma (MTC), the aim of our study was to evaluate the utility of scintigraphy with the somatostatin analogue (99m)Tc-EDDA/HYNIC-TOC in MTC in comparison with other diagnostic techniques. Forty-five patients with MTC, aged 14-83 years, were investigated. Scintigraphy using (99m)Tc-EDDA/HYNIC-TOC (Tektrotyd) was performed 2 and 4 h post injection of 740 MBq (20 mCi) of the tracer. Other imaging techniques were also applied and analysed in individual cases (ultrasonography, computed tomography, (99m)Tc(V)-DMSA, (131)I-MIBG, (99m)Tc-MDP, (111)In-DTPA-octreotide and (18)F-FDG-PET) and compared with (99m)Tc-EDDA/HYNIC-TOC. In group 1 (eight patients before thyroidectomy), uptake of the tracer was found in the primary tumours. In group 2 (six patients with remission), a false positive result was found in one patient; in the remaining five patients, no pathological foci were visualised. In group 3 (31 patients with post-surgical hypercalcitoninaemia), scintigraphy was true positive in 23 patients (74.2%): uptake in the thyroid bed was found in five patients, in the lymph nodes in 18 and in bone metastases in four. Using (99m)Tc-EDDA/HYNIC-TOC scintigraphy, the overall sensitivity was 79.5%, specificity 83.3%, accuracy 80.0%, positive predictive value 96.9% and negative predictive value 38.5%. (99m)Tc-EDDA/HYNIC-TOC is clinically useful for scintigraphy in the follow-up of patients with MTC. It can be used in clinical practice for preoperative evaluation, for localisation of local recurrence or distant metastases and particularly for therapy decision making.

TSH Compensates Thyroid-Specific IGF-I Receptor Knockout and Causes Papillary Thyroid Hyperplasia

PubMed Central

Müller, Kathrin; Führer, Dagmar; Mittag, Jens; Klöting, Nora; Blüher, Matthias; Weiss, Roy E.; Many, Marie-Christine; Schmid, Kurt Werner

2011-01-01

Although TSH stimulates all aspects of thyroid physiology IGF-I signaling through a tyrosine kinase-containing transmembrane receptor exhibits a permissive impact on TSH action. To better understand the importance of the IGF-I receptor in the thyroid in vivo, we inactivated the Igf1r with a Tg promoter-driven Cre-lox system in mice. We studied male and female mice with thyroidal wild-type, Igf1r+/−, and Igf1r−/− genotypes. Targeted Igf1r inactivation did transiently reduce thyroid hormone levels and significantly increased TSH levels in both heterozygous and homozygous mice without affecting thyroid weight. Histological analysis of thyroid tissue with Igf1r inactivation revealed hyperplasia and heterogeneous follicle structure. From 4 months of age, we detected papillary thyroid architecture in heterozygous and homozygous mice. We also noted increased body weight of male mice with a homozygous thyroidal null mutation in the Igf1r locus, compared with wild-type mice, respectively. A decrease of mRNA and protein for thyroid peroxidase and increased mRNA and protein for IGF-II receptor but no significant mRNA changes for the insulin receptor, the TSH receptor, and the sodium-iodide-symporter in both Igf1r+/− and Igf1r−/− mice were detected. Our results suggest that the strong increase of TSH benefits papillary thyroid hyperplasia and completely compensates the loss of IGF-I receptor signaling at the level of thyroid hormones without significant increase in thyroid weight. This could indicate that the IGF-I receptor signaling is less essential for thyroid hormone synthesis but maintains homeostasis and normal thyroid morphogenesis. PMID:21980075

Characteristics of patients with graves disease and intrathyroid hypovascularity compared to painless thyroiditis.

PubMed

Uchida, Toyoyoshi; Shigihara, Nayumi; Takeno, Kageumi; Komiya, Koji; Goto, Hiromasa; Abe, Hiroko; Sato, Junko; Honda, Akira; Fujitani, Yoshio; Watada, Hirotaka

2014-10-01

The purpose of this study was to assess the frequency and sonographic and laboratory characteristics of Graves disease with intrathyroid hypovascularity in Japanese patients and to compare these characteristics in patients with painless thyroiditis. A total of 194 consecutive patients with Graves disease and 21 patients with painless thyroiditis were enrolled. The patients underwent thyroid volume measurement, mean superior thyroid artery peak systolic velocity (PSV) measurement, power Doppler sonography, and proper blood testing to discriminate between Graves disease and painless thyroiditis. Based on the power Doppler sonographic findings, they were divided into 4 groups: from pattern 0 (most hypovascular thyroid) to pattern III (most hypervascular thyroid). Comparisons of multiple thyroid parameters were made among the groups. The prevalence of Graves disease with pattern 0 (n = 27) was 13.9% among the patients with Graves disease. The sonographic and laboratory data for patients with Graves disease and pattern 0 were compared to those of the 21 patients with painless thyroiditis, which typically shows intrathyroid hypovascularity. Free triiodothyronine and thyroxine levels and the superior thyroid artery PSV were significantly lower in patients with Graves disease and pattern 0 than those with patterns I, II, and III (P < .05). The thyroid volume and thyrotropin receptor antibody level were significantly lower in patients with Graves disease and pattern 0 than those with pattern III. In the comparison between patients with Graves disease and pattern 0 and those with painless thyroiditis and pattern 0, apart from thyrotropin receptor antibody, only the superior thyroid artery PSV was different. Although the clinical features of patients with Graves disease and intrathyroid hypovascularity were similar to those patients with painless thyroiditis, the superior thyroid artery PSV showed a moderate ability to discriminate these patients. © 2014 by the American Institute of Ultrasound in Medicine.

The association between thyroid malignancy and chronic lymphocytic thyroiditis: should it alter the surgical approach?

PubMed

Büyükaşık, Oktay; Hasdemir, Ahmet Oğuz; Yalçın, Erol; Celep, Bahadır; Sengül, Serkan; Yandakçı, Kemal; Tunç, Gündüz; Küçükpınar, Tevfik; Alkoy, Seval; Cöl, Cavit

2011-01-01

The relation between thyroid neoplasms and chronic lymphocytic thyroiditis (CLT) is controversial. While it is accepted that focal lymphocytic thyroiditis develops secondarily to malignancy, it is not clear whether diffuse lymphocytic thyroiditis has a tendency to develop into thyroid cancer. The aim of this study was to investigate the relation between CLT and malignant tumours of the thyroid and evaluate the surgical approach to CLT cases. In this study, 917 patients operated on for thyroid diseases were investigated retrospectively. Seventy-seven (8.4%) patients histopathologically diagnosed as having CLT (either non-specific or Hashimoto's thyroiditis) were investigated for any concurrent malignant neoplasm. Fifteen patients in whom CLT and thyroid malignancy were coexisting were included in the study. In the pathological evaluation of 917 cases, malignancy in the thyroid was found in 97 (10.6%) cases. Seventy-seven cases were categorised as CLT. Of these 77, 16 (20.8%) were Hashimoto's thyroiditis (specific CLT) and the other 61 (79.2%) were non-specific CLT. In 15 cases, thyroid malignancy was found to be concurrent with CLT. Of the malignities, nine (60%) were papillary carcinoma, three (20%) medullar carcinoma, one (6.6%) follicular carcinoma, one (6.6%) Hurthle cell carcinoma, and one (6.6%) lymphoma. In our series, the rate of the development of malignancy against the background of CLT was 19.48%, while the rate in the groups without CLT was 9.76%, with a statistically significant difference between the groups (p = 0.008). CLT cases should be evaluated more carefully in terms of malignancy. If a nodule is detected on thyroiditis, the minimal surgical intervention should be lobectomy. Total thyroidectomy should be considered as preferable to subtotal thyroidectomy because of its many advantages such as controlling thyroiditis, removing the probability of reoperation, and hormonal stability.

True Aneurysm of the Inferior Thyroid Artery: A Case Report and Literature Review.

PubMed

Venturini, Luigi; Sapienza, Paolo; Grande, Raffaele; Scarano Catanzaro, Valerio; Fanelli, Fabrizio; di Marzo, Luca

2017-04-01

Aneurysms of the inferior thyroid artery (ITA) are extremely rare and potentially determine severe sequelae. We report a case of true ITA aneurysm in a 45-year-old Caucasian woman treated with endovascular embolization; postoperative course was uneventful and, at 6-month follow-up, the aneurysm is completely thrombized. A systematic review of the literature has been also performed to identify the epidemiologic and clinical characteristics and diagnostic and operative options of this disease. Size alone is not able to predict the fate of the aneurysm and an aggressive treatment seems to be justified because of the high risk of complications in case of rupture. In an emergency setting, the endovascular procedures associated to hematoma evacuation or open surgery should be rapidly performed to save patient life. Copyright © 2016 Elsevier Inc. All rights reserved.

Thyroid Volume and Its Relation to Anthropometric Measures in a Healthy Cuban Population

PubMed Central

Turcios, Silvia; Lence-Anta, Juan J.; Santana, Jose-Luis; Pereda, Celia M.; Velasco, Milagros; Chappe, Mae; Infante, Idalmis; Bustillo, Marlene; García, Anabel; Clero, Enora; Maillard, Stephane; Rodriguez, Regla; Xhaard, Constance; Ren, Yan; Rubino, Carole; Ortiz, Rosa M.; de Vathaire, Florent

2015-01-01

Objectives The aim of this study was to describe the thyroid volume in healthy adults by ultrasound and to correlate this volume with some anthropometric measures and other differentiated thyroid cancer risk factors. Study Design Thyroid volume and anthropometric measures were recorded in a sample of 100 healthy adults, including 21 men and 79 women aged 18-50 years, living in a non-iodine-deficient area of Havana city. Results The average thyroid volume was 6.6 ± 0.26 ml; it was higher in men (7.3 ml) than in women (6.4 ml; p = 0.15). In the univariate analysis, thyroid volume was correlated with all anthropometric measures, but in the multivariate analysis, body surface area was found to be the only significant anthropometric parameter. Thyroid volume was also higher in current or former smokers and in persons with blood group AB or B. Conclusion Specific reference values of thyroid volume as a function of body surface area could be used for evaluating thyroid volume in clinical practice. The relation between body surface area and thyroid volume is coherent with what is known about the relation of thyroid volume to thyroid cancer risk, but the same is not true about the relation between thyroid volume and smoking habit. PMID:25960963

Thyroid nodules, thyroid function and dietary iodine in the Marshall islands.

PubMed

Takahashi, T; Fujimori, K; Simon, S L; Bechtner, G; Edwards, R; Trott, K R

1999-08-01

Thyroid nodules have been found to be common in the population of the Marshall Islands. This has been attributed to potential exposure of radioiodines from the nuclear weapons tests on Bikini and Eniwetok between 1946 and 1958. In order to get a full picture of thyroid pathology in the Marshallese population potentially exposed to radioactive fallout we performed a large thyroid screening programme using palpation, high resolution ultrasound and fine needle biopsies of palpable nodules. In addition, various parameters of thyroid function (free T3, free T4, thyroid stimulating hormone [TSH]) and anti-thyroid antibodies were examined in large proportions of the total population at risk. Since dietary iodine deficiency is an established risk factor for thyroid nodules, iodine concentration in urine samples of 362 adults and 119 children was measured as well as the iodine content of selected staple food products. The expected high prevalence of thyroid nodules was confirmed. There was no indication of an increased rate of impaired thyroid function in the Marshallese population. A moderate degree of iodine deficiency was found which may be responsible for some of the increased prevalence of thyroid nodules in the Marshallese population. Studies on the relationship between exposure to radioiodines and thyroid nodules need to take dietary iodine deficiency into account in the interpretation of findings.

Immunological Reactivity Using Monoclonal and Polyclonal Antibodies of Autoimmune Thyroid Target Sites with Dietary Proteins

PubMed Central

Herbert, Martha

2017-01-01

Many hypothyroid and autoimmune thyroid patients experience reactions with specific foods. Additionally, food interactions may play a role in a subset of individuals who have difficulty finding a suitable thyroid hormone dosage. Our study was designed to investigate the potential role of dietary protein immune reactivity with thyroid hormones and thyroid axis target sites. We identified immune reactivity between dietary proteins and target sites on the thyroid axis that includes thyroid hormones, thyroid receptors, enzymes, and transport proteins. We also measured immune reactivity of either target specific monoclonal or polyclonal antibodies for thyroid-stimulating hormone (TSH) receptor, 5′deiodinase, thyroid peroxidase, thyroglobulin, thyroxine-binding globulin, thyroxine, and triiodothyronine against 204 purified dietary proteins commonly consumed in cooked and raw forms. Dietary protein determinants included unmodified (raw) and modified (cooked and roasted) foods, herbs, spices, food gums, brewed beverages, and additives. There were no dietary protein immune reactions with TSH receptor, thyroid peroxidase, and thyroxine-binding globulin. However, specific antigen-antibody immune reactivity was identified with several purified food proteins with triiodothyronine, thyroxine, thyroglobulin, and 5′deiodinase. Laboratory analysis of immunological cross-reactivity between thyroid target sites and dietary proteins is the initial step necessary in determining whether dietary proteins may play a potential immunoreactive role in autoimmune thyroid disease. PMID:28894619

Occult lymph node metastasis and risk of regional recurrence in papillary thyroid cancer after bilateral prophylactic central neck dissection: A multi-institutional study.

PubMed

Lee, Young Chan; Na, Se Young; Park, Gi Cheol; Han, Ju Hyun; Kim, Seung Woo; Eun, Young Gyu

2017-02-01

The impact of occult lymph node metastasis on regional recurrence after prophylactic central neck dissection for preoperative, nodal-negative papillary thyroid cancer is controversial. We investigated risk factors for regional lymph node recurrence in papillary thyroid cancer patients who underwent total thyroidectomy and bilateral prophylactic central neck dissection. Analysis was according to clinicopathologic characteristics and occult lymph node metastasis patterns. This multicenter study enrolled 211 consecutive patients who underwent total thyroidectomy with bilateral prophylactic central neck dissection for papillary thyroid cancer without evidence of central lymph node metastasis on preoperative imaging. Clinicopathologic features and central lymph node metastasis patterns were analyzed for predicting regional recurrence. Multivariate Cox regression analysis was used to identify independent factors for recurrence. Median follow-up time was 43 months (24-95 months). Ten patients (4.7%) showed regional lymph node recurrence. The estimated 5-year, regional recurrence-free survival was 95.2%. Tumor size ≥1 cm, central lymph node metastasis, lymph node ratio, and prelaryngeal lymph node metastasis were associated with regional recurrence in univariate analysis (P < .05). In multivariate analysis, a lymph node ratio ≥ 0.26 was a significant risk factor for regional lymph node recurrence (odds ratio = 11.63, P = .003). Lymph node ratio ≥ 0.26 was an independent predictor of worse recurrence-free survival on Cox regression analysis (hazard ratio = 11.49, P = .002). Although no significant association was observed between the presence of occult lymph node metastasis and regional recurrence, lymph node ratio ≥ 0.26 was an independent predictor of regional lymph node recurrence in papillary thyroid cancer patients who underwent total thyroidectomy and bilateral prophylactic central neck dissection. Copyright © 2016 Elsevier Inc. All rights reserved.

Plasma proteome and metabolome characterization of an experimental human thyrotoxicosis model.

PubMed

Pietzner, Maik; Engelmann, Beatrice; Kacprowski, Tim; Golchert, Janine; Dirk, Anna-Luise; Hammer, Elke; Iwen, K Alexander; Nauck, Matthias; Wallaschofski, Henri; Führer, Dagmar; Münte, Thomas F; Friedrich, Nele; Völker, Uwe; Homuth, Georg; Brabant, Georg

2017-01-09

Determinations of thyrotropin (TSH) and free thyroxine (FT 4 ) represent the gold standard in evaluation of thyroid function. To screen for novel peripheral biomarkers of thyroid function and to characterize FT 4 -associated physiological signatures in human plasma we used an untargeted OMICS approach in a thyrotoxicosis model. A sample of 16 healthy young men were treated with levothyroxine for 8 weeks and plasma was sampled before the intake was started as well as at two points during treatment and after its completion, respectively. Mass spectrometry-derived metabolite and protein levels were related to FT 4 serum concentrations using mixed-effect linear regression models in a robust setting. To compile a molecular signature discriminating between thyrotoxicosis and euthyroidism, a random forest was trained and validated in a two-stage cross-validation procedure. Despite the absence of obvious clinical symptoms, mass spectrometry analyses detected 65 metabolites and 63 proteins exhibiting significant associations with serum FT 4 . A subset of 15 molecules allowed a robust and good prediction of thyroid hormone function (AUC = 0.86) without prior information on TSH or FT 4 . Main FT 4 -associated signatures indicated increased resting energy expenditure, augmented defense against systemic oxidative stress, decreased lipoprotein particle levels, and increased levels of complement system proteins and coagulation factors. Further association findings question the reliability of kidney function assessment under hyperthyroid conditions and suggest a link between hyperthyroidism and cardiovascular diseases via increased dimethylarginine levels. Our results emphasize the power of untargeted OMICs approaches to detect novel pathways of thyroid hormone action. Furthermore, beyond TSH and FT 4 , we demonstrated the potential of such analyses to identify new molecular signatures for diagnosis and treatment of thyroid disorders. This study was registered at the German Clinical Trials Register (DRKS) [DRKS00011275] on the 16th of November 2016.

Thyroid STAtus and 6-Year Mortality in Elderly People Living in a Mildly Iodine-Deficient Area: The Aging in the Chianti Area (InCHIANTI) Study

PubMed Central

Ceresini, Graziano; Ceda, Gian Paolo; Lauretani, Fulvio; Maggio, Marcello; Usberti, Elisa; Marina, Michela; Bandinelli, Stefania; Guralnik, Jack M.; Valenti, Giorgio; Ferrucci, Luigi

2013-01-01

Objectives The relationship between thyroid dysfunction and mortality in elderly subjects is still undefined. In this population study we tested the hypothesis that in older subjects, living in a mildly iodine-deficient area, thyroid dysfunction may be associated with increased mortality independent of potential confounders. Design Longitudinal study Setting Community-based Participants Total of 951 subjects aged 65 years and older Measurements Plasma thyrotropin (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) concentrations and demographic features were evaluated in participants of the Aging in the Chianti Area (InCHIANTI) study, aged 65 years or older. Participants were classified according to thyroid function test. Kaplan-Meier survival and Cox proportional hazards models adjusted for confounders were used in the analysis. Results A total of 819 participants were euthyroid, 83 had Subclinical hyperthyroidism (SHyper), and 29 had Subclinical hypothyroidism (SHypo). Overt Hypo- and Hyperthyroidism were found in 5 and 15 subjects, respectively. During a median of six-years of follow-up, N 210 deaths occurred (22.1 %) of which 98 (46.6%) due to cardiovascular causes. Kaplan–Meier analysis revealed higher overall mortality for SHyper (P<0.04) as compared to euthyroid subjects. After adjusting for multiple confounders, participants with SHyper (Hazard Ratio[HR]:1.65; 95% Confidence Interval [CI]: 1.02–2.69) had significantly higher all-cause mortality than those with normal thyroid function. No significant association was found between SHyper and cardiovascular mortality. In euthyroid subjects, TSH was found to be predictive of a reduced risk of all-cause mortality (HR: 0.76; 95% CI, 0.57–0.99) Conclusion SHyper is an independent risk factor for all-cause mortality in the older population. Low-normal circulating TSH should be carefully monitored in euthyroid elderly individuals. PMID:23647402

Factors affecting the sensitivity of Tc-99m methoxyisobutylisonitrile dual-phase parathyroid single photon emission computed tomography in primary hyperparathyroidism.

PubMed

Araz, Mine; Çayir, Derya; Erdoğan, Mehmet; Uçan, Bekir; Çakal, Erman

2017-02-01

The aim of this study was to investigate the effects of thyroid diseases and regularly used medications on the sensitivity of Tc-99m methoxyisobutylisonitrile (MIBI) dual-phase parathyroid single photon emission computed tomography (SPECT) and to define indicatives of the result of the study. Overall, 218 primary hyperparathyroidism patients (190 women, 28 men, mean age: 57±14 years) with thyroid-parathyroid ultrasonography and Tc-99m MIBI dual-phase parathyroid SPECT were retrospectively enrolled. Patients were divided as follows: a positive SPECT group [119 (54.6%) patients] and a negative SPECT group [99 (45.4%) patients]. The effects of thyroid diseases and use of calcium channel blockers, β-blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, oral antidiabetics, thyroid hormone preparates, nonsteroidal anti-inflammatory drugs, and proton pump inhibitors on the sensitivity of Tc-99m MIBI dual-phase parathyroid SPECT were investigated. The frequency of NSAID usage was higher in the negative scan group (P<0.001). No significant difference was detected in terms of coexisting thyroid disease or usage of other medications. Overall sensitivity, specificity, positive, and negative predictive value of Tc-99m MIBI dual-phase parathyroid SPECT were calculated to be 89.6, 92.5, 94.1, and 86.9%. The sensitivity was low only in nonsteroidal anti-inflammatory drug users (75.6%) compared with nonusers (96.5%). Logistic regression showed that ultrasonography was indicative of a positive scan and the possibility of a negative result was increased by regular usage of nonsteroid anti-inflammatory drugs (odds ratio: 0.262, confidence interval: 0.128-0.538; P<0.001) CONCLUSION: Among various drug groups, NSAIDs may decrease the sensitivity of Tc-99m MIBI SPECT and, provided that these novel data are supported by other studies, patient preparation may be modified to stop NSAIDs before Tc-99m MIBI dual-phase parathyroid SPECT.

Loss-of-function mutations in the thyrotropin receptor gene as a major determinant of hyperthyrotropinemia in a consanguineous community.

PubMed

Tenenbaum-Rakover, Yardena; Grasberger, Helmut; Mamanasiri, Sunee; Ringkananont, Usanee; Montanelli, Lucia; Barkoff, Marla S; Dahood, Ahmad Mahameed-Hag; Refetoff, Samuel

2009-05-01

Resistance to TSH (RTSH) is a condition of impaired responsiveness of the thyroid gland to TSH, characterized by elevated serum TSH, low or normal thyroid hormone levels, and hypoplastic or normal-sized thyroid gland. The aim of the study was to evaluate the clinical course and the genotype-phenotype relationship of RTSH caused by two different TSH receptor (TSHR) gene mutations in a consanguineous population. We conducted a clinical and genetic investigation of 46 members of an extended family and 163 individuals living in the same town. In vitro functional studies of the mutant TSHRs were also performed. Two TSHR gene mutations (P68S and L653V) were identified in 33 subjects occurring as homozygous L653V (five subjects), heterozygous L653V (20 subjects), heterozygous P68S (four subjects), and compound heterozygous L653V/P68S (four subjects). With the exception of one individual with concomitant autoimmune thyroid disease, all homozygotes and compound heterozygotes presented with compensated RTSH (high TSH with free T(4) and T(3) in the normal range). Only nine of 24 heterozygotes had mild hyperthyrotropinemia. The L653V mutation resulted in a higher serum TSH concentration and showed a more severe in vitro abnormality than P68S. Haplotype analysis predicted a founder of the L653V six to seven generations earlier, whereas the P68S is older. Cross-sectional and prospective longitudinal studies indicate that TSH and T(4) concentrations remain stable over time. High frequency hyperthyrotropinemia in an Israeli Arab-Muslim consanguineous community is attributed to two inactivating TSHR gene mutations. Concordant genotype-phenotype was demonstrated clinically and by in vitro functional analysis. Retrospective and prospective studies indicate that in the absence of concomitant autoimmune thyroid disease, elevated TSH levels reflect stable compensated RTSH.

Thyroid Swelling and Thyroiditis in the Setting of Recent hCG Injections and Fine Needle Aspiration

PubMed Central

Lamos, Elizabeth M.; Munir, Kashif M.

2016-01-01

A 60-year-old woman presented with a neck mass and underwent fine needle aspiration of a left thyroid nodule. During this time, she had been injected with hCG for weight loss. Soon after, she developed rapid diffuse thyroid growth with pain. She was ultimately diagnosed with thyrotoxicosis due to postaspiration subacute thyroiditis and subsequently became hypothyroid. This condition is rare in the nonpregnant state in noncystic nodules with a smaller needle gauge approach. The incidence of thyroid nodule discovery and evaluation is increasing. As more procedures are undertaken, understanding of potential complications is important. This case highlights potential complications of thyroid fine needle aspiration including diffuse thyroid swelling and thyroiditis. The role of hCG injections is speculated to have potentially stimulated thyroid follicular epithelium via cross-reactivity with the TSH receptor and contributed to the acute inflammatory response after fine needle aspiration. PMID:26942022

American Thyroid Association Guide to Investigating Thyroid Hormone Economy and Action in Rodent and Cell Models

PubMed Central

Anderson, Grant; Forrest, Douglas; Galton, Valerie Anne; Gereben, Balázs; Kim, Brian W.; Kopp, Peter A.; Liao, Xiao Hui; Obregon, Maria Jesus; Peeters, Robin P.; Refetoff, Samuel; Sharlin, David S.; Simonides, Warner S.; Weiss, Roy E.; Williams, Graham R.

2014-01-01

Background: An in-depth understanding of the fundamental principles that regulate thyroid hormone homeostasis is critical for the development of new diagnostic and treatment approaches for patients with thyroid disease. Summary: Important clinical practices in use today for the treatment of patients with hypothyroidism, hyperthyroidism, or thyroid cancer are the result of laboratory discoveries made by scientists investigating the most basic aspects of thyroid structure and molecular biology. In this document, a panel of experts commissioned by the American Thyroid Association makes a series of recommendations related to the study of thyroid hormone economy and action. These recommendations are intended to promote standardization of study design, which should in turn increase the comparability and reproducibility of experimental findings. Conclusions: It is expected that adherence to these recommendations by investigators in the field will facilitate progress towards a better understanding of the thyroid gland and thyroid hormone dependent processes. PMID:24001133

Diagnostic value of antithyroid peroxidase antibody for incidental autoimmune thyroiditis based on histopathologic results.

PubMed

Rho, Myung Ho; Kim, Dong Wook; Hong, Hyun Pyo; Park, Young Mi; Kwon, Min Jeong; Jung, Soo Jin; Kim, Young Wook; Kang, Taewoo

2012-12-01

Detection of antithyroid peroxidase antibody (TPOAb) is widely used in the diagnosis of autoimmune thyroiditis (AIT), but no research has evaluated the diagnostic accuracy of TPOAb detection using histopathologic reference standards. To fill this research gap, this study assessed the diagnostic accuracy of detection of TPOAb and that of other serological markers in asymptomatic patients who had been diagnosed with AIT by histopathologic analysis after thyroid surgery. After review of patient records, 598 patients who had undergone thyroid nodule surgery were enrolled for examination for thyroid parenchyma by a pathologist and classification into no co-existing lymphocytic thyroiditis, Hashimoto thyroiditis, or non-Hashimoto type of lymphocytic thyroiditis (NHLT). The correlation between patient serological data and thyroid parenchyma pathology was analyzed. Statistically significant differences (P < 0.05) were found between co-existing lymphocytic thyroiditis and no co-existing lymphocytic thyroiditis groups regarding thyroid-stimulating hormone (TSH) and TPOAb levels. And, TPOAb titer was significantly associated with the degree of inflammation. An abnormal TPOAb titer was found in 86 of the 598 patients (14.4 %) and the specificity of TPOAb detection for AIT diagnosis was found to be 96.9 %. The prevalence of Hashimoto thyroiditis and NHLT in the 560 papillary thyroid cancer (PTC) patients was found to be 7.9 and 17.9 %, respectively. The results indicate that TPOAb titer is associated with the degree of thyroid inflammation and that detection of TPOAb is a very specific means of diagnosing AIT. The results also indicate that the incidence of AIT and PTC coexistence is relatively high.

Effect of adrenal hormones on thyroid secretion and thyroid hormones on adrenal secretion in the sheep.

PubMed Central

Falconer, I R; Jacks, F

1975-01-01

1. Previous work has shown that after stressful stimuli, sheep initially secrete increased amounts of thyroid hormone, at a time when adrenal secretion is also elevated. 2. This study was designed to evaluate (a) any short-term activation or inhibition of thyroid secretion by exogenous cortisol or ACTH administered in quantities comparable to those secreted after stress in sheep and (b) any short-term effect that exogenous thyroxine or triiodothyronine may have on the concentration of plasma cortisol in the sheep. 3. Thyroid activity was measured by determination of plasma protein bound 125I (PB125I) and total 125I in thyroid vein and mixed venous (jugular) blood. Plasma cortisol and thyroxine concentrations were measured by a competitive protein-binding assay at intervals for up to 5 hr after commencement of the experiment. 4. No evidence of an activation of thyroid secretion was found during cortisol or ACTH infusion, as monitored by thyroid vein PB125I. Similarly there was no evidence of any inhibition of thyroid function, as measured by continued secretion of thyroid hormones into thyroid vein blood. 5. No effect on plasma cortisol concentration due to thyroid hormone treatment was observed. 6. It was concluded that (a) elevated circulating corticosteroids in physiological concentrations have no short-term effects on thyroid activity in the sheep and (b) the short-term alterations in thyroid and adrenal cortical secretion observed during stress in the sheep could not be attributed to direct interaction of elevated thyroid hormone concentrations with adrenal cortical secretion. PMID:170400

Risk of Thyroid Cancer in Euthyroid Asymptomatic Patients with Thyroid Nodules with an Emphasis on Family History of Thyroid Cancer.

PubMed

Hwang, Shin Hye; Kim, Eun-Kyung; Moon, Hee Jung; Yoon, Jung Hyun; Kwak, Jin Young

2016-01-01

To determine the factors associated with thyroid cancer, focusing on first-degree family history and ultrasonography (US) features, in euthyroid asymptomatic patients with thyroid nodules. This retrospective study included 1310 thyroid nodules of 1254 euthyroid asymptomatic patients who underwent US-guided fine-needle aspiration biopsy between November 2012 and August 2013. Nodule size and clinical risk factors-such as patient age, gender, first-degree family history of thyroid cancer, multiplicity on US and serum thyroid stimulating hormone (TSH) levels-were considered together with US features to compare benign and malignant nodules. Multiple logistic regression analysis was performed to assess the risk of thyroid malignancy according to clinical and US characteristics. Although all of the clinical factors and US findings were significantly different between patients with benign and malignant nodules, a solitary lesion on US (p = 0.041-0.043), US features and male gender (p < 0.001) were significant independent risk factors for thyroid malignancy in a multivariate analysis. Patient age, a first-degree family history of thyroid cancer and high normal serum TSH levels did not independently significantly increase the risk of thyroid cancer. However, multicollinearity existed between US assessment and patient age, first-degree family history of thyroid cancer and serum TSH values. Ultrasonography findings should be the primary criterion used to decide the management of euthyroid asymptomatic patients with thyroid nodules. The concept of first-degree family history as a risk factor for thyroid malignancy should be further studied in asymptomatic patients.