Progressive Ischemic Stroke due to Thyroid Storm-Associated Cerebral Venous Thrombosis

PubMed Central

Tanabe, Natsumi; Hiraoka, Eiji; Hoshino, Masataka; Deshpande, Gautam A.; Sawada, Kana; Norisue, Yasuhiro; Tsukuda, Jumpei; Suzuki, Toshihiko

2017-01-01

Patient: Female, 49 Final Diagnosis: Cerebral venous thrombosis Symptoms: Altered mental state • weakness in limbs Medication: — Clinical Procedure: — Specialty: Endocrinology and Metabolic Objective: Rare co-existance of disease or pathology Background: Cerebral venous thrombosis (CVT) is a rare but fatal complication of hyperthyroidism that is induced by the hypercoagulable state of thyrotoxicosis. Although it is frequently difficult to diagnose CVT promptly, it is important to consider it in the differential diagnosis when a hyperthyroid patient presents with atypical neurologic symptoms. Care Report: A 49-year-old Japanese female with unremarkable medical history came in with thyroid storm and multiple progressive ischemic stroke identified at another hospital. Treatment for thyroid storm with beta-blocker, glucocorticoid, and potassium iodide-iodine was started and MR venography was performed on hospital day 3 for further evaluation of her progressive ischemic stroke. The MRI showed CVT, and anticoagulation therapy, in addition to the anti-thyroid agents, was initiated. The patient’s thyroid function was successfully stabilized by hospital day 10 and further progression of CVT was prevented. Conclusions: Physicians should consider CVT when a patient presents with atypical course of stroke or with atypical MRI findings such as high intensity area in apparent diffusion coefficient (ADC) mapping. Not only is an early diagnosis and initiation of anticoagulation important, but identifying and treating the underlying disease is essential to avoid the progression of CVT. PMID:28228636

Progress in molecular-based management of differentiated thyroid cancer

PubMed Central

Xing, Mingzhao; Haugen, Bryan R; Schlumberger, Martin

2014-01-01

Substantial developments have occurred in the past 5–10 years in clinical translational research of thyroid cancer. Diagnostic molecular markers, such as RET-PTC, RAS, and BRAFV600E mutations; galectin 3; and a new gene expression classifier, are outstanding examples that have improved diagnosis of thyroid nodules. BRAF mutation is a prognostic genetic marker that has improved risk stratification and hence tailored management of patients with thyroid cancer, including those with conventionally low risks. Novel molecular-targeted treatments hold great promise for radioiodine-refractory and surgically inoperable thyroid cancers as shown in clinical trials; such treatments are likely to become a component of the standard treatment regimen for patients with thyroid cancer in the near future. These novel molecular-based management strategies for thyroid nodules and thyroid cancer are the most exciting developments in this unprecedented era of molecular thyroid-cancer medicine. PMID:23668556

I-131 Radiation-Induced Myelosuppression in Differentiated Thyroid Cancer Therapy.

PubMed

Probst, Stephan; Abikhzer, Gad; Chaussé, Guillaume; Tamilia, Michael

2018-06-07

Radioactive iodine (RAI) treatment of differentiated thyroid cancer has been used in clinical practice for almost 60 years and is generally accepted to be a safe and efficacious treatment. Severe toxicity in the form of radiation pneumonitis, sometimes progressing to fibrosis, and bone marrow suppression are reported but remain rare. We present a case of severe myelosuppression requiring hospitalization and transfusion support in an otherwise well, young female patient who had received 175 mCi I-131 for low-volume micronodular lung disease one month prior, with a cumulative lifetime administered activity of 575 mCi. The most important risk factors for myelosuppression following RAI are the activity received, the amount of functioning thyroid tissue present, and the lifetime cumulative activity received.

Curcumin induces G2/M arrest, apoptosis, NF-κB inhibition, and expression of differentiation genes in thyroid carcinoma cells.

PubMed

Schwertheim, Suzan; Wein, Frederik; Lennartz, Klaus; Worm, Karl; Schmid, Kurt Werner; Sheu-Grabellus, Sien-Yi

2017-07-01

The therapy of unresectable advanced thyroid carcinomas shows unfavorable outcome. Constitutive nuclear factor-κB (NF-κB) activation in thyroid carcinomas frequently contributes to therapeutic resistance; the radioiodine therapy often fails due to the loss of differentiated functions in advanced thyroid carcinomas. Curcumin is known for its anticancer properties in a series of cancers, but only few studies have focused on thyroid cancer. Our aim was to evaluate curcumin's molecular mechanisms and to estimate if curcumin could be a new therapeutic option in advanced thyroid cancer. Human thyroid cancer cell lines TPC-1 (papillary), FTC-133 (follicular), and BHT-101 (anaplastic) were treated with curcumin. Using real-time PCR analysis, we investigated microRNA (miRNA) and mRNA expression levels. Cell cycle, Annexin V/PI staining, and caspase-3 activity analysis were performed to detect apoptosis. NF-κB p65 activity and cell proliferation were analyzed using appropriate ELISA-based colorimetric assay kits. Treatment with 50 μM curcumin significantly increased the mRNA expression of the differentiation genes thyroglobulin (TG) and sodium iodide symporter (NIS) in all three cell lines and induced inhibition of cell proliferation, apoptosis, and decrease of NF-κB p65 activity. The miRNA expression analyses showed a significant deregulation of miRNA-200c, -21, -let7c, -26a, and -125b, known to regulate cell differentiation and tumor progression. Curcumin arrested cell growth at the G2/M phase. Curcumin increases the expression of redifferentiation markers and induces G2/M arrest, apoptosis, and downregulation of NF-κB activity in thyroid carcinoma cells. Thus, curcumin appears to be a promising agent to overcome resistance to the conventional cancer therapy.

Loss of One or Two PATZ1 Alleles Has a Critical Role in the Progression of Thyroid Carcinomas Induced by the RET/PTC1 Oncogene

PubMed Central

Palma, Giuseppe; Vitiello, Michela; Capiluongo, Anna; D’Andrea, Barbara; Vuttariello, Emilia; Luciano, Antonio; Cerchia, Laura; Chiappetta, Gennaro; Arra, Claudio; Fusco, Alfredo

2018-01-01

POZ/BTB and AT-hook-containing zinc finger protein 1 (PATZ1) is an emerging cancer-related gene that is downregulated in different human malignancies, including thyroid cancer, where its levels gradually decrease going from papillary thyroid carcinomas (PTC) to poorly differentiated and undifferentiated highly aggressive anaplastic carcinomas (ATC). The restoration of PATZ1 expression in thyroid cancer cells reverted their malignant phenotype by inducing mesenchymal-to-epithelial transition, thus validating a tumor suppressor role for PATZ1 and suggesting its involvement in thyroid cancer progression. Here, we investigated the consequences of the homozygous and heterozygous loss of PATZ1 in the context of a mouse modeling of PTC, represented by mice carrying the RET/PTC1 oncogene under the thyroid specific control of the thyroglobulin promoter RET/PTC1 (RET/PTC1TG). The phenotypic analysis of RET/PTC1TG mice intercrossed with Patz1-knockout mice revealed that deficiency of both Patz1 alleles enhanced thyroid cancer incidence in RET/PTC1TG mice, but not the heterozygous knockout of the Patz1 gene. However, both RET/PTC1TG;Patz1+/− and RET/PTC1TG;Patz1−/− mice developed a more aggressive thyroid cancer phenotype—characterized by higher Ki-67 expression, presence of ATCs, and increased incidence of solid variants of PTC—than that shown by RET/PTC1TG; Patz1+/+ compound mice. These results confirm that PATZ1 downregulation has a critical role in thyroid carcinogenesis, showing that it cooperates with RET/PTC1 in thyroid cancer progression. PMID:29584698

LYMPHOCYTIC THYROIDITIS IS ASSOCIATED WITH INCREASED NUMBER OF BENIGN CERVICAL NODES AND FEWER CENTRAL NECK COMPARTMENT METASTATIC LYMPH NODES IN PATIENTS WITH DIFFERENTIATED THYROID CANCER.

PubMed

Donangelo, Ines; Walts, Ann E; Bresee, Catherine; Braunstein, Glenn D

2016-10-01

Whether or not autoimmune thyroid disease influences the progression of differentiated thyroid cancer (DTC) remains controversial. Findings of previous studies are influenced by lead time bias and/or procedure bias selection. These biases can be reduced by studying a single-institution patient population that underwent a similar extent of surgical resection. From a cohort of 660 patients with DTC who underwent thyroidectomy, we retrospectively studied 357 patients who underwent total thyroidectomy and central compartment node dissection (CCND) for DTC between 2003 and 2013. Forty-one percent (140/345) of study patients had lymphocytic thyroiditis (LT), and 30% (91/301) had serum positive for thyroglobulin antibody (TgAb). LT was reported in 78% of the TgAb-positive cases. Sixty percent (213/357) of cases had metastatic thyroid carcinoma in 1 or more neck lymph nodes (55% [198/357] central compartment, and 22% [77/356] lateral compartment). Patients with LT had fewer metastatic cervical lymph nodes than those with no LT (2.7 ± 4.7 vs 3.5 ± 4.8, respectively, P = .0285). Patients with positive TgAb and thyroiditis had a larger number of benign cervical lymph nodes removed than those with negative TgAb or no LT. No significant difference was observed in age, tumor size, multifocality, extrathyroidal extension, vascular invasion, or frequency of cervical lymph node metastasis between TgAb-negative and -positive cases or between cases with and without LT. Lymphocytic thyroiditis is associated with fewer central neck compartment metastatic lymph nodes and a larger number of excised reactive benign cervical lymph nodes. Whether this association indicates a protective role of thyroid autoimmunity in lymph node spreading remains unclear. CCND = central compartment node dissection DTC = differentiated thyroid cancer HT = Hashimoto thyroiditis LT = lymphocytic thyroiditis TgAb = thyroglobulin antibody TPO = thyroid peroxidase.

Orthotopic mouse models for the preclinical and translational study of targeted therapies against metastatic human thyroid carcinoma with BRAFV600E or wild-type BRAF

PubMed Central

Antonello, ZA; Nucera, C

2015-01-01

Molecular signature of advanced and metastatic thyroid carcinoma involves deregulation of multiple fundamental pathways activated in the tumor microenvironment. They include BRAFV600E and AKT that affect tumor initiation, progression and metastasis. Human thyroid cancer orthotopic mouse models are based on human cell lines that generally harbor genetic alterations found in human thyroid cancers. They can reproduce in vivo and in situ (into the thyroid) many features of aggressive and refractory human advanced thyroid carcinomas, including local invasion and metastasis. Humanized orthotopic mouse models seem to be ideal and commonly used for preclinical and translational studies of compounds and therapies not only because they may mimic key aspects of human diseases (e.g. metastasis), but also for their reproducibility. In addition, they might provide the possibility to evaluate systemic effects of treatments. So far, human thyroid cancer in vivo models were mainly used to test single compounds, non selective and selective. Despite the greater antitumor activity and lower toxicity obtained with different selective drugs in respect to non-selective ones, most of them are only able to delay disease progression, which ultimately could restart with similar aggressive behavior. Aggressive thyroid tumors (for example, anaplastic or poorly differentiated thyroid carcinoma) carry several complex genetic alterations that are likely cooperating to promote disease progression and might confer resistance to single-compound approaches. Orthotopic models of human thyroid cancer also hold the potential to be good models for testing novel combinatorial therapies. In this article, we will summarize results on preclinical testing of selective and nonselective single compounds in orthotopic mouse models based on validated human thyroid cancer cell lines harboring the BRAFV600E mutation or with wild-type BRAF. Furthermore, we will discuss the potential use of this model also for combinatorial approaches, which are expected to take place in the upcoming human thyroid cancer basic and clinical research. PMID:24362526

Axitinib treatment in advanced RAI-resistant differentiated thyroid cancer (DTC) and refractory medullary thyroid cancer (MTC).

PubMed

Capdevila, Jaume; Trigo, José Manuel; Aller, Javier; Manzano, José Luís; Adrián, Silvia García; Llopis, Carles Zafón; Reig, Òscar; Bohn, Uriel; Cajal, Teresa Ramón Y; Duran-Poveda, Manuel; Astorga, Beatriz González; López-Alfonso, Ana; Martínez, Javier Medina; Porras, Ignacio; Reina, Juan Jose; Palacios, Nuria; Grande, Enrique; Cillán, Elena; Matos, Ignacio; Grau, Juan Jose

2017-10-01

Axitinib, an antiangiogenic multikinase inhibitor (MKI), was evaluated in the compassionate use programme (CUP) in Spain (October 2012-November 2014). 47 patients with advanced radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC, n  = 34) or medullary thyroid cancer (MTC, n  = 13) with documented disease progression were treated with axitinib 5 mg b.i.d. The primary efficacy endpoint was objective response rate (ORR) by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. Progression-free survival (PFS) and adverse events (AEs) were secondary objectives. Regulatory authorities validated the CUP, and all patients signed informed consent form. Axitinib was administered as first-line therapy in 17 patients (36.2%), as second-line in 18 patients (38.3%) and as third/fourth-line in 12 patients (25.5%). With a median follow-up of 11.5 months (0-24.3), ORR was 27.7% (DTC: 29.4% and MTC: 23.1%) and median PFS was 8.1 months (95% CI: 4.1-12.2) (DTC: 7.4 months (95% CI: 3.1-11.8) and MTC: 9.4 months (95% CI: 4.8-13.9)). Better outcomes were reported with first-line axitinib, with an ORR of 53% and a median PFS of 13.6 months compared with 16.7% and 10.6 months as second-line treatment. Twelve (25.5%) patients required dose reduction to 3 mg b.i.d. All-grade AEs included asthenia (53.2%), diarrhoea (36.2%), hypertension (31.9%) and mucositis (29.8%); grade 3/4 AEs included anorexia (6.4%), diarrhoea (4.3%) and cardiac toxicity (4.3%). Axitinib had a tolerable safety profile and clinically meaningful activity in refractory and progressive thyroid cancer regardless of histology as first-line therapy. To our knowledge, this is the first time that cross-resistance between MKIs is suggested in thyroid cancer, highlighting the importance of prospective sequential clinical studies. © 2017 European Society of Endocrinology.

Molecular perspectives in differentiated thyroid cancer.

PubMed

Buffet, C; Groussin, L

2015-02-01

Progress in understanding the molecular genetics of thyroid cancer in the last 20 years has accelerated recently with the advent of high-throughput sequencing technologies known as Next-Generation Sequencing. Besides classical molecular abnormalities involving the MAPK (Mitogen Activated Protein Kinase) and PI3K (PhosphoInositide 3-Kinase) pathways that play a key role in follicular-derived thyroid tumorigenesis, new molecular abnormalities have been discovered. The major advances in recent years have been the discovery of new somatic driver gene point mutations (such as RASAL1 [RAS protein activator Like 1] mutations in follicular cancer) and/or mutations that have prognostic value (such as TERT [Telomerase reverse transcriptase] promoter mutations); new chromosomal rearrangements, usually having close connection with exposure to ionizing radiation (such as ALK [Anaplastic Lymphoma Kinase] rearrangements); and deregulation of some gene or microRNA expression representing a molecular signature. Progress made in understanding the molecular mechanisms of thyroid cancer offers new perspectives for the diagnosis of the benign or malignant status of a thyroid nodule, to refine prognosis and offer new perspectives of targeted therapy for radioiodine-refractory cancers. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

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

p53 constrains progression to anaplastic thyroid carcinoma in a Braf-mutant mouse model of papillary thyroid cancer

PubMed Central

McFadden, David G.; Vernon, Amanda; Santiago, Philip M.; Martinez-McFaline, Raul; Bhutkar, Arjun; Crowley, Denise M.; McMahon, Martin; Sadow, Peter M.; Jacks, Tyler

2014-01-01

Anaplastic thyroid carcinoma (ATC) has among the worst prognoses of any solid malignancy. The low incidence of the disease has in part precluded systematic clinical trials and tissue collection, and there has been little progress in developing effective therapies. v-raf murine sarcoma viral oncogene homolog B (BRAF) and tumor protein p53 (TP53) mutations cooccur in a high proportion of ATCs, particularly those associated with a precursor papillary thyroid carcinoma (PTC). To develop an adult-onset model of BRAF-mutant ATC, we generated a thyroid-specific CreER transgenic mouse. We used a Cre-regulated BrafV600E mouse and a conditional Trp53 allelic series to demonstrate that p53 constrains progression from PTC to ATC. Gene expression and immunohistochemical analyses of murine tumors identified the cardinal features of human ATC including loss of differentiation, local invasion, distant metastasis, and rapid lethality. We used small-animal ultrasound imaging to monitor autochthonous tumors and showed that treatment with the selective BRAF inhibitor PLX4720 improved survival but did not lead to tumor regression or suppress signaling through the MAPK pathway. The combination of PLX4720 and the mapk/Erk kinase (MEK) inhibitor PD0325901 more completely suppressed MAPK pathway activation in mouse and human ATC cell lines and improved the structural response and survival of ATC-bearing animals. This model expands the limited repertoire of autochthonous models of clinically aggressive thyroid cancer, and these data suggest that small-molecule MAPK pathway inhibitors hold clinical promise in the treatment of advanced thyroid carcinoma. PMID:24711431

A primary cavernous hemangioma of the thyroid gland: A case report and literature review.

PubMed

Miao, Jie; Chen, Shubo; Li, Yongcai; Fu, Lin; Li, Hui

2017-12-01

Thyroid hemangioma is benign and associated with fine-needle aspiration (FNA) biopsy or trauma in most cases. Its differential diagnosis is very difficult. We presented the case of a 48-year-old man complained of slowly progressed swelling in the anterior neck for 20 years. Ultrasound and CT scan revealed a hypoechogenic and heterogeneous mass measuring 4 × 3.5 cm located in the right lobe of thyroid gland. Postoperative pathological and immunohistochemical examinations of the surgical specimen revealed a primary hemangioma of the thyroid gland. The patient received a right lobectomy of the thyroid. The patient had been followed up for 10 months after surgery without complications and remained asymptomatic. Primary thyroid hemangioma should be considered when there is a well-circumscribed capsule mass on medical imaging without history of FNA or any other cervical procedures or trauma.

Human a-L-fucosidase-1 attenuates the invasive properties of thyroid cancer.

PubMed

Vecchio, Giancarlo; Parascandolo, Alessia; Allocca, Chiara; Ugolini, Clara; Basolo, Fulvio; Moracci, Marco; Strazzulli, Andrea; Cobucci-Ponzano, Beatrice; Laukkanen, Mikko O; Castellone, Maria Domenica; Tsuchida, Nobuo

2017-04-18

Glycans containing α-L-fucose participate in diverse interactions between cells and extracellular matrix. High glycan expression on cell surface is often associated with neoplastic progression. The lysosomal exoenzyme, α-L-fucosidase-1 (FUCA-1) removes fucose residues from glycans. The FUCA-1 gene is down-regulated in highly aggressive and metastatic human tumors. However, the role of FUCA-1 in tumor progression remains unclear. It is speculated that its inactivation perturbs glycosylation of proteins involved in cell adhesion and promotes cancer. FUCA-1 expression of various thyroid normal and cancer tissues assayed by immunohistochemical (IHC) staining was high in normal thyroids and papillary thyroid carcinomas (PTC), whereas it progressively decreased in poorly differentiated, metastatic and anaplastic thyroid carcinomas (ATC). FUCA-1 mRNA expression from tissue samples and cell lines and protein expression levels and enzyme activity in thyroid cancer cell lines paralleled those of IHC staining. Furthermore, ATC-derived 8505C cells adhesion to human E-selectin and HUVEC cells was inhibited by bovine α-L-fucosidase or Lewis antigens, thus pointing to an essential role of fucose residues in the adhesive phenotype of this cancer cell line. Finally, 8505C cells transfected with a FUCA-1 containing plasmid displayed a less invasive phenotype versus the parental 8505C. These results demonstrate that FUCA-1 is down-regulated in ATC compared to PTC and normal thyroid tissues and cell lines. As shown for other human cancers, the down-regulation of FUCA-1 correlates with increased aggressiveness of the cancer type. This is the first report indicating that the down-regulation of FUCA-1 is related to the increased aggressiveness of thyroid cancer.

Overview of Genetically Engineered Mouse Models of Papillary and Anaplastic Thyroid Cancers: Enabling Translational Biology for Patient Care Improvement.

PubMed

Charles, Roch-Philippe

2015-06-01

The prognosis from thyroid cancer subtypes in humans covers a spectrum from "cured at almost 90%" to "100% lethal." Invasive and poorly differentiated forms of thyroid cancer are among the most aggressive human cancers, and there are few effective therapeutic options. Genetically engineered mice, based on mutations observed in patients, can accurately recapitulate the human disease and its progression, providing invaluable tools for the preclinical evaluation of novel therapeutic approaches. This overview details models developed to date as well as their uses for identifying novel anticancer agents. Copyright © 2013 John Wiley & Sons, Inc. All rights reserved.

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

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.

[Rarer causes of thyrotoxicosis].

PubMed

Krysiak, Robert; Kowalcze, Karolina; Okopień, Bogusław

2016-01-01

Thyrotoxicosis is a pathological syndrome in which tissue is exposed to excessive amounts of circulating thyroid hormones. Including its subclinical form, it is considered as one of the most frequent endocrine disorders in the general population. If not detected in a timely fashion, thyrotoxicosis can have serious health consequences. The most common forms of thyrotoxicosis include diffuse toxic goiter (Graves' disease), toxic multinodular goiter (Plummer's disease), and toxic adenoma (Goetsch's disease). The significant progress in the fields of hormonal assessment, imaging procedures and molecular biology made in recent years has brought about great improvement in the identification, differentiation and treatment of many other disorders associated with thyrotoxicosis. Therefore, this paper discusses the etiopathogenesis, clinical manifestation, biochemical abnormalities and management of thyrotropinoma, resistance to thyroid hormone, de Quervain's, silent, acute, posttraumatic and radiation-induced thyroiditis, Riedel's goiter, differentiated thyroid cancer, struma ovarii, thyrotoxicosis factitia, other forms of iatrogenic thyrotoxicosis, gestational trophoblastic disease, neonatal Graves's disease, familial nonautoimmune hyperthyroidism and McCune-Albright syndrome. On the basis of available studies, some of whom were carried out in the recent years, we provide practical guidelines for clinical endocrinologists dealing with the diagnosis and treatment of thyrotoxicosis.

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.

Small cell lung cancer with metastasis to the thyroid in a patient with toxic multinodular goiter.

PubMed

Ozgu, Eylem Sercan; Gen, Ramazan; Ilvan, Ahmet; Ozge, Cengiz; Polat, Ayşe; Vayisoglu, Yusuf

2012-11-01

Thyroid metastasis of lung cancer is rarely observed in clinical practice. The primary cancers which metastasize to the thyroid gland are mostly renal cell carcinoma, lung cancer, and breast cancer. Transient destructive thyrotoxicosis is caused by massive metastasis of extrathyroid tumors. We herein present a case report of a patient with small cell carcinoma of lung with metastasis to the thyroid and thyrotoxicosis due to toxic multinodular goiter. A 66-year-old man complained of swelling around the right side of the neck, dyspnea, progressive weight loss, and palpitation starting since 3 months before his admission. The patient was diagnosed with small cell carcinoma of lung with metastasis to the thyroid and thyrotoxicosis due to toxic multinodular goiter. The case report presented here illustrates the challenge of making a definitive and adequate diagnosis, particularly if the patient presents with 2 potential causes of thyrotoxicosis. Thyroid scintigraphy is an important tool for differential diagnosis of thyrotoxicosis.

Poorly Differentiated Thyroid Carcinoma.

PubMed

Setia, Namrata; Barletta, Justine A

2014-12-01

Poorly differentiated thyroid carcinoma (PDTC) has been recognized for the past 30 years as an entity showing intermediate differentiation and clinical behavior between well-differentiated thyroid carcinomas (ie, papillary thyroid carcinoma and follicular thyroid carcinoma) and anaplastic thyroid carcinoma; however, there has been considerable controversy around the definition of PDTC. In this review, the evolution in the definition of PDTC, current diagnostic criteria, differential diagnoses, potentially helpful immunohistochemical studies, and molecular alterations are discussed with the aim of highlighting where the diagnosis of PDTC currently stands. Published by Elsevier Inc.

[Incidence of anaplastic tumor in structure of other histologic forms of the thyroid gland cancer].

PubMed

Vinnik, Iu A; Gorbenko, V N; Vas'ko, A R; Kikhtenko, E V; Gargin, V V

2014-01-01

The degrees of invasiveness, proliferative activity, morphofunctional activity of nuclei in the thyroidal gland tumors were studied, while analyzing material, obtained in 1343 patients, suffering thyroidal gland cancer (THGC) and operated on in 2000-2013 yrs. Morphological point quantity of malignancy (as a criterion of the tumor progression grade) and mitotic activity in cellular population were determined in various kinds of THGC. Undifferentiated (anaplastic carcinoma) type of THGC is the most malignant one. There were determined a spindle-like, giant-cell and squamous-cell forms of undifferentiated THGC. The presence of sites of differentiated cancer in 33% of histological preparations witnesses the interrelationship with the earlier existed pathological process.

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

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

[Hyperfunctioning thyroid carcinoma. Description of a case].

PubMed

Pandolfi, C; Colecchia, M; Gianini, A

1997-09-01

Differentiated thyroid cancers account for 1% of all neoplasias but only for 2.3% of thyroid nodules. A particular condition is represented by the association with hyperthyroidism, which is found in about 7% of cases. Even more rarely may be themselves cause of thyrotoxicosis. In the present paper, the case of a 66-year old male patient, bearing a recently appeared goiter, referred to us for suspicion of lung cancer and hyperthyroid symptoms, is reported. Among appropriate investigations, the finding of high titer of thyroglobulin in the aspiration needle and cytology examination suggested that thyroid lesion was primary and not metastatic, while scintiscan with J-131 isotope showed that excess of thyroid hormones was just due to it; histological diagnosis was of papillary carcinoma. As to the pathogenesis of the neoplasma during hyperthyroidism, a causal role of thyroid stimulating auto-antibodies has been suggested in the cases associated with Graves' disease, absent in our patient, which could elicitate cancer progression in the mean time. Interestingly, activating mutation of thyroid hormone receptor (TSH-r) gene has been demonstrated in a hyperfunctioning differentiated cancer. Notwithstanding the unexpected clinical behaviour may appear very rare, molecular biology studies on aspiration biopsies (FNAB) will allow, in the future, to better define the neoplastic nature of some hot nodules. In personal opinion, this particular pathology must be attently searched both for its implications in the prognosis and therapeutic strategy and because it could be less rare than generally considered up to now.

Extracellular ATP is Differentially Metabolized on Papillary Thyroid Carcinoma Cells Surface in Comparison to Normal Cells.

PubMed

Bertoni, Ana Paula Santin; de Campos, Rafael Paschoal; Tsao, Marisa; Braganhol, Elizandra; Furlanetto, Tania Weber; Wink, Márcia Rosângela

2018-02-17

The incidence of differentiated thyroid cancer has been increasing. Nevertheless, its molecular mechanisms are not well understood. In recent years, extracellular nucleotides and nucleosides have emerged as important modulators of tumor microenvironment. Extracellular ATP is mainly hydrolyzed by NTPDase1/CD39 and NTPDase2/CD39L1, generating AMP, which is hydrolyzed by ecto-5'-nucleotidase (CD73) to adenosine, a possible promoter of tumor growth and metastasis. There are no studies evaluating the expression and functionality of these ectonucleotidases on normal or tumor-derived thyroid cells. Thus, we investigated the ability of thyroid cancer cells to hydrolyze extracellular ATP generating adenosine, and the expression of ecto-enzymes, as compared to normal cells. We found that normal thyroid derived cells presented a higher ability to hydrolyze ATP and higher mRNA levels for ENTDP1-2, when compared to papillary thyroid carcinoma (PTC) derived cells, which had a higher ability to hydrolyze AMP and expressed CD73 mRNA and protein at higher levels. In addition, adenosine induced an increase in proliferation and migration in PTC derived cells, whose effect was blocked by APCP, a non-hydrolysable ADP analogue, which is an inhibitor of CD73. Taken together, these results showed that thyroid follicular cells have a functional purinergic signaling. The higher expression of CD73 in PTC derived cells might favor the accumulation of extracellular adenosine in the tumor microenvironment, which could promote tumor progression. Therefore, as already shown for other tumors, the purinergic signaling should be considered a potential target for thyroid cancer management and treatment.

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.

The Next Generation of Orthotopic Thyroid Cancer Models: Immunocompetent Orthotopic Mouse Models of BRAFV600E-Positive Papillary and Anaplastic Thyroid Carcinoma

PubMed Central

Vanden Borre, Pierre; McFadden, David G.; Gunda, Viswanath; Sadow, Peter M.; Varmeh, Shohreh; Bernasconi, Maria; Jacks, Tyler

2014-01-01

Background: While the development of new treatments for aggressive thyroid cancer has advanced in the last 10 years, progress has trailed headways made with other malignancies. A lack of reliable authenticated human cell lines and reproducible animal models is one major roadblock to preclinical testing of novel therapeutics. Existing xenograft and orthotopic mouse models of aggressive thyroid cancer rely on the implantation of highly passaged human thyroid carcinoma lines in immunodeficient mice. Genetically engineered models of papillary and undifferentiated (anaplastic) thyroid carcinoma (PTC and ATC) are immunocompetent; however, slow and stochastic tumor development hinders high-throughput testing. Novel models of PTC and ATC in which tumors arise rapidly and synchronously in immunocompetent mice would facilitate the investigation of novel therapeutics and approaches. Methods: We characterized and utilized mouse cell lines derived from PTC and ATC tumors arising in genetically engineered mice with thyroid-specific expression of endogenous BrafV600E/WT and deletion of either Trp53 (p53) or Pten. These murine thyroid cancer cells were transduced with luciferase- and GFP-expressing lentivirus and implanted into the thyroid glands of immunocompetent syngeneic B6129SF1/J mice in which the growth characteristics were assessed. Results: Large locally aggressive thyroid tumors form within one week of implantation. Tumors recapitulate their histologic subtype, including well-differentiated PTC and ATC, and exhibit CD3+, CD8+, B220+, and CD163+ immune cell infiltration. Tumor progression can be followed in vivo using luciferase and ex vivo using GFP. Metastatic spread is not detected at early time points. Conclusions: We describe the development of the next generation of murine orthotopic thyroid cancer models. The implantation of genetically defined murine BRAF-mutated PTC and ATC cell lines into syngeneic mice results in rapid and synchronous tumor formation. This model allows for preclinical investigation of novel therapeutics and/or therapeutic combinations in the context of a functional immune system. PMID:24295207

[The importance of bisoprolol in prevention of heart left ventricular hypertrophy in patients with long term L-thyroxin suppressive therapy, after the operation of differentiated thyroid carcinoma].

PubMed

Matuszewska, Gabriela; Marek, Bogdan; Kajdaniuk, Dariusz; Przywara-Chowaniec, Brygida; Jarzab, Jerzy; Jarzab, Barbara

2007-01-01

Patients with differentiated thyroid carcinoma have to undergo radical surgical treatment, which includes total thyreoidectomy, radioiodine therapy and a life-time suppressive therapy with L-thyroxine. The aim of this study was a prospective evaluation of left ventricular hypertrophy during L suppressive-thyroxine treatment in patients treated for differentiated thyroid carcinoma. The examined group comprised 50 patients with differentiated thyroid carcinoma, treated by total thyroidectomy and 131I therapy. Echocardiographic measurements were needed for estimation of left ventricular mass and its index, according to recommendations of American Echocardiography Society. During two-years long suppressive therapy we observed a significant rise in left ventricular mass. In woman group left ventricular mass was increased from 168+/-39 g to 204+/-45 g (p<0.001) and in men from 205+/-60 to 320+/-21 g. Likewise, left ventricular mass index was increased in women group from 96+/-18 g/m(2) to 116+/-25 g/m(2) (p<0.001) and in men group from 107+/-37 g/m(2) to 158+/-28 g/m(2). Simultaneous treatment with bisoprolol caused a regression of left myocardial hypertrophy. Already after 6 months of simultaneous treatment with L-thyroxin and bisoprolol, for left ventricular mass was reduced to normal: in woman 165+/-35 g, and in men to 178+/-38 g. Analogous results were obtained left ventricular mass index. After 6 months it was reduced to 94+/-12 g/m(2) in woman and in men to 132+/-32 g/m(2). 1. In differentiated thyroid cancer patients, treated postoperatively with L-thyroxine suppressive therapy, left ventricular hypertrophy is observed already during the first year of suppressive therapy and progresses during the next year of treatment. 2 Addition of a beta-adrenergic antagonist to suppressive doses of L-thyroxine causes a regression of left ventricular hypertrophy, thus, beta-adrenergic antagonists should be administered in this group of patients.

NEW DEVELOPMENTS IN THE DIAGNOSIS AND TREATMENT OF THYROID CANCER

PubMed Central

Schneider, David F.; Chen, Herbert

2013-01-01

Thyroid cancer exists in several forms. Differentiated thyroid cancers include papillary and follicular histologies. These tumors exist along a spectrum of differentiation, and their incidence continues to climb. A number of advances in the diagnosis and treatment of differentiated thyroid cancers now exist. These include molecular diagnostics and more advanced strategies for risk stratification. Medullary cancer arises from the parafollicular cells and not the follicular cells. Therefore, diagnosis and treatment differs from differentiated thyroid tumors. Genetic testing and newer adjuvant therapies has changed the diagnosis and treatment of medullary thyroid cancer. This review will focus on the epidemiology, diagnosis, work-up, and treatment of both differentiated and medullary thyroid cancers, focusing specifically on newer developments in the field. PMID:23797834

Peptide receptor radionuclide therapy of treatment-refractory metastatic thyroid cancer using 90Yttrium and 177Lutetium labeled somatostatin analogs: toxicity, response and survival analysis

PubMed Central

Budiawan, Hendra; Salavati, Ali; Kulkarni, Harshad R; Baum, Richard P

2014-01-01

The overall survival rate of non-radioiodine avid differentiated (follicular, papillary, medullary) thyroid carcinoma is significantly lower than for patients with iodine-avid lesions. The purpose of this study was to evaluate toxicity and efficacy (response and survival) of peptide receptor radionuclide therapy (PRRT) in non-radioiodine-avid or radioiodine therapy refractory thyroid cancer patients. Sixteen non-radioiodine-avid and/or radioiodine therapy refractory thyroid cancer patients, including follicular thyroid carcinoma (n = 4), medullary thyroid carcinoma (n = 8), Hürthle cell thyroid carcinoma (n = 3), and mixed carcinoma (n = 1) were treated with PRRT by using 90Yttrium and/or 177Lutetium labeled somatostatin analogs. 68Ga somatostatin receptor PET/CT was used to determine the somatostatin receptor density in the residual tumor/metastatic lesions and to assess the treatment response. Hematological profiles and renal function were periodically examined after treatment. By using fractionated regimen, only mild, reversible hematological toxicity (grade 1) or nephrotoxicity (grade 1) were seen. Response assessment (using EORTC criteria) was performed in 11 patients treated with 2 or more (maximum 5) cycles of PRRT and showed disease stabilization in 4 (36.4%) patients. Two patients (18.2%) showed partial remission, in the remaining 5 patients (45.5%) disease remained progressive. Kaplan-Meier analysis resulted in a mean survival after the first PRRT of 4.2 years (95% CI, range 2.9-5.5) and median progression free survival of 25 months (inter-quartiles: 12-43). In non-radioiodine-avid/radioiodine therapy refractory thyroid cancer patients, PRRT is a promising therapeutic option with minimal toxicity, good response rate and excellent survival benefits. PMID:24380044

Infiltration of the thyroid gland by T-cell prolymphocytic leukemia.

PubMed

Fujiwara, Kazunori; Fukuhara, Takahiro; Kitano, Hiroya; Okazaki, Toshiro

2014-08-01

T-cell prolymphocytic leukemia (T-PLL) is rare, accounting for only 0.06% of all malignant lymphomas, and is classified as a T-cell mature lymphoma. The disease affects mainly elderly patients and is characterized by splenomegaly, lymphadenopathy, skin infiltration, and a high leukocyte count, but thyroid filtration has never been detected as far as we could determine. We report here a case of infiltration of the thyroid gland by T-PLL. An 89-year-old woman who had been treated for Hashimoto's thyroiditis for 20 years presented with a progressively enlarging thyroid mass accompanied by dyspnea and dysphasia. Atypical lymphocytes with irregular nuclei were observed in the peripheral blood. An open biopsy of the thyroid provided pathological evidence of T-PLL, and bone marrow examination showed infiltration by T-PLL. The diagnosis was therefore infiltration of the thyroid gland by T-PLL. Chemotherapy was initiated, but six months after termination, recurrence of neck swelling was observed. The patient was then treated with radiotherapy, but she died of a major stroke 15 months after onset. This is the first report of T-PLL infiltration of the thyroid gland, reminding physicians to keep in mind a broad differential diagnosis when encountering a patient with diffuse thyroid lesions and abnormal lymphocytes in the peripheral blood.

Mathematical Modeling of the Pituitary–Thyroid Feedback Loop: Role of a TSH-T3-Shunt and Sensitivity Analysis

PubMed Central

Berberich, Julian; Dietrich, Johannes W.; Hoermann, Rudolf; Müller, Matthias A.

2018-01-01

Despite significant progress in assay technology, diagnosis of functional thyroid disorders may still be a challenge, as illustrated by the vague upper limit of the reference range for serum thyrotropin (TSH). Diagnostical problems also apply to subjects affected by syndrome T, i.e., those 10% of hypothyroid patients who continue to suffer from poor quality of life despite normal TSH concentrations under substitution therapy with levothyroxine (L-T4). In this paper, we extend a mathematical model of the pituitary–thyroid feedback loop in order to improve the understanding of thyroid hormone homeostasis. In particular, we incorporate a TSH-T3-shunt inside the thyroid, whose existence has recently been demonstrated in several clinical studies. The resulting extended model shows good accordance with various clinical observations, such as a circadian rhythm in free peripheral triiodothyronine (FT3). Furthermore, we perform a sensitivity analysis of the derived model, revealing the dependence of TSH and hormone concentrations on different system parameters. The results have implications for clinical interpretation of thyroid tests, e.g., in the differential diagnosis of subclinical hypothyroidism. PMID:29619006

Mathematical Modeling of the Pituitary-Thyroid Feedback Loop: Role of a TSH-T3-Shunt and Sensitivity Analysis.

PubMed

Berberich, Julian; Dietrich, Johannes W; Hoermann, Rudolf; Müller, Matthias A

2018-01-01

Despite significant progress in assay technology, diagnosis of functional thyroid disorders may still be a challenge, as illustrated by the vague upper limit of the reference range for serum thyrotropin ( TSH ). Diagnostical problems also apply to subjects affected by syndrome T, i.e., those 10% of hypothyroid patients who continue to suffer from poor quality of life despite normal TSH concentrations under substitution therapy with levothyroxine ( L - T 4 ). In this paper, we extend a mathematical model of the pituitary-thyroid feedback loop in order to improve the understanding of thyroid hormone homeostasis. In particular, we incorporate a TSH - T 3 -shunt inside the thyroid, whose existence has recently been demonstrated in several clinical studies. The resulting extended model shows good accordance with various clinical observations, such as a circadian rhythm in free peripheral triiodothyronine ( FT 3 ). Furthermore, we perform a sensitivity analysis of the derived model, revealing the dependence of TSH and hormone concentrations on different system parameters. The results have implications for clinical interpretation of thyroid tests, e.g., in the differential diagnosis of subclinical hypothyroidism.

TPA induces a block of differentiation and increases the susceptibility to neoplastic transformation of a rat thyroid epithelial cell line.

PubMed

Portella, G; Vitagliano, D; Li, Z; Sferratore, F; Santoro, M; Vecchio, G; Fusco, A

1998-01-01

The PC Cl 3 cell line is a well-characterized epithelial cell line of rat thyroid origin. This cell line retains in vitro the typical markers of thyroid differentiation: thyroglobulin (TG) synthesis and secretion, iodide uptake, thyroperoxidase (TPO) expression, and dependency on TSH for growth. Although the differentiated phenotype of thyroid cells has been relatively well described, the molecular mechanisms that regulate both differentiation and neoplastic transformation of thyroid cells still need to be investigated in detail. Protein kinase C (PKC), the target of tetradecanoylphorbol acetate (TPA), regulates growth and differentiation of several cell types. Here we show that treatment of PC Cl 3 cells with TPA induces an acute block of thyroid differentiation. TPA-treated PC Cl 3 cells are unable to trap iodide and the expression levels of thyroglobulin, TSH receptor, and TPO genes are drastically reduced by TPA treatment. This differentiation block is not caused by a reduced expression of one of the master genes of thyroid differentiation, the thyroid transcription factor 1 (TTF-1). TPA-treated PC Cl 3 cells display an increased growth rate indicating that, in addition to the differentiation block, TPA also significantly affects the growth regulation of thyroid cells. Finally, TPA treatment dramatically increases the number of transformation foci induced in PC Cl 3 cells by retroviruses carrying v-Ki-ras, v-Ha-ras, and v-mos oncogenes. These findings support the notion that the PKC pathway can influence proliferation, differentiation, and neoplastic transformation of thyroid cells in culture.

Serum miRNAs as Biomarkers for the Diagnosis and Prognosis of Thyroid Cancer: A Comprehensive Review of the Literature.

PubMed

Mahmoudian-Sani, Mohammad-Reza; Mehri-Ghahfarrokhi, Ameneh; Asadi-Samani, Majid; Mobini, Gholam-Reza

2017-07-01

Thyroid cancer is the most common endocrine malignancy and accounts for 1% of cancers. In recent years, there has been much interest in the feasibility of using miRNAs or miRNA panels as biomarkers for the diagnosis of thyroid cancer. miRNAs are noncoding RNAs with 21-23 nucleotides that are highly conserved during evolution. They have been proposed as regulators of gene expression, apoptosis, cancer, and cell growth and differentiation. The Directory of Open Access Journals (DOAJ), Google Scholar, PubMed (NLM), LISTA (EBSCO), and Web of Science were searched. The serum level of miRNAs (miRNA-375, 34a, 145b, 221, 222, 155, Let-7, 181b) can be used as molecular markers for the diagnosis and prognosis of thyroid cancer in the serum samples of patients with thyroid glands. Given that most common methods for the screening of thyroid cancer cannot detect the disease in its early stages, identifying miRNAs that are released in the bloodstream during the gradual progression of the disease is considered a key method in the early diagnosis of thyroid cancers.

Antineoplastic Effects of PPARγ Agonists, with a Special Focus on Thyroid Cancer.

PubMed

Ferrari, Silvia Martina; Materazzi, Gabriele; Baldini, Enke; Ulisse, Salvatore; Miccoli, Paolo; Antonelli, Alessandro; Fallahi, Poupak

2016-01-01

Peroxisome Proliferator-Activated Receptor-γ (PPARγ) is a ligand-activated nuclear hormone receptor that functions as transcription factor and plays an important role in lipid metabolism and insulin sensitization. Recent studies have shown that PPARγ is overexpressed in many tumor types, including cancers of breast, lung, pancreas, colon, glioblastoma, prostate and thyroid differentiated/anaplastic cancers. These data suggest a role of PPARγ in tumor development and/or progression. PPARγ is emerging as a growth-limiting and differentiation-promoting factor, and it exerts a tumor suppressor role. Moreover, naturally-occurring and synthetic PPARγ agonists promote growth inhibition and apoptosis. Thiazolidinediones (TZDs) are synthetic agonists of PPARγ that were developed to treat type II diabetes. These compounds also display anticancer effects which appear mainly to be independent of their PPARγ agonist activity. Various preclinical and clinical studies strongly suggest a role for TZDs both alone and in combination with existing chemotherapeutic agents, for the treatment of cancer. Differentiation therapy involves the use of agents with the ability to induce differentiation in cells that have lost this ability, i.e. cancer cells, targeting pathways capable of re-activating blocked terminal differentiation programs. PPARγ agonists have been shown to induce differentiation in solid tumors such as thyroid differentiated/ anaplastic cancers and sarcomas. However, emerging data suggest that chronic use of TZDs is associated with increased risk of adverse cardiovascular events. The exploration of newer PPARγ agonists can help in unveiling the underlying mechanisms of these drugs, providing new molecules that are able to treat cancer, without increasing the cardiovascular risk of neoplastic patients.

[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.

Emerging Therapeutics for Advanced Thyroid Malignancies: Rationale and Targeted Approaches

PubMed Central

Harris, Pamela; Bible, Keith C.

2011-01-01

Introduction Thyroid cancer is an emerging public health concern. In the U.S., its incidence has doubled in the past decade, making it the 8th most commonly diagnosed neoplasm in 2010. Despite this alarming increase, most thyroid cancer patients benefit from conventional approaches (surgery, radioiodine, radiotherapy, TSH suppression with levothyroxine) and are often cured. Nevertheless, a minority have aggressive tumors resistant to cytotoxic and other historical therapies; these patients sorely need new treatment options. Areas covered Herein the biology and molecular characteristics of the common histological types of thyroid cancer are reviewed to provide context for subsequent discussion of recent developments and emerging therapeutics for advanced thyroid cancers. Expert opinion Several kinase inhibitors, especially those targeting VEGFR and/or RET, have already demonstrated promising activity in differentiated and medullary thyroid cancers (DTC, MTC). Although of minimal benefit in DTC and MTC, cytotoxic chemotherapy with anti-microtubule agents and/or anthracyclines in combination with intensity modulated radiation therapy appears to extend survival for patients with locoregionally-confined anaplastic thyroid cancer (ATC), but to have only modest benefit in metastatic ATC. Further discovery and development of novel agents and combinations of agents will be critical to further progress in treating advanced thyroid cancers of all histotypes. PMID:21910667

miRNA expression and function in thyroid carcinomas: a comparative and critical analysis and a model for other cancers.

PubMed

Saiselet, Manuel; Pita, Jaime M; Augenlicht, Alice; Dom, Geneviève; Tarabichi, Maxime; Fimereli, Danai; Dumont, Jacques E; Detours, Vincent; Maenhaut, Carine

2016-08-09

As in many cancer types, miRNA expression profiles and functions have become an important field of research on non-medullary thyroid carcinomas, the most common endocrine cancers. This could lead to the establishment of new diagnostic tests and new cancer therapies. However, different studies showed important variations in their research strategies and results. In addition, the action of miRNAs is poorly considered as a whole because of the use of underlying dogmatic truncated concepts. These lead to discrepancies and limits rarely considered. Recently, this field has been enlarged by new miRNA functional and expression studies. Moreover, studies using next generation sequencing give a new view of general miRNA differential expression profiles of papillary thyroid carcinoma. We analyzed in detail this literature from both physiological and differential expression points of view. Based on explicit examples, we reviewed the progresses but also the discrepancies and limits trying to provide a critical approach of where this literature may lead. We also provide recommendations for future studies. The conclusions of this systematic analysis could be extended to other cancer types.

RNA interference targeting CD147 inhibits the proliferation, invasiveness, and metastatic activity of thyroid carcinoma cells by down-regulating glycolysis

PubMed Central

Huang, Peng; Chang, Shi; Jiang, Xiaolin; Su, Juan; Dong, Chao; Liu, Xu; Yuan, Zhengtai; Zhang, Zhipeng; Liao, Huijun

2015-01-01

A high rate of glycolytic flux, even in the presence of oxygen, is a key metabolic hallmark of cancer cells. Lactate, the end product of glycolysis, decreases the extracellular pH and contributes to the proliferation, invasiveness and metastasis of tumor cells. CD147 play a crucial role in tumorigenicity, invasion and metastasis; and CD147 also interacts strongly and specifically with monocarboxylate transporter1 (MCT1) that mediates the transport of lactate. The objective of this study was to determine whether CD147 is involved, via its association with MCT1 to transport lactate, in glycolysis, contributing to the progression of thyroid carcinoma. The expression levels of CD147 in surgical specimens of normal thyroid, nodular goiter (NG), well-differentiated thyroid carcinoma (WDTC), and undifferentiated thyroid carcinoma (UDTC) were determined using immunohistochemical techniques. The effects of CD147 silencing on cell proliferation, invasiveness, metastasis, co-localization with MCT1, glycolysis rate and extracellular pH of thyroid cancer cells (WRO and FRO cell lines) were measured after CD147 was knocked-down using siRNA targeting CD147. Immunohistochemical analysis of thyroid carcinoma (TC) tissues revealed significant increases in signal for CD147 compared with normal tissue or NG, while UDTC expressed remarkably higher levels of CD147 compared with WDTC. Furthermore, silencing of CD147 in TC cells clearly abrogated the expression of MCT1 and its co-localization with CD147 and dramatically decreased both the glycolysis rate and extracellular pH. Thus, cell proliferation, invasiveness, and metastasis were all significantly decreased by siRNA. These results demonstrate in vitro that the expression of CD147 correlates with the degree of dedifferentiation of thyroid cancer, and show that CD147 interacts with MCT1 to regulate tumor cell glycolysis, resulting in the progression of thyroid carcinoma. PMID:25755717

Clinical factors related to the efficacy of tyrosine kinase inhibitor therapy in radioactive iodine refractory recurrent differentiated thyroid cancer patients.

PubMed

Sugino, Kiminori; Nagahama, Mitsuji; Kitagawa, Wataru; Ohkuwa, Keiko; Uruno, Takashi; Matsuzu, Kenichi; Suzuki, Akifumi; Masaki, Chie; Akaishi, Junko; Hames, Kiyomi Y; Tomoda, Chisato; Ogimi, Yuna; Ito, Koichi

2018-03-28

New insights in thyroid cancer biology propelled the development of targeted therapies as salvage treatment for radioiodine-refractory differentiated thyroid cancer (RR-DTC), and the tyrosine kinase inhibitor (TKI) lenvatinib has recently become available as a new line of therapy for RR-DTC. The aim of this study is to investigate clinical factors related to the efficacy of TKI therapy in recurrent RR-DTC patients and identify the optimal timing for the start of TKI therapy. The subjects consisted of 29 patients with progressive RR-DTC, 9 males and 20 females, median age 66 years. A univariate analysis was conducted in relation to progression free survival (PFS) and overall survival (OS) by the Kaplan-Meier method for the following variables: age, sex, histology of the primary tumor, thyroglobulin doubling time before the start of lenvatinib therapy, site of the target lesions, presence of a tumor-mediated symptom at the start of lenvatinib therapy, and baseline tumor size of the target lesions. Median duration of lenvatinib therapy was 14.7 months and median drug intensity was 9.5 mg. At the time of the data cut-off for the analysis, 9 patients (31.0%) have died of their disease (DOD), and a PR (partial response), SD (stable disease), and PD (progressive disease) were observed in 20 patients (69%), 6 patients (20.7%), 3 patients (10.3%), respectively. Univariate analyses showed that the presence of a symptom was the only factor significantly related to poorer PFS and OS. Clinical benefit of TKI therapy will be possibly limited when the therapy starts after tumor-mediated symptoms appear.

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.

A Multicenter Phase 2 Trial of Pazopanib in Metastatic and Progressive Medullary Thyroid Carcinoma: MC057H

PubMed Central

Suman, Vera J.; Molina, Julian R.; Smallridge, Robert C.; Maples, William J.; Menefee, Michael E.; Rubin, Joseph; Karlin, Nina; Sideras, Kostandinos; Morris, John C.; McIver, Bryan; Hay, Ian; Fatourechi, Vahab; Burton, Jill K.; Webster, Kevin P.; Bieber, Carolyn; Traynor, Anne M.; Flynn, Patrick J.; Cher Goh, Boon; Isham, Crescent R.; Harris, Pamela; Erlichman, Charles

2014-01-01

Context: Pazopanib is a small molecule inhibitor of kinases principally including vascular endothelial growth factor receptors-1, -2, and -3; platelet-derived growth factor receptors-α and -β; and c-Kit. We previously reported a tumor response rate of 49% in patients with advanced differentiated thyroid cancer and 0% in patients with advanced anaplastic thyroid cancer. The present report details results of pazopanib therapy in advanced medullary thyroid cancer (MTC). Objective, Design, Setting, Patients, Intervention, and Outcome Measures: Having noted preclinical activity of pazopanib in MTC, patients with advanced MTC who had disease progression within the preceding 6 months were accrued to this multiinstitutional phase II clinical trial to assess tumor response rate (by Response Evaluation Criteria In Solid Tumors criteria) and safety of pazopanib given orally once daily at 800 mg until disease progression or intolerability. Results: From September 22, 2008, to December 11, 2011, 35 individuals (80% males, median age 60 y) were enrolled. All patients have been followed up until treatment discontinuation or for a minimum of four cycles. Eight patients (23%) are still on the study treatment. The median number of therapy cycles was eight. Five patients attained partial Response Evaluation Criteria In Solid Tumors responses (14.3%; 90% confidence interval 5.8%–27.7%), with a median progression-free survival and overall survival of 9.4 and 19.9 months, respectively. Side effects included treatment-requiring (new) hypertension (33%), fatigue (14%), diarrhea (9%), and abnormal liver tests (6%); 3 of 35 patients (8.6%) discontinued therapy due to adverse events. There was one death of a study patient after withdrawal from the trial deemed potentially treatment related. Conclusions: Pazopanib has promising clinical activity in metastatic MTC with overall manageable toxicities. PMID:24606083

Current practice of radioiodine treatment in the management of differentiated thyroid cancer in Germany.

PubMed

Hoelzer, S; Steiner, D; Bauer, R; Reiners, C; Farahati, J; Hundahl, S A; Dudeck, J

2000-10-01

This prospective, observational study of a cohort of thyroid cancer patients in Germany focusses on the "real-world" practice in the management of thyroid cancer patients. This report includes data from 2376 patients with primary differentiated thyroid carcinoma first diagnosed in the year 1996. The study reveals considerable differences in actual practice concerning surgery and radioiodine treatment. The results indicate that consensus is lacking with respect to the multimodality treatment approach for differentiated thyroid carcinoma. Our analysis represents the most current and comprehensive national assessment of presenting patient characteristics, diagnostic tests, treatment and complications for thyroid cancer.

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

Variants and pitfalls on radioiodine scans in pediatric patients with differentiated thyroid carcinoma.

PubMed

Mostafa, Mohamed; Vali, Reza; Chan, Jeffrey; Omarkhail, Yusuaf; Shammas, Amer

2016-10-01

Potentially false-positive findings on radioiodine scans in children with differentiated thyroid carcinoma can mimic functioning thyroid tissue and functioning thyroid carcinomatous tissue. Such false-positive findings comprise variants and pitfalls that can vary slightly in children as compared with adults. To determine the patterns and frequency of these potential false-positive findings on radioiodine scans in children with differentiated thyroid carcinoma. We reviewed a total of 223 radioiodine scans from 53 pediatric patients (mean age 13.3 years, 37 girls) with differentiated thyroid carcinoma. Focal or regional activity that likely did not represent functioning thyroid tissue or functioning thyroid carcinomatous tissue were categorized as variants or pitfalls. The final diagnosis was confirmed by reviewing the concurrent and follow-up clinical data, correlative ultrasonography, CT scanning, serum thyroglobulin and antithyroglobulin antibody levels. We calculated the frequency of these variants and pitfalls from diagnostic and post-therapy radioiodine scans. The most common variant on the radioiodine scans was the thymic activity (24/223, 10.8%) followed by the cardiac activity (8/223, 3.6%). Salivary contamination and star artifact, caused by prominent thyroid remnant, were the most important observed pitfalls. Variants and pitfalls that mimic functioning thyroid tissue or functioning thyroid carcinomatous tissue on radioiodine scan in children with differentiated thyroid carcinoma are not infrequent, but they decrease in frequency on successive radioiodine scans. Potential false-positive findings can be minimized with proper knowledge of the common variants and pitfalls in children and correlation with clinical, laboratory and imaging data.

The evolving field of kinase inhibitors in thyroid cancer.

PubMed

Marotta, V; Sciammarella, C; Vitale, M; Colao, A; Faggiano, A

2015-01-01

Most of the genetic events implicated in the pathogenesis of thyroid cancer (TC) involve genes with kinase activity. Thus, kinase inhibitors (KIs) are very relevant in this field. KIs are considered the most suitable treatment for patients with iodine-refractory differentiated TC; these patients comprise the subgroup with the poorer prognosis. To date, only sorafenib has been approved for this indication, but promising results have been reported with several other KIs. In particular, lenvatinib has demonstrated excellent efficacy, with both progression-free survival and objective tumour response being better than with sorafenib. Despite being considered to be well tolerated, both sorafenib and lenvatinib have shown a remarkable toxicity, which has led to dose reductions in the majority of patients and to treatment discontinuation in a significant proportion of cases. The role of KIs in differentiated TC may be revolutionised by the finding that selumetinib may restore a clinical response to radioactive iodine (RAI). Vandetanib and cabozantinib have been approved for the treatment of advanced, progressive medullary TC (MTC). Nevertheless, the toxicity of both compounds suggests their selective use in those patients with strong disease progression. Treatment with the mTOR-inhibitor everolimus, alone or in combination with somatostatin analogues, should be studied in metastatic MTC patients with slow progression of disease, these representing the vast majority of patients. KIs did not significantly impact on the clinical features of anaplastic TC (ATC). Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The treatment landscape in thyroid cancer: a focus on cabozantinib.

PubMed

Weitzman, Steven P; Cabanillas, Maria E

2015-01-01

Although patients with thyroid cancer generally fare well, there is a subset for which this is not necessarily true. Progress in understanding the molecular aberrations in thyroid cancer has led to a change in the management of these cases. Since 2011, four multikinase inhibitors (MKIs) have been approved by the US Food and Drug Administration for thyroid cancer - cabozantinib and vandetanib for medullary thyroid cancer and sorafenib and lenvatinib for differentiated thyroid cancer. This change in the treatment landscape has raised challenges for practitioners who may not be familiar with the use of MKIs or with the treatment and natural history of advanced thyroid cancer in general. This article reviews the epidemiology, molecular drivers, and initial treatment of patients with thyroid cancer and offers practical guidance to assist with the determination of when to appropriately start an MKI. As an example, cabozantinib and its efficacy are discussed in detail. Close monitoring is required for all patients on targeted agents to assess for adverse effects and response to therapy. An approach to managing drug-related adverse events is detailed. Since these drugs are not curative and have not yet proven to prolong overall survival, it is critical to weigh the risks and benefits of treatment at every visit. The potential value of changing to a different agent following failure of an MKI is also addressed.

Differentiated thyroid cancer associated with intestinal polyposis syndromes: a review.

PubMed

Harb, William J; Sturgis, Erich M

2009-11-01

Intestinal polyposis syndromes, such as familial adenomatous polyposis (FAP) and Cowden's syndrome, are often associated with extraintestinal manifestations, and while many of these manifestations are benign, malignant extraintestinal manifestations, such as differentiated thyroid cancers, do occur. Although differentiated thyroid cancers (ie, papillary and follicular thyroid carcinomas) are associated with multiple syndromes, they are most commonly associated with intestinal polyposis syndromes. In the general population, the probability of developing thyroid cancer by age 65 years is only .5%. However, 1% to 2% of patients with FAP develop papillary thyroid carcinoma, the most common extraintestinal malignancy in patients with FAP. Also, up to 10% of patients with Cowden's syndrome will develop follicular thyroid carcinoma. The purpose of this review was to provide an overview of FAP, Cowden's syndrome, and Peutz-Jeghers syndrome, to discuss in detail the associations between intestinal polyposis syndromes and differentiated thyroid cancers, and to provide suggestions for screening and managing these diseases. (c) 2009 Wiley Periodicals, Inc. Head Neck, 2009.

2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer

PubMed Central

Alexander, Erik K.; Bible, Keith C.; Doherty, Gerard M.; Mandel, Susan J.; Nikiforov, Yuri E.; Pacini, Furio; Randolph, Gregory W.; Sawka, Anna M.; Schlumberger, Martin; Schuff, Kathryn G.; Sherman, Steven I.; Sosa, Julie Ann; Steward, David L.; Tuttle, R. Michael; Wartofsky, Leonard

2016-01-01

Background: Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Since the American Thyroid Association's (ATA's) guidelines for the management of these disorders were revised in 2009, significant scientific advances have occurred in the field. The aim of these guidelines is to inform clinicians, patients, researchers, and health policy makers on published evidence relating to the diagnosis and management of thyroid nodules and differentiated thyroid cancer. Methods: The specific clinical questions addressed in these guidelines were based on prior versions of the guidelines, stakeholder input, and input of task force members. Task force panel members were educated on knowledge synthesis methods, including electronic database searching, review and selection of relevant citations, and critical appraisal of selected studies. Published English language articles on adults were eligible for inclusion. The American College of Physicians Guideline Grading System was used for critical appraisal of evidence and grading strength of recommendations for therapeutic interventions. We developed a similarly formatted system to appraise the quality of such studies and resultant recommendations. The guideline panel had complete editorial independence from the ATA. Competing interests of guideline task force members were regularly updated, managed, and communicated to the ATA and task force members. Results: The revised guidelines for the management of thyroid nodules include recommendations regarding initial evaluation, clinical and ultrasound criteria for fine-needle aspiration biopsy, interpretation of fine-needle aspiration biopsy results, use of molecular markers, and management of benign thyroid nodules. Recommendations regarding the initial management of thyroid cancer include those relating to screening for thyroid cancer, staging and risk assessment, surgical management, radioiodine remnant ablation and therapy, and thyrotropin suppression therapy using levothyroxine. Recommendations related to long-term management of differentiated thyroid cancer include those related to surveillance for recurrent disease using imaging and serum thyroglobulin, thyroid hormone therapy, management of recurrent and metastatic disease, consideration for clinical trials and targeted therapy, as well as directions for future research. Conclusions: We have developed evidence-based recommendations to inform clinical decision-making in the management of thyroid nodules and differentiated thyroid cancer. They represent, in our opinion, contemporary optimal care for patients with these disorders. PMID:26462967

2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer.

PubMed

Haugen, Bryan R; Alexander, Erik K; Bible, Keith C; Doherty, Gerard M; Mandel, Susan J; Nikiforov, Yuri E; Pacini, Furio; Randolph, Gregory W; Sawka, Anna M; Schlumberger, Martin; Schuff, Kathryn G; Sherman, Steven I; Sosa, Julie Ann; Steward, David L; Tuttle, R Michael; Wartofsky, Leonard

2016-01-01

Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Since the American Thyroid Association's (ATA's) guidelines for the management of these disorders were revised in 2009, significant scientific advances have occurred in the field. The aim of these guidelines is to inform clinicians, patients, researchers, and health policy makers on published evidence relating to the diagnosis and management of thyroid nodules and differentiated thyroid cancer. The specific clinical questions addressed in these guidelines were based on prior versions of the guidelines, stakeholder input, and input of task force members. Task force panel members were educated on knowledge synthesis methods, including electronic database searching, review and selection of relevant citations, and critical appraisal of selected studies. Published English language articles on adults were eligible for inclusion. The American College of Physicians Guideline Grading System was used for critical appraisal of evidence and grading strength of recommendations for therapeutic interventions. We developed a similarly formatted system to appraise the quality of such studies and resultant recommendations. The guideline panel had complete editorial independence from the ATA. Competing interests of guideline task force members were regularly updated, managed, and communicated to the ATA and task force members. The revised guidelines for the management of thyroid nodules include recommendations regarding initial evaluation, clinical and ultrasound criteria for fine-needle aspiration biopsy, interpretation of fine-needle aspiration biopsy results, use of molecular markers, and management of benign thyroid nodules. Recommendations regarding the initial management of thyroid cancer include those relating to screening for thyroid cancer, staging and risk assessment, surgical management, radioiodine remnant ablation and therapy, and thyrotropin suppression therapy using levothyroxine. Recommendations related to long-term management of differentiated thyroid cancer include those related to surveillance for recurrent disease using imaging and serum thyroglobulin, thyroid hormone therapy, management of recurrent and metastatic disease, consideration for clinical trials and targeted therapy, as well as directions for future research. We have developed evidence-based recommendations to inform clinical decision-making in the management of thyroid nodules and differentiated thyroid cancer. They represent, in our opinion, contemporary optimal care for patients with these disorders.

Clinical utility of TERT promoter mutations and ALK rearrangement in thyroid cancer patients with a high prevalence of the BRAF V600E mutation.

PubMed

Bae, Ja Seong; Kim, Yourha; Jeon, Sora; Kim, Se Hee; Kim, Tae Jung; Lee, Sohee; Kim, Min-Hee; Lim, Dong Jun; Lee, Youn Soo; Jung, Chan Kwon

2016-02-09

Mutations in the TERT promoter, ALK rearrangement, and the BRAF V600E mutation are associated with aggressive clinicopathologic features in thyroid cancers. However, little is known about the impact of TERT promoter mutations and ALK rearrangement in thyroid cancer patients with a high prevalence of BRAF mutations. We performed Sanger sequencing to detect BRAF V600E and TERT promoter mutations and both immunohistochemistry and fluorescence in situ hybridization to identify ALK rearrangement on 243 thyroid cancers. TERT promoter mutations were not present in 192 well-differentiated thyroid carcinomas (WDTC) without distant metastasis or in 9 medullary carcinomas. However, the mutations did occur in 40 % (12/30) of WDTC with distant metastasis, 29 % (2/7) of poorly differentiated carcinomas and 60 % (3/5) of anaplastic carcinomas. ALK rearrangement was not present in all thyroid cancers. The BRAF V600E mutation was more frequently found in WDTC without distant metastasis than in WDTC with distant metastasis (p = 0.007). In the cohort of WDTC with distant metastasis, patients with wild-type BRAF and TERT promoter had a significantly higher response rate after radioiodine therapy (p = 0.024), whereas the BRAF V600E mutation was significantly correlated with progressive disease (p = 0.025). The TERT promoter mutation is an independent predictor for distant metastasis of WDTC, but ALK testing is not useful for clinical decision-making in Korean patients with a high prevalence of the BRAF V600E mutation. Radioiodine therapy for distant metastasis of WDTC is most effective in patients without BRAF V600E and TERT promoter mutations.

German Association of Endocrine Surgeons practice guideline for the surgical management of malignant thyroid tumors.

PubMed

Dralle, Henning; Musholt, Thomas J; Schabram, Jochen; Steinmüller, Thomas; Frilling, Andreja; Simon, Dietmar; Goretzki, Peter E; Niederle, Bruno; Scheuba, Christian; Clerici, Thomas; Hermann, Michael; Kußmann, Jochen; Lorenz, Kerstin; Nies, Christoph; Schabram, Peter; Trupka, Arnold; Zielke, Andreas; Karges, Wolfram; Luster, Markus; Schmid, Kurt W; Vordermark, Dirk; Schmoll, Hans-Joachim; Mühlenberg, Reinhard; Schober, Otmar; Rimmele, Harald; Machens, Andreas

2013-03-01

Over the past years, the incidence of thyroid cancer has surged not only in Germany but also in other countries of the Western hemisphere. This surge was first and foremost due to an increase of prognostically favorable ("low risk") papillary thyroid microcarcinomas, for which limited surgical procedures are often sufficient without loss of oncological benefit. These developments called for an update of the previous practice guideline to detail the surgical treatment options that are available for the various disease entities and tumor stages. The present German Association of Endocrine Surgeons practice guideline was developed on the basis of clinical evidence considering current national and international treatment recommendations through a formal expert consensus process in collaboration with the German Societies of General and Visceral Surgery, Endocrinology, Nuclear Medicine, Pathology, Radiooncology, Oncological Hematology, and a German thyroid cancer patient support organization. The practice guideline for the surgical management of malignant thyroid tumors includes recommendations regarding preoperative workup; classification of locoregional nodes and terminology of surgical procedures; frequency, clinical, and histopathological features of occult and clinically apparent papillary, follicular, poorly differentiated, undifferentiated, and sporadic and hereditary medullary thyroid cancers, thyroid lymphoma and thyroid metastases from primaries outside the thyroid gland; extent of thyroidectomy; extent of lymph node dissection; aerodigestive tract resection; postoperative follow-up and surgery for recurrence and distant metastases. These evidence-based recommendations for surgical therapy reflect various "treatment corridors" that are best discussed within multidisciplinary teams and the patient considering tumor type, stage, progression, and inherent surgical risk.

Personalized Medicine Based on Theranostic Radioiodine Molecular Imaging for Differentiated Thyroid Cancer.

PubMed

Ahn, Byeong-Cheol

2016-01-01

Molecular imaging based personalized therapy has been a fascinating concept for individualized therapeutic strategy, which is able to attain the highest efficacy and reduce adverse effects in certain patients. Theranostics, which integrates diagnostic testing to detect molecular targets for particular therapeutic modalities, is one of the key technologies that contribute to the success of personalized medicine. Although the term "theranostics" was used after the second millennium, its basic principle was applied more than 70 years ago in the field of thyroidology with radioiodine molecular imaging. Differentiated thyroid cancer, which arises from follicular cells in the thyroid, is the most common endocrine malignancy, and theranostic radioiodine has been successfully applied to diagnose and treat differentiated thyroid cancer, the applications of which were included in the guidelines published by various thyroid or nuclear medicine societies. Through better pathophysiologic understanding of thyroid cancer and advancements in nuclear technologies, theranostic radioiodine contributes more to modern tailored personalized management by providing high therapeutic effect and by avoiding significant adverse effects in differentiated thyroid cancer. This review details the inception of theranostic radioiodine and recent radioiodine applications for differentiated thyroid cancer management as a prototype of personalized medicine based on molecular imaging.

Thyroid hormone accelerates the differentiation of adult hippocampal progenitors.

PubMed

Kapoor, R; Desouza, L A; Nanavaty, I N; Kernie, S G; Vaidya, V A

2012-09-01

Disrupted thyroid hormone function evokes severe physiological consequences in the immature brain. In adulthood, although clinical reports document an effect of thyroid hormone status on mood and cognition, the molecular and cellular changes underlying these behavioural effects are poorly understood. More recently, the subtle effects of thyroid hormone on structural plasticity in the mature brain, in particular on adult hippocampal neurogenesis, have come to be appreciated. However, the specific stages of adult hippocampal progenitor development that are sensitive to thyroid hormone are not defined. Using nestin-green fluorescent protein reporter mice, we demonstrate that thyroid hormone mediates its effects on hippocampal neurogenesis by influencing Type 2b and Type 3 progenitors, although it does not alter proliferation of either the Type 1 quiescent progenitor or the Type 2a amplifying neural progenitor. Thyroid hormone increases the number of doublecortin (DCX)-positive Type 3 progenitors, and accelerates neuronal differentiation into both DCX-positive immature neurones and neuronal nuclei-positive granule cell neurones. Furthermore, we show that this increase in neuronal differentiation is accompanied by a significant induction of specific transcription factors involved in hippocampal progenitor differentiation. In vitro studies using the neurosphere assay support a direct effect of thyroid hormone on progenitor development because neurospheres treated with thyroid hormone are shifted to a more differentiated state. Taken together, our results indicate that thyroid hormone mediates its neurogenic effects via targeting Type 2b and Type 3 hippocampal progenitors, and suggests a role for proneural transcription factors in contributing to the effects of thyroid hormone on neuronal differentiation of adult hippocampal progenitors. © 2012 The Authors. Journal of Neuroendocrinology © 2012 British Society for Neuroendocrinology.

Genetic alterations in the phosphatidylinositol-3 kinase/Akt pathway in thyroid cancer.

PubMed

Xing, Mingzhao

2010-07-01

Aberrant activation of the phosphatidylinositol-3 kinase (PI3K)/Akt pathway plays a fundamental role in thyroid tumorigenesis, particularly in follicular thyroid cancer (FTC) and aggressive thyroid cancer, such as anaplastic thyroid cancer (ATC). As the drivers of this process, many genetic alterations activating the PI3K/Akt pathway have been identified in thyroid cancer in recent years. This review summarizes the current knowledge on major genetic alterations in the PI3K/Akt pathway. These include PIK3CA mutations and genomic amplification/copy gain, Ras mutations, PTEN mutations, RET/PTC and PPARgamma/Pax8 rearrangements, as well as amplification/copy gain of PIK3CB, PDK1, Akt, and various receptor tyrosine kinase genes. Most of these genetic alterations are particularly common in FTC and many of them are even more common in ATC; they are generally less common in papillary thyroid cancer (PTC), in which the MAP kinase (MAPK) pathway activated by the BRAF mutation instead plays a major role. Methylation and, thus, epigenetic silencing of PTEN, a major negative regulator of the PI3K/Akt pathway, occurs in close association with activating genetic alterations of the PI3K/Akt pathway, constituting a unique self-enhancement mechanism for this pathway. Many of these genetic alterations are mutually exclusive in differentiated thyroid tumors, but with increasing concurrence from benign tumors to FTC to ATC. RET/PTC, Ras, and receptor tyrosine kinase could dually activate the PI3K/Akt and MAPK pathways. Most cases of ATC harbor genetic alterations in these genes or other genetic combinations that can activate both pathways. It is proposed that genetic alterations in the PI3K/Akt pathway promote thyroid cell transformation to FTC and that genetic alterations in the MAPK pathway promote cell transformation to PTC; accumulation of multiple genetic alterations that can activate both pathways promotes thyroid cancer aggressiveness and progression to ATC. Genetic alterations are common in the PI3K/Akt pathway in thyroid cancer and play a fundamental role in the tumorigenesis and progression of this cancer. This provides a strong basis for the emerging development of novel genetic-based diagnostic, prognostic, and therapeutic strategies for thyroid cancer.

Role of Dicer1 in thyroid cell proliferation and differentiation.

PubMed

Penha, Ricardo Cortez Cardoso; Sepe, Romina; De Martino, Marco; Esposito, Francesco; Pellecchia, Simona; Raia, Maddalena; Del Vecchio, Luigi; Decaussin-Petrucci, Myriam; De Vita, Gabriella; Pinto, Luis Felipe Ribeiro; Fusco, Alfredo

2017-01-01

DICER1 plays a central role in the biogenesis of microRNAs and it is important for normal development. Altered microRNA expression and DICER1 dysregulation have been described in several types of tumors, including thyroid carcinomas. Recently, our group identified a new somatic mutation (c.5438A>G; E1813G) within DICER1 gene of an unknown function. Herein, we show that DICER1 is overexpressed, at mRNA level, in a significant-relative number of papillary (70%) and anaplastic (42%) thyroid carcinoma samples, whereas is drastically downregulated in all the analyzed human thyroid carcinoma cell lines (TPC-1, BCPAP, FRO and 8505c) in comparison with normal thyroid tissue samples. Conversely, DICER1 is downregulated, at protein level, in PTC in comparison with normal thyroid tissues. Our data also reveals that DICER1 overexpression positively regulates thyroid cell proliferation, whereas its silencing impairs thyroid cell differentiation. The expression of DICER1 gene mutation (c.5438A>G; E1813G) negatively affects the microRNA machinery and cell proliferation as well as upregulates DICER1 protein levels of thyroid cells but has no impact on thyroid differentiation. In conclusion, DICER1 protein is downregulated in papillary thyroid carcinomas and affects thyroid proliferation and differentiation, while DICER1 gene mutation (c.5438A>G; E1813G) compromises the DICER1 wild-type-mediated microRNA processing and cell proliferation.

Hypocalcaemia after thyroid surgery for differentiated thyroid carcinoma: preliminary study report.

PubMed

Radivojević, Renata Curić; Prgomet, Drago; Markesić, Josip; Ezgeta, Carmen

2012-11-01

Hypocalcaemia is one of the most common major complications after thyroid surgery with the wide range of incidence from 6.9 to 46%. Thyroidectomy is usually first choice treatment for differentiated thyroid carcinoma (DTC). The study comprised 46 adult patients operated at Zagreb University Hospital Centre. Intraoperative and postoperative ionized calcium and intact parathyroid hormone (iPTH) were studied. The object of this study is to investigate risk factors, incidence of hypocalcaemia after surgical treatment of differentiated thyroid carcinoma, and the role of iPTH in comparison to ionized calcium as a predictor for hypocalcaemia.

Prior irradiation and the development of coexistent differentiated thyroid cancer and hyperparathyroidism

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

Prinz, R.A.; Barbato, A.L.; Braithwaite, S.S.

1982-03-01

Twelve patients with coexistent well-differentiated thyroid carcinoma and primary hyperparathyoidism were studied to determine the frequency of previous radiation exposure. Eight were found to have received prior irradiation. External radiation was administered to the head and neck region for benign conditions such as tonsillar enlargement, acne, scrofula, and thyroid enlargement. One patient received 131I therapy for carcinoma of the thyroid. The observation that 67% of the patients in this series had previous radiation to the head and neck strongly implicates radiation exposure in the development of coexistent well-differentiated thyroid carcinoma and hyperparathyroidism.

A case of metastatic follicular thyroid carcinoma complicated with Graves' disease after total thyroidectomy.

PubMed

Aoyama, Mariko; Takizawa, Hiromitsu; Tsuboi, Mitsuhiro; Nakagawa, Yasushi; Tangoku, Akira

2017-12-28

Thyroid cancer and Graves' disease may present simultaneously in one patient. The incidence of the development of hyperthyroidism from metastatic differentiated thyroid carcinoma is rare. We herein report a case of metastatic follicular carcinoma complicated with Graves' disease after total thyroidectomy. A 57-year-old woman underwent right hemithyroidectomy for follicular carcinoma. Metastatic lesions appeared in the lungs and skull two years after the first surgery, and remnant thyroidectomy was performed for radioactive iodine-131 (RAI) therapy, during which the TSH receptor antibody (TRAb) was found to be negative. The patient was treated with RAI therapy four times for four years and was receiving levothyroxine suppressive therapy. Although radioiodine uptake was observed in the lesions after the fourth course of RAI therapy, metastatic lesions had progressed. Four years after the second surgery, she had heart palpitations and tremors. Laboratory data revealed hyperthyroidism and positive TRAb. She was diagnosed with Graves' disease and received a fifth course of RAI therapy. 131I scintigraphy after RAI therapy showed strong radioiodine uptake in the metastatic lesions. As a result, the sizes and numbers of metastatic lesions decreased, and thyroid function improved. Metastatic lesions produced thyroid hormone and caused hyperthyroidism. RAI therapy was effective for Graves' disease and thyroid carcinoma.

Defects in iodide metabolism in thyroid cancer and implications for the follow-up and treatment of patients.

PubMed

Schlumberger, Martin; Lacroix, Ludovic; Russo, Diego; Filetti, Sebastiano; Bidart, Jean-Michel

2007-03-01

The two major steps of iodine metabolism--uptake and organification--are altered in thyroid cancer tissues. Organification defects result in a rapid discharge of radioiodine from thyroid cells, a short effective half-life of iodine, and a low rate of thyroid hormone synthesis. These defects are mainly due to decreased expression of functional genes encoding the sodium-iodide symporter and thyroid peroxidase and could result in a low radiation dose to thyroid cancer cells. TSH stimulation that is achieved with injections of recombinant human TSH, or long-term withdrawal of thyroid hormone treatment increases iodine-131 uptake in two-thirds of patients with metastatic disease and increases thyroglobulin production in all patients with metastases, even in the absence of detectable uptake. Serum thyroglobulin determination obtained following TSH stimulation and neck ultrasonography is the most sensitive combination for the detection of small tumor foci. Radioiodine treatment is effective when a high radiation dose can be delivered (in patients with high uptake and retention of radioiodine) and when tumor foci are sensitive to the effects of radiation therapy (younger patients, with a well-differentiated tumor and/or with small metastases). The other patients rarely respond to radioiodine treatment, and when progression occurs, other treatment modalities should be considered. Novel strategies are currently being explored to restore iodine uptake in cancer cells that are unable to concentrate radioiodine.

An Adult Mouse Thyroid Side Population Cell Line that Exhibits Enriched Epithelial–Mesenchymal Transition

PubMed Central

Murata, Tsubasa; Iwadate, Manabu; Takizawa, Yoshinori; Miyakoshi, Masaaki; Hayase, Suguru; Yang, Wenjing; Cai, Yan; Yokoyama, Shigetoshi; Nagashima, Kunio; Wakabayashi, Yoshiyuki; Zhu, Jun

2017-01-01

Background: Studies of thyroid stem/progenitor cells have been hampered due to the small organ size and lack of tissue, which limits the yield of these cells. A continuous source that allows the study and characterization of thyroid stem/progenitor cells is desired to push the field forward. Method: A cell line was established from Hoechst-resistant side population cells derived from mouse thyroid that were previously shown to contain stem/progenitor-like cells. Characterization of these cells were carried out by using in vitro two- and three-dimensional cultures and in vivo reconstitution of mice after orthotopic or intravenous injection, in conjunction with quantitative reverse transcription polymerase chain reaction, Western blotting, immunohisto(cyto)chemistry/immunofluorescence, and RNA seq analysis. Results: These cells were named SPTL (side population cell-derived thyroid cell line). Under low serum culturing conditions, SPTL cells expressed the thyroid differentiation marker NKX2-1, a transcription factor critical for thyroid differentiation and function, while no expression of other thyroid differentiation marker genes were observed. SPTL cells formed follicle-like structures in Matrigel® cultures, which did not express thyroid differentiation marker genes. In mouse models of orthotopic and intravenous injection, the latter following partial thyroidectomy, a few SPTL cells were found in part of the follicles, most of which expressed NKX2-1. SPTL cells highly express genes involved in epithelial–mesenchymal transition, as demonstrated by RNA seq analysis, and exhibit a gene-expression pattern similar to anaplastic thyroid carcinoma. Conclusion: These results demonstrate that SPTL cells have the capacity to differentiate into thyroid to a limited degree. SPTL cells may provide an excellent tool to study stem cells, including cancer stem cells of the thyroid. PMID:28125936

Follow-up of differentiated thyroid carcinoma.

PubMed

Pagano, L; Klain, M; Pulcrano, M; Angellotti, G; Pasano, F; Salvatore, M; Lombardi, G; Biondi, B

2004-12-01

Thyroid cancer is the most common endocrine malignancy. More than 90% of primary thyroid cancers are differentiated papillary or follicular types. The treatment of differentiated thyroid carcinoma (DTC) consists of total thyroidectomy and radioactive iodine ablation therapy, followed by L-thyroxine therapy. The extent of initial surgery, the indication for radioiodine ablation therapy and the degree of TSH-suppression are all issues that are still being debated cancers are in relation to the risk of recurrence. Total thyroidectomy reduces the risk of recurrence and facilitates (131)I ablation of thyroid remnants. The aim of radioiodine ablation is to destroy any normal or neoplastic residuals of thyroid tissue. These procedures also improve the sensitivity of thyroglobulin (Tg) as a marker of disease, and increase the sensitivity of (131)I total body scan (TBS) for the detection of persistent or recurrent disease. The aim of TSH-suppressive therapy is to restore euthyroidism and to decrease serum TSH levels, in order to reduce the growth and progression of thyroid cancer. After initial treatment, the objectives of the follow-up of DTC is to maintain adequate thyroxine therapy and to detect persistent or recurrent disease through the combined use of neck ultrasound (US) and serum Tg and (131)I TBS after TSH stimulation. The follow-up protocol should be adapted to the risk of recurrence. Recent advances in the follow-up of DTC are related to the use of recombinant human TSH (rhTSH) in order to stimulate Tg production and the ultrasensitive methods for Tg measurement. Undetectable serum Tg during TSH suppressive therapy with L-T4 does not exclude persistent disease, therefore serum Tg should be measured after TSH stimulation. The results of rhTSH administration and L-thyroxine therapy withdrawal are equivalent in detecting recurrent thyroid cancer, but the use of rhTSH helps to avoid the onset of hypothyroid symptoms and the negative effects of acute hypothyroidism on cardiovascular, hepatic, renal and neurological function. In low-risk DTC patients serum Tg after TSH stimulation, together with ultrasound of the neck, should be used to monitor persistent disease, avoiding diagnostic TBS which has a poor sensitivity. These recommendations do not apply when Tg antibodies are present in the serum, in patients with persistent or recurrent disease or limited thyroid surgery. Low-risk patients may be considered to be in remission when undetectable Tg after TSH stimulation and negative US evaluation of the neck are present. On the contrary, detectable Tg after TSH stimulation is an indicator in selecting patients who are candidates for further diagnostic procedures.

Insulin-like growth factor-I and risk of differentiated thyroid carcinoma in the European Prospective Investigation into Cancer and Nutrition

PubMed Central

Schmidt, Julie A.; Allen, Naomi E.; Almquist, Martin; Franceschi, Silvia; Rinaldi, Sabina; Tipper, Sarah J.; Tsilidis, Konstantinos K.; Weiderpass, Elisabete; Overvad, Kim; Tjønneland, Anne; Boutron-Ruault, Marie-Christine; Dossus, Laure; Mesrine, Sylvie; Kaaks, Rudolf; Lukanova, Annekatrin; Boeing, Heiner; Lagiou, Pagona; Trichopoulos, Dimitrios; Trichopoulou, Antonia; Palli, Domenico; Krogh, Vittorio; Panico, Salvatore; Tumino, Rosario; Zanetti, Roberto; Bueno-de-Mesquita, H Bas; Peeters, Petra H; Lund, Eiliv; Menéndez, Virginia; Agudo, Antonio; Sánchez, María-José; Chirlaque, Maria-Dolores; Ardanaz, Eva; Larrañaga, Nerea; Hennings, Joakim; Sandström, Maria; Khaw, Kay-Tee; Wareham, Nick; Romieu, Isabelle; Gunter, Marc J.; Riboli, Elio; Key, Timothy J.; Travis, Ruth C.

2014-01-01

Background Little is known about the causes of thyroid cancer, but insulin-like growth factor-I (IGF-I) might play an important role in its development due to its mitogenic and anti-apoptotic properties. Methods This study prospectively investigated the association between serum IGF-I concentrations and risk of differentiated thyroid carcinoma in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition. 345 incident cases of differentiated thyroid carcinoma were individually matched to 735 controls by study centre, sex, and age, date, time, and fasting status at blood collection, follow-up duration, and for women menopausal status, use of exogenous hormones, and phase of menstrual cycle at blood collection. Serum IGF-I concentrations were measured by immunoassay, and risk of differentiated thyroid cancer in relation to IGF-I concentration was estimated using conditional logistic regression. Results There was a positive association between IGF-I concentrations and risk of differentiated thyroid carcinoma: the odds ratio for a doubling in IGF-I concentration was 1.48 (95% confidence interval: 1.06 – 2.08; ptrend = 0.02). The positive association with IGF-I was stable over time between blood collection and cancer diagnosis. Conclusion These findings suggest that IGF-I concentrations may be positively associated with risk of differentiated thyroid carcinoma. Impact This study provides the first prospective evidence of a potential association between circulating IGF-I concentrations and risk of differentiated thyroid carcinoma and may prompt the further investigations needed to confirm the association. PMID:24646451

MicroRNAs in thyroid development, function and tumorigenesis.

PubMed

Fuziwara, Cesar Seigi; Kimura, Edna Teruko

2017-11-15

MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression that modulate the vast majority of cellular processes. During development, the correct timing and expression of miRNAs in the tissue differentiation is essential for organogenesis and functionality. In thyroid gland, DICER and miRNAs are necessary for accurately establishing thyroid follicles and hormone synthesis. Moreover, DICER1 mutations and miRNA deregulation observed in human goiter influence thyroid tumorigenesis. The thyroid malignant transformation by MAPK oncogenes is accompanied by global miRNA changes, with a marked reduction of "tumor-suppressor" miRNAs and activation of oncogenic miRNAs. Loss of thyroid cell differentiation/function, and consequently iodine trapping impairment, is an important clinical characteristic of radioiodine-refractory thyroid cancer. However, few studies have addressed the direct role of miRNAs in thyroid gland physiology. Here, we focus on what we have learned in the thyroid follicular cell differentiation and function as revealed by cell and animal models and miRNA modulation in thyroid tumorigenesis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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.

Transcriptome Network Analysis Reveals Aging-Related Mitochondrial and Proteasomal Dysfunction and Immune Activation in Human Thyroid

PubMed Central

Cho, Byuri Angela; Yoo, Seong-Keun; Song, Young Shin; Kim, Su-jin; Lee, Kyu Eun; Shong, Minho

2018-01-01

Background: Elucidating aging-related transcriptomic changes in human organs is necessary to understand the aging physiology and mechanisms, but little is known regarding the thyroid gland. We investigated aging-related transcriptomic alterations in the human thyroid gland and characterized the related molecular functions. Methods: Publicly available RNA sequencing data of 322 thyroid tissue samples from the Genotype-Tissue Expression project were analyzed. In addition, our own 64 RNA sequencing data of normal thyroid tissue samples were used as a validation set. To comprehensively evaluate the associations between aging and transcriptomic changes, we performed a weighted gene coexpression network analysis and pathway enrichment analysis. The thyroid differentiation score was then used for further analysis, defining the correlations between thyroid differentiation and aging. Results: The most significant aging-related transcriptomic change in thyroid was the downregulation of genes related to the mitochondrial and proteasomal functions (p = 3 × 10−6). Moreover, genes that are associated with immune processes were significantly upregulated with age (p = 3 × 10−4), and all of them overlapped with the upregulated genes in the thyroid glands affected by lymphocytic thyroiditis. Furthermore, these aging-related changes were not significantly different according to sex, but in terms of the thyroid differentiation, females were more susceptible to aging-related changes (p for trend = 0.03). Conclusions: Aging-related transcriptomic changes in the thyroid gland were associated with mitochondrial and proteasomal dysfunction, loss of differentiation, and activation of autoimmune processes. Our results provide clues to better understanding the age-related decline in thyroid function and higher susceptibility to autoimmune thyroid disease. PMID:29652618

Causes of referral to the first endocrine visit of patients with thyroid carcinoma in a mildly iodine-deficient area.

PubMed

Marina, Michela; Ceda, Gian Paolo; Aldigeri, Raffaella; Ceresini, Graziano

2017-08-01

To evaluate the causes of the first referral to an endocrine visit of patients with thyroid cancer in a mildly iodine-deficient area and to correlate them with prognostic features. We studied 298 consecutive patients (64 M and 234 F) with thyroid cancer. Of these, 281 had differentiated thyroid cancer. The causes of referral were categorized as follows: (Group A) clinical evidence of a neck lump; (Group B) incidental imaging in subjects without known thyroid diseases; (Group C) incidental imaging during a workup of thyroid disorders. Also, in differentiated thyroid cancer cases, clinical, histomorphologic, and prognostic parameters were compared among the three different groups of referral causes. In both total thyroid cancer and differentiated thyroid cancer cohorts, Group A, B, and C accounted for about 25, 35, and 40 % of causes, respectively. Considering the differentiated thyroid cancer, in Group B, ultrasound accounted for 94 % of cases, with 73 % resulting from screening or serendipitous study. Within a median follow-up of 5.6 [IQR: 2.7-9.5] years, disease-free survival was significantly lower in patients of Group A (Log-Rank test p = 0.030 vs. the other groups of causes). However, at the Cox multivariate analysis only male sex (p = 0.002) and stage (p = 0.005), but not referral cause, resulted independent predictors of events. In patients without known thyroid disease, unjustified thyroid ultrasound represents the main cause of referral of thyroid cancer patients to the first endocrine visit. The fact that this is not related to the disease-free survival strengthens the concept of the uselessness of thyroid cancer screening.

Clinical Value of Thyrotropin Receptor Antibodies for the Differential Diagnosis of Interferon Induced Thyroiditis.

PubMed

Benaiges, D; Garcia-Retortillo, M; Mas, A; Cañete, N; Broquetas, T; Puigvehi, M; Chillarón, J J; Flores-Le Roux, J A; Sagarra, E; Cabrero, B; Zaffalon, D; Solà, R; Pedro-Botet, J; Carrión, J A

2016-01-01

The clinical value of thyrotropin receptor antibodies for the differential diagnosis of thyrotoxicosis induced by pegylated interferon-alpha remains unknown. We analyzed the diagnostic accuracy of thyrotropin receptor antibodies in the differential diagnosis of thyrotoxicosis in patients with chronic hepatitis C (CHC) receiving pegylated interferon-alpha plus ribavirin. Retrospective analysis of 274 patients with CHC receiving pegylated interferon-alpha plus ribavirin. Interferon-induced thyrotoxicosis was classified according to clinical guidelines as Graves disease, autoimmune and non- autoimmune destructive thyroiditis. 48 (17.5%) patients developed hypothyroidism, 17 (6.2%) thyrotoxicosis (6 non- autoimmune destructive thyroiditis, 8 autoimmune destructive thyroiditis and 3 Graves disease) and 22 "de novo" thyrotropin receptor antibodies (all Graves disease, 2 of the 8 autoimmune destructive thyroiditis and 17 with normal thyroid function). The sensitivity and specificity of thyrotropin receptor antibodies for Graves disease diagnosis in patients with thyrotoxicosis were 100 and 85%, respectively. Patients with destructive thyroiditis developed hypothyroidism in 87.5% of autoimmune cases and in none of those with a non- autoimmune etiology (p<0.001). Thyrotropin receptor antibodies determination cannot replace thyroid scintigraphy for the differential diagnosis of thyrotoxicosis in CHC patients treated with pegylated interferon. © Georg Thieme Verlag KG Stuttgart · New York.

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.

Sclerosing mucoepidermoid carcinoma with eosinophilia of thyroid gland in a male patient: a case report and literature review.

PubMed

Lai, Chi-Yun; Chao, Tzu-Chieh; Lin, Jen-Der; Hsueh, Chuen

2015-01-01

Sclerosing mucoepidermoid carcinoma with eosinophilia (SMECE) was first described by Chan et al in 1991. It is characterized by nest or strands of epidermoid tumor cells with squamous differentiation, rare mucous cells, prominent sclerotic stroma, eosinophilic and lymphoplasmacytic infiltration, and a background of chronic lymphocytic thyroiditis in the non-neoplastic thyroid gland. It is important to recognize SMECE of thyroid and differentiate it from squamous cell carcinoma or other neoplasms with squamous differentiation/metaplasia. In published cases, the SMECE of thyroid gland predominantly occurs in women. We report a case of SMECE of thyroid in a 45-year-old male patient. All cases in male patients were Caucasian described in English literature, and our case is the first one in Asian.

Role of Diffusion-Weighted Magnetic Resonance (MR) Imaging in Differentiation Between Graves’ Disease and Painless Thyroiditis

PubMed Central

Abdel Razek, Ahmed Abdel Khalek; El-Said, Amr Abd El-hamid

2017-01-01

Summary Background To assess the role of diffusion-weighted MR imaging in differentiation between Graves’ disease and painless thyroiditis. Material/Methods A prospective study was conducted among 37 consecutive patients with untreated thyrotoxicosis (25 female and 12 male; mean age of 44 years) and 15 ageand sex-matched controls. Diffusion-weighted MR imaging of the thyroid gland was performed in patients and controls. The apparent diffusion coefficient (ADC) value of the thyroid gland was calculated and correlated with Tc-99m uptake and thyroid function tests of the patients. Results There was a significant difference in the ADC value of the thyroid gland between patients and the control group (P=0.001). The mean ADC value of the thyroid gland in Graves’ disease was 2.03±0.28×10–3 mm2/sec, and in patients with painless thyroiditis 1.46±0.22×10–3 mm2/sec, respectively. There was a significant difference in the ADC values between Graves’ disease and painless thyroiditis (P=0.001). When the ADC value of 1.45×10–3 mm2/sec was used as a threshold value for differentiating Graves’ disease from painless thyroiditis, the best result was obtained with area under the curve of 0.934, accuracy of 83.8%, sensitivity of 95.8%, and specificity of 61.5%. The mean ADC value of the thyroid gland in patients positively correlated with serum TRAb and Tc-99m uptake (r=0.57, P=0.001 and r=0.74, P=0.001, respectively). Conclusions We concluded that ADC values of the thyroid gland can be used to differentiate Graves’ disease from painless thyroiditis in patients with untreated thyrotoxicosis. PMID:29662585

Role of Diffusion-Weighted Magnetic Resonance (MR) Imaging in Differentiation Between Graves' Disease and Painless Thyroiditis.

PubMed

Abdel Razek, Ahmed Abdel Khalek; Abd Allah, Sieza Samir; El-Said, Amr Abd El-Hamid

2017-01-01

To assess the role of diffusion-weighted MR imaging in differentiation between Graves' disease and painless thyroiditis. A prospective study was conducted among 37 consecutive patients with untreated thyrotoxicosis (25 female and 12 male; mean age of 44 years) and 15 ageand sex-matched controls. Diffusion-weighted MR imaging of the thyroid gland was performed in patients and controls. The apparent diffusion coefficient (ADC) value of the thyroid gland was calculated and correlated with Tc-99m uptake and thyroid function tests of the patients. There was a significant difference in the ADC value of the thyroid gland between patients and the control group ( P =0.001). The mean ADC value of the thyroid gland in Graves' disease was 2.03±0.28×10 -3 mm 2 /sec, and in patients with painless thyroiditis 1.46±0.22×10 -3 mm 2 /sec, respectively. There was a significant difference in the ADC values between Graves' disease and painless thyroiditis ( P =0.001). When the ADC value of 1.45×10 -3 mm 2 /sec was used as a threshold value for differentiating Graves' disease from painless thyroiditis, the best result was obtained with area under the curve of 0.934, accuracy of 83.8%, sensitivity of 95.8%, and specificity of 61.5%. The mean ADC value of the thyroid gland in patients positively correlated with serum TRAb and Tc-99m uptake ( r =0.57, P =0.001 and r =0.74, P =0.001, respectively). We concluded that ADC values of the thyroid gland can be used to differentiate Graves' disease from painless thyroiditis in patients with untreated thyrotoxicosis.

[Thyroid nodules and differentiated thyroid cancer: Brazilian consensus].

PubMed

Maia, Ana Luiza; Ward, Laura S; Carvalho, Gisah A; Graf, Hans; Maciel, Rui M B; Maciel, Léa M Zanini; Rosário, Pedro W; Vaisman, Mario

2007-07-01

Thyroid nodules are a common manifestation of thyroid diseases. It is estimated that approximately 10% of adults have palpable thyroid nodules with the frequency increasing throughout life. The major concern on nodule evaluation is the risk of malignancy (5-10%). Differentiated thyroid carcinoma accounts for 90% of all thyroid malignant neoplasias. Although most patients with cancer have a favorable outcome, some individuals present an aggressive form of the disease and poor prognostic despite recent advances in diagnosis and treatment. Here, a set of clinical guidelines for the evaluation and management of patients with thyroid nodules or differentiated thyroid cancer was developed through consensus by 8 member of the Department of Thyroid, Sociedade Brasileira de Endocrinologia e Metabologia. The participants are from different reference medical centers within Brazil, to reflect different practice patterns. Each committee participant was initially assigned to write a section of the document and to submit it to the chairperson, who revised and assembled the sections into a complete draft document, which was then circulated among all committee members for further revision. All committee members further revised and refined the document. The guidelines were developed based on the expert opinion of the committee participants, as well as on previously published information.

Management of thyroid carcinoma with radioactive 131I.

PubMed

Paryani, S B; Chobe, R J; Scott, W; Wells, J; Johnson, D; Kuruvilla, A; Schoeppel, S; Deshmukh, A; Miller, R; Dajani, L; Montgomery, C T; Puestow, E; Purcell, J; Roura, M; Sutton, D; Mallett, R; Peer, J

1996-08-01

To evaluate the role of radioactive 131I in the management of patients with well differentiated carcinoma of the thyroid. Between 1965 and 1995, a total of 117 patients with well-differentiated carcinoma of the thyroid underwent either lobectomy or thyroidectomy followed by 100-150 mCi of 131I. With a median follow-up of 8 years, only four patients (3%) developed a recurrence of their disease. The 5-year actuarial survival was 97% with a 10-year survival of 91%. There were no severe side effects noted after 131I therapy. Radioactive 131I is a safe and effective procedure for the majority of patients with well-differentiated thyroid carcinoma. We currently recommend that all patients undergo a subtotal or total thyroidectomy followed by 131I thyroid scanning approximately 4 weeks after surgery. If the thyroid scan shows no residual uptake and all disease is confined to the thyroid, we recommend following patients with annual thyroid scans and serum thyroglobulin levels. If there is any residual uptake detected in the neck or if the tumor extends beyond the thyroid, we recommend routine thyroid ablation of 100-150 mCi of radioactive 131I.

Twenty-five years after Chernobyl: outcome of radioiodine treatment in children and adolescents with very high-risk radiation-induced differentiated thyroid carcinoma.

PubMed

Reiners, Christoph; Biko, Johannes; Haenscheid, Heribert; Hebestreit, Helge; Kirinjuk, Stalina; Baranowski, Oleg; Marlowe, Robert J; Demidchik, Ewgeni; Drozd, Valentina; Demidchik, Yuri

2013-07-01

After severe reactor emergencies with release of radioactive iodine, elevated thyroid cancer risk in children and adolescents is considered the main health consequence for the population exposed. We studied thyroid cancer outcome after 11.3 years' median follow-up in a selected, very high-risk cohort, 234 Chernobyl-exposed Belarusian children and adolescents undergoing postsurgical radioiodine therapy (RIT) in Germany. Cumulatively 100 children with or (without; n = 134) distant metastasis received a median 4 (2) RITs and 16.9 (6.6) GBq, corresponding to 368 (141) MBq/kg iodine-131. Outcomes were response to therapy and disease status, mortality, and treatment toxicity. Of 229 patients evaluable for outcome, 147 (64.2%) attained complete remission [negative iodine-131 whole-body scan and TSH-stimulated serum thyroglobulin (Tg) < 1 μg /L], 69 (30.1%) showed nearly complete remission (complete response, except stimulated Tg 1-10 μg/L), and 11 (4.8%) had partial remission (Tg > 10 μg/L, decrease from baseline in radioiodine uptake intensity in ≥ 1 focus, in tumor volume or in Tg). Except for 2 recurrences (0.9%) after partial remission, no recurrences, progression, or disease-specific mortality were noted. One patient died of lung fibrosis 17.5 years after therapy, 2 of apparently thyroid cancer-unrelated causes. The only RIT side effect observed was pulmonary fibrosis in 5 of 69 patients (7.2%) with disseminated lung metastases undergoing intensive pulmonary surveillance. Experience of a large, very high-risk pediatric cohort with radiation-induced differentiated thyroid carcinoma suggests that even when such disease is advanced and initially suboptimally treated, response to subsequent RIT and final outcomes are mostly favorable.

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

BRAFV600E mutation is highly prevalent in thyroid carcinomas in the young population in Fukushima: a different oncogenic profile from Chernobyl

PubMed Central

Mitsutake, Norisato; Fukushima, Toshihiko; Matsuse, Michiko; Rogounovitch, Tatiana; Saenko, Vladimir; Uchino, Shinya; Ito, Masahiro; Suzuki, Keiji; Suzuki, Shinichi; Yamashita, Shunichi

2015-01-01

After the accident at the Fukushima Daiichi Nuclear Power Plant, the thyroid ultrasound screening program for children aged 0–18 at the time of the accident was started from October 2011. The prevalence of thyroid carcinomas in that population has appeared to be very high (84 cases per 296,253). To clarify the pathogenesis, we investigated the presence of driver mutations in these tumours. 61 classic papillary thyroid carcinomas (PTCs), two follicular variant PTCs, four cribriform-morular variant PTCs and one poorly-differentiated thyroid carcinoma were analysed. We detected BRAFV600E in 43 cases (63.2%), RET/PTC1 in six (8.8%), RET/PTC3 in one (1.5%) and ETV6/NTRK3 in four (5.9%). Among classic and follicular variant PTCs, BRAFV600E was significantly associated with the smaller size. The genetic pattern was completely different from post-Chernobyl PTCs, suggesting non-radiogenic etiology of these cancers. This is the first study demonstrating the oncogene profile in the thyroid cancers discovered by large mass screening, which probably reflects genetic status of all sporadic and latent tumours in the young Japanese population. It is assumed that BRAFV600E may not confer growth advantage on paediatric PTCs, and many of these cases grow slowly, suggesting that additional factors may be important for tumour progression in paediatric PTCs. PMID:26584635

[Intracellular signaling mechanisms in thyroid cancer].

PubMed

Mondragón-Terán, Paul; López-Hernández, Luz Berenice; Gutiérrez-Salinas, José; Suárez-Cuenca, Juan Antonio; Luna-Ceballos, Rosa Isela; Erazo Valle-Solís, Aura

2016-01-01

Thyroid cancer is the most common malignancy of the endocrine system, the papillary variant accounts for 80-90% of all diagnosed cases. In the development of papillary thyroid cancer, BRAF and RAS genes are mainly affected, resulting in a modification of the system of intracellular signaling proteins known as «protein kinase mitogen-activated» (MAPK) which consist of «modules» of internal signaling proteins (Receptor/Ras/Raf/MEK/ERK) from the cell membrane to the nucleus. In thyroid cancer, these signanling proteins regulate diverse cellular processes such as differentiation, growth, development and apoptosis. MAPK play an important role in the pathogenesis of thyroid cancer as they are used as molecular biomarkers for diagnostic, prognostic and as possible therapeutic molecular targets. Mutations in BRAF gene have been correlated with poor response to treatment with traditional chemotherapy and as an indicator of poor prognosis. To review the molecular mechanisms involved in intracellular signaling of BRAF and RAS genes in thyroid cancer. Molecular therapy research is in progress for this type of cancer as new molecules have been developed in order to inhibit any of the components of the signaling pathway (RET/PTC)/Ras/Raf/MEK/ERK; with special emphasis on the (RET/PTC)/Ras/Raf section, which is a major effector of ERK pathway. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

The transcriptional repressor DREAM is involved in thyroid gene expression

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

D'Andrea, Barbara; Di Palma, Tina; Mascia, Anna

2005-04-15

Downstream regulatory element antagonistic modulator (DREAM) was originally identified in neuroendocrine cells as a calcium-binding protein that specifically binds to downstream regulatory elements (DRE) on DNA, and represses transcription of its target genes. To explore the possibility that DREAM may regulate the endocrine activity of the thyroid gland, we analyzed its mRNA expression in undifferentiated and differentiated thyroid cells. We demonstrated that DREAM is expressed in the normal thyroid tissue as well as in differentiated thyroid cells in culture while it is absent in FRT poorly differentiated cells. In the present work, we also show that DREAM specifically binds tomore » DRE sites identified in the 5' untranslated region (UTR) of the thyroid-specific transcription factors Pax8 and TTF-2/FoxE1 in a calcium-dependent manner. By gel retardation assays we demonstrated that thapsigargin treatment increases the binding of DREAM to the DRE sequences present in Pax8 and TTF-2/Foxe1 5' UTRs, and this correlates with a significant reduction of the expression of these genes. Interestingly, in poorly differentiated thyroid cells overexpression of exogenous DREAM strongly inhibits Pax8 expression. Moreover, we provide evidence that a mutated form of DREAM unable to bind Ca{sup 2+} interferes with thyroid cell proliferation. Therefore, we propose that in thyroid cells DREAM is a mediator of the calcium-signaling pathway and it is involved in the regulation of thyroid cell function.« less

Primary mucinous carcinoma of thyroid gland with prominent signet-ring-cell differentiation: a case report and review of the literature.

PubMed

Wang, Jian; Guli, Qie-Re; Ming, Xiao-Cui; Zhou, Hai-Tao; Cui, Yong-Jie; Jiang, Yue-Feng; Zhang, Di; Liu, Yang

2018-01-01

This study reports a case of primary mucinous carcinoma of the thyroid gland with signet-ring-cell differentiation, and reviews the literature to evaluate its real incidence and the prognosis of these patients. A 74-year-old Chinese woman, presenting with a mass in the right lobe of thyroid gland, came to the hospital. Computed tomography revealed a mass in the right lobe of the thyroid gland, accompanied with right neck lymphadenectasis and airway deviation caused by tumor compression. Thyroid imaging suggested a thyroid malignant tumor and suspicious lymph node metastasis. Histologically, the tumor was characterized by the tumor cells arranged in small nests or trabeculae with an abundant extracellular mucoid matrix. The tumor cells formed diffuse invasion among thyroid follicles. In the peripheral regions, prominent signet-ring-cells formed a sheet-like structure and extended into the extrathyroidal fat tissue. The tumor cells were diffusely positive for thyroid transcription factor-1 (TTF-1) and PAX8, while they were focally positive for pan-cytokeratin (AE1/AE3) and weakly expressed thyroglobulin. Based on the histological features and immunohistochemical profile, a diagnosis of primary mucinous carcinoma of the thyroid gland with signet-ring-cell differentiation was rendered. Using a panel of immunohistochemical markers may be helpful for differential diagnosis and for determining whether the tumor is primary or not.

Metastatic thyroid carcinoma without identifiable primary tumor within the thyroid gland: a retrospective study of a rare phenomenon.

PubMed

Xu, Bin; Scognamiglio, Theresa; Cohen, Perry R; Prasad, Manju L; Hasanovic, Adnan; Tuttle, Robert Michael; Katabi, Nora; Ghossein, Ronald A

2017-07-01

Metastatic papillary thyroid carcinoma (PTC) without an identifiable primary tumor despite extensive microscopic examination of the thyroid gland is a rare but true phenomenon.We retrieved 7 of such cases and described in detail the clinical and pathologic features of these tumors. BRAF V600E immunohistochemistry and Sequenom molecular profile were conducted in selected cases. All patients harbored metastatic disease in the central (n=3), lateral (n=3), or both neck compartments (n=1). The histotype of the metastatic disease was PTC (n=5), poorly differentiated thyroid carcinoma in association with a PTC columnar variant (n=1), and anaplastic thyroid carcinoma in association with a PTC tall cell variant (n=1). Fibrosis was present in the thyroid of 5 patients. All patients with PTC were alive without evidence of recurrence. The 76-year-old patient with poorly differentiated thyroid carcinoma did not recur and died of unknown causes. Finally, the patient with anaplastic thyroid carcinoma was alive with distant metastasis at last follow-up. The median follow-up for this cohort was 2.2years (range, 0.8-17). BRAF V600E was detected in 4 of 6 cases by immunohistochemistry. In conclusion, metastatic nodal disease without identifiable thyroid primary is a rare but real phenomenon of unknown mechanisms. Although most tumors are low grade and well differentiated, aggressive behavior due to poorly differentiated or anaplastic carcinoma can happen. Most cases are BRAF V600E -positive thyroid tumors. A papillary carcinoma phenotype is found in all reported cases. Copyright © 2017 Elsevier Inc. All rights reserved.

Flow cytometry in the differential diagnostics of Hashimoto's thyroiditis and MALT lymphoma of the thyroid.

PubMed

Adamczewski, Zbigniew; Stasiołek, Mariusz; Dedecjus, Marek; Smolewski, Piotr; Lewiński, Andrzej

2015-01-01

A combination of traditional cytology methods with fluorescence activated cell sorting (FACS) analysis of fine-needle aspiration biopsy (FNAB) material is considered a powerful diagnostic tool in the differential diagnosis of thyroid lesions suspected of mucosa-associated lymphoid tissue lymphoma (MALT-L). The aim of this study was to demonstrate the FACS-based diagnostic process of thyroid lesions in a clinical situation where ultrasound and cytological examinations did not allow differentiation between Hashimoto's thyroiditis (HT) and MALT-L. The patients analysed in this study presented significantly different clinical courses of thyroid disease: quickly enlarging painless tumour of the thyroid right lobe in the first case, and chronic HT with palpable tumour in the thyroid isthmus in the second patient. Due to the suspicion of MALT-L resulting from indeterminate ultrasound and FNAB-cytology results, FNAB material was obtained from all the previously examined thyroid lesions and directly subjected to FACS assessment, encompassing κ/λ light chain restriction analysis, as well as measurements of B and T cell surface antigens. The FACS analysis of FNAB material obtained from our patients did not show any definite signs of light chain restriction. Although one of the samples showed a borderline value of κ/λ ratio (κ/λ = 0.31), further immunophenotyping confirmed clonal expansion in none of the examined thyroid regions. Histopathological findings documented the diagnosis of HT in both clinical cases. We believe that FACS represents a useful and reliable complementary diagnostic measure in FNAB-based differential diagnosis of lymphoproliferative thyroid disorders.

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

Gao, Xuemei; Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, Hubei Province; Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province

Thyroid cancer is a common malignancy of the endocrine system. Although radioiodine {sup 131}I treatment on differentiated thyroid cancer is widely used, many patients still fail to benefit from {sup 131}I therapy. Therefore, exploration of novel targeted therapies to suppress tumor growth and improve radioiodine uptake remains necessary. Bromodomain-containing protein 4 (BRD4) is an important member of the bromodomain and extra terminal domain family that influences transcription of downstream genes by binding to acetylated histones. In the present study, we found that BRD4 was up-regulated in thyroid cancer tissues and cell lines. Inhibition of BRD4 in thyroid cancer cells bymore » JQ1 resulted in cell cycle arrest at G0/G1 phase and enhanced {sup 131}I uptake in vitro and suppressed tumor growth in vivo. Moreover, JQ1 treatment suppressed C-MYC but enhanced NIS expression. We further demonstrated that BRD4 was enriched in the promoter region of C-MYC, which could be markedly blocked by JQ1 treatment. In conclusion, our findings revealed that the aberrant expression of BRD4 in thyroid cancer is possibly involved in tumor progression, and JQ1 is potentially an effective chemotherapeutic agent against human thyroid cancer. - Highlights: • BRD4 is upregulated in thyroid cancer tissues and cell lines. • Inhibition of BRD4 induced cell cycle arrest and enhanced radioiodine uptake in vitro and impaired tumor growth in vivo. • JQ1 suppressed the expression of C-MYC and promoted the expression of NIS and P21. • JQ1 attenuated the recruitment of BRD4 to MYC promoter in thyroid cancer.« less

Differential expression of galectin-1 and galectin-3 in thyroid tumors. Potential diagnostic implications.

PubMed Central

Xu, X. C.; el-Naggar, A. K.; Lotan, R.

1995-01-01

Carcinoma of the thyroid gland, the most frequently diagnosed endocrine malignancy, is often associated with early regional metastases. With the exception of papillary carcinoma, distinguishing benign from malignant thyroid neoplasms in the absence of metastatic disease is difficult. Recently, the vertebrate lectins galectin-1 and galectin-3 have been implicated in the regulation of cellular growth, differentiation, and malignant transformation of a variety of tissues. To determine whether these galectins have a role in thyroid neoplasia, we analyzed 32 specimens from thyroid malignancies (16 papillary, 7 follicular, 8 medullary carcinomas, and 1 metastasis to lymph node), 10 benign thyroid adenomas, 1 nodular goiter, and 33 specimens from adjacent normal thyroid tissue for the expression of galectin-1 and galectin-3 with immunohistochemical and immunoblotting techniques utilizing anti-galectin antibodies. All thyroid malignancies of epithelial origin (ie, papillary and follicular carcinomas) and a metastatic lymph node from a papillary carcinoma expressed high levels of both galectin-1 and galectin-3. The medullary thyroid carcinomas, which are of parafollicular C cell origin, showed a weaker and variable expression of these galectins. In contrast, neither benign thyroid adenomas nor adjacent normal thyroid tissue expressed galectin-1 or galectin-3. These results suggest that galectin-1 and galectin-3 may be associated with malignant transformation of thyroid epithelium and may potentially serve as markers for distinguishing benign thyroid adenomas from differentiated thyroid carcinomas. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:7677193

Shear Wave Elastography May Add a New Dimension to Ultrasound Evaluation of Thyroid Nodules: Case Series with Comparative Evaluation

PubMed Central

Slapa, Rafal Z.; Piwowonski, Antoni; Jakubowski, Wieslaw S.; Bierca, Jacek; Szopinski, Kazimierz T.; Slowinska-Srzednicka, Jadwiga; Migda, Bartosz; Mlosek, R. Krzysztof

2012-01-01

Although elastography can enhance the differential diagnosis of thyroid nodules, its diagnostic performance is not ideal at present. Further improvements in the technique and creation of robust diagnostic criteria are necessary. The purpose of this study was to compare the usefulness of strain elastography and a new generation of elasticity imaging called supersonic shear wave elastography (SSWE) in differential evaluation of thyroid nodules. Six thyroid nodules in 4 patients were studied. SSWE yielded 1 true-positive and 5 true-negative results. Strain elastography yielded 5 false-positive results and 1 false-negative result. A novel finding appreciated with SSWE, were punctate foci of increased stiffness corresponding to microcalcifications in 4 nodules, some not visible on B-mode ultrasound, as opposed to soft, colloid-inspissated areas visible on B-mode ultrasound in 2 nodules. This preliminary paper indicates that SSWE may outperform strain elastography in differentiation of thyroid nodules with regard to their stiffness. SSWE showed the possibility of differentiation of high echogenic foci into microcalcifications and inspissated colloid, adding a new dimension to thyroid elastography. Further multicenter large-scale studies of thyroid nodules evaluating different elastographic methods are warranted. PMID:22685685

NF-κB Essential Modulator (NEMO) Is Critical for Thyroid Function.

PubMed

Reale, Carla; Iervolino, Anna; Scudiero, Ivan; Ferravante, Angela; D'Andrea, Luca Egildo; Mazzone, Pellegrino; Zotti, Tiziana; Leonardi, Antonio; Roberto, Luca; Zannini, Mariastella; de Cristofaro, Tiziana; Shanmugakonar, Muralitharan; Capasso, Giovambattista; Pasparakis, Manolis; Vito, Pasquale; Stilo, Romania

2016-03-11

The I-κB kinase (IKK) subunit NEMO/IKKγ (NEMO) is an adapter molecule that is critical for canonical activation of NF-κB, a pleiotropic transcription factor controlling immunity, differentiation, cell growth, tumorigenesis, and apoptosis. To explore the functional role of canonical NF-κB signaling in thyroid gland differentiation and function, we have generated a murine strain bearing a genetic deletion of the NEMO locus in thyroid. Here we show that thyrocyte-specific NEMO knock-out mice gradually develop hypothyroidism after birth, which leads to reduced body weight and shortened life span. Histological and molecular analysis indicate that absence of NEMO in thyrocytes results in a dramatic loss of the thyroid gland cellularity, associated with down-regulation of thyroid differentiation markers and ongoing apoptosis. Thus, NEMO-dependent signaling is essential for normal thyroid physiology. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

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.

A Multiinstitutional Phase 2 Trial of Pazopanib Monotherapy in Advanced Anaplastic Thyroid Cancer

PubMed Central

Suman, Vera J.; Menefee, Michael E.; Smallridge, Robert C.; Molina, Julian R.; Maples, William J.; Karlin, Nina J.; Traynor, Anne M.; Kumar, Priya; Goh, Boon Cher; Lim, Wan-Teck; Bossou, Ayoko R.; Isham, Crescent R.; Webster, Kevin P.; Kukla, Andrea K.; Bieber, Carolyn; Burton, Jill K.; Harris, Pamela; Erlichman, Charles

2012-01-01

Context/Objectives: Pazopanib, an inhibitor of kinases including vascular endothelial growth factor receptor, demonstrated impressive activity in progressive metastatic differentiated thyroid cancer, prompting its evaluation in anaplastic thyroid cancer (ATC). Design/Setting/Patients/Interventions/Outcome Measures: Preclinical studies, followed by a multicenter single arm phase 2 trial of continuously administered 800 mg pazopanib daily by mouth (designed to provide 90% chance of detecting a response rate of >20% at the 0.10 significance level when the true response rate is >5%), were undertaken. The primary trial end point was Response Evaluation Criteria in Solid Tumors (RECIST) response. Results: Pazopanib displayed activity in the KTC2 ATC xenograft model, prompting clinical evaluation. Sixteen trial patients were enrolled; 15 were treated: 66.7% were female, median age was 66 yr (range 45–77 yr), and 11 of 15 had progressed through prior systemic therapy. Enrollment was halted, triggered by a stopping rule requiring more than one confirmed RECIST response among the first 14 of 33 potential patients. Four patients required one to two dose reductions; severe toxicities (National Cancer Institute Common Toxicity Criteria-Adverse Events version 3.0 grades >3) were hypertension (13%) and pharyngolaryngeal pain (13%). Treatment was discontinued because of the following: disease progression (12 patients), death due to a possibly treatment-related tumor hemorrhage (one patient), and intolerability (radiation recall tracheitis and uncontrolled hypertension, one patient each). Although transient disease regression was observed in several patients, there were no confirmed RECIST responses. Median time to progression was 62 d; median survival time was 111 d. Two patients are alive with disease 9.9 and 35 months after the registration; 13 died of disease. Conclusions: Despite preclinical in vivo activity in ATC, pazopanib has minimal single-agent clinical activity in advanced ATC. PMID:22774206

[Thyroid carcinoma--differentiated, poorly differentiated and anaplastic carcinoma].

PubMed

Kakudo, Kennichi; Bai, Yanhua; Li, Yaqiong; Wakasa, Tomoko; Mori, Ichiro

2007-11-01

The poorly differentiated carcinoma was first added as a new member in the lists of classification of thyroid carcinomas in the WHO 2004 edition. However its histological criteria include necrosis and increased mitoses in addition to the original definition by Sakamoto's proposal, solid, trabecular and schirrhous growth. This modification creates a significant change in the incidence and prognosis of this carcinoma. This carcinoma, defined by the new WHO classification, is about 1-5% of all thyroid malignancy and has more aggressive outcome than the previous definition.

Molecular markers in well-differentiated thyroid cancer.

PubMed

D'Cruz, Anil K; Vaish, Richa; Vaidya, Abhishek; Nixon, Iain J; Williams, Michelle D; Vander Poorten, Vincent; López, Fernando; Angelos, Peter; Shaha, Ashok R; Khafif, Avi; Skalova, Alena; Rinaldo, Alessandra; Hunt, Jennifer L; Ferlito, Alfio

2018-06-01

Thyroid nodules are of common occurrence in the general population. About a fourth of these nodules are indeterminate on aspiration cytology placing many a patient at risk of unwanted surgery. The purpose of this review is to discuss various molecular markers described to date and place their role in proper perspective. This review covers the fundamental role of the signaling pathways and genetic changes involved in thyroid carcinogenesis. The current literature on the prognostic significance of these markers is also described. PubMed was used to search relevant articles. The key terms "thyroid nodules", "thyroid cancer papillary", "carcinoma papillary follicular", "carcinoma papillary", "adenocarcinoma follicular" were searched in MeSH, and "molecular markers", "molecular testing", mutation, BRAF, RAS, RET/PTC, PAX 8, miRNA, NIFTP in title and abstract fields. Multiple combinations were done and a group of experts in the subject from the International Head and Neck Scientific Group extracted the relevant articles and formulated the review. There has been considerable progress in the understanding of thyroid carcinogenesis and the emergence of numerous molecular markers in the recent years with potential to be used in the diagnostic algorithm of these nodules. However, their precise role in routine clinical practice continues to be a contentious issue. Majority of the studies in this context are retrospective and impact of these mutations is not independent of other prognostic factors making the interpretation difficult. The prevalence of these mutations in thyroid nodule is high and it is a continuously evolving field. Clinicians should stay informed as recommendation on the use of these markers is expected to evolve.

BRAF(V600E) mutation is highly prevalent in thyroid carcinomas in the young population in Fukushima: a different oncogenic profile from Chernobyl.

PubMed

Mitsutake, Norisato; Fukushima, Toshihiko; Matsuse, Michiko; Rogounovitch, Tatiana; Saenko, Vladimir; Uchino, Shinya; Ito, Masahiro; Suzuki, Keiji; Suzuki, Shinichi; Yamashita, Shunichi

2015-11-20

After the accident at the Fukushima Daiichi Nuclear Power Plant, the thyroid ultrasound screening program for children aged 0-18 at the time of the accident was started from October 2011. The prevalence of thyroid carcinomas in that population has appeared to be very high (84 cases per 296,253). To clarify the pathogenesis, we investigated the presence of driver mutations in these tumours. 61 classic papillary thyroid carcinomas (PTCs), two follicular variant PTCs, four cribriform-morular variant PTCs and one poorly-differentiated thyroid carcinoma were analysed. We detected BRAF(V600E) in 43 cases (63.2%), RET/PTC1 in six (8.8%), RET/PTC3 in one (1.5%) and ETV6/NTRK3 in four (5.9%). Among classic and follicular variant PTCs, BRAF(V600E) was significantly associated with the smaller size. The genetic pattern was completely different from post-Chernobyl PTCs, suggesting non-radiogenic etiology of these cancers. This is the first study demonstrating the oncogene profile in the thyroid cancers discovered by large mass screening, which probably reflects genetic status of all sporadic and latent tumours in the young Japanese population. It is assumed that BRAF(V600E) may not confer growth advantage on paediatric PTCs, and many of these cases grow slowly, suggesting that additional factors may be important for tumour progression in paediatric PTCs.

Thyroid cancer: what to do after fine needle aspiration.

PubMed

Rometo, David A; Baranski, Thomas J

2011-01-01

The incidence of differentiated thyroid cancer (including papillary, follicular, and Hurthle cell carcinoma) has nearly tripled in the past 20 years. Diagnosis, treatment, and long-term management are evolving with advances in radiology, surgical techniques, nuclear medicine, genetics, and targeted therapeutics. Here we detail the current recommended course of action for differentiated thyroid cancer and options on the horizon.

Thyroid Ultrasonography in Differentiation between Graves' Disease and Hashimoto's Thyroiditis.

PubMed

Pishdad, P; Pishdad, G R; Tavanaa, S; Pishdad, R; Jalli, R

2017-03-01

Graves' disease and Hashimoto's thyroiditis are the most common causes of hyper and hypothyroidism, respectively. Differentiation of these 2 diseases, if the patient is euthyroid, may sometimes be extremely difficult on the basis of clinical and laboratory findings. The purpose of this study was to determine the sensitivity and specificity of gray scale sonography in differentiation of Graves' disease from Hashimoto's thyroiditis. This study included 149 patients divided into three groups, patients with Graves' disease (34 patients, mean age = 36.8 ± 10.17 years), Patients with Hashimoto's thyroiditis (62 patients, mean age = 33.4 ± 12.16 years) and control group (53 healthy people, mean age = 34.74 ± 16.87 years). Members of all groups were referred to a single radiologist for thyroid sonography for evaluation of thyroid echogenicity pattern. A total of 117 women and 32 men were examined by sonography. The most common sonographic pattern in Hashimoto and Graves' was homogenous hypo-echogenicity which was observed in 45.2% and 47.1% of cases, respectively. Peripheral hypo-echogenicity pattern was seen in 40.3% of Hashimoto's group with 100% specificity and 40.3% sensitivity. Central-hypoechogenic pattern was observed in 17.6% of Graves' group with 100% and 17.6% specificity and sensitivity, respectively. Our findings indicate that sonography has high specificity but low sensitivity in the diagnosis of either Graves' disease or Hashimoto's thyroiditis. It is therefore not possible to differentiate between these two diseases using sonography alone. Confirmation by laboratory data is also needed.

Ultrasound sonoelastography in the evaluation of thyroiditis and autoimmune thyroid disease.

PubMed

Ruchała, Marek; Szmyt, Krzysztof; Sławek, Sylwia; Zybek, Ariadna; Szczepanek-Parulska, Ewelina

2014-01-01

Sonoelastography (USE) is a constantly evolving imaging technique used for the noninvasive and objective estimation of tissue stiffness. Several USE methods have been developed, including Quasi-Static or Strain Elastography and Shear Wave Elastography. The utility of USE has been demonstrated in differentiating between malignant and benign thyroid lesions. Recently, USE has been applied in the evaluation of thyroiditis and autoimmune thyroid disease (AITD).Thyroid inflammatory illnesses constitute a diverse group of diseases and may manifest various symptoms. These conditions may share some parallel clinical, biochemical, and ultrasonographic features, which can lead to diagnostic difficulties. USE may be an additional tool, supporting other methods in the diagnosis and treatment monitoring of thyroid diseases, other than thyroid nodular disease.The aim of this article was to analyse and summarise the available literature on the applicability of different elastographic techniques in the diagnosis, differentiation and monitoring of various types of thyroiditis and AITD. Advantages and limitations of this technique are also discussed.

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

Quantitative evaluation of contrast-enhanced ultrasound after intravenous administration of a microbubble contrast agent for differentiation of benign and malignant thyroid nodules: assessment of diagnostic accuracy.

PubMed

Nemec, Ursula; Nemec, Stefan F; Novotny, Clemens; Weber, Michael; Czerny, Christian; Krestan, Christian R

2012-06-01

To investigate the diagnostic accuracy, through quantitative analysis, of contrast-enhanced ultrasound (CEUS), using a microbubble contrast agent, in the differentiation of thyroid nodules. This prospective study enrolled 46 patients with solitary, scintigraphically non-functional thyroid nodules. These patients were scheduled for surgery and underwent preoperative CEUS with pulse-inversion harmonic imaging after intravenous microbubble contrast medium administration. Using histology as a standard of reference, time-intensity curves of benign and malignant nodules were compared by means of peak enhancement and wash-out enhancement relative to the baseline intensity using a mixed model ANOVA. ROC analysis was performed to assess the diagnostic accuracy in the differentiation of benign and malignant nodules on CEUS. The complete CEUS data of 42 patients (31/42 [73.8%] benign and 11/42 [26.2%] malignant nodules) revealed a significant difference (P < 0.001) in enhancement between benign and malignant nodules. Furthermore, based on ROC analysis, CEUS demonstrated sensitivity of 76.9%, specificity of 84.8% and accuracy of 82.6%. Quantitative analysis of CEUS using a microbubble contrast agent allows the differentiation of benign and malignant thyroid nodules and may potentially serve, in addition to grey-scale and Doppler ultrasound, as an adjunctive tool in the assessment of patients with thyroid nodules. • Contrast-enhanced ultrasound (CEUS) helps differentiate between benign and malignant thyroid nodules. • Quantitative CEUS analysis yields sensitivity of 76.9% and specificity of 84.8%. • CEUS may be a potentially useful adjunct in assessing thyroid nodules.

Differentiated and Medullary Thyroid Cancer: Surgical Management of Cervical Lymph Nodes

PubMed Central

Asimakopoulos, P.; Nixon, I.J.; Shaha, A.R.

2017-01-01

Thyroid cancer metastasises to the central and lateral compartments of the neck frequently and early. The impact of nodal metastases on outcome is affected by the histological subtype of the primary tumour and the patient’s age, as well as the size, number and location of those metastases. The impact of extranodal extension has recently been highlighted as an important prognosticating factor. Although clinically evident nodal disease in the lateral neck compartments has a significant impact on both survival and recurrence, microscopic metastases to the central or the lateral neck in well-differentiated thyroid cancer do not significantly affect outcome. Here we discuss the surgical management of neck metastases in well-differentiated and medullary thyroid carcinoma. PMID:28094086

Hyperthyroidism

PubMed Central

Whitner, Tanya E.; Hudson, Christopher J.; Smith, Timothy D.; Littmann, Laszlo

2005-01-01

Although hyperthyroidism has many signs and symptoms, right heart failure can occasionally be the main presenting symptom. We describe the case of a previously healthy 42-year-old woman whose chief complaint was progressive bilateral lower extremity edema. The echocardiogram revealed right atrial dilatation and moderate-to-severe tricuspid regurgitation. Results of laboratory studies were consistent with hyperthyroidism. Thyroid ablation resulted in permanent resolution of symptoms and resolution of tricuspid incompetence on echocardiography. In a case of isolated, unexplained tricuspid regurgitation, it is important to consider indolent hyperthyroidism in the differential diagnosis. PMID:16107128

Serum human chorionic gonadotropin levels and thyroid hormone levels in gestational transient thyrotoxicosis: Is the serum hCG level useful for differentiating between active Graves' disease and GTT?

PubMed

Yoshihara, Ai; Noh, Jaeduk Yoshimura; Mukasa, Koji; Suzuki, Miho; Ohye, Hidemi; Matsumoto, Masako; Kunii, Yo; Watanabe, Natsuko; Suzuki, Nami; Kameda, Toshiaki; Sugino, Kiminori; Ito, Koichi

2015-01-01

Gestational transient thyrotoxicosis (GTT) is defined as transient thyrotoxicosis caused by the stimulating effect of human chorionic gonadotropin (hCG) during pregnancy. We attempted to identify the serum hCG level that causes GTT, and we compared the serum hCG levels and thyroid hormone levels of GTT patients according to whether they had a background of thyroid disease. We also evaluated serum hCG as a parameter for differentiating between active Graves' disease (GD) and GTT. We reviewed the 135 cases of pregnant women who came to our hospital to be evaluated for thyrotoxicosis during their 7th to 14th week of pregnancy, and their serum hCG level was measured at that time. Among the 135 pregnant women with thyrotoxicosis; 103 of the women had GTT, and the other 32 women had active GD. There were no correlations between their serum hCG levels and free thyroid hormone levels. There were no significant differences in thyroid hormone levels or hCG levels among the GTT groups with different thyroid disease backgrounds; i.e., the GTT group without thyroid disease, GTT group with chronic thyroiditis, GTT group with non-functioning thyroid nodules, and GTT group with GD in remission. The serum hCG level of the GTT group was significantly higher than in the active GD group, but it was not a good parameter for differentiating between the two groups. The FT3/FT4 ratio of the active GD was significantly higher than in GTT group, and was a better parameter for differentiation.

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

The Interaction Between Thyroid and Kidney Disease: An Overview of the Evidence

PubMed Central

Rhee, Connie M.

2016-01-01

Purpose of Review Hypothyroidism is highly prevalent in chronic kidney disease (CKD) patients, including those receiving dialysis. This review examines potential mechanistic links between thyroid and kidney disease; current evidence for hypothyroidism as a risk factor for de novo CKD and CKD progression; and studies of thyroid functional disorders, cardiovascular disease, and death in the CKD population. Recent Findings Epidemiologic data have demonstrated an incrementally higher prevalence of hypothyroidism with increasing severity of kidney dysfunction. Various thyroid functional test abnormalities are also commonly observed in CKD, due to alterations in thyroid hormone synthesis, metabolism, and regulation. While the mechanistic link between thyroid and kidney disease remains unclear, observational studies suggest hypothyroidism is associated with abnormal kidney structure and function. Previously thought to be a physiologic adaptation, recent studies show that hypothyroidism is associated with higher risk of cardiovascular disease and death in CKD. Summary A growing body of evidence suggests that hypothyroidism is a risk factor for incident CKD, CKD progression, and higher death risk in kidney disease patients. Rigorous studies are needed to determine impact of thyroid hormone replacement upon kidney disease progression, cardiovascular disease, and mortality, which may shed light into the causal implications of hypothyroidism in CKD. PMID:27428519

Functional insulin receptors are overexpressed in thyroid tumors: is this an early event in thyroid tumorigenesis?

PubMed

Frittitta, L; Sciacca, L; Catalfamo, R; Ippolito, A; Gangemi, P; Pezzino, V; Filetti, S; Vigneri, R

1999-01-15

Insulin receptor (IR), a member of the receptor tyrosine kinase family, is expressed in normal thyroid cells and affects thyroid cell proliferation and differentiation. The authors measured IR content in benign and malignant thyroid tumors by three independent methods: a specific radioimmunoassay, 125I-insulin binding studies, and immunohistochemistry. The results obtained were compared with the IR content in paired, adjacent, normal thyroid tissue. To assess IR function in thyroid carcinoma cells, glucose uptake responsiveness to insulin was also studied in a human transformed thyroid cell line (B-CPAP) and in follicular carcinoma cells in primary culture. In 9 toxic adenomas, the average IR content was similar to that observed in the 9 paired normal thyroid tissue specimens from the same patients (2.2+/-0.3 vs. 2.1+/-0.3). In 13 benign nonfunctioning, or "cold," adenomas, the average IR content was significantly higher (P < 0.001) than in paired normal tissue specimens (4.3+/-0.5 vs. 1.8+/-0.1). In 12 papillary and 10 follicular carcinomas, IR content was significantly higher (P < 0.001) than in the adjacent normal thyroid tissue (4.0+/-0.4 vs. 1.6+/-0.2 and 5.6+/-1.0 vs. 1.8+/-0.2, respectively). The finding of a higher IR content in benign "cold" adenomas and in thyroid carcinomas was confirmed by both binding and immunostaining studies. The current studies indicate that 1) IR content is elevated in most follicular and papillary differentiated thyroid carcinomas, and 2) IR content is also elevated in most benign follicular adenomas ("cold" nodules) but not in highly differentiated, hyperfunctioning follicular adenomas ("hot" nodules), which very rarely become malignant. This observation suggests that increased IR expression is not restricted to the thyroid malignant phenotype but is already present in the premalignant "cold" adenomas. It may contribute, therefore, to thyroid tumorigenesis and/or represent an early event that gives a selective growth advantage to transformed thyroid cells.

Hexamethylenebisacetamide (HMBA) is a growth factor for human, ovine and porcine thyroid cells.

PubMed

Fayet, G; Amphoux-Fazekas, T; Aouani, A; Hovsépian, S

1996-03-01

Hexamethylenebisacetamide (HMBA) provokes in murine erythroleukemia cells (MELC) a commitment to terminal differentiation leading to the activation of the expression of hemoglobin. HMBA has been tested also in other cells from colon cancer, melanoma or lung cancer. However it has not yet been tested in the thyroid. We demonstrate in this paper that HMBA in kinetics and concentration-response experiments increases the proliferation of human thyroid cells isolated from Graves'-Basedow patients. It also acts like a growth factor for ovine and porcine thyroid cells, respectively, from the OVNIS line and the ATHOS line. This molecule which is a differentiating factor in the MELC system and a growth factor in human thyroid cell cultures represents a potential to get human thyroid cell lines expressing specialized functions.

The Role of Radiopharmaceuticals in Amiodarone-Induced Thyroid Pathology.

PubMed

Irimie, Alexandru; Piciu, Doina

2017-11-10

The use of amiodarone for the treatment of ventricular and supraventricular dysrhythmias brings in organism an increased amount of iodine, interfering with thyroid function. If the treatment needs to be interrupted, iodine remains at abnormal levels for months or even years. The aim of the study was to review the literature regarding the optimal tests for early diagnostic and to analyze the role of nuclear medicine tests in the differential and correct assessment of the amiodarone-induced thyroid pathology. We made a review of available publications in PUBMED referring the amiodaroneinduced thyroid pathology, focusing on the differential diagnosis, made by nuclear medicine tests, of hypothyroidism (AIH) and hyperthyroidism expressed as: type I amiodarone induced thyrotoxicosis (AIT I), type II amiodarone induced thyrotoxicosis (AIT II), and less frequently as a mixt form, type III amiodarone induced thyrotoxicosis (AIT III). We presented cases from the database of a tertiary center in Cluj-Napoca, Romania. Despite the frequent complication of thyroid function, this pathology is underestimated and diagnosed. There is a limited number of studies and clear protocols, especially in the mixed forms cases. This increase in iodine uptake interferes seriously with thyroid hormone production and release. The nuclear medicine tests are essential in the correct assessment and differential diagnosis of different forms of induced thyroid dysfunction. The destruction of the follicular cells can result in the release of excessive thyroid hormone into the circulation, with potential development of atrial fibrillation, worsening the cardiac disease, so any benefic therapeutic procedure should be known; the use of radioiodine as therapy alternative, despite the known limitations induced by blockade was clear benefic in the case presented. A special attention needs to be addressed to those patients with differentiated thyroid cancer, which will be submitted to radioiodine therapy and are under chronic therapy with amiodarone. The nuclear medicine procedures are essential in the correct assessment and differential diagnosis of different forms of induced thyroid dysfunction. The radioiodine is not recommended in AIT, due to stunning effect induced by iodine excess, but in some special, lifethreatening condition, radioiodine I-131 might be a treatment option. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

Incidental nodal metastasis of differentiated thyroid carcinoma in neck dissection specimens from head and neck cancer patients.

PubMed

Lenzi, R; Marchetti, M; Muscatello, L

2017-04-01

Occult differentiated thyroid carcinomas are not uncommon. The initial presentation of a thyroid carcinoma is often detection of a metastatic cervical lymph node. A retrospective review was performed of the medical records of 304 patients who underwent neck dissection between 1996 and 2008 for squamous cell carcinoma of the head and neck. Ten patients (3.3 per cent) had nodal metastasis originating from papillary thyroid cancer. All of these patients underwent thyroidectomy and post-operative 131iodine radiometabolic therapy. No patient developed a thyroid tumour after surgery. Despite its metastatic spread, thyroid cancer does not affect the overall prognosis of patients who are already being treated for a more aggressive malignancy. However, in otherwise healthy patients, it is worth treating this second malignancy to avoid potential complications related to local disease or metastatic thyroid cancer.

Sorafenib in Japanese Patients with Locally Advanced or Metastatic Medullary Thyroid Carcinoma and Anaplastic Thyroid Carcinoma.

PubMed

Ito, Yasuhiro; Onoda, Naoyoshi; Ito, Ken-Ichi; Sugitani, Iwao; Takahashi, Shunji; Yamaguchi, Iku; Kabu, Koki; Tsukada, Katsuya

2017-09-01

Therapeutic options for treating advanced or metastatic medullary thyroid carcinoma (MTC) and anaplastic thyroid carcinoma (ATC) are still limited in Japan, even though vandetanib for MTC and lenvatinib for MTC and ATC have been approved. Sorafenib is an oral multikinase inhibitor approved for the treatment of patients with radioactive iodine-refractory differentiated thyroid cancer (DTC). An uncontrolled, open-label, multicenter, single-arm, Phase 2 clinical study was conducted to evaluate the safety and efficacy of sorafenib in Japanese patients with MTC and ATC. Japanese patients with histologically confirmed ATC and locally advanced or metastatic MTC were enrolled from April to September 2014. The primary endpoint was to evaluate the safety of sorafenib. Treatment efficacy variables including progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and maximum reduction in tumor size were evaluated as secondary endpoints. Patients received sorafenib 400 mg orally twice daily on a continuous basis and then continued treatment until the occurrence of disease progression, unacceptable toxicity, or withdrawal of consent. A total of 20 patients were screened, and 18 (8 with MTC and 10 with ATC) were enrolled. The most common drug-related adverse events were palmar-plantar erythrodysesthesia (72%), alopecia (56%), hypertension (56%), and diarrhea (44%). In the ATC patients, median PFS was 2.8 months [confidence interval 0.7-5.6], and median OS was 5.0 months [confidence interval 0.7-5.7]; ORR and DCR were 0% and 40%, respectively. In the MTC population, neither median PFS nor OS had been reached at the time of this analysis; ORR was 25% and DCR was 75%. The toxicities reported in this study were consistent with the known safety profile of sorafenib. Sorafenib seems to be effective in the treatment of advanced MTC but not ATC, and could be a new treatment option for locally advanced or metastatic MTC and radioactive iodine-refractory DTC.

Thyroid Ultrasonography in Differentiation between Graves’ Disease and Hashimoto’s Thyroiditis

PubMed Central

Pishdad, P.; Pishdad, G.R.; Tavanaa, S.; Pishdad, R.; Jalli, R.

2017-01-01

Objective: Graves’ disease and Hashimoto’s thyroiditis are the most common causes of hyper and hypothyroidism, respectively. Differentiation of these 2 diseases, if the patient is euthyroid, may sometimes be extremely difficult on the basis of clinical and laboratory findings. The purpose of this study was to determine the sensitivity and specificity of gray scale sonography in differentiation of Graves’ disease from Hashimoto’s thyroiditis. Methods: This study included 149 patients divided into three groups, patients with Graves’ disease (34 patients, mean age = 36.8 ± 10.17 years), Patients with Hashimoto’s thyroiditis (62 patients, mean age = 33.4 ± 12.16 years) and control group (53 healthy people, mean age = 34.74 ± 16.87 years). Members of all groups were referred to a single radiologist for thyroid sonography for evaluation of thyroid echogenicity pattern. Results: A total of 117 women and 32 men were examined by sonography. The most common sonographic pattern in Hashimoto and Graves’ was homogenous hypo-echogenicity which was observed in 45.2% and 47.1% of cases, respectively. Peripheral hypo-echogenicity pattern was seen in 40.3% of Hashimoto’s group with 100% specificity and 40.3% sensitivity. Central-hypoechogenic pattern was observed in 17.6% of Graves’ group with 100% and 17.6% specificity and sensitivity, respectively. Conclusion: Our findings indicate that sonography has high specificity but low sensitivity in the diagnosis of either Graves’ disease or Hashimoto’s thyroiditis. It is therefore not possible to differentiate between these two diseases using sonography alone. Confirmation by laboratory data is also needed. PMID:28451576

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.

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.

Selenoproteins in human body: focus on thyroid pathophysiology.

PubMed

Valea, Ana; Georgescu, Carmen Emanuela

2018-06-05

Selenium (Se) has a multilevel, complex and dynamic effect on the human body as a major component of selenocysteine, incorporated into selenoproteins, which include the selenocysteine-containing enzymes iodothyronine deiodinases. At the thyroid level, these proteins play an essential role in antioxidant protection and hormone metabolism. This is a narrative review based on PubMed/Medline database research regarding thyroid physiology and conditions with Se and Se-protein interferences. In humans, Se-dependent enzyme functions are best expressed through optimal Se intake, although there is gap in our knowledge concerning the precise mechanisms underlying the interrelation. There is a good level of evidence linking low serum Se to autoimmune thyroid diseases and, to a lesser extent, differentiated thyroid cancer. However, when it comes to routine supplementation, the results are heterogeneous, except in the case of mild Graves' orbitopathy. Autoimmune hypothyroidism is associated with a state of higher oxidative stress, but not all studies found an improvement of thyroid function after Se was introduced as antioxidant support. Meanwhile, no routine supplementation is recommended. Low Se intake is correlated with an increased risk of developing antithyroid antibodies, its supplementation decreasing their titres; there is also a potential reduction in levothyroxine replacement dose required for hypothyroidism and/or the possibility that it prevents progression of subclinical hypothyroidism, although not all studies agree. In thyroid-associated orbitopathy, euthyroidism is more rapidly achieved if the micronutrient is added to traditional drugs, while controls appear to benefit from the microelement only if they are deficient; thus, a basal assay of Se appears advisable to better select patients who need substitution. Clearly, further Se status biomarkers are required. Future introduction of individual supplementation algorithms based on baseline micronutrient levels, underlying or at-risk clinical conditions, and perhaps selenoprotein gene polymorphisms is envisaged.

Thyroid hormone receptor inhibits hepatoma cell migration through transcriptional activation of Dickkopf 4

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

Chi, Hsiang-Cheng; Liao, Chen-Hsin; Huang, Ya-Hui

Highlights: •T{sub 3} affects DKK4 mRNA and protein expression in HepG2-TR cells. •Regulation of DKK4 by T{sub 3} is at transcriptional level. •DKK4 overexpression suppresses hepatoma cell metastasis. -- Abstract: Triiodothyronine (T{sub 3}) is a potent form of thyroid hormone mediates several physiological processes including cellular growth, development, and differentiation via binding to the nuclear thyroid hormone receptor (TR). Recent studies have demonstrated critical roles of T{sub 3}/TR in tumor progression. Moreover, long-term hypothyroidism appears to be associated with the incidence of human hepatocellular carcinoma (HCC), independent of other major HCC risk factors. Dickkopf (DKK) 4, a secreted protein thatmore » antagonizes the canonical Wnt signaling pathway, is induced by T{sub 3} at both mRNA and protein levels in HCC cell lines. However, the mechanism underlying T{sub 3}-mediated regulation of DKK4 remains unknown. In the present study, the 5′ promoter region of DKK4 was serially deleted, and the reporter assay performed to localize the T{sub 3} response element (TRE). Consequently, we identified an atypical direct repeat TRE between nucleotides −1645 and −1629 conferring T{sub 3} responsiveness to the DKK4 gene. This region was further validated using chromatin immunoprecipitation (ChIP) and electrophoretic mobility shift assay (EMSA). Stable DKK4 overexpression in SK-Hep-1 cells suppressed cell invasion and metastatic potential, both in vivo andin vitro, via reduction of matrix metalloproteinase-2 (MMP-2) expression. Our findings collectively suggest that DKK4 upregulated by T{sub 3}/TR antagonizes the Wnt signal pathway to suppress tumor cell progression, thus providing new insights into the molecular mechanism underlying thyroid hormone activity in HCC.« less

Lenvatinib in Advanced Radioiodine-Refractory Thyroid Cancer - A Retrospective Analysis of the Swiss Lenvatinib Named Patient Program.

PubMed

Balmelli, Catharina; Railic, Nikola; Siano, Marco; Feuerlein, Kristin; Cathomas, Richard; Cristina, Valerie; Güthner, Christiane; Zimmermann, Stefan; Weidner, Sabine; Pless, Miklos; Stenner, Frank; Rothschild, Sacha I

2018-01-01

Purpose: Differentiated thyroid cancer (DTC) accounts for approximately 95% of thyroid carcinomas. In the metastatic RAI-refractory disease, chemotherapy has very limited efficacy and is associated with substantial toxicity. With increasing knowledge of the molecular pathogenesis of DTC, novel targeted therapies have been developed. Lenvatinib is a tyrosine kinase inhibitor (TKI) with promising clinical activity based on the randomized phase III SELECT trial. In Switzerland, a Named Patient Program (NPP) was installed to bridge the time gap to Swissmedic approval. Here, we report the results from the Swiss Lenvatinib NPP including patients with metastatic RAI-refractory DTC. Methods: Main inclusion criteria for the Swiss NPP were RAI-refractory DTC, documented disease progression, Eastern Cooperative Oncology Group (ECOG) performance status 0-3. The number of previous therapies was not limited. The Swiss Lenvatinib NPP was initiated in June 2014 and was closed in October 2015 with the approval of the drug. Results: Between June 2014 and October 2015, 13 patients with a median age of 72 years have been enrolled. Most patients (69%) had at least one prior systemic therapy, mainly sorafenib. 31% of patients showed a PR and 31% SD. Median progression free survival was 7.2 months and the median overall survival was 22.7 months. Dose reduction due to adverse events was necessary in 7 patients (53%). At the time of analysis 6 patients (47%) were still on treatment with a median time on treatment of 9.98 months. Conclusions: Our results show that lenvatinib has reasonable clinical activity in unselected patients with RAI-refractory thyroid cancer with nearly two-third of patients showing clinical benefit. The toxicity profile of lenvatinib is manageable.

Lenvatinib in Advanced Radioiodine-Refractory Thyroid Cancer - A Retrospective Analysis of the Swiss Lenvatinib Named Patient Program

PubMed Central

Balmelli, Catharina; Railic, Nikola; Siano, Marco; Feuerlein, Kristin; Cathomas, Richard; Cristina, Valerie; Güthner, Christiane; Zimmermann, Stefan; Weidner, Sabine; Pless, Miklos; Stenner, Frank; Rothschild, Sacha I.

2018-01-01

Purpose:Differentiated thyroid cancer (DTC) accounts for approximately 95% of thyroid carcinomas. In the metastatic RAI-refractory disease, chemotherapy has very limited efficacy and is associated with substantial toxicity. With increasing knowledge of the molecular pathogenesis of DTC, novel targeted therapies have been developed. Lenvatinib is a tyrosine kinase inhibitor (TKI) with promising clinical activity based on the randomized phase III SELECT trial. In Switzerland, a Named Patient Program (NPP) was installed to bridge the time gap to Swissmedic approval. Here, we report the results from the Swiss Lenvatinib NPP including patients with metastatic RAI-refractory DTC. Methods:Main inclusion criteria for the Swiss NPP were RAI-refractory DTC, documented disease progression, Eastern Cooperative Oncology Group (ECOG) performance status 0-3. The number of previous therapies was not limited. The Swiss Lenvatinib NPP was initiated in June 2014 and was closed in October 2015 with the approval of the drug. Results:Between June 2014 and October 2015, 13 patients with a median age of 72 years have been enrolled. Most patients (69%) had at least one prior systemic therapy, mainly sorafenib. 31% of patients showed a PR and 31% SD. Median progression free survival was 7.2 months and the median overall survival was 22.7 months. Dose reduction due to adverse events was necessary in 7 patients (53%). At the time of analysis 6 patients (47%) were still on treatment with a median time on treatment of 9.98 months. Conclusions:Our results show that lenvatinib has reasonable clinical activity in unselected patients with RAI-refractory thyroid cancer with nearly two-third of patients showing clinical benefit. The toxicity profile of lenvatinib is manageable. PMID:29344270

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

Application of Sonoelastography in Differential Diagnosis of Benign and Malignant Thyroid Nodules.

PubMed

Esfahanian, Fatemeh; Aryan, Arvin; Ghajarzadeh, Mahsa; Yazdi, Meisam Hosein; Nobakht, Nasir; Burchi, Mehdi

2016-01-01

Sonoelastography is a new ultrasound method which could be helpful to determine which thyroid nodule is malignant. We designed this study to evaluate the accuracy of sonoelastography in differentiating of benign and malignant thyroid nodules in Iranian patients. Forty thyroid nodules in forty consecutive patients who had been referred for sonography-guided fine-needle aspiration biopsy were evaluated. Gray scale ultrasound and elastosonography by real-time, freehand technique applied for all patients. Elastography findings were classified into four groups. Nodules which were classified as patterns 1 or 2 in elastogram evaluation were classified as benign and probably malignant if elastogram scans were patterns 3 and 4 of elastogram scan. Mean age ± standard deviation (SD) was 42.2 ± 12.6 years, and mean ± SD thyroid-stimulating hormone level was 1.4 ± 1.9 IU/ml. Thirty-five cases (87.5%) were female and 5 (12.5%) were male. Histological examination indicated 27 (67.5%) benign and 13 (32.5%) malignant nodules. The most elastogram score was 2 (50%) followed by score 3. The cut-off point of 2 considered as the best value to differentiate benign and malignant thyroid nodules with sensitivity and specificity of 61% and 78% (area under the curve = 0.76, 95% confidence interval: 0.6-0.92, P = 0.007). Sonoelastography could help to differentiate benign and malignant thyroid nodules. As our sample size was limited, larger studies are recommended.

Aggressive Variants of Papillary Thyroid Carcinoma: Hobnail, Tall Cell, Columnar, and Solid.

PubMed

Nath, Meryl C; Erickson, Lori A

2018-05-01

Papillary thyroid carcinomas are the most common endocrine cancer and are usually associated with good survival. However, some variants of papillary thyroid carcinomas may behave more aggressively than classic papillary thyroid carcinomas. The tall cell variant of papillary thyroid carcinoma is the most common aggressive variant of papillary thyroid carcinoma. The aggressive behavior has been ascribed to the histologic subtype and/or to the clinicopathologic features, an issue that remains controversial. The columnar variant of papillary thyroid carcinoma can be aggressive, particularly in older patients, with larger tumors showing a diffusely infiltrative growth pattern and extrathyroidal extension. A papillary thyroid carcinoma is designated as solid/trabecular variant when all or nearly all of a tumor not belonging to any of the other variants has a solid, trabecular, or nested (insular) appearance. This tumor must be distinguished from poorly differentiated thyroid carcinoma which has the same growth pattern but lacks nuclear features of papillary thyroid carcinoma and may show tumor necrosis and high mitotic activity. New to the fourth edition of the WHO Classification of Tumours of Endocrine Organs, the hobnail variant of papillary thyroid carcinoma is a moderately differentiated papillary thyroid carcinoma variant with aggressive clinical behavior and significant mortality. All of these variants are histologically unique and important to recognize due to their aggressive behavior.

Surgical management of medullary thyroid cancer.

PubMed

Mazeh, H; Sippel, R S

2012-12-01

Although thyroid cancer accounts for only 1.5% of all malignancies in the US it is the most rapidly increasing cancer in incidence and it is the most common endocrine malignancy that accounts for over 95% of the endocrine malignancies. Medullary thyroid cancer (MTC) originates from the parafollicular C cells and it represents 6-8% of all thyroid cancer cases. As many as 25% of the MTCs are familial and carry a specific germline mutation as compared to only than 10% familial inheritance in non-medullary thyroid cancers. While well-differentiated thyroid malignancies carry a very good prognosis, recurrence and survival rates of patients with MTC are significantly worse. The difference in cell origin and differentiation also results in different available adjunct therapy. The aim of this study is to review in detail the surgical management of patients with MTC.

Sodium/iodide symporter: a key transport system in thyroid cancer cell metabolism.

PubMed

Filetti, S; Bidart, J M; Arturi, F; Caillou, B; Russo, D; Schlumberger, M

1999-11-01

The recent cloning of the gene encoding the sodium/iodide symporter (NIS) has enabled better characterization of the molecular mechanisms underlying iodide transport, thus opening the way to clarifying its role in thyroid diseases. Several studies, at both the mRNA and the protein expression levels, have demonstrated that TSH, the primary regulator of iodide uptake, upregulates NIS gene expression and NIS protein abundance, both in vitro and in vivo. However, other factors, including iodide, retinoic acid, transforming growth factor-beta, interleukin-1alpha and tumour necrosis factor alpha, may participate in the regulation of NIS expression. Investigation of NIS mRNA expression in different thyroid tissues has revealed increased levels of expression in Graves' disease and toxic adenomas, whereas a reduction or loss of NIS transcript was detected in differentiated thyroid carcinomas, despite the expression of other specific thyroid markers. NIS mRNA was also detected in non-thyroid tissues able to concentrate radioiodine, including salivary glands, stomach, thymus and breast. The production of specific antibodies against the NIS has facilitated study of the expression of the symporter protein. Despite of the presence of high levels of human (h)NIS mRNA, normal thyroid glands exhibit a heterogeneous expression of NIS protein, limited to the basolateral membrane of the thyrocytes. By immunohistochemistry, staining of hNIS protein was stronger in Graves' and toxic adenomas and reduced in thyroid carcinomas. Measurement of iodide uptake by thyroid cancer cells is the cornerstone of the follow-up and treatment of patients with thyroid cancer. However, radioiodide uptake is found only in about 67% of patients with persistent or recurrent disease. Several studies have demonstrated a decrease in or a loss of NIS expression in primary human thyroid carcinomas, and immunohistochemical studies have confirmed this considerably decreased expression of the NIS protein in thyroid cancer tissues, suggesting that the low expression of NIS may represent an early abnormality in the pathway of thyroid cell transformation, rather than being a consequence of cancer progression. The relationship between radioiodine uptake and NIS expression by thyroid cancer cells require further study. New strategies, based on manipulation of NIS expression, to obtain NIS gene reactivation or for use as NIS gene therapy in the treatment of radiosensitive cancer, are also being investigated.

A human thyroid cancer cell line, DH-14-3, newly established from poorly differentiated thyroid carcinoma.

PubMed

Teshima, Jin; Doi, Hideyuki; Fujimori, Keisei; Watanabe, Michio; Nakajima, Noriaki; Nakano, Tomoyuki; Takahashi, Yoshio; Ohuchi, Noriaki; Satomi, Susumu

2013-06-01

Poorly differentiated thyroid carcinoma (PDTC) is a newly recognized histological type of malignant thyroid tumor, accounting for about 2 - 13% of all thyroid carcinomas. PDTC is considered as a morphologically and biologically intermediate stage between well-differentiated thyroid carcinoma and anaplastic thyroid carcinoma. PDTC preferentially manifests bone metastases. We here established a cell line from a resected tumor specimen from a 70-year-old male patient with PDTC who presented with multiple bone metastases. This new thyroid tumor cell line was designated as DH-14-3 and was subsequently grown in culture for several years. DH-14-3 cells express thyroglobulin in the cytoplasm and thyroid transcription factor-1 in the nuclei, both proteins of which are specific markers for the thyroid gland. Importantly, triiodothyronine (T3) was detected in the cultured medium of DH-14-3 cells, in which, however, thyroxine (T4) was undetectable. Moreover, DH-14-3 cells secreted interleukin-8, transforming growth factor-β1, vascular endothelial growth factor, matrix metalloproteinase-1 and parathyroid hormone-related protein, all of which may be responsible for the aggressiveness or bone metastasis of PDTC. Thus, the production of these proteins may reflect the metastatic potential of this cell line. DH-14-3 cells also express CXC chemokine receptor-4 and epidermal growth factor receptor, and carry a missense mutation in the p53 tumor suppressor gene. In fact, transplantation of DH-14-3 cells into the back of nude mice resulted in the formation of tumors, thereby confirming the capability of tumorigenesis. DH-14-3 cells may be useful for investigating the biological features of PDTC and will contribute to the therapeutic study of thyroid cancer.

Thyroid Hormone, Cancer, and Apoptosis.

PubMed

Lin, Hung-Yun; Chin, Yu-Tan; Yang, Yu-Chen S H; Lai, Husan-Yu; Wang-Peng, Jacqueline; Liu, Leory F; Tang, Heng-Yuan; Davis, Paul J

2016-06-13

Thyroid hormones play important roles in regulating normal metabolism, development, and growth. They also stimulate cancer cell proliferation. Their metabolic and developmental effects and growth effects in normal tissues are mediated primarily by nuclear hormone receptors. A cell surface receptor for the hormone on integrin [alpha]vβ3 is the initiation site for effects on tumor cells. Clinical hypothyroidism may retard cancer growth, and hyperthyroidism was recently linked to the prevalence of certain cancers. Local levels of thyroid hormones are controlled through activation and deactivation of iodothyronine deiodinases in different organs. The relative activities of different deiodinases that exist in tissues or organs also affect the progression and development of specific types of cancers. In this review, the effects of thyroid hormone on signaling pathways in breast, brain, liver, thyroid, and colon cancers are discussed. The importance of nuclear thyroid hormone receptor isoforms and of the hormone receptor on the extracellular domain of integrin [alpha]vβ3 as potential cancer risk factors and therapeutic targets are addressed. We analyze the intracellular signaling pathways activated by thyroid hormones in cancer progression in hyperthyroidism or at physiological concentrations in the euthyroid state. Determining how to utilize the deaminated thyroid hormone analog (tetrac), and its nanoparticulate derivative to reduce risks of cancer progression, enhance therapeutic outcomes, and prevent cancer recurrence is also deliberated. © 2016 American Physiological Society. Compr Physiol 6:1221-1237, 2016. Copyright © 2016 John Wiley & Sons, Inc.

Prognostic indicators of outcomes in patients with lung metastases from differentiated thyroid carcinoma during long-term follow-up.

PubMed

Sohn, Seo Young; Kim, Hye In; Kim, Young Nam; Kim, Tae Hyuk; Kim, Sun Wook; Chung, Jae Hoon

2018-02-01

Distant metastases, although uncommon, represent maximum disease-related mortality in differentiated thyroid carcinoma (DTC). Lungs are the most frequent sites of metastases. We aimed to evaluate long-term outcomes and identify prognostic factors in metastatic DTC limited to the lungs. This retrospective study included 89 patients with DTC and metastases limited to the lungs, who were treated between 1996 and 2012 at Samsung Medical Center. Progression-free survival (PFS) and cancer-specific survival (CSS) rates were evaluated according to clinicopathologic factors. Cox regression analysis was used to identify independent factors associated with structural progressive disease (PD) and cancer-specific death. With a median follow-up of 84 months, the 5- and 10-year CSS rates were 78% and 73%, respectively. Older age at diagnosis (≥55 years), radioactive iodine (RAI) nonavidity, preoperative or late diagnosis of metastasis and macro-nodular metastasis (≥1 cm) were predictive of decreased PFS and CSS. Multivariate analysis identified older age (P = .002), RAI nonavidity (P = .045) and preoperative (P = .030) or late diagnosis (P = .026) as independent predictors of structural PD. RAI avidity was also independent predictor of cancer-specific death (P = .025). Patients with DTC and metastatic disease limited to the lungs had favourable long-term outcomes. Age, RAI avidity and timing of metastasis were found to be major factors for predicting prognosis. © 2017 John Wiley & Sons Ltd.

Sustained ERK inhibition maximizes responses of BrafV600E thyroid cancers to radioiodine

PubMed Central

Nagarajah, James; Le, Mina; Montero-Conde, Cristina; Pillarsetty, Nagavarakishore; Bolaender, Alexander; Irwin, Christopher; Krishnamoorthy, Gnana Prakasam; Larson, Steven M.; Ho, Alan L.; Seshan, Venkatraman; Ishii, Nobuya; Carrasco, Nancy; Rosen, Neal; Weber, Wolfgang A.; Fagin, James A.

2016-01-01

Radioiodide (RAI) therapy of thyroid cancer exploits the relatively selective ability of thyroid cells to transport and accumulate iodide. Iodide uptake requires expression of critical genes that are involved in various steps of thyroid hormone biosynthesis. ERK signaling, which is markedly increased in thyroid cancer cells driven by oncogenic BRAF, represses the genetic program that enables iodide transport. Here, we determined that a critical threshold for inhibition of MAPK signaling is required to optimally restore expression of thyroid differentiation genes in thyroid cells and in mice with BrafV600E-induced thyroid cancer. Although the MEK inhibitor selumetinib transiently inhibited ERK signaling, which subsequently rebounded, the MEK inhibitor CKI suppressed ERK signaling in a sustained manner by preventing RAF reactivation. A small increase in ERK inhibition markedly increased the expression of thyroid differentiation genes, increased iodide accumulation in cancer cells, and thereby improved responses to RAI therapy. Only a short exposure to the drug was necessary to obtain a maximal response to RAI. These data suggest that potent inhibition of ERK signaling is required to adequately induce iodide uptake and indicate that this is a promising strategy for the treatment of BRAF-mutant thyroid cancer. PMID:27669459

Sustained ERK inhibition maximizes responses of BrafV600E thyroid cancers to radioiodine.

PubMed

Nagarajah, James; Le, Mina; Knauf, Jeffrey A; Ferrandino, Giuseppe; Montero-Conde, Cristina; Pillarsetty, Nagavarakishore; Bolaender, Alexander; Irwin, Christopher; Krishnamoorthy, Gnana Prakasam; Saqcena, Mahesh; Larson, Steven M; Ho, Alan L; Seshan, Venkatraman; Ishii, Nobuya; Carrasco, Nancy; Rosen, Neal; Weber, Wolfgang A; Fagin, James A

2016-11-01

Radioiodide (RAI) therapy of thyroid cancer exploits the relatively selective ability of thyroid cells to transport and accumulate iodide. Iodide uptake requires expression of critical genes that are involved in various steps of thyroid hormone biosynthesis. ERK signaling, which is markedly increased in thyroid cancer cells driven by oncogenic BRAF, represses the genetic program that enables iodide transport. Here, we determined that a critical threshold for inhibition of MAPK signaling is required to optimally restore expression of thyroid differentiation genes in thyroid cells and in mice with BrafV600E-induced thyroid cancer. Although the MEK inhibitor selumetinib transiently inhibited ERK signaling, which subsequently rebounded, the MEK inhibitor CKI suppressed ERK signaling in a sustained manner by preventing RAF reactivation. A small increase in ERK inhibition markedly increased the expression of thyroid differentiation genes, increased iodide accumulation in cancer cells, and thereby improved responses to RAI therapy. Only a short exposure to the drug was necessary to obtain a maximal response to RAI. These data suggest that potent inhibition of ERK signaling is required to adequately induce iodide uptake and indicate that this is a promising strategy for the treatment of BRAF-mutant 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.

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.

Differentiated thyroid cancer. Impact of adjuvant external radiotherapy in patients with perithyroidal tumor infiltration (stage pT4).

PubMed

Farahati, J; Reiners, C; Stuschke, M; Müller, S P; Stüben, G; Sauerwein, W; Sack, H

1996-01-01

The role of adjuvant external radiotherapy in the survival of patients with differentiated thyroid cancer (DTC) is controversial. To our knowledge, no attempt has been undertaken thus far to assess the impact of this therapy with respect to the papillary and follicular types of thyroid cancer as separate entities. Between 1979 and 1992, 238 patients with differentiated papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC) with Stage pT4 have been treated and followed in our clinic. One hundred sixty-nine patients free of metastases at the final staging, which was performed after the second radioiodine therapy, were included in this study. The standard treatment comprised total thyroidectomy, ablative radioiodine therapy, and thyroid-stimulating hormone-suppressive therapy with levothyroxin. Ninety-nine patients free of disease after the final staging received additional external radiotherapy to the neck (with a dose of 50-60 Gy), whereas the remaining 70 patients were treated with the standard treatment protocol only. Distributions of age, sex, and follow-up time were comparable in both irradiated and nonirradiated groups. Multivariate analysis of the influence of age, sex, histologic subtype, and lymph node status as well as of external radiotherapy on the time to first locoregional and distant failure (LDF), and the time to locoregional recurrence (LR), was accomplished using Cox's proportional hazard model. In patients with DTC, external radiotherapy was a predictive factor for improvement of both LR (P = 0.004) and locoregional and distant failure (P = 0.0003). When the time to first locoregional and distant failure was calculated separately for patients with PTC and FTC, there was a significant difference in the PTC group in favor of irradiated patients (P = 0.0001), whereas there was no effect of external radiotherapy in the FTC group (P = 0.38). Further analyses disclosed that this effect was significantly present only in patients with PTC and lymph node involvement (P = 0.002), whereas those without lymph node involvement did not benefit from an additional adjuvant radiotherapy (P = 0.27). Because none of the patients younger than age 40 years died due to the disease nor had progressive disease during follow-up, we reassessed our results in patients older than age 40 years. The effect of external radiotherapy could be confirmed in this subgroup of patients (P = 0.0009) and in the subgroup of lymph node positive patients older than age 40 years with invasive PTC (P = 0.01). In addition to total thyroidectomy, treatment with radioiodine, and TSH-suppressive therapy with thyroid hormone, adjuvant external radiotherapy improves the recurrence-free survival in patients older than age 40 years with invasive PTC and lymph node involvement.

Endogenous Thyrotropin and Triiodothyronine Concentrations in Individuals with Thyroid Cancer

PubMed Central

Nsouli-Maktabi, Hala; Soldin, Steven J.

2008-01-01

Background Thyroid hormone suppression therapy is associated with decreased recurrence rates and improved survival in patients with differentiated thyroid cancer. Recently higher baseline thyrotropin (TSH) levels have been found to be associated with a postoperative diagnosis of differentiated thyroid cancer. Our objective was to confirm whether preoperative TSH levels were higher in patients who were diagnosed with differentiated thyroid cancer after undergoing thyroidectomy, compared with patients who were found to have benign disease. We also sought to determine whether thyroid hormone levels were lower in the patients with malignancy. Methods The study was a retrospective analysis of a prospective study. The study setting was the General Clinical Research Center of an Academic Medical Center. Participants were 50 euthyroid patients undergoing thyroidectomy. Thyroxine, triiodothyronine (T3), and TSH levels were documented in patients prior to their scheduled thyroidectomy. Following thyroidectomy, patients were divided into those with a histologic diagnosis of either differentiated thyroid cancer or benign disease. Preoperative thyroid profiles were correlated with patients' postoperative diagnoses. Results All patients had a normal serum TSH concentration preoperatively. One-third of the group was diagnosed with thyroid cancer as a result of their thyroidectomy. These patients had a higher serum TSH level (mean = 1.50 mIU/L, CI 1.22–1.78 mIU/L) than patients with benign disease (mean = 1.01 mIU/mL, CI 0.84–1.18 mIU/L). There was a greater risk of having thyroid cancer in patients with TSH levels in the upper three quartiles of TSH values, compared with patients with TSH concentrations in the lowest quartile of TSH values (odd ratio = 8.7, CI 2.2–33.7). Patients with a thyroid cancer diagnosis also had lower T3 concentrations measured by liquid chromatography tandem mass spectrometry (mean = 112.6 ng/dL, CI 103.8–121.4 ng/dL) than did patients with a benign diagnosis (mean 129.9 ng/dL, CI 121.4–138.4 ng/dL). Conclusion These data confirm that higher TSH concentrations, even within the normal range, are associated with a subsequent diagnosis of thyroid cancer in individuals with thyroid abnormalities. This further supports the hypothesis that TSH stimulates the growth or development of thyroid malignancy during its early or preclinical phase. We also show for the first time that patients with thyroid cancer also have lower T3 levels than patients with benign disease. PMID:18788918

Trefoil factor 3 is required for differentiation of thyroid follicular cells and acts as a context-dependent tumor suppressor.

PubMed

Abols, A; Ducena, K; Andrejeva, D; Sadovska, L; Zandberga, E; Vilmanis, J; Narbuts, Z; Tars, J; Eglitis, J; Pirags, V; Line, A

2015-01-01

Trefoil factor 3 (TFF3) is overexpressed in a variety of solid epithelial cancers, where it has been shown to promote migration, invasion, proliferation, survival and angiogenesis. On the contrary, in the majority of thyroid tumors, it is downregulated, yet its role in the development of thyroid cancer remains unknown. Here we show that TFF3 exhibits strong cytoplasmic staining of normal thyroid follicular cells and colloid and the staining is increased in hyperfunctioning thyroid nodules, while it is decreased in all thyroid cancers of follicular cell origin. By meta-analysis of gene expression datasets, we found that in the thyroid cancer, conversely to the breast cancer, the expression of TFF3 mRNA was downregulated by estrogen signaling and confirmed this by treating thyroid cancer cells with estradiol. Forced expression of TFF3 in anaplastic thyroid cancer cells resulted in decreased cell proliferation, clonal spheroid formation and entry into the S phase. Furthermore, it induced acquisition of epithelial-like cell morphology and expression of the differentiation markers of thyroid follicular cells and transcription factors implicated in the thyroid morphogenesis and function. Taken together, this study provides the first evidence that TFF3 may act as a tumor suppressor or an oncogene depending on the cellular context.

Label-free Imaging of Thyroid and Parathyroid Glands Using Coherent Anti-Stokes Raman Scattering (CARS) Microscopy

NASA Astrophysics Data System (ADS)

Weng, Sheng

Thyroid and parathyroid glands play a vital role in regulating the body's metabolism and calcium levels. Surgical removal of the glands is the main treatment for both thyroid cancer and parathyroid adenoma. In thyroidectomy and parathyroidectomy, it's very important to differentiate thyroid, parathyroid, and the other tissues around the neck. Traditionally, physicians use ultrasound guided fine needle aspiration (FNA) to evaluate thyroid nodules, but up to 30% of FNA results are "inconclusive". The sestamibi scan can localize parathyroid adenoma, but currently it only has 50% accuracy. Here we applied the emerging CARS technique to image both thyroid and parathyroid tissues, which has potential to be used in real-time in vivo examination of different structures. We also developed algorithms to differentiate different cellular structures based on CARS images. When incorporated with a fiber optic endoscope in the future, CARS imaging technique can help surgeons identify cancerous thyroid tissue intraoperatively, preserve good parathyroid glands during thyroidectomy and find parathyroid adenoma during parathyroidectomy.

[Incidence of familial non-medullary thyroid carcinoma in the patient register of the Clinic and Polyclinic of Nuclear Medicine, University of Würzburg].

PubMed

Körber, C; Geling, M; Werner, E; Mörtl, M; Mäder, U; Reiners, C; Farahati, J

2000-01-01

In this study the incidence rate of familial non-medullary thyroid carcinoma was investigated in the first and second grade relatives of patients registered at the Clinic and Polyclinic for Nuclear Medicine, University of Würzburg. In this study 596 patients with differentiated thyroid carcinoma were enclosed, who were treated between 01.01.81 and 31.12.95. The data concerning a familial occurrence were studied by a retrospective survey-based analysis. These data were compared to a literature analysis for familial non-medullary thyroid carcinoma. 14 patients of the 596 patients treated showed a familial occurrence (2.3%). All these patients suffered from papillary thyroid carcinoma. According to the prognostic factors (tumor state, lymph node involvement, metastatic disease) no differences could be evaluated in the different groups (sporadic versus familial non-medullary thyroid disease). A familial occurrence of differentiated thyroid carcinomas is not frequently observed, but should be considered due to further genetic diseases.

Progressive Non-familial Adult onset Cerebellar Degeneration: An Unusual Occurrence with Hashimoto's Thyroiditis.

PubMed

Rao, Raghavendra S; Sheshadri, Shubha; Bhattacharjee, Dipanjan; Patil, Navin; Rao, Karthik

2018-03-13

Progressive non-familial adult onset cerebellar degeneration has been rarely associated with hypothyroidism and is known to be reversible after therapy. We report a case of cerebellar atrophy in a 31 year old female whose detailed evaluation had revealed sub-clinical hypothyroidism secondary to autoimmune thyroiditis with a very high anti-TPO (anti-thyroid peroxidase) antibody levels. MRI (Magnetic Resonanace Imaging) of brain showed diffuse bilateral cerebellar atrophy. She was treated with thyroid hormone supplementation and after one year of follow up, cerebellar signs had disappeared completely with significant reduction in anti-TPO antibody levels. Imaging of the brain post one year of follow-up revealed normal cerebellum. Hence, we opine that thyroid dysfunction should always be kept in mind while evaluating patients presenting with acute onset cerebellar ataxia as it can be easily reversed with thyroid hormone replacement therapy.

Establishment of a non-tumorigenic papillary thyroid cell line (FB-2) carrying the RET/PTC1 rearrangement.

PubMed

Basolo, Fulvio; Giannini, Riccardo; Toniolo, Antonio; Casalone, Rosario; Nikiforova, Marina; Pacini, Furio; Elisei, Rossella; Miccoli, Paolo; Berti, Piero; Faviana, Pinuccia; Fiore, Lisa; Monaco, Carmen; Pierantoni, Giovanna Maria; Fedele, Monica; Nikiforov, Yuri E; Santoro, Massimo; Fusco, Alfredo

2002-02-10

A novel human thyroid papillary carcinoma cell line (FB-2) has been established and characterized. FB-2 cells harbor the RET/PTC1 chimeric oncogene in which the RET kinase domain is fused to the H4 gene. FB-2 cells neither formed colonies in semisolid media nor induced tumors after heterotransplant into severe combined immunodeficient mice. However, HMGI(Y), HMGI-C and c-myc genes, which are associated to thyroid cell transformation, were abundantly expressed in FB-2 cells but not in normal thyroid cells. FB-2 cells only partially retained the differentiated thyroid phenotype. In fact, the PAX-8 gene, which codes for a transcriptional factor required for thyroid cell differentiation, was expressed, while thyroglobulin, TSH-receptor and thyroperoxidase genes were not. Moreover, FB-2 cells produced high levels of interleukin (IL)-6 and IL-8. Copyright 2001 Wiley-Liss, Inc.

Surface-enhanced Raman spectroscopy for differentiation between benign and malignant thyroid tissues

NASA Astrophysics Data System (ADS)

Li, Zuanfang; Li, Chao; Lin, Duo; Huang, Zufang; Pan, Jianji; Chen, Guannan; Lin, Juqiang; Liu, Nenrong; Yu, Yun; Feng, Shangyuan; Chen, Rong

2014-04-01

The aim of this study was to evaluate the potential of applying silver nano-particle based surface-enhanced Raman scattering (SERS) to discriminate different types of human thyroid tissues. SERS measurements were performed on three groups of tissue samples including thyroid cancers (n = 32), nodular goiters (n = 20) and normal thyroid tissues (n = 25). Tentative assignments of the measured tissue SERS spectra suggest interesting cancer specific biomolecular differences. The principal component analysis (PCA) and linear discriminate analysis (LDA) together with the leave-one-out, cross-validated technique yielded diagnostic sensitivities of 92%, 75% and 87.5%; and specificities of 82.6%, 89.4% and 84.4%, respectively, for differentiation among normal, nodular and malignant thyroid tissue samples. This work demonstrates that tissue SERS spectroscopy associated with multivariate analysis diagnostic algorithms has great potential for detection of thyroid cancer at the molecular level.

The microRNA-processing enzyme Dicer is essential for thyroid function.

PubMed

Frezzetti, Daniela; Reale, Carla; Calì, Gaetano; Nitsch, Lucio; Fagman, Henrik; Nilsson, Ola; Scarfò, Marzia; De Vita, Gabriella; Di Lauro, Roberto

2011-01-01

Dicer is a type III ribonuclease required for the biogenesis of microRNAs (miRNAs), a class of small non-coding RNAs regulating gene expression at the post-transcriptional level. To explore the functional role of miRNAs in thyroid gland function, we generated a thyrocyte-specific Dicer conditional knockout mouse. Here we show that development and early differentiation of the thyroid gland are not affected by the absence of Dicer, while severe hypothyroidism gradually develops after birth, leading to reduced body weight and shortened life span. Histological and molecular characterization of knockout mice reveals a dramatic loss of the thyroid gland follicular architecture associated with functional aberrations and down-regulation of several differentiation markers. The data presented in this study show for the first time that an intact miRNAs processing machinery is essential for thyroid physiology, suggesting that deregulation of specific miRNAs could be also involved in human thyroid dysfunctions.

Immune Response in Thyroid Cancer: Widening the Boundaries

PubMed Central

Ward, Laura Sterian

2014-01-01

The association between thyroid cancer and thyroid inflammation has been repeatedly reported and highly debated in the literature. In fact, both molecular and epidemiological data suggest that these diseases are closely related and this association reinforces that the immune system is important for thyroid cancer progression. Innate immunity is the first line of defensive response. Unlike innate immune responses, adaptive responses are highly specific to the particular antigen that induced them. Both branches of the immune system may interact in antitumor immune response. Major effector cells of the immune system that directly target thyroid cancer cells include dendritic cells, macrophages, polymorphonuclear leukocytes, mast cells, and lymphocytes. A mixture of immune cells may infiltrate thyroid cancer microenvironment and the balance of protumor and antitumor activity of these cells may be associated with prognosis. Herein, we describe some evidences that immune response may be important for thyroid cancer progression and may help us identify more aggressive tumors, sparing the vast majority of patients from costly unnecessary invasive procedures. The future trend in thyroid cancer is an individualized therapy. PMID:25328756

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.

Hyperthyroidism presenting as isolated tricuspid regurgitation and right heart failure.

PubMed

Whitner, Tanya E; Hudson, Christopher J; Smith, Timothy D; Littmann, Laszlo

2005-01-01

Although hyperthyroidism has many signs and symptoms, right heart failure can occasionally be the main presenting symptom. We describe the case of a previously healthy 42-year-old woman whose chief complaint was progressive bilateral lower extremity edema. The echocardiogram revealed right atrial dilatation and moderate-to-severe tricuspid regurgitation. Results of laboratory studies were consistent with hyperthyroidism. Thyroid ablation resulted in permanent resolution of symptoms and resolution of tricuspid incompetence on echocardiography. In a case of isolated, unexplained tricuspid regurgitation, it is important to consider indolent hyperthyroidism in the differential diagnosis.

Dedifferentiation of Human Primary Thyrocytes into Multilineage Progenitor Cells without Gene Introduction

PubMed Central

Saenko, Vladimir; Suzuki, Masatoshi; Matsuse, Michiko; Ohtsuru, Akira; Kumagai, Atsushi; Uga, Tatsuya; Yano, Hiroshi; Nagayama, Yuji; Yamashita, Shunichi

2011-01-01

While identification and isolation of adult stem cells have potentially important implications, recent reports regarding dedifferentiation/reprogramming from differentiated cells have provided another clue to gain insight into source of tissue stem/progenitor cells. In this study, we developed a novel culture system to obtain dedifferentiated progenitor cells from normal human thyroid tissues. After enzymatic digestion, primary thyrocytes, expressing thyroglobulin, vimentin and cytokeratin-18, were cultured in a serum-free medium called SAGM. Although the vast majority of cells died, a small proportion (∼0.5%) survived and proliferated. During initial cell expansion, thyroglobulin/cytokeratin-18 expression was gradually declined in the proliferating cells. Moreover, sorted cells expressing thyroid peroxidase gave rise to proliferating clones in SAGM. These data suggest that those cells are derived from thyroid follicular cells or at least thyroid-committed cells. The SAGM-grown cells did not express any thyroid-specific genes. However, after four-week incubation with FBS and TSH, cytokeratin-18, thyroglobulin, TSH receptor, PAX8 and TTF1 expressions re-emerged. Moreover, surprisingly, the cells were capable of differentiating into neuronal or adipogenic lineage depending on differentiating conditions. In summary, we have developed a novel system to generate multilineage progenitor cells from normal human thyroid tissues. This seems to be achieved by dedifferentiation of thyroid follicular cells. The presently described culture system may be useful for regenerative medicine, but the primary importance will be as a tool to elucidate the mechanisms of thyroid diseases. PMID:21556376

Papillary Carcinoma in Median Aberrant Thyroid (Ectopic) - Case Report

PubMed Central

K, Shashidhar; Deshmane, Vijaya Laxmi; Kumar, Veerendra; Arjunan, Ravi

2014-01-01

Median ectopic thyroid may be encountered anywhere from the foramen caecum to the diaphragm. Non lingual median aberrant thyroid (incomplete descent) usually found in the infrahyoid region and malignant transformation in this ectopic thyroid tissue is very rare. We report an extremely rare case of papillary carcinoma in non lingual median aberrant thyroid in a 25-year-old female. The differentiation between a carcinoma arising in the median ectopic thyroid tissue and a metastatic papillary carcinoma from an occult primary in the main thyroid gland is also discussed. PMID:25121039

Papillary carcinoma in median aberrant thyroid (ectopic) - case report.

PubMed

Hebbar K, Ashwin; K, Shashidhar; Deshmane, Vijaya Laxmi; Kumar, Veerendra; Arjunan, Ravi

2014-06-01

Median ectopic thyroid may be encountered anywhere from the foramen caecum to the diaphragm. Non lingual median aberrant thyroid (incomplete descent) usually found in the infrahyoid region and malignant transformation in this ectopic thyroid tissue is very rare. We report an extremely rare case of papillary carcinoma in non lingual median aberrant thyroid in a 25-year-old female. The differentiation between a carcinoma arising in the median ectopic thyroid tissue and a metastatic papillary carcinoma from an occult primary in the main thyroid gland is also discussed.

A phase II study tests a new drug for patients with advanced thyroid cancer | Center for Cancer Research

Cancer.gov

A phase II trial of CUDC-907, a new drug that may be able to shrink thyroid tumors that have spread or gotten worse, is being tested in metastatic or advanced thyroid cancer.  Currently, there is no standard or effective treatment for the most aggressive types of thyroid cancer such as anaplastic and poorly differentiated thyroid cancer.  Learn more...

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.

Thyroid-Like Follicular Carcinoma of the Kidney in a Patient with Skull and Meningeal Metastasis: A Unique Case Report and Review of the Literature.

PubMed

Dong, Liang; Huang, Jiayu; Huang, Luke; Shi, Oumin; Liu, Qiang; Chen, Haige; Xue, Wei; Huang, Yiran

2016-04-01

Thyroid-like follicular carcinoma of the kidney (TLFCK) is an extremely rare subtype of renal cell carcinoma with close resemblance to the well-differentiated thyroid follicular neoplasms. TLFCK has not been included in the 2004 World Health Organization (WHO) classification due to the limited data available. Only 27 cases have been reported in the literature to date. Herein, we report a unique case of TLFCK that presented as a striking skull and meningeal metastasis 5 years after the initial diagnosis; this is the first case of TLFCK with such a novel metastasis pattern. A 68-year-old woman was found to have a right renal lesion using computed tomography (CT) during her regular clinical follow-up visit for bladder cancer, but she exhibited no obvious clinical symptoms. The CT scan showed a 4.4-cm diameter, slightly lobulated soft tissue mass in the right lower kidney, the pathological findings of which showed a TLFCK. Five years later, the patient had progressed to skull and meningeal metastasis. Both the renal tumor and the metastasis lesion were composed almost entirely of follicles with a dense, colloid-like material that resembled thyroid follicular carcinoma. However, no lesion was found in the thyroid gland. The neoplastic epithelial cells were strongly immunoreactive for cytokeratin 7 (and vimentin but negative for thyroid transcription factor-1 and thyroglobulin. This is the first reported case of TLFCK to consist of widespread metastases to the skull and meninges and provides evidence that this rare variant of renal cell carcinoma has uncertain malignant potential and can be more clinically aggressive than previously believed.

Epidermal growth factor receptor expression is related to post-mitotic events in cerebellar development: regulation by thyroid hormone.

PubMed

Carrasco, Emilce; Blum, Mariann; Weickert, Cynthia Shannon; Casper, Diana

2003-01-10

It has been established that thyroid hormone and neurotrophic factors both orchestrate developmental events in the brain. However, it is not clear how these two influences are related. In this study, we investigated the effects of thyroid hormone on cerebellar development and the coincident expression of transforming growth factor-alpha (TGF-alpha), a ligand in the epidermal growth factor (EGF) family, and the epidermal growth factor receptor (EGFR). Profiles of thyroid hormone expression were measured in postnatal animals and were found to peak at postnatal day 15 (P15). These levels dropped below detectable levels when mice were made hypothyroid with propylthiouracil (PTU). TGF-alpha and EGFR expression, as determined by RNAse protection assay, was maximal at P6 in normal animals, but remained low in hypothyroid animals, suggesting that thyroid hormone was responsible for their induction. In situ hybridization and immunohistochemical analysis of EGFR expression revealed that this receptor was present on granule cells within the inner zone of the external granule cell layer (EGL), suggesting that EGFR-ligands were not inducing granule cell proliferation. The persistence of EGFR expression on migrating granule cells and subsequent down-regulation of expression in the internal granule cell layer (IGL) implicates a role for EGFR-ligands in differentiation and/or migration. In hypothyroid animals, we observed a delayed progression of granule cell migration, consistent with the persistence of EGFR labeling in the EGL, and in the 'pile-up' of labeled cells at the interface between the molecular layer and the Purkinje cell layer. Taken together, these results implicate thyroid hormone in the coordinated expression of TGF-alpha and EGFR, which are positioned to play a role in post-mitotic developmental events in the cerebellum.

Thyroidectomy Practice After Implementation of the 2015 American Thyroid Association Guidelines on Surgical Options for Patients With Well-Differentiated Thyroid Carcinoma.

PubMed

Hirshoren, Nir; Kaganov, Kira; Weinberger, Jeffrey M; Glaser, Benjamin; Uziely, Beatrice; Mizrahi, Ido; Eliashar, Ron; Mazeh, Haggi

2018-03-29

The recommended extent of surgery for well-differentiated thyroid carcinoma has been modified considerably in the updated 2015 American Thyroid Association guidelines published in January 2016. To date, the changes in clinical practice after publication of these new guidelines have not been demonstrated. The aim of this study was to evaluate clinical practice changes associated with implementation of the updated guidelines on the surgical procedure rates of total thyroidectomy, thyroid lobectomy, and completion thyroidectomy at a single tertiary medical center. This is a retrospective cohort study of 169 patients at the Hadassah-Hebrew University Medical Center, Jerusalem, Israel. Patients with pathologically proved, well-differentiated thyroid carcinoma who underwent surgery between January 1, 2013, and December 31, 2014, were compared with patients who underwent surgery from January 1 to December 31, 2016. A total of 434 thyroidectomy procedures were performed during the study period, and 251 had pathologically proved, well-differentiated thyroid carcinoma. Patients with tumors larger than 4 cm, involved lymph nodes, or bilateral nodules were excluded. Primary outcomes were the rate of up-front total thyroidectomy vs lobectomy and the rates of completion thyroidectomy before and after the implementation of the new guidelines. Of the 169 patients in the final analysis, 118 (69.8%) were included from 2013 to 2014 and 51 (30.2%) in 2016. The mean (SD) age for the entire cohort was 44 (13.8) years, and 129 (76.3%) were women. Up-front total thyroidectomy was performed in 72 of 118 patients (61.0%) prior to the 2015 American Thyroid Association guidelines and 16 of 51 (31.4%) following their implementation (odds ratio, 0.29; 95% CI, 0.14-0.59). The rate of completion thyroidectomy also significantly decreased between these periods (73.9% vs 20.0%; odds ratio, 0.09; 95% CI, 0.04-0.19). The updated 2015 American Thyroid Association guidelines implementation was associated with a significant decrease in the rates of both up-front total thyroidectomy and completion thyroidectomy. According to these findings, only 1 of 5 patients who undergoes thyroid lobectomy will require a completion procedure.

Secondary and tertiary preventions of thyroid disease.

PubMed

Azizi, Fereidoun; Mehran, Ladan; Hosseinpanah, Farhad; Delshad, Hossein; Amouzegar, Atieh

2018-05-01

Secondary and tertiary preventions are concerned with the recognition of the disease process in a very early stage and delay in progression to complete disease and minimization of complications and the impact of illness. All articles related to secondary and tertiary prevention of thyroid diseases were reviewed. Using related key words, articles published between 2001 and 2015 were evaluated, categorized, and analyzed. In secondary prevention, congenital hypothyroidism and subclinical hypo and hyperthyroidism are equally important. Routine screening of patients with multinodular goiter by either ultrasonography or calcitonin is a controversial issue, while calcitonin assessments in medullary cancer and RET in family members are recommended. Screening of thyroid disease in pregnancy is limited to those with risk factors. Views regarding the importance of thyroid autoimmunity in secondary prevention are also presented. In tertiary prevention, prescribing excessive doses of levothyroxine, in the elderly in particular and appropriate care of all patients to avoid progression and complications are the key issues. Optimization of management of thyroid diseases requires timely screening, prevention of progression to more sever disease, optimal medical care, and avoidance of iatrogenic conditions.

Values of molecular markers in the differential diagnosis of thyroid abnormalities.

PubMed

Tennakoon, T M P B; Rushdhi, M; Ranasinghe, A D C U; Dassanayake, R S

2017-06-01

Thyroid cancer (TC), follicular adenoma (FA) and Hashimoto's thyroiditis (HT) are three of the most frequently reported abnormalities that affect the thyroid gland. A frequent co-occurrence along with similar histopathological features is observed between TC and FA as well as between TC and HT. The conventional diagnostic methods such as histochemical analysis present complications in differential diagnosis when these abnormalities occur simultaneously. Hence, the authors recognize novel methods based on screening genetic defects of thyroid abnormalities as viable diagnostic and prognostic methods that could complement the conventional methods. We have extensively reviewed the existing literature on TC, FA and HT and also on three genes, namely braf, nras and ret/ptc, that could be used to differentially diagnose the three abnormalities. Emphasis was also given to the screening methods available to detect the said molecular markers. It can be conferred from the analysis of the available data that the utilization of braf, nras and ret/ptc as markers for the therapeutic evaluation of FA and HT is debatable. However, molecular screening for braf, nras and ret/ptc mutations proves to be a conclusive method that could be employed to differentially diagnose TC from HT and FA in the instance of a suspected co-occurrence. Thyroid cancer patients can be highly benefited from the screening for the said genetic markers, especially the braf gene due to its diagnostic value as well as due to the availability of personalized medicine targeted specifically for braf mutants.

An Interesting Case of Retropharyngeal Lymph Nodal Metastases in a Case of Iodine-Refractory Thyroid Cancer.

PubMed

Harisankar, Chidambaram Natrajan Balasubramanian; Vijayabhaskar, Ramakrishnan

2018-01-01

Metastases to cervical lymph node are fairly common in differentiated thyroid cancer. In iodine-refractory disease, the disease may persist in the thyroid bed, cervical lymph nodes, lungs, or the bones commonly. Retropharyngeal lymph nodal involvement in thyroid cancer is unusual and may even be the presenting complaint. We represent a case of iodine-refractory thyroid cancer with retropharyngeal lymph nodal involvement in addition to lung metastases.

Molecular-Directed Treatment of Differentiated Thyroid Cancer: Advances in Diagnosis and Treatment.

PubMed

Yip, Linwah; Sosa, Julie Ann

2016-07-01

Thyroid cancer incidence is increasing, and when fine-needle aspiration biopsy results are cytologically indeterminate, the diagnosis is often still established only after thyroidectomy. Molecular marker testing may be helpful in guiding patient-oriented and tailored management of thyroid nodules and thyroid cancer. To summarize available data on the use of molecular testing to improve the diagnosis and prognostication of thyroid cancer. A MEDLINE review was conducted using the primary search terms molecular, thyroid cancer, thyroid nodule, and gene expression classifier in search strings. Articles were restricted to those published between January 1, 2010, and June 1, 2015, inclusive of adult humans, and reported in the English language only. Of 867 titles screened, 67 articles were further identified for review of the full text. The 2 most studied molecular marker testing techniques for indeterminate thyroid nodules include gene expression classifier analysis and evaluation for somatic mutations or rearrangements that are commonly found in thyroid cancer (7-gene panel). Nodules with benign results on gene expression classifier analysis can be associated with less than a 5% risk of cancer and may be observed, while nodules with positive results on the 7-gene panel may have a higher risk of cancer (80%-100%) and definitive surgery can be recommended. However, cancer prevalence and geographic variations in histologic subtypes may affect accuracy and clinical applicability of both tests. Molecular marker tests such as ThyroSeq version 2.1 are more comprehensive, but they need further validation. Preoperative risk stratification using molecular markers also may be used to better define the optimal extent of thyroidectomy for patients with thyroid cancer. Molecular markers potentially can augment the diagnostic specificity of fine-needle aspiration biopsy to better differentiate cytologically indeterminate nodules that can be safely observed from cytologically indeterminate nodules that may be associated with differentiated thyroid cancer. Long-term follow-up data are still needed; in the end, patient preference regarding the relative risks and benefits of molecular testing is at the crux of decision making.

Quantitative Shear Wave Velocity Measurement on Acoustic Radiation Force Impulse Elastography for Differential Diagnosis between Benign and Malignant Thyroid Nodules: A Meta-analysis.

PubMed

Liu, Bo-Ji; Li, Dan-Dan; Xu, Hui-Xiong; Guo, Le-Hang; Zhang, Yi-Feng; Xu, Jun-Mei; Liu, Chang; Liu, Lin-Na; Li, Xiao-Long; Xu, Xiao-Hong; Qu, Shen; Xing, Mingzhao

2015-12-01

The aim of this study was to evaluate the diagnostic performance of quantitative shear wave velocity (SWV) measurement on acoustic radiation force impulse (ARFI) elastography for differentiation between benign and malignant thyroid nodules using meta-analysis. The databases of PubMed and the Web of Science were searched. Studies published in English on assessment of the sensitivity and specificity of ARFI elastography for the differentiation of thyroid nodules were collected. The quantitative measurement of ARFI elastography was evaluated by SWV (m/s). Meta-Disc Version 1.4 software was used to describe and calculate the sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and summary receiver operating characteristic curves. We analyzed a total of 13 studies, which included 1,854 thyroid nodules (including 1,339 benign nodules and 515 malignant nodules) from 1,641 patients. The summary sensitivity and specificity for differential diagnosis between benign and malignant thyroid nodules by SWV were 0.81 (95% confidence interval [CI]: 0.77-0.84) and 0.84 (95% CI: 0.81-0.86), respectively. The pooled positive and negative likelihood ratios were 5.21 (95% CI: 3.56-7.62) and 0.23 (95% CI: 0.17-0.32), respectively. The pooled diagnostic odds ratio was 27.53 (95% CI: 14.58-52.01), and the area under the summary receiver operating characteristic curve was 0.91 (Q* = 0.84). In conclusion, SWV measurement on ARFI elastography has high sensitivity and specificity for differential diagnosis between benign and malignant thyroid nodules and can be used in combination with conventional ultrasound. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Transcriptome Analysis of Orbital Adipose Tissue in Active Thyroid Eye Disease Using Next Generation RNA Sequencing Technology

PubMed Central

Lee, Bradford W.; Kumar, Virender B.; Biswas, Pooja; Ko, Audrey C.; Alameddine, Ramzi M.; Granet, David B.; Ayyagari, Radha; Kikkawa, Don O.; Korn, Bobby S.

2018-01-01

Objective: This study utilized Next Generation Sequencing (NGS) to identify differentially expressed transcripts in orbital adipose tissue from patients with active Thyroid Eye Disease (TED) versus healthy controls. Method: This prospective, case-control study enrolled three patients with severe, active thyroid eye disease undergoing orbital decompression, and three healthy controls undergoing routine eyelid surgery with removal of orbital fat. RNA Sequencing (RNA-Seq) was performed on freshly obtained orbital adipose tissue from study patients to analyze the transcriptome. Bioinformatics analysis was performed to determine pathways and processes enriched for the differential expression profile. Quantitative Reverse Transcriptase-Polymerase Chain Reaction (qRT-PCR) was performed to validate the differential expression of selected genes identified by RNA-Seq. Results: RNA-Seq identified 328 differentially expressed genes associated with active thyroid eye disease, many of which were responsible for mediating inflammation, cytokine signaling, adipogenesis, IGF-1 signaling, and glycosaminoglycan binding. The IL-5 and chemokine signaling pathways were highly enriched, and very-low-density-lipoprotein receptor activity and statin medications were implicated as having a potential role in TED. Conclusion: This study is the first to use RNA-Seq technology to elucidate differential gene expression associated with active, severe TED. This study suggests a transcriptional basis for the role of statins in modulating differentially expressed genes that mediate the pathogenesis of thyroid eye disease. Furthermore, the identification of genes with altered levels of expression in active, severe TED may inform the molecular pathways central to this clinical phenotype and guide the development of novel therapeutic agents. PMID:29760827

Selective Ablation of Tumor Suppressors in Parafollicular C Cells Elicits Medullary Thyroid Carcinoma.

PubMed

Song, Hai; Lin, Chuwen; Yao, Erica; Zhang, Kuan; Li, Xiaoling; Wu, Qingzhe; Chuang, Pao-Tien

2017-03-03

Among the four different types of thyroid cancer, treatment of medullary thyroid carcinoma poses a major challenge because of its propensity of early metastasis. To further investigate the molecular mechanisms of medullary thyroid carcinoma and discover candidates for targeted therapies, we developed a new mouse model of medullary thyroid carcinoma based on our CGRP CreER mouse line. This system enables gene manipulation in parafollicular C cells in the thyroid, the purported cells of origin of medullary thyroid carcinoma. Selective inactivation of tumor suppressors, such as p53 , Rb , and Pten , in mature parafollicular C cells via an inducible Cre recombinase from CGRP CreER led to development of murine medullary thyroid carcinoma. Loss of Pten accelerated p53 / Rb -induced medullary thyroid carcinoma, indicating interactions between pathways controlled by tumor suppressors. Moreover, labeling differentiated parafollicular C cells by CGRP CreER allows us to follow their fate during malignant transformation to medullary thyroid tumor. Our findings support a model in which mutational events in differentiated parafollicular C cells result in medullary thyroid carcinoma. Through expression analysis including RNA-Seq, we uncovered major signaling pathways and networks that are perturbed following the removal of tumor suppressors. Taken together, these studies not only increase our molecular understanding of medullary thyroid carcinoma but also offer new candidates for designing targeted therapies or other treatment modalities. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

What is your diagnosis? Ventral neck mass in a dog.

PubMed

Fernandez, Nicole J; Clark, Edward G; Larson, Victoria S

2008-12-01

: A 14-year-old male Labrador Retriever was presented for lethargy and collapse. On physical examination, numerous abnormalities were found, including a large ventral neck mass (100 cm(3)) in the area of the thyroid gland. Fine-needle aspirates revealed 2 apparent populations of cells: one suspected to be a well-differentiated thyroid carcinoma, and the other consisting of large pleomorphic to spindloid cells suggestive of sarcoma. Two days later, the dog died at home. A full necropsy was not performed, but examination of the head and neck revealed a well-encapsulated mass adjacent to the cranial trachea and larynx. A section of the mass was evaluated histologically and a diagnosis of anaplastic thyroid carcinoma was made. Immunohistochemical evaluation with antibodies to thyroglobulin, cytokeratin, and vimentin confirmed distinct populations of malignant epithelial and malignant mesenchymal cells, and the diagnosis was amended to thyroid carcinosarcoma. Thyroid carcinosarcoma is a rare neoplasm in dogs in which the cell type comprising the mesenchymal component can vary. Immunochemistry to demonstrate the 2 cell types may be necessary to differentiate thyroid carcinosarcoma from anaplastic thyroid carcinoma.

The value of quantitative shear wave elastography in differentiating the cervical lymph nodes in patients with thyroid nodules.

PubMed

You, Jun; Chen, Juan; Xiang, Feixiang; Song, Yue; Khamis, Simai; Lu, Chengfa; Lv, Qing; Zhang, Yanrong; Xie, Mingxing

2018-04-01

This study aimed at evaluating the diagnostic performance of quantitative shear wave elastography (SWE) in differentiating metastatic cervical lymph nodes from benign nodes in patients with thyroid nodules. One hundred and forty-one cervical lymph nodes from 39 patients with thyroid nodules that were diagnosed as papillary thyroid cancer had been imaged with SWE. The shear elasticity modulus, which indicates the stiffness of the lymph nodes, was measured in terms of maximum shear elasticity modulus (maxSM), minimum shear elasticity modulus (minSM), mean shear elasticity modulus (meanSM), and standard deviation (SD) of the shear elasticity modulus. All the patients underwent thyroid surgery, 50 of the suspicious lymph nodes were resected, and 91 lymph nodes were followed up for 6 months. The maxSM value, minSM value, meanSM value, and SD value of the metastatic lymph nodes were significantly higher than those of the benign nodes. The area under the curve of the maxSM value, minSM value, meanSM value, and SD value were 0.918, 0.606, 0.865, and 0.915, respectively. SWE can differentiate metastasis from benign cervical lymph nodes in patients with thyroid nodules, and the maxSM, meanSM, and SD may be valuable quantitative indicators for characterizing cervical lymph nodes.

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.

Natural history of thyroid cancer [Review].

PubMed

Takano, Toru

2017-03-31

Thyroid cancers have long been considered to arise in middle age and, after their repeated proliferation, resulting in further damage to the genome, they progress to more aggressive and lethal cancers. However, in 2014, some studies were reported that might lead to a marked change in our understanding of the natural history of thyroid cancer. A high prevalence of papillary carcinoma in the young suggested that the first initiation of thyroid cancer is likely to occur in the infantile period. Such a conclusion was also supported by a very slow growth rate of papillary microcarcinomas (PMCs) in an observation trial. The proliferation rate of PMCs was negatively correlated with the age, and surgery to remove PMCs did not contribute to reduce mortality from thyroid cancer. These findings strongly suggested the existence of self-limiting cancers, which are truly malignant but do not progress to lethal cancers, for the first time in human history. The early detection of self-limiting cancers results in overdiagnosis. Ultrasonographic screening of the thyroid in the young should be avoided. Lethal thyroid cancers, whose origin is still unknown, appear suddenly after middle age. In the elderly, thyroid cancers are a mixture of self-limiting and lethal cancers; thus, when thyroid cancer is detected, careful follow-up with examination of its growth rate is required.

Treatment-emergent hypertension and efficacy in the phase 3 Study of (E7080) lenvatinib in differentiated cancer of the thyroid (SELECT).

PubMed

Wirth, Lori J; Tahara, Makoto; Robinson, Bruce; Francis, Sanjeev; Brose, Marcia S; Habra, Mouhammed Amir; Newbold, Kate; Kiyota, Naomi; Dutcus, Corina E; Mathias, Elton; Guo, Matthew; Sherman, Steven I; Schlumberger, Martin

2018-06-01

Hypertension (HTN) is an established class effect of vascular endothelial growth factor receptor (VEGFR) inhibition. In the phase 3 Study of (E7080) Lenvatinib in Differentiated Cancer of the Thyroid (SELECT) trial, HTN was the most frequent adverse event of lenvatinib, an inhibitor of VEGFR1, VEGFR2, VEGFR3, fibroblast growth factor receptor 1 (FGFR1), FGFR2, FGFR3, FGFR4, platelet-derived growth factor receptor α (PDGFRα), ret proto-oncogene (RET), and stem cell factor receptor (KIT). This exploratory analysis examined treatment-emergent hypertension (TE-HTN) and its relation with lenvatinib efficacy and safety in SELECT. In the multicenter, double-blind SELECT trial, 392 patients with progressive radioiodine-refractory differentiated thyroid cancer (RR-DTC) were randomized 2:1 to lenvatinib (24 mg/d on a 28-day cycle) or placebo. Survival endpoints were assessed with Kaplan-Meier estimates and log-rank tests. The influence of TE-HTN on progression-free survival (PFS) and overall survival (OS) was analyzed with univariate and multivariate Cox proportional hazards models. Overall, 73% of lenvatinib-treated patients and 15% of placebo-treated patients experienced TE-HTN. The median PFS for lenvatinib-treated patients with (n = 190) and without TE-HTN (n = 71) was 18.8 and 12.9 months, respectively (hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.39-0.88; P = .0085). For lenvatinib-treated patients, the objective response rate was 69% with TE-HTN and 56% without TE-HTN (odds ratio, 1.72; 95% CI, 0.98-3.01). The median change in tumor size for patients with and without TE-HTN was -45% and -40%, respectively (P = .2). The median OS was not reached for patients with TE-HTN; for those without TE-HTN, it was 21.7 months (HR, 0.43; 95% CI, 0.27-0.69; P = .0003). Although HTN is a clinically significant adverse event that warrants monitoring and management, TE-HTN was significantly correlated with improved outcomes in patients with RR-DTC, indicating that HTN may be predictive for lenvatinib efficacy in this population. Cancer 2018;124:2365-72. © 2018 American Cancer Society. © 2018 American Cancer Society.

Subclinical hypothyroidism in children.

PubMed

Shriraam, M; Sridhar, M

2014-11-01

Subclinical hypothyroidism is a biochemical diagnosis characterized by raised thyroid stimulating hormone and normal free T4, without clinical features of hypothyroidism. This review analyzes the current evidence to arrive at a consensus and algorithm to manage this condition. We searched Pubmed, Cochrane and Embase for articles published between 1990 to 2014, and identified 13 relevant articles dealing with pediatric subclinical hypothyroidism which were suitable to include in our review. Subclinical hypothyroidism is often a benign problem which requires expectant management with periodic monitoring of thyroid function tests and natural progression to overt hypothyroidism occur lot less frequently than expected. There is a paucity of robust randomized intervention studies, especially studies focusing on clinical outcomes. Thyroid replacement therapy is not justified in children with subclinical hypothyroidism when Thyroid stimulating hormone is <10 mIU/L. The main risk factors for progression to overt hypothyroidism are female sex, goiter, family history of thyroid disorder, strongly positive thyroid peroxidase antibodies and symptoms suggesting hypothyroidism. An algorithm for managing this condition is suggested.

Radiofrequency ablation for postsurgical thyroid removal of differentiated thyroid carcinoma

PubMed Central

Xu, Dong; Wang, Lipin; Long, Bin; Ye, Xuemei; Ge, Minghua; Wang, Kejing; Guo, Liang; Li, Linfa

2016-01-01

Differentiated thyroid carcinoma (DTC) is the most common endocrine malignancy. Surgical removal with radioactive iodine therapy is recommended for recurrent thyroid carcinoma, and the postsurgical thyroid removal is critical. This study evaluated the clinical values of radiofrequency ablation (RFA) in the postsurgical thyroid removal for DTC. 35 DTC patients who had been treated by subtotal thyroidectomy received RFA for postsurgical thyroid removal. Before and two weeks after RFA, the thyroid was examined by ultrasonography and 99mTcO4 - thyroid imaging, and the serum levels of free triiodothyronine (FT3), free thyroxin (FT4), thyroid stimulating hormone (TSH) and thyroglobulin (Tg) were detected. The efficacy and complications of RFA were evaluated. Results showed that, the postsurgical thyroid removal by RFA was successfully performed in 35 patients, with no significant complication. After RFA, the average largest diameter and volume were significantly decreased in 35 patients (P > 0.05), and no obvious contrast media was observed in ablation area in the majority of patients. After RFA, the serum FT3, FT4 and Tg levels were markedly decreased (P < 0.05), and TSH level was significantly increased (P < 0.05). After RFA, radioiodine concentration in the ablation area was significantly reduced in the majority of patients. The reduction rate of thyroid update was 0.69±0.20%. DTC staging and interval between surgery and RFA had negative correlation (Pearson coefficient = -0.543; P = 0.001), with no obvious correlation among others influential factors. RFA is an effective and safe method for postsurgical thyroid removal of DTC. PMID:27186311

Neovascular PSMA expression is a common feature in malignant neoplasms of the thyroid

PubMed Central

Heitkötter, Birthe; Steinestel, Konrad; Trautmann, Marcel; Grünewald, Inga; Barth, Peter; Gevensleben, Heidrun; Bögemann, Martin; Wardelmann, Eva; Hartmann, Wolfgang; Rahbar, Kambiz; Huss, Sebastian

2018-01-01

Aim PSMA (prostate-specific membrane antigen) is physiologically expressed in normal prostate tissue and over expressed in prostate cancer cells, therefore constituting a potential target for antibody-based radioligand therapy. Very recent imaging findings reported PSMA-PET/CT uptake in various thyroid lesions. We were therefore encouraged to systematically analyse PSMA expression in different benign and malignant thyroid lesions. Methods Immunohistochemistry was used to detect PSMA expression in 101 thyroid lesions, while neovasculature was identified by CD34 immunostaining. Results PSMA expression in the neovasculature was significantly more frequent in malignant tumors (36/63; 57.1%) compared to benign diseases (5/38; 13.2%; p = 0.0001). In addition, PSMA expression levels in the neovasculature of poorly and undifferentiated thyroid cancers were significantly higher compared to differentiated thyroid tumors (p = 0.021). However, one case with a strong expression in follicular adenoma was identified. Conclusions We conclude that neovascular PSMA expression is common in thyroid cancer but may also rarely be found in benign thyroid diseases, such as follicular adenoma. High expression in the tumor-associated neovasculature is predominantly found in poorly differentiated and undifferentiated (anaplastic) thyroid cancer. This knowledge is highly relevant when interpreting PSMA/PET-CT scans from patients with prostate cancer. In addition, our findings might provide a rationale for further evaluation of PSMA-targeted anti-neovascular or radioligand therapy in metastatic dedifferentiated thyroid cancer. PMID:29515776

131I therapy of thyroid cancer patients.

PubMed

Reiners, C; Farahati, J

1999-12-01

Thyroid cancer is a rare malignancy with wide interethnic and geographic variations. In Germany thyroid carcinoma is the 13th most frequent malignancy (2.7 new cases yearly per 100,000 inhabitants). The overall temporal incidence is increasing slightly in recent years. The most common types of cancer are papillary (60-80%) and follicular cancers (10-20%). The relevant prognostic indicators are tumor stage and distant metastases. The mean survival rates in papillary thyroid cancer usually exceed 90%, whereas in follicular thyroid cancer they amount to approximately 80%. The standard treatment procedure in differentiated papillary and follicular thyroid cancer consists of total thyroidectomy followed by adjuvant ablative therapy with radioiodine. Only in papillary thyroid cancer stage pT1N0M0 lobectomy alone is considered to be appropriate. In patients with locally invasive differentiated thyroid cancers stage pT4 adjuvant percutaneous radiation therapy is a treatment option. Radioiodine therapy has to be performed under the stimulative influence of TSH. Usually TSH suppressive medication with Levothyroxine has to be withdrawn approximately 4 weeks prior to radioiodine therapy. In the future, exogenous stimulation by recombinant TSH may be used instead of thyroid hormone withdrawal. It has been proven by different studies that ablative radioiodine therapy reduces the frequency of recurrences and tumor spread in patients with thyroid cancer significantly. In patients with distant metastases, up to 50% of complete responses may be achieved with radioiodine treatment.

The effect of Ginkgo biloba extract on genotoxic damage in patients with differentiated thyroid carcinoma receiving thyroid remnant ablation with iodine-131.

PubMed

Dardano, Angela; Ballardin, Michela; Caraccio, Nadia; Boni, Giuseppe; Traino, Claudio; Mariani, Giuliano; Ferdeghini, Marco; Barale, Roberto; Monzani, Fabio

2012-03-01

Radioiodine ((131)I) therapy is usually performed in patients with differentiated thyroid cancer (DTC). Although (131)I is generally considered safe, genotoxic damage has been demonstrated both in vivo and in vitro. The aim of the current study was to evaluate the effect of Ginkgo biloba extract (GBE) on the time-course of appearance, after (131)I therapy for DTC, of plasma factors with chromosome-damaging properties (so-called "clastogenic" factors [CFs]) and of micronuclei (MN) in lymphocytes. Twenty-three patients (median age 42 years, range 18-73) with DTC receiving (131)I activity (3.7 GBq) for thyroid remnant ablation were randomly assigned to receive GBE (120 mg/day for one month; n=10) or placebo (n=13) in a double-blind manner. Blood samples were taken at various intervals (from baseline to 90 days) after (131)I therapy. The frequency of MN in blood lymphocytes was determined, and CFs were assayed in plasma by a method that used MN increase in lymphocytes from an healthy donor as the endpoint of the assay. MN in blood lymphocytes increased significantly after (131)I treatment in the placebo group, peaking at the 7th day (p=0.002) and slowly declining thereafter. In contrast, in similarly treated patients who were also treated with GBE both before and after (131)I treatment, a significant increase of blood lymphocyte MN level was not observed. In addition, only the placebo group showed a significant, progressive increase in CFs activity. This peaked at the 14th day (p=0.003 vs. baseline) and was still noted for the last plasma sample. The differences in the change in lymphocyte MN and CFs activity between the placebo and GBE-treated groups were significant (p<0.01 and p<0.05, respectively). Thyroid function tests, including serum thyroglobulin (Tg) and anti-Tg antibody levels, were never significantly different. GBE may protect from possible oxidative and genotoxic damage associated with (131)I treatment in patients requiring (131)I therapy for thyroid cancer, without affecting the clinical outcome. Further studies with larger cohorts of patients are needed to confirm this report and verify the beneficial effect of GBE in patients requiring (131)I therapy, particularly for those in whom repeated treatments and high activities of (131)I are required.

Differential regulation of monocarboxylate transporter 8 expression in thyroid cancer and hyperthyroidism.

PubMed

Badziong, Julia; Ting, Saskia; Synoracki, Sarah; Tiedje, Vera; Brix, Klaudia; Brabant, Georg; Moeller, Lars Christian; Schmid, Kurt Werner; Fuhrer, Dagmar; Zwanziger, Denise

2017-09-01

Thyroid hormone (TH) transporters are expressed in thyrocytes and most play a role in TH release. We asked whether expression of the monocarboxylate transporter 8 (MCT8) and the L-type amino acid transporters LAT2 and LAT4 is changed with thyrocyte dedifferentiation and in hyperfunctioning thyroid tissues. Protein expression and localization of transporters was determined by immunohistochemistry in human thyroid specimen including normal thyroid tissue (NT, n  = 19), follicular adenoma (FA, n  = 44), follicular thyroid carcinoma (FTC, n  = 45), papillary thyroid carcinoma (PTC, n  = 40), anaplastic thyroid carcinoma (ATC, n  = 40) and Graves' disease (GD, n  = 50) by calculating the 'hybrid' (H) score. Regulation of transporter expression was investigated in the rat follicular thyroid cell line PCCL3 under basal and thyroid stimulating hormone (TSH) conditions. MCT8 and LAT4 were localized at the plasma membrane, while LAT2 transporter showed cytoplasmic localization. MCT8 expression was downregulated in benign and malignant thyroid tumours as compared to NT. In contrast, significant upregulation of MCT8, LAT2 and LAT4 was found in GD. Furthermore, a stronger expression of MCT8 was demonstrated in PCCL3 cells after TSH stimulation. Downregulation of MCT8 in thyroid cancers qualifies MCT8 as a marker of thyroid differentiation. The more variable expression of LATs in distinct thyroid malignancies may be linked with other transporter properties relevant to altered metabolism in cancer cells, i.e. amino acid transport. Consistent upregulation of MCT8 in GD is in line with increased TH release in hyperthyroidism, an assumption supported by our in vitro results showing TSH-dependent upregulation of MCT8. © 2017 European Society of Endocrinology.

Chronic lymphocytic thyroiditis is associated with invasive characteristics of differentiated thyroid carcinoma in children and adolescents.

PubMed

Iliadou, Paschalia K; Effraimidis, Grigoris; Konstantinos, Michalakis; Grigorios, Panagiotou; Mitsakis, Periklis; Patakiouta, Frideriki; Pazaitou-Panayiotou, Kalliopi

2015-12-01

The association between chronic lymphocytic thyroiditis (CLT) and thyroid cancer is an interesting topic. The aim of the present study was to evaluate if demographic and histological characteristics as well as the long-term outcome of thyroid cancer was different in children and adolescents with and without CLT. The medical records of children and adolescents (≤21 years old) were reviewed. The following data were recorded: gender, year and age at diagnosis, family history of thyroid cancer, history of external radiation therapy, histological type (papillary and variants, follicular and variants), tumour size, multifocality, infiltration of thyroid parenchyma or surrounding soft tissues, vascular invasion, presence of lymph node and distant metastases. Information about the presence of TgAb and TPOAb was also collected. One hundred eight children and adolescents (median age 19.0, interquartile range 4.0 years) were diagnosed with differentiated thyroid carcinoma (DTC); 31 patients (28.7%) presented histological characteristics compatible with CLT. Infiltration of thyroid parenchyma was more frequent in patients with CLT compared to patients without (74.2% vs 48.1% respectively, P=0.024). Familial papillary thyroid carcinoma (PTC) was more frequent in patients with CLT compared to those without CLT (20.7% vs 2.8% respectively, P=0.009). There was no better outcome with respect to the presence of CLT or not. Children and adolescents with CLT present more frequently familial PTC as well as thyroid cancer with invasive characteristics. © 2015 European Society of Endocrinology.

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

Hes1 Is Required for Appropriate Morphogenesis and Differentiation during Mouse Thyroid Gland Development

PubMed Central

Carre, Aurore; Rachdi, Latif; Tron, Elodie; Richard, Bénédicte; Castanet, Mireille; Schlumberger, Martin; Bidart, Jean-Michel

2011-01-01

Notch signalling plays an important role in endocrine development, through its target gene Hes1. Hes1, a bHLH transcriptional repressor, influences progenitor cell proliferation and differentiation. Recently, Hes1 was shown to be expressed in the thyroid and regulate expression of the sodium iodide symporter (Nis). To investigate the role of Hes1 for thyroid development, we studied thyroid morphology and function in mice lacking Hes1. During normal mouse thyroid development, Hes1 was detected from E9.5 onwards in the median anlage, and at E11.5 in the ultimobranchial bodies. Hes1 −/− mouse embryos had a significantly lower number of Nkx2-1-positive progenitor cells (p<0.05) at E9.5 and at E11.5. Moreover, Hes1 −/− mouse embryos showed a significantly smaller total thyroid surface area (−40 to −60%) compared to wild type mice at all study time points (E9.5−E16.5). In both Hes1 −/− and wild type mouse embryos, most Nkx2-1-positive thyroid cells expressed the cell cycle inhibitor p57 at E9.5 in correlation with low proliferation index. In Hes1 −/− mouse embryos, fusion of the median anlage with the ultimobranchial bodies was delayed by 3 days (E16.5 vs. E13.5 in wild type mice). After fusion of thyroid anlages, hypoplastic Hes1 −/− thyroids revealed a significantly decreased labelling area for T4 (−78%) and calcitonin (−65%) normalized to Nkx2-1 positive cells. Decreased T4-synthesis might be due to reduced Nis labelling area (−69%). These findings suggest a dual role of Hes1 during thyroid development: first, control of the number of both thyrocyte and C-cell progenitors, via a p57-independent mechanism; second, adequate differentiation and endocrine function of thyrocytes and C-cells. PMID:21364918

Using Acoustic Structure Quantification During B-Mode Sonography for Evaluation of Hashimoto Thyroiditis.

PubMed

Rhee, Sun Jung; Hong, Hyun Sook; Kim, Chul-Hee; Lee, Eun Hye; Cha, Jang Gyu; Jeong, Sun Hye

2015-12-01

This study aimed to evaluate the usefulness of Acoustic Structure Quantification (ASQ; Toshiba Medical Systems Corporation, Nasushiobara, Japan) values in the diagnosis of Hashimoto thyroiditis using B-mode sonography and to identify a cutoff ASQ level that differentiates Hashimoto thyroiditis from normal thyroid tissue. A total of 186 thyroid lobes with Hashimoto thyroiditis and normal thyroid glands underwent sonography with ASQ imaging. The quantitative results were reported in an echo amplitude analysis (Cm(2)) histogram with average, mode, ratio, standard deviation, blue mode, and blue average values. Receiver operating characteristic curve analysis was performed to assess the diagnostic ability of the ASQ values in differentiating Hashimoto thyroiditis from normal thyroid tissue. Intraclass correlation coefficients of the ASQ values were obtained between 2 observers. Of the 186 thyroid lobes, 103 (55%) had Hashimoto thyroiditis, and 83 (45%) were normal. There was a significant difference between the ASQ values of Hashimoto thyroiditis glands and those of normal glands (P < .001). The ASQ values in patients with Hashimoto thyroiditis were significantly greater than those in patients with normal thyroid glands. The areas under the receiver operating characteristic curves for the ratio, blue average, average, blue mode, mode, and standard deviation were: 0.936, 0.902, 0.893, 0.855, 0.846, and 0.842, respectively. The ratio cutoff value of 0.27 offered the best diagnostic performance, with sensitivity of 87.38% and specificity of 95.18%. The intraclass correlation coefficients ranged from 0.86 to 0.94, which indicated substantial agreement between the observers. Acoustic Structure Quantification is a useful and promising sonographic method for diagnosing Hashimoto thyroiditis. Not only could it be a helpful tool for quantifying thyroid echogenicity, but it also would be useful for diagnosis of Hashimoto thyroiditis. © 2015 by the American Institute of Ultrasound in Medicine.

Pleural epithelioid angiosarcoma with lymphatic differentiation arisen after radiometabolic therapy for thyroid carcinoma: immunohistochemical findings and review of the literature.

PubMed

Cabibi, Daniela; Pipitone, Giulia; Porcasi, Rossana; Ingrao, Sabrina; Benza, Ignazio; Porrello, Calogero; Cajozzo, Massimo; Giannone, Antonino Giulio

2017-08-15

Pleural angiosarcoma is a rare tumor that causes diffuse pleural thickening and effusion, mimicking mesothelioma. Immunohistochemistry is needed to highlight endothelial differentiation. We describe the first case of pleural angiosarcoma with lymphatic differentiation following radiometabolic therapy for thyroid carcinoma. A 50-year-old man showed diffuse pleural thickening and effusion. Nine years earlier, he underwent thyroidectomy and radiometabolic therapy for thyroid carcinoma with lymph node metastases. Histologically, the tumor consisted of a solid proliferation of atypical epithelioid cells and anastomosed vascular spaces, lacking of red blood cells and containing Alcian blue positive material. The tumor showed positive immunostaining for Vimentin, CD31, CK7, D2-40, c-MYC, Ki67, focal positivity for PanCK, and negative immunostaining for Factor VIII, CD34, WT1, CK5/6, Calretinin, EMA, HBME-1, CEA, p63, EpCAM, Bcl-2, TTF1 and Thyroglobulin. CD99 showed a granular/paranuclear pattern of positivity. The histological and immunohistochemical features were consistent with "pleural angiosarcoma with lymphatic differentiation, epithelioid variant". Epithelioid angiosarcoma with lymphatic differentiation is very rare and aggressive. Moreover, the positivity for c-MYC suggests the relationship with radiometabolic therapy. To our knowledge, this is the first case of pleural c-MYC-positive angiosarcoma with lymphatic differentiation reported in the literature and the first one arisen after radiometabolic therapy for thyroid carcinoma.

Thyroid storm with multiple organ failure, disseminated intravascular coagulation, and stroke with a normal serum FT3 level.

PubMed

Harada, Yuko; Akiyama, Hisanao; Yoshimoto, Tatsuji; Urao, Yasuko; Ryuzaki, Munekazu; Handa, Michiko

2012-01-01

Thyroid storm is a rare disorder with a sudden onset, rapid progression and high mortality. We experienced a case of thyroid storm which had a devastating course, including multiple organ failure (MOF), severe hypoglycemia, disseminated intravascular coagulation (DIC), and stroke. It was difficult to make a diagnosis of thyroid storm in the present patient, because she did not have a history of thyroid disease and her serum FT3 level was normal. Clinicians should be aware that thyroid storm can occur even when there is an almost normal level of thyroid hormones, and that intensive anticoagulation is required for patients with atrial fibrillation to prevent stroke after thyroid storm.

Acute respiratory failure due to thyroid storm developing immediately after delivery.

PubMed

Kitazawa, Chie; Aoki, Shigeru; Takahashi, Tsuneo; Hirahara, Fumiki

2015-12-01

Acute respiratory failure occurs in less than 0.1% of pregnancies. Thyroid storm should be included in the differential diagnosis of possible causes of acute respiratory failure occurring immediately after delivery, and delivery is a high risk factor for thyroid storm in pregnant women with thyrotoxicosis.

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.

Histogram and gray level co-occurrence matrix on gray-scale ultrasound images for diagnosing lymphocytic thyroiditis.

PubMed

Shin, Young Gyung; Yoo, Jaeheung; Kwon, Hyeong Ju; Hong, Jung Hwa; Lee, Hye Sun; Yoon, Jung Hyun; Kim, Eun-Kyung; Moon, Hee Jung; Han, Kyunghwa; Kwak, Jin Young

2016-08-01

The objective of the study was to evaluate whether texture analysis using histogram and gray level co-occurrence matrix (GLCM) parameters can help clinicians diagnose lymphocytic thyroiditis (LT) and differentiate LT according to pathologic grade. The background thyroid pathology of 441 patients was classified into no evidence of LT, chronic LT (CLT), and Hashimoto's thyroiditis (HT). Histogram and GLCM parameters were extracted from the regions of interest on ultrasound. The diagnostic performances of the parameters for diagnosing and differentiating LT were calculated. Of the histogram and GLCM parameters, the mean on histogram had the highest Az (0.63) and VUS (0.303). As the degrees of LT increased, the mean decreased and the standard deviation and entropy increased. The mean on histogram from gray-scale ultrasound showed the best diagnostic performance as a single parameter in differentiating LT according to pathologic grade as well as in diagnosing LT. Copyright © 2016 Elsevier Ltd. All rights reserved.

Typical thyroid-type carcinoma arising in struma ovarii: a report of 4 cases and review of the literature.

PubMed

Roth, Lawrence M; Miller, Alexander W; Talerman, Aleksander

2008-10-01

Struma ovarii has elicited considerable interest because of its many unique features since Ludwig Pick first elucidated its relationship to teratoma in the early part of the 20th century. In this article, we report 3 cases of papillary and 1 of follicular thyroid carcinoma; 2 of these cases were associated with mature cystic teratoma. Metastases occurred in 2 patients, and 1 died of neoplasm. In regard to the occurrence of thyroid-type carcinoma in struma ovarii, precise terminology should be used, and the expression malignant struma ovarii was avoided as a diagnostic term. Upon review of the literature, papillary carcinoma and follicular carcinoma are the most frequent types of malignancy to occur in ovarian struma; other forms of thyroid carcinoma occur only rarely. The diagnostic criteria for cases of papillary carcinoma are similar to those described in the cervical thyroid gland and are based primarily on nuclear and architectural features. In reference to follicular carcinoma, invasion into the surrounding ovarian tissue, vascular invasion, or metastasis is evidence of malignancy. Histological malignancy in a struma does not necessarily equate with biological malignancy, and the majority of thyroid-type carcinomas do not spread beyond the ovary. Occasionally, metastases of ovarian struma have an innocuous histological appearance, and such cases are referred to as highly differentiated follicular carcinoma of ovarian origin (HDFCO). Because its histological appearance resembles that of nonneoplastic thyroid, HDFCO characteristically cannot be diagnosed until the neoplasm spreads beyond the ovary. In this article, we apply the term typical thyroid carcinoma to those forms of thyroid malignancy arising in ovarian struma that closely resemble the types described in the cervical thyroid gland to distinguish them from HDFCO. Typical follicular carcinoma is more aggressive than the somewhat more common papillary carcinoma, and HDFCO is the least aggressive of these tumor types. Cases of thyroid-type carcinoma arising in the ovary sometimes lack evidence of preexisting struma. The more aggressive thyroid-type neoplasms can arise in thyroid tissue within a mature cystic teratoma, or they may overgrow and replace the struma. Primary thyroid-type carcinoma must be distinguished from rare instances of ovarian metastases that originate in the cervical thyroid gland and the less differentiated forms from other ovarian neoplasms such as clear cell adenocarcinoma and tumors with an oxyphilic appearance. In the differential diagnosis with other ovarian neoplasms, cases of thyroid-type carcinoma associated with strumal carcinoid should not be diagnosed as malignant strumal carcinoid because the latter diagnosis might lead to suboptimal therapy.

miR-29a-3p/T-bet Regulatory Circuit Is Altered in T Cells of Patients With Hashimoto's Thyroiditis.

PubMed

Tokić, Stana; Štefanić, Mario; Glavaš-Obrovac, Ljubica; Kishore, Amit; Navratilova, Zdenka; Petrek, Martin

2018-01-01

Hashimoto's thyroiditis (HT) is a common autoimmune thyroid disorder that frequently evolves from asymptomatic, T-cell mediated chronic inflammation toward overt hypothyroidism. Previously, we have demonstrated a role for T-bet, a T helper 1/CD8 + T cell transcription factor (TF), and FoxP3, a regulatory T cell TF, in disease progression and severity, but the basis behind their altered mRNA expression remains unknown. In this study, we aimed to leverage the role for microRNAs, representing negative transcriptional regulators, across the spectrum of HT clinical presentations using the same, well-characterized RNA sample cohort. Ten hypothyroid, untreated patients (hypoHT), 10 hypothyroid cases rendered euthyroid by l-thyroxine therapy (substHT), 11 spontaneously euthyroid HT subjects (euHT), and 10 healthy controls (ctrl) were probed for three candidate immunoregulatory miRNA (miR-9-5p, miR-29a-3p, and miR-210-3p) using quantitative real-time PCR measurements. Data were normalized to U6snRNA and fold difference in expression calculated by the efficiency corrected 2 -ΔΔCt model. Compared to healthy controls, peripheral blood (PB) T cells of HT patients exhibited significantly diminished miR-29a-3p expression levels [median expression levels (IQR), HT vs CTRL, 0.62 (0.44-1.01) vs 1.373 (0.63-2.7), P  = 0.046], and a similar, but not significant decline in miR-210-3p abundance [HT vs CTRL, 0.64 (0.39-1.31) vs 1.2 (0.5-2.56), P  = 0.24, Wilcoxon test]. A significant inverse correlation was observed between the two differentially expressed transcripts, T-bet mRNA and miR-29a-3p. Moreover, altered miR-29a-3p/T-bet expression in T cells of untreated HT patients was related to low serum FT4, high serum thyrotropin, and decreased thyroid volumes. Of note, miR-210-3p expression was positively correlated to HIF1α, and inversely to FoxP3 mRNA levels, but no evidence of differential expression for any of these miRNA-mRNA pairs was observed. Finally, miR-9-5p expression levels were no different in HT vs control comparisons, or related to clinicopathological features. T cell miR-29a-3p is downregulated in HT patients and associated with clinical and biochemical parameters of progressive thyroid injury, plausibly subsequent to altered control of T-bet expression in PB T cells. As such miR-29a-3p/T-bet axis should be further explored as a biomarker or as a plausible target for therapeutic interventions in HT.

Thyroid cancer profile in Mures County (Romania): a 20 years study.

PubMed

Cătană, Ramona; Boilă, Adela; Borda, Angela

2012-01-01

The aim of the present study was to present data on frequency of thyroid cancer in Mures County (Romania) and border counties, a goiter endemic area, and to analyze its histopathological characteristics, over a 20 years period (1990-2009). Demographic, clinical and pathological data were obtained from database registries. Histological subtypes of thyroid cancer were classified according to the WHO criteria (sixth edition, 2004) in the following categories: papillary thyroid carcinoma with its histological subtypes, follicular thyroid carcinoma, poorly differentiated thyroid carcinoma, undifferentiated thyroid carcinoma, medullary carcinoma, lymphoma, metastatic tumors. Our analyze included 524 cases of thyroid cancer of the 3460 surgical thyroid specimens resected between 1990-2009: 410 (78.2%) cases of papillary carcinoma, 19 (3.6%) cases of follicular carcinoma, 24 (4.6%) cases of poorly differentiated carcinoma, 33 (6.3%) cases of undifferentiated carcinoma, 22 (4.1%) medullary carcinomas, eight (1.6%) lymphomas, and eight (1.6%) metastatic tumors. Papillary thyroid carcinoma is the most common histological form (78%) and an increasing incidence of this form was observed. A statistical significant increase in the incidence of the follicular variant of papillary carcinoma was noticed between 2000-2009, compared to 1990-2000. An increased incidence of small tumors was also found (6.66%, 1990-1999 vs. 23.5%, 2000-2009). The undifferentiated thyroid cancer had a marked decreasing trend (20%, 1990-1999 vs. 3.45%, 2000-2009). Our study demonstrates an increasing trend in the incidence of thyroid cancer in the last 20 years. This increase is mainly due to the small papillary cancers, by contrast to the undifferentiated thyroid cancers that have a decreasing trend. A better understanding and description of the morphological criteria could explained the increasing incidence of the follicular variant of papillary carcinoma.

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.

An unusual metastasis of a papillary thyroidian carcinoma with follicular pattern.

PubMed

Coconu, M; Berdan, G; Roşculescu, I; Herlea, V

1998-01-01

The case of a 67-year-old man is presented. He was admitted for the presence of a left parietal tumour with progressive growing, without any other objective or subjective symptomatology. CT-scan detects a left parietal osteolytic area. The histopathological aspect suggested an adenocarcinomatous metastasis with papillary pattern, moderately differentiated. With the purpose of diagnosing the original tumour, immunnohistochemical techniques were performed, which led to a diagnosis of a thyroidian carcinoma. At the histological examination of the surgical extirpated thyroid, it was proved to be a papillary carcinoma (Chan, 1990, Hay, 1990), the follicular pattern.

Is the measurement of inferior thyroid artery blood flow velocity by color-flow Doppler ultrasonography useful for differential diagnosis between gestational transient thyrotoxicosis and Graves' disease? A prospective study.

PubMed

Zuhur, Sayid Shafi; Ozel, Alper; Velet, Selvinaz; Buğdacı, Mehmet Sait; Cil, Esra; Altuntas, Yüksel

2012-01-01

To determine the role of peak systolic velocity, end-diastolic velocity and resistance indices of both the right and left inferior thyroid arteries measured by color-flow Doppler ultrasonography for a differential diagnosis between gestational transient thyrotoxicosis and Graves' disease during pregnancy. The right and left inferior thyroid artery-peak systolic velocity, end-diastolic velocity and resistance indices of 96 patients with thyrotoxicosis (41 with gestational transient thyrotoxicosis, 31 age-matched pregnant patients with Graves' disease and 24 age- and sex-matched non-pregnant patients with Graves' disease) and 25 age and sex-matched healthy euthyroid subjects were assessed with color-flow Doppler ultrasonography. The right and left inferior thyroid artery-peak systolic and end-diastolic velocities in patients with gestational transient thyrotoxicosis were found to be significantly lower than those of pregnant patients with Graves' disease and higher than those of healthy euthyroid subjects. However, the right and left inferior thyroid artery peak systolic and end-diastolic velocities in pregnant patients with Graves' disease were significantly lower than those of non-pregnant patients with Graves' disease. The right and left inferior thyroid artery peak systolic and end-diastolic velocities were positively correlated with TSH-receptor antibody levels. We found an overlap between the inferior thyroid artery-blood flow velocities in a considerable number of patients with gestational transient thyrotoxicosis and pregnant patients with Graves' disease. This study suggests that the measurement of inferior thyroid artery-blood flow velocities with color-flow Doppler ultrasonography does not have sufficient sensitivity and specificity to be recommended as an initial diagnostic test for a differential diagnosis between gestational transient thyrotoxicosis and Graves' disease during pregnancy.

Is the measurement of inferior thyroid artery blood flow velocity by color-flow Doppler ultrasonography useful for differential diagnosis between gestational transient thyrotoxicosis and Graves' disease? A prospective study

PubMed Central

Zuhur, Sayid Shafi; Özel, Alper; Velet, Selvinaz; Buğdacı, Mehmet Sait; Çil, Esra; Altuntas, Yüksel

2012-01-01

OBJECTIVE: To determine the role of peak systolic velocity, end-diastolic velocity and resistance indices of both the right and left inferior thyroid arteries measured by color-flow Doppler ultrasonography for a differential diagnosis between gestational transient thyrotoxicosis and Graves' disease during pregnancy. METHODS: The right and left inferior thyroid artery-peak systolic velocity, end-diastolic velocity and resistance indices of 96 patients with thyrotoxicosis (41 with gestational transient thyrotoxicosis, 31 age-matched pregnant patients with Graves' disease and 24 age- and sex-matched non-pregnant patients with Graves' disease) and 25 age- and sex-matched healthy euthyroid subjects were assessed with color-flow Doppler ultrasonography. RESULTS: The right and left inferior thyroid artery-peak systolic and end-diastolic velocities in patients with gestational transient thyrotoxicosis were found to be significantly lower than those of pregnant patients with Graves' disease and higher than those of healthy euthyroid subjects. However, the right and left inferior thyroid artery peak systolic and end-diastolic velocities in pregnant patients with Graves' disease were significantly lower than those of non-pregnant patients with Graves' disease. The right and left inferior thyroid artery peak systolic and end-diastolic velocities were positively correlated with TSH-receptor antibody levels. We found an overlap between the inferior thyroid artery-blood flow velocities in a considerable number of patients with gestational transient thyrotoxicosis and pregnant patients with Graves' disease. CONCLUSIONS: This study suggests that the measurement of inferior thyroid artery-blood flow velocities with color-flow Doppler ultrasonography does not have sufficient sensitivity and specificity to be recommended as an initial diagnostic test for a differential diagnosis between gestational transient thyrotoxicosis and Graves' disease during pregnancy. PMID:22358236

Implications of prognostic factors and risk groups in the management of differentiated thyroid cancer.

PubMed

Shaha, Ashok R

2004-03-01

The outcome in differentiated thyroid cancer generally depends on the stage of the disease at the time of presentation; prognostic factors such as age, grade, size, extension, or distant metastasis; and risk groups (eg, low or high risk). The author has reviewed a large number of patients with differentiated thyroid cancer to analyze their hypothesis and to confirm that various risk groups have a major implication in relation to extent of the treatment and outcome. Differentiated thyroid cancers make up 90% of all thyroid tumors. The prognostic factors are well defined, such as age, size of the tumor, extrathyroidal extension, presence of distant metastasis, histological appearance, and grade of the tumor. The author has previously divided the risk groups into low-, intermediate-, and high-risk categories based on prognostic factors. The study describes the author's treatment approach related to the extent of thyroidectomy and adjuvant therapy based on various risk groups and the long-term survival. Retrospective. In a retrospective review of 1038 patients with differentiated thyroid carcinoma, various prognostic factors were studied by univariate and multivariate analysis. The significant prognostic factors were studied in detail and, based on these prognostic factors, the patients were divided into low-, intermediate- and high-risk groups. The survival curves were plotted by Kaplan-Meier method. The long-term survivals in low-, intermediate- and high-risk groups were 99%, 87%, and 57% respectively. Based on these risk groups, a decision tree was made regarding extent of thyroidectomy and adjuvant treatment. In the high-risk group and selected patients in the intermediate-risk group, aggressive surgery including removal of all gross disease and extrathyroidal extension with postoperative radioactive iodine ablation is recommended. In the low-risk group and selected patients in the intermediate-risk group, lobectomy appears to be satisfactory with excellent long-term outcome. The surgical treatment offers the best long-term results in low-risk patients, and the role of adjuvant treatment in this group is questionable. The decisions in the management of well-differentiated thyroid cancer should be based on various prognostic factors and risk groups. The long-term survival in the low-risk group is excellent, and consideration should be given to conservative surgical resection depending on the extent of the disease. In the high-risk group and selected patients in the intermediate-risk group, total thyroidectomy with radioactive ablation is warranted. A consideration may be given to external-beam radiation therapy in selected high-risk patients. It is apparent, based on the author's clinical experience and critical retrospective analysis, that the author's hypothesis that risk groups are extremely important in the long-term outcome of patients with differentiated thyroid cancer is correct. Based on various risk groups, the author currently is able to guide the treatment policies for thyroid cancer.

Ultrasonography and the Ultrasound-Based Management of Thyroid Nodules: Consensus Statement and Recommendations

PubMed Central

Baek, Jung Hwan; Jung, So Lyung; Kim, Dong Wook; Kim, Eun Kyung; Kim, Ji Young; Kwak, Jin Young; Lee, Jeong Hyun; Lee, Joon Hyung; Lee, Young Hen; Na, Dong Gyu; Park, Jeong Seon; Park, Sun Won

2011-01-01

The detection of thyroid nodules has become more common with the widespread use of ultrasonography (US). US is the mainstay for detecting and making the differential diagnosis of thyroid nodules as well as for providing guidance for a biopsy. The Task Force on Thyroid Nodules of the Korean Society of Thyroid Radiology has developed recommendations for the US diagnosis and US-based management of thyroid nodules. The review and recommendations in this report have been based on a comprehensive analysis of the current literature, the results of multicenter studies and from the consensus of experts. PMID:21228935

Zebrafish hhex, nk2.1a, and pax2.1 regulate thyroid growth and differentiation downstream of Nodal-dependent transcription factors.

PubMed

Elsalini, Osama A; von Gartzen, Julia; Cramer, Matthias; Rohr, Klaus B

2003-11-01

During zebrafish development, the thyroid primordium initiates expression of molecular markers such as hhex and nk2.1a in the endoderm prior to pharynx formation. As expected for an endodermally derived organ, initiation of thyroid development depends on Nodal signalling. We find that it also depends on three downstream effectors of Nodal activity, casanova (cas), bonnie and clyde (bon), and faust (fau)/gata5. Despite their early Nodal-dependent expression in the endoderm, both hhex and nk2.1a are only required relatively late during thyroid development. In hhex and nk2.1a loss-of-function phenotypes, thyroid development is initiated and arrests only after the primordium has evaginated from the pharyngeal epithelium. Thus, like pax2.1, both hhex and nk2.1a have similarly late roles in differentiation or growth of thyroid follicular cells, and here, we show that all three genes act in parallel rather than in a single pathway. Our functional analysis suggests that these genes have similar roles as in mammalian thyroid development, albeit in a different temporal mode of organogenesis.

Sarcoma of the thyroid region mimicking Riedel's thyroiditis

PubMed Central

Torres-Montaner, A; Beltran, M; d Romero; Oliva, H

2001-01-01

Because sarcomas of the anterior lower neck region occur so infrequently, they are not usually considered in the differential diagnosis of Riedel's thyroiditis. Riedel's thyroiditis itself may be confused on clinical grounds alone with malignant neoplasms because of its invasive features. Sarcomatoid carcinoma is the main entity to be discarded in this regard. This is accomplished through histological examination by the finding of carcinomatous areas and/or reactivity with epithelial markers. These features also set apart sarcomatoid carcinoma from true sarcomas. This report concerns a patient with a sarcoma of the anterior lower neck region which was initially suspected to be Riedel's thyroiditis or sarcomatoid carcinoma on clinical and radiological grounds. A peroperative biopsy was interpreted by two independent pathologists as consistent with Riedel's thyroiditis. The subsequent clinical course and postmortem examination demonstrated a high grade sarcoma with metastasis to both lungs and the pleura, and invasion of adjacent neck structures. Nevertheless, some areas of the postmortem material showed a microscopic pattern similar to mediastinal fibrosis, raising the possibility of the malignant transformation of a fibrosclerotic lesion. Key Words: Riedel's thyroiditis • sarcomatoid carcinoma • fibrous histiocytoma • differential diagnosis PMID:11429435

The Predictive Values of Lesion Size, F-18 FDG Avidity and I-131 Avidity for the Clinical Outcome of I-131 Treatment in Patients with Metastatic Differentiated Thyroid Carcinoma Only in the Lung.

PubMed

Choi, Joon Ho; Byun, Byung Hyun; Lim, Ilhan; Moon, Hansol; Park, Jihyun; Chang, Kyoung Jin; Kim, Byung Il; Choi, Chang Woon; Lim, Sang Moo

2018-04-01

We aimed to evaluate the prognostic values of radiography, F-18 FDG PET, and I-131 whole body scans in patients with lung-only metastasis from differentiated thyroid carcinoma (DTC). Between 1998 and 2013, we included 31 patients (F: 26, M: 5) with lung-only metastasis from DTC who had been treated with I-131 and underwent PET. Lung metastasis was categorized according to the size (macronodular ≥1.0 cm vs. micronodular <1.0 cm), FDG avidity (avid vs. non-avid), and I-131 avidity (avid vs. non-avid). Progression-free survival (PFS) was evaluated for each patient. Among 31 patients, seven (23%) had macronodular lung metastasis, 26 (84%) had FDG avid lung metastasis, and 16 (52%) had I-131 avid lung metastasis. During the median follow-up period of 9.4 y, median PFS was 6.1 y. Based on Kaplan-Meier analysis, macronodular lung metastasis ( p  = 0.017) and I-131 non-avid lung metastasis ( p  = 0.059) were significantly associated with worse outcomes, but FDG avid lung metastasis was not ( p  = 0.135). Patients with FDG non-avid lung metastasis did not experience disease progression during follow-up, while 11 of 26 patients (42%) experienced disease progression. Based on univariate analysis, the hazard ratio for a poor prognosis was 3.78 ( p  = 0.029) for macronodular lung metastasis and 3.29 ( p  = 0.079) for I-131 non-avid lung metastasis. Macronodular and I-131 non-avid lung metastasis were associated with a poor prognosis in lung-only metastasis from DTC. Although FDG avid lung metastasis may be associated with a poor prognosis, a larger-scale study is needed.

PD-1+Tim-3+ CD8+ T Lymphocytes Display Varied Degrees of Functional Exhaustion in Patients with Regionally Metastatic Differentiated Thyroid Cancer

PubMed Central

Severson, Jill J.; Serracino, Hilary S.; Mateescu, Valerica; Raeburn, Christopher D.; C.McIntyre, Robert; Sams, Sharon B.; Haugen, Bryan R.; French, Jena D.

2015-01-01

Regional metastatic differentiated thyroid cancer (mDTC) provides a unique model in which to study the tumor-immune interface. These lymph node (LN) metastases persist for years, generally without progression to distant metastases. While the immune system likely impedes disease progression, it is unsuccessful in eliminating disease. Our previous studies revealed that programmed death-1 (PD-1)+ T cells were enriched in tumor-involved lymph nodes (TILN). Tumor-associated leukocytes and tumor cells were collected from grossly involved LNs from 12 patients to further characterize the phenotype and functional potential of mDTC-associated PD-1+ T cells. PD-1+CD4+ and PD-1+CD8+ T cells were enriched in 8/12 TILN samples. PD-1+ T cells co-expressed Tim-3 and CD69 and failed to down-regulate CD27. CD8+ T cells, but not CD4+ T cells, from these samples were variably deficient in their ability to produce effector cytokines when compared to control TILNs that lacked resident PD-1+ T cells. PD-1+CD8+ T cells were capable of exocytosis but lacked intracellular perforin. Surprisingly, T-cell proliferative capacity was largely maintained in all samples. Thus, while PD-1 expression by mDTC-associated CD8+ T cells was associated with dysfunction, exhaustion was not complete. Notably, molecular markers of exhaustion did not translate to dysfunction in all samples or in CD4+ T cells. Regulatory T (Treg) cells, PD-L1, and galectin-9 were commonly found in mDTC and likely contributed to the initiation of T-cell exhaustion and disease progression. Therapies that release the effects of PD-1 and Tim-3 and reduce the suppressive effects of Tregs may encourage tumor elimination in patients with mDTC. PMID:25701326

Extrathyroidal Extension Is Associated with Compromised Survival in Patients with Thyroid Cancer.

PubMed

Youngwirth, Linda M; Adam, Mohamed A; Scheri, Randall P; Roman, Sanziana A; Sosa, Julie A

2017-05-01

Patients with thyroid cancer who have extrathyroidal extension (ETE) are considered to have more advanced tumors. However, data on the impact of ETE on patient outcomes remain limited. The purpose of this study was to evaluate the association between ETE and survival in patients with thyroid cancer. The National Cancer Database (1998-2012) was queried for all adult patients with differentiated thyroid cancer and medullary thyroid cancer. Patients were divided into three groups: no ETE (T1 and T2 tumors), minimal ETE (T3 tumors <4 cm), and extensive ETE (T4 tumors <4 cm). Patient demographic, clinical, and pathologic factors were evaluated for all patients. A Cox proportional hazards model was developed for each histology to identify factors associated with survival. In total, 241,118 patients with differentiated thyroid cancer met the inclusion criteria; 86.9% had no ETE, 9.1% minimal ETE, and 4.0% extensive ETE. Compared with patients with no ETE, patients with minimal and extensive ETE were more likely to have larger tumors (1.4 cm vs. 1.8 cm and 2.0 cm, respectively), lymphovascular invasion (8.6% vs. 28.0% and 35.1%, respectively), positive margins after thyroidectomy (6.1% vs. 35.2% and 45.9%, respectively), and regional lymph node metastases (32.5% vs. 67.0% and 74.6%, respectively; all p < 0.01). After adjustment, minimal ETE (hazard ratio [HR] = 1.13; p < 0.01) and extensive ETE (HR = 1.74; p < 0.01) were associated with compromised survival for patients with differentiated thyroid cancer. In total, 3415 patients with medullary thyroid cancer met the inclusion criteria; 87.9% had no ETE, 7.1% minimal ETE, and 5.0% extensive ETE. Compared with patients with no ETE, patients with minimal and extensive ETE were more likely to have larger tumors (1.7 cm vs. 2.2 cm and 2.2 cm, respectively), lymphovascular invasion (19.2% vs. 68.9% and 79.3%, respectively), positive margins after thyroidectomy (5.8% vs. 44.1% and 51.9%, respectively), and regional lymph node metastases (39.0% vs. 90.5% and 94.4%, respectively; all p < 0.01). After adjustment, extensive ETE (HR = 1.63; p = 0.01) was associated with compromised survival for patients with medullary thyroid cancer. In patients with differentiated and medullary thyroid cancers, ETE is associated with compromised survival. Given these findings, ETE should be included in the thyroid cancer treatment guidelines.

Influence of thyroid in nervous system growth.

PubMed

Mussa, G C; Mussa, F; Bretto, R; Zambelli, M C; Silvestro, L

2001-08-01

Nervous system growth and differentiation are closely correlated with the presence of iodine and thyroid hormones in initial development stages. In the human species, encephalon maturation during the first quarter of pregnancy is affected according to recent studies by the transplacenta passage of maternal thyroid hormones while it depends on initial iodiothyronin secretion by the foetal gland after the 12th week of pregnancy. Thyroid hormone deficiency during nervous system development causes altered noble nervous cells, such as the pyramidal cortical and Purkinje cells, during glial cell proliferation and differentiation alike. Neurons present cell hypoplasia with reduced axon count, dendritic branching, synaptic spikes and interneuron connections. Oligodendrocytes decrease in number and average myelin content consequently drops. Biochemical studies on hypothyroid rats have demonstrated alterations to neuron intraplasmatic microtubule content and organisation, changed mitochondria number and arrangement and anomalies in T3 nuclear and citoplasmatic receptor maturation. Alterations to microtubules are probably responsible for involvement of the axon-dendrite system, and are the consequence of deficient thyroid hormone action on the mitochondria, the mitochondria enzymes and proteins associated with microtubules. Nuclear and citoplasmatic receptors have been identified and gene clonation studies have shown two families of nuclear receptors that include several sub-groups in their turn. A complex scheme of temporal and spatial expression of these receptors exists, so they probably contribute with one complementary function, although their physiological role differs. The action of thyroid hormones occurs by changing cell protein levels because of their regulation at the transcriptional or post-transcriptional level. Genes submitted to thyroid hormone control are either expressed by oligodendrytes, which are myelin protein coders or glial differentiation mediators, or are nervous cell specific, genes coding neurotropins or proteins involved in synaptic excitation. The use of new PMRS and MRI non-invasive techniques has enabled identification of metabolic and biochemical markers for alterations in the encephalon of untreated hypothyroid children. Even an excess of thyroid hormones during early nervous system development can cause permanent effects. Hyperthyroidism in fact initially induces accelerated maturation process including cell migration and differentiation, extension of dendritic processes and synaptogenesis but a later excess of thyroid hormones causes reduction of the total number of dendritic spikes, due to early interruption of neuron proliferation. Experimental studies and clinical research have clarified not only the correlation between nervous system maturation and thyroid function during early development stages and the certain finding from this research is that both excess and deficient thyroid hormones can cause permanent anatomo-functional alterations to the nervous system.

Targeted Therapy Shows Benefit in Rare Type of Thyroid Cancer

Cancer.gov

Treatment with the multitargeted agent vandetanib (Caprelsa) improved progression-free survival in patients with medullary thyroid cancer (MTC), according to findings from a randomized clinical trial.

Oncogenesis of Thyroid Cancer

PubMed Central

Younis, Enas

2017-01-01

Thyroid neoplasms encompass a variety of lesions that range from benign adenomas to malignancies. These latter can be well-differentiated, poorly differentiated or undifferentiated (anaplastic) carcinomas. More than 95% of thyroid cancers are derived from thyroid follicular cells, while 2-3% (medullary thyroid cancers, MTC) originate from calcitonin producing C-cells. Over the last decade, investigators have developed a clearer understanding of genetic alterations underlying thyroid carcinogenesis. A number of point mutations and translocations are involved, not only in its tumorigenesis, but also as have potential use as diagnostic and prognostic indicators and therapeutic targets. Many occur in genes for several important signaling pathways, in particular the mitogen-activated protein kinase (MAPK) pathway. Sporadic (isolated) lesions account for 75% of MTC cases, while inherited MTC, often in association with multiple endocrine neoplasia (MEN) type 2A and 2B syndromes, constitute the remainder. However, non-MEN familial MTC may also occur. Advances in genetic testing have revolutionized the management of MTC, with prospects of genetic screening, testing and early prophylactic thyroidectomy. Ethical concerns of these advances are addressed. PMID:28610401

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.

Radioactive iodine therapy: Effect on functioning metastases of adenocarcinoma of the thyroid

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

Seidlin, S.M.; Marinelli, L.D.; Oshry, E.

1990-09-01

A case of metastatic adenocarcinoma of the thyroid is reported in which treatment by means of radioactive iodine has been successful. The patient was completely thyroidectomized for malignant adenoma in 1923, with neither thyrotoxicosis then nor hypothyroidism postoperatively; 15 years later there developed classic symptoms of hyperthyroidism and severe pain in the lower back. In October 1939 a pulsating tumor removed from the level of the 12th thoracic vertebra proved to be metastatic thyroid adenocarcinoma (histologically well differentiated, with small follicles and colloid). In the next two years hyperthyroidism increased and roentgenograms revealed new metastases in the lungs, upper partmore » of the right femur, second rib on the left side, left ilium, and skull. Roentgenologic irradiation of the metastases proved ineffectual. In March 1943 a tracer dose of radioactive iodine revealed iodine retention by all the known lesions and no evidence of residual thyroid tissue in the neck. Therapeutic amounts of radioactive iodine were administered orally between May and October 1943. Definite and lasting clinical improvement followed. In April 1944 and March 1945 additional I* was administered with a resultant disappearance of pain, increase in weight, and progressive change in all clinical criteria in the direction of hypothyroidism. Roentgenographic evidence pointed to an arrest if not a regression of the disease. No untoward effects followed this therapy. Radioactive iodine seems to be an effective therapeutic agent in the control of this type of tumor.« less

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 continuing importance of thyroid scintigraphy in the era of high-resolution ultrasound.

PubMed

Meller, J; Becker, W

2002-08-01

At the molecular level, the uptake of radioiodine and pertechnetate is proportional to the expression of the thyroidal sodium/iodine symporter (NIS). Qualitative and quantitative scintigraphic evaluation of the thyroid is performed with a gamma camera fitted with an on-line computer system and enables determination of the iodine uptake or the technetium uptake (TCTU) as an iodine clearance equivalent. Despite new molecular genetic insights into congenital hypothyroidism, the iodine-123 or pertechnetate scan remains the most accurate test for the detection of ectopic thyroid tissue. Following the identification of specific mutations of the genes coding for the NIS, thyroid peroxidase and pendrin, the discharge test has lost its role in establishing the diagnosis of inherited dyshormonogenesis, but it is still of value in the assessment of defect severity. In PDS mutations the test can be used to establish the diagnosis of syndromic disease. Quantitative pertechnetate scintigraphy is the most sensitive and specific technique for the diagnosis and quantification of thyroid autonomy. The method has proved to be valuable in risk stratification of spontaneous or iodine-induced hyperthyroidism, in the estimation of the target volume prior to radioiodine therapy and in the evaluation of therapeutic success after definitive treatment. In iodine deficiency areas the thyroid scan remains indispensable for the functional characterisation of a thyroid nodule and is still a first-line diagnostic procedure in cases of suspected thyroid malignancy. This is especially of importance in patients with Graves' disease, among whom a relatively high prevalence of cancer has been found in cold thyroid nodules. While determination of the TCTU is without any value in the differentiation between autoimmune thyroiditis and Graves' disease in most cases, it is of substantial importance in the differentiation between hyperthyroid autoimmune thyroiditis and Graves' disease.

Molecular imaging with (99m)Tc-MIBI and molecular testing for mutations in differentiating benign from malignant follicular neoplasm: a prospective comparison.

PubMed

Giovanella, L; Campenni, A; Treglia, G; Verburg, F A; Trimboli, P; Ceriani, L; Bongiovanni, M

2016-06-01

To compare mutation analysis of cytology specimens and (99m)Tc-MIBI thyroid scintigraphy for differentiating benign from malignant thyroid nodules in patients with a cytological reading of follicular neoplasm. Patients ≥18 years of age with a solitary hypofunctioning thyroid nodule (≥10 mm), normal thyrotropin and calcitonin levels, and a cytological diagnosis of follicular neoplasm were prospectively enrolled. Mutation analysis and (99m)Tc-MIBI scintigraphy were performed and patients were subsequently operated on to confirm or exclude a malignant lesion. Mutations for KRAS, HRAS and NRAS and for BRAF and translocations of PAX8/PPARγ, RET/PTC1 and RET/PTC3 were investigated. Static thyroid scintigraphic images were acquired 10 and 60 min after intravenous injection of 200 MBq of (99m)Tc-MIBI and visually assessed. Additionally, the MIBI washout index was calculated using a semiquantitative method. In our series, 26 % of nodules with a follicular pattern on cytology were malignant with a prevalence of follicular carcinomas. (99m)Tc-MIBI scintigraphy was found to be significantly more accurate (positive likelihood ratio 4.56 for visual assessment and 12.35 for semiquantitative assessment) than mutation analysis (positive likelihood ratio 1.74). A negative (99m)Tc-MIBI scan reliably excluded malignancy. In patients with a thyroid nodule cytologically diagnosed as a follicular proliferation, semiquantitative analysis of (99m)Tc-MIBI scintigraphy should be the preferred method for differentiating benign from malignant nodules. It is superior to molecular testing for the presence of differentiated thyroid cancer-associated mutations in fine-needle aspiration cytology sample material.

Incidence of thyroid cancer in the selected areas of iodine deficiency in Poland.

PubMed

Szybiński, Z; Huszno, B; Zemla, B; Bandurska-Stankiewicz, E; Przybylik-Mazurek, E; Nowak, W; Cichon, S; Buziak-Bereza, M; Trofimiuk, M; Szybiński, P

2003-01-01

The aim of the study was to evaluate the incidence rate (IR), trend and histotype of the differentiated thyroid cancer in the selected areas with varying iodine deficiency. The study was carried out in three areas: Krakow, (Carpathian endemic goiter area with 1.99 million mixed rural and urban population), Gliwice (Upper Silesia--moderate iodine deficiency area mostly industrial with 4.89 million inhabitants) and Olsztyn (slight iodine deficiency area, mainly rural with 0.77 million inhabitants). Between 1990 and 2001, in the study area 2691 newly diagnosed cases of malignant neoplasms of the thyroid gland were registered. In over 80% of patients it was differentiated thyroid cancer: mainly in women over 40 years, with F/M ratio 5.8. The highest percentage of papillary cancer 72.9% was observed in Olsztyn and lowest--50.0%--in Krakow and Nowy Sacz districts. In this period of time incidence rate of differentiated thyroid cancer in women increased in Kraków, Gliwice, and Olsztyn from 1.51 to 9.34 in 1998 1.27 to 5.74 in 1999 and from 2.52 to 11.35 in 2001 respectively. In the youngest (0-20 years) age group no significant increase of IR was observed. Between 1998 and 2001 the dynamics of increase of the thyroid cancer incidence markedly diminished. In conclusion it was hypothesised that an increase in IR of differentiated thyroid cancer in the study area was caused mainly by the suspension of iodine prophylaxis in 1980 and was diminished by the introduction of an obligatory model of iodine prophylaxis in 1996/1997. It was modified in terms of histotype and dynamics of increase by exposure to ionizing radiation. A very specific group at risk on the population level were women aged 20-40 years in the reproductive age exposed to iodine deficiency after suspension of iodine prophylaxis in 1980 and to radiation after the Chernobyl accident in 1986.

[Painless thyroiditis].

PubMed

Okamura, Ken; Fujikawa, Megumi; Bandai, Sachiko

2006-12-01

Painless thyroiditis is characterized by painless low-uptake thyrotoxicosis (thyrotoxicosis without hyperthyroidism). Destructive damage of the thyroid has been thought to be the mechanism for self-limited thyrotoxicosis. However, hydrolysis of thyroglobulin must be responsible for the release of excessive thyroid hormone. Low-uptake of iodine and excessive release of thyroid hormone suggest the uncoupling of hormone synthesis and hormone secretion in the thyroid gland. Suppressed serum TSH level, various cytokines or growth factors including TGFbeta1, and thyroglobulin itself may be responsible for the suppressed hormone synthesis. The mechanism for persistent hormone release despite suppressed hormone synthesis should be clarified. Quantitative TSH binding inhibitor immunoglobulin assay is helpful for the differential diagnosis of painless thyroiditis and Graves' hyperthyroidism.

Thyroid nodules and differentiated thyroid cancer: update on the Brazilian consensus.

PubMed

Rosário, Pedro Weslley; Ward, Laura S; Carvalho, Gisah A; Graf, Hans; Maciel, Rui M B; Maciel, Léa Maria Z; Maia, Ana Luiza; Vaisman, Mário

2013-06-01

Thyroid nodules are frequent findings, especially when sensitive imaging methods are used. Although thyroid cancer is relatively rare, its incidence is increasing, particularly in terms of small tumors, which have an uncertain clinical relevance. Most patients with differentiated thyroid cancer exhibit satisfactory clinical outcomes when treatment is appropriate, and their mortality rate is similar to that of the overall population. However, relapse occurs in a considerable fraction of these patients, and some patients stop responding to conventional treatment and eventually die from their disease. Therefore, the challenge is how to identify the individuals who require more aggressive disease management while sparing the majority of patients from unnecessary treatments and procedures. We have updated the Brazilian Consensus that was published in 2007, emphasizing the diagnostic and therapeutic advances that the participants, representing several Brazilian university centers, consider most relevant in clinical practice. The formulation of the present guidelines was based on the participants' experience and a review of the relevant literature.

Temporary ovarian failure in thyroid cancer patients after thyroid remnant ablation with radioactive iodine

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

Raymond, J.P.; Izembart, M.; Marliac, V.

We studied ovarian function retrospectively in 66 women who had regular menstrual cycles before undergoing complete thyroidectomy for differentiated thyroid cancer and subsequent thyroid remnant ablation with /sup 131/I. Eighteen women developed temporary amenorrhea accompanied by increased serum gonadotropin concentrations during the first year after /sup 131/I therapy. No correlation was found between the radioactive iodine dose absorbed, thyroid uptake before treatment, oral contraceptive use, or thyroid autoimmunity. Only age was a determining factor, with the older women being the most affected. We conclude that radioiodine ablation therapy is followed by transient ovarian failure, especially in older women.

Postotic and preotic cranial neural crest cells differently contribute to thyroid development.

PubMed

Maeda, Kazuhiro; Asai, Rieko; Maruyama, Kazuaki; Kurihara, Yukiko; Nakanishi, Toshio; Kurihara, Hiroki; Miyagawa-Tomita, Sachiko

2016-01-01

Thyroid development and formation vary among species, but in most species the thyroid morphogenesis consists of five stages: specification, budding, descent, bilobation and folliculogenesis. The detailed mechanisms of these stages have not been fully clarified. During early development, the cranial neural crest (CNC) contributes to the thyroid gland. The removal of the postotic CNC (corresponding to rhombomeres 6, 7 and 8, also known as the cardiac neural crest) results in abnormalities of the cardiovascular system, thymus, parathyroid glands, and thyroid gland. To investigate the influence of the CNC on thyroid bilobation process, we divided the CNC into two regions, the postotic CNC and the preotic CNC (from the mesencephalon to rhombomere 5) regions and examined. We found that preotic CNC-ablated embryos had a unilateral thyroid lobe, and confirmed the presence of a single lobe or the absence of lobes in postotic CNC-ablated chick embryos. The thyroid anlage in each region-ablated embryos was of a normal size at the descent stage, but at a later stage, the thyroid in preotic CNC-ablated embryos was of a normal size, conflicting with a previous report in which the thyroid was reduced in size in the postotic CNC-ablated embryos. The postotic CNC cells differentiated into connective tissues of the thyroid in quail-to-chick chimeras. In contrast, the preotic CNC cells did not differentiate into connective tissues of the thyroid. We found that preotic CNC cells encompassed the thyroid anlage from the specification stage to the descent stage. Finally, we found that endothelin-1 and endothelin type A receptor-knockout mice and bosentan (endothelin receptor antagonist)-treated chick embryos showed bilobation anomalies that included single-lobe formation. Therefore, not only the postotic CNC, but also the preotic CNC plays an important role in thyroid morphogenesis. Copyright © 2015 Elsevier Inc. All rights reserved.

PROGRESS TOWARDS DEVELOPMENT OF AN AMPHIBIAN-BASED THYROID SCREENING ASSAY USING XENOPUS LAEVIS: ORGANISMAL AND THYROIDAL RESPONSES TO THE MODEL COMPOUNDS 6-PROPYLTHIOURACIL, METHIMAZOLE, AND THYROXINE.

EPA Science Inventory

The data presented in this manuscript specifically addresses the development and standardization needs associated with an amphibian thyroid axis screening assay. A protocol for an amphibian growth and reproduction test has been requested by the Office of Science Council and Polic...

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

[Possibilities of ultrasonic investigations in differentiation of a small-foci impairment of thyroid gland].

PubMed

Reyti, A O; Vityuk, N V; Medvedev, V E; Starushok, I O

2015-03-01

The results of ultrasound investigation of microcarcinomas and nontumoral foci of thyroid gland up to 10 mm in diameter and malignant foci over 10 mm are presented. Ultrasound signs are depicted, in accordance to which a potentially malignant thyroid gland foci are delineated, what demands a morphological (cytological) verification conduction.

Characterisation of human thyroid epithelial cells immortalised in vitro by simian virus 40 DNA transfection.

PubMed Central

Lemoine, N. R.; Mayall, E. S.; Jones, T.; Sheer, D.; McDermid, S.; Kendall-Taylor, P.; Wynford-Thomas, D.

1989-01-01

Human primary thyroid follicular epithelial cells were transfected with a plasmid containing an origin-defective SV40 genome (SVori-) to produce several immortal cell lines. Two of the 10 cell lines analysed expressed specific features of thyroid epithelial function (iodide-trapping and thyroglobulin production). These two lines were characterised in detail and found to be growth factor-independent, capable of anchorage-independent growth at low frequency but non-tumorigenic in nude mice. These differentiated, These differentiated, partially transformed cell lines were shown to be suitable for gene transfer at high frequency using simple coprecipitation techniques. Images Figure 2 Figure 3 Figure 4 PMID:2557880

A progress report of the Marshall Islands nationwide thyroid study: an international cooperative scientific study.

PubMed

Takahashi, T; Simon, S L; Trott, K R; Fujimori, K; Nakashima, N; Arisawa, K; Schoemaker, M J

1999-04-01

The objective of this report is to present a summary of progress of the Marshall Islands Nationwide Thyroid Study. As well known, the US atomic weapons testing program in the Pacific was conducted primarily between 1946 and 1958 in the Marshall Islands. The nuclear tests resulted in radioactive contamination of a number of atolls and resulted in exposure of Marshallese to undefined levels before our study. Little information has been paid to health consequences among residents of the nearly twenty inhibited atolls except for some information about nodular thyroid disease which was reported on by an US group. In a cooperative agreement with the Government of the Marshall Islands, between 1993 and 1997 we studied the prevalence of both thyroid nodules and thyroid cancer among 4766 Marshallese potentially exposed to radioiodines from bomb test fallout. That group represents more than 65% of the population at risk. We diagnosed 45 thyroid cancers and 1398 benign thyroid nodules. In addition, 23 study participants had been operated on prior to our study for thyroid cancer. Presently, we are developing a database of information to estimate radiation doses and planning a statistical analysis to determine if a dose-response relationship exists. These data will be important for the health promotion of exposed people all over the world including Hiroshima, Nagasaki, Semipalatinsk, Chernobyl and other locations. A timely completion is important for purpose of assisting Marshallese as well as to add the global understanding of radiation induced thyroid cancer.

Transposon mutagenesis identifies chromatin modifiers cooperating with Ras in thyroid tumorigenesis and detects ATXN7 as a cancer gene.

PubMed

Montero-Conde, Cristina; Leandro-Garcia, Luis J; Chen, Xu; Oler, Gisele; Ruiz-Llorente, Sergio; Ryder, Mabel; Landa, Iñigo; Sanchez-Vega, Francisco; La, Konnor; Ghossein, Ronald A; Bajorin, Dean F; Knauf, Jeffrey A; Riordan, Jesse D; Dupuy, Adam J; Fagin, James A

2017-06-20

Oncogenic RAS mutations are present in 15-30% of thyroid carcinomas. Endogenous expression of mutant Ras is insufficient to initiate thyroid tumorigenesis in murine models, indicating that additional genetic alterations are required. We used Sleeping Beauty (SB) transposon mutagenesis to identify events that cooperate with Hras G12V in thyroid tumor development. Random genomic integration of SB transposons primarily generated loss-of-function events that significantly increased thyroid tumor penetrance in Tpo-Cre/homozygous FR-Hras G12V mice. The thyroid tumors closely phenocopied the histological features of human RAS-driven, poorly differentiated thyroid cancers. Characterization of transposon insertion sites in the SB-induced tumors identified 45 recurrently mutated candidate cancer genes. These mutation profiles were remarkably concordant with mutated cancer genes identified in a large series of human poorly differentiated and anaplastic thyroid cancers screened by next-generation sequencing using the MSK-IMPACT panel of cancer genes, which we modified to include all SB candidates. The disrupted genes primarily clustered in chromatin remodeling functional nodes and in the PI3K pathway. ATXN7 , a component of a multiprotein complex with histone acetylase activity, scored as a significant SB hit. It was recurrently mutated in advanced human cancers and significantly co-occurred with RAS or NF1 mutations. Expression of ATXN7 mutants cooperated with oncogenic RAS to induce thyroid cell proliferation, pointing to ATXN7 as a previously unrecognized cancer gene.

Transposon mutagenesis identifies chromatin modifiers cooperating with Ras in thyroid tumorigenesis and detects ATXN7 as a cancer gene

PubMed Central

Montero-Conde, Cristina; Leandro-Garcia, Luis J.; Chen, Xu; Oler, Gisele; Ruiz-Llorente, Sergio; Ryder, Mabel; Landa, Iñigo; Sanchez-Vega, Francisco; La, Konnor; Ghossein, Ronald A.; Bajorin, Dean F.; Knauf, Jeffrey A.; Riordan, Jesse D.; Dupuy, Adam J.; Fagin, James A.

2017-01-01

Oncogenic RAS mutations are present in 15–30% of thyroid carcinomas. Endogenous expression of mutant Ras is insufficient to initiate thyroid tumorigenesis in murine models, indicating that additional genetic alterations are required. We used Sleeping Beauty (SB) transposon mutagenesis to identify events that cooperate with HrasG12V in thyroid tumor development. Random genomic integration of SB transposons primarily generated loss-of-function events that significantly increased thyroid tumor penetrance in Tpo-Cre/homozygous FR-HrasG12V mice. The thyroid tumors closely phenocopied the histological features of human RAS-driven, poorly differentiated thyroid cancers. Characterization of transposon insertion sites in the SB-induced tumors identified 45 recurrently mutated candidate cancer genes. These mutation profiles were remarkably concordant with mutated cancer genes identified in a large series of human poorly differentiated and anaplastic thyroid cancers screened by next-generation sequencing using the MSK-IMPACT panel of cancer genes, which we modified to include all SB candidates. The disrupted genes primarily clustered in chromatin remodeling functional nodes and in the PI3K pathway. ATXN7, a component of a multiprotein complex with histone acetylase activity, scored as a significant SB hit. It was recurrently mutated in advanced human cancers and significantly co-occurred with RAS or NF1 mutations. Expression of ATXN7 mutants cooperated with oncogenic RAS to induce thyroid cell proliferation, pointing to ATXN7 as a previously unrecognized cancer gene. PMID:28584132

Feasibility of Intravoxel Incoherent Motion for Differentiating Benign and Malignant Thyroid Nodules.

PubMed

Tan, Hui; Chen, Jun; Zhao, Yi Ling; Liu, Jin Huan; Zhang, Liang; Liu, Chang Sheng; Huang, Dongjie

2018-06-13

This study aimed to preliminarily investigate the feasibility of intravoxel incoherent motion (IVIM) theory in the differential diagnosis of benign and malignant thyroid nodules. Forty-five patients with 56 confirmed thyroid nodules underwent preoperative routine magnetic resonance imaging and IVIM diffusion-weighted imaging. The histopathologic diagnosis was confirmed by surgery. Apparent diffusion coefficient (ADC), perfusion fraction f, diffusivity D, and pseudo-diffusivity D* were quantified. Independent samples t test of IVIM-derived metrics were conducted between benign and malignant nodules. Receiver-operating characteristic analyses were performed to determine the optimal thresholds as well as the sensitivity and specificity for differentiating. Significant intergroup difference was observed in ADC, D, D*, and f (p < 0.001). Malignant tumors featured significantly lower ADC, D and D* values and a higher f value than that of benign nodules. The ADC, D, and D* could distinguish the benign from malignant thyroid nodules, and parameter f differentiate the malignant tumors from benign nodules. The values of the area under the curve for parameter ADC, D, and D* were 0.784 (p = 0.001), 0.795 (p = 0.001), and 0.850 (p < 0.001), separately, of which the area under the curve of f value was the maximum for identifying the malignant from benign nodules, which was 0.841 (p < 0.001). This study suggested that ADC and IVIM-derived metrics, including D, D*, and f, could potentially serve as noninvasive predictors for the preoperative differentiating of thyroid nodules, and f value performed best in identifying the malignant from benign nodules among these parameters. Copyright © 2018 Academic Radiology. Published by Elsevier Inc. All rights reserved.

[Cranial metastasis of thyroid follicular carcinoma. Report of a case].

PubMed

Calderón-Garcidueñas, A L; González-Schaffinni, M A; Farías-García, R; Rey-Laborde, R

2001-01-01

Thyroid follicular carcinoma is able to produce metastatic lesions before the vanishing of the primary lesion. We present a case of a woman with a lytic, solitary, asymptomatic parietal bone lesion of 2 years of evolution. Autopsy revealed a thyroid gland with two small cystic areas and renal metastasis. Thyroid carcinoma should be included in the differential diagnosis in cases of lytic bone lesions with long evolution in patients 60 years of age or older.

Preoperative Cytologic Diagnosis of Warthin-like Variant of Papillary Thyroid Carcinoma.

PubMed

Kim, Jisup; Lim, Beom Jin; Hong, Soon Won; Pyo, Ju Yeon

2018-03-01

Warthin-like variant of papillary thyroid carcinoma (WLV-PTC) is a relatively rare variant of papillary thyroid carcinoma with favorable prognosis. However, preoperative diagnosis using fine-needle aspiration (FNA) specimens is challenging especially with lymphocytic thyroiditis characterized by Hürthle cells and lymphocytic background. To determine a helpful cytological differential point, we compared WLV-PTC FNA findings with conventional papillary thyroid carcinoma with lymphocytic thyroiditis (PTC-LT) and conventional papillary thyroid carcinoma without lymphocytic thyroiditis (PTC) regarding infiltrating inflammatory cells and their distribution. Preoperative diagnosis or potential for WLV-PTC will be helpful for surgeons to decide the scope of operation. Of the 8,179 patients treated for papillary thyroid carcinoma between January 2007 and December 2012, 16 patients (0.2%) were pathologically confirmed as WLV-PTC and four cases were available for cytologic review. For comparison, we randomly selected six PTC-LT cases and five PTC cases during the same period. The number of intratumoral and background lymphocytes, histiocytes, neutrophils, and the presence of giant cells were evaluated and compared using conventional smear and ThinPrep preparations. WLV-PTC showed extensive lymphocytic smear with incorporation of thyroid follicular tumor cell clusters and frequent histiocytes. WLV-PTC was associated with higher intratumoral and background lymphocytes and histiocytes compared with PTC-LT or PTC. The difference was more distinct in liquid-based cytology. The lymphocytic smear pattern and the number of inflammatory cells of WLV-PTC are different from those of PTC-LT or PTC and will be helpful for the differential diagnosis of WLV-PTC in preoperative FNA.

Preoperative Cytologic Diagnosis of Warthin-like Variant of Papillary Thyroid Carcinoma

PubMed Central

Kim, Jisup; Lim, Beom Jin; Hong, Soon Won; Pyo, Ju Yeon

2018-01-01

Background Warthin-like variant of papillary thyroid carcinoma (WLV-PTC) is a relatively rare variant of papillary thyroid carcinoma with favorable prognosis. However, preoperative diagnosis using fine-needle aspiration (FNA) specimens is challenging especially with lymphocytic thyroiditis characterized by Hürthle cells and lymphocytic background. To determine a helpful cytological differential point, we compared WLV-PTC FNA findings with conventional papillary thyroid carcinoma with lymphocytic thyroiditis (PTC-LT) and conventional papillary thyroid carcinoma without lymphocytic thyroiditis (PTC) regarding infiltrating inflammatory cells and their distribution. Preoperative diagnosis or potential for WLV-PTC will be helpful for surgeons to decide the scope of operation. Methods Of the 8,179 patients treated for papillary thyroid carcinoma between January 2007 and December 2012, 16 patients (0.2%) were pathologically confirmed as WLV-PTC and four cases were available for cytologic review. For comparison, we randomly selected six PTC-LT cases and five PTC cases during the same period. The number of intratumoral and background lymphocytes, histiocytes, neutrophils, and the presence of giant cells were evaluated and compared using conventional smear and ThinPrep preparations. Results WLV-PTC showed extensive lymphocytic smear with incorporation of thyroid follicular tumor cell clusters and frequent histiocytes. WLV-PTC was associated with higher intratumoral and background lymphocytes and histiocytes compared with PTC-LT or PTC. The difference was more distinct in liquid-based cytology. Conclusions The lymphocytic smear pattern and the number of inflammatory cells of WLV-PTC are different from those of PTC-LT or PTC and will be helpful for the differential diagnosis of WLV-PTC in preoperative FNA. PMID:29429327

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.

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.

An inducible knockout mouse to model the cell-autonomous role of PTEN in initiating endometrial, prostate and thyroid neoplasias.

PubMed

Mirantes, Cristina; Eritja, Núria; Dosil, Maria Alba; Santacana, Maria; Pallares, Judit; Gatius, Sónia; Bergadà, Laura; Maiques, Oscar; Matias-Guiu, Xavier; Dolcet, Xavier

2013-05-01

PTEN is one of the most frequently mutated tumor suppressor genes in human cancers. The role of PTEN in carcinogenesis has been validated by knockout mouse models. PTEN heterozygous mice develop neoplasms in multiple organs. Unfortunately, the embryonic lethality of biallelic excision of PTEN has inhibited the study of complete PTEN deletion in the development and progression of cancer. By crossing PTEN conditional knockout mice with transgenic mice expressing a tamoxifen-inducible Cre-ER(T) under the control of a chicken actin promoter, we have generated a tamoxifen-inducible mouse model that allows temporal control of PTEN deletion. Interestingly, administration of a single dose of tamoxifen resulted in PTEN deletion mainly in epithelial cells, but not in stromal, mesenchymal or hematopoietic cells. Using the mT/mG double-fluorescent Cre reporter mice, we demonstrate that epithelial-specific PTEN excision was caused by differential Cre activity among tissues and cells types. Tamoxifen-induced deletion of PTEN resulted in extremely rapid and consistent formation of endometrial in situ adenocarcinoma, prostate intraepithelial neoplasia and thyroid hyperplasia. We also analyzed the role of PTEN ablation in other epithelial cells, such as the tubular cells of the kidney, hepatocytes, colonic epithelial cells or bronchiolar epithelium, but those tissues did not exhibit neoplastic growth. Finally, to validate this model as a tool to assay the efficacy of anti-tumor drugs in PTEN deficiency, we administered the mTOR inhibitor everolimus to mice with induced PTEN deletion. Everolimus dramatically reduced the progression of endometrial proliferations and significantly reduced thyroid hyperplasia. This model could be a valuable tool to study the cell-autonomous mechanisms involved in PTEN-loss-induced carcinogenesis and provides a good platform to study the effect of anti-neoplastic drugs on PTEN-negative tumors.

An inducible knockout mouse to model the cell-autonomous role of PTEN in initiating endometrial, prostate and thyroid neoplasias

PubMed Central

Mirantes, Cristina; Eritja, Núria; Dosil, Maria Alba; Santacana, Maria; Pallares, Judit; Gatius, Sónia; Bergadà, Laura; Maiques, Oscar; Matias-Guiu, Xavier; Dolcet, Xavier

2013-01-01

SUMMARY PTEN is one of the most frequently mutated tumor suppressor genes in human cancers. The role of PTEN in carcinogenesis has been validated by knockout mouse models. PTEN heterozygous mice develop neoplasms in multiple organs. Unfortunately, the embryonic lethality of biallelic excision of PTEN has inhibited the study of complete PTEN deletion in the development and progression of cancer. By crossing PTEN conditional knockout mice with transgenic mice expressing a tamoxifen-inducible Cre-ERT under the control of a chicken actin promoter, we have generated a tamoxifen-inducible mouse model that allows temporal control of PTEN deletion. Interestingly, administration of a single dose of tamoxifen resulted in PTEN deletion mainly in epithelial cells, but not in stromal, mesenchymal or hematopoietic cells. Using the mT/mG double-fluorescent Cre reporter mice, we demonstrate that epithelial-specific PTEN excision was caused by differential Cre activity among tissues and cells types. Tamoxifen-induced deletion of PTEN resulted in extremely rapid and consistent formation of endometrial in situ adenocarcinoma, prostate intraepithelial neoplasia and thyroid hyperplasia. We also analyzed the role of PTEN ablation in other epithelial cells, such as the tubular cells of the kidney, hepatocytes, colonic epithelial cells or bronchiolar epithelium, but those tissues did not exhibit neoplastic growth. Finally, to validate this model as a tool to assay the efficacy of anti-tumor drugs in PTEN deficiency, we administered the mTOR inhibitor everolimus to mice with induced PTEN deletion. Everolimus dramatically reduced the progression of endometrial proliferations and significantly reduced thyroid hyperplasia. This model could be a valuable tool to study the cell-autonomous mechanisms involved in PTEN-loss-induced carcinogenesis and provides a good platform to study the effect of anti-neoplastic drugs on PTEN-negative tumors. PMID:23471917

Role of morphometry in the cytological differentiation of benign and malignant thyroid lesions

PubMed Central

Khatri, Pallavi; Choudhury, Monisha; Jain, Manjula; Thomas, Shaji

2017-01-01

Context: Thyroid nodules represent a common problem, with an estimated prevalence of 4–7%. Although fine needle aspiration cytology (FNAC) has been accepted as a first line diagnostic test, the rate of false negative reports of malignancy is still high. Nuclear morphometry is the measurement of nuclear parameters by image analysis. Image analysis can merge the advantages of morphologic interpretation with those of quantitative data. Aims: To evaluate the nuclear morphometric parameters in fine needle aspirates of thyroid lesions and to study its role in differentiating benign from malignant thyroid lesions. Material and Methods: The study included 19 benign and 16 malignant thyroid lesions. Image analysis was performed on Giemsa-stained FNAC slides by Nikon NIS-Elements Advanced Research software (Version 4.00). Nuclear morphometric parameters analyzed included nuclear size, shape, texture, and density parameters. Statistical Analysis: Normally distributed continuous variables were compared using the unpaired t-test for two groups and analysis of variance was used for three or more groups. Tukey or Tamhane's T2 multiple comparison test was used to assess the differences between the individual groups. Categorical variables were analyzed using the chi square test. Results and Conclusion: Five out of the six nuclear size parameters as well as all the texture and density parameters studied were significant in distinguishing between benign and malignant thyroid lesions (P < 0.05). Cut-off values were derived to differentiate between benign and malignant cases. PMID:28182069

Influence of iodine deficiency and iodine prophylaxis on thyroid cancer histotypes and incidence in endemic goiter area.

PubMed

Huszno, B; Szybiński, Z; Przybylik-Mazurek, E; Stachura, J; Trofimiuk, M; Buziak-Bereza, M; Gołkowski, F; Pantoflinski, J

2003-01-01

The aim of the study was to evaluate the correlation between thyroid cancer histotype and incidence rate (IR) and iodine nutrition level in two endemic goiter areas: the districts of Krakow and Nowy Sacz. The suspension of iodine prophylaxis in Poland in 1980 resulted in increased goiter prevalence in schoolchildren and adults and elevated TSH levels in newborns in the early 1990s. Since 1992 a rise in thyroid cancer IR was observed. Thyroid cancer IR in the Krakow population was 2.22 in 1986; 3.62 in 1995 and 6.02 in 2001; in Nowy Sacz: 1.52; 2.59 and 3.88 respectively. In 1986 papillary/follicular cancer ratio in both areas was about 1.0--the value typical of iodine deficient areas. After restoring the obligatory iodine prophylaxis in 1997, a significant decrease in elevated TSH concentration in newborns and urinary iodine concentration increase in schoolchildren were observed. A relative rise in the incidence of papillary thyroid cancer and decrease in follicular cancer, resulting in rise in papillary/follicular thyroid cancer ratio up to 5.9 in 2001 was also observed. Since 1999 no further thyroid cancer IR increase was noted. In conclusion, a significant increase in differentiated thyroid cancer IR was observed in association with the iodine prophylaxis suspension. Changes in thyroid cancer histotypes in 1986-2001 and a significant decrease in incremental rate of differentiated thyroid cancer probably reflect the influence of effective iodine prophylaxis. The significant difference between IR of thyroid cancer incidence in the districts of Krakow and Nowy Sacz may be related to differences in the exposure to radiation after the Chernobyl accident.

Transcriptional response to 131I exposure of rat thyroid gland.

PubMed

Rudqvist, Nils; Spetz, Johan; Schüler, Emil; Parris, Toshima Z; Langen, Britta; Helou, Khalil; Forssell-Aronsson, Eva

2017-01-01

Humans are exposed to 131I in medical diagnostics and treatment but also from nuclear accidents, and better knowledge of the molecular response in thyroid is needed. The aim of the study was to examine the transcriptional response in thyroid tissue 24 h after 131I administration in rats. The exposure levels were chosen to simulate both the clinical situation and the case of nuclear fallout. Thirty-six male rats were i.v. injected with 0-4700 kBq 131I, and killed at 24 h after injection (Dthyroid = 0.0058-3.0 Gy). Total RNA was extracted from individual thyroid tissue samples and mRNA levels were determined using oligonucleotide microarray technique. Differentially expressed transcripts were determined using Nexus Expression 3.0. Hierarchical clustering was performed in the R statistical computing environment. Pathway analysis was performed using the Ingenuity Pathway Analysis tool and the Gene Ontology database. T4 and TSH plasma concentrations were measured using ELISA. Totally, 429 differentially regulated transcripts were identified. Downregulation of thyroid hormone biosynthesis associated genes (e.g. thyroglobulin, thyroid peroxidase, the sodium-iodine symporter) was identified in some groups, and an impact on thyroid function was supported by the pathway analysis. Recurring downregulation of Dbp and Slc47a2 was found. Dbp exhibited a pattern with monotonous reduction of downregulation with absorbed dose at 0.0058-0.22 Gy. T4 plasma levels were increased and decreased in rats whose thyroids were exposed to 0.057 and 0.22 Gy, respectively. Different amounts of injected 131I gave distinct transcriptional responses in the rat thyroid. Transcriptional response related to thyroid function and changes in T4 plasma levels were found already at very low absorbed doses to thyroid.

Family history of cancer and risk of sporadic differentiated thyroid carcinoma.

PubMed

Xu, Li; Li, Guojun; Wei, Qingyi; El-Naggar, Adel K; Sturgis, Erich M

2012-03-01

Thyroid cancer incidence in the United States, particularly in women, has increased dramatically since the 1980s. Although the causes of thyroid cancer in most patients remain largely unknown, evidence suggests the existence of an inherited predisposition to development of differentiated thyroid carcinoma (DTC). Therefore, the authors explored the association between sporadic DTC and family history of cancer. In a retrospective hospital-based case-control study of prospectively recruited subjects who completed the study questionnaire upon enrollment, unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) as estimates of the DTC risk associated with first-degree family history of cancer. The study included 288 patients with sporadic DTC and 591 cancer-free controls. Family history of thyroid cancer in first-degree relatives was associated with increased DTC risk (adjusted OR, 4.1; 95% CI, 1.7-9.9). All DTC cases in patients with a first-degree family history of thyroid cancer were cases of papillary thyroid carcinoma (PTC) (adjusted OR, 4.6; 95% CI, 1.9-11.1). Notably, the risk of PTC was highest in subjects with a family history of thyroid cancer in siblings (OR, 7.4; 95% CI, 1.8-30.4). In addition, multifocal primary tumor was more common among PTC patients with first-degree family history of thyroid cancer than among PTC patients with no first-degree family history of thyroid cancer (68.8% vs 35.5%, P = .01). The study suggests that family history of thyroid cancer in first-degree relatives, particularly in siblings, is associated with an increased risk of sporadic PTC. Copyright © 2011 American Cancer Society.

Family History of Cancer and Risk of Sporadic Differentiated Thyroid Carcinoma

PubMed Central

Xu, Li; Li, Guojun; Wei, Qingyi; El-Naggar, Adel K.; Sturgis, Erich M.

2011-01-01

BACKGROUND Thyroid cancer incidence in the United States, particularly in women, has increased dramatically since 1980s. While the causes of thyroid cancer in most patients remain largely unknown, evidence suggests the existence of an inherited predisposition to development of differentiated thyroid cancer (DTC). Therefore, we explored the association between sporadic DTC and family history of cancer. METHODS In a retrospective hospital-based case-control study of prospectively recruited subjects who completed the study questionnaire upon enrollment, unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) as estimates of the DTC risk associated with first-degree family history of cancer. RESULTS The study included 288 patients with sporadic DTC and 591 cancer-free controls. Family history of thyroid cancer in first-degree relatives was associated with increased DTC risk (adjusted OR = 4.1, 95% CI: 1.7–9.9). All DTC cases in patients with a first-degree family history of thyroid cancer were cases of papillary thyroid carcinoma (PTC) (adjusted OR = 4.6, 95 CI%: 1.9–11.1). Notably, the risk of PTC was highest in subjects with a family history of thyroid cancer in siblings (OR = 7.4, 95% CI: 1.8–30.4). In addition, multifocal primary tumor was more common among PTC patients with first-degree family history of thyroid cancer than among PTC patients with no first-degree family history of thyroid cancer (68.8% vs. 35.5%, p = 0.01). CONCLUSIONS Our study suggests that family history of thyroid cancer in first-degree relatives, particularly in siblings, is associated with an increased risk of sporadic PTC. PMID:21800288

Update on the treatment of hypothyroidism.

PubMed

Jonklaas, Jacqueline

2016-01-01

Differentiated thyroid cancer is a malignancy that is rapidly increasing in frequency. As thyroidectomy plays a central role in the treatment of thyroid cancer, it is incumbent on physicians treating this patient group to be well versed in the intricacies of treating hypothyroidism. Treatment of hypothyroidism may be refined by careful attention to dose selection, monitoring of therapy and achievement of thyrotropin goals that are specific to the individual patient's overall clinical situation. These goals are common not only to patients with a sole diagnosis of hypothyroidism, as discussed in the recent American Thyroid Association Guidelines, but also to patients with hypothyroidism in the setting of thyroid cancer. Several recent studies have illuminated our understanding of the benefits and risks of thyrotropin suppression therapy in patients with differentiated thyroid cancer. Multiple studies of combination therapy with levothyroxine and liothyronine for treating hypothyroidism have not led to a clear conclusion about its benefits over levothyroxine monotherapy. Animal studies have advanced our understanding of the altered serum and tissue milieu that characterizes levothyroxine monotherapy. Crossing the bridge from this translational research into clinical research using sustained release triiodothyronine preparations may ultimately enhance the health of our patients. Continued refinement of our understanding of thyroid status and our ability to flawlessly implement thyroid hormone replacement is an active area of research.

The cytology of a thyroid granular cell tumor.

PubMed

Chang, Shu-Mei; Wei, Chang-Kuo; Tseng, Chih-En

2009-01-01

Granular cell tumor (GCT) of the thyroid is rare. Before this report, only four cases of thyroid GCT have been reported, none of which presented a cytopathological examination. In this paper, we report the fine needle aspiration cytology and pathological analysis of a thyroid GCT from a 12-year-old girl who presented with a painless neck mass. The tumor cells were single, in syncytial clusters, or pseudofollicles, contained small round, oval, or spindle nuclei, indistinct nucleoli, and a large amount of grayish, granular fragile cytoplasm. The background contained granular debris and naked nuclei. A differential diagnosis of thyroid GCT with more frequent thyroid lesions containing cytoplasmic granules, including Hurthle cells, macrophages, follicular cells, and cells of black thyroid syndrome, was also performed.

Bexarotene via CBP/p300 induces suppression of NF-κB-dependent cell growth and invasion in thyroid cancer.

PubMed

Cras, Audrey; Politis, Béatrice; Balitrand, Nicole; Darsin-Bettinger, Diane; Boelle, Pierre Yves; Cassinat, Bruno; Toubert, Marie-Elisabeth; Chomienne, Christine

2012-01-15

Retinoic acid (RA) treatment has been used for redifferentiation of metastatic thyroid cancer with loss of radioiodine uptake. The aim of this study was to improve the understanding of RA resistance and investigate the role of bexarotene in thyroid cancer cells. A model of thyroid cancer cell lines with differential response to RA was used to evaluate the biological effects of retinoid and rexinoid and to correlate this with RA receptor levels. Subsequently, thyroid cancer patients were treated with 13-cis RA and bexarotene and response evaluated on radioiodine uptake reinduction on posttherapy scan and conventional imaging. In thyroid cancer patients, 13-cis RA resistance can be bypassed in some tumors by bexarotene. A decreased tumor growth without differentiation was observed confirming our in vitro data. Indeed, we show that ligands of RARs or RXRs exert different effects in thyroid cancer cell lines through either differentiation or inhibition of cell growth and invasion. These effects are associated with restoration of RARβ and RXRγ levels and downregulation of NF-κB targets genes. We show that bexarotene inhibits the transactivation potential of NF-κB in an RXR-dependent manner through decreased promoter permissiveness without interfering with NF-κB nuclear translocation and binding to its responsive elements. Inhibition of transcription results from the release of p300 coactivator from NF-κB target gene promoters and subsequent histone deacetylation. This study highlights dual mechanisms by which retinoids and rexinoids may target cell tumorigenicity, not only via RARs and RXRs, as expected, but also via NF-κB pathway. ©2011 AACR.

Effect of central compartment neck dissection on hypocalcaemia incidence after total thyroidectomy for carcinoma.

PubMed

Mitra, I; Nichani, J R; Yap, B; Homer, J J

2011-05-01

Central compartment neck dissection is increasingly performed as part of surgical management of differentiated thyroid carcinoma. However, elective central neck dissection remains controversial due to complications and lack of evidence of survival benefit. To investigate and compare rates of transient and permanent hypocalcaemia following total thyroidectomy alone, compared with total thyroidectomy with central neck dissection, for differentiated thyroid carcinoma. Retrospective study of 127 consecutive patients referred with differentiated thyroid carcinoma, 2004-2006; 78 patients had undergone total thyroidectomy (group one) and 49 total thyroidectomy with central compartment node dissection (group two). Surgery was performed in various hospitals by both otolaryngologists and endocrine surgeons. In groups one and two, the incidence of transient hypocalcaemia was 18 per cent (14/78) and 51 per cent (25/49) (p < 0.001), and the incidence of permanent hypocalcaemia 1 per cent (one of 77) and 12 per cent (six of 49) (p < 0.01), respectively. Most patients undergoing central neck dissection had evidence of pathological level six lymphadenopathy (29/49). Total thyroidectomy combined with central neck dissection for the treatment of differentiated thyroid carcinoma is more likely to result in transient (51 per cent) and permanent (12 per cent) hypocalcaemia. Elective neck dissection should be performed selectively, with a high expectation of post-operative hypocalcaemia.

[Dental periimplantitis distinctive features diagnostic in cases of minimal thyroid insufficiency].

PubMed

Shcherbakov, M V; Golovina, E S; Gil'miiarova, F N

2008-01-01

There were disclosed syndrome of minimal thyroid insufficiency in each fourth patient with dental periimplantitis and absence of thyroid gland dysfunction in case of mucositis of periimplantitis origin. The data were presented of minimal thyroid insufficiency manifestations in cases of inflammatory complications of dental implantations the indicator of which was the content of overall and free thyroxin in oral fluid. There were determined common and differentiating peculiarities of oral fluid homeostasis in cases of dental periimplantitis and mucositis of periimplantitis origin.

Assessment of thyroid function in dogs with low plasma thyroxine concentration.

PubMed

Diaz Espineira, M M; Mol, J A; Peeters, M E; Pollak, Y W E A; Iversen, L; van Dijk, J E; Rijnberk, A; Kooistra, H S

2007-01-01

Differentiation between hypothyroidism and nonthyroidal illness in dogs poses specific problems, because plasma total thyroxine (TT4) concentrations are often low in nonthyroidal illness, and plasma thyroid stimulating hormone (TSH) concentrations are frequently not high in primary hypothyroidism. The serum concentrations of the common basal biochemical variables (TT4, freeT4 [fT4], and TSH) overlap between dogs with hypothyroidism and dogs with nonthyroidal illness, but, with stimulation tests and quantitative measurement of thyroidal 99mTcO4(-) uptake, differentiation will be possible. In 30 dogs with low plasma TT4 concentration, the final diagnosis was based upon histopathologic examination of thyroid tissue obtained by biopsy. Fourteen dogs had primary hypothyroidism, and 13 dogs had nonthyroidal illness. Two dogs had secondary hypothyroidism, and 1 dog had metastatic thyroid cancer. The diagnostic value was assessed for (1) plasma concentrations of TT4, fT4, and TSH; (2) TSH-stimulation test; (3) plasma TSH concentration after stimulation with TSH-releasing hormone (TRH); (4) occurrence of thyroglobulin antibodies (TgAbs); and (5) thyroidal 99mTcO4(-) uptake. Plasma concentrations of TT4, fT4, TSH, and the hormone pairs TT4/TSH and fT4/TSH overlapped in the 2 groups, whereas, with TgAbs, there was 1 false-negative result. Results of the TSH- and TRH-stimulation tests did not meet earlier established diagnostic criteria, overlapped, or both. With a quantitative measurement of thyroidal 99mTcO4(-) uptake, there was no overlap between dogs with primary hypothyroidism and dogs with nonthyroidal illness. The results of this study confirm earlier observations that, in dogs, accurate biochemical diagnosis of primary hypothyroidism poses specific problems. Previous studies, in which the TSH-stimulation test was used as the "gold standard" for the diagnosis of hypothyroidism may have suffered from misclassification. Quantitative measurement of thyroidal 99mTcO- uptake has the highest discriminatory power with regard to the differentiation between primary hypothyroidism and nonthyroidal illness.

Mapping fundamental life elements in papillary thyroid carcinoma tissue

NASA Astrophysics Data System (ADS)

Merolle, L.; Ragazzi, M.; Gianoncelli, A.; Altissimo, M.; Ciarrocchi, A.; Bedolla, D. E.; Marraccini, C.; Baricchi, R.; Pertinhez, T. A.

2018-05-01

Well-differentiated papillary thyroid carcinomas (PTCs) are the most common type of thyroid cancer. Thyroid function depends on the presence of certain trace elements necessary for both the synthesis and the metabolism of thyroid hormones. We conducted an observational translational study on formalin fixed paraffin embedded thyroid tissue slices collected from five patients who underwent surgical resection of thyroid gland after thyroid cancer diagnosis. A synchrotron-based XRF set up was used to map the distribution of oxygen, sodium, aluminum, selenium and magnesium in PTC sections. These experiments were performed at the TwinMic beamline (Elettra—Sincrotrone Trieste, Trieste, Italy). Our results show that Mg levels in PTC tissues are significantly higher than in the control ones. The results seem to provide highly valuable information suggesting that Mg may play a role in the development and metabolic process of PTC.

Thyroid Disease and Teens

MedlinePlus

... levels might change over just a few months. Hypothyroidism A person with mild hypothyroidism may feel just fine — in fact, the condition ... all. However, symptoms can become more obvious if hypothyroidism progresses. People with underactive thyroids might feel depressed ...

Thyroid Disease (for Parents)

MedlinePlus

... levels might change over just a few months. Hypothyroidism A person with mild hypothyroidism may feel just fine — in fact, the condition ... all. However, symptoms can become more obvious if hypothyroidism progresses. People with underactive thyroids might feel depressed ...

Sorafenib for Metastatic Thyroid Cancer

Cancer.gov

A summary of results from an international phase III trial that compared sorafenib (Nexavar®) and a placebo for the treatment of locally advanced or metastatic differentiated thyroid cancer that is no longer responding to treatment with radioactive iodine

IgG4-Related Disease of the Thyroid Gland Requiring Emergent Total Thyroidectomy: A Case Report.

PubMed

Zhao, Zitong; Lee, Yu Jin; Zheng, Shuwei; Khor, Li Yan; Lim, Kok Hing

2018-05-31

IgG4-related disease of the thyroid gland is a recently recognized subtype of thyroiditis, often with rapid progression requiring surgical treatment. It is considered as a spectrum of disease varying from early IgG4-related Hashimoto's thyroiditis (HT) pattern to late fibrosing HT or Riedel's thyroiditis patterns. Here, we report a 47-year-old Malay woman presenting with progressively painless neck swelling over 3 years and subclinical hypothyroidism. Computed tomography (CT) scan revealed diffuse thyroid enlargement (up to 13 cm) with retrosternal extension and without regional lymphadenopathy. Fine needle aspiration of the thyroid showed a limited number of follicular epithelial cell groups with widespread Hurthle cell change and scanty background colloid, but no evidence of lymphocytosis. The cytologic features fell into the category of 'atypia of undetermined significance'. Subsequently, the patient developed hypercapnic respiratory failure secondary to extrinsic upper airway compression by the thyroid mass and underwent emergent total thyroidectomy. Histology of the thyroid showed diffuse dense lymphoplasmacytic infiltrate and fibrosis. Follicular cells exhibited reactive nuclear features and some Hurthle cell change. IgG4+ plasma cells were over 40/high power field while overall IgG4/IgG ratio was above 50%. The overall features suggest the diagnosis of IgG4-related disease of the thyroid gland in the form of IgG4-related HT. Post-surgery, the patient was found to have markedly elevated serum IgG4 concentration but PET/CT did not show significant increased fludeoxyglucose uptake in other areas. Her recovery was complicated by a ventilator-associated pneumonia with empyema, limiting early use of corticosteroids for treatment of IgG4-related disease.

The role of diffusion weighted MR imaging for differentiation between Graves' disease and Hashimoto thyroiditis.

PubMed

Ozturk, T; Bozgeyik, Z; Ozturk, F; Burakgazi, G; Akyol, M; Coskun, S; Ozkan, Y; Ogur, E

2015-08-01

The aim of this study was to evaluate the usefulness of diffusion-weighted magnetic resonance imaging (DWMRI) for differentation between Graves' disease and Hashimoto's thyroiditis. Fifty patients (27 Graves diseases and 23 Hashimoto thyroiditis) and twenty healthy volunteers were examined using T1, T2 and DWMRI. The patients were diagnosed on the basis of physical findings and the results of thyroid function tests and serological tests. Circular ROIs were positioned on the bilateral thyroid lobes and isthmus. All measurements were repeated three different b values including 100, 600 and 1000 s/mm2 in all cases. ADC (Apparent diffusion coefficient) maps were calculated automatically with the MR system. Mean ADC values were 2.93 × 10-3, 1.97 × 10-3 and 1.62 × 10-3 mm2/s in the healthy volunteers; 3.47 × 10-3, 2.25 × 10-3 and 1.64 × 10-3 mm2/s in Graves' disease; 2.53 × 10-3, 1.76 × 10-3, 1.28 × 10-3 mm2/s in Hashimoto thyroiditis for b100, b600 and b1000, respectively. The ADC values of the Graves diseases were higher than healty volunteers and Hashimoto thyroiditis. ADC values were statistically significant for differentation between Hashimoto thyroiditis and Graves' disease all b values (p < 0.05). DWMRI is fast sequence and does not require contrast agent. Quantitative assessment of the lesion is possible using ADC map. So, DWMRI may be useful differentiation of the Hashimoto thyroiditis and Graves' disease.

Differentiated thyroid cancer in children and adolescents.

PubMed

Farahati, J; Parlowsky, T; Mäder, U; Reiners, C; Bucsky, P

1998-08-01

There have been only a few studies on differentiated childhood thyroid cancer (DTC) in children and adolescents. We analyzed the characteristics of DTC with respect to age, gender and histology in 114 patients under 18 years of age. In a questionnaire-based survey, data of 114 patients, aged between 3 years and 18 years, was collected from 65 clinical institutions in Germany. Characteristics of 80 females and 34 males were evaluated, and the prognostic effect of age, gender, histology, multicentric growth, tumor stage and N-status on distant metastases was tested using multivariate discriminant analysis. Between-group comparison was performed using student t-test and chi-squared test. The incidence of DTC in females was higher than in males with a peak of female:male ratio at puberty, which was more pronounced in children with papillary thyroid cancer, but not with follicular thyroid cancer. Papillary thyroid cancer was associated with more advanced disease (P=0.009), more lymph-node involvement (P=0.007) and more distant metastases (P=0.02) compared with follicular thyroid cancer. Multivariate analysis showed advanced tumor stage as the only significant factor (P=0.02) associating with distant metastasis. It can be concluded that in children and adolescents: 1. The incidence of papillary thyroid cancer is higher in females than males, with a peak at puberty. 2. The only significant factor associated with distant metastases is the advanced tumor stage. 3. Childhood thyroid cancer is frequently associated with lymph-node involvement, distant metastases and advanced tumor stage. 4. Papillary childhood thyroid cancer is more aggressive than follicular type.

The role of external beam radiation therapy in well-differentiated thyroid cancer.

PubMed

Hamilton, Sarah N; Tran, Eric; Berthelet, Eric; Wu, Jonn

2017-10-01

This review article explores the use of external beam radiotherapy (EBRT) in well differentiated thyroid cancer. Areas covered: The published literature on EBRT for advanced pT4 disease and macroscopic unresectable disease to improve locoregional control is reviewed. EBRT techniques, volumes and doses are discussed in detail. The potential acute and late toxicities of EBRT are discussed in the context of the published literature. The use of EBRT for patients with metastatic disease is also described. Expert commentary: There is good retrospective evidence for EBRT in the setting of unresectable gross residual well-differentiated thyroid cancer as this can result in long-term local control. However, the benefit of EBRT in patients with locally advanced disease that is completely resected is less clear. The use of EBRT for these patients requires careful consideration of age, pathologic factors, comorbidities and patient preference, preferably by a multi-disciplinary team.

Mutationally activated BRAF(V600E) elicits papillary thyroid cancer in the adult mouse.

PubMed

Charles, Roch-Philippe; Iezza, Gioia; Amendola, Elena; Dankort, David; McMahon, Martin

2011-06-01

Mutated BRAF is detected in approximately 45% of papillary thyroid carcinomas (PTC). To model PTC, we bred mice with adult-onset, thyrocyte-specific expression of BRAF(V600E). One month following BRAF(V600E) expression, mice displayed increased thyroid size, widespread alterations in thyroid architecture, and dramatic hypothyroidism. Over 1 year, without any deliberate manipulation of tumor suppressor genes, all mice developed PTC displaying nuclear atypia and marker expression characteristic of the human disease. Pharmacologic inhibition of MEK1/2 led to decreased thyroid size, restoration of thyroid form and function, and inhibition of tumorigenesis. Mice with BRAF(V600E)-induced PTC will provide an excellent system to study thyroid tumor initiation and progression and the evaluation of inhibitors of oncogenic BRAF signaling.

Pathogenesis of thyroid nodules: histological classification?

PubMed

Salabè, G B

2001-02-01

Thyroid nodule genesis may be considered as an amplification of thyroid heterogeneity due to genetic and/or epigenetic mechanisms. We classified the thyroid nodules in five types with distinct histological features: hyperplastic, neoplastic, colloid, cystic and thyroiditic nodules. Hyperplastic: Thyrocyte proliferation is under the control of TSH but several other paracrine and autocrine factors are secreted by follicular cells, the stromal apparatus and the lymphocytes, which are implicated in initiation and perpetuation of thyroid hyperplasia. Growth occurs mainly through TSHR, cAMP and PKA. Constitutive cAMP overproduction has been shown to be due to point mutation of the TSHR or Gs protein, producing overgrowth and hyperfunction. Neoplastic: Several activated oncogenes have been identified in thyroid malignancies. Oncogenes relevant to the thyroid carcinogenesis are: mutated TSHR and gsp (constitutive activation of cAMP); TRK (receptor for NGF); RET/PTC (phosphorylation of tyrosine kinase receptor)--an isoform of this oncogene is induced by radiation: ras (it encodes Gs proteins transducing mitogenic signals); and c-MET (receptor for hepatocyte growth factor). The evolution of a differentiated thyroid cancer towards an undifferentiated cancer is due to a mutation of a family of proteins (i.e., p53), which acts as a brake, preventing the genomic instability of cancer. It is suggested that a tumor initiates by RET or ras and possibly progresses--as a result of additional mutations and by p53 mutation--to anaplastic carcinoma. Colloid: Flattening of the epithelium and dilatation of follicles containing viscous material--made up by a concentrated solution of thyroglobulin (hTg)--is the characteristic of the colloid nodule. A defect of intraluminal reabsorption of hTg has been suggested but not proven. Experimentally, a load of iodine is able to change thyroid hyperplasia to a colloid feature; however, a load of iodine is rarely found in the clinical history of patients. A new clue to the pathogenesis comes from the finding that a relevant part of the colloid (10-20%) is made up of insoluble globules, where hTg is compacted in a polymeric form. It is suggested that stocking hTg into globules is defective in colloid nodules, leading to enormous enlargement of the follicle. Cystic: It is estimated that between 15 and 40% of thyroid nodules are partly or entirely cystic. The 'true cyst' is rare; most of the so-called cystic nodules are 'pseudocysts', which follow necrosis and colliquation. Necrosis issues as an imbalance between growth and the precisely regulated process of angiogenesis. More recently, the VEGF/VPF has been found to be at the origin of recent and recurrent cysts. Immunotoxic and apoptotic mechanisms have also been suggested. Chemical analysis of cystic fluid showed a 'denatured' and 'serum-like' pattern suggesting different mechanisms in the pathogenesis of the pseudocystic thyroid nodules. Thyroiditic: Nodular lymphocytic thyroiditis (NLT) includes two different entities: 1) lymphocyte thyroiditis growing as a nodule in a hyperplastic or normal gland, and 2) lymphocyte thyroiditis associated in the same nodule with other nodular diseases of the thyroid: papillary thyroid carcinoma and lymphoma have been found to be associated to chronic lymphocytic thyroiditis.

Fetal cell carcinogenesis of the thyroid: a modified theory based on recent evidence.

PubMed

Takano, Toru

2014-01-01

Thyroid cancer cells were believed to be generated by multi-step carcinogenesis, in which cancer cells are derived from thyrocytes, via multiple incidences of damage to their genome, especially in oncogenes or anti-oncogenes that accelerate proliferation or foster malignant phenotypes, such as the ability to invade the surrounding tissue or metastasize to distant organs, until a new hypothesis, fetal cell carcinogenesis, was presented. In fetal cell carcinogenesis, thyroid tumor cells are assumed to be derived from three types of fetal thyroid cell which only exist in fetuses or young children, namely, thyroid stem cells (TSCs), thyroblasts and prothyrocytes, by proliferation without differentiation. Genomic alternations, such as RET/PTC and PAX8-PPARγ1 rearrangements and a mutation in the BRAF gene, play an oncogenic role by preventing thyroid fetal cells from differentiating. Fetal cell carcinogenesis effectively explains recent molecular and clinical evidence regarding thyroid cancer, including thyroid cancer initiating cells (TCICs), and it underscores the importance of identifying a stem cells and clarifying the molecular mechanism of organ development in cancer research. It introduces three important concepts, the reverse approach, stem cell crisis and mature and immature cancers. Further, it implies that analysis of a small population of cells in a cancer tissue will be a key technique in establishing future laboratory tests. In the contrary, mass analysis such as gene expression profiling, whole genomic scan, and proteomics analysis may have definite limitations since they can only provide information based on many cells.

Thyroid cancer following nuclear tests in French Polynesia

PubMed Central

de Vathaire, F; Drozdovitch, V; Brindel, P; Rachedi, F; Boissin, J-L; Sebbag, J; Shan, L; Bost-Bezeaud, F; Petitdidier, P; Paoaafaite, J; Teuri, J; Iltis, J; Bouville, A; Cardis, E; Hill, C; Doyon, F

2010-01-01

Background: Between 1966 and 1974, France conducted 41 atmospheric nuclear tests in Polynesia, but their potential health effects have not previously been investigated. Methods: In a case–control study, we compared the radiation exposure of almost all the French Polynesians diagnosed with differentiated thyroid carcinoma between 1981 and 2003 (n=229) to the exposure of 373 French Polynesian control individuals without cancer from the general population. Radiation exposures were estimated using measurements after the nuclear tests, age at time of each test, residential and dietary information. Results: The average thyroid dose before 15 years of age was about 1.8 mGy, and 5% of the cases and 3% of the controls received a dose above 10 mGy. Despite this low level of dose, and after adjusting for ethnic group, level of education, body surface area, family history of thyroid cancer and number of pregnancies for women, we observed an increasing risk (P=0.04) of thyroid cancer with increasing thyroid dose received before age of 15 years, which remained after excluding non-aggressive differentiated thyroid micro-carcinomas. This increase of risk per unit of thyroid radiation dose was higher (P=0.03) in women who later experienced four or more pregnancies than among other women. Conclusion: The risk estimate is low, but is based on limited exposure data. The release of information on exposure, currently classified, would greatly improve the reliability of the risk estimation. PMID:20808313

Q-elastography in the presurgical diagnosis of thyroid nodules with indeterminate cytology.

PubMed

Cantisani, Vito; Ulisse, Salvatore; Guaitoli, Eleonora; De Vito, Corrado; Caruso, Riccardo; Mocini, Renzo; D'Andrea, Vito; Ascoli, Valeria; Antonaci, Alfredo; Catalano, Carlo; Nardi, Francesco; Redler, Adriano; Ricci, Paolo; De Antoni, Enrico; Sorrenti, Salvatore

2012-01-01

Quantitative ultrasound (US) elastography (Q-USE), able to evaluate tissue stiffness has been indicated as a new diagnostic tool to differentiate benign from malignant thyroid lesions. Aim of this prospective study, conducted at the Department of Surgical Sciences, of the "Sapienza" University of Rome, was to evaluate the diagnostic accuracy of Q-USE, compared with US parameters, in thyroid nodules with indeterminate cytology (Thy3).The case study included 140 nodules from 140 consecutive patients. Patient's thyroid nodules were evaluated by Q-USE, measuring the strain ratio (SR) of stiffness between nodular and surrounding normal thyroid tissue, and conventional US parameters prior fine-needle aspiration cytology. Those with Thy3 diagnosis were included in the study. Forty of the nodules analyzed harbored a malignant lesion. Q-USE demonstrated that malignant nodules have a significant higher stiffness with respect to benign one and an optimun SR cut-off value of 2.05 was individuated following ROC analysis. Univariate analysis showed that hypoechogenicity, irregular margins and SR >2.05 associated with malignancy, with an accuracy of 67.2%, 81,0% and 89.8%, respectively. Data were unaffected by nodule size or thyroiditis. These findings were confirmed in multivariate analysis demonstrating a significant association of the SR and the irregular margins with thyroid nodule's malignancy. In conclusion, we demonstrated the diagnostic utility of Q-USE in the differential diagnosis of thyroid nodules with indeterminate cytology that, if confirmed, could be of major clinical utility in patients' presurgical selection.

Q-Elastography in the Presurgical Diagnosis of Thyroid Nodules with Indeterminate Cytology

PubMed Central

Guaitoli, Eleonora; De Vito, Corrado; Caruso, Riccardo; Mocini, Renzo; D’Andrea, Vito; Ascoli, Valeria; Antonaci, Alfredo; Catalano, Carlo; Nardi, Francesco; Redler, Adriano; Ricci, Paolo; De Antoni, Enrico; Sorrenti, Salvatore

2012-01-01

Quantitative ultrasound (US) elastography (Q-USE), able to evaluate tissue stiffness has been indicated as a new diagnostic tool to differentiate benign from malignant thyroid lesions. Aim of this prospective study, conducted at the Department of Surgical Sciences, of the “Sapienza” University of Rome, was to evaluate the diagnostic accuracy of Q-USE, compared with US parameters, in thyroid nodules with indeterminate cytology (Thy3).The case study included 140 nodules from 140 consecutive patients. Patient’s thyroid nodules were evaluated by Q-USE, measuring the strain ratio (SR) of stiffness between nodular and surrounding normal thyroid tissue, and conventional US parameters prior fine-needle aspiration cytology. Those with Thy3 diagnosis were included in the study. Forty of the nodules analyzed harbored a malignant lesion. Q-USE demonstrated that malignant nodules have a significant higher stiffness with respect to benign one and an optimun SR cut-off value of 2.05 was individuated following ROC analysis. Univariate analysis showed that hypoechogenicity, irregular margins and SR >2.05 associated with malignancy, with an accuracy of 67.2%, 81,0% and 89.8%, respectively. Data were unaffected by nodule size or thyroiditis. These findings were confirmed in multivariate analysis demonstrating a significant association of the SR and the irregular margins with thyroid nodule’s malignancy. In conclusion, we demonstrated the diagnostic utility of Q-USE in the differential diagnosis of thyroid nodules with indeterminate cytology that, if confirmed, could be of major clinical utility in patients’ presurgical selection. PMID:23209819

[Lymph node and distant metastases of thyroid gland cancer. Metastases in the thyroid glands].

PubMed

Schmid, K W

2015-11-01

The different biological features of the various major entities of thyroid cancer, e.g. papillary, follicular, poorly differentiated, anaplastic and medullary, depend to a large extent on their different metastatic spread. Papillary thyroid cancer (PTC) has a propensity for cervical lymphatic spread that occurs in 20-50 % of patients whereas distant metastasis occurs in < 5 % of cases. Cervical lymphadenopathy may be the first symptom particularly of (micro) PTC. In contrast follicular thyroid cancer (FTC) has a marked propensity for vascular but not lymphatic invasion and 10-20 % of FTC develop distant metastases. At the time of diagnosis approximately one third of medullary thyroid cancer (MTC) cases show lymph node metastases, in 10-15 % distant metastases and 25 % develop metastases during the course of the disease. Poorly differentiated (PDTC) and anaplastic thyroid cancer (ATC) spread via both lymphatic and vascular invasion. Thus distant metastases are relatively uncommon in DTC and when they occur, long-term stable disease is the typical clinical course. The major sites of distant metastases are the lungs and bone. Metastases to the brain, breasts, liver, kidneys, muscle and skin are relatively rare or even rare. The thyroid gland itself can be a site of metastases from a variety of other tumors. In autopsy series of patients with disseminated cancer disease, metastases to the thyroid gland were found in up to 10 % of cases. Metastases from other primary tumors to the thyroid gland have been reported in 1.4-3 % of patients who have surgery for suspected cancer of the thyroid gland. The most common primary cancers that metastasize to the thyroid gland are renal cell (48.1 %), colorectal (10.4 %), lung (8.3 %) and breast cancer (7.8 %) and surprisingly often sarcomas (4.0 %).

Gelsolin: a novel thyroid hormone receptor-beta interacting protein that modulates tumor progression in a mouse model of follicular thyroid cancer.

PubMed

Kim, Caroline S; Furuya, Fumihiko; Ying, Hao; Kato, Yasuhito; Hanover, John A; Cheng, Sheue-yann

2007-03-01

Follicular thyroid cancer (FTC) is known to metastasize to distant sites via hematogenous spread; however, the underlying pathways that contribute to metastasis remain unknown. Recent creation of a knockin mutant mouse that expresses a mutant thyroid hormone receptor-beta (TRbeta(PV/PV) mouse) that spontaneously develops thyroid cancer with metastasis similar to humans has provided new opportunities to study contributors to FTC metastasis. This study evaluates the role of gelsolin, an actin-regulatory protein, in modulating the metastatic potential of FTC. Gelsolin was previously found by cDNA microarray analysis to be down-regulated in TRbeta(PV/PV) mice as compared with wild-type mice. This study found an age-dependent reduction of gelsolin protein abundance in TRbeta(PV/PV) mice as tumorigenesis progressed. Knockdown of gelsolin by small interfering RNA resulted in increased tumor cell motility and increased gelsolin expression by histone deacetylase inhibitor (trichostatin A) led to decreased cell motility. Additional biochemical analyses demonstrated that gelsolin physically interacted with TRbeta1 or PV in vivo and in vitro. The interaction regions were mapped to the C terminus of gelsolin and the DNA binding domain of TR. The physical interaction of gelsolin with PV reduced its binding to actin, leading to disarrayed cytoskeletal architectures. These results suggest that PV-induced alteration of the actin/gelsolin cytoskeleton contributes to increased cell motility. Thus, the present study uncovered a novel PV-mediated oncogenic pathway that could contribute to the local tumor progression and metastatic potential of thyroid carcinogenesis.

Carcinoma showing thymus-like elements of the thyroid gland: report of three cases including one case with breast cancer history.

PubMed

Zhang, Guanjun; Liu, Xi; Huang, Wei; Li, Xiaofeng; Johnstone, Marianne; Deng, Yuan; Ke, Yongqiang; Nunes, Quentin M; Wang, Hongyan; Wang, Yili; Zhang, Xuebin

2015-01-01

Carcinoma showing thymus-like elements (CASTLE) is a rare malignant tumor of the thyroid or adjacent neck soft tissues, whose histogenesis is still debated. It may resemble other primary or metastatic poorly differentiated tumors histologically and the differential diagnosis is crucial for CASTLE has a better prognosis. However, CASTLE as a second primary tumor has not been reported in the literature. We report three cases of thyroid CASTLE, including a unique tumor following breast-conserving surgery for early-stage breast invasive carcinoma. There were two female and one male. All three tumors were located in the right lobe of the thyroid, and one tumor showed extension into the surrounding soft tissue. Histologically, all tumors showed expansive growth and consisted of cords, nests or sheets of epithelial cells divided into irregularly shaped lobules by fibrous connective tissue with lymphoplasmacytic infiltration. Focal squamous differentiation resembling Hassall's corpuscles were observed. All cases stained positively for CD5, CD117, high molecular weight cytokeratin, cytokeratin, P63, carcinoembryonic antigen and epithelial membrane antigen. Positive staining for Bcl-2 in two cases and chromogranin A in one case was noted. Ki-67 expression ranged from 15 to 25%. Thyroid transcription factor and CD3 were negative. There was no evidence of recurrent or metastatic disease at following surgery. These features demonstrated CASTLE may arise from branchial pouch remnants, the thyroid solid cell nests. CASTLE is a rare entity, awareness of its occurrence as a second primary tumor is important to avoid overtreatment because it is associated with a favorable prognosis.

[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.

[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.

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

The Correlation of the Initial Rate of I131 Uptake in the Thyroid with the Clinical Evaluation of the Thyroid Function,

DTIC Science & Technology

1950-10-01

the need for definitive treatment of the patient suspected of having hyperthyroidism . These studies are time-consuming. At the suggestion of A.V.H in...curve in differentiating the normal from the hyperthyroid patient. The rate of uptake of I131 in the thyroid during the interval of a few hours after

[[Is it necessary to perform a central lymphodissection in highly differentiated iviicrocarcinoiva of thyroid gland?].

PubMed

Zavgorodniy, S N; Danilyuk, M B; Rylov, A I; Dolya, O S

2016-08-01

The rate of the highly differentiated thyroid microcarcinoma methastasizing in central (6th) group of cervical lymph nodes was studied. In the clinic in 2013 - 2015 yrs 62 patients were operated for primary thyroid microcarcinoma. In accordance to TNM (UICC, AJCC, 2009) classification, papillary cancer in stage TlaNOMO was diagnosed in 35 (56.5%) patients, T1aN1MO - in 22 (35.5%); follicular cancer stage T1aNOMO - in 2 (3.2%); papillary cancer, follicular variant in stage T1aN1 MO - in 2 (3.2%); follicu- lar cancer, papillary variant in stage T1aNOMO - in 1 (1.6%). In 8 (12.9%) patients intraorgan multifocal metastasizing into contralateral thyroid lobe was revealed. In accordance to morphological investigation date of the excised samples, in 24 (38.7%) patients the metastases into the 6th group lymph nodes were revealed. In 4 (16.7%) patients, to whom lateral cervical lymphodissection was done, metastases in 2 - 5th groups of lymph nodes on the thyroid affection side were revealed.

Fine needle aspiration biopsy of three cases of squamous cell carcinoma presenting as a thyroid mass: cytological findings and differential diagnosis.

PubMed

Rosa, M; Toronczyk, K

2012-02-01

Primary squamous cell carcinomas of the thyroid gland are extremely rare, comprising about 1% of thyroid malignancies. Although squamous cell carcinomas are readily identified as such on aspiration cytology in the majority of cases, the differentiation of primary versus metastatic tumour might not always be easy. Herein, we report three cases of squamous cell carcinomas involving the thyroid gland. Fine needle aspiration cytology (FNAC) was performed in three patients with a thyroid mass using standard guidelines. Smears were stained with Diff-Quik and Papanicolaou stains. Two patients were male and one was female, aged 59, 45 and 35 years, respectively. In all three patients a thyroid mass was present. FNAC smears in all cases showed cytological features of squamous cell carcinoma including keratinization and necrosis. After clinical and cytological correlation, one case appeared to be primary, one case metastatic, and in the third case no additional clinical information or biopsy follow-up was available for further characterization. Because primary squamous cell carcinoma of the thyroid is a rare finding, metastatic squamous cell carcinoma should always be excluded first. Metastatic disease usually presents in the setting of widespread malignancy, therefore a dedicated clinical and radiological investigation is necessary in these cases. In both clinical scenarios the patient's prognosis is poor. © 2010 Blackwell Publishing Ltd.

KT5823 Differentially Modulates Sodium Iodide Symporter Expression, Activity, and Glycosylation between Thyroid and Breast Cancer Cells

PubMed Central

Beyer, Sasha; Lakshmanan, Aparna; Liu, Yu-Yu; Zhang, Xiaoli; Wapnir, Irene; Smolenski, Albert

2011-01-01

Na+/I− symporter (NIS)-mediated iodide uptake into thyroid follicular cells serves as the basis of radioiodine therapy for thyroid cancer. NIS protein is also expressed in the majority of breast tumors, raising potential for radionuclide therapy of breast cancer. KT5823, a staurosporine-related protein kinase inhibitor, has been shown to increase thyroid-stimulating hormone-induced NIS expression, and thus iodide uptake, in thyroid cells. In this study, we found that KT5823 does not increase but decreases iodide uptake within 0.5 h of treatment in trans-retinoic acid and hydrocortisone-treated MCF-7 breast cancer cells. Moreover, KT5823 accumulates hypoglycosylated NIS, and this effect is much more evident in breast cancer cells than thyroid cells. The hypoglycosylated NIS is core glycosylated, has not been processed through the Golgi apparatus, but is capable of trafficking to the cell surface. KT5823 impedes complex NIS glycosylation at a regulatory point similar to brefeldin A along the N-linked glycosylation pathway, rather than targeting a specific N-glycosylated site of NIS. KT5823-mediated effects on NIS activity and glycosylation are also observed in other breast cancer cells as well as human embryonic kidney cells expressing exogenous NIS. Taken together, KT5823 will serve as a valuable pharmacological reagent to uncover mechanisms underlying differential NIS regulation between thyroid and breast cancer cells at multiple levels. PMID:21209020

Photoacoustic spectroscopic differences between normal and malignant thyroid tissues

NASA Astrophysics Data System (ADS)

Li, Li; Xie, Wengming; Li, Hui

2012-12-01

The thyroid is one of the main endocrine glands of human body, which plays a crucial role in the body's metabolism. Thyroid cancer mortality ranks only second to ovarian cancer in endocrine cancer. Routine diagnostic methods of thyroid diseases in present clinic exist misdiagnosis and missed diagnosis to varying degrees. Those lead to miss the best period of cancer treatment--early. Photoacoustic spectroscopy technology is a new tool, which provides an effective and noninvasive way for biomedical materials research, being highly sensitive and without sample pretreatment. In this paper, we use photoacoustic spectroscopy technology (PAST) to detect the absorption spectrum between normal and malignant thyroid tissues. The result shows that the photoacoustic spectroscopy technology (PAST) could differentiate malignant thyroid tissue from normal thyroid tissue very well. This technique combined with routine diagnostic methods has the potential to increase the diagnostic accuracy in clinical thyroid cancer diagnosis.

A thyroid nodule classification method based on TI-RADS

NASA Astrophysics Data System (ADS)

Wang, Hao; Yang, Yang; Peng, Bo; Chen, Qin

2017-07-01

Thyroid Imaging Reporting and Data System(TI-RADS) is a valuable tool for differentiating the benign and the malignant thyroid nodules. In clinic, doctors can determine the extent of being benign or malignant in terms of different classes by using TI-RADS. Classification represents the degree of malignancy of thyroid nodules. TI-RADS as a classification standard can be used to guide the ultrasonic doctor to examine thyroid nodules more accurately and reliably. In this paper, we aim to classify the thyroid nodules with the help of TI-RADS. To this end, four ultrasound signs, i.e., cystic and solid, echo pattern, boundary feature and calcification of thyroid nodules are extracted and converted into feature vectors. Then semi-supervised fuzzy C-means ensemble (SS-FCME) model is applied to obtain the classification results. The experimental results demonstrate that the proposed method can help doctors diagnose the thyroid nodules effectively.

[Usefulness of galectin-3 expression in the clinical behavior of differentiated thyroid carcinoma].

PubMed

López Mondéjar, Pedro; Picó, Antonio; Seguí, Javier; López Maciá, Alicia

2008-02-16

Our objective was to quantify the galectin-3 (gal-3) expression in differentiated thyroid carcinoma and study its relation with the clinical behavior of these tumors. We investigated the immunohistochemical reaction of gal-3 in patients with papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) and performed a retrospective study in order to find correlations with clinical features. Gal-3 expression was studied in 53 differentiated tyroid carcinomas (42 PTC and 11 FTC), and was related with clinical features: metastases, extrathyroid invasion and initial stage in the diagnosis and persistence disease and relapses in the follow up. Gal-3 expression positivity in PTC had a median of 60% (percentil 25 [p25], 17.5%; percentil 75 [p75], 100%), and was significantly higher (p < 0.0001) than in FTC (median, 0%; p25, 0%; p75, 15%). In PTC, gal-3 expression was significantly higher in advanced stages at the time of initial diagnosis (p = 0.014), persistent disease (p = 0.012) and relapses (p = 0.012) during the follow up. We did not find any significant association between gal-3 expression and clinical features of FTC. Gal-3 is a negative prognosis marker in PTC but not in FTC.

Thyroid screening program for irradiated population. [/sup 123/I

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

Shimaoka, K.; Getaz, E.P.; Razack, M.

A screening program was set up at RPMI (Roswell Park Memorial Institute) for those who are at a higher risk of developing benign and malignant goiter, due to radiation therapy for benign conditions in the head and neck areas during infancy and cildhood. During the first year, 735 patients were screened, and 159 patients were found to have palpable abnormalities of the thyroid. Ninety patients participated in a randomized suppressive therapy trial, and 24 patients achieved complete disappearance thyroid operations; eight were found to have well-differentiated thyroid carcinoma and two parathyroid adenoma.

A case of coexistence of TSH/GH-secreting pituitary tumor and papillary thyroid carcinoma: Challenges in pathogenesis and management.

PubMed

Kiatpanabhikul, Phatharaporn; Shuangshoti, Shanop; Chantra, Kraisri; Navicharern, Patpong; Kingpetch, Kanaungnit; Houngngam, Natnicha; Snabboon, Thiti

2017-07-01

Co-existence of thyrotropin/growth hormone-secreting pituitary adenoma with differentiated thyroid carcinoma is exceedingly rare, with less than 15 cases having been reported. Its clinical presentation and treatment strategy are challenging. We report a case of pituitary macroadenoma, with clinical syndromes of acromegaly and hyperthyroidism, and a thyroid nodule, with cytologically confirmed to be a papillary thyroid carcinoma. Clinical implications, focusing on the strategy for proper management, and possible pathogenesis were discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Landscape of Circular RNA Expression Profiles in Papillary Thyroid Carcinoma Based on RNA Sequencing.

PubMed

Lan, Xiabin; Xu, Jiajie; Chen, Chao; Zheng, Chuanming; Wang, Jiafeng; Cao, Jun; Zhu, Xuhang; Ge, Minghua

2018-05-25

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. However, the molecular mechanisms responsible for its tumorigenesis and progression remain largely unknown. Circular RNA (circRNA) is a novel type of noncoding RNA that can serve as an ideal biomarker due to its stability. Recent evidence suggests that circRNAs play important roles in tumorigenesis. This study aims to investigate circRNA expression profiles and their potential biological functions in PTC. High-throughput RNA sequencing was used to assess circRNA expression profiles in PTC, and quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate dysregulated circRNAs. Receiver operating characteristic (ROC) curves were generated to evaluate the diagnostic value of circRNAs for PTC. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were employed to determine the biological functions of differentially expressed circRNAs. Bioinformatic analyses were applied to predict interactions between circRNAs and microRNAs (miRNAs), and a circRNA-miRNA-mRNA network was constructed using Cytoscape software. We identified a number of differentially expressed circRNAs in PTC tissues compared with paired normal thyroid tissues, with chr5: 160757890-160763776-, chr12: 40696591-40697936+, chr7: 22330794-22357656-, and chr21: 16386665-16415895- being upregulated, and chr7: 91924203-91957214+, chr2: 179514891-179516047-, chr9: 16435553-16437522-, and chr22: 36006931-36007153- being downregulated. These findings were confirmed by qRT-PCR, and ROC curves indicated that they can serve as potential biomarkers for PTC. GO and KEGG pathway analyses showed that some of these circRNAs are related to cancers. Additionally, bioinformatic analyses revealed a potential competing-endogenous-RNA-regulating network among circRNAs, miRNAs, and mRNAs. Our study results depict the landscape of circRNA expression profiles in PTC and also provide potential biomarkers for PTC. Further functional and mechanistic studies of these circRNAs may improve our understanding of PTC tumorigenesis. © 2018 The Author(s). Published by S. Karger AG, Basel.

Metastatic squamous cell carcinoma thyroid from functionally cured cancer cervix

PubMed Central

Vamsy, Mohana; Dattatreya, Palanki Satya; Sarma, Lella Yugandhar; Dayal, Monal; Janardhan, Nandigam; Rao, Vatturi Venkata Satya Prabhakar

2013-01-01

The authors report a very unusual occurrence of a metastatic squamous carcinoma to thyroid gland from a treated squamous cell carcinoma cervix 12 years before with no recurrence at the primary site. The case also has an additional complexity of rapid progression of the metastatic thyroid carcinoma to wide spread dissemination to lungs and bones while on concurrent chemo radio therapy confirming the aggressiveness of the entity. PMID:24163519

The role of positron emission tomography and positron emission tomography/computed tomography in thyroid tumours: an overview.

PubMed

Treglia, Giorgio; Muoio, Barbara; Giovanella, Luca; Salvatori, Massimo

2013-05-01

Positron emission tomography (PET) and PET/computed tomography (PET/CT) with different tracers have been increasingly used in patients with thyroid tumours. The aim of this article is to perform an overview based on literature data about the usefulness of PET imaging in this setting. The role of Fluorine-18-Fluorodeoxyglucose (FDG) PET and PET/CT in differentiated thyroid carcinoma (DTC) is well established, particularly in patients presenting with elevated serum thyroglobulin levels and negative radioiodine whole-body scan. Iodine-124 PET and PET/CT may serve a role in staging DTC and obtaining lesional dosimetry for a better and more rationale planning of treatment with Iodine-131. FDG-PET and PET/CT are useful in the post-thyroidectomy staging of high-risk patients with less differentiated histological subtypes. PET and PET/CT with different tracers seem to be useful methods in localizing the source of elevated calcitonin levels in patients with recurrent medullary thyroid carcinoma. Incorporation of FDG-PET or PET/CT into the initial workup of patients with indeterminate thyroid nodules at fine needle aspiration biopsy deserves further investigation. FDG-PET report should suggest further evaluation when focal thyroid incidentalomas are described because these findings are associated with a significant risk of cancer.

Successful treatment of thyroid storm presenting as recurrent cardiac arrest and subsequent multiorgan failure by continuous renal replacement therapy.

PubMed

Park, Han Soo; Kwon, Su Kyoung; Kim, Ye Na

2017-01-01

Thyroid storm is a rare and potentially life-threatening medical emergency. We experienced a case of thyroid storm associated with sepsis caused by pneumonia, which had a catastrophic course including recurrent cardiac arrest and subsequent multiple organ failure (MOF). A 22-year-old female patient with a 10-year history of Graves' disease was transferred to our emergency department (ED). She had a cardiac arrest at her home and a second cardiac arrest at the ED. Her heart recovered after 20 min of cardiac resuscitation. She was diagnosed with thyroid storm associated with hyperthyroidism complicated by pneumonia and sepsis. Although full conventional medical treatment was given, she had progressive MOF and hemodynamic instability consisting of hyperthermia, tachycardia and hypotension. Because of hepatic and renal failure with refractory hypotension, we reduced the patient's dose of beta-blocker and antithyroid drug, and she was started on continuous veno-venous renal replacement therapy (CRRT) with intravenous albumin and plasma supplementation. Subsequently, her body temperature and pulse rate began to stabilize within 1 h, and her blood pressure reached 120/60 mmHg after 6 h. We discontinued antithyroid drug 3 days after admission because of aggravated hyperbilirubinemia. The patient exhibited progressive improvement in thyroid function even after cessation of antithyroid drug, and she successfully recovered from thyroid storm and MOF. This is the first case of thyroid storm successfully treated by CRRT in a patient considered unfit for antithyroid drug treatment. The presenting manifestations of thyroid storm vary and can include cardiac arrest with multiorgan failure in rare cases.In some patients with thyroid storm, especially those with severe complications, conventional medical treatment may be ineffective or inappropriate.During thyroid storm, the initiation of CRRT can immediately lower body temperature and subsequently stabilize vital signs.Early initiation of CRRT can be life-saving in patients with thyroid storm complicated by MOF, even when used in combination with suboptimal medical treatment.

Management Guidelines for Children with Thyroid Nodules and Differentiated Thyroid Cancer

PubMed Central

Waguespack, Steven G.; Bauer, Andrew J.; Angelos, Peter; Benvenga, Salvatore; Cerutti, Janete M.; Dinauer, Catherine A.; Hamilton, Jill; Hay, Ian D.; Luster, Markus; Parisi, Marguerite T.; Rachmiel, Marianna; Thompson, Geoffrey B.; Yamashita, Shunichi

2015-01-01

Background: Previous guidelines for the management of thyroid nodules and cancers were geared toward adults. Compared with thyroid neoplasms in adults, however, those in the pediatric population exhibit differences in pathophysiology, clinical presentation, and long-term outcomes. Furthermore, therapy that may be recommended for an adult may not be appropriate for a child who is at low risk for death but at higher risk for long-term harm from overly aggressive treatment. For these reasons, unique guidelines for children and adolescents with thyroid tumors are needed. Methods: A task force commissioned by the American Thyroid Association (ATA) developed a series of clinically relevant questions pertaining to the management of children with thyroid nodules and differentiated thyroid cancer (DTC). Using an extensive literature search, primarily focused on studies that included subjects ≤18 years of age, the task force identified and reviewed relevant articles through April 2014. Recommendations were made based upon scientific evidence and expert opinion and were graded using a modified schema from the United States Preventive Services Task Force. Results: These inaugural guidelines provide recommendations for the evaluation and management of thyroid nodules in children and adolescents, including the role and interpretation of ultrasound, fine-needle aspiration cytology, and the management of benign nodules. Recommendations for the evaluation, treatment, and follow-up of children and adolescents with DTC are outlined and include preoperative staging, surgical management, postoperative staging, the role of radioactive iodine therapy, and goals for thyrotropin suppression. Management algorithms are proposed and separate recommendations for papillary and follicular thyroid cancers are provided. Conclusions: In response to our charge as an independent task force appointed by the ATA, we developed recommendations based on scientific evidence and expert opinion for the management of thyroid nodules and DTC in children and adolescents. In our opinion, these represent the current optimal care for children and adolescents with these conditions. PMID:25900731

Management Guidelines for Children with Thyroid Nodules and Differentiated Thyroid Cancer.

PubMed

Francis, Gary L; Waguespack, Steven G; Bauer, Andrew J; Angelos, Peter; Benvenga, Salvatore; Cerutti, Janete M; Dinauer, Catherine A; Hamilton, Jill; Hay, Ian D; Luster, Markus; Parisi, Marguerite T; Rachmiel, Marianna; Thompson, Geoffrey B; Yamashita, Shunichi

2015-07-01

Previous guidelines for the management of thyroid nodules and cancers were geared toward adults. Compared with thyroid neoplasms in adults, however, those in the pediatric population exhibit differences in pathophysiology, clinical presentation, and long-term outcomes. Furthermore, therapy that may be recommended for an adult may not be appropriate for a child who is at low risk for death but at higher risk for long-term harm from overly aggressive treatment. For these reasons, unique guidelines for children and adolescents with thyroid tumors are needed. A task force commissioned by the American Thyroid Association (ATA) developed a series of clinically relevant questions pertaining to the management of children with thyroid nodules and differentiated thyroid cancer (DTC). Using an extensive literature search, primarily focused on studies that included subjects ≤18 years of age, the task force identified and reviewed relevant articles through April 2014. Recommendations were made based upon scientific evidence and expert opinion and were graded using a modified schema from the United States Preventive Services Task Force. These inaugural guidelines provide recommendations for the evaluation and management of thyroid nodules in children and adolescents, including the role and interpretation of ultrasound, fine-needle aspiration cytology, and the management of benign nodules. Recommendations for the evaluation, treatment, and follow-up of children and adolescents with DTC are outlined and include preoperative staging, surgical management, postoperative staging, the role of radioactive iodine therapy, and goals for thyrotropin suppression. Management algorithms are proposed and separate recommendations for papillary and follicular thyroid cancers are provided. In response to our charge as an independent task force appointed by the ATA, we developed recommendations based on scientific evidence and expert opinion for the management of thyroid nodules and DTC in children and adolescents. In our opinion, these represent the current optimal care for children and adolescents with these conditions.

Thyroid hormones and fetal brain development.

PubMed

Pemberton, H N; Franklyn, J A; Kilby, M D

2005-08-01

Thyroid hormones are intricately involved in the developing fetal brain. The fetal central nervous system is sensitive to the maternal thyroid status. Critical amounts of maternal T3 and T4 must be transported across the placenta to the fetus to ensure the correct development of the brain throughout ontogeny. Severe mental retardation of the child can occur due to compromised iodine intake or thyroid disease. This has been reported in areas of the world with iodine insufficiency, New Guinea, and also in mother with thyroid complications such as hypothyroxinaemia and hyperthyroidism. The molecular control of thyroid hormones by deiodinases for the activation of thyroid hormones is critical to ensure the correct amount of active thyroid hormones are temporally supplied to the fetus. These hormones provide timing signals for the induction of programmes for differentiation and maturation at specific stages of development. Understanding these molecular mechanisms further will have profound implications in the clinical management of individuals affected by abnormal maternal of fetal thyroid status.

On-line transmission electron microscopic image analysis of chromatin texture for differentiation of thyroid gland tumors.

PubMed

Kriete, A; Schäffer, R; Harms, H; Aus, H M

1987-06-01

Nuclei of the cells from the thyroid gland were analyzed in a transmission electron microscope by direct TV scanning and on-line image processing. The method uses the advantages of a visual-perception model to detect structures in noisy and low-contrast images. The features analyzed include area, a form factor and texture parameters from the second derivative stage. Three tumor-free thyroid tissues, three follicular adenomas, three follicular carcinomas and three papillary carcinomas were studied. The computer-aided cytophotometric method showed that the most significant differences were the statistics of the chromatin texture features of homogeneity and regularity. These findings document the possibility of an automated differentiation of tumors at the ultrastructural level.

(131)I treatment in Differentiated Thyroid Cancer and End-Stage Renal Disease.

PubMed

Ortega, A J M; Vázquez, R G; Cuenca, J I C; Brocca, M A M; Castilla, J; Martínez, J M M; González, E N

2016-01-01

Radioiodine (RAI) is a cornerstone in the treatment of Differentiated Thyroid Cancer (DTC). In patients on haemodialysis due to End-Stage Renal Disease (ESRD), it must be used cautiously, considering the renal clearance of this radionuclide. Also, the safety of the procedure and subsequent long-term outcome is still not well defined. In 2001, we described a dosimetric method and short-term results in three patients, with a good safety profile. We hypothesize that our method is safe in a long-term scenario without compromising the prognosis of both renal and thyroid disease. Descriptive-retrospective study. A systematic search was carried out using our clinical database from 2000 to 2014. DTC and radioiodine treatment while on haemodialysis. peritoneal dialysis. Final sample n=9 patients (n=5 males), age 48 years (median age 51 years males, 67 years female group); n=8 papillary thyroid cancer, n=1 follicular thyroid cancer; n=5 lymph node invasion; n=1 metastatic disease. Median RAI dose administered on haemodialysis 100mCi. 7.5 years after radioiodine treatment on haemodialysis, n=7 deemed free of thyroid disease, n=1 persistent non-localised disease. No complications related to the procedure or other target organs were registered. After 3.25 years, n=4 patients underwent successful renal transplantation; n=4 patients did not meet transplantation criteria due to other conditions unrelated to the thyroid disease or its treatment. One patient died due to ischemic cardiomyopathy (free of thyroid disease). Radioiodine treatment during haemodialysis is a long-term, safe procedure without worsening prognosis of either renal or thyroid disease. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

Autonomic Dysreflexia-Like Syndrome in a T12 Paraplegic During Thoracic Spine Surgery

DTIC Science & Technology

2010-11-01

pheochromocytoma , carcinoid syndrome, or thyroid storm. This presentation differs from autonomic dysreflexia because the spinal cord lesion was well below T6...instability. The differential diagnosis of isolated, abrupt intraopera- tive hypertension includes pheochromocytoma , carcinoid syndrome, thyroid storm

[Thyroid hormones and the development of the nervous system].

PubMed

Mussa, G C; Zaffaroni, M; Mussa, F

1990-09-01

The growth and differentiation of the central nervous system are closely related to the presence of iodine and thyroid hormones. During the first trimester of human pregnancy the development of the nervous system depends entirely on the availability of iodine; after 12 week of pregnancy it depends on the initial secretion of iodothyronine by the fetal thyroid gland. During the early stages of the development of the nervous system a thyroid hormone deficit may provoke alterations in the maturation of both noble nervous cells (cortical pyramidal cells, Purkinje cells) and glial cells. Hypothyroidism may lead to cellular hypoplasia and reduced dendritic ramification, gemmules and interneuronal connections. Experimental studies in hypothyroid rats have also shown alterations in the content and organization of neuronal intracytoplasmatic microtubules, the biochemical maturation of synaptosomes and the maturation of nuclear and cytoplasmatic T3 receptors. Excess thyroid hormones during the early stages of development may also cause permanent damage to the central nervous system. Hyperthyroidism may initially induce an acceleration of the maturation processes, including the migration and differentiation of cells, the extension of the dendritic processes and synaptogenesis. An excess of thyroid hormones therefore causes neuronal proliferation to end precociously leading to a reduction of the total number of gemmules. Experimental research and clinical studies have partially clarified the correlation between the maturation of the nervous system and thyroid function during the early stages of development; both a deficit and excess of thyroid hormones may lead to permanent anatomo-functional damage to the central nervous system.(ABSTRACT TRUNCATED AT 250 WORDS)

The role of hypothyroidism in the etiology and progression of dilated cardiomyopathy in Doberman Pinschers.

PubMed

Beier, P; Reese, S; Holler, P J; Simak, J; Tater, G; Wess, G

2015-01-01

Hypothyroidism and dilated cardiomyopathy (DCM) are both common diseases in Doberman Pinschers. A possible influence of hypothyroidism on the etiology and progression of DCM is controversial. Evaluation of the role of hypothyroidism in etiology and progression of DCM. A total of 175 Doberman Pinschers. In this longitudinal prospective study, echocardiography and 24-hour ambulatory ECG recordings were performed in all dogs as screening tests for DCM. Total thyroxine (TT4 ) and thyroid ultrasonography served as initial screening tests for hypothyroidism and low TT4 values were followed up by a thyroid stimulating hormone (TSH) test or free total thyroxine (fT4 )/cTSH measurements. Additionally, a follow-up study of dogs affected by both DCM and hypothyroidism under optimal treatment for hypothyroidism was conducted. A total of 107 dogs were healthy, 45 dogs had DCM, 11 hypothyroidism, and 12 dogs had both DCM and hypothyroidism. TT4 values as well as the thyroid volumes were equivalent in the healthy dogs and in those with DCM. Neither ventricular premature complexes nor echocardiographic parameters differed between healthy and hypothyroid dogs. Dogs with DCM had a 2.26-fold (CI0.95 = 1.1-4.8) higher risk of also being affected by hypothyroidism. Despite optimal thyroid treatment of dogs with hypothyroidism and DCM, there was a progression of the heart disease. This study did not confirm a role of hypothyroidism in the etiology or progression of DCM. Treatment of hypothyroidism did not improve the clinical outcome. Copyright © 2014 by the American College of Veterinary Internal Medicine.

Molecular differential diagnosis of follicular thyroid carcinoma and adenoma based on gene expression profiling by using formalin-fixed paraffin-embedded tissues

PubMed Central

2013-01-01

Background Differential diagnosis between malignant follicular thyroid cancer (FTC) and benign follicular thyroid adenoma (FTA) is a great challenge for even an experienced pathologist and requires special effort. Molecular markers may potentially support a differential diagnosis between FTC and FTA in postoperative specimens. The purpose of this study was to derive molecular support for differential post-operative diagnosis, in the form of a simple multigene mRNA-based classifier that would differentiate between FTC and FTA tissue samples. Methods A molecular classifier was created based on a combined analysis of two microarray datasets (using 66 thyroid samples). The performance of the classifier was assessed using an independent dataset comprising 71 formalin-fixed paraffin-embedded (FFPE) samples (31 FTC and 40 FTA), which were analysed by quantitative real-time PCR (qPCR). In addition, three other microarray datasets (62 samples) were used to confirm the utility of the classifier. Results Five of 8 genes selected from training datasets (ELMO1, EMCN, ITIH5, KCNAB1, SLCO2A1) were amplified by qPCR in FFPE material from an independent sample set. Three other genes did not amplify in FFPE material, probably due to low abundance. All 5 analysed genes were downregulated in FTC compared to FTA. The sensitivity and specificity of the 5-gene classifier tested on the FFPE dataset were 71% and 72%, respectively. Conclusions The proposed approach could support histopathological examination: 5-gene classifier may aid in molecular discrimination between FTC and FTA in FFPE material. PMID:24099521

Thyroid abnormalities after therapeutic external radiation

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

Hancock, S.L.; McDougall, I.R.; Constine, L.S.

1995-03-30

The thyroid gland is the largest pure endocrine gland in the body and one of the organs most likely to produce clinically significant abnormalities after therapeutic external radiation. Radiation doses to the thyroid that exceed approximately 26 Gy frequently produce hypothyroidism, which may be clinically overt or subclinical, as manifested by increased serum thyrotropin and normal serum-free thyroxine concentrations. Pituitary or hypothalamic hypothyroidism may arise when the pituitary region receives doses exceeding 50 Gy with conventional, 1.8-2 Gy fractionation. Direct irradiation of the thyroid may increase the risk of Graves` disease or euthyroid Graves` ophthalmopathy. Silent thyroiditis, cystic degeneration, benignmore » adenoma, and thyroid cancer have been observed after therapeutically relevant doses of external radiation. Direct or incidental thyroid irradiation increases the risk for well-differentiated, papillary, and follicular thyroid cancer from 15- to 53-fold. Thyroid cancer risk is highest following radiation at a young age, decreases with increasing age at treatment, and increases with follow-up duration. The potentially prolonged latent period between radiation exposure and the development of thyroid dysfunction, thyroid nodularity, and thyroid cancer means that individuals who have received neck or pituitary irradiation require careful, periodic clinical and laboratory evaluation to avoid excess morbidity. 39 refs.« less

OPTIMIZING LENVATINIB THERAPY IN PATIENTS WITH METASTATIC RADIOACTIVE IODINE-RESISTANT DIFFERENTIATED THYROID CANCERS.

PubMed

Jasim, Sina; Iniguez-Ariza, Nicole M; Hilger, Crystal R; Chintakuntlawar, Ashish V; Ryder, Mabel M; Morris, John C; Bible, Keith C

2017-10-01

Lenvatinib is approved for use in advanced radioactive iodine-resistant differentiated thyroid cancers (RAIR-DTCs). Its efficacy is indisputable, but toxicities are great, creating daunting challenges for patients and providers. Few data regarding early adverse events and impact on quality of life (QOL) exist; we sought to clarify these issues by analyzing our initial postapproval lenvatinib experience. Standardized patient education was implemented, providing detailed instructions and expert provider contacts to facilitate timely reporting of toxicities and guide responsive actions. Early adverse events, QOL outcomes, and response data from 25 consecutively treated DTC patients (02/2015 and 05/2016) were retrospectively analyzed. The median age was 55 years (range 27-81); 52% were female. Fourteen (56%) were on antihypertensive medication(s) at baseline. Most patients (21/25, 84%) developed adverse events during the first month of therapy. Hypertension arose in 16/25 (64%), requiring antihypertensive dose adjustment/addition in 6 (24%)/12 (48%) patients, respectively, during the first month of therapy. Dose reduction was required in 11 (44%) due to multiple adverse events; the median time to first dose reduction was 33 days (range 11-84); 8 (32%) required multiple dose reductions. Therapy interruption >3 weeks occurred in 4 (16%). The median change in patient-reported fatigue score was +2 (worsening, range -2 to +10, P<.007; 0-10 scales), but the median QOL change was 0 (range +4 to -9, P = .57). The mean duration of lenvatinib therapy was 6.5 months (range 1-12); median overall and progression-free survival have not yet been reached. Lenvatinib was discontinued in 7 (28%) patients; among 20 patients with available RECIST (Response Evaluation Criteria In Solid Tumors) measurements, 10 (50%) achieved partial response. Lenvatinib has promising efficacy in RAIR-DTC, but toxicities require frequent early interventions. QOL can be maintained on lenvatinib therapy. DTC = differentiated thyroid cancer; LASA = linear analog self-assessment; PR = partial response; QOL = quality of life; RAI = radioactive iodine; RAIR = RAI-resistant; RECIST = Response Evaluation Criteria In Solid Tumors; Tg = thyroglobulin; VEGFR = vascular endothelial growth factor receptor.

Thyroid hormone and the central control of homeostasis.

PubMed

Warner, Amy; Mittag, Jens

2012-08-01

It has long been known that thyroid hormone has profound direct effects on metabolism and cardiovascular function. More recently, it was shown that the hormone also modulates these systems by actions on the central autonomic control. Recent studies that either manipulated thyroid hormone signalling in anatomical areas of the brain or analysed seasonal models with an endogenous fluctuation in hypothalamic thyroid hormone levels revealed that the hormone controls energy turnover. However, most of these studies did not progress beyond the level of anatomical nuclei; thus, the neuronal substrates as well as the molecular mechanisms remain largely enigmatic. This review summarises the evidence for a role of thyroid hormone in the central autonomic control of peripheral homeostasis and advocates novel strategies to address thyroid hormone action in the brain on a cellular level.

The management of metastatic radioiodine-refractory differentiated thyroid cancer requires an integrated approach including both directed and systemic therapies.

PubMed

Cooray, Shamil D; Topliss, Duncan J

2017-01-01

A 58-year-old man with metastatic radioiodine-refractory differentiated thyroid cancer (DTC) presented with left thigh and right flank numbness. He had known progressive and widespread bony metastases, for which he received palliative radiotherapy, and multiple bilateral asymptomatic pulmonary metastases. CT scan and MRI of the spine revealed metastases at right T10-L1 vertebrae with extension into the central canal and epidural disease at T10 and T11 causing cord displacement and canal stenosis but retention of spinal cord signal. Spinal surgery was followed by palliative radiotherapy resulting in symptom resolution. Two months later, sorafenib received approval for use in Australia and was commenced and up-titrated with symptomatic management of mild adverse effects. Follow-up CT scan three months after commencement of sorafenib revealed regression of pulmonary metastases but no evident change in most bone metastases except for an advancing lesion eroding into the right acetabulum. The patient underwent a right total hip replacement, intra-lesional curettage and cementing. After six months of sorafenib therapy, CT scanning showed enlarging liver lesions with marked elevation of serum thyroglobulin. Lenvatinib was commenced and sorafenib was ceased. He now has stable disease with a falling thyroglobulin more than 5 years after metastatic radioiodine-refractory DTC was diagnosed. In DTC, 5% of distant metastases become radioiodine-refractory, resulting in a median overall survival of 2.5-3.5 years. Tyrosine kinase inhibitor (TKI) therapy has recently been demonstrated to increase progression-free survival in these patients but poses some unique management issues and is best used as part of an integrated approach with directed therapy. Directed therapies may have greater potential to control localised disease and related symptoms when compared to systemic therapies.Consider TKI therapy in progressive disease where benefits outweigh risks.Active surveillance and timely intervention are required for TKI-related adverse effects.There is a need for further research on the clinical application of TKI therapy in advanced DTC, including comparative efficacy, sequencing and identifying responders.

Mechanism-based testing strategy using in vitro approaches for identification of thyroid hormone disrupting chemicals

EPA Science Inventory

The thyroid hormone (TH) system is involved in several important physiological processes, including regulation of energy metabolism, growth and differentiation, development and maintenance of brain function, thermo-regulation, osmo-regulation, and axis of regulation of other endo...

Outcome of radioiodine-131 therapy in hyperfunctioning thyroid nodules: a 20 years' retrospective study.

PubMed

Ceccarelli, Claudia; Bencivelli, Walter; Vitti, Paolo; Grasso, Lucia; Pinchera, Aldo

2005-03-01

To investigate the risk of hypothyroidism after radioiodine (131I) treatment for hyperfunctioning thyroid nodules. Retrospective analysis of patients treated with 131I for hyperfunctioning thyroid nodules and followed up for a maximum of 20 years. A total of 346 patients treated with 131I in the years 1975-95, for a single hyperfunctioning nodule. Hypothyroidism was defined as TSH levels > 3.7 mU/l. Kaplan-Meier survival analysis was used to analyse permanence of euthyroidism after 131I. A stepwise Cox proportional hazard model was used to identify factors influencing the progression to hypothyroidism. The cumulative incidence of hypothyroidism was 7.6% at 1 year, 28% at 5 years, 46% at 10 years and 60% at 20 years. Age (P < 0.01), 24-th 131I uptake (P < 0.05) and previous treatment with methimazole (MMI, P < 0.1) were associated with a faster progression towards hypothyroidism, while thyroid and nodule size, thyroid status at diagnosis and degree of extranodular thyroid parenchymal suppression had no influence. In hyperthyroid patients with partial parenchymal suppression, however, previous MMI treatment was the most important prognostic factor (P < 0.01). After 20 years of follow-up, 60% of patients treated with 131I for a single hyperfunctioning nodule are hypothyroid. Factors increasing the risk of hypothyroidism are age, 131I uptake and MMI pretreatment. The prognostic value of this last factor, however, depends on the degree of suppression of the extranodular thyroid parenchyma at the scan.

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

The Treatment of Differentiated Thyroid Cancer in Children: Emphasis on Surgical Approach and Radioactive Iodine Therapy

PubMed Central

Mazzaferri, Ernest L.; Verburg, Frederik A.; Reiners, Christoph; Luster, Markus; Breuer, Christopher K.; Dinauer, Catherine A.; Udelsman, Robert

2011-01-01

Pediatric thyroid cancer is a rare disease with an excellent prognosis. Compared with adults, epithelial-derived differentiated thyroid cancer (DTC), which includes papillary and follicular thyroid cancer, presents at more advanced stages in children and is associated with higher rates of recurrence. Because of its uncommon occurrence, randomized trials have not been applied to test best-care options in children. Even in adults that have a 10-fold or higher incidence of thyroid cancer than children, few prospective trials have been executed to compare treatment approaches. We recognize that treatment recommendations have changed over the past few decades and will continue to do so. Respecting the aggressiveness of pediatric thyroid cancer, high recurrence rates, and the problems associated with decades of long-term follow-up, a premium should be placed on treatments that minimize risk of recurrence and the adverse effects of treatments and facilitate follow-up. We recommend that total thyroidectomy and central compartment lymph node dissection is the surgical procedure of choice for children with DTC if it can be performed by a high-volume thyroid surgeon. We recommend radioactive iodine therapy for remnant ablation or residual disease for most children with DTC. We recommend long-term follow-up because disease can recur decades after initial diagnosis and therapy. Considering the complexity of DTC management and the potential complications associated with therapy, it is essential that pediatric DTC be managed by physicians with expertise in this area. PMID:21880704

American Thyroid Association consensus review and statement regarding the anatomy, terminology, and rationale for lateral neck dissection in differentiated thyroid cancer.

PubMed

Stack, Brendan C; Ferris, Robert L; Goldenberg, David; Haymart, Megan; Shaha, Ashok; Sheth, Sheila; Sosa, Julie Ann; Tufano, Ralph P

2012-05-01

Cervical lymph node metastases from differentiated thyroid cancer (DTC) are common. Thirty to eighty percent of patients with papillary thyroid cancer harbor lymph node metastases, with the central neck being the most common compartment involved. The goals of this study were to: (1) identify appropriate methods for determining metastatic DTC in the lateral neck and (2) address the extent of lymph node dissection for the lateral neck necessary to control nodal disease balanced against known risks of surgery. A literature review followed by formulation of a consensus statement was performed. Four proposals regarding management of the lateral neck are made for consideration by organizations developing management guidelines for patients with thyroid nodules and DTC including the next iteration of management guidelines developed by the American Thyroid Association (ATA). Metastases to lateral neck nodes must be considered in the evaluation of the newly diagnosed thyroid cancer patient and for surveillance of the previously treated DTC patient. Lateral neck lymph nodes are a significant consideration in the surgical management of patients with DTC. When current guidelines formulated by the ATA and by other international medical societies are followed, initial evaluation of the DTC patient with ultrasound (or other modalities when indicated) will help to identify lateral neck lymph nodes of concern. These findings should be addressed using fine-needle aspiration biopsy. A comprehensive neck dissection of at least nodal levels IIa, III, IV, and Vb should be performed when indicated to optimize disease control.

Radioiodine thyroid remnant ablation after recombinant human thyrotropin or thyroid hormone withdrawal in patients with high-risk differentiated thyroid cancer.

PubMed

Pitoia, Fabián; Marlowe, Robert J; Abelleira, Erika; Faure, Eduardo N; Bueno, Fernanda; Schwarzstein, Diego; Lutfi, Rubén Julio; Niepomniszcze, Hugo

2012-01-01

To supplement limited relevant literature, we retrospectively compared ablation and disease outcomes in high-risk differentiated thyroid carcinoma (DTC) patients undergoing radioiodine thyroid remnant ablation aided by recombinant human thyrotropin (rhTSH) versus thyroid hormone withdrawal/withholding (THW). Our cohort was 45 consecutive antithyroglobulin antibody- (TgAb-) negative, T3-T4/N0-N1-Nx/M0 adults ablated with high activities at three referral centers. Ablation success comprised negative (<1 μg/L) stimulated serum thyroglobulin (Tg) and TgAb, with absent or <0.1% scintigraphic thyroid bed uptake. "No evidence of disease" (NED) comprised negative unstimulated/stimulated Tg and no suspicious neck ultrasonography or pathological imaging or biopsy. "Persistent disease" was failure to achieve NED, "recurrence," loss of NED status. rhTSH patients (n = 18) were oftener ≥45 years old and higher stage (P = 0.01), but otherwise not different than THW patients (n = 27) at baseline. rhTSH patients were significantly oftener successfully ablated compared to THW patients (83% versus 67%, P < 0.02). After respective 3.3 yr and 4.5 yr mean follow-ups (P = 0.02), NED was achieved oftener (72% versus 59%) and persistent disease was less frequent in rhTSH patients (22% versus 33%) (both comparisons P = 0.03). rhTSH stimulation is associated with at least as good outcomes as is THW in ablation of high-risk DTC patients.

Hexamethylenebisacetamide modulation of thyroglobulin and protein levels in thyroid cells is not mediated by phosphatidylinositol-3-kinase: a study with wortmannin.

PubMed

Aouani, A; Samih, N; Amphoux-Fazekas, T; Hovsépian, S; Fayet, G

1999-04-01

Hexamethylenebisacetamide (HMBA) induces in murine erythroleukemia cells (MELC) the commitment to terminal differentiation leading to globin gene expression. In the thyroid, HMBA acts as a growth factor and also as a differentiating agent. In the present paper, we studied the effect of HMBA on the very specific thyroid marker thyroglobulin (Tg) in two different thyroid cell systems, i.e., porcine cells in primary culture and ovine cells in long term culture. Using wortmannin, a specific inhibitor of phosphatidylinositol-3-kinase, we investigated whether this enzyme is involved in HMBA mode of action. We found that HMBA is a positive modulator of Tg production in porcine cells, but a negative effector in the OVNIS cell line. As all HMBA effects studied in the present paper, i.e., Tg production and total protein levels, are not inhibited by wortmannin, we suggest the non-involvement of phosphatidylinositol-3-kinase in HMBA mode of action.

Follicular thyroid cancer and Hürthle cell carcinoma: challenges in diagnosis, treatment, and clinical management.

PubMed

Grani, Giorgio; Lamartina, Livia; Durante, Cosimo; Filetti, Sebastiano; Cooper, David S

2018-06-01

Follicular thyroid cancer is the second most common differentiated thyroid cancer histological type and has been overshadowed by its more common counterpart-papillary thyroid cancer-despite its unique biological behaviour and less favourable outcomes. In this Review, we comprehensively review the literature on follicular thyroid cancer to provide an evidence-based guide to the management of these tumours, to highlight the lack of evidence behind guideline recommendations, and to identify changes and challenges over the past decades in diagnosis, prognosis, and treatment. We highlight that correct identification of cancer in indeterminate cytological samples is challenging and ultrasonographic features can be misleading. Despite certain unique aspects of follicular thyroid cancer presentation and prognosis, no specific recommendations exist for follicular thyroid cancer and Hürthle cell carcinoma in evidence-based guidelines. Efforts should be made to stimulate additional research in this field. Copyright © 2018 Elsevier Ltd. All rights reserved.

Iodine-induced hyperthyroidism as combination of different etiologies: an overlooked entity in the elderly.

PubMed

Foppiani, Luca; Cascio, Christian; Lo Pinto, Giuliano

2016-10-01

Iodine-induced thyrotoxicosis, which raises several diagnostic and therapeutical challenges, is often overlooked. Hyperthyroidism can induce atrial fibrillation, a harmful arrhythmia which can precipitate heart failure and cause stroke. We report the case of an elderly man who was diagnosed with tachyfibrillation secondary to hyperthyroidism. Thyroid hyperfunction was subsequently related both to previous amiodarone therapy (probably mixed form) and the recent use of iodinated contrast medium for computed tomography scan. Thyroid ultrasonography showed a plongeant multinodular goitre. After initial worsening, thyroid function improved slowly but progressively on high-dose thyreostatic therapy combined with steroid therapy; tachyfibrillation caused heart failure and a thrombus in the left atrium, and proved initially resistant to combined antiarrhythmic treatments. Progressive reduction in thyroid hormone levels, together with combined cardiologic therapies, controlled the heart rate, though atrial fibrillation persisted; anticoagulant therapy resolved the atrial thrombus. Alterations in thyroid function are common in amiodarone-treated patients, who therefore require regular hormonal checks. The different forms of amiodarone-induced thyrotoxicosis must be investigated, since they require different therapies, though mixed forms often occur. The superimposition of further iodine excess due to other causes may be catastrophic and cause severe cardiac problems in these patients.

Regional approaches to the management of patients with advanced, radioactive iodine-refractory differentiated thyroid carcinoma.

PubMed

Brose, Marcia S; Smit, Johannes; Capdevila, Jaume; Elisei, Rossella; Nutting, Christopher; Pitoia, Fabian; Robinson, Bruce; Schlumberger, Martin; Shong, Young Kee; Takami, Hiroshi

2012-09-01

For patients with advanced, radioactive iodine-refractory differentiated thyroid cancer, current treatment guidelines recommend clinical trial enrollment or small-molecule kinase inhibitor therapy. However, details of patient management vary between countries depending on trial availability and national regulatory policies. Insufficient clinical trial data and variable disease characteristics challenge the creation of universal guidelines, and treatment plans often reflect regional influences. A multidisciplinary, multiregional panel of experts met to discuss regional approaches to managing patients with advanced, radioactive iodine-refractory differentiated thyroid cancer and the potential impact of emerging therapies on current treatment strategies. Despite process-oriented regional differences, the decision-making strategies were similar. Multidisciplinary teams used to manage high-risk patients varied in composition across regions, particularly regarding the responsible physician's specialty. Cytotoxic chemotherapy was viewed as limited in clinical benefit, and targeted agents as attractive, based on promising data. Panel members support clinical trial enrollment as the preferred treatment strategy for managing these patients.

[Sclerosing mucoepidermoid carcinoma with eosinophilia of the thyroid: description of a case].

PubMed

Cavazza, A; Toschi, E; Valcavi, R; Piana, S; Scotti, R; Carlinfante, G; Gardini, G

1999-02-01

A case of sclerosing mucoepidermoid carcinoma with eosinophilia of the thyroid gland is described. The patient, a 32 year-old female with Hashimoto's thyroiditis, presented with a 4 cm nodule of the right lobe of the thyroid gland. The tumour was constituted by squamoid cords infiltrating a dense fibro-jaline stroma rich in eosinophils. The patient is alive and well 14 months after surgery. The literature is briefly reviewed and the differential diagnosis is discussed. In the Author's opinion, sclerosing mucoepidermoid carcinoma with eosinophilia of the tyroid is a well defined clinicopathological entity.

False-positive iodine-131 whole-body scan findings in patients with differentiated thyroid carcinoma: report of 11 cases and review of the literature.

PubMed

Buton, Leckzinscka; Morel, Olivier; Gault, Patricia; Illouz, Frédéric; Rodien, Patrice; Rohmer, Vincent

2013-07-01

Iodine-131 (I-131) whole-body scan (WBS) plays an important role in the management of patients with differentiated thyroid carcinoma (DTC), to detect normal thyroid remnants and recurrent or metastatic disease. A focus of I-131 accumulation outside the thyroid bed and the areas of physiological uptake is strongly suggestive of a distant functioning metastasis. However, many false-positive I-131 WBS findings have been reported in the literature. We describe a series of 11 personal cases of patients with DTC, collected from 1992 to 2011, in whom diagnostic or post-treatment WBS showed false-positive retention of I-131 in various locations. False-positive accumulations of I-131 on WBS may be classified according to the underlying pathophysiological mechanisms: external and internal contaminations by body secretions, ectopic normal thyroid and gastric tissues, inflammatory and infectious diseases, benign and malignant tumors, cysts and effusions of serous cavities, thymic uptake, and other non classified causes. Clinicians must be aware of possible false-positive findings to avoid misinterpretations of the I-131 WBS, which could lead to inappropriate treatments. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Role of ultrasonography in the differential diagnosis of thyrotoxicosis: a noninvasive, cost-effective, and widely available but underutilized diagnostic tool.

PubMed

Alzahrani, Ali S; Ceresini, Graziano; Aldasouqi, Saleh A

2012-01-01

To explore the use of ultrasonography as a diagnostic alternative to the traditional "gold standard" imaging study of nuclear scintigraphy in the evaluation of thyrotoxicosis. We review the relevant literature and share our own experience to highlight the promising role of ultrasonography in thyrotoxicosis. In addition, we present a diagnostic algorithm suggesting liberal use of ultrasonography in the evaluation of thyrotoxicosis. Ultrasonography has proved effective not only in the differentiation of Graves disease from other types and causes of thyrotoxicosis but also in the detection of subtle thyroid nodules. The latter role is emphasized in light of the recent observation of an increased risk of occurrence of papillary thyroid carcinoma in patients with Graves disease. Ultrasonography is a cost-effective, noninvasive, portable, and safe imaging modality in the evaluation of thyrotoxicosis, both for physiologic assessment and for detection of nonpalpable thyroid cancers that may elude identification on physical examination and nuclear imaging studies. Although thyroid scintigraphy remains a standard radiologic study, thyroid ultrasonography can be a practical alternative in many cases and the primary imaging modality in some situations such as during pregnancy and lactation and for evaluation and management of amiodarone-induced thyrotoxicosis.

Thyroid Hormone Differentially Modulates Warburg Phenotype in Breast Cancer Cells

PubMed Central

Suhane, Sonal; Ramanujan, V Krishnan

2011-01-01

Sustenance of cancer cells in vivo critically depends on a variety of genetic and metabolic adaptations. Aerobic glycolysis or Warburg effect has been a defining biochemical hallmark of transformed cells for more than five decades although a clear molecular basis of this observation is emerging only in recent years. In this study, we present our findings that thyroid hormone exerts its non-genomic and genomic actions in two model human breast cancer cell lines differentially. By laying a clear foundation for experimentally monitoring the Warburg phenotype in living cancer cells, we demonstrate that thyroid hormone-induced modulation of bioenergetic profiles in these two model cell lines depends on the degree of Warburg phenotype that they display. Further we also show that thyroid hormone can sensitize mitochondria in aggressive, triple-negative breast cancer cells favorably to increase the chemotherapeutic efficacy in these cells. Even though the role of thyroid hormone in modulating mitochondrial metabolism has been known, the current study accentuates the critical role it plays in modulating Warburg phenotype in breast cancer cells. The clinical significance of this finding is the possibility to devise strategies for metabolically modulating aggressive triple-negative tumors so as to enhance their chemosensitivity in vivo. PMID:21945435

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.

Dosimetry in differentiated thyroid carcinoma (12-1402R)

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

Minguez, Pablo; Genolla, Jose; Celeiro, Jose Javier

2013-01-15

Purpose: The aim of this study has been to perform a dosimetric study in the treatments of differentiated thyroid cancer (DTC) performed in our center in order to find a dose-effect correlation. Methods: Thirty patients treated for DTC with 3700 MBq of {sup 131}I have been included in this study. For reasons of radiological protection all of them spent two nights as inpatients. Dose rate at 1 m from all patients was measured approximately 20 and 44 h after the administration of the radioiodine and a whole body scan in the gamma camera was performed approximately 1 week later. Withmore » those measurements and by using a model of two compartments the activities in thyroid bed remnants and in the whole body were calculated as a function of time. The integration of both activities yields the corresponding cumulated activities. Absorbed doses to thyroid bed remnants and to the whole body can be calculated following the MIRDOSE method-that is, by multiplying the corresponding cumulated activities by the corresponding S factors. Results: The absorbed doses to thyroid bed remnants calculated in this study fall into a very wide range (13-1161 Gy) and showed the highest correlation factors with the following parameters: the absorbed dose rate to thyroid bed remnants, the cumulated activity in thyroid bed remnants, and the maximum radioiodine uptake in thyroid bed remnants. The absorbed doses to the whole body range from 0.12 to 0.23 Gy. The ablation was successful in all patients, and in spite of the wide range of absorbed doses to thyroid bed remnants obtained, no dose-effect correlation could be obtained. Conclusions: Facing DTC treatments from a dosimetric viewpoint in which a predosimetry to calculate the activity of {sup 131}I to be administered is performed is a subject difficult to handle. This statement is based on the fact that although a very wide range of absorbed doses to thyroid bed remnants was obtained (including several absorbed doses well below some dose thresholds previously published to achieve ablation of thyroid bed remnants), ablation of thyroid bed remnants was successful for all patients and therefore no dose-effect correlation could be determined.« less

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

Incidence of breast carcinoma in women with thyroid carcinoma.

PubMed

Vassilopoulou-Sellin, R; Palmer, L; Taylor, S; Cooksley, C S

1999-02-01

Breast carcinoma and differentiated thyroid carcinoma(the most common endocrine malignancy) occur predominantly in women. An association between the two tumors has been suggested by some investigators, but the potential impact of treatment of one of these diseases on the development of the other remains unclear. The authors examined the relation between the occurrence of these two tumors. There were 41,686 patients with breast carcinoma and 3662 with thyroid carcinoma who registered at The University of Texas M. D. Anderson Cancer Center between March 1944 and April 1997. Women who received both diagnoses since 1976 were identified and incidence rates and relative risks of secondary tumor development were calculated. Surveillance, Epidemiology and End Results (SEER) program data on the age-adjusted incidences of these diseases during the same time period were used for the expected incidences in the same population. Among 18,931 women with a diagnosis of breast carcinoma since 1976, 11 developed differentiated thyroid carcinoma > or = 2 years after the diagnosis of breast carcinoma. These breast carcinoma patients contributed 129,336 person-years of follow-up; the observed incidence of thyroid carcinoma in this group was not different from that in a similar age group of women in the SEER database. Among 1013 women with a diagnosis of thyroid carcinoma since 1976, 24 developed breast carcinoma > or = 2 years after the diagnosis of thyroid carcinoma. These thyroid carcinoma patients contributed 8380 person-years of follow-up; the observed incidence of breast carcinoma in women ages 40-49 years was significantly higher than the expected incidence for women in the same age group in the SEER database. Breast carcinoma developing after thyroid carcinoma was diagnosed more frequently than expected in young adult women seen at the study institution since 1976. This potential association and plausible mechanisms of breast carcinoma development after thyroid carcinoma should be evaluated in larger cohorts of patients.

A comparative study of cell cycle mediator protein expression patterns in anaplastic and papillary thyroid carcinoma.

PubMed

Evans, Juanita J; Crist, Henry S; Durvesh, Saima; Bruggeman, Richard D; Goldenberg, David

2012-07-01

Anaplastic thyroid carcinoma (ATC) is an extremely aggressive and rapidly fatal neoplasm. The aim of this study was to identify a limited cell cycle associated protein expression pattern unique to ATC and to correlate that pattern with clinical outcome. This represents one of the largest tissue micro-array projects comparing the cell cycle protein expression data of ATC to other well-differentiated tumors in the literature. Tissue microarrays were created from 21 patients with ATC and an age and gender matched cohort of patients with papillary thyroid carcinoma (PTC). Expression of epidermal growth factor receptor, cyclin D1, cyclin E, p53, p21, p16, aurora kinase A, opioid growth factor (OGF), OGF-receptor, thyroglobulin and Ki-67 was evaluated in a semi-quantitative fashion. Differences in protein expression between the cohorts were evaluated using chi-square tests with Bonferroni adjustments. Survival time and presence of metastasis at presentation were collected. The ATC cohort showed a statistically significant decrease (p < 0.05) in thyroglobulin expression and statistically significant increases (p < 0.05) in Ki-67 and p53 expression as compared with the PTC cohort. A trend toward loss of p16 and p21 expression was noted in the ATC cohort. A trend toward decreased survival was noted with p21 expression. These data indicate disruption of the normal cell cycle with aberrant expression of multiple protein markers suggesting increased proliferative activity and loss of control of cell cycle progression to G₁ phase. These findings support the assertion that ATC may represent the furthest end of a continuum of thyroid carcinoma dedifferentiation.

[Procedure guidelines for radioiodine therapy of differentiated thyroid cancer (version 2)].

PubMed

Dietlein, M; Dressler, J; Farahati, J; Grünwald, F; Leisner, B; Moser, E; Reiners, C; Schicha, H; Schober, O

2004-08-01

The procedure guidelines for radioiodine therapy (RIT) of differentiated thyroid cancer (version 2) are the counter-part to the procedure guidelines for (131)I whole-body scintigraphy (version 2) and specify the interdisciplinary guidelines for thyroid cancer of the Deutsche Krebsgesellschaft and the Deutsche Gesellschaft für Chirurgie concerning the nuclear medicine part. Compared with version 1 facultative options for RIT can be chosen in special cases: ablative RIT for papillary microcarcinoma

VEGF-C Is a Thyroid Marker of Malignancy Superior to VEGF-A in the Differential Diagnostics of Thyroid Lesions

PubMed Central

Woliński, Kosma; Stangierski, Adam; Szczepanek-Parulska, Ewelina; Gurgul, Edyta; Budny, Bartłomiej; Wrotkowska, Elzbieta; Biczysko, Maciej; Ruchala, Marek

2016-01-01

Introduction Thyroid nodular goiter is one of the most common medical conditions affecting even over a half of adult population. The risk of malignancy is rather small but noticeable–estimated by numerous studies to be about 3–10%. The definite differentiation between benign and malignant ones is a vital issue in endocrine practice. The aim of the current study was to assess the expression of vascular endothelial growth factor A (VEGF-A) and VEGF-C on the mRNA level in FNAB washouts in case of benign and malignant thyroid nodules and to evaluate the diagnostic value of these markers of malignancy. Materials and Methods Patients undergoing fine-needle aspiration biopsy (FNAB) in our department between January 2013 and May 2014 were included. In case of all patients who gave the written consent, after ultrasonography (US) and fine-needle aspiration biopsy (FNAB) performed as routine medical procedure the needle was flushed with RNA Later solution, the washouts were frozen in -80 Celsius degrees. Expression of VEGF-A and VEGF-C and GADPH (reference gene) was assessed in washouts on the mRNA level using the real-time PCR technique. Probes of patients who underwent subsequent thyroidectomy and were diagnosed with differentiated thyroid cancer (DTC; proved by post-surgical histopathology) were analyzed. Similar number of patients with benign cytology were randomly selected to be a control group. Results Thirty one DTCs and 28 benign thyroid lesions were analyzed. Expression of VEGF-A was insignificantly higher in patients with DTCs (p = 0.13). Expression of VEGF-C was significantly higher in patients with DTC. The relative expression of VEGF-C (in comparison with GAPDH) was 0.0049 for DTCs and 0.00070 for benign lesions, medians – 0.0036 and 0.000024 respectively (p<0.0001). Conclusions Measurement of expression VEGF-C on the mRNA level in washouts from FNAB is more useful than more commonly investigated VEGF-A. Measurement of VEGF-C in FNAB washouts do not allow for fully reliable differentiation of benign and malignant thyroid nodules and should be interpreted carefully. Further studies on larger groups are indicated. However, measurement of VEGF-C on mRNA level can bring important information without exposing patient for additional risk and invasive procedures. PMID:26900960

Paradigm Shift in Thyroid Hormone Mechanism of Action | Center for Cancer Research

Cancer.gov

Thyroid hormone (TH) is one of the primary endocrine regulators of human metabolism and homeostasis. Acting through three forms of the thyroid hormone receptor (THR; alpha-1, beta-1, and beta-2), TH regulates target gene expression in nearly every cell in the body, modulating fundamental processes, such as basal metabolic rate, long bone growth, and neural maturation. TH is also essential for proper development and differentiation of all cells of the human body.

Management of locally invasive well-differentiated thyroid cancer.

PubMed

Ark, Nebil; Zemo, Sessunu; Nolen, David; Holsinger, F Christopher; Weber, Randal S

2008-01-01

Thyroid carcinoma invasion of the aerodigestive tract and recurrent laryngeal nerve (RLN) are important factors with increase in morbidity and mortality. Primary treatment is surgery; the decision about the extent of surgery is difficult, because preserving function is as essential as removal of the tumor. This article discusses the literature relating to the assessment of disease, surgical management, and adjuvant therapy for invasive thyroid cancer of the aerodigestive tract and RLN and makes suggestions based on the authors' experience.

Diffuse skeletal metastasis and low thyroglobulin level in a pediatric patient with papillary thyroid carcinoma.

PubMed

Zakavi, Seyed Rasoul; Ayati, Narjess; Farahati, Jamshid; Davachi, Behrooz

2015-01-01

Thyroglobulin (Tg) is frequently measured in follow-up of patients with differentiated thyroid carcinoma. A low stimulated Tg level (<1 ng/ml) associated with normal neck ultrasonography is considered as the most reliable criteria for complete remission in low risk patients. We are reporting a case of pediatric thyroid cancer with diffuse skeletal metastasis associated with low serum Tg level bringing a point of caution in evaluation of patients with low Tg.

Hypothyroidism in the elderly: diagnosis and management

PubMed Central

Bensenor, Isabela M; Olmos, Rodrigo D; Lotufo, Paulo A

2012-01-01

Thyroid disorders are highly prevalent, occurring most frequently in aging women. Thyroid-associated symptoms are very similar to symptoms of the aging process; thus, improved methods for diagnosing overt and subclinical hypothyroidism in elderly people are crucial. Thyrotropin measurement is considered to be the main test for detecting hypothyroidism. Combined evaluations of thyroid stimulating hormone (TSH) and free-thyroxine can detect overt hypothyroidism (high TSH with low free-thyroxine levels) and subclinical hypothyroidism (high TSH with normal free-thyroxine levels). It is difficult to confirm the diagnosis of thyroid diseases based only on symptoms, but presence of symptoms could be an indicator of who should be evaluated for thyroid function. The most important reasons to treat overt hypothyroidism are to relieve symptoms and avoid progression to myxedema. Overt hypothyroidism is classically treated using L-thyroxine; elderly patients require a low initial dose that is increased every 4 to 6 weeks until normalization of TSH levels. After stabilization, TSH levels are monitored yearly. There is no doubt about the indication for treatment of overt hypothyroidism, but indications for treatment of subclinical disease are controversial. Although treatment of subclinical hypothyroidism may result in lipid profile improvement, there is no evidence that this improvement is associated with decreased cardiovascular or all-cause mortality in elderly patients. In patients with a high risk of progression from subclinical to overt disease, close monitoring of thyroid function could be the best option. PMID:22573936

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.

Metabolic Reprogramming in Thyroid Carcinoma

PubMed Central

Coelho, Raquel Guimaraes; Fortunato, Rodrigo S.; Carvalho, Denise P.

2018-01-01

Among all the adaptations of cancer cells, their ability to change metabolism from the oxidative to the glycolytic phenotype is a hallmark called the Warburg effect. Studies on tumor metabolism show that improved glycolysis and glutaminolysis are necessary to maintain rapid cell proliferation, tumor progression, and resistance to cell death. Thyroid neoplasms are common endocrine tumors that are more prevalent in women and elderly individuals. The incidence of thyroid cancer has increased in the Past decades, and recent findings describing the metabolic profiles of thyroid tumors have emerged. Currently, several drugs are in development or clinical trials that target the altered metabolic pathways of tumors are undergoing. We present a review of the metabolic reprogramming in cancerous thyroid tissues with a focus on the factors that promote enhanced glycolysis and the possible identification of promising metabolic targets in thyroid cancer. PMID:29629339

Animal models of medullary thyroid cancer: state of the art and view to the future.

PubMed

Vitale, Giovanni; Gaudenzi, Germano; Circelli, Luisa; Manzoni, Marco F; Bassi, Andrea; Fioritti, Niccolò; Faggiano, Antongiulio; Colao, Annamaria

2017-01-01

Medullary thyroid carcinoma is a neuroendocrine tumour originating from parafollicular C cells accounting for 5-10% of thyroid cancers. Increased understanding of disease-specific molecular targets of therapy has led to the regulatory approval of two drugs (vandetanib and cabozantinib) for the treatment of medullary thyroid carcinoma. These drugs increase progression-free survival; however, they are often poorly tolerated and most treatment responses are transient. Animal models are indispensable tools for investigating the pathogenesis, mechanisms for tumour invasion and metastasis and new therapeutic approaches for cancer. Unfortunately, only few models are available for medullary thyroid carcinoma. This review provides an overview of the state of the art of animal models in medullary thyroid carcinoma and highlights future developments in this field, with the aim of addressing salient features and clinical relevance. © 2017 Society for Endocrinology.

Submandibular Lateral Ectopic Thyroid Tissue: Ultrasonography, Computed Tomography, and Scintigraphic Findings

PubMed Central

Çeliker, Metin; Beyazal Çeliker, Fatma; Turan, Arzu; Beyazal, Mehmet; Beyazal Polat, Hatice

2015-01-01

Ectopic thyroid can be encountered anywhere between the base of tongue and pretracheal region. The most common form is euthyroid neck mass. Herein, we aimed to present the findings of a female case with ectopic thyroid tissue localized in the left submandibular region. A 44-year-old female patient, who underwent bilateral subtotal thyroidectomy four years ago with the diagnosis of multinodular goiter, was admitted to our hospital due to a mass localized in the left submandibular area that gradually increased in the last six months. Neck ultrasonography, contrast-enhanced computed tomography, and scintigraphic examination were performed on the patient. On thyroid scintigraphy with Tc-99m pertechnetate, thyroid tissue activity uptake showing massive radioactivity was observed in the normal localization of the thyroid gland and in the submandibular localization. The focus in the submandibular region was excised. Pathological examination of the specimen showed normal thyroid follicle cells with no signs of malignancy. The submandibular mass is a rarely encountered lateral ectopic thyroid tissue. Accordingly, ectopic thyroid tissue should also be considered in the differential diagnosis of masses in the submandibular region. PMID:26634164

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.

Thyroid remnant ablation success and disease outcome in stage III or IV differentiated thyroid carcinoma: recombinant human thyrotropin versus thyroid hormone withdrawal.

PubMed

Vallejo Casas, Juan A; Mena Bares, Luisa M; Gálvez Moreno, Maria A; Moreno Ortega, Estefanía; Marlowe, Robert J; Maza Muret, Francisco R; Albalá González, María D

2016-06-01

Most publications to date compare outcomes after post-surgical thyroid remnant ablation stimulated by recombinant human thyrotropin (rhTSH) versus thyroid hormone withholding/withdrawal (THW) in low-recurrence risk differentiated thyroid carcinoma (DTC) patients. We sought to perform this comparison in high-risk patients. We retrospectively analyzed ~9-year single-center experience in 70 consecutive adults with initial UICC (Union for International Cancer Control) stage III/IV, M0 DTC undergoing rhTSH-aided (N.=54) or THW-aided (N.=16) high-activity ablation. Endpoints included ablation success and DTC outcome. Assessed ≥1 year post-ablation, ablation success comprised a) no visible scintigraphic thyroid bed uptake or pathological extra-thyroidal uptake; b) undetectable stimulated serum thyroglobulin (Tg) without interfering autoantibodies; c) both criteria. DTC outcome, determined at the latest visit, comprised either 1) "no evidence of disease" (NED): undetectable Tg, negative Tg autoantibodies, negative most recent whole-body scan, no suspicious findings clinically, on neck ultrasonography, or on other imaging; 2) persistent disease: failure to attain NED; or 3) recurrence: loss of NED. After the first ablative activity, ablation success by scintigraphic plus biochemical criteria was 64.8% in rhTSH patients, 56.3% in THW patients (P=NS). After 3.5-year versus 6.2-year median follow-up (P<0.05), DTC outcomes were NED, 85.2%, persistent disease, 13.0%, recurrence, 1.9%, in the rhTSH group and NED, 87.5%, persistent or recurrent disease, 6.3% each, in the THW group (P=NS). In patients with initial stage III/IV, M0 DTC, rhTSH-aided and THW-assisted ablation were associated with comparable remnant eradication or DTC cure rates.

AVIAN THYROID DEVELOPMENT IN CHEMICALLY CONTAMINATED ENVIRONMENTS: IS THERE EVIDENCE OF ALTERATIONS IN THYROID FUNCTION AND DEVELOPMENT? (R827400)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

Developmental Exposure to Perfluorohexane Sulfonate (PFHxS) Induces Hypothyroxinemia in Rat Dams and Offspring: Examination of Thyroid Gland and Behavior

EPA Science Inventory

The developing mammalian central nervous system is dependent on thyroid hormones (TH) to control neurogenesis, differentiation and migration. In humans, low maternal serum thyroxine (T4) levels have been correlated to impaired child brain development. Perfluorinated chemicals are...

Novel Cause of 'Black Thyroid': Intraoperative Use of Indocyanine Green.

PubMed

Chernock, Rebecca D; Jackson, Ryan S

2017-09-01

The antibiotic minocycline is virtually pathognomonic for brown-black discoloration of the thyroid gland referred to as 'black thyroid'. Black thyroid' is an incidental finding in patients taking the drug who undergo thyroid surgery for another indication and is not of known clinical significance. However, its recognition is important so as not to raise concern for a disease process. Here, we present the first case of 'black thyroid' attributable to the iodine-containing compound indocyanine green. Intraoperative indocyanine green was administered as part of a research protocol transoral robotic-assisted surgery for a base of tongue cancer in a 44-year-old man. Hemithyroidectomy was subsequently performed during the same operation for further evaluation of an indeterminate thyroid nodule. The resected thyroid lobe was dark, nearly black in color, and histologically showed extensive brown pigment deposition in the follicular epithelial cells and colloid, mimicking minocycline-induced 'black thyroid'. In this case, however, the patient was not taking minocycline; instead the 'black thyroid' was attributed to the iodine-containing compound indocyanine green. Indocyanine green is a hereto unreported cause of 'black thyroid' with histopathologic features that are remarkably similar to that induced by minocycline. Indocyanine green should be included the differential diagnosis of 'black thyroid'. Clinical history is important so as not to raise concern for a disease process.

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.

Re-induction of cell differentiation and (131)I uptake in dedifferentiated FTC-133 cell line by TSHR gene transfection.

PubMed

Feng, Fang; Wang, Hui; Hou, Shasha; Fu, Hongliang

2012-11-01

Radioiodine therapy is commonly used to treat differentiated thyroid cancer (DTC), but a major challenge is dedifferentiation of DTC with the loss of radioiodine uptake. TSHR is a key molecule regulating thyrocyte proliferation and function. This study aimed to test the therapeutic potential of TSHR in dedifferentiated DTC by gene transfection in order to restore cell differentiation and radioiodine uptake. Dedifferentiated FTC-133 (dFTC-133) cells were obtained by monoclonal culture of FTC-133 cell line after (131)I radiation. Recombinant plasmid pcDNA3.1-hTSHR was transfected into dFTC-133 cells by using Lipofectamine 2000 reagent. Immunofluorescence analysis was carried out to confirm TSHR expression and its location. Radioiodine uptake assay was thereafter investigated. mRNAs and proteins of TSHR and other thyroid differentiated markers were detected by real-time PCR and western blot respectively. Among the thyroid specific genes in dFTC-133 cells with stable low radioiodine uptake, TSHR was down-regulated most significantly compared with FTC-133. Then, after TSHR gene transfection, augmented expression of TSHR was observed in dFTC-133 cell surface and cytoplasm by immunofluorescence analysis. It was found that (125)I uptake was 2.9 times higher (t=28.63, P<.01) in cells with TSHR transfection than control. The mRNAs of TSHR, NIS, TPO and Tg were also significantly increased by 1.7 times (t=13.8, P<.05), 4 times (t=28.52, P<.05), 1.5 times (t=14.43, P<.05) and 2.2 times (t=19.83, P<.05) respectively compared with control group. Decreased TSHR expression correlated with FTC-133 ongoing dedifferentiation. TSHR transfection contributed to the re-differentiation of dedifferentiated thyroid follicular carcinoma cells. Copyright © 2012 Elsevier Inc. All rights reserved.

Histogram analysis of greyscale sonograms to differentiate between the subtypes of follicular variant of papillary thyroid cancer.

PubMed

Kwon, M-R; Shin, J H; Hahn, S Y; Oh, Y L; Kwak, J Y; Lee, E; Lim, Y

2018-06-01

To evaluate the diagnostic value of histogram analysis using ultrasound (US) to differentiate between the subtypes of follicular variant of papillary thyroid carcinoma (FVPTC). The present study included 151 patients with surgically confirmed FVPTC diagnosed between January 2014 and May 2016. Their preoperative US features were reviewed retrospectively. Histogram parameters (mean, maximum, minimum, range, root mean square, skewness, kurtosis, energy, entropy, and correlation) were obtained for each nodule. The 152 nodules in 151 patients comprised 48 non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTPs; 31.6%), 60 invasive encapsulated FVPTCs (EFVPTCs; 39.5%), and 44 infiltrative FVPTCs (28.9%). The US features differed significantly between the subtypes of FVPTC. Discrimination was achieved between NIFTPs and infiltrative FVPTC, and between invasive EFVPTC and infiltrative FVPTC using histogram parameters; however, the parameters were not significantly different between NIFTP and invasive EFVPTC. It is feasible to use greyscale histogram analysis to differentiate between NIFTP and infiltrative FVPTC, but not between NIFTP and invasive EFVPTC. Histograms can be used as a supplementary tool to differentiate the subtypes of FVPTC. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

A case of sudden onset of thyroid storm just before cesarean section manifesting congestive heart failure and pulmonary edema.

PubMed

Sugiyama, Yuki; Tanaka, Ryusuke; Yoshiyama, Yuki; Ichino, Takashi; Hishinuma, Norimasa; Shimizu, Sari; Imai, Noriko; Mitsuzawa, Kunihiro; Kawamata, Mikito

2017-01-01

Since acute respiratory failure (ARF) is a life-threatening complication, particularly in the gestational period, differential diagnosis and rapid treatment are required. Among the various causes of sudden onset of ARF, thyroid storm is a rare cause in a parturient complicated with well-controlled hyperthyroidism. In this case report, we describe a parturient with hyperthyroidism in whom a thyroid storm manifesting congestive heart failure and pulmonary edema developed just before an emergency ceasarean section, even though hyperthyroidism was well-controlled with antithyroid drugs. A 36-year-old pregnant woman was diagnosed as having clinical chorioamnionitis, and an emergency cesarean section was performed at 25 weeks of pregnancy. She had a complication of hyperthyroidism accompanied by mild mitral regurgitation, and she had been treated with methimazole. She was treated with ritodrine and MgSO 4 for the threat of premature delivery. At the preoperative consultation, her percutaneous oxygen saturation (SpO 2 ) was 98% on room air. When she was admitted to the operating room, her heart rate and blood pressure were 130 beats/min and 196/78 mmHg, respectively. SpO 2 was 88% on room air without any symptoms; however, just after starting oxygen administration via a facemask, she complained of severe respiratory distress and became agitated. Partial pressure of arterial oxygen was 108 mmHg with an inspiratory oxygen fraction of 1.0. Chest radiography revealed pulmonary congestion, and transesophageal echocardiography revealed normal right ventricular function without an embolus and severe mitral regurgitation with preserved left ventricular function. Contrast-enhanced computed tomography after the operation revealed no pulmonary embolus but revealed a pulmonary effusion, and free triiodothyronine level was increased at the onset of dyspnea. Therefore, we diagnosed the causes of sudden onset of dyspnea as pulmonary edema and congestive heart failure induced by a thyroid storm. Sudden onset of a thyroid storm just before a cesarean section occurred in a patient with several risk factors of thyroid storm and pulmonary edema, including pregnancy, treatment with tocolytic agents, and infection. The involvement of these multiple factors was considered to be the cause of the sudden onset of the thyroid storm and the cause of rapidly progressive pulmonary edema.

Obatoclax and LY3009120 Efficiently Overcome Vemurafenib Resistance in Differentiated Thyroid Cancer.

PubMed

Wei, Wei-Jun; Sun, Zhen-Kui; Shen, Chen-Tian; Song, Hong-Jun; Zhang, Xin-Yun; Qiu, Zhong-Ling; Luo, Quan-Yong

2017-01-01

Although the prognosis of differentiated thyroid cancer (DTC) is relatively good, 30-40% of patients with distant metastases develop resistance to radioactive iodine therapy due to tumor dedifferentiation. For DTC patients harboring BRAF V600E mutation, Vemurafenib, a BRAF kinase inhibitor, has dramatically changed the therapeutic landscape, but side effects and drug resistance often lead to termination of the single agent treatment. In the present study, we showed that either LY3009120 or Obatoclax (GX15-070) efficiently inhibited cell cycle progression and induced massive death of DTC cells. We established that BRAF/CRAF dimerization was an underlying mechanism for Vemurafenib resistance. LY3009120, the newly discovered pan-RAF inhibitor, successfully overcame Vemurafenib resistance and suppressed the growth of DTC cells in vitro and in vivo. We also observed that expression of anti-apoptotic Bcl-2 increased substantially following BRAF inhibitor treatment in Vemurafenib-resistant K1 cells, and both Obatoclax and LY3009120 efficiently induced apoptosis of these resistant cells. Specifically, Obatoclax exerted its anti-cancer activity by inducing loss of mitochondrial membrane potential (ΔΨm), dysfunction of mitochondrial respiration, reduction of cellular glycolysis, autophagy, neutralization of lysosomes, and caspase-related apoptosis. Furthermore, the cancer killing effects of LY3009120 and Obatoclax extended to two more Vemurafenib-resistant DTC cell lines, KTC-1 and BCPAP. Taken together, our results highlighted the potential value of LY3009120 for both Vemurafenib-sensitive and -resistant DTC and provided evidence for the combination therapy using Vemurafenib and Obatoclax for radioiodine-refractory DTC.

FOXE1 Association with Differentiated Thyroid Cancer and Its Progression

PubMed Central

Penna-Martinez, Marissa; Epp, Friederike; Kahles, Heinrich; Ramos-Lopez, Elizabeth; Hinsch, Nora; Hansmann, Martin-Leo; Selkinski, Ivan; Grünwald, Frank; Holzer, Katharina; Bechstein, Wolf O.; Zeuzem, Stefan; Vorländer, Christian

2014-01-01

Background: Single nucleotide polymorphisms (SNPs) near thyroid transcription factor genes (FOXE1 rs965513/NKX2-1 rs944289) have been shown to be associated with differentiated thyroid cancer (DTC) in Caucasoid populations. We investigated the role of those SNPs in German patients with DTC and also extended our analysis to tumor stages and lymphocytic infiltration of the tumors (ITL). Methods: Patients with DTC (n=243; papillary, PTC; follicular, FTC) and healthy controls (HC; n=270) were analyzed for the rs965513 and rs944289 SNPs. Results: The case-control analysis for rs965513 SNP showed that the genotypes “AA,” “AG,” and minor allele “A” were more frequent in patients with DTC than in HC (pronounced in PTC pgenotype=0.000084, pallele=0.006 than FTC pgenotype=0.29 and pallele=0.06). Furthermore, subgroup analysis of the DTC patients stratified for primary tumor stage (T1–T2, T3–T4), the absence or presence of regional lymph node metastases (N0, N1), for distant metastases (M0, M1), as well as for ITL, showed an association of rs965513 with stages T1–T2, T1–T3, N1, and absence of ITL. The NKX2-1 SNP rs944289, however, was not associated with DTC. Conclusion: Our results confirm that the FOXE1 rs965513 SNP confers an increased risk for DTC in the German population, particularly allele “A” and the genotypes “AA” and “AG” for PTC. This increased risk was also observed in advanced tumor stages and absence of ITL, which may reflect the course of a more aggressive disease. The NKX2-1 rs944289 SNP, however, appears to play a secondary role in the development of DTC in the German population. PMID:24325646

Testicular function in patients with differentiated thyroid carcinoma treated with radioiodine

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

Pacini, F.; Gasperi, M.; Fugazzola, L.

1994-09-01

The aim of the present study was to assess whether {sup 131}I therapy for differentiated thyroid carcinoma (DTC) can affect endocrine testicular function. Serum follicle-stimulating hormone (FSH) and testosterone (T) concentrations were measured in 103 patients periodically submitted for radioiodine therapy for residual or metastatic disease. Mean follow-up was 93.7{+-}54 mo (range 10-243 mo). Mean FSH values in {sup 131}I-treated patients tested after their last treatment were 15.3{+-}9.9 mU/ml, significantly higher than those of 19 untreated patients (6.5{+-}3.1 mU/ml). Considering the mean +3 s.d. FSH of untreated subjects as the upper limit of normal range, 36.8% of the patients hadmore » an abnormal increase in serum FSH. Longitudinal analysis performed in 21 patients showed that the behavior of FSH in response to {sup 131}I therapy was not universal. Six patients had no change or a slight increase in serum FSH after {sup 131}I administration; eleven patients had a transient increase above normal values 6-12 mo after {sup 131}I treatment, with return to normal levels in subsequent months. The administration of a second dose was followed by a similar increase in FSH levels. Finally, four patients, followed for a long period of time and treated with several {sup 131}I doses, showed a progressive increase in serum FSH, which eventually became permanent. Semen analysis, performed in a small subgroup of patients, showed a consistent reduction in the number of normokinetic sperm. No change was found in serum T levels between treated and untreated patients. The results indicate that {sup 131}I therapy for thyroid carcinoma is associated with transient impairment of testicular germinal cell function. The damage may become permanent for high-radiation activities delivered year after year and might pose a significant risk of infertility. 14 refs., 8 figs., 1 tab.« less

Differentiating Graves' disease from subacute thyroiditis using ratio of serum free triiodothyronine to free thyroxine.

PubMed

Sriphrapradang, Chutintorn; Bhasipol, Adikan

2016-09-01

The measurement of free thyroid hormone, instead of the total form, is more commonly used in current practice. We aimed to evaluate the usefulness of the ratio of serum free triiodothyronine (FT3, pg/mL) to free thyroxine (FT4, ng/dL) for differentiating Graves' disease from subacute thyroiditis. Medical records of thyrotoxic patients aged >15 years who had measurement of FT3, FT4 and thyrotropin on the first diagnosis of thyrotoxicosis before initiating treatment were retrospectively reviewed. Data were collected from all clinics, and were not limited to the endocrine clinic. Pregnant women were excluded. A total of 548 patients (468 with Graves' disease, 40 with subacute thyroiditis and 40 with toxic adenoma/multinodular goiter) were recruited. Mean age was 43.9 ± 15.4 years. Most were female 434 (79.2%), and goiter was present in 55.3%. Prevalence of T3-toxicosis and T4-toxicosis were 5.6% and 6.6%, respectively. Mean FT3/FT4 ratios were 4.62 ± 2 (10(-2) pg/ng) in patients with Graves' disease and 2.73 ± 0.5 in subacute thyroiditis. The area under the ROC curve of the FT3/FT4 ratio for diagnosis of Graves' disease was 0.83 (95%CI, 0.76-0.91). Cutoff level of this ratio >4.4 offered sensitivity of 47.2% and specificity of 92.8%. FT3/FT4 ratio of >4.4 (10(-2) pg/ng) may help in differentiating the cause of thyrotoxicosis.

Unstable Thyroid Function in Older Adults Is Caused by Alterations in Both Thyroid and Pituitary Physiology and Is Associated with Increased Mortality.

PubMed

Mammen, Jennifer S; McGready, John; Ladenson, Paul W; Simonsick, Eleanor M

2017-11-01

Average thyrotropin (TSH) levels are known to be higher in older adults when measured in cross-sectional populations. Possible etiologies include differential survival, neutral aging changes, or increased disease prevalence at older ages. This study aimed to elucidate the mechanisms underlying changing thyroid function during aging, and to determine the association of changes with survival, by analyzing the individual thyroid axis over time. Individual patterns of changing TSH and free thyroxine (fT4) were determined in 640 participants in the Baltimore Longitudinal Study of Aging who had at least three measures of serum TSH and fT4, not on medications, over an average of seven years of follow-up. Participants with changing phenotypes were identified based on quintiles for both slopes. Those with alterations in primary thyroid gland function demonstrated intact negative feedback (rising TSH with declining fT4 or declining TSH with rising fT4). Other participants had a parallel rise or fall of TSH and fT4 levels, consistent with pituitary dysfunction. Predictors of phenotype were analyzed by logistic regression. Differential survival between thyroid aging phenotypes was analyzed using multivariate Cox regression. While the majority of participants at all ages had stable thyroid function, changes were more common among older adults, with 32.3% of those aged >80 years but only 9.5% of those aged <60 years demonstrating thyroid function changes in the highest and lowest quintiles. Regression to the mean accounts for some of the changes, for example increased baseline TSH was associated with a falling TSH pattern (odds ratio = 1.4 [confidence interval 1.1-1.7] per 1 mIU/L). Importantly, changing thyroid function in either the upper or lower quintiles of slope for TSH and fT4 was associated with increased risk of death compared to stable thyroid status (hazard ratio = 5.4 [confidence interval 3.1-9.5]). Changing thyroid hormone function is increasingly common at older ages and is associated with decreased survival. Nonetheless, the tendency for abnormal thyroid function tests to resolve, along with altered pituitary responsiveness underlying some TSH elevations, suggests that an elevated TSH level should be not assumed to represent subclinical hypothyroidism in older adults. Thus, caution is appropriate when determining the need for thyroid hormone supplements in older adults.

[Is our approach to thyroid nodules and differentiated thyroid carcinoma in agreement with the American guideline and European consensus?].

PubMed

Gómez Sáez, José Manuel

2010-10-01

The aim of this study was to assess the approaches of specialists in Spain to patients with thyroid nodules and differentiated thyroid carcinoma and to compare them with the American guideline and European consensus. We performed a cross-sectional study based on a questionnaire addressed to clinical endocrinologists specialized in thyroid cancer and specialists in nuclear medicine throughout Spain. A total of 177 questionnaires were completed, representing an overall response rate of 85%; 74% of responses were from endocrinologists and 24% from physicians active in nuclear medicine; 82% of respondents worked in third-level hospitals, 10% in second level hospitals and the remainder in private practice. Most used ultrasonography and cytology to assess thyroid nodules and collaborated with a group of surgeons expert in thyroid surgery. The majority preferred total or subtotal thyroidectomy in tumors with a diameter of 1 cm or more, and systematic lymph node dissection. Only 43 (24%) preferred prophylactic central lymph node dissection. Eighty-one respondents (45%) would still use whole body scan with ¹³¹I or ¹²³I before ¹³¹I ablation. Follow-up was based on cervical echography and thyroglobulin determination; however, 101 (57%) respondents continued to use diagnostic whole body scan in the follow-up. The approaches of the respondents were mainly in accordance with the guideline and consensus, although some variations were found, especially in the use of whole body scan with ¹³¹I before ablation and in follow-up. Copyright © 2010 SEEN. Published by Elsevier Espana. All rights reserved.

A clinical case report of Hashimoto's thyroiditis and its impact on the treatment of chronic periodontitis.

PubMed

Patil, B S; Giri, G R

2012-01-01

Periodontitis is a multifactorial disease with microbial dental plaque as the initiator of periodontal disease. However, the manifestation and progression of the disease is influenced by a wide variety of determinants and factors. The strongest type of causal relationship is the association of systemic and periodontal disease. Hashimoto's thyroiditis has also been considered as one of the causes of periodontal disease. This clinical case report highlights the impact of Hashimoto's thyroiditis on the outcome of periodontal therapy.

Diffuse skeletal metastasis and low thyroglobulin level in a pediatric patient with papillary thyroid carcinoma

PubMed Central

Zakavi, Seyed Rasoul; Ayati, Narjess; Farahati, Jamshid; Davachi, Behrooz

2015-01-01

Thyroglobulin (Tg) is frequently measured in follow-up of patients with differentiated thyroid carcinoma. A low stimulated Tg level (<1 ng/ml) associated with normal neck ultrasonography is considered as the most reliable criteria for complete remission in low risk patients. We are reporting a case of pediatric thyroid cancer with diffuse skeletal metastasis associated with low serum Tg level bringing a point of caution in evaluation of patients with low Tg. PMID:26170580

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.

Less aggressive disease in patients with primary squamous cell carcinomas of the thyroid gland and coexisting lymphocytic thyroiditis.

PubMed

Asik, Mehmet; Binnetoglu, Emine; Sen, Hacer; Gunes, Fahri; Muratli, Asli; Kankaya, Duygu; Uysal, Fatma; Sahin, Mustafa; Ukinc, Kubilay

2015-01-01

Primary squamous cell carcinoma (SCC) of the thyroid gland is extremely rare. Infrequently, primary SCC of the thyroid gland is accompanied by other thyroid diseases such as Hashimoto's thyroiditis (HT). Recently, studies have demonstrated that differentiated thyroid cancer with coexisting HT has a better prognosis. However, the prognosis of patients with primary SCC of the thyroid gland and coexistent HT has not been clearly identified. We compared the clinical characteristics and disease stages of patients with primary SCC with and without lymphocytic thyroiditis (LT). We reviewed reports of primary SCC of the thyroid gland published in the English literature. We identified 46 papers that included 17 cases of primary SCC of the thyroid gland with LT and 77 cases of primary SCC of the thyroid gland without LT. Lymph node metastasis and local invasion rates did not differ between these two groups. Distant metastases were absent in patients with LT, and were observed in 13 (16.9%) patients without LT. A greater proportion of patients without LT had advanced stage disease (stage IV A-B-C) than patients with LT (p < 0.05). Patients with primary SCC of the thyroid gland and coexisting LT had lower tumour-node-metastasis stage and frequency of distant metastasis than those without LT. Lymphocytic infiltration in patients with SCC appears to limit tumour growth and distant metastases.

[Thyroid emergencies : Thyroid storm and myxedema coma].

PubMed

Spitzweg, C; Reincke, M; Gärtner, R

2017-10-01

Thyroid emergencies are rare life-threatening endocrine conditions resulting from either decompensated thyrotoxicosis (thyroid storm) or severe thyroid hormone deficiency (myxedema coma). Both conditions develop out of a long-standing undiagnosed or untreated hyper- or hypothyroidism, respectively, precipitated by an acute stress-associated event, such as infection, trauma, or surgery. Cardinal features of thyroid storm are myasthenia, cardiovascular symptoms, in particular tachycardia, as well as hyperthermia and central nervous system dysfunction. The diagnosis is made based on clinical criteria only as thyroid hormone measurements do not differentiate between thyroid storm and uncomplicated hyperthyroidism. In addition to critical care measures therapy focusses on inhibition of thyroid hormone synthesis and secretion (antithyroid drugs, perchlorate, Lugol's solution, cholestyramine, thyroidectomy) as well as inhibition of thyroid hormone effects in the periphery (β-blocker, glucocorticoids).Cardinal symptoms of myxedema coma are hypothermia, decreased mental status, and hypoventilation with risk of pneumonia and hyponatremia. The diagnosis is also purely based on clinical criteria as measurements of thyroid hormone levels do not differ between uncomplicated severe hypothyroidism and myxedema coma. In addition to substitution of thyroid hormones and glucocorticoids, therapy focusses on critical care measures to treat hypoventilation and hypercapnia, correction of hyponatremia and hypothermia.Survival of both thyroid emergencies can only be optimized by early diagnosis based on clinical criteria and prompt initiation of multimodal therapy including supportive measures and treatment of the precipitating event.

SPORADIC GOITROUS CRETINISM

PubMed Central

Mosier, H. David

1959-01-01

Five to 10 per cent of cretinism in the United States is due to some congenital enzymatic defect in thyroid hormone synthesis. The clinical signs of hypothyroidism appear in early infancy. Differentiation from athyreotic cretinism is important because the metabolic defect tends to be familial and its presence in the patient's infant relatives should be diagnosed as early as possible. The differentiation is easily made if a goiter is discernible, but if it is not, radioiodine uptake should be measured, for in this condition the uptake is normal or greater. Thyroid replacement is the treatment in either the athyreotic state or the metabolic deficiency. The three known defects in thyroid hormone synthesis are (1) failure to oxidize iodine to elemental iodine resulting in failure of all subsequent processes; (2) failure to deiodinate free iodotyrosine, and (3) failure to form iodothyronine although the previous steps are accomplished. PMID:13618742

Analysis of differential secondary effects of novel rexinoids: select rexinoid X receptor ligands demonstrate differentiated side effect profiles

PubMed Central

Marshall, Pamela A; Jurutka, Peter W; Wagner, Carl E; van der Vaart, Arjan; Kaneko, Ichiro; Chavez, Pedro I; Ma, Ning; Bhogal, Jaskaran S; Shahani, Pritika; Swierski, Johnathon C; MacNeill, Mairi

2015-01-01

In order to determine the feasibility of utilizing novel rexinoids for chemotherapeutics and as potential treatments for neurological conditions, we undertook an assessment of the side effect profile of select rexinoid X receptor (RXR) analogs that we reported previously. We assessed pharmacokinetic profiles, lipid and thyroid-stimulating hormone (TSH) levels in rats, and cell culture activity of rexinoids in sterol regulatory element-binding protein (SREBP) induction and thyroid hormone inhibition assays. We also performed RNA sequencing of the brain tissues of rats that had been dosed with the compounds. We show here for the first time that potent rexinoid activity can be uncoupled from drastic lipid changes and thyroid axis variations, and we propose that rexinoids can be developed with improved side effect profiles than the parent compound, bexarotene (1). PMID:26038698

Inhibition of STAT3 activity delays obesity-induced thyroid carcinogenesis in a mouse model

PubMed Central

Park, Jeong Won; Han, Cho Rong; Zhao, Li; Willingham, Mark C.; Cheng, Sheue-yann

2015-01-01

Compelling epidemiologic studies indicate that obesity is a risk factor for many human cancers, including thyroid cancer. In recent decades, the incidence of thyroid cancer has dramatically increased along with a marked rise in obesity prevalence. We previously demonstrated that a high fat diet (HFD) effectively induced the obese phenotype in a mouse model of thyroid cancer (ThrbPV/PVPten+/− mice). Moreover, HFD activates the STAT3 signal pathway to promote more aggressive tumor phenotypes. The aim of the present study was to evaluate the effect of S3I-201, a specific inhibitor of STAT3 activity, on HFD-induced aggressive cancer progression in the mouse model of thyroid cancer. Wild type and ThrbPV/PVPten+/− mice were treated with HFD together with S3I-201 or vehicle-only as controls. We assessed the effects of S3I-201 on HFD-induced thyroid cancer progression, the leptin-JAK2-STAT3 signaling pathway, and key regulators of epithelial-mesenchymal transition. S3I-201 effectively inhibited HFD-induced aberrant activation of STAT3 and its downstream targets to markedly inhibit thyroid tumor growth and to prolong survival. Decreased protein levels of cyclins D1 and B1, cyclin dependent kinase (CDK) 4, CDK 6, and phosphorylated retinoblastoma protein led to the inhibition of tumor cell proliferation in S3I-201-treated ThrbPV/PVPten+/− mice. Reduced occurrence of vascular invasion and blocking of anaplasia and lung metastasis in thyroid tumors of S3I-201-treated ThrbPV/PVPten+/− mice were mediated via decreased expression of vimentin and matrix metalloproteinases, two key effectors of epithelial-mesenchymal transition. The present findings suggest that inhibition of the STAT3 activity would be a novel treatment strategy for obesity-induced thyroid cancer. PMID:26552408

Subclinical hypothyroidism: A common finding in adult patients with cyanotic congenital heart disease.

PubMed

Bak, Peter; Hjortshøj, Cristel S; Gaede, Peter; Idorn, Lars; Søndergaard, Lars; Jensen, Annette S

2018-03-01

Cyanotic congenital heart disease is a systemic disease, with effects on multiple organ systems. A high prevalence of subclinical hypothyroidism (SCH) has been reported in a small cohort of cyanotic congenital heart disease patients. Subclinical hypothyroidism has been associated with various adverse cardiovascular effects, as well as an increased risk of progression to overt hypothyroidism. The aim of this study was to examine the prevalence of SCH in cyanotic congenital heart disease patients, consider possible etiologies, and evaluate thyroid function over time. First, 90 clinically stable cyanotic congenital heart disease patients were examined with blood samples (thyroid-stimulating hormone, C-reactive protein, hemoglobin, hematocrit, and N-terminal pro-brain-natriuretic peptide) in a cross-sectional descriptive study. Second, a longitudinal follow-up study of 43 patients originating from the first study part, was carried out. These patients had thyroid function parameters (thyroid-stimulating hormone, thyroid hormones, and thyroid peroxidase antibodies) evaluated biannually. Elevated thyroid-stimulating hormone was present in 24% of the 90 screened patients. During follow-up (6.5 ± 1.0 years), SCH (defined as ≥2 consecutive elevated thyroid-stimulating hormone values) was present in 26%. Three patients progressed to overt hypothyroidism. Patients with SCH were younger (34 ± 12 vs 42 ± 16 years; P = .01) and had a lower oxygen saturation (80 ± 5 vs 84 ± 6%; P = .03). Subclinical hypothyroidism is a very common finding in cyanotic congenital heart disease. This is not associated with increased levels of C-reactive protein, heart failure, or autoimmunity but appears to be associated with cyanosis and age. Since the clinical impact of SCH is uncertain, further studies are needed to determine this. Regular thyroid evaluation is recommended in cyanotic congenital heart disease patients since SCH can develop to overt hypothyroidism. © 2017 Wiley Periodicals, Inc.

Pooled analysis of two case-control studies in New Caledonia and French Polynesia of body mass index and differentiated thyroid cancer: the importance of body surface area.

PubMed

Cléro, Enora; Leux, Christophe; Brindel, Pauline; Truong, Thérèse; Anger, Antoinette; Teinturier, Cécile; Diallo, Ibrahima; Doyon, Françoise; Guénel, Pascal; de Vathaire, Florent

2010-11-01

New Caledonia and French Polynesia have among of the world highest thyroid cancer incidence rates. Studies have demonstrated a relationship between anthropometric parameters and the prevalence of cancer. In this study we evaluated further the relationship between body mass index (BMI) and other anthropometric parameters on the incidence of thyroid cancer in the New Caledonia and French Polynesia populations. We performed a pooled analysis of two case-control studies in New Caledonia and French Polynesia. We included a total of 554 cases (65 men and 489 women) of differentiated thyroid cancers and 776 population control subjects matched on sex, age, and study. Anthropometric factors (height, weight, BMI, body fat percentage [BF%], and body surface area [BSA]), at age 18 and before diagnosis, were analyzed by conditional logistic regression, adjusting for other independent risk factors. A high proportion of cases (73%) were overweight (25-29.9 kg/m(2)) or obese (≥30 kg/m(2)) before diagnosis of thyroid cancer (against 57% of control subjects). An increased risk of thyroid cancer was observed with greater height, weight, BMI, BF%, and BSA. The association of thyroid cancer risk with height, weight, BMI, and BF% did not remain when adjustment was made for BSA. By comparison, the odds ratios for the highest versus the lowest quartile of BSA at age 18 were 3.97 (95% confidence interval, 2.57-6.15; p < 0.001) for women and 4.06 (95% confidence interval, 1.03-16.06; p = 0.04) for men. The association between thyroid cancer risk and each of anthropometric factors did not depend on tumor size or menopausal status before diagnosis. Among anthropometric factors, BSA plays a dominant role in thyroid cancer risk and explains the apparent role of BMI.

Impact of Reclassification on Thyroid Nodules with Architectural Atypia: From Non-Invasive Encapsulated Follicular Variant Papillary Thyroid Carcinomas to Non-Invasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features

PubMed Central

Jeon, Min Ji; Song, Dong Eun; Jung, Chan Kwon; Kim, Won Gu; Kwon, Hyemi; Lee, Yu-Mi; Sung, Tae-Yon; Yoon, Jong Ho; Chung, Ki-Wook; Hong, Suck Joon; Baek, Jung Hwan; Lee, Jeong Hyun; Kim, Tae Yong; Shong, Young Kee; Kim, Won Bae

2016-01-01

Background The follicular variant of papillary thyroid cancer (FVPTC), especially the encapsulated non-invasive subtype, is a controversial entity. Recent study suggested using ‘non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP)’ for these indolent carcinomas. We evaluated the impact of reclassification from non-invasive encapsulated FVPTCs (EFVPTCs) to NIFTPs in the diagnosis of thyroid nodules with architectural atypia. Methods We reviewed 1301 thyroid nodules with architectural atypia in core needle biopsy (CNB) specimens obtained from March 2012 to February 2013. Nodules were classified into atypia of undetermined significance with architectural atypia (AUS-A, 984, 76%) or follicular neoplasm/suspicious for a follicular neoplasm (FN/SFN, 317, 24%). Among them, diagnostic surgery was performed in 384 nodules (30%). Results In total, 160 nodules (42%) presented final malignant diagnoses including 39 non-invasive encapsulated FVPTCs (10%). The malignancy rate was estimated to be 7–35% in AUS-A nodules and 28–49% in FN/SFN nodules. After reclassification, the malignancy rate was much decreased and estimated to be 5–24% in AUS-A nodules, and 23–39% in FN/SFN nodules. Thyroid nodules with final malignant diagnoses were significantly more likely to have a FN/SFN CNB diagnosis, malignant US features and concomitant nuclear atypia in CNB specimens. However, these factors could not differentiate NIFTPs from other malignancies. Conclusions After reclassification of non-invasive EFVPTCs to NIFTPs, the malignancy rate of thyroid nodules with architectural atypia in CNB specimens was decreased. However, there were no preoperative factors differentiating other malignancies from NIFTPs. The presence of malignant US features or concomitant nuclear atypia might help clinicians deciding diagnostic surgery but, these features also might indicate NIFTPs. PMID:27936121

The pharmacists' role in improving guideline compliance for thyroid function testing in patients with heart failure.

PubMed

Ziman, Melanie E; Bui, Hien T; Smith, Craig S; Tsukiji, Lori A; Asmatey, Veda M; Chu, Steven B; Miano, John S

2012-04-01

This single-center retrospective pilot program's objective was to utilize outpatient pharmacists to improve laboratory test adherence in chronic heart failure (CHF) patients overdue for thyroid function testing, thereby demonstrating the value of the outpatient pharmacist and justifying possible clinical role expansion. Thyroid disorders may contribute to CHF development, progression, and exacerbation. Testing is the standard of care in CHF patients per American Heart Association's 2009 Guidelines. Delinquency was defined as labs not conducted within 1 year in patients with euthyroid history, within 6 months in patients with thyroid dysfunction, abnormal labs at any time without follow-up, or lab absence after thyroid medication initiation, adjustment, or discontinuation. Targeted 80 nonpregnant adult CHF patients with delinquent thyroid function tests were counseled to get thyroid labs at point of sale, via telephone, e-mail, or letter. In collaboration with physicians, pharmacists ordered thyroid-stimulating hormone (TSH) and free T4 (FT4) labs. For patients with abnormal laboratory results, pharmacists coordinated drug therapy and follow-up labs. Data were collected from November 1, 2009 to March 30, 2010. Seventy-two patients (90%) previously delinquent for thyroid function testing received relevant thyroid labs. Ten patients (12.5%) with abnormal thyroid function tests not on prior drug therapy received treatment.

Hyoid Bone and Thyroid Cartilage Metastases from Sigmoid Colon Adenocarcinoma: A Case Report.

PubMed

Bracanovic, Djurdja; Vukovic, Vesna; Janovic, Aleksa; Radosavljevic, Davorin; Rakocevic, Zoran

2017-05-05

Secondary tumours of the hyoid bone and thyroid cartilage are extremely rare. In this paper, we present a case of the hyoid bone and thyroid cartilage metastases in a patient treated for sigmoid colon adenocarcinoma. Four years after sigmoid colon adenocarcinoma was diagnosed and treated with surgery and chemotherapy, the patient developed bone metastases in the left sacroiliac joint and right proximal humerus. Although the patient did not complain of any related symptoms, in a bone scintigraphy the accumulation of Technetium-99m was incidentally detected in the two sites of the anterior neck. On ultrasound examination there were two hyperechoic and heterogeneous masses with calcifications placed in front of the hyoid bone and thyroid cartilage. Computerized tomography demonstrated massive hyoid bone and thyroid cartilage destruction. In patients with progressive sigmoid colon adenocarcinoma, destruction of the hyoid bone and thyroid cartilage could be suspected for metastases.

Hyperfunctioning thyroid cancer: a five-year follow-up.

PubMed

Azevedo, Monalisa Ferreira; Casulari, Luiz Augusto

2010-02-01

Differentiated thyroid cancer rarely occurs in association with hyperfunctioning nodules. We describe a case of a 47-year-old woman who developed symptoms of hyperthyroidism associated with a palpable thyroid nodule. Thyroid scintigraphy showed an autonomous nodule, and fine-needle aspiration biopsy was suggestive of papillary carcinoma. Laboratorial findings were consistent with the diagnosis of hyperthyroidism. The patient underwent thyroidectomy and a papillary carcinoma of 3.0 x 3.0 x 2.0 cm, follicular variant, was described by histological examination. The surrounding thyroid tissue was normal. Postoperatively, the patient received 100 mCi of (131)I, and whole body scans detected only residual uptake. No evidence of metastasis was detected during five years of follow-up. Hot thyroid nodules rarely harbor malignancies, and this case illustrated that, when a carcinoma occurs the prognosis seems to be very good with no evidence of metastatic dissemination during a long-term follow-up.

Clinical guidelines for management of thyroid nodule and cancer during pregnancy.

PubMed

Galofré, Juan Carlos; Riesco-Eizaguirre, Garcilaso; Alvarez-Escolá, Cristina

2014-03-01

Special considerations are warranted in management of thyroid nodule and thyroid cancer during pregnancy. The diagnostic and therapeutic approach of thyroid nodules follows the standard practice in non-pregnant women. On the other hand, differentiated thyroid cancer management during pregnancy poses a number of challenges for the mother and fetus. The available data show that pregnancy is not a risk factor for thyroid cancer development or recurrence, although flare-ups cannot be completely ruled out in women with active disease. If surgery is needed, it should be performed during the second term or, preferably, after delivery. A majority of pregnant patients with low-risk disease only need adjustment in levothyroxine therapy. However, women with increased serum thyroglobulin levels before pregnancy or structural disease require regular thyroglobulin measurements and neck ultrasound throughout pregnancy. Pregnancy is an absolute contraindication for radioactive iodine administration. Copyright © 2013 SEEN. Published by Elsevier Espana. All rights reserved.

[Trends in thyroid surgery at the Instituto Nacional de la Nutrición Salvador Zubirán].

PubMed

Herrera, M F; López, C M; Saldaña, J; Pérez, B; Rivera, R; González, O; Angeles, A; Letayf, V

1995-01-01

The diagnosis and treatment of thyroid disease has significantly changed with time. With the aim of analysing changes in thyroid surgery in our institution, a representative sample of patients from the first three years in four decades (1960-1992) were comparatively analysed. In the sixties, the diagnosis of thyroid cancer was made during surgery; by contrast, this diagnosis was correctly done by fine needle aspiration (FNA) in most patients of the last decade. Thyroid lobectomy, infrequently used in the treatment of differentiated thyroid carcinoma in earlier times, has now been abandoned and currently most patients undergo total or near-total thyroidectomy. Complications such as hypoparathyroidism and recurrent laryngeal nerve paralysis have importantly decreased with time and were not seen in the last decade. A trend toward an earlier diagnosis of thyroid carcinoma was also observed. In summary, the number of thyroidectomies for benign diseases has been importantly reduced by the use of FNA with the proportional increment of surgery for malignant disease.

[Autoimmune thyroiditis and thyroid cancer].

PubMed

Krátký, Jan; Jiskra, Jan

2015-10-01

Association between autoimmune thyroiditis (CLT) and thyroid cancer remains not clear. Although both diseases often occur simultaneously in histological samples, it is not yet clear whether CLT can be regarded as a risk factor for thyroid malignancy. This review focus on the known epidemiological and molecular genetics links between both diseases. Most studies have shown a significant association between thyroid cancer and positive antibodies to thyroglobulin and histological evidence of CLT, as well. Both disorders share some risk factors (greater incidence in women, in areas with adequate supply of iodine and in patients after radiotherapy of the neck) and molecular genetics linkage. For example: RET/PTC rearrangements could be more often found in carcinomas associated with CLT, but this mutation could be found in benign lesions such as CLT, as well. CLT seems to be a positive prognostic factor in patients with differentiated thyroid cancer. It is associated with less invasive forms of tumor, lower occurrence of infiltrated lymphatic nodes and a lower risk of recurrence.

Association of low baseline free thyroxin levels with progression of coronary artery calcification over 4 years in euthyroid subjects: the Kangbuk Samsung Health Study.

PubMed

Park, Hye-Jeong; Kim, Jihyun; Han, Eun Jin; Park, Se Eun; Park, Cheol-Young; Lee, Won-Young; Oh, Ki-Won; Park, Sung-Woo; Rhee, Eun-Jung

2016-06-01

Overt and subclinical hypothyroidism are risk factors for atherosclerosis and cardiovascular diseases. It is unclear whether thyroid hormone levels within the normal range are also associated with atherosclerosis measured by coronary artery calcium (CAC). This study aimed to examine the relationship between normal variations in thyroid function and changes in CAC. We conducted a 4-year retrospective study of 2173 apparently healthy men and women with normal thyroid hormone levels. Their free thyroxin (FT4), free triiodothyronin (FT3) and thyroid-stimulating hormone (TSH) levels were measured by electrochemiluminescent immunoassay. The CAC score (CACS) of each subject was measured by multidetector computed tomography in both 2010 and 2014. Progression of CAC was defined as a CACS change over 4 years > 0. The mean CACS changes over 4 years by quartiles of baseline FT4 level (lowest to highest) were 12·9, 8·43, 7·82 and 7·81 (P = 0·028). CAC progression was not significantly associated with either the baseline FT3 or TSH levels. The odds ratios (OR) for CAC progression over 4 years (highest vs lowest quartile for baseline FT4) were 0·647 (95% confidence interval (CI) 0·472-0·886) after adjustment for confounding factor, which were attenuated with further adjustment for lipid profiles, homoeostasis model assessment of insulin resistance, high-sensitivity C-reactive protein and hypertension [0·747 (95% CI 0·537-1·038)]. Quartiles of baseline FT3 or TSH level did not show any increased OR for CAC progression after adjustment for confounding factors. In this cohort of euthyroid men and women, a low baseline FT4 level was associated with a high risk of CACS progression over 4 years. © 2015 John Wiley & Sons Ltd.

[Treatment of difficult endocrine orbitopathy cases].

PubMed

Breuer, T; Ammann-Rauch, D; Tasman, A J

2007-05-01

There can be many differences between the clinical presentation and disease development of endocrine orbitopathy. Uncommon clinical expressions of the disease may lead to misinterpretations causing difficulties in treatment. Misdiagnosed forms of the disease can end with irreversible vision loss. A 79-year old female with severe bilateral thyroid eye disease, progressive almost blinding visual loss, with the absence of exophthalmos is described. Second, a 39 year old female with a unilateral thyroid eye disease and relapsing episodes of the disease is reported. Exophthalmos, as a symptom, occurs in about 60 % of the patients diagnosed with thyroid eye disease. The absence of exophthalmos may be due to a reduced volume (atrophy ) of retrobulbar fat tissue. Progressive visual loss can be related to direct compression of the optic nerve by thickened eye muscles in the orbital apex. Thyroid eye disease presents itself unilaterally in 5-11 % of all cases and involvement of the contra lateral orbit may occur years later. A relapse of the disease may be triggered by episodes of hypo- or hyperthyroidism. Smoking is a significant risk factor for orbitopathy relapse. Physicians treating thyroid eye disease should be aware of atypical clinical presentations in order for early satisfactory treatment. An interdisciplinary approach including ophthalmologists, endocrinologists and oto-rhino-laryngologists is necessary for optimal management.

Robotic versus Open Thyroidectomy for Differentiated Thyroid Cancer: An Evidence-Based Review.

PubMed

Liu, Shirley Yuk Wah; Ng, Enders Kwok Wai

2016-01-01

While open thyroidectomy (OT) is advocated as the gold standard treatment for differentiated thyroid cancer, the contemporary use of robotic thyroidectomy (RT) is often controversial. Although RT combines the unique benefits of the surgical robot and remote access thyroidectomy, its applicability on cancer patients is challenged by the questionable oncological benefits and safety. This review aims to analyze the current literature evidence in comparing RT to OT on thyroid cancers for their perioperative and oncological outcomes. To date, no randomized controlled trial is available in comparing RT to OT. All published studies are nonrandomized or retrospective comparisons. Current data suggests that RT compares less favorably than OT for longer operative time, higher cost, and possibly inferior oncological control with lower number of central lymph nodes retrieved. In terms of morbidity, quality of life outcomes, and short-term recurrence rates, RT and OT are comparable. While conventional OT continues to be appropriate for most thyroid cancers, RT should better be continued by expert surgeons on selected patients who have low-risk thyroid cancers and have high expectations on cosmetic outcomes. Future research should embark on prospective randomized studies for unbiased comparisons. Long-term follow-up studies are also needed to evaluate outcomes on recurrence and survival.

Simultaneous immunohistochemical expression of HBME-1 and galectin-3 differentiates papillary carcinomas from hyperfunctioning lesions of the thyroid.

PubMed

Rossi, E D; Raffaelli, M; Mule', A; Miraglia, A; Lombardi, C P; Vecchio, F M; Fadda, G

2006-06-01

The histological diagnosis is critical for the postsurgical management and follow-up of thyroid malignancies. The differential diagnosis between papillary carcinoma and hyperfunctioning lesions, either with papillary hyperplasia or with a follicular architecture, can create real diagnostic difficulty. The aim of this study was to evaluate the expression of several antibodies considered to be markers of malignancy in malignant and hyperfunctioning thyroid neoplasms and to include the most effective of them in a diagnostic panel. One hundred resected thyroid nodules--58 hyperfunctioning benign lesions and 42 papillary carcinomas (14 follicular variant, 14 macrofollicular variant and 14 classic type)--were immunohistochemically studied for HBME-1, galectin-3, cytokeratin (CK) 19 and RET-proto-oncogene. HBME-1 and galectin-3 showed 92.8% and 89% sensitivity, respectively, and their coexpression was present in 36 out of 42 papillary carcinomas (85.7%) and absent in non-malignant lesions. Their association increased sensitivity to 94.7% and the diagnostic accuracy to 97.9% and involved the highest number of cases (95%) in comparison with two other panels including, respectively, three (HBME-1, galectin-3, CK19) and all four antibodies. An immunohistochemical panel consisting of HBME-1 and galectin-3 can make a correct distinction between malignant and hyperfunctioning thyroid neoplasms with high diagnostic accuracy.

RAMAN spectroscopy imaging improves the diagnosis of papillary thyroid carcinoma

NASA Astrophysics Data System (ADS)

Rau, Julietta V.; Graziani, Valerio; Fosca, Marco; Taffon, Chiara; Rocchia, Massimiliano; Crucitti, Pierfilippo; Pozzilli, Paolo; Onetti Muda, Andrea; Caricato, Marco; Crescenzi, Anna

2016-10-01

Recent investigations strongly suggest that Raman spectroscopy (RS) can be used as a clinical tool in cancer diagnosis to improve diagnostic accuracy. In this study, we evaluated the efficiency of Raman imaging microscopy to discriminate between healthy and neoplastic thyroid tissue, by analyzing main variants of Papillary Thyroid Carcinoma (PTC), the most common type of thyroid cancer. We performed Raman imaging of large tissue areas (from 100 × 100 μm2 up to 1 × 1 mm2), collecting 38 maps containing about 9000 Raman spectra. Multivariate statistical methods, including Linear Discriminant Analysis (LDA), were applied to translate Raman spectra differences between healthy and PTC tissues into diagnostically useful information for a reliable tissue classification. Our study is the first demonstration of specific biochemical features of the PTC profile, characterized by significant presence of carotenoids with respect to the healthy tissue. Moreover, this is the first evidence of Raman spectra differentiation between classical and follicular variant of PTC, discriminated by LDA with high efficiency. The combined histological and Raman microscopy analyses allow clear-cut integration of morphological and biochemical observations, with dramatic improvement of efficiency and reliability in the differential diagnosis of neoplastic thyroid nodules, paving the way to integrative findings for tumorigenesis and novel therapeutic strategies.

Computerized study with 201T1 of the cold thyroid node.

PubMed

Palermo, F; Saitta, B; Coghetto, F; Tiberio, M; Caldato, L

1982-02-01

Because of its physical and potassium-metabolic characteristics 201T1 is more suitable than 131Cs for radioisotopic studies of the cold thyroid nodule, with the further diagnostic possibility of quantitatively assessing intranodular behavior for a specific differentiation among different kinds of neoformations. Using a gamma-camera on line with a computer data processing device, sequential scintiscans were recorded for the first 20-30 min after i.v. administration of 15-20 microCi/kg of radiothallium; delayed sequences were taken at 40-60 min if intranodular uptake appeared. A quantitative appraisal was made of the differential 201T1 uptake-ratio between nodule and healthy thyroid tissue (density-index) and the multiparameter analysis of thyroid time/activity curves generated on the relative regions of interest (ROIs). This computerized study, in 120 out of 293 patients submitted to this radiothallium test, has shown a) diagnostic agreement between clinical-histological and radioisotopic findings in 76 out of 79 colloid-cystic or degenerative neoformations, in all 16 malignant and in 23 out of 25 hyperplastic benign nodules; b) significant statistical difference of the density-index in solid versus cystic but not between benign and malignant nodules; c) different 201T1 kinetics behaviour in different kinds of solid thyroid lesions with a satisfactory statistical difference of the radiothallium nodular disappearance-index.

COUP-TF1 Modulates Thyroid Hormone Action in an Embryonic Stem-Cell Model of Cortical Pyramidal Neuronal Differentiation.

PubMed

Teng, Xiaochun; Liu, Yan-Yun; Teng, Weiping; Brent, Gregory A

2018-05-01

Thyroid hormone is critical for normal brain development and acts in a spatial and temporal specific pattern. Thyroid hormone excess, or deficiency, can lead to irreversible impairment of brain and sensory development. Chicken ovalbumin upstream-transcription factor 1 (COUP-TF1), expressed early in neuronal development, is essential to achieve normal brain structure. Thyroid hormone stimulation of gene expression is inversely correlated with the level of COUP-TF1 expression. An in vitro method of differentiating mouse embryonic stem (mES) cells into cortical neurons was utilized to study the influence of COUP-TF1 on thyroid hormone signaling in brain development. mES cells were cultured and differentiated in specific conditioned media, and a high percentage of nestin-positive progenitor neurons in the first stage, and cortical neurons in the second stage, was obtained with characteristic neuronal firing. The number of nestin-positive progenitors, as determined by fluorescence-activated cell sorting analysis, was significantly greater with triiodothyronine (T3) treatment compared to control (p < 0.05). T3 enhanced the expression of cortical neuron marker (Tbr1 and Rc3) mRNAs. After COUP-TF1 knockdown, the number of nestin-positive progenitors was reduced compared to control (p < 0.05), but the number increased with T3 treatment. The mRNA of cortical neuronal gene markers was measured after COUP-TF1 knockdown. In the presence of T3, the peak expression of neuron markers Emx1, Tbr1, Camkiv, and Rc3 mRNA was earlier, at day 18 of differentiation, compared to control cells, at day 22. Furthermore, after COUP-TF1 knockdown, T3 induction of Rc3 and Tbr1 mRNA was significantly enhanced compared to cells expressing COUP-TF1. These results indicate that COUP-TF1 plays an important role in modulating the timing and magnitude of T3-stimulated gene expression required for normal corticogenesis.

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.

Thyroid Carcinoma

PubMed

Ahmed, Najeeb; Niyaz, Kashif; Borakati, Aditya; Marafi, Fahad; Birk, Rubinder; Usmani, Sharjeel

2018-02-26

Differentiated thyroid cancer (DTC) has a good prognosis overall; however, lifelong follow-up is required for many cases. Radioiodine planar imaging with iodine-123 (I-123) or radioiodine-131 (I-131) remains the standard in the follow-up after initial surgery and ablation of residual thyroid tissue using I-131 therapy. Radioiodine imaging is also used in risk-stratifying and for staging of thyroid cancer, and in long-term follow-up. Unfortunately, the lack of anatomical detail on planar gamma camera imaging and superimposition of areas presenting with increased radioiodine uptake can make accurate diagnosis and localization of radioiodine-avid metastatic disease challenging, leading to false positive results and potentially to over-treatment of patients. Hybrid SPECT/CT allows precise anatomical localization and superior characterization of foci of increased tracer uptake when compared to planar imaging. This, in turn, allows the differentiation of pathological and physiological uptake, increasing the accuracy of image interpretation and ultimately improving the accuracy of DTC staging and subsequent patient management. In this review, we look at the unique and emerging role that SPECT/CT plays in the management of DTC, illustrated by examples from our own clinical practice. Creative Commons Attribution License

Tuberculous Lymphadenitis Mimicking Nodal Metastasis in Follicular Variant Papillary Thyroid Carcinoma.

PubMed

Yu, Marc Gregory; Atun, Jenny Maureen

2016-01-01

Tuberculous (TB) lymphadenitis can mimic cervical node metastasis from papillary thyroid carcinoma (PTC) since the distribution and appearance of affected lymph nodes are similar. We present the case of an asymptomatic 50-year-old Filipino who sought consult for a gradually enlarging anterior neck mass and a single palpable cervical lymph node. Preoperative workup suggested a thyroid malignancy with nodal metastasis. He underwent total thyroidectomy with node dissection where histopathology confirmed follicular variant- (FV-) PTC. Lymph node examination, however, revealed TB lymphadenitis, and the patient was given standard antimycobacterial therapy. This is the first documented case in Southeast Asia, a high TB burden region. This is also the first report involving FV-PTC, which has features between those of conventional PTC and follicular thyroid carcinoma. The case suggests that, in endemic areas, TB should be a differential in the etiology of cervical lymphadenopathy in PTC patients. In developed countries, this differential diagnosis is also valuable because of the increasing incidence of HIV and TB coinfection. Proper preoperative evaluation is important and needs to be highlighted in the formulation of local guidelines.

Tuberculous Lymphadenitis Mimicking Nodal Metastasis in Follicular Variant Papillary Thyroid Carcinoma

PubMed Central

Atun, Jenny Maureen

2016-01-01

Tuberculous (TB) lymphadenitis can mimic cervical node metastasis from papillary thyroid carcinoma (PTC) since the distribution and appearance of affected lymph nodes are similar. We present the case of an asymptomatic 50-year-old Filipino who sought consult for a gradually enlarging anterior neck mass and a single palpable cervical lymph node. Preoperative workup suggested a thyroid malignancy with nodal metastasis. He underwent total thyroidectomy with node dissection where histopathology confirmed follicular variant- (FV-) PTC. Lymph node examination, however, revealed TB lymphadenitis, and the patient was given standard antimycobacterial therapy. This is the first documented case in Southeast Asia, a high TB burden region. This is also the first report involving FV-PTC, which has features between those of conventional PTC and follicular thyroid carcinoma. The case suggests that, in endemic areas, TB should be a differential in the etiology of cervical lymphadenopathy in PTC patients. In developed countries, this differential diagnosis is also valuable because of the increasing incidence of HIV and TB coinfection. Proper preoperative evaluation is important and needs to be highlighted in the formulation of local guidelines. PMID:27746818

[Selenium treatment in thyreopathies].

PubMed

Sotak, Štefan

Selenium (latin Selenium) is a micronutrient embedded in several proteins. In adults, the thyroid is the organ with the highest amount of selenium per gram of tissue. Selenium levels in the body depend on the characteristics of the population and its diet and geographic area. In the thyroid, selenium is required for the antioxidant function and for the metabolism of thyroid hormones. The literature suggests that selenium supplementation of patients with Hashimotos thyroiditis is associated with a reduction in antithyroperoxidase antibody levels. Selenium supplementation also in mild Graves orbitopathy is associated with delayed progression of ocular disorders. As a consequence of this observation The European Group on Graves Orbitopathy recommend six months selenium preparates supportive therapy for patients with mild form of Graves orbitopathy.Key words: Graves-Basedows disease - Hashimotos thyroiditis - selenium - supplementation.

Molecular Approaches to Thyroid Cancer Diagnosis

PubMed Central

Hsiao, Susan J.; Nikiforov, Yuri E.

2014-01-01

Thyroid nodules are common, and the accurate diagnosis of cancer or benign disease is important for the effective clinical management of these patients. Molecular markers are a helpful diagnostic tool, particularly for cytologically indeterminate thyroid nodules. In the past few years, significant progress has been made in developing molecular markers for clinical use in fine needle aspiration (FNA) specimens, including gene mutation panels and gene expression classifiers. With the availability of next generation sequencing technology, gene mutation panels can be expanded to interrogate multiple genes simultaneously and to provide yet more accurate diagnostic information. In addition, recently several new molecular markers in thyroid cancer have been identified that offer diagnostic, prognostic, and therapeutic information that could potentially be of value in guiding individualized management of patients with thyroid nodules. PMID:24829266

Unusual presentation of Warthin variant of Papillary thyroid carcinoma with lymph nodal metastases in a patient of Graves' disease.

PubMed

Padma, Subramanyam; Sundaram, Palaniswamy Shanmuga; Arun, B R

2015-01-01

Warthin-like Papillary thyroid carcinoma (WPTC) is a rare variant of papillary carcinoma of thyroid, PTC which derives its name by closely resembling Warthin's tumor of salivary gland. Hallmark histological feature of this variant is papillary folding lined by oncocytic neoplastic cells with clear nuclei and nuclear pseudoinclusions, accompanied by prominent lymphocytic infiltrate in the papillary stalks. It is thought to be one of those differentiated thyroid cancers with favorable prognosis. We report a case of Graves' disease with a cold nodule harboring WPTC with initial presentation of lymph nodal metastases. It is important to identify this peculiar variant of PTC as 5 to 10% of them undergo dedifferentiation and 30% have the lymph nodal metastases and extra thyroidal extension.

Incidentally Detected Thyroid Follicular Neoplasm on Somatostatin Receptor Imaging and Post-therapy Scan.

PubMed

Sood, Apurva; Singh, Harpreet; Sood, Ashwani; Basher, Rajender Kumar; Mittal, Bhagwant Rai

2017-01-01

Peptide receptor radionuclide therapy (PRRT) either using Lu-177 or Y-90 peptide radiopharmaceuticals has emerged as promising treatment modality in patients with inoperable metastatic neuroendocrine tumour (NET) including medullary thyroid cancer, because of overexpression of somatostatin receptor 2 (sstr-2) on these cells. The several investigators have used PRRT in non-iodine avid differentiated thyroid cancer patients with limited success, where other treatment modalities have failed, probably due to faint sstr-2 expression in these lesions. However Hurthle cell neoplasms being predominantly non-iodine avid lesions have shown sstr-2 over-expression. The present case of inoperable NET patient imaged and treated with radiolabelled somatostatin analogue showed incidentally detected thyroid lesion highlighting the its importance in imaging and treatment in these type of thyroid malignancies.

Incidentally Detected Thyroid Follicular Neoplasm on Somatostatin Receptor Imaging and Post-therapy Scan

PubMed Central

Sood, Apurva; Singh, Harpreet; Sood, Ashwani; Basher, Rajender Kumar; Mittal, Bhagwant Rai

2017-01-01

Peptide receptor radionuclide therapy (PRRT) either using Lu-177 or Y-90 peptide radiopharmaceuticals has emerged as promising treatment modality in patients with inoperable metastatic neuroendocrine tumour (NET) including medullary thyroid cancer, because of overexpression of somatostatin receptor 2 (sstr-2) on these cells. The several investigators have used PRRT in non-iodine avid differentiated thyroid cancer patients with limited success, where other treatment modalities have failed, probably due to faint sstr-2 expression in these lesions. However Hurthle cell neoplasms being predominantly non-iodine avid lesions have shown sstr-2 over-expression. The present case of inoperable NET patient imaged and treated with radiolabelled somatostatin analogue showed incidentally detected thyroid lesion highlighting the its importance in imaging and treatment in these type of thyroid malignancies. PMID:28680210

[Thyroid and treatment with amiodarone diagnosis, therapy and clinical management].

PubMed

Mikosch, Peter

2008-01-01

Amiodarone is a frequently used antiarrhythmic drug with a high antiarrhythmic potency. However, beside its antiarrhythmic effects Amiodarone also reveals a variety of adverse effects and drug-related complications. The affected organs include the eyes, skin, lungs, nervous system, liver, gastrointestinal tract and the thyroid. The thyroid is one of the most frequently affected organs by Amiodarone. An altered hormone equilibrium always occurs and has to be distinguished from Amiodarone induced hyperthyroidism and hypothyroidism. The differentiation of these states frequently causes problems and may even be a diagnostic and therapeutic challenge in certain cases. The article gives an overview on the interactions between Amiodarone and the thyroid, the diagnostic and therapeutic options and management strategies of patient on Amiodarone therapy in the view of thyroid function.

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

The role of thyroid hormone signaling in the prevention of digestive system cancers.

PubMed

Brown, Adam R; Simmen, Rosalia C M; Simmen, Frank A

2013-08-06

Thyroid hormones play a critical role in the growth and development of the alimentary tract in vertebrates. Their effects are mediated by nuclear receptors as well as the cell surface receptor integrin αVβ3. Systemic thyroid hormone levels are controlled via activation and deactivation by iodothyronine deiodinases in the liver and other tissues. Given that thyroid hormone signaling has been characterized as a major effector of digestive system growth and homeostasis, numerous investigations have examined its role in the occurrence and progression of cancers in various tissues of this organ system. The present review summarizes current findings regarding the effects of thyroid hormone signaling on cancers of the esophagus, stomach, liver, pancreas, and colon. Particular attention is given to the roles of different thyroid hormone receptor isoforms, the novel integrin αVβ3 receptor, and thyroid hormone-related nutrients as possible protective agents and therapeutic targets. Future investigations geared towards a better understanding of thyroid hormone signaling in digestive system cancers may provide preventive or therapeutic strategies to diminish risk, improve outcome and avert recurrence in afflicted individuals.

The Role of Thyroid Hormone Signaling in the Prevention of Digestive System Cancers

PubMed Central

Brown, Adam R.; Simmen, Rosalia C. M.; Simmen, Frank A.

2013-01-01

Thyroid hormones play a critical role in the growth and development of the alimentary tract in vertebrates. Their effects are mediated by nuclear receptors as well as the cell surface receptor integrin αVβ3. Systemic thyroid hormone levels are controlled via activation and deactivation by iodothyronine deiodinases in the liver and other tissues. Given that thyroid hormone signaling has been characterized as a major effector of digestive system growth and homeostasis, numerous investigations have examined its role in the occurrence and progression of cancers in various tissues of this organ system. The present review summarizes current findings regarding the effects of thyroid hormone signaling on cancers of the esophagus, stomach, liver, pancreas, and colon. Particular attention is given to the roles of different thyroid hormone receptor isoforms, the novel integrin αVβ3 receptor, and thyroid hormone-related nutrients as possible protective agents and therapeutic targets. Future investigations geared towards a better understanding of thyroid hormone signaling in digestive system cancers may provide preventive or therapeutic strategies to diminish risk, improve outcome and avert recurrence in afflicted individuals. PMID:23924944

The Clinical and Thyroid Function Studies of Lymphocytic Thyroiditis with Spontaneously Resolving Hyperthyroidism: Comparison to Subacute Thyroiditis

PubMed Central

Koh, Eun Hee; Park, Yong Joon; Lee, Hyun Chul; Hong, Chein Soo; Huh, Kap Bum; Lee, Sang Yong; Ryu, Kyung Za

1986-01-01

Lymphocytic thyroiditis with spontaneously resolving hyperthyroidism (LT-SRH) has been reported in the past years, and is referred to as “silent thyroiditis.” It is characterized by a low or decreased radioactive iodine uptake (RAIU) of thyroid in a patient with hyperthyroidism in whom initial diagnosis is generally thought to be Graves’ disease. Thirty-five patients who had hyperthyroidism or goiter with decreased RAIU have been assessed. Twenty-four (68.6%) of 35 patients had LT-SRH and the remaining patients, subacute thyroiditis (SAT). The clinical characteristics of the patients with LT-SRH were a history of delivery, painless goiter, elevated T3 and T4 levels and positive anti-microsomal antibodies. Anti-microsomal antibodies were positive in 70.8% of the LT-SRH group, whereas 12.5% in the SAT group. Resolution of the hyperthyroidism took 8 to 12 months. It is considered that LT-SRH is an autoimmune thyroiditis with spontaneously resolving hyperthyroidism and determination of the RAIU is very useful in differentiating from other forms of hyperthyroidism. PMID:15759376

Dietary patterns, goitrogenic food, and thyroid cancer: a case-control study in French Polynesia.

PubMed

Cléro, Énora; Doyon, Françoise; Chungue, Vaïana; Rachédi, Frédérique; Boissin, Jean-Louis; Sebbag, Joseph; Shan, Larrys; Rubino, Carole; de Vathaire, Florent

2012-01-01

French Polynesia has one of the world's highest thyroid cancer incidence rates. A case-control study among native residents of French Polynesia included 229 cases of differentiated thyroid cancer diagnosed between 1979 and 2004, and 371 population controls. Dietary patterns and goitrogenic food consumption (cabbage, cassava) were analyzed. We used a factor analysis to identify dietary patterns and a conditional logistic regression analysis to investigate the association between dietary patterns or food items and thyroid cancer risk. Two distinct dietary patterns were identified: traditional Polynesian and Western. A nonsignificant inverse association was observed between the traditional Polynesian dietary pattern and thyroid cancer risk. The Western pattern was not associated with thyroid cancer risk. Cassava consumption was significantly associated with a decreased risk of thyroid cancer. In conclusion, a traditional Polynesian dietary pattern led to a weak reduced risk of thyroid cancer in French Polynesia. The protective effect of cassava on this cancer does not seem to be substantially different from that of cabbage, which was the main goitrogenic food studied to date.

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.

An evaluation of the value of first thyroglobulin determination in the diagnostics of metastases immediately following differentiated thyroid carcinoma surgery.

PubMed

Makarewicz, Jacek; Adamczewski, Zbigniew; Rutkowski, Antoni; Mikosiński, Sławomir; Knapska-Kucharska, Małgorzata; Gonerska-Szadkowska, Anna; Oszukowska, Lidia; Karwowska, Anzelmina; Lewiński, Andrzej

2006-01-01

Evaluation of the differential value of the first thyroglobulin (Tg) concentration, measured after thyroidectomy (Tx) but before thyroid remnant ablation, in patients with differentiated thyroid carcinoma (DTC) as a marker of either metastases or residual cancer (M). Data from 517 patients with DTC after Tx, with follow-up > 1.5 year were analysed retrospectively. Patients in whom either the course of the disease was unclear or interference in the Tg test was possible (a-TgAb [+], Tg recovery < 80%) were excluded from the study. Finally, the data from 247 patients were evaluated (age: 14-79 years; 223 women, 24 men). The results of TSH, thyroid radioiodine uptake (T(up24)), thyroid remnant volume (V) and Tg in patients with diagnosed M (group M1; n = 35) were compared with the same parameters in patients with remission > 1.5 year (group M0; n = 212). The area under the ROC curve was calculated. The clinical decision limit of Tg level to be suggestive of metastases was determined by means of efficiency curve. Groups M0 and M1 did not differ from each other with respect to TSH concentration (median 49.7 mIU/l vs 44.3; p = 0.16) or thyroid remnant volume (1.4 vs 1.1 ml; p = 0.79). However, they did differ with respect to T(up24) (7.6 vs 3.2%; p = 0.01) and Tg (4.5 vs 96.7 ng/ml; p = 0.000000). Area under ROC for Tg was 0.78 +/- 0.05 (mean +/- s.e.m.). The decision limit of Tg for suspected M was determined at 38.1 ng/ml, Tg sensitivity was 0.57 (95%CI 0.39-0.74) and specificity 0.96 (95%CI 0.92-0.98). First thyroglobulin concentration, determined after thyroidectomy but before other treatment, is higher in patients with metastatic DTC than in patients without such metastases. This indicates that Tg level may be used as an early marker of either residual or metastatic DTC (even if thyroid remnants are present).

[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.

Subclinical hypothyroidism: Should we treat?

PubMed

Redford, Christopher; Vaidya, Bijay

2017-06-01

Subclinical hypothyroidism (also known as compensated hypothyroidism or mild hypothyroidism) is a condition associated with a raised serum concentration of thyroid stimulating hormone (TSH) but a normal serum free thyroxine (FT4). It is common, affecting about 10% of women above the age of 55 years. Autoimmunity is the commonest cause of subclinical hypothyroidism. About 2.5% of patients with subclinical hypothyroidism progress to clinically overt hypothyroidism each year; the rate of progression is higher in patients with thyroid autoantibodies and higher thyroid stimulating hormone levels. However, thyroid function normalises spontaneously in up to 40% cases. Only a small minority of patients with subclinical hypothyroidism have symptoms, and the evidence to support that levothyroxine ameliorate the symptoms in these patients is weak. Subclinical hypothyroidism in younger patients (<65 years) is associated with an increased risk of coronary heart disease, heart failure and cerebrovascular disease. The risk increases with increasing levels of thyroid stimulating hormone, and is particularly high in patients with TSH levels ≥10.0 mu/L. There is lack of evidence from randomised controlled trials as to whether levothyroxine treatment can prevent these risks, although a large observational study of the UK general practice research database has shown that levothyroxine may reduce the risk of coronary heart disease in younger patients (<70 years). Therefore, the decision whether to treat or not to treat subclinical hypothyroidism should be made after careful consideration of the patient's age, the presence of symptoms, the presence of thyroid antibodies and other risk factors such as cardiovascular disease.

A comparison of 1850 (50 mCi) and 3700 MBq (100 mCi) 131-iodine administered doses for recombinant thyrotropin-stimulated postoperative thyroid remnant ablation in differentiated thyroid cancer.

PubMed

Pilli, Tania; Brianzoni, Ernesto; Capoccetti, Francesca; Castagna, Maria Grazia; Fattori, Sara; Poggiu, Angela; Rossi, Gloria; Ferretti, Francesca; Guarino, Elisa; Burroni, Luca; Vattimo, Angelo; Cipri, Claudia; Pacini, Furio

2007-09-01

Recently, a multicenter study in differentiated thyroid cancer (DTC) patients showed that 3700 MBq 131-iodine ((131)I) after recombinant human TSH (rhTSH) had a successful thyroid ablation rate similar to that obtained after thyroid hormone withdrawal. We investigated whether 1850 MBq (131)I had a similar successful rate to 3700 MBq in patients prepared with rhTSH. A total of 72 patients with DTC were randomly assigned to receive 1850 (group A, n = 36) or 3700 MBq (group B, n = 36) (131)I after rhTSH. One injection of 0.9 mg rhTSH was administered for 2 consecutive days; (131)I therapy was delivered 24 h after the last injection, followed by a posttherapy whole-body scan. Successful ablation was assessed 6-8 months later. Successful ablation (no visible uptake in the diagnostic whole-body scan after rhTSH stimulation) was achieved in 88.9% of group A and B patients. Basal and rhTSH-stimulated serum thyroglobulin was undetectable (<1 ng/ml) in 78.9% of group A and 66.6% of group B patients (P = 0.46). Similar rates of ablation were obtained in both groups also in patients with node metastases. Therapeutic (131)I activities of 1850 MBq are equally effective as 3700 MBq for thyroid ablation in DTC patients prepared with rhTSH, even in the presence of node metastases.

Modulation of Sodium Iodide Symporter in Thyroid Cancer

PubMed Central

Lakshmanan, Aparna; Scarberry, Daniel

2015-01-01

Radioactive iodine (RAI) is a key therapeutic modality for thyroid cancer. Loss of RAI uptake in thyroid cancer inversely correlates with patient’s survival. In this review, we focus on the challenges encountered in delivering sufficient doses of I-131 to eradicate metastatic lesions without increasing the risk of unwanted side effects. Sodium iodide symporter (NIS) mediates iodide influx, and NIS expression and function can be selectively enhanced in thyroid cells by thyroid-stimulating hormone. We summarize our current knowledge of NIS modulation in normal and cancer thyroid cells, and we propose that several reagents evaluated in clinical trials for other diseases can be used to restore or further increase RAI accumulation in thyroid cancer. Once validated in preclinical mouse models and clinical trials, these reagents, mostly small-molecule inhibitors, can be readily translated into clinical practice. We review available genetically engineered mouse models of thyroid cancer in terms of their tumor development and progression as well as their thyroid function. These mice will not only provide important insights into the mechanisms underlying the loss of RAI uptake in thyroid tumors but will also serve as preclinical animal models to evaluate the efficacy of candidate reagents to selectively increase RAI uptake in thyroid cancers. Taken together, we anticipate that the optimal use of RAI in the clinical management of thyroid cancer is yet to come in the near future. PMID:25234361

Comparison of the symptoms of menopause and symptoms of thyroid disease in Japanese women aged 35-59 years.

PubMed

Oi, N; Ohi, K

2013-10-01

In this study, we surveyed thyroid function abnormalities and menopausal symptoms in young as well as in menopausal women. We conducted a random survey among outpatients at our facility from September 2008 to June 2011. The study included 853 women aged 35-59 years. We assessed the subjects according to the Simplified Menopause Index, menstrual status, thyroid hormone measurements (thyroid stimulating hormone, free thyroxine, free triiodothyronine), the presence of Hashimoto's disease antibodies (anti-thyroid peroxidase antibody or anti-thyroglobulin antibody), the presence of Grave's disease (anti-TSH receptor antibody), markers of thyroid tumor (high thyroglobulin), and thyroid ultrasonography studies. The data were analyzed by means of the statistical program JMP version 8.0. 'Facial flushing', 'sweating', and 'thyroid tumor' were all positively related with age and menstrual status. 'Breathlessness and palpitations' were positively related to Grave's disease. Moreover, 'sweating', 'irritability', and 'stiff shoulders, low back pain, and joint pain' were related to thyroid tumors. 'Insomnia' decreased with age. Patients with Hashimoto's disease were very rare because they were usually treated at other hospitals that specialize in thyroid disease. The symptoms of thyroid function abnormalities were shown to be very similar to menopausal symptoms and were found to occur in younger women before the onset of menopause. This study shows the need to differentiate menopausal symptoms from those of thyroid diseases.

Multiparametric ultrasonography and ultrasound elastography in the differentiation of parathyroid lesions from ectopic thyroid lesions or lymphadenopathies.

PubMed

Isidori, Andrea M; Cantisani, Vito; Giannetta, Elisa; Diacinti, Daniele; David, Emanuele; Forte, Valerio; Elia, Daniela; De Vito, Corrado; Sbardella, Emilia; Gianfrilli, Daniele; Monteleone, Francesco; Pepe, Jessica; Minisola, Salvatore; Ascenti, Giorgio; D'Andrea, Vito; Catalano, Carlo; D'Ambrosio, Ferdinando

2017-08-01

To evaluate the accuracy of ultrasound elastography with Elastoscan TM Core Index in the differential diagnosis of parathyroid lesions from ectopic thyroid nodules and lymph nodes. Seventy nine patients with repeatedly high levels of circulating intact parathyroid hormone, normal vitamin D and renal function tests, with an ultrasound scan showing a neck lesion, sharply demarcated from the thyroid lobules, were consecutively enrolled. Ultrasound with and without Color Doppler and ultrasound elastography were performed before histological examination. All ultrasound features, vascularization and ultrasound elastography diagnostic performance were assessed using ROC curves. Histological examination confirmed 47 parathyroid lesions, 18 thyroid ectopic nodules and 14 reactive lymph nodes. In distinguishing parathyroid from thyroid nodules, shape had a 100 % sensitivity (95 % CI 92.4-100) and 50 % specificity (95 % CI 37.2-64.7), cleavage had a 85.1 % sensitivity (95 % CI 72.3-92.6) and 77.8 % specificity (95 % CI 65.1-88) while peripheral vascularization had a sensitivity of 91.5 (95 % CI 79.6-97.6) and specificity of 72.2 (95 % CI 46.5-90.3). An Elastoscan TM Core Indexof 1.28 was 46 % sensitive (95 % CI 33.4-58.7) and 77 % specific (95 % CI 66.2-89.1) in discriminating parathyroid lesions from thyroid nodules. An Elastoscan TM Core Index of 1.0 was 78 % sensitive (95 % CI 65.1-88) and 71 % specific (95 % CI 56-81.3) in discriminating parathyroid lesions from lymph nodes (p = 0.045). An Elastoscan TM Core Index greater than 2.58 had a 100 % sensitivity (95 % CI 43.8-100) and 95.4 % specificity (95 % CI 38.3-99.7) in discriminating malignant from benign parathyroid nodules. Elastoscan TM Core Index was significantly higher in thyroid nodules than in reactive lymph nodes (1.18 ± 0.62, p = 0.008). The ultrasound features of cleavage and peripheral vascularization help to differentiate parathyroid from thyroid nodules. Elastoscan TM Core Index can improve ultrasound discrimination of parathyroid lesions from lymph nodes. The Elastoscan TM Core Index is significantly higher in malignant than in benign parathyroid lesions.

Thyroid Follicular Carcinoma in a Fourteen-year-old Girl with Graves’ Disease

PubMed Central

Kojima-Ishii, Kanako; Ihara, Kenji; Ohkubo, Kazuhiro; Matsuo, Terumichi; Toda, Naoko; Yamashita, Hiroyuki; Kono, Shinji; Hara, Toshiro

2014-01-01

Abstract Here we present the case of a 14-yr-old girl who developed thyroid follicular carcinoma accompanied by Graves’ disease. She was diagnosed with Graves’ disease at 10 yr of age and soon achieved a euthyroid state after starting treatment. When she was 13 yr of age, her hyperthyroidism and goiter worsened despite medical therapy. Multiple nodules were found in her enlarged thyroid gland by ultrasonography. Her serum Tg level seemed within the normal range. She underwent near-total thyroidectomy for control of thyroid function. Histopathological study demonstrated that multiple oxyphilic follicular neoplasms were surrounded by the thyroid tissue compatible with Graves’ disease. Capsular invasion was identified in one of the nodules, and thus the histological diagnosis was minimally invasive follicular carcinoma. She did not have signs suggesting metastasis, and has had no relapse for 18 mo after the operation. Although some previous studies showed a high prevalence of thyroid cancer with an aggressive nature in adult patients with Graves’ disease, few reports about thyroid cancer accompanied by Graves’ disease are available in children. The present case, however, suggests that careful investigation is needed when we detect thyroid nodules or progressive thyroid enlargement, especially in children with Graves’ disease. PMID:24790388

Thyroid Follicular Carcinoma in a Fourteen-year-old Girl with Graves' Disease.

PubMed

Kojima-Ishii, Kanako; Ihara, Kenji; Ohkubo, Kazuhiro; Matsuo, Terumichi; Toda, Naoko; Yamashita, Hiroyuki; Kono, Shinji; Hara, Toshiro

2014-04-01

Here we present the case of a 14-yr-old girl who developed thyroid follicular carcinoma accompanied by Graves' disease. She was diagnosed with Graves' disease at 10 yr of age and soon achieved a euthyroid state after starting treatment. When she was 13 yr of age, her hyperthyroidism and goiter worsened despite medical therapy. Multiple nodules were found in her enlarged thyroid gland by ultrasonography. Her serum Tg level seemed within the normal range. She underwent near-total thyroidectomy for control of thyroid function. Histopathological study demonstrated that multiple oxyphilic follicular neoplasms were surrounded by the thyroid tissue compatible with Graves' disease. Capsular invasion was identified in one of the nodules, and thus the histological diagnosis was minimally invasive follicular carcinoma. She did not have signs suggesting metastasis, and has had no relapse for 18 mo after the operation. Although some previous studies showed a high prevalence of thyroid cancer with an aggressive nature in adult patients with Graves' disease, few reports about thyroid cancer accompanied by Graves' disease are available in children. The present case, however, suggests that careful investigation is needed when we detect thyroid nodules or progressive thyroid enlargement, especially in children with Graves' disease.

HISTOPATHOLOGIC CHARACTERISTICS OF THYROID GLAND NEOPLASMS IN THOMSON'S GAZELLES ( EUDORCUS THOMSONII).

PubMed

French, Stephanie J; Garner, Michael M; Kiupel, Matti

2018-03-01

Published reports of neoplasms in Thomson's gazelles ( Eudorcas thomsonii) are very rare, but thyroid tumors were the most common neoplasm of this species, accounting for 12% of reported pathologies in a 1998-2012 retrospective study of cases submitted for histologic review of grossly enlarged thyroid glands. This report describes the histological and immunohistochemical characteristics of thyroid neoplasms in 10 Thomson's gazelles from five different zoological collections. Neoplasms were submitted as biopsies from six gazelles or collected during necropsy from four gazelles. The most common clinical findings included a palpable mass on the ventral neck and progressive weight loss. Radiographic mineral density was detected in one of the neoplastic masses. Histologically, the neoplasms were classified as microfollicular thyroid adenoma ( n = 2), solid thyroid adenoma ( n = 2), papillary thyroid adenoma ( n = 1), and solid thyroid carcinoma ( n = 5). Neoplastic cells in all 10 neoplasms were positive for thyroid transcription factor 1 and thyroglobulin, but negative for calcitonin. While five cases had histologic features of malignancy, there was no evidence of metastatic disease either clinically (biopsies) or on necropsy. Numerous concurrent diseases, including cardiomyopathies and nephropathies, were present and led to choice for euthanasia in several cases.

CHIP promotes thyroid cancer proliferation via activation of the MAPK and AKT pathways

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

Zhang, Li; Liu, Lianyong; Department of Endocrinology, Shanghai Punan Hospital, Shanghai 200125

The carboxyl terminus of Hsp70-interacting protein (CHIP) is a U box-type ubiquitin ligase that plays crucial roles in various biological processes, including tumor progression. To date, the functional mechanism of CHIP in thyroid cancer remains unknown. Here, we obtained evidence of upregulation of CHIP in thyroid cancer tissues and cell lines. CHIP overexpression markedly enhanced thyroid cancer cell viability and colony formation in vitro and accelerated tumor growth in vivo. Conversely, CHIP knockdown impaired cell proliferation and tumor growth. Notably, CHIP promoted cell growth through activation of MAPK and AKT pathways, subsequently decreasing p27 and increasing cyclin D1 and p-FOXO3a expression. Ourmore » findings collectively indicate that CHIP functions as an oncogene in thyroid cancer, and is therefore a potential therapeutic target for this disease. - Highlights: • CHIP is significantly upregulated in thyroid cancer cells. • Overexpression of CHIP facilitates proliferation and tumorigenesis of thyroid cancer cells. • Silencing of CHIP inhibits the proliferation and tumorigenesis of thyroid cancer cells. • CHIP promotes thyroid cancer cell proliferation via activating the MAPK and AKT pathways.« less

Warthin-Like Papillary Carcinoma of the Thyroid Gland: Case Report and Review of the Literature

PubMed Central

Paliogiannis, Panagiotis; Attene, Federico; Trogu, Federica; Trignano, Mario

2012-01-01

We present a case of Warthin-like papillary thyroid carcinoma in a 22-year-old woman and a review of the literature on the topic. The patient had the occasional discovery of a hypoechoic thyroid nodule of approximately 18 mm, characterized by irregular margins, hyperechoic spots, rich intra- and perilesional vascularization, and a suspicious enlarged right laterocervical lymph node. Fine-needle aspiration was performed for both lesions and the diagnosis of papillary thyroid carcinoma without lymph node involvement was made. The patient underwent thyroidectomy and central neck lymphadenectomy without complications. Histopathological examination suggested a Warthin-like papillary carcinoma of the thyroid gland, with all the removed lymph nodes being free of disease. The patient subsequently underwent iodine ablative therapy and she remains free of disease one year after surgery. Warthin-like papillary thyroid carcinoma is a recently described variant of papillary thyroid cancer that is frequently associated with lymphocytic thyroiditis. Morphologically, it resembles Warthin tumors of the salivary glands, with T and B lymphocytes infiltrating the stalks of papillae lined with oncocytic cells. Surgical and postoperative management is identical to that of classic differentiated thyroid cancer, while prognosis seems to be favourable. PMID:23243533

Warthin-like papillary carcinoma of the thyroid gland: case report and review of the literature.

PubMed

Paliogiannis, Panagiotis; Attene, Federico; Trogu, Federica; Trignano, Mario

2012-01-01

We present a case of Warthin-like papillary thyroid carcinoma in a 22-year-old woman and a review of the literature on the topic. The patient had the occasional discovery of a hypoechoic thyroid nodule of approximately 18 mm, characterized by irregular margins, hyperechoic spots, rich intra- and perilesional vascularization, and a suspicious enlarged right laterocervical lymph node. Fine-needle aspiration was performed for both lesions and the diagnosis of papillary thyroid carcinoma without lymph node involvement was made. The patient underwent thyroidectomy and central neck lymphadenectomy without complications. Histopathological examination suggested a Warthin-like papillary carcinoma of the thyroid gland, with all the removed lymph nodes being free of disease. The patient subsequently underwent iodine ablative therapy and she remains free of disease one year after surgery. Warthin-like papillary thyroid carcinoma is a recently described variant of papillary thyroid cancer that is frequently associated with lymphocytic thyroiditis. Morphologically, it resembles Warthin tumors of the salivary glands, with T and B lymphocytes infiltrating the stalks of papillae lined with oncocytic cells. Surgical and postoperative management is identical to that of classic differentiated thyroid cancer, while prognosis seems to be favourable.

A branching morphogenesis program governs embryonic growth of the thyroid gland

PubMed Central

Liang, Shawn; Johansson, Ellen; Barila, Guillermo; Altschuler, Daniel L.; Fagman, Henrik

2018-01-01

ABSTRACT The developmental program that regulates thyroid progenitor cell proliferation is largely unknown. Here, we show that branching-like morphogenesis is a driving force to attain final size of the embryonic thyroid gland in mice. Sox9, a key factor in branching organ development, distinguishes Nkx2-1+ cells in the thyroid bud from the progenitors that originally form the thyroid placode in anterior endoderm. As lobes develop the thyroid primordial tissue branches several generations. Sox9 and Fgfr2b are co-expressed distally in the branching epithelium prior to folliculogenesis. The thyroid in Fgf10 null mutants has a normal shape but is severely hypoplastic. Absence of Fgf10 leads to defective branching and disorganized angiofollicular units although Sox9/Fgfr2b expression and the ability of cells to differentiate and form nascent follicles are not impaired. These findings demonstrate a novel mechanism of thyroid development reminiscent of the Fgf10-Sox9 program that characterizes organogenesis in classical branching organs, and provide clues to aid understanding of how the endocrine thyroid gland once evolved from an exocrine ancestor present in the invertebrate endostyle. PMID:29361553

A branching morphogenesis program governs embryonic growth of the thyroid gland.

PubMed

Liang, Shawn; Johansson, Ellen; Barila, Guillermo; Altschuler, Daniel L; Fagman, Henrik; Nilsson, Mikael

2018-01-25

The developmental program that regulates thyroid progenitor cell proliferation is largely unknown. Here, we show that branching-like morphogenesis is a driving force to attain final size of the embryonic thyroid gland in mice. Sox9, a key factor in branching organ development, distinguishes Nkx2-1 + cells in the thyroid bud from the progenitors that originally form the thyroid placode in anterior endoderm. As lobes develop the thyroid primordial tissue branches several generations. Sox9 and Fgfr2b are co-expressed distally in the branching epithelium prior to folliculogenesis. The thyroid in Fgf10 null mutants has a normal shape but is severely hypoplastic. Absence of Fgf10 leads to defective branching and disorganized angiofollicular units although Sox9/Fgfr2b expression and the ability of cells to differentiate and form nascent follicles are not impaired. These findings demonstrate a novel mechanism of thyroid development reminiscent of the Fgf10-Sox9 program that characterizes organogenesis in classical branching organs, and provide clues to aid understanding of how the endocrine thyroid gland once evolved from an exocrine ancestor present in the invertebrate endostyle. © 2018. Published by The Company of Biologists Ltd.

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

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

Warthin-Like Papillary Thyroid Carcinoma Associated with Lymphadenopathy and Hashimoto's Thyroiditis.

PubMed

González-Colunga, Karla Judith; Loya-Solis, Abelardo; Ceceñas-Falcón, Luis Ángel; Barboza-Quintana, Oralia; Rodríguez-Gutiérrez, René

2015-01-01

Defining the histologic variant of thyroid carcinoma is an important clinical implication as their progression, recurrence, aggressiveness, and prognosis differ. Warthin-like variant is one of the rarest histologic variants of papillary thyroid cancer. A 36-year-old female sought consult for assessment of a painless right neck tumor. High-resolution neck ultrasound revealed a right hypoechoic, 1.71 × 1.05 cm thyroid nodule. Ultrasound-guided fine-needle aspiration biopsy report was a Bethesda grade III. Thyroid function tests showed Hashimoto's thyroiditis. The patient underwent right hemithyroidectomy. Microscopically, the tumor was composed of papillae lined by cells with eosinophilic cytoplasm, nuclear chromatin clearing, grooves, and pseudoinclusions and a characteristic lymphoplasmacytic infiltrate of the papillae cores. Extension into the perithyroidal soft tissue and 3 ipsilateral lymph nodes was found to be positive for cancer. Warthin-like variant is an uncommon and relatively unknown variant of papillary thyroid carcinoma that has been usually associated with an excellent prognosis. Interestingly, BRAF mutations have been reported to be present in up to 75% of the patients. It is frequently associated with Hashimoto's thyroiditis and presents unique morphological features that make it recognizable on histologic examination. The cytological diagnosis is difficult to assess due to the overlap in its findings with the classical variant and Hashimoto's thyroiditis.

Warthin-Like Papillary Thyroid Carcinoma Associated with Lymphadenopathy and Hashimoto's Thyroiditis

PubMed Central

González-Colunga, Karla Judith; Loya-Solis, Abelardo; Ceceñas-Falcón, Luis Ángel; Barboza-Quintana, Oralia; Rodríguez-Gutiérrez, René

2015-01-01

Defining the histologic variant of thyroid carcinoma is an important clinical implication as their progression, recurrence, aggressiveness, and prognosis differ. Warthin-like variant is one of the rarest histologic variants of papillary thyroid cancer. A 36-year-old female sought consult for assessment of a painless right neck tumor. High-resolution neck ultrasound revealed a right hypoechoic, 1.71 × 1.05 cm thyroid nodule. Ultrasound-guided fine-needle aspiration biopsy report was a Bethesda grade III. Thyroid function tests showed Hashimoto's thyroiditis. The patient underwent right hemithyroidectomy. Microscopically, the tumor was composed of papillae lined by cells with eosinophilic cytoplasm, nuclear chromatin clearing, grooves, and pseudoinclusions and a characteristic lymphoplasmacytic infiltrate of the papillae cores. Extension into the perithyroidal soft tissue and 3 ipsilateral lymph nodes was found to be positive for cancer. Warthin-like variant is an uncommon and relatively unknown variant of papillary thyroid carcinoma that has been usually associated with an excellent prognosis. Interestingly, BRAF mutations have been reported to be present in up to 75% of the patients. It is frequently associated with Hashimoto's thyroiditis and presents unique morphological features that make it recognizable on histologic examination. The cytological diagnosis is difficult to assess due to the overlap in its findings with the classical variant and Hashimoto's thyroiditis. PMID:25821606

Mixed primary squamous cell carcinoma, follicular carcinoma, and micropapillary carcinoma of the thyroid gland: A case report.

PubMed

Dong, Su; Song, Xue-Song; Chen, Guang; Liu, Jia

2016-08-01

Primary squamous cell carcinoma of the thyroid gland is rare, and mixed squamous cell and follicular carcinoma is even rarer still, with only a few cases reported in the literature. The simultaneous presentation of three primary cancers of the thyroid has not been reported previously. Here we report a case of primary squamous cell carcinoma of the thyroid, follicular thyroid carcinoma, and micropapillary thyroid carcinoma. A 62-year-old female patient presented with complaints of pain and a 2-month history of progressively increased swelling in the anterior region of the neck. Fine-needle-aspiration cytology of both lobes indicated the possibility of the presence of a follicular neoplasm. Total thyroidectomy with left-sided modified radical neck dissection was performed. Postoperative pathological examination confirmed the diagnosis of thyroid follicular carcinoma with squamous cell carcinoma and micropapillary carcinoma of the thyroid. Thyroid-stimulating hormone suppressive therapy with l-thyroxine was administered. Radioiodine and radiotherapy also were recommended, but the patient did not complete treatment as scheduled. The patient remained alive more than 9 months after operation. The present case report provides an example of the coexistence of multiple distinct malignancies in the thyroid. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Concurrence of Grave's disease and Hashimoto's thyroiditis.

PubMed Central

Sato, T; Takata, I; Taketani, T; Saida, K; Nakajima, H

1977-01-01

Early histological changes in the thyroid gland were examined in 30 patients with juvenile thyrotoxicosis, by means of needle biopsy. Based on the degree of lymphocytic infiltration and degenerative changes in follicular epithelium, results were classified into four groups. A: hyperplastic changes without cellular infiltration (6 patients, 20%); B: hyperplastic changes with areas of focal thyroiditis less than 30% of specimen (10 patients, 33%); C: those with 30 to 60% areas ot thyroiditis (10 patients, 33%); D: almost diffuse thyroiditis (4 patients, 13%). Moderate to severe lymphocytic thyroiditis was frequently present in the early stage of hyperplastic thyroid glands. The clinical significance of the 4 histological groups was evaluated. Neither clinical signs nor routine laboratory tests could differentiate these groups except group D, in which thyrotoxic signs were mild and transient. However, serum antithyroid antibodies tended to increase in accordance with severity of thyroiditis. The rate of remission was high in groups C and D, whereas relapse was frequent in group A. These results suggest that Grave's disease and chronic lymphocytic thyroiditis are closely related in the early stage of thyrotoxicosis in children, and that the clinical course may be considerably altered by the degree of associated thyroiditis. Images Fig. 1 Fig. 2 Fig. 3 Fig. 3 PMID:580172

Ultrasound findings of diffuse metastasis of gastric signet-ring-cell carcinoma to the thyroid gland.

PubMed

Morita, Koji; Sakamoto, Takahiko; Ota, Shuji; Masugi, Hideo; Chikuta, Ikumi; Mashimo, Yamato; Edo, Naoki; Tokairin, Takuo; Seki, Nobuhiko; Ishikawa, Toshio

2017-01-01

It has been shown that metastases to the thyroid from extrathyroidal malignancies occur as solitary or multiple nodules, or may involve the whole thyroid gland diffusely. However, diffuse metastasis of gastric cancer to the thyroid is extremely rare. Here, we report a case of a 74-year-old woman with diffuse infiltration of gastric adenocarcinoma (signet-ring-cell carcinoma/poorly differentiated adenocarcinoma) cells in the thyroid. The pathological diagnosis was made based on upper gastrointestinal endoscopy with biopsy and fine-needle aspiration cytology of the thyroid. An 18F-FDG PET/CT revealed multiple lesions with increased uptake, including the bilateral thyroid gland. On thyroid ultrasound examination, diffuse enlargement with internal heterogeneity and hypoechoic reticular lines was observed. On color Doppler imaging, a blood-flow signal was not detected in these hypoechoic lines. These findings were similar to those of diffuse metastases caused by other primary cancers, such as lung cancer, as reported earlier. Therefore, the presence of hypoechoic reticular lines without blood-flow signals is probably common to diffuse thyroid metastasis from any origin and an important diagnostic finding. This is the first report to show detailed ultrasound findings of diffuse gastric cancer metastasis to the thyroid gland using color Doppler.

Multivariate evaluation of Thyroid Imaging Reporting and Data System (TI-RADS) in diagnosis malignant thyroid nodule: application to PCA and PLS-DA analysis.

PubMed

Zhang, Tan; Li, Fangxuan; Mu, Jiali; Liu, Juntian; Zhang, Sheng

2017-06-01

To explore the significance of ultrasonic features in differential diagnosis of thyroid nodules via combining the thyroid imaging reporting and data system (TI-RADS) and multivariate statistical analysis. Patients who received surgical treatment and was diagnosed with single thyroid nodule by postoperative pathology and preoperative ultrasound were enrolled in this study. Multivariate analysis was applied to assess the significant ultrasonic features which correlated with identifying benign or malignance and grading the TI-RADS classification of thyroid nodule. There were significant differences in the nodule size, aspect ratio, internal, echogenicity, boundary, presence or absence of calcifications, calcification type and CDFI between benign and malignant thyroid nodules. Multivariate analysis showed clear-cut distinction both between benign and malignance and among different TI-RADS categories of malignancy nodules. The shape and calcification of the nodule were important factors for distinguish the benign and malignance. Height of the nodule, aspect and calcification was important factors for grading TI-RADS categories of malignancy thyroid nodules. Ill-defined boundary, irregular shape and presence of calcification related with highly malignant risk for thyroid nodule. The larger height and aspect and presence of calcification related with higher TI-RADS classification of malignancy thyroid nodule.

Morphological and immunohistochemical characterization of spontaneous thyroid gland neoplasms in guinea pigs (Cavia porcellus).

PubMed

Gibbons, P M; Garner, M M; Kiupel, M

2013-03-01

Reports of thyroid gland neoplasms in guinea pigs (Cavia porcellus) are rare, but thyroid tumors are among the most common neoplasms seen in cases submitted to Northwest ZooPath. This report describes the histological and immunohistochemical characteristics of thyroid neoplasms and lists the concurrent conditions found in guinea pig cases submitted to Northwest ZooPath during 1998 to 2008. Of 526 guinea pig case submissions, 19 had thyroid neoplasms. The most common clinical findings included a palpable mass on the ventral neck and progressive weight loss. Neoplasms were removed as an excisional biopsy from 7 guinea pigs, and 3 of these animals died within a few days after surgery. Radiographic mineral density was detected in 2 masses. Five of the neoplasms were reported as cystic; 5 were black or a dark color. Histologically, the neoplasms were classified as macrofollicular thyroid adenoma (8), thyroid cystadenoma (1), papillary thyroid adenoma (3), follicular thyroid carcinoma (5), follicular-compact thyroid carcinoma (1), and small-cell thyroid carcinoma (1). Osseous metaplasia was present in 8 neoplasms, and myeloid hyperplasia was present in 1 neoplasm. All 19 neoplasms were positive for thyroid transcription factor 1 and thyroglobulin but negative for parathyroid hormone and calcitonin. Numerous concurrent diseases, including hepatopathies, cardiomyopathies, and nephropathies, were present and considered to be the cause of death in many cases. Research is needed to determine the appropriate modalities for antemortem diagnosis and treatment and whether thyroid disease plays a role in the pathogenesis of chronic degenerative diseases in guinea pigs.

Cytological features of warthin-like papillary thyroid carcinoma: A case report with review of previous cytology cases.

PubMed

Vallonthaiel, Archana George; Agarwal, Shipra; Jain, Deepali; Yadav, Rajni; Damle, Nishikant A

2017-09-01

Warthin-like papillary thyroid carcinoma (WLPTC) is a rare morphological variant of papillary thyroid carcinoma which mimics various benign and malignant lesions on thyroid aspiration cytology. As correct cytological diagnosis is the cornerstone for appropriate patient management, awareness of the salient cytomorphological characteristics of this tumor is essential. Here, we present cytological features of a case of WLPTC along with discussion of the common differential diagnoses and a brief review of the literature to ascertain the most consistent cytological findings of WLPTC. The present case also harboured BRAFV600E mutation which is the commonest molecular alteration seen in WLPTC. © 2017 Wiley Periodicals, Inc.

SPECT/CT demonstrating 131I retention in Warthin tumor on thyroid cancer survey scan.

PubMed

Zhang, Yuyang; Minoshima, Satoshi

2013-09-01

A 48-year-old male patient of papillary thyroid cancer, status post-thyroidectomy and node dissection, was referred to (131)I scan prior to radioiodine treatment. The images showed 1 additional focus of (131)I uptake in the right upper neck outside of the thyroid bed. SPECT/CT demonstrated 2 separate foci of radioiodine uptake in the right parotid gland, instead of neck lymph nodes. Diagnostic CT showed 2 corresponding soft tissue nodules in the right parotid gland which were confirmed latter by fine-needle aspiration to be Warthin tumors. This case illustrates a pivotal role of SPECT/CT in differential diagnosis of abnormal neck uptake on (131)I thyroid cancer scan.

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.

The 2015 European Thyroid Association Guidelines on Diagnosis and Treatment of Endogenous Subclinical Hyperthyroidism

PubMed Central

Biondi, Bernadette; Bartalena, Luigi; Cooper, David S.; Hegedüs, Laszlo; Laurberg, Peter; Kahaly, George J.

2015-01-01

Endogenous subclinical hyperthyroidism (SHyper) is caused by Graves' disease, autonomously functioning thyroid nodules and multinodular goitre. Its diagnosis is based on a persistently subnormal serum thyroid-stimulating hormone (TSH) level with free thyroid hormone levels within their respective reference intervals. In 2014 the European Thyroid Association Executive Committee, given the controversies regarding the treatment of Endo SHyper, formed a task force to develop clinical practice guidelines based on the principles of evidence-based medicine. The task force recognized that recent meta-analyses, including those based on large prospective cohort studies, indicate that SHyper is associated with increased risk of coronary heart disease mortality, incident atrial fibrillation, heart failure, fractures and excess mortality in patients with serum TSH levels <0.1 mIU/l (grade 2 SHyper). Therefore, despite the absence of randomized prospective trials, there is evidence that treatment is indicated in patients older than 65 years with grade 2 SHyper to potentially avoid these serious cardiovascular events, fractures and the risk of progression to overt hyperthyroidism. Treatment could be considered in patients older than 65 years with TSH levels 0.1-0.39 mIU/l (grade 1 SHyper) because of their increased risk of atrial fibrillation, and might also be reasonable in younger (<65 years) symptomatic patients with grade 2 SHyper because of the risk of progression, especially in the presence of symptoms and/or underlying risk factors or co-morbidity. Finally, the task force concluded that there are no data to support treating SHyper in younger asymptomatic patients with grade 1 SHyper. These patients should be followed without treatment due to the low risk of progression to overt hyperthyroidism and the weaker evidence for adverse health outcomes. PMID:26558232

Influence of human body composition on serum peak thyrotropin (TSH) after recombinant human TSH administration in patients with differentiated thyroid carcinoma.

PubMed

Castagna, Maria Grazia; Pinchera, Aldo; Marsili, Alessandro; Giannetti, Monica; Molinaro, Eleonora; Fierabracci, Paola; Grasso, Lucia; Pacini, Furio; Santini, Ferruccio; Elisei, Rossella

2005-07-01

In this study, we evaluated the influence of height, weight, body mass index (BMI), body surface area, and body composition [total lean body mass (LBM) and fat body mass] on serum peak TSH levels obtained after recombinant human (rh)TSH. Furthermore, to verify whether the serum peak TSH influenced the efficacy of radioiodine ((131)I), we compared the rate of thyroid remnant ablation according to the patients' BMI. We studied 105 patients with differentiated thyroid carcinoma who underwent rhTSH stimulation test. Serum TSH measurements were performed before and 24, 48, and 72 h after rhTSH administration. We also compared the rate of thyroid remnant ablation among 70 differentiated thyroid carcinoma patients with different BMI. The serum peak TSH after rhTSH was significantly lower in overweight and obese subjects compared with normal-weight subjects (92.1 +/- 41.8, 82.4 +/- 24.2, and 112.7 +/- 46.3 microU/ml, respectively; P = 0.01) and in males compared with females (74.6 +/- 22.3 and 105.0 +/- 43.0 microU/ml, respectively; P = 0.0002). By univariate analysis, serum peak TSH was negatively related to weight, height, body surface area, BMI, LBM, and fat body mass, but only LBM was independently associated with serum peak TSH levels. Although it was confirmed that overweight and obese patients had a lower serum peak TSH, the rate of ablation did not differ among normal-weight, overweight, and obese patients. With this study we demonstrated that LBM is the only parameter independently associated with serum peak TSH after rhTSH administration. However, the serum peak TSH does not influence the rate of (131)I remnant ablation.

Altered balance between self-reactive T helper (Th)17 cells and Th10 cells and between full-length forkhead box protein 3 (FoxP3) and FoxP3 splice variants in Hashimoto's thyroiditis.

PubMed

Kristensen, B; Hegedüs, L; Madsen, H O; Smith, T J; Nielsen, C H

2015-04-01

T helper type 17 (Th17) cells play a pathogenic role in autoimmune disease, while interleukin (IL)-10-producing Th10 cells serve a protective role. The balance between the two subsets is regulated by the local cytokine milieu and by the relative expression of intact forkhead box protein 3 (FoxP3) compared to FoxP3Δ2, missing exon 2. Th17 and Th10 cell differentiation has usually been studied using polyclonal stimuli, and little is known about the ability of physiologically relevant self-antigens to induce Th17 or Th10 cell differentiation in autoimmune thyroid disease. We subjected mononuclear cells from healthy donors and patients with Hashimoto's thyroiditis (HT) or Graves' disease (GD) to polyclonal stimulation, or stimulation with human thyroglobulin (TG), human thyroid peroxidase (TPO), or Esherichia coli lipopolysaccharide (LPS). TPO and LPS induced increased differentiation of naive CD4(+) CD45RA(+) CD45R0(-) T cells from HT patients into Th17 cells. Th10 cell proportions were decreased in HT after polyclonal stimulation, but were comparable to those of healthy donors after antigen-specific stimulation. Taken together, our data show that an increased Th17 : Th10 ratio was found in HT patients after stimulation with thyroid-specific self-antigens. We also observed an elevated baseline production of IL-6 and transforming growth factor (TGF)-β1 and of mRNA encoding FoxP3Δ2 rather than intact FoxP3. This may contribute to the skewing towards Th17 cell responses in HT. © 2014 British Society for Immunology.

Acoustic radiation force impulse elastography for differentiation of benign and malignant thyroid nodules with concurrent Hashimoto's thyroiditis.

PubMed

Liu, Bo-Ji; Xu, Hui-Xiong; Zhang, Yi-Feng; Xu, Jun-Mei; Li, Dan-Dan; Bo, Xiao-Wan; Li, Xiao-Long; Guo, Le-Hang; Xu, Xiao-Hong; Qu, Shen

2015-03-01

The purpose of the study was to explore the diagnostic performance of acoustic radiation force impulse (ARFI) elastography in differential diagnosis between benign and malignant thyroid nodules in patients with coexistent Hashimoto's thyroiditis (HT). A total of 141 pathological proven nodules in 141 HT patients (7 males and 134 females, mean age 50.1 years, range 23-75 years) received conventional ultrasound (US), elasticity imaging (EI) and ARFI elastography, including virtual touch tissue imaging (VTI) and virtual touch tissue quantification (VTQ), before surgery. Shear wave velocity (SWV) and SWV ratio were measured for each nodule on VTQ. The US, EI and ARFI elastography features were compared between benign and malignant nodules in HT patients. Receiver operating characteristic curve (ROC) analyses and area under curve (AUC) were performed to assess the diagnostic performance. Pathologically, 70 nodules were benign and 71 nodules were malignant. Significant differences were found between benign and malignant nodules in HT patients for EI (EI score) and ARFI (VTI grade and SWV) (all P value <0.05). The AUCs for EI, VTI, SWV and SWV ratio were 0.68 [95% confidence interval (CI): 0.59-0.77], 0.90 (95% CI: 0.84-0.95), 0.77 (95%CI: 0.70-0.85) and 0.74 (95%CI: 0.66-0.82), respectively. The cut-off points were EI score ≥3, VTI grade ≥4, SWV ≥2.58 m/s and SWV ratio ≥1.03, respectively. In conclusion, ARFI elastography is useful for differentiation between benign and malignant thyroid nodules in HT patients. The diagnostic performance of ARFI elastography is better than EI.

Genes that characterize T3-predominant Graves' thyroid tissues.

PubMed

Matsumoto, Chisa; Ito, Mitsuru; Yamada, Hiroya; Yamakawa, Noriko; Yoshida, Hiroshi; Date, Arisa; Watanabe, Mikio; Hidaka, Yoh; Iwatani, Yoshinori; Miyauchi, Akira; Takano, Toru

2013-02-01

3,5,3'-Triiodothyronine (T(3))-predominant Graves' disease is characterized by the increasing volume of thyroid goiter resulting in poor prognosis. Although type 1 and type 2 iodothyronine deiodinases (DIO1 and DIO2 respectively) are known to be overexpressed in the thyroid tissues of T(3)-predominant Graves' disease, the pathogenesis of this disease is still unclear. The aim of our study is to identify genes that characterize T(3)-predominant Graves' disease tissue in order to clarify the molecular mechanism of this disease. mRNAs from two thyroid tissues of both typical T(3)-predominant and common-type Graves' disease were analyzed with DNA microarrays with probes for 28 869 genes. Genes identified to be differentially expressed between the two groups were further analyzed in the second and third screenings using 70 Graves' thyroid tissues by real-time quantitative RT-PCR. Twenty-three candidate genes were selected as being differentially expressed in the first screening with microarrays. Among these, seven genes, leucine-rich repeat neuronal 1 (LRRN1), bone morphogenetic protein 8a (BMP8A), N-cadherin (CDH2), phosphodiesterase 1A (PDE1A), creatine kinase mitochondrial 2 (CKMT2), integrin beta-3 (ITGB3), and protein tyrosine phosphatase non-receptor type 4 (PTPN4), were confirmed to be differentially expressed in DIO1 or DIO2 over- and underexpressing Graves' tissues. These genes are related to the characteristics of T(3)-predominant Graves' disease, such as high titer level of serum anti-TSH receptor antibody, high free T(3) to free thyroxine ratio, and a large goiter size. They might play a role in the pathogenesis of T(3)-predominant Graves' disease.

Development and Characterization of a Differentiated Thyroid Cancer Cell Line Resistant to VEGFR-Targeted Kinase Inhibitors

PubMed Central

Isham, Crescent R.; Netzel, Brian C.; Bossou, Ayoko R.; Milosevic, Dragana; Cradic, Kendall W.; Grebe, Stefan K.

2014-01-01

Background: Vascular endothelial growth factor-targeted kinase inhibitors have emerged as highly promising therapies for radioiodine-refractory metastatic differentiated thyroid cancer. Unfortunately, drug resistance uniformly develops, limiting their therapeutic efficacies and thereby constituting a major clinical problem. Approach and Methods: To study acquired drug resistance and elucidate underlying mechanisms in this setting, BHP2–7 human differentiated thyroid cancer cells were subjected to prolonged continuous in vitro selection with 18 μM pazopanib, a clinically relevant concentration; acquisition of pazopanib resistance was serially assessed, with the resulting resistant cells thereafter subcloned and characterized to assess potential mechanisms of acquired pazopanib resistance. Results: Stable 2- to 4-fold in vitro pazopanib resistance emerged in response to pazopanib selection associated with similar in vitro growth characteristics but with markedly more aggressive in vivo xenograft growth. Selected cells were cross-resistant to sunitinib and to a lesser extent sorafenib but not to MAPK kinase (MEK1/2) inhibition by GSK1120212. Genotyping demonstrated acquisition of a novel activating KRAS codon 13 GGC to GTT (glycine to valine) mutation, consistent with the observed resistance to upstream vascular endothelial growth factor receptor inhibition yet sensitivity to downstream MAPK kinase (MEK1/2) inhibition. Conclusions: Selection of thyroid cancer cells with clinically utilized therapeutics can lead to acquired drug resistance and altered in vivo xenograft behavior that can recapitulate analogous drug resistance observed in patients. This approach has the potential to lead to insights into acquired treatment-related drug resistance in thyroid cancers that can be subjected to subsequent validation in serially collected patient samples and that has the potential to yield preemptive and responsive approaches to dealing with this important clinical problem. PMID:24628546

Spindle epithelial tumor with thymus-like differentiation: a case report and review of literature.

PubMed

Misra, R K; Mitra, Shaila; Yadav, Rajesh; Bundela, Alpana

2013-01-01

Spindle epithelial tumor with thymus-like differentiation (SETTLE) is an extremely rare type of thyroid tumor with fewer than 35 reported cases available in the literature so far, most of them having been diagnosed histologically after resection. The tumor is believed to be derived from branchial-pouch or thymic remnants, occurring in young adults, predominantly in males, with a male:female ratio 1.8:1. A 14-year-old girl presented with a nodular mass in her right thyroid that had been present for 1 year. Ultrasonological study revealed a heterogeneous solid mass (2.5 × 1.5 × 1.5 cm) in the right lobe of the thyroid. Fine-needle aspiration (FNA) smears were highly cellular and comprised of predominantly dissociated uniform spindle cells with naked oval nuclei along with some aggregates and groups. Occasional islands of epithelial cells were also present. Cytologically, the spindle cells had bland nuclear chromatin, with very scanty mitotic figures. Upon examination of the FNA smears, a provisional diagnosis of SETTLE was suggested along with a request for an incisional biopsy to rule out another differential diagnosis of medullary carcinoma thyroid. On the resected tissue specimen, diagnosis was histologically confirmed to be SETTLE. Immunohistochemical study revealed a strong and diffuse positivity for high-molecular-weight keratin and vimentin, and negativity for thyroglobulin, calcitonin, S-100 protein, desmin, chromogranin and synaptophysin. Cytologically, SETTLE can safely be considered, especially if spindle elements are observed along with the occasional group of epithelial cells in FNA smears from the thyroid of young adults. It can help in the preoperative recognition of lesions based on distinctive cytomorphological features and immunohistochemical characteristics, allowing a more sound therapeutic approach because these patients can present with delayed metastasis. Copyright © 2013 S. Karger AG, Basel.

[Thyroid orbitopathy, an overview with special attention to the role of radiotherapy].

PubMed

Vilar-González, Santiago; Lamas-Oliveira, Cristina; Fagúndez-Vargas, María A; Núñez-Quintanilla, Ana T; Pérez-Rozos, Alberto; Merayo-Lloves, Jesús; Escobar-Barranco, José J; Rico-Pérez, José M

2015-04-01

Thyroid orbitopathy is the most prevalent non-thyroid symptom in Graves' syndrome. It has a high incidence and particularly affects young women. Smoking is clearly involved in its development and progress, and in its response to different treatments. This autoimmune condition usually has a benign course, independent from hyperthyroidism, but its severe, progressive forms represent a major therapeutic challenge. Clinical evaluation poses great difficulties, as there is no truly objective rating scale representing disease activity. New molecular or inflammation markers may prove to be useful in this regard. This review reports new findings about its pathophysiology and the different techniques used for treatment over time. Discussion particularly focuses on the immunomodulatory role of radiotherapy, as well as on its role together with corticosteroids. Copyright © 2014 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

Spindle epithelial tumor with thymus-like differentiation of the thyroid in a 70-year-old man.

PubMed

Lee, Sunhye; Kim, Yon Seon; Lee, Jeong Hyeon; Hwang, Sung Ho; Oh, Yu-Hwan; Ko, Byung Kyun; Ham, Soo-Youn

2018-06-01

Spindle epithelial tumor with thymus-like differentiation (SETTLE) is a very rare tumor of the thyroid gland mostly occurring in young patients. The imaging findings of SETTLE tumors are yet to be defined. However, they are usually described as well-defined heterogeneously enhanced masses on CT scan. The current case has the potential growth as compared with a 2009 chest radiography. We took into account the possibility of SETTLE in the case of a bulky mass in patients over 70 years old, particularly in the lower neck. Herein, we report a case of the oldest patient so far. The patient underwent a right lobectomy of the thyroid and mass excision. Follow-up CT scans after 6 months revealed no local recurrence. Surgery is the gold standard treatment for SETTLE. Chemotherapy and radiotherapy could be another possible option for patients with advanced stage SETTLE.

Subclinical thyrotoxicosis in an outpatient population - predictors of outcome.

PubMed

Schouten, Belinda J; Brownlie, Bevan E W; Frampton, Chris M; Turner, John G

2011-02-01

Individuals with endogenous subclinical thyrotoxicosis (SCT) may subsequently require treatment for overt disease. We aimed to evaluate the frequency of progression to hyperthyroidism and factors influencing this outcome. This is a retrospective analysis of outcome in 96 consecutive patients (aged 16-91 years) diagnosed with SCT over a 6-year period. Individuals with secondary causes of TSH suppression were excluded. Mean follow-up was 3·8 years. The significance of age, gender, family history of thyrotoxicosis, symptoms at presentation, thyroid nodule(s) on clinical examination, entry TSH level, antithyroid antibody status and (99m) Tc pertechnetate thyroid imaging results on subsequent development of overt thyrotoxicosis was assessed. Progression to overt thyrotoxicosis was seen in 8% at 1 year, 16% at 2 years, 21% at 3 years and 26% at 5 years. Multivariate analysis determined that diagnosis as determined by scintiscan to be the only independent predictor of outcome (P = 0·003) with the cumulative percentage requiring therapy at 5 years being 9% for subclinical Graves' disease, 21% for multinodular goitre and 61% for the autonomous nodule subgroup. Progression of SCT to overt hyperthyroidism occurred at a rate of 5-8% per year with disease aetiology, as determined by thyroid scintigraphy, significantly influencing risk of progression. © 2011 Blackwell Publishing Ltd.

Anaplastic carcinoma of the thyroid in a population irradiated for Hodgkin Disease, 1910-1960

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

Getaz, E.P.; Shimaoka, K.

Post-irradiation carcinoma of the thyroid is usually histologically well-differentiated. In general, those subjects who developed carcinoma had been exposed to low-to-moderate doses of irradiation for benign conditions. We reviewed the charts of 520 patients with Hodgkin's disease seen at Roswell Park Memorial Institute, and found 2 cases of anaplastic carcinoma amongst other thyroidal abnormalities. The existing reports of post-irradiation carcinoma are reviewed and suggestions are made for the management of heavily irradiated, potentially cured patients with Hodgkin's disease.

Implication of intracellular localization of transcriptional repressor PLZF in thyroid neoplasms.

PubMed

Matsuzawa, Kazuhiko; Izawa, Shoichiro; Ohkura, Tsuyoshi; Ohkura, Hiroko; Ishiguro, Kiyosuke; Yoshida, Akio; Takiyama, Yumi; Haneda, Masakazu; Shigemasa, Chiaki; Yamamoto, Kazuhiro; Taniguchi, Shin-ichi

2014-07-03

Promyelocytic leukaemia zinc finger (PLZF) is a transcriptional repressor that was originally isolated from a patient with promyelocytic leukaemia. PLZF also affects key elements for cell cycle progression, such as cyclin A, and can affect the tumourigenicity of various cancers. Thus far, the behaviour of PLZF in thyroid carcinoma remains unclear. We analysed the expression profile of PLZF in different types of benign and malignant thyroid lesions as well as in normal thyroid tissue. Specifically, we examined PLZF expression in normal thyroid (N; n = 4), adenomatous lesion (AL; n = 5), follicular adenoma (FA; n = 2), papillary thyroid carcinoma (PTC; n = 20), and anaplastic thyroid carcinoma (ATC; n = 3) samples. PLZF expression was estimated by western blotting and immunohistochemical (IHC) staining. PLZF was expressed in all samples of thyroid lesions examined. In N, AL, and FA, PLZF was mainly localized in the nucleus. In contrast, in PTC and ATC, PLZF was mainly expressed in the cytosol with high intensity. In more detail, the cytoplasmic IHC scores in PTC with capsular invasion (CI) and lymph node (LN) metastasis were higher than those in PTC without CI and LN metastasis. PLZF shows different subcellular localizations among PTC, ATC, and other thyroid lesions. Furthermore, high cytoplasmic expression of PLZF may be correlated with CI and LN metastasis in thyroid carcinoma. The present report is the first to describe the implications of intracellular PLZF expression in thyroid carcinomas.

Zebrafish bcl2l is a survival factor in thyroid development.

PubMed

Porreca, Immacolata; De Felice, Elena; Fagman, Henrik; Di Lauro, Roberto; Sordino, Paolo

2012-06-15

Regulated cell death, defined in morphological terms as apoptosis, is crucial for organ morphogenesis. While differentiation of the thyroid gland has been extensively studied, nothing is yet known about the survival mechanisms involved in the development of this endocrine gland. Using the zebrafish model system, we aim to understand whether genes belonging to the Bcl-2 family that control apoptosis are implicated in regulation of cell survival during thyroid development. Evidence of strong Bcl-2 gene expression in mouse thyroid precursors prompted us to investigate the functions played by its zebrafish homologs during thyroid development. We show that the bcl2-like (bcl2l) gene is expressed in the zebrafish thyroid primordium. Morpholino-mediated knockdown and mutant analyses revealed that bcl2l is crucial for thyroid cell survival and that this function is tightly modulated by the transcription factors pax2a, nk2.1a and hhex. Also, the bcl2l gene appears to control a caspase-3-dependent apoptotic mechanism during thyroid development. Thyroid precursor cells require an actively maintained survival mechanism to properly proceed through development. The bcl2l gene operates in the inhibition of cell death under direct regulation of a thyroid specific set of transcription factors. This is the first demonstration of an active mechanism to ensure survival of the thyroid primordium during morphogenesis. Copyright © 2012 Elsevier Inc. All rights reserved.

Post-treatment cognitive dysfunction in women treated with thyroidectomy for papillary thyroid carcinoma.

PubMed

Jung, Mi Sook; Visovatti, Moira

2017-03-01

The purpose of the study is to assess cognitive function in papillary thyroid cancer, one type of differentiated thyroid cancer, and to identify factors associated with cognitive dysfunction. Korean women treated with papillary thyroid cancer post thyroidectomy (n = 90) and healthy women similar in age and educational level (n = 90) performed attention and working memory tests and completed self-report questionnaires on cognitive complaints, psychological distress, symptom distress, and cultural characteristics. Comparative and multivariable regression analyses were performed to determine differences in cognitive function and possible predictors of neurocognitive performance and cognitive complaints. Thyroid cancer survivors performed and perceived their function to be significantly worse on tests of attention and working memory compared to individuals without thyroid cancer. Regression analyses found that having thyroid cancer, older age, and lower educational level were associated with worse neurocognitive performance, while greater fatigue, more sleep problems, and higher levels of childrearing burden but not having thyroid cancer were associated with lower perceived effectiveness in cognitive functioning. Findings suggest that women receiving thyroid hormone replacement therapy after thyroidectomy for papillary thyroid cancer are at risk for attention and working memory problems. Coexisting symptoms and culture-related women's burden affected perceived cognitive dysfunction. Health care providers should assess for cognitive problems in women with thyroid cancer and intervene to reduce distress and improve quality of life.

IgG4-related Mikulicz's disease associated with thyroiditis: a case report and review of the literature.

PubMed

Zhang, Yujiao; Du, Yi; Li, Kaijun; He, Jianfeng

2014-03-01

To report an unusual case of IgG4-related Mikulicz's disease associated with thyroiditis. We describe a 25-year-old Chinese man who presented with bilateral, painless swellings of the lachrymal glands, parotid glands, and thyroid nodules. The patient underwent left-sided dacryoadenectomy and the diagnosis of IgG4-related Mikulicz's disease was pathologically confirmed. The size of the right-sided lachrymal gland and parotid glands recovered fundamentally after one month of glucocorticoid therapy. IgG4-related Mikulicz's disease associated with thyroiditis should be considered in the differential diagnosis of bilateral swellings of lachrymal glands, salivary glands, and thyroid nodules. Surgical excision is recommended in order to treat the tumor and to ensure the pathological diagnosis. Glucocorticoid therapy should be considered in association with surgery after removal.

The effect of chronic lymphocytic thyroiditis on patients with thyroid cancer.

PubMed

Zhang, Yi; Ma, Xiao-Peng; Deng, Fu-Sheng; Liu, Zheng-Rong; Wei, Hou-Qing; Wang, Xi-Hong; Chen, Hao

2014-09-01

The purpose of this study was to investigate the association between chronic lymphocytic thyroiditis (CLT) and malignant tumors of the thyroid. A retrospective review of 647 patients who underwent thyroid surgery at the Department of Breast and Thyroid Surgery in Anhui Provincial Hospital, China in 2012 was performed. The clinicopathological characteristics of patients with thyroid malignancies and CLT were collected. CLT was diagnosed by histopathological method. Among 647 patients, 144 patients had thyroid malignancies and 108 patients had been diagnosed with CLT. Moreover, in total, 44 patients had thyroid malignancies coexistent with CLT: forty-one (93.2%) patients had been diagnosed with the papillary thyroid cancer (PTC); two (4.5%) patients suffered from medullary carcinoma; and one (2.3%) patient suffered from lymphoma. The morbidity of thyroid malignancies in patients with CLT was significantly higher than that in patients without CLT (40.7% versus 18.6%; P <0.001). A female preponderance was observed in the patients with CLT compared with those without CLT (P <0.001). There was no statistically significant difference in the tumor size (P = 0.073), multifocality (P = 0.0871), neck lymph node metastasis (P = 0.350), age (P = 0.316), microcarcinoma (P = 0.983) and tumor-node-metastasis (TNM) stage (P = 0.949) between the patients of thyroid malignancies with CLT and without CLT. Female predominance was observed in patients with CLT. CLT may have no effect on the progression of thyroid malignant tumor. Nevertheless, the influences of CLT on the prognosis of the thyroid carcinoma still need to be investigated with a larger sample size.

Pax2.1 is required for the development of thyroid follicles in zebrafish.

PubMed

Wendl, Thomas; Lun, Klaus; Mione, Marina; Favor, Jack; Brand, Michael; Wilson, Stephen W; Rohr, Klaus B

2002-08-01

The thyroid gland is an organ primarily composed of endoderm-derived follicular cells. Although disturbed embryonic development of the thyroid gland leads to congenital hypothyroidism in humans and mammals, the underlying principles of thyroid organogenesis are largely unknown. In this study, we introduce zebrafish as a model to investigate the molecular and genetic mechanisms that control thyroid development. Marker gene expression suggests that the molecular pathways of early thyroid development are essentially conserved between fish and mammals. However during larval stages, we find both conserved and divergent features of development compared with mammals. A major difference is that in fish, we find evidence for hormone production not only in thyroid follicular cells, but also in an anterior non-follicular group of cells. We show that pax2.1 and pax8, members of the zebrafish pax2/5/8 paralogue group, are expressed in the thyroid primordium. Whereas in mice, only Pax8 has a function during thyroid development, analysis of the zebrafish pax2.1 mutant no isthmus (noi(-/-)) demonstrates that pax2.1 has a role comparable with mouse Pax8 in differentiation of the thyroid follicular cells. Early steps of thyroid development are normal in noi(-/-), but later expression of molecular markers is lost and the formation of follicles fails. Interestingly, the anterior non-follicular site of thyroid hormone production is not affected in noi(-/-). Thus, in zebrafish, some remaining thyroid hormone synthesis takes place independent of the pathway leading to thyroid follicle formation. We suggest that the noi(-/-) mutant serves as a new zebrafish model for hypothyroidism.

Expression of stanniocalcin 1 in thyroid side population cells and thyroid cancer cells.

PubMed

Hayase, Suguru; Sasaki, Yoshihito; Matsubara, Tsutomu; Seo, Daekwan; Miyakoshi, Masaaki; Murata, Tsubasa; Ozaki, Takashi; Kakudo, Kennichi; Kumamoto, Kensuke; Ylaya, Kris; Cheng, Sheue-yann; Thorgeirsson, Snorri S; Hewitt, Stephen M; Ward, Jerrold M; Kimura, Shioko

2015-04-01

Mouse thyroid side population (SP) cells consist of a minor population of mouse thyroid cells that may have multipotent thyroid stem cell characteristics. However the nature of thyroid SP cells remains elusive, particularly in relation to thyroid cancer. Stanniocalcin (STC) 1 and 2 are secreted glycoproteins known to regulate serum calcium and phosphate homeostasis. In recent years, the relationship of STC1/2 expression to cancer has been described in various tissues. Microarray analysis was carried out to determine genes up- and down-regulated in thyroid SP cells as compared with non-SP cells. Among genes up-regulated, stanniocalcin 1 (STC1) was chosen for study because of its expression in various thyroid cells by Western blotting and immunohistochemistry. Gene expression analysis revealed that genes known to be highly expressed in cancer cells and/or involved in cancer invasion/metastasis were markedly up-regulated in SP cells from both intact as well as partial thyroidectomized thyroids. Among these genes, expression of STC1 was found in five human thyroid carcinoma-derived cell lines as revealed by analysis of mRNA and protein, and its expression was inversely correlated with the differentiation status of the cells. Immunohistochemical analysis demonstrated higher expression of STC1 in the thyroid tumor cell line and thyroid tumor tissues from humans and mice. These results suggest that SP cells contain a population of cells that express genes also highly expressed in cancer cells including Stc1, which warrants further study on the role of SP cells and/or STC1 expression in thyroid cancer.

Expression of Stanniocalcin 1 in Thyroid Side Population Cells and Thyroid Cancer Cells

PubMed Central

Hayase, Suguru; Sasaki, Yoshihito; Matsubara, Tsutomu; Seo, Daekwan; Miyakoshi, Masaaki; Murata, Tsubasa; Ozaki, Takashi; Kakudo, Kennichi; Kumamoto, Kensuke; Ylaya, Kris; Cheng, Sheue-yann; Thorgeirsson, Snorri S.; Hewitt, Stephen M.; Ward, Jerrold M.

2015-01-01

Background: Mouse thyroid side population (SP) cells consist of a minor population of mouse thyroid cells that may have multipotent thyroid stem cell characteristics. However the nature of thyroid SP cells remains elusive, particularly in relation to thyroid cancer. Stanniocalcin (STC) 1 and 2 are secreted glycoproteins known to regulate serum calcium and phosphate homeostasis. In recent years, the relationship of STC1/2 expression to cancer has been described in various tissues. Method: Microarray analysis was carried out to determine genes up- and down-regulated in thyroid SP cells as compared with non-SP cells. Among genes up-regulated, stanniocalcin 1 (STC1) was chosen for study because of its expression in various thyroid cells by Western blotting and immunohistochemistry. Results: Gene expression analysis revealed that genes known to be highly expressed in cancer cells and/or involved in cancer invasion/metastasis were markedly up-regulated in SP cells from both intact as well as partial thyroidectomized thyroids. Among these genes, expression of STC1 was found in five human thyroid carcinoma–derived cell lines as revealed by analysis of mRNA and protein, and its expression was inversely correlated with the differentiation status of the cells. Immunohistochemical analysis demonstrated higher expression of STC1 in the thyroid tumor cell line and thyroid tumor tissues from humans and mice. Conclusion: These results suggest that SP cells contain a population of cells that express genes also highly expressed in cancer cells including Stc1, which warrants further study on the role of SP cells and/or STC1 expression in thyroid cancer. PMID:25647164

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.

[F-18-fluordeoxyglucose positron emission tomography on patients with differentiated thyroid cancer who present elevated human serum thyroglobulin levels and negative I-131 whole body scan].

PubMed

Ruiz Franco-Baux, J V; Borrego Dorado, I; Gómez Camarero, P; Rodríguez Rodríguez, J R; Vázquez Albertino, R J; Navarro González, E; Astorga Jiménez, R

2005-01-01

This study aimed to evaluate the role of Fluorine-18-fluorodeoxyglucose positron emission tomography (PET-FDG) in patients with elevated serum thyroglobulin (hTg) levels where thyroid cancer tissue does not concentrate radioiodine, rendering false-negative results on I-131 scanning. Whole-body PET imaging using FDG was performed in 54 patients (37 female, 17 male) aged 17-88 years: 45 with papillary tumors and 9 with follicular tumors who were suspected of having recurrent thyroid carcinoma due to elevated thyroglobulin levels (hTg > 2 ng/ml) under thyroid-stimulating hormone (TSH > or = 30 microIU/ml) in whom the iodine scan was negative. All whole body scans were obtained with diagnostic doses (185 MBq). Whole body PET imaging was performed in fasting patients following i.v. administration of 370 MBq FDG while the patients were receiving full thyroid hormone replacement. Before PET, 99mTc methoxyisobutylisonitrile scintigraphy (99mTc-MIBI) was done in 14 patients and morphologic imaging in 26 by CT scan. Positive PET results confirmed the presence of hypermetabolic foci in 25/54 patients (46.29 %). Positive findings were found for PET-FDG in patients with hTg levels higher than 10 ng/ml receiving full thyroid hormone replacement. 99mTc-MIBI demonstrated lesions in 7/14 patients (50 %). PET-FDG and 99mTc-MIBI had congruent positive results in 4/7 patients. All the lesions found by CT were detected by PET-FDG, while recurrent disease was found in 12/21 patients with previous negative CT. These results suggest that PET-FDG seems to be a promising tool in the follow-up of thyroid cancer and should be considered in patients suffering from differentiated thyroid cancer with suspected recurrence and/or metastases by elevated thyroglobulin levels, and negative I-131 whole body scans. PET-FDG might be more useful at hTg levels > 10 ng/ml.

Inhibition of miR-146b expression increases radioiodine-sensitivity in poorly differential thyroid carcinoma via positively regulating NIS expression

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

Li, Luchuan; Lv, Bin; Chen, Bo

2015-07-10

Dedifferentiated thyroid carcinoma (DTC) with the loss of radioiodine uptake (RAIU) is often observed in clinical practice under radioiodine therapy, indicating the challenge for poor prognosis. MicroRNA (miRNA) has emerged as a promising therapeutic target in many diseases; yet, the role of miRNAs in RAIU has not been generally investigated. Based on recent studies about miRNA expression in papillary or follicular thyroid carcinomas, the expression profiles of several thyroid relative miRNAs were investigated in one DTC cell line, derived from normal DTC cells by radioiodine treatment. The top candidate miR-146b, with the most significant overexpression profiles in dedifferentiated cells, wasmore » picked up. Further research found that miR-146b could be negatively regulated by histone deacetylase 3 (HDAC3) in normal cells, indicating the correlation between miR-146b and Na{sup +}/I{sup −} symporter (NIS)-mediated RAIU. Fortunately, it was confirmed that miR-146b could regulate NIS expression/activity; what is more important, miR-146b interference would contribute to the recovery of radioiodine-sensitivity in dedifferentiated cells via positively regulating NIS. In the present study, it was concluded that NIS-mediated RAIU could be modulated by miR-146b; accordingly, miR-146b might serve as one of targets to enhance efficacy of radioactive therapy against poorly differential thyroid carcinoma (PDTC). - Highlights: • Significant upregulated miR-146b was picked up from thyroid relative miRNAs in DTC. • MiR-146b was negatively regulated by HDAC3 in normal thyroid carcinoma cells. • NIS activity and expression could be regulated by miR-146b in thyroid carcinoma. • MiR-146b inhibition could recover the decreased radioiodine-sensitivity of DTC cells.« less

Influence of cigarette smoking on thyroid gland--an update.

PubMed

Sawicka-Gutaj, Nadia; Gutaj, Paweł; Sowiński, Jerzy; Wender-Ożegowska, Ewa; Czarnywojtek, Agata; Brązert, Jacek; Ruchała, Marek

2014-01-01

Many studies have shown that cigarette smoking exerts multiple effects on the thyroid gland. Smoking seems to induce changes in thyroid function tests, like decrease in TSH and increase in thyroid hormones. However, these alterations are usually mild. In addition, tobacco smoking may also play a role in thyroid autoimmunity. Many studies have confirmed a significant influence of smoking on Graves' hyperthyroidism and particularly on Graves' orbitopathy. Here, smoking may increase the risk of disease development, may reduce the effectiveness of treatment, and eventually induce relapse. The role of smoking in Hashimoto's thyroiditis is not as well established as in Graves' disease. Nonetheless, lower prevalence of thyroglobulin antibodies, thyroperoxidase antibodies and hypothyroidism were found in smokers. These findings contrast with a study that reported increased risk of hypothyroidism in smokers with Hashimoto's thyroiditis. Moreover, cigarette smoking increases the incidence of multinodular goitre, especially in iodine-deficient areas. Some studies have examined cigarette smoking in relation to the risk of thyroid cancer. Interestingly, many of them have shown that smoking may reduce the risk of differentiated thyroid cancer. Furthermore, both active and passive smoking during pregnancy might modify maternal and foetal thyroid function. This review evaluates the current data concerning the influence of cigarette smoking on thyroid gland, including hormonal changes, autoimmunity and selected diseases. These findings, however, in our opinion, should be carefully evaluated and some of them are not totally evidence-based. Further studies are required to explain the effects of smoking upon thyroid pathophysiology.

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.

Radiation Dose-rate Reduction Pattern in Well-differentiated Thyroid Cancer Treated with I-131.

PubMed

Khan, Shahbaz Ahmad; Khan, Muhammad Saqib; Arif, Muhammad; Durr-e-Sabih; Rahim, Muhammad Kashif; Ahmad, Israr

2015-07-01

To determine the patterns of dose rate reduction in single and multiple radioiodine (I-131) therapies in cases of well differentiated thyroid cancer patients. Analytical series. Department of Nuclear Medicine and Radiation Physics, Multan Institute of Nuclear Medicine and Radiotherapy (MINAR), Multan, Pakistan, from December 2006 to December 2013. Ninety three patients (167 therapies) with well differentiated thyroid cancer treated with different doses of I-131 as an in-patient were inducted. Fifty four patients were given only single I-131 therapy dose ranging from 70 mCi (2590 MBq) to 150 mCi (5550 MBq). Thirty nine patients were treated with multiple I-131 radioisotope therapy doses ranging from 80 mCi (2960 MBq) to 250 mCi (9250 MBq). T-test was applied on the sample data showed statistically significant difference between the two groups with p-value (p < 0.01) less than 0.05 taken as significant. There were 68 females and 25 males with an age range of 15 to 80 years. Mean age of the patients were 36 years. Among the 93 cases of first time Radio Active Iodine (RAI) therapy, 59 cases (63%) were discharged after 48 hours. Among 39 patients who received RAI therapy second time or more, most were discharged earlier after achieving acceptable discharge dose rate i.e 25 µSv/hour; 2 out of 39 (5%) were discharged after 48 hours. In 58% patients, given single I-131 therapy dose, majority of these were discharged after 48 hours without any major complications. For well differentiated thyroid cancer patients, rapid dose rate reduction is seen in patients receiving second or subsequent radioiodine (RAI) therapy, as compared to first time receiving RAI therapy.

Refuse leachate exposure causes changes of thyroid hormone level and related gene expression in female goldfish (Carassius auratus).

PubMed

Gong, Yufeng; Tian, Hua; Zhang, Xiaona; Dong, Yifei; Wang, Wei; Ru, Shaoguo

2016-12-01

To elucidate the potential thyroid disrupting effects of refuse leachate on females, female goldfish (Carassius auratus) were exposed to 0.5% diluted leachates from each step of a leachate treatment process (i.e. raw leachate before treatment, after membrane bioreactor treatment, and the final treated leachate) for 21days. Raw leachate exposure caused disturbances in the thyroid cascade of female fish, as evidenced by the elevated plasma 3,3',5-triiodo-l-thyronine (p<0.05) and thyroid-stimulating hormone (p<0.01) levels as well as up-regulated hepatic and gonadal type I deiodinase (p<0.01), type II deiodinase (p<0.01) and thyroid receptor (p<0.05) mRNA levels. Thyroid disrupting potency decreased markedly as raw leachate progressed through the "membrane bioreactor + reverse osmosis" treatment but could still be detected in the treated leachate. As our results indicated, thyroid system in female goldfish was more sensitive to leachate exposure than that of the male fish. Copyright © 2016 Elsevier B.V. All rights reserved.

Oxidative Stress and Heart Failure in Altered Thyroid States

PubMed Central

Mishra, Pallavi; Samanta, Luna

2012-01-01

Increased or reduced action of thyroid hormone on certain molecular pathways in the heart and vasculature causes relevant cardiovascular derangements. It is well established that hyperthyroidism induces a hyperdynamic cardiovascular state, which is associated with a faster heart rate, enhanced left ventricular systolic and diastolic function whereas hypothyroidism is characterized by the opposite changes. Hyperthyroidism and hypothyroidism represent opposite clinical conditions, albeit not mirror images. Recent experimental and clinical studies have suggested the involvement of ROS tissue damage under altered thyroid status. Altered-thyroid state-linked changes in heart modify their susceptibility to oxidants and the extent of the oxidative damage they suffer following oxidative challenge. Chronic increase in the cellular levels of ROS can lead to a catastrophic cycle of DNA damage, mitochondrial dysfunction, further ROS generation and cellular injury. Thus, these cellular events might play an important role in the development and progression of myocardial remodeling and heart failure in altered thyroid states (hypo- and hyper-thyroidism). The present review aims at elucidating the various signaling pathways mediated via ROS and their modulation under altered thyroid state and the possibility of antioxidant therapy. PMID:22649319

Size of thyroid carcinoma by histotype and variants: A population-based study in a mildly iodine-deficient area.

PubMed

Marina, Michela; Ceda, Gian Paolo; Corcione, Luigi; Sgargi, Paolo; Michiara, Maria; Silini, Enrico Maria; Ceresini, Graziano

2017-10-01

Data relating the size of thyroid cancer with histological types and variants are scarce. All incident thyroid cancer diagnosed between 2003 and 2012 in a mildly iodine-deficient area were derived from a population-based tumor registry. Undifferentiated/anaplastic thyroid cancer and incidental cases were excluded. Major diameter of thyroid cancer, as assessed by pathological examination, was stratified in classes: ≤10 mm; 11-20 mm; 21-40 mm; and >40 mm. For each class, absolute and relative frequencies of histological types were calculated. Tumors >20 mm were more frequent among follicular thyroid carcinoma (FTC) and Hürthle cell carcinoma than in other histotypes, with median size of 22.50 mm (95% confidence interval [CI] 16.71-28.29) and 25.00 mm (95% CI 17.04-32.96) in FTC and Hürthle cell carcinoma, respectively. Odds ratio for tumors >20 mm was significant for FTC and Hürthle cell carcinoma only (P < .0001). Among the histotypes and variants of differentiated thyroid cancer, FTC and Hürthle cell carcinoma are characterized by the largest size. © 2017 Wiley Periodicals, Inc.

Interaction of thyroid state and denervation on skeletal myosin heavy chain expression

NASA Technical Reports Server (NTRS)

Haddad, F.; Arnold, C.; Zeng, M.; Baldwin, K.

1997-01-01

The goal of this study was to examine the effects of altered thyroid state and denervation (Den) on skeletal myosin heavy chain (MHC) expression in the plantaris and soleus muscles. Rats were subjected to unilateral denervation (Den) and randomly assigned to one of three groups: (1) euthyroid; (2) hyperthyroid; (3) and hypothyroid. Denervation caused severe muscle atrophy and muscle-type specific MHC transformation. Denervation transformed the soleus to a faster muscle, and its effects required the presence of circulating thyroid hormone. In contrast, denervation transformed the plantaris to a slower muscle independently of thyroid state. Furthermore, thyroid hormone effects did not depend upon innervation status in the soleus, while they required the presence of the nerve in the plantaris. Collectively, these findings suggest that both thyroid hormone and intact nerve (a) differentially affect MHC transformations in fast and slow muscle; and (b) are important factors in regulating the optimal expression of both type I and IIB MHC genes. This research suggests that for patients with nerve damage and/or paralysis, both muscle mass and biochemical properties can also be affected by the thyroid state.

Molecular pathobiology of thyroid neoplasms.

PubMed

Tallini, Giovanni

2002-01-01

Tumors of thyroid follicular cells provide a very interesting model to understand the development of human cancer. It is becoming apparent that distinct molecular events are associated with specific stages in a multistep tumorigenic process with good genotype/ phenotype correlation. For instance, mutations of the gsp and thyroid-stimulating hormone receptor genes are associated with benign hyperfunctioning thyroid nodules and adenomas while alterations of other specific genes, such as oncogenic tyrosine kinase alterations (RET/PTC, TRK) in papillary carcinoma and the newly discovered PAX8/peroxisome proliferator-activated receptor gamma rearrangement, are distinctive features of cancer. Although activating RAS mutations occur at all stages of thyroid tumorigenesis, evidence is accumulating that they may also play an important role in tumor progression, a role that is well documented for p53. Environmental factors (iodine deficiency, ionizing radiations) have been shown to play a crucial role in promoting the development of thyroid cancer, influencing both its genotypic and phenotypic features. It is possible that the follicular thyroid cell has unique ways to respond to DNA damage. Similarly to leukemia or sarcomas (and unlike most epithelial cancers), numerous specific rearrangements are being discovered in thyroid cancer suggesting preferential activation of DNA repair instead of cell death programs after environmentally induced genetic alterations.

Simultaneous occurrence of diabetic ketoacidosis, thyroid storm, and multiple cerebral infarctions due to Moyamoya disease.

PubMed

Noh, Byoungho H; Cho, Sang-Won; Ahn, Sung Yeon

2016-02-01

Diabetic ketoacidosis (DKA) is one of the precipitating factors that can evoke a thyroid storm. Thyroid storm may cause cerebral ischemia in Moyamoya disease, which can coexist in patients with Graves' disease. A 16-year-old girl complaining of dizziness and palpitations visited the emergency department and was diagnosed with DKA combined with hyperthyroidism. A thyroid storm occurred 6 h after the start of DKA management. Her Burch and Wartofsky score was 65 points. Right hemiplegia developed during the thyroid storm, and brain magnetic resonance (MR) diffusion-weighted images revealed multiple acute infarcts in both hemispheres. MR angiography showed stenosis of both distal internal carotid arteries and both M1 portions of the middle cerebral arteries, consistent with Moyamoya disease. After acute management for the thyroid storm with methimazole, Lugol solution and hydrocortisone, the patient's neurological symptoms completely resolved within 1 month, and free T4 level normalized within 2 months. Thyroid storm may trigger cerebral ischemia in Moyamoya disease and lead to rapid progression of cerebrovascular occlusive disease. As a simultaneous occurrence of DKA, thyroid storm and cerebrovascular accident in Moyamoya disease highly elevates morbidity and mortality, prompt recognition and management are critical to save the patient's life.

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.

Achalasia and thyroid disease: possible autoimmune connection?

PubMed

Quidute, Ana Rosa P; Freitas, Eduardo Vasconcelos de; Lima, Tadeu Gonçalves de; Feitosa, Ana Márcia Lima; Santos, Joyce Paiva dos; Correia, José Walter

2012-12-01

Many cases have been published showing a co-existence of autoimmune thyroid diseases (AITDs) and other autoimmune diseases. About a quarter of patients with achalasia have a concurrent thyroid disease, most commonly associated with hypothyroidism. Although relatively rare, the association of achalasia and hyperthyroidism requires attention. The physiopathology of Grave's Disease (GD) involves B- and T-mediator lymphocytes, which have an affinity for known thyroid antigens: thyroglobulin, thyroid-peroxidase, and thyrotrophin receptor. Currently, however, the real physiopathogenesis of achalasia continues to be unknown. Some important findings are suggestive of an autoimmune mechanism: significant infiltration of the myoenteric plexus by monocytes, presence of the class II-Human Histocompatibility Complex DQwl antigen and antibodies to myoenteric neurons. The present case reports a patient who, despite testing negative for Chagas' disease, had achalasia, progressed to developing significant wasting and worsening of his quality of life, was later diagnosed with hyperthyroidism. After endoscopic esophageal dilatation and radioiodine ablation of the thyroid gland, there was great improvement in the patient clinical condition.

The role of molecular diagnostic testing in the management of thyroid nodules.

PubMed

Moore, Maureen D; Panjwani, Suraj; Gray, Katherine D; Finnerty, Brendan M; Zarnegar, Rasa; Fahey, Thomas J

2017-06-01

Fine needle aspiration (FNA) with cytologic examination remains the standard of care for investigation of thyroid nodules. However, as many as 30% of FNA samples are cytologically indeterminate for malignancy, which confounds clinical management. To reduce the burden of repeat diagnostic testing and unnecessary surgery, there has been extensive investigation into molecular markers that can be detected on FNA specimens to more accurately stratify a patient's risk of malignancy. Areas covered: In this review, the authors discuss recent evidence and progress in molecular markers used in the diagnosis of thyroid cancer highlighting somatic gene alterations, molecular technologies and microRNA analysis. Expert commentary: The goal of molecular markers is to improve diagnostic accuracy and aid clinicians in the preoperative management of thyroid lesions. Modalities such as direct mutation analysis, mRNA gene expression profiling, next-generation sequencing, and miRNA expression profiling have been explored to improve the diagnostic accuracy of thyroid nodule FNA. Although no perfect test has been discovered, molecular diagnostic testing has revolutionized the management of thyroid nodules.

Sciatica as a presenting feature of thyroid follicular adenocarcinoma in a 79-year-old woman

PubMed Central

Ogbodo, Elisha; Kaliaperumal, Chandrasekaran; Keohane, Catherine; Bermingham, Niamh; Kaar, George

2011-01-01

The authors describe an unusual case of metastatic thyroid follicular adenocarcinoma presenting with sciatica in a 79-year-old woman. The primary thyroid tumour was undiagnosed until this clinical presentation. The patient gave a short history of back pain and right-sided sciatica, which was progressive and nocturnal in nature. Neuroimaging revealed an enhancing intradural mass lesion, which was completely excised through a right L1-L3 hemilaminectomy. Histopathological examination of the excised tissue revealed a follicular thyroid carcinoma. Subsequent metastatic investigation revealed a heterogeneously attenuating mixed solid cystic mass in a retrosternal thyroid gland, with multiple solid pulmonary nodules suggestive of metastatic disease. She opted for palliative radiotherapy for the primary thyroid cancer and made remarkable postoperative improvement. The authors conclude that surgical treatment of solitary metastatic lesion may produce good symptomatic relief irrespective of patient’s age and primary pathology, while emphasising the need for detailed clinical evaluation of patients with ‘red flag’ symptoms. PMID:22674960

Semiquantitative immunohistochemical marker staining and localization in canine thyroid carcinoma and normal thyroid gland.

PubMed

Pessina, P; Castillo, V; Sartore, I; Borrego, J; Meikle, A

2016-09-01

Immunoreactive proteins in follicular cells, fibroblasts and endothelial cells were assessed in canine thyroid carcinomas and healthy thyroid glands. No differences were detected in thyrotropin receptor and thyroglobulin staining between cancer and normal tissues, but expression was higher in follicular cells than in fibroblasts. Fibroblast growth factor-2 staining was more intense in healthy follicular cells than in those of carcinomas. Follicular cells in carcinomas presented two- to three-fold greater staining intensity of thyroid transcription factor-1 and proliferating cell nuclear antigen, respectively, than healthy cells, and a similar trend was found for the latter antigen in fibroblasts. Vascular endothelial growth factor staining was more intense in the endothelial cells of tumours than in those of normal tissues. In conclusion, greater expression of factors related to proliferation and angiogenesis was demonstrated in several cell types within thyroid carcinomas compared to healthy tissues, which may represent mechanisms of tumour progression in this disease. © 2014 John Wiley & Sons Ltd.

Computer-aided system for diagnosing thyroid nodules on ultrasound: A comparison with radiologist-based clinical assessments.

PubMed

Gao, Luying; Liu, Ruyu; Jiang, Yuxin; Song, Wenfeng; Wang, Ying; Liu, Jia; Wang, Juanjuan; Wu, Dongqian; Li, Shuai; Hao, Aimin; Zhang, Bo

2018-04-01

The purpose of this study was to compare the diagnostic efficiency of a thyroid ultrasound computer-aided diagnosis (CAD) system with that of 1 radiologist. This study retrospectively reviewed 342 surgically resected thyroid nodules from July 2013 to December 2013 at our center. The nodules were assessed on typical ultrasound images using the CAD system and reviewed by 1 experienced radiologist. The radiologist stratified the risk of malignancy using the Thyroid Imaging Reporting and Data Systems (TIRADS) and the American Thyroid Association (ATA) guidelines. The radiologist, using TI-RADS and ATA guidelines, performed better than the CAD system (P < .01). The sensitivity of the CAD system was similar to that of an experienced radiologist (P > .05; P < .01; and P > .05). However, we found that the CAD system had lower specificity (P < .01). The sensitivity of a thyroid ultrasound CAD system in differentiating nodules was similar to that of an experienced radiologist. However, the CAD system had lower specificity. © 2017 Wiley Periodicals, Inc.

Primary thyroid tuberculosis: a rare etiology of hypothyroidism and anterior cervical mass mimicking carcinoma.

PubMed

Silva, Bradley Paulino da; Amorim, Erico Gurgel; Pavin, Elizabeth João; Martins, Antonio Santos; Matos, Patrícia Sabino de; Zantut-Wittmann, Denise Engelbrecht

2009-06-01

The involvement of the thyroid by tuberculosis (TB) is rare. Hypothyroidism caused by tissue destruction is an extremely rare report. Our aim was to report a patient with primary thyroid TB emphasizing the importance of diagnosis, despite the rarity of the occurrence. Women, 62 years old, showing extensive cervical mass since four months, referring lack of appetite, weight loss, dysphagia and dysphonia. Laboratorial investigation revealed primary hypothyroidism. Cervical ultrasound: expansive lesion in left thyroid lobe, involving adjacent muscle. Computed tomography scan: 13 cm diameter cervical mass with central necrosis. Fine needle biopsy: hemorrhagic material. total thyroidectomy, left radical neck dissection and protective tracheotomy. The pathological examination showed chronic granulomatous inflammatory process with areas of caseous necrosis and lymph node involvement. The thyroid baciloscopy was positive. Pulmonary disease was absent. The patient was treated with antituberculosis drugs. Thyroid TB is not frequent, and should be considered as differential diagnosis of hypothyroidism and anterior cervical mass.

A rare cause of hyperthyroidism: functioning thyroid metastases.

PubMed

Gardner, Daphne; Ho, Su Chin

2014-10-09

Hyperthyroidism is a common medical problem that is readily treated with antithyroid medications. However, attributing the correct aetiology of hyperthyroidism alters management and outcome. We present a case of a 66-year-old woman with a seemingly common problem of hyperthyroidism associated with a goitre, which was initially attributed to a toxic nodule. However, Tc-99m pertechnetate uptake scan and thyroid-stimulating hormone receptor antibody were negative, inconsistent with a toxic nodule or Grave's disease. Her thyroid function tests proved difficult to control over the next few months. She eventually proceeded to a total thyroidectomy and histology revealed follicular variant papillary thyroid carcinoma. She was started on levothyroxine postoperatively but developed severe hyperthyroidism, revealing the cause of hyperthyroidism to be autonomously functioning thyroid metastases. Although functioning thyroid metastases are very rare, they need to be considered among the differential diagnoses of hyperthyroidism, as there are nuances in management that could alter the eventual outcome. 2014 BMJ Publishing Group Ltd.

Clinical determinants of fluorodeoxyglucose positron emission tomography/computed tomography in differentiated thyroid cancer patients with elevated thyroglobulin and negative (131)iodine whole body scans after (131)iodine therapy.

PubMed

Shamim, Syed Ejaz; Nang, Lee Boon; Shuaib, Ibrahim Lutfi; Muhamad, Nor Asiah

2014-05-01

A cross-sectional prospective study has been conducted on differentiated thyroid cancer (DTC) patients using negative (131)Iodine ((131)I) whole body scans and elevated thyroglobulin (Tg) levels. The main objective of this research was to determine the prevalence of the conversion of differentiated to dedifferentiated thyroid cancer patients during follow up at the Hospital Kuala Lumpur. It has been demonstrated that fluorodeoxyglucose (FDG) uptake is inversely proportional to the iodine concentration and to differentiation of the cells. Thirty-five patients with histologically proven DTC that have undergone total or near total thyroidectomy, and post (131)I radioactive iodine ablation therapy, were selected and prospectively analysed. The patients also had to show at least one negative whole body scan and Tg levels of 10 μg/L and above. The results of the FDG-Positron Emission Tomography/Computed Tomography (PET/CT) were then studied to determine the association and the predictors influencing the outcome by using univariable and multivariable analyses. Out of the thirty-five patients, 60% of them (twenty-one) showed positive results and 40% (fourteen) showed negative. Age, gender, and type of histopathology (HPE) showed significant associations with the positive results of the FDG-PET/CT. The results also showed no correlations observed between the Tg levels and standardised uptake value (SUV)max in the DTC patients with positive disease findings in the FDG-PET/CT. The predictor for this study was age. The prevalence of the conversion of differentiated to dedifferentiated thyroid cancer among patients with negative (131)I and elevated Tg was 60%, with age as the predictor. DTC patients aged 45 year-old and older were seven times more likely to have positive results of FDG-PET/CT imaging.

Clinical Determinants of Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Differentiated Thyroid Cancer Patients with Elevated Thyroglobulin and Negative 131Iodine Whole Body Scans after 131Iodine Therapy

PubMed Central

SHAMIM, Syed Ejaz; NANG, Lee Boon; SHUAIB, Ibrahim Lutfi; MUHAMAD, Nor Asiah

2014-01-01

Background: A cross-sectional prospective study has been conducted on differentiated thyroid cancer (DTC) patients using negative 131Iodine (131I) whole body scans and elevated thyroglobulin (Tg) levels. The main objective of this research was to determine the prevalence of the conversion of differentiated to dedifferentiated thyroid cancer patients during follow up at the Hospital Kuala Lumpur. It has been demonstrated that fluorodeoxyglucose (FDG) uptake is inversely proportional to the iodine concentration and to differentiation of the cells. Methods: Thirty-five patients with histologically proven DTC that have undergone total or near total thyroidectomy, and post 131I radioactive iodine ablation therapy, were selected and prospectively analysed. The patients also had to show at least one negative whole body scan and Tg levels of 10 μg/L and above. The results of the FDG-Positron Emission Tomography/Computed Tomography (PET/CT) were then studied to determine the association and the predictors influencing the outcome by using univariable and multivariable analyses. Results: Out of the thirty-five patients, 60% of them (twenty-one) showed positive results and 40% (fourteen) showed negative. Age, gender, and type of histopathology (HPE) showed significant associations with the positive results of the FDG-PET/CT. The results also showed no correlations observed between the Tg levels and standardised uptake value (SUV)max in the DTC patients with positive disease findings in the FDG-PET/CT. The predictor for this study was age. Conclusion: The prevalence of the conversion of differentiated to dedifferentiated thyroid cancer among patients with negative 131I and elevated Tg was 60%, with age as the predictor. DTC patients aged 45 year-old and older were seven times more likely to have positive results of FDG-PET/CT imaging. PMID:25246834

Loss of p53 promotes anaplasia and local invasion in ret/PTC1-induced thyroid carcinomas.

PubMed

La Perle, K M; Jhiang, S M; Capen, C C

2000-08-01

Papillary thyroid carcinomas in humans are associated with the ret/PTC oncogene and, following loss of p53 function, may progress to anaplastic carcinomas. Mice with thyroid-targeted expression of ret/PTC1 developed papillary thyroid carcinomas that were minimally invasive and did not metastasize. These mice were crossed with p53-/- mice to investigate whether loss of p53 would promote anaplasia and metastasis of ret/PTC1-induced thyroid tumors. The majority of p53-/- mice died or were euthanized by 17 weeks of age due to the development of thymic lymphomas, soft tissue sarcomas, and testicular teratomas. All ret/PTC1 mice developed thyroid carcinomas, but tumors in p53-/- mice were more anaplastic, larger in diameter, more invasive, and had a higher mitotic index than tumors in p53+/+ and p53+/- mice. Thyroid tumors did not metastasize in any of the experimental p53+/+ and p53+/- mice

Identification of thyroid tumor cell vulnerabilities through a siRNA-based functional screening.

PubMed

Anania, Maria; Gasparri, Fabio; Cetti, Elena; Fraietta, Ivan; Todoerti, Katia; Miranda, Claudia; Mazzoni, Mara; Re, Claudia; Colombo, Riccardo; Ukmar, Giorgio; Camisasca, Stefano; Pagliardini, Sonia; Pierotti, Marco; Neri, Antonino; Galvani, Arturo; Greco, Angela

2015-10-27

The incidence of thyroid carcinoma is rapidly increasing. Although generally associated with good prognosis, a fraction of thyroid tumors are not cured by standard therapy and progress to aggressive forms for which no effective treatments are currently available. In order to identify novel therapeutic targets for thyroid carcinoma, we focused on the discovery of genes essential for sustaining the oncogenic phenotype of thyroid tumor cells, but not required to the same degree for the viability of normal cells (non-oncogene addiction paradigm). We screened a siRNA oligonucleotide library targeting the human druggable genome in thyroid cancer BCPAP cell line in comparison with immortalized normal human thyrocytes (Nthy-ori 3-1). We identified a panel of hit genes whose silencing interferes with the growth of tumor cells, while sparing that of normal ones. Further analysis of three selected hit genes, namely Cyclin D1, MASTL and COPZ1, showed that they represent common vulnerabilities for thyroid tumor cells, as their inhibition reduced the viability of several thyroid tumor cell lines, regardless the histotype or oncogenic lesion. This work identified non-oncogenes essential for sustaining the phenotype of thyroid tumor cells, but not of normal cells, thus suggesting that they might represent promising targets for new therapeutic strategies.

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.

Diffuse large B cell lymphoma of thyroid as a masquerader of anaplastic carcinoma of thyroid, diagnosed by FNA: a case report.

PubMed

Daneshbod, Yahya; Omidvari, Shapour; Daneshbod, Khosrow; Negahban, Shahrzad; Dehghani, Mehdi

2006-10-19

Both thyroid lymphoma and anaplastic carcinoma of thyroid present with rapidly growing mass in eldery patients. Anaplastic carcinoma has high mortality rate and combination of surgery, radiation therapy and multidrug chemotherapy are the best chance for cure. Prognosis of thyroid lymphoma is excellent and chemotherapy for widespred lymphoms and radiotherapy with or without adjuvant chemotherapy for tumors localized to the gland, are the treatment of choice. This article reports a 70 year old man presenting with diffuse neck swelling and hoarseness of few weeks duration. Fine needle aspiration was done and reported as anaplastic carcinoma of thyroid which thyroidectomy was planned. The slides were sent for second opinion. After review, with initial diagnosis of anaplastic carcinoma versus lymphoma, immunocytochemical study was performed. Smears were positive for B cell markers and negative for cytokeratin, so with the impression of diffuse large B cell lymphoma, the patient received two courses of chemotherapy by which the tumor disappeared during two weaks. Despite previous reports, stating easy diagnosis of high-grade thyroid lymphoma on the grounds of cytomorphological features we like to emphasize, overlapping cytologic features of the curable high grade thyroid lymphoma form noncurable anaplastic thyroid carcinoma and usefulness of immunocytochemistry to differentiate these two disease.

Diffuse large B cell lymphoma of thyroid as a masquerader of anaplastic carcinoma of thyroid, diagnosed by FNA: a case report

PubMed Central

Daneshbod, Yahya; Omidvari, Shapour; Daneshbod, Khosrow; Negahban, Shahrzad; Dehghani, Mehdi

2006-01-01

Background Both thyroid lymphoma and anaplastic carcinoma of thyroid present with rapidly growing mass in eldery patients. Anaplastic carcinoma has high mortality rate and combination of surgery, radiation therapy and multidrug chemotherapy are the best chance for cure. Prognosis of thyroid lymphoma is excellent and chemotherapy for widespred lymphoms and radiotherapy with or without adjuvant chemotherapy for tumors localized to the gland, are the treatment of choice. Case report This article reports a 70 year old man presenting with diffuse neck swelling and hoarseness of few weeks duration. Fine needle aspiration was done and reported as anaplastic carcinoma of thyroid which thyroidectomy was planned. The slides were sent for second opinion. After review, with initial diagnosis of anaplastic carcinoma versus lymphoma, immunocytochemical study was performed. Smears were positive for B cell markers and negative for cytokeratin, so with the impression of diffuse large B cell lymphoma, the patient received two courses of chemotherapy by which the tumor disappeared during two weaks. Conclusion Despite previous reports, stating easy diagnosis of high-grade thyroid lymphoma on the grounds of cytomorphological features we like to emphasize, overlapping cytologic features of the curable high grade thyroid lymphoma form noncurable anaplastic thyroid carcinoma and usefulness of immunocytochemistry to differentiate these two disease. PMID:17052355

Methamphetamine Use With Subsequent Thyrotoxicosis/Thyroid Storm, Agranulocytosis, and Modified Total Thyroidectomy: A Case Report.

PubMed

Viswanath, Omar; Menapace, Deanna C; Headley, Don B

2017-01-01

Thyroid storm is a rare, potentially lethal condition involving collapse of the hypothalamic-pituitary-thyroid feedback loop. Thyroid storm carries a significant mortality rate, thus requiring prompt identification and treatment. A 47-year-old woman presented to the emergency department complaining of palpitations, shortness of breath, and emesis for 24 hours after using methamphetamine. Past medical history was significant for untreated hyperthyroidism. Physical examination revealed a prominent, palpable thyroid. The Burch-Wartofsky-Score was 35. Management for thyroid storm included propylthiouracil (PTU), super saturated potassium iodide, intravenous hydrocortisone, and propranolol. However, a rare drug reaction to PTU on day 3 resulted in agranulocytosis. Propylthiouracil was withheld and a modified total thyroidectomy performed on day 8 without complications and the patient discharged on day 10 with levothyroxine. Undertreated hyperthyroidism may predispose patients to catecholamine-induced thyrotoxicosis due to catecholamine hypersensitivity. With known methamphetamine use, methamphetamine toxicity and a methamphetamine-exacerbated thyroid storm need to be included in the differential diagnosis in a patient presenting with signs of thyrotoxicosis. In addition, treating patients with agranulocytosis from PTU with a modified total thyroidectomy using ligation of the vascular supply as the initial surgical step limits release of thyroid hormone into the blood stream during thyroidectomy and decreases the possibility of intra operative thyroid storm.

Human amniotic fluid contaminants alter thyroid hormone signalling and early brain development in Xenopus embryos

NASA Astrophysics Data System (ADS)

Fini, Jean-Baptiste; Mughal, Bilal B.; Le Mével, Sébastien; Leemans, Michelle; Lettmann, Mélodie; Spirhanzlova, Petra; Affaticati, Pierre; Jenett, Arnim; Demeneix, Barbara A.

2017-03-01

Thyroid hormones are essential for normal brain development in vertebrates. In humans, abnormal maternal thyroid hormone levels during early pregnancy are associated with decreased offspring IQ and modified brain structure. As numerous environmental chemicals disrupt thyroid hormone signalling, we questioned whether exposure to ubiquitous chemicals affects thyroid hormone responses during early neurogenesis. We established a mixture of 15 common chemicals at concentrations reported in human amniotic fluid. An in vivo larval reporter (GFP) assay served to determine integrated thyroid hormone transcriptional responses. Dose-dependent effects of short-term (72 h) exposure to single chemicals and the mixture were found. qPCR on dissected brains showed significant changes in thyroid hormone-related genes including receptors, deiodinases and neural differentiation markers. Further, exposure to mixture also modified neural proliferation as well as neuron and oligodendrocyte size. Finally, exposed tadpoles showed behavioural responses with dose-dependent reductions in mobility. In conclusion, exposure to a mixture of ubiquitous chemicals at concentrations found in human amniotic fluid affect thyroid hormone-dependent transcription, gene expression, brain development and behaviour in early embryogenesis. As thyroid hormone signalling is strongly conserved across vertebrates the results suggest that ubiquitous chemical mixtures could be exerting adverse effects on foetal human brain development.

Thyroid Ultrasound Pitfalls: Esophageal Fibrovascular Polyp Mimicking Thyroid Nodule

PubMed Central

Brigante, G.; Madeo, B.

2016-01-01

Background. Ultrasound (US) is the most accurate tool in the diagnosis of thyroid nodules if performed by expert physician. Misdiagnosis due to extrathyroidal lesions mimicking thyroid nodules is reported in literature. We describe the first case of an esophageal fibrovascular polyp misdiagnosed as a thyroid nodule on US examination. Patient Findings. A 54-year-old woman presented to emergency department for headache and underwent carotid Doppler extended to neck ultrasound with incidental finding of a nodule in the posterior side of the left thyroid lobe. A following thyroid US performed by an endocrinologist allowed the characterization of the lesion as an esophageal pathology, considering the extrathyroidal position, the typical peripheral hyperechoic spots and hypoechoic rim, the connection to the esophagus, and the swallowing connected movement. The patient was addressed to further investigations and finally to anterior pharyngotomy with histological diagnosis of esophageal fibrovascular polyp. Summary. Differential diagnosis between thyroid nodules and other neck lesions is important to prevent an unnecessary fine needle aspiration biopsy and to treat the extrathyroidal pathology. In this case, an US performed by an expert endocrinologist allowed detecting an esophageal fibrovascular polyp requiring surgical removal. In conclusion, the possibility of an esophageal pathology, and even fibrovascular polyp, should be considered during US thyroid examination. PMID:27022492

Prolonged duration of response in lenvatinib responders with thyroid cancer.

PubMed

Gianoukakis, Andrew G; Dutcus, Corina E; Batty, Nicolas; Guo, Matthew; Baig, Mahadi

2018-06-01

We present an updated analysis of lenvatinib in radioiodine-refractory differentiated thyroid cancer (RR-DTC) with new duration of response (DOR) data unavailable for the primary analysis. In this randomized, double-blind, multicenter, placebo-controlled phase 3 study, patients ≥18 years old with measurable, pathologically confirmed RR-DTC with independent radiologic confirmation of disease progression within the previous 13 months were randomized 2:1 to oral lenvatinib 24 mg/day or placebo. The main outcome measures for this analysis are DOR and progression-free survival (PFS). The median DOR for all lenvatinib responders (patients with complete or partial responses; objective response rate: 60.2%; 95% confidence interval (CI) 54.2-66.1) was 30.0 months (95% CI 18.4-36.7) and was generally similar across subgroups. DOR was shorter in patients with greater disease burden and with brain and liver metastases. Updated median PFS was longer in the overall lenvatinib group vs placebo (19.4 vs 3.7 months; hazard ratio (HR) 0.24; 99% CI 0.17-0.35; nominal P  < 0.0001). In lenvatinib responders, median PFS was 33.1 months (95% CI 27.8-44.6) vs 7.9 months (95% CI 5.8-10.7) in non-responders. The median DOR of 30.0 months seen with patients who achieved complete or partial responses with lenvatinib (60.2%) demonstrates that lenvatinib responders can have prolonged, durable and clinically meaningful responses. Prolonged PFS (33.1 months) was also observed in these lenvatinib responders. © 2018 The authors.

Obatoclax and LY3009120 Efficiently Overcome Vemurafenib Resistance in Differentiated Thyroid Cancer

PubMed Central

Wei, Wei-Jun; Sun, Zhen-Kui; Shen, Chen-Tian; Song, Hong-Jun; Zhang, Xin-Yun; Qiu, Zhong-Ling; Luo, Quan-Yong

2017-01-01

Although the prognosis of differentiated thyroid cancer (DTC) is relatively good, 30-40% of patients with distant metastases develop resistance to radioactive iodine therapy due to tumor dedifferentiation. For DTC patients harboring BRAFV600E mutation, Vemurafenib, a BRAF kinase inhibitor, has dramatically changed the therapeutic landscape, but side effects and drug resistance often lead to termination of the single agent treatment. In the present study, we showed that either LY3009120 or Obatoclax (GX15-070) efficiently inhibited cell cycle progression and induced massive death of DTC cells. We established that BRAF/CRAF dimerization was an underlying mechanism for Vemurafenib resistance. LY3009120, the newly discovered pan-RAF inhibitor, successfully overcame Vemurafenib resistance and suppressed the growth of DTC cells in vitro and in vivo. We also observed that expression of anti-apoptotic Bcl-2 increased substantially following BRAF inhibitor treatment in Vemurafenib-resistant K1 cells, and both Obatoclax and LY3009120 efficiently induced apoptosis of these resistant cells. Specifically, Obatoclax exerted its anti-cancer activity by inducing loss of mitochondrial membrane potential (ΔΨm), dysfunction of mitochondrial respiration, reduction of cellular glycolysis, autophagy, neutralization of lysosomes, and caspase-related apoptosis. Furthermore, the cancer killing effects of LY3009120 and Obatoclax extended to two more Vemurafenib-resistant DTC cell lines, KTC-1 and BCPAP. Taken together, our results highlighted the potential value of LY3009120 for both Vemurafenib-sensitive and -resistant DTC and provided evidence for the combination therapy using Vemurafenib and Obatoclax for radioiodine-refractory DTC. PMID:28382170

Common variants in the G protein beta3 subunit gene and thyroid disorders in a formerly iodine-deficient population.

PubMed

Völzke, Henry; Bornhorst, Alexa; Rimmbach, Christian; Petersenn, Holger; Geissler, Ingrid; Nauck, Matthias; Wallaschofski, Henri; Kroemer, Heyo K; Rosskopf, Dieter

2009-10-01

Heterotrimeric G proteins are key mediators of signals from membrane receptors-including the thyroid-stimulating hormone (TSH) receptor-to cellular effectors. Gain-of-function mutations in the TSH receptor and the Galpha(S) subunit occur frequently in hyperfunctioning thyroid nodules and differentiated thyroid carcinomas, whereby the T allele of a common polymorphism (825C>T, rs5443) in the G protein beta3 subunit gene (GNB3) is associated with increased G protein-mediated signal transduction and a complex phenotype. The aim of this study was to investigate whether this common polymorphism affects key parameters of thyroid function and morphology and influences the pathogenesis of thyroid diseases in the general population. The population-based cross-sectional Study of Health in Pomerania is a general health survey with focus on thyroid diseases in northeast Germany, a formerly iodine-deficient area. Data from 3428 subjects (1800 men and 1628 women) were analyzed for an association of the GNB3 genotype with TSH, free triiodothyronine and thyroxine levels, urine iodine and thiocyanate excretion, and thyroid ultrasound morphology including thyroid volume, presence of goiter, and thyroid nodules. There was no association between GNB3 genotype status and the functional or morphological thyroid parameters investigated, neither in crude analyses nor upon multivariable analyses including known confounders of thyroid disorders. Based on the data from this large population-based survey, we conclude that the GNB3 825C>T polymorphism does not affect key parameters of thyroid function and morphology in the general population of a formerly iodine-deficient area.

[Diagnostic difficulties in Grave's orbitopathy--case report].

PubMed

Jedrzejowski, Maciej; Grzesiuk, Wiesław; Szwejda, Elzbieta; Bar-Andziak, Ewa

2004-03-01

Graves' orbitopathy is caused by intraorbital inflammatory reaction due to autoimmune thyroid disease. In most cases the diagnosis is based on the coexistence of typical eye signs and hyperthyroidism symptoms. In presented case, the absence of thyroid dysfunction implicated performance of differential diagnosis. Among many available diagnostic tools nuclear magnetic resonance seems to be the most accurate in confirmation of diagnosis of Graves' orbitopathy.

Mechanisms and kinetics of proliferation and fibrosis development in a mouse model of thyrocyte hyperplasia.

PubMed

Ciornei, Radu Tudor; Hong, So-Hee; Fang, Yujiang; Zhu, Ziwen; Braley-Mullen, Helen

2016-01-01

IFN-γ(-/-) NOD.H-2h4 mice develop autoimmune disease with extensive hyperplasia and proliferation of thyroid epithelial cells (TEC H/P) and fibrosis. Splenic T cells from donors with severe TEC H/P transfer TEC H/P to SCID recipients. The goal of this study was to determine what factors control TEC H/P development/progression by examining T cells, markers of apoptosis, senescence and proliferation in thyroids of SCID recipients over time. At 28days, T cell infiltration was maximal, thyrocytes were proliferating, and fibrosis was moderate. At days 60 and 90, thyroids were larger with more fibrosis. T cells, cytokines and thyrocyte proliferation decreased, and cell cycle inhibitor proteins, and anti-apoptotic molecules increased. T cells and thyrocytes had foci of phosphorylated histone protein H2A.X, indicative of cellular senescence, when TEC H/P progressed and thyrocyte proliferation declined. Some thyrocytes were regenerating at day 90, with irregularly shaped empty follicles and ciliated epithelium. Proliferating thyrocytes were thyroid transcription factor (TTF1)-positive, suggesting they derived from epithelial cells and not brachial cleft remnants. Copyright © 2016 Elsevier Inc. All rights reserved.

Hyperfunctioning thyroid nodules in children and adolescents.

PubMed

de Luca, F; Chaussain, J L; Job, J C

1986-01-01

Eight children and adolescents, seven female and one male, aged 7.1 to 15.0 years, referred over a 12-year period for a solitary mass in an otherwise normal thyroid gland, exhibited a hyperfunctioning nodule on thyroid scintiscan. Tracer uptake in the surrounding thyroid tissue was reduced or completely suppressed, but could be restored after TSH stimulation. Only one patient had mild clinical hyperthyroidism with normal T4 but increased T3 serum levels and blunted TSH responsiveness to TRH. A similar hormonal pattern suggestive of subclinical hyperthyroidism was found in three other subjects who were clinically euthyroid. One patient initially euthyroid progressed to subclinical hyperthyroidism two years later. In the whole group a significant negative relationship was found between serum T3 level and TRH-stimulated TSH peak (r = -0.829, p less than 0.02). All the patients underwent selective surgery after a 3-month to 2-year period of follow-up. Microscopic examination was consistent with adenoma in seven patients, while in one case a well-encapsulated papillary adenocarcinoma was found. Though hyperfunctioning nodules are seldom malignant, their surgical removal must be recommended when they become thyrotoxic, exceed 3 cm or show progressive enlargement.

Fra-1 promotes growth and survival in RAS-transformed thyroid cells by controlling cyclin A transcription

PubMed Central

Casalino, Laura; Bakiri, Latifa; Talotta, Francesco; Weitzman, Jonathan B; Fusco, Alfredo; Yaniv, Moshe; Verde, Pasquale

2007-01-01

Fra-1 is frequently overexpressed in epithelial cancers and implicated in invasiveness. We previously showed that Fra-1 plays crucial roles in RAS transformation in rat thyroid cells and mouse fibroblasts. Here, we report a novel role for Fra-1 as a regulator of mitotic progression in RAS-transformed thyroid cells. Fra-1 expression and phosphorylation are regulated during the cell cycle, peaking at G2/M. Knockdown of Fra-1 caused a proliferative block and apoptosis. Although most Fra-1-knockdown cells accumulated in G2, a fraction of cells entering M-phase underwent abortive cell division and exhibited hallmarks of genomic instability (micronuclei, lagging chromosomes and anaphase bridges). Furthermore, we established a link between Fra-1 and the cell-cycle machinery by identifying cyclin A as a novel transcriptional target of Fra-1. During the cell cycle, Fra-1 was recruited to the cyclin A gene (ccna2) promoter, binding to previously unidentified AP-1 sites and the CRE. Fra-1 also induced the expression of JunB, which in turn interacts with the cyclin A promoter. Hence, Fra-1 induction is important in thyroid tumorigenesis, critically regulating cyclin expression and cell-cycle progression. PMID:17347653

Diagnostic value of Tg and TgAb for metastasis following ablation in patients with differentiated thyroid carcinoma coexistent with Hashimoto thyroiditis.

PubMed

Chai, Hong; Zhu, Zhao-Jin; Chen, Ze-Quan; Yu, Yong-Li

2016-08-01

This study was designed to investigate the clinical value of serum thyroglobulin (Tg) and antithyroglobulin antibody (TgAb) measurements and the cutoff value after ablation in differentiated thyroid carcinoma (DTC) complicated by Hashimoto thyroiditis (HT) with metastasis. We measured serum Tg and TgAb levels and evaluated the disease status in 164 cases of DTC coexistent with HT in pathologically confirmed patients after surgery and post-remnant ablation during a 3-year follow-up. All Tg and TgAb levels were assessed by chemiluminescent immunoassay (IMA). Receiver operating characteristic (ROC) curve analysis was used to evaluate the prognostic value of Tg and TgAb for disease metastasis. The relationship between Tg and TgAb was analyzed using the scatter diagram distribution method. We found that the cutoff values of Tg and TgAb were 1.48 µg/L and 45 kIU/L, respectively. The area under the ROC curve (AUC) of Tg and TgAb was 0.907 and 0.650, respectively. In DTC coexistent with HT patients, the optimal cutoff value correlated with metastasis in Tg and TgAb was 1.48 µg/L and 45 kIU/L, respectively.

Hashimoto's encephalopathy : epidemiology, pathogenesis and management.

PubMed

Mocellin, Ramon; Walterfang, Mark; Velakoulis, Dennis

2007-01-01

Hashimoto's encephalopathy is a term used to describe an encephalopathy of presumed autoimmune origin characterised by high titres of antithyroid peroxidase antibodies. In a similar fashion to autoimmune thyroid disease, Hashimoto's encephalopathy is more common in women than in men. It has been reported in paediatric, adult and elderly populations throughout the world. The clinical presentation may involve a relapsing and remitting course and include seizures, stroke-like episodes, cognitive decline, neuropsychiatric symptoms and myoclonus. Thyroid function is usually clinically and biochemically normal.Hashimoto's encephalopathy appears to be a rare disorder, but, as it is responsive to treatment with corticosteroids, it must be considered in cases of 'investigation negative encephalopathies'. Diagnosis is made in the first instance by excluding other toxic, metabolic and infectious causes of encephalopathy with neuroimaging and CSF examination. Neuroimaging findings are often not helpful in clarifying the diagnosis. Common differential diagnoses when these conditions are excluded are Creutzfeldt-Jakob disease, rapidly progressive dementias, and paraneoplastic and nonparaneoplastic limbic encephalitis. In the context of the typical clinical picture, high titres of antithyroid antibodies, in particular antithyroid peroxidase antibodies, are diagnostic. These antibodies, however, can be detected in elevated titres in the healthy general population. Treatment with corticosteroids is almost always successful, although relapse may occur if this treatment is ceased abruptly. Other forms of immunomodulation, such as intravenous immune-globulin and plasma exchange, may also be effective. Despite the link to autoimmune thyroid disease, the aetiology of Hashimoto's encephalopathy is unknown. It is likely that antithyroid antibodies are not pathogenic, but titres can be a marker of treatment response. Pathological findings can suggest an inflammatory process, but features of a severe vasculitis are often absent. The links between the clinical pictures, thyroid disease, auto-antibody pattern and brain pathology await further clarification through research. It may be that Hashimoto's encephalopathy will be subsumed into a group of nonvasculitic autoimmune inflammatory meningoencephalopathies. This group may include disorders such as limbic encephalitis associated with voltage-gated potassium channel antibodies. Some authors have suggested abandoning any link to Hashimoto and renaming the condition 'steroid responsive encephalopathy associated with autoimmune thyroiditis' to better reflect current, if limited, understanding of this condition.

BRAF Inhibitors: Experience in Thyroid Cancer and General Review of Toxicity

PubMed Central

Cabanillas, M.E.; Patel, A.; Danysh, B. P.; Dadu, R.; Kopetz, S.; Falchook, G.

2014-01-01

The U.S. Food and Drug Administration–approved BRAF inhibitors, vemurafenib and dabrafenib, have demonstrated superior efficacy in patients with BRAF-mutant melanomas but have limited efficacy in BRAF-mutant colorectal cancer. Little is known at this time regarding BRAF inhibitors in thyroid cancer. Initial reports in patients with progressive, radioactive iodine–refractory BRAF-mutant papillary thyroid cancer suggest response rates of approximately 30–40%. In this review, we discuss BRAF inhibitors in the context of thyroid cancer, the toxicities associated with BRAF inhibitors, and the suggested management of those toxicities. The management of vemurafenib and dabrafenib toxicities is applicable across all tumor types and may serve as a practical guide to their use. PMID:25467940

Optimized FPGA Implementation of the Thyroid Hormone Secretion Mechanism Using CAD Tools.

PubMed

Alghazo, Jaafar M

2017-02-01

The goal of this paper is to implement the secretion mechanism of the Thyroid Hormone (TH) based on bio-mathematical differential eqs. (DE) on an FPGA chip. Hardware Descriptive Language (HDL) is used to develop a behavioral model of the mechanism derived from the DE. The Thyroid Hormone secretion mechanism is simulated with the interaction of the related stimulating and inhibiting hormones. Synthesis of the simulation is done with the aid of CAD tools and downloaded on a Field Programmable Gate Arrays (FPGAs) Chip. The chip output shows identical behavior to that of the designed algorithm through simulation. It is concluded that the chip mimics the Thyroid Hormone secretion mechanism. The chip, operating in real-time, is computer-independent stand-alone system.

The bioartificial thyroid: a biotechnological perspective in endocrine organ engineering for transplantation replacement.

PubMed

Toni, Roberto; Casa, Claudia Della; Spaletta, Giulia; Marchetti, Giacomo; Mazzoni, Perseo; Bodria, Monica; Ravera, Simone; Dallatana, Davide; Castorina, Sergio; Riccioli, Vincenzo; Castorina, Emilio Giovanni; Antoci, Salvatore; Campanile, Enrico; Raise, Gabriella; Scalise, Gabriella; Rossi, Raffaella; Rossio, Raffaella; Ugolotti, Giorgio; Ugolottio, Giorgio; Martorella, Andrew; Roti, Elio; Rot, Elio; Sgallari, Fiorella; Pinchera, Aldo

2007-01-01

A new concept for ex situ endocrine organ bioengineering is presented, focused on the realization of a human bioartificial thyroid gland. It is based on the theoretical assumption and experimental evidence that symmetries in geometrical coordinates of the thyroid tissue remain invariant with respect to developmental, physiological or pathophysiological transformations occuring in the gland architecture. This topological arrangement is dependent upon physical connections established between cells, cell adhesion molecules and extracellular matrix, leading to the view that the thyroid parenchyma behaves like a deformable "putty", moulded onto an elastic stromal/vascular scaffold (SVS) dictating the final morphology of the gland. In particular, we have raised the idea that the geometry of the SVS per se provides pivotal epigenetic information to address the genetically-programmed, thyrocyte and endothelial/vascular proliferation and differentiation towards a functionally mature gland, making organ form a pre-requirementfor organ function. A number of experimental approaches are explored to obtain a reliable replica of a human thyroid SVS, and an informatic simulation is designed based on fractal growth of the thyroid intraparenchymal arterial tree. Various tissue-compatible and degradable synthetic or biomimetic polymers are discussed to act as a template of the thyroid SVS, onto which to co-seed autologous human thyrocyte (TPC) and endothelial/vascular (EVPC) progenitor cells. Harvest and expansion of both TPC and EVPC in primary culture are considered, with specific attention to the selection of normal thyrocytes growing at a satisfactory rate to colonize the synthetic matrix. In addition, both in vitro and in vivo techniques to authenticate TPC and EVPC lineage differentiation are reviewed, including immunocytochemistry, reverse trascriptase-polymerase chain reaction, flow cytomery and proteomics. Finally, analysis of viability of the thyroid construct following implantation in animal hosts is proposed, with the intent to obtain a bioartificial thyroid gland morphologically and functionally adequate for transplantation. We believe that the biotechnological scenario proposed herein may provide a template to construct other, more complex and clinically-relevant bioartificial endocrine organs ex situ, such as human pancreatic islets and the liver, and perhaps a new approach to brain bioengineering.

Iodide transport: implications for health and disease

PubMed Central

2014-01-01

Disorders of the thyroid gland are among the most common conditions diagnosed and managed by pediatric endocrinologists. Thyroid hormone synthesis depends on normal iodide transport and knowledge of its regulation is fundamental to understand the etiology and management of congenital and acquired thyroid conditions such as hypothyroidism and hyperthyroidism. The ability of the thyroid to concentrate iodine is also widely used as a tool for the diagnosis of thyroid diseases and in the management and follow up of the most common type of endocrine cancers: papillary and follicular thyroid cancer. More recently, the regulation of iodide transport has also been the center of attention to improve the management of poorly differentiated thyroid cancer. Iodine deficiency disorders (goiter, impaired mental development) due to insufficient nutritional intake remain a universal public health problem. Thyroid function can also be influenced by medications that contain iodide or interfere with iodide metabolism such as iodinated contrast agents, povidone, lithium and amiodarone. In addition, some environmental pollutants such as perchlorate, thiocyanate and nitrates may affect iodide transport. Furthermore, nuclear accidents increase the risk of developing thyroid cancer and the therapy used to prevent exposure to these isotopes relies on the ability of the thyroid to concentrate iodine. The array of disorders involving iodide transport affect individuals during the whole life span and, if undiagnosed or improperly managed, they can have a profound impact on growth, metabolism, cognitive development and quality of life. PMID:25009573

ErbB2 and EGFR are downmodulated during the differentiation of 3T3-L1 preadipocytes.

PubMed

Pagano, Eleonora; Calvo, Juan Carlos

2003-10-15

The expression of receptors belonging to the epidermal growth factor receptor subfamily has been largely studied these last years in epithelial cells mainly as involved in cell proliferation and malignant progression. Although much work has focused on the role of these growth factor receptors in the differentiation of a variety of tissues, there is little information in regards to normal stromal cells. We investigated erbB2 expression in the murine fibroblast cell line Swiss 3T3L1, which naturally or hormonally induced undergoes adipocyte differentiation. We found that the Swiss 3T3-L1 fibroblasts express erbB2, in addition to EGFR, and in a quantity comparable to or even greater than the breast cancer cell line T47D. Proliferating cells increased erbB2 and EGFR levels when reaching confluence up to 4- and 10-fold, respectively. This expression showed a significant decrease when growth-arrested cells were stimulated to differentiate with dexamethasone and isobutyl-methylxanthine. Differentiated cells presented a decreased expression of both erbB2 and EGFR regardless of whether the cells were hormonally or spontaneously differentiated. EGF stimulation of serum-starved cells increased erbB2 tyrosine phosphorylation and retarded erbB2 migration in SDS-PAGE, suggesting receptor association and activation. Heregulin-alpha1 and -beta1, two EGF related factors, had no effect on erbB2 or EGFR phosphorylation. Although 3T3-L1 cells expressed heregulin, its specific receptors, erbB3 and erbB4, were not found. This is the first time in which erbB2 is reported to be expressed in an adipocytic cell line which does not depend on non EGF family growth factors (thyroid hormone, growth hormone, etc.) to accomplish adipose differentiation. Since erbB2 and EGFR expression were downmodulated as differentiation progressed it is conceivable that a mechanism of switching from a mitogenic to a differentiating signaling pathway may be involved, through regulation of the expression of these growth factor receptors. Copyright 2003 Wiley-Liss, Inc.

CHIP promotes thyroid cancer proliferation via activation of the MAPK and AKT pathways.

PubMed

Zhang, Li; Liu, Lianyong; He, Xiaohua; Shen, Yunling; Liu, Xuerong; Wei, Jing; Yu, Fang; Tian, Jianqing

2016-08-26

The carboxyl terminus of Hsp70-interacting protein (CHIP) is a U box-type ubiquitin ligase that plays crucial roles in various biological processes, including tumor progression. To date, the functional mechanism of CHIP in thyroid cancer remains unknown. Here, we obtained evidence of upregulation of CHIP in thyroid cancer tissues and cell lines. CHIP overexpression markedly enhanced thyroid cancer cell viability and colony formation in vitro and accelerated tumor growth in vivo. Conversely, CHIP knockdown impaired cell proliferation and tumor growth. Notably, CHIP promoted cell growth through activation of MAPK and AKT pathways, subsequently decreasing p27 and increasing cyclin D1 and p-FOXO3a expression. Our findings collectively indicate that CHIP functions as an oncogene in thyroid cancer, and is therefore a potential therapeutic target for this disease. Copyright © 2016 Elsevier Inc. All rights reserved.

Autoimmune mechanisms in pernicious anaemia & thyroid disease.

PubMed

Osborne, David; Sobczyńska-Malefora, Agata

2015-09-01

Pernicious anaemia (PA) and some types of thyroid disease result from autoimmune processes. The autoimmune mechanisms in these conditions have not been fully elucidated. This review discusses the autoimmune mechanisms involved in PA and how these affect diagnosis and disease progression. In addition to gastric antibodies, antibodies to the vitamin B12 binding protein transcobalamin which can result in high serum B12 levels are also addressed with regard to how they affect clinical practice. The role of autoimmune susceptibility is investigated by comparing PA to one of its most common comorbidities, autoimmune thyroid disease (AITD). Thyroid disease (although not exclusively AITD) and B12 deficiency are both also implicated in the pathology of hyperhomocysteinemia, an elevated homocysteine in plasma. Since hyperhomocysteinemia is a risk factor for cardiovascular occlusive disease, this review also addresses how thyroid disease in particular leads to changes in homocysteine levels. Copyright © 2015 Elsevier B.V. All rights reserved.

Transcriptomic and phenotypic profiling in developing zebrafish exposed to thyroid hormone receptor agonists

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

Haggard, Derik E.; Noyes, Pamela D.; Waters, Katrina M.

There is a need to develop novel, high-throughput screening and prioritization methods to identify chemicals with adverse estrogen, androgen, and thyroid activity to protect human health and the environment and is of interest to the Endocrine Disruptor Screening Program. The current aim is to explore the utility of zebrafish as a testing paradigm to classify endocrine activity using phenotypically anchored transcriptome profiling. Transcriptome analysis was conducted on embryos exposed to 25 estrogen-, androgen-, or thyroid-active chemicals at a concentration that elicited adverse malformations or mortality at 120 hours post-fertilization in 80% of the animals exposed. Analysis of the top 1000more » significant differentially expressed transcripts across all treatments identified a unique transcriptional and phenotypic profile for thyroid hormone receptor agonists, which can be used as a biomarker screen for potential thyroid hormone agonists.« less

Diffuse lipomatosis of the thyroid gland with papillary microcarcinoma: Report of a rare entity.

PubMed

Nandyala, Hariharanadha Sarma; Madapuram, Srinivasulu; Yadav, Megha; Katamala, Sudheer Kumar

2015-01-01

Presence of lobules of adipose tissue either focally or diffusely is very rare in the thyroid gland. Fat accumulation can be macroscopic or microscopic. Focal infiltrates of fat have been reported in conditions such as adenolipoma, intrathyroid lipoma, and encapsulated papillary carcinoma. Diffuse lipomatosis has been reported in conditions such as amyloid goitre, heterotopic fat nests, thyrolipoma and liposarcoma. The exact mechanism of fat accumulation is not known although there are many theories postulated. Investigations such as ultrasound, computed tomography scan, and magnetic resonance imaging can detect the presence of macroscopic fat in the thyroid gland. Accurate diagnosis of the type of fat accumulation is necessary because tumorous and nontumorous conditions fall into the differential diagnosis. Only nine cases of papillary carcinoma associated with lipomatosis of thyroid are reported so far. We report possibly the first case of diffuse lipomatosis of the thyroid gland with a focus of papillary microcarcinoma.

New approaches to thyroid hormones and purinergic signaling.

PubMed

Silveira, Gabriel Fernandes; Buffon, Andréia; Bruno, Alessandra Nejar

2013-01-01

It is known that thyroid hormones influence a wide variety of events at the molecular, cellular, and functional levels. Thyroid hormones (TH) play pivotal roles in growth, cell proliferation, differentiation, apoptosis, development, and metabolic homeostasis via thyroid hormone receptors (TRs) by controlling the expression of TR target genes. Most of these effects result in pathological and physiological events and are already well described in the literature. Even so, many recent studies have been devoted to bringing new information on problems in controlling the synthesis and release of these hormones and to elucidating mechanisms of the action of these hormones unconventionally. The purinergic system was recently linked to thyroid diseases, including enzymes, receptors, and enzyme products related to neurotransmitter release, nociception, behavior, and other vascular systems. Thus, throughout this text we intend to relate the relationship between the TH in physiological and pathological situations with the purinergic signaling.

New Approaches to Thyroid Hormones and Purinergic Signaling

PubMed Central

Silveira, Gabriel Fernandes; Buffon, Andréia; Bruno, Alessandra Nejar

2013-01-01

It is known that thyroid hormones influence a wide variety of events at the molecular, cellular, and functional levels. Thyroid hormones (TH) play pivotal roles in growth, cell proliferation, differentiation, apoptosis, development, and metabolic homeostasis via thyroid hormone receptors (TRs) by controlling the expression of TR target genes. Most of these effects result in pathological and physiological events and are already well described in the literature. Even so, many recent studies have been devoted to bringing new information on problems in controlling the synthesis and release of these hormones and to elucidating mechanisms of the action of these hormones unconventionally. The purinergic system was recently linked to thyroid diseases, including enzymes, receptors, and enzyme products related to neurotransmitter release, nociception, behavior, and other vascular systems. Thus, throughout this text we intend to relate the relationship between the TH in physiological and pathological situations with the purinergic signaling. PMID:23956925

[A case of mixed connective tissue disease positive for proteinase 3 antineutrophil cytoplasmic antibody in a patient with slowly progressive type 1 diabetes mellitus and chronic thyroiditis].

PubMed

Michitsuji, Tohru; Horai, Yoshiro; Sako, Ayaka; Asano, Taro; Iwanaga, Nozomi; Izumi, Yasumori; Kawakami, Atsushi

2017-01-01

  A female in her sixties with slowly progressive type 1 diabetes mellitus (SPT1DM) and chronic thyroiditis was referred to our rheumatology department with swelling in her fingers. A prominent atherosclerotic lesion was revealed upon brain magnetic resonance imaging, and she was found to have mixed connective tissue disease (MCTD) positive for proteinase 3 (PR3)-antineutrophil cytoplasmic antibody (ANCA). This rare case of MCTD accompanying SPT1DM and PR3-ANCA suggested that a synergy between MCTD and PR3-ANCA triggers atherosclerosis.

Lipid peroxidation and antioxidants status in human malignant and non-malignant thyroid tumours.

PubMed

Stanley, J A; Neelamohan, R; Suthagar, E; Vengatesh, G; Jayakumar, J; Chandrasekaran, M; Banu, S K; Aruldhas, M M

2016-06-01

Thyroid epithelial cells produce moderate amounts of reactive oxygen species that are physiologically required for thyroid hormone synthesis. Nevertheless, when they are produced in excessive amounts, they may become toxic. The present study is aimed to compare the lipid peroxidation (LPO), antioxidant enzymes - superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and non-protein thiols (reduced glutathione (GSH)) in human thyroid tissues with malignant and non-malignant disorders. The study used human thyroid tissues and blood samples from 157 women (147 diseased and 10 normal). Thyroid hormones, oxidative stress markers and antioxidants were estimated by standard methods. LPO significantly increased in most of the papillary thyroid carcinoma (PTC: 82.9%) and follicular thyroid adenoma (FTA: 72.9%) tissues, whilst in a majority of nodular goitre (69.2%) and Hashimoto's thyroiditis (HT: 73.7%) thyroid tissues, it remained unaltered. GSH increased in PTC (55.3%), remained unaltered in FTA (97.3%) and all other goiter samples studied. SOD increased in PTC (51.1%) and all other malignant thyroid tissues studied. CAT remained unaltered in PTC (95.7%), FTA (97.3%) and all other non-malignant samples (HT, MNG, TMNG) studied. GPx increased in PTC (63.8%), all other malignant thyroid tissues and remained unaltered in many of the FTA (91.9%) tissues and all other non-malignant samples (HT, MNG, TMNG) studied. In the case of non-malignant thyroid tumours, the oxidant-antioxidant balance was undisturbed, whilst in malignant tumours the balance was altered, and the change in r value observed in the LPO and SOD pairs between normal and PTC tissues and also in many pairs with multi-nodular goitre (MNG)/toxic MNG tissues may be used as a marker to differentiate/detect different malignant/non-malignant thyroid tumours. © The Author(s) 2015.

Role of Nuclear Medicine in the Diagnosis of Benign Thyroid Diseases.

PubMed

Garberoglio, Sara; Testori, Ornella

2016-01-01

A deep understanding of thyroid pathophysiology is the basis for diagnosing and treating benign thyroid diseases with radioactive materials, known as radiopharmaceuticals, which are introduced into the body by injection or orally. After the radiotracer administration, the patient becomes the emitting source, and several devices have been studied to detect and capture these emissions (gamma or beta-negative) and transform them into photons, parametric images, numbers and molecular information. Thyroid scintigraphy is the only technique that allows the assessment of thyroid regional function and, therefore, the detection of areas of autonomously functioning thyroid nodules. Scintigraphy visualizes the distribution of active thyroid tissue and displays the differential accumulation of radionuclides in the investigated cells, thus providing a functional map. Moreover, this technique is a fundamental tool in the clinical and surgical management of thyroid diseases, including: single thyroid nodules with a suppressed thyroid-stimulating hormone level, for which fine-needle aspiration biopsy (FNAB) is used to identify hot nodules; multinodular goiters, especially larger ones, to identify cold or indeterminate areas requiring FNAB and hot areas that do not need cytologic evaluation, and to evaluate mediastinal extension; the diagnosis of ectopic thyroid tissue; subclinical hyperthyroidism to identify occult hyperfunctioning tissue; follicular lesions to identify a functioning cellular adenoma that could be benign, although such nodules are mostly cold on scintigraphy; to distinguish low-uptake from high-uptake thyrotoxicosis, and to determine eligibility for radioiodine therapy. © 2016 S. Karger AG, Basel.

Clinical Characteristics of Patients With Renal Cell Carcinoma and Metastasis to the Thyroid Gland.

PubMed

Jackson, Gregory; Fino, Nora; Bitting, Rhonda L

2017-01-01

Renal cell carcinoma (RCC) is the most common malignancy to metastasize to the thyroid gland. The aims of this study are as follows: (1) to analyze the clinical characteristics of patients with thyroid involvement of RCC and (2) in patients with RCC thyroid metastasis, to determine whether RCC metastasis to glandular organs only portends a better prognosis compared with other patterns of RCC metastasis. Patients from Wake Forest Baptist Medical Center (WFBMC) diagnosed with thyroid metastasis from RCC were identified and medical records retrospectively examined. A systematic review of the literature for cases of RCC involving the thyroid gland was also performed. The clinical characteristics of the institutional cohort and the cases from the literature review were compared. Descriptive statistical analysis was performed, and overall survival (OS) was summarized using Kaplan-Meier methods. The median OS for the WFBMC cohort was 56.4 months. In the literature review cohort, OS of patients with RCC thyroid metastasis was 213.6 months, and there was no statistically significant survival difference based on the site of metastasis. Median survival after thyroid metastasis from RCC for the WFBMC and literature cohort was 21.6 and 45.6 months, respectively. Metastatic RCC should be included in the differential of a new thyroid mass. Treatment directed at the thyroid metastasis results in prolonged survival in some cases. Further analysis into the genomic differences and mechanisms of thyroid metastasis is warranted.

Molecular pathogenesis and mechanisms of thyroid cancer

PubMed Central

Xing, Mingzhao

2013-01-01

Thyroid cancer is a common endocrine malignancy. There has been exciting progress in understanding its molecular pathogenesis in recent years, as best exemplified by the elucidation of the fundamental role of several major signalling pathways and related molecular derangements. Central to these mechanisms are the genetic and epigenetic alterations in these pathways, such as mutation, gene copy-number gain and aberrant gene methylation. Many of these molecular alterations represent novel diagnostic and prognostic molecular markers and therapeutic targets for thyroid cancer, which provide unprecedented opportunities for further research and clinical development of novel treatment strategies for this cancer. PMID:23429735

Comparison of 800 and 3700 MBq iodine-131 for the postoperative ablation of thyroid remnant in patients with low-risk differentiated thyroid cancer.

PubMed

Caglar, Meltem; Bozkurt, Fani M; Akca, Ceren Kapulu; Vargol, Sezen Elhan; Bayraktar, Miyase; Ugur, Omer; Karaağaoğlu, Ergun

2012-03-01

The initial treatment of differentiated thyroid cancer is thyroidectomy, followed by remnant ablation with iodine-131 (I-131) in some patients. However, controversy exists concerning the appropriate radioiodine dose. The aim of the study is to compare the success rate of low and high activities of I-131 for postoperative remnant ablation. A total of 108 nonmetastatic low-risk patients (mean age: 46, 85% women) with papillary and follicular carcinoma had I-131 ablation for the postoperative thyroid remnant. Fifty-three patients received a low dose (L) (800 MBq) and 55 patients received a high dose (H) (3700 MBq) of I-131. After total thyroidectomy, thyroid bed I-131 uptake (RAIU) and neck ultrasonography (USG) were performed to determine the remnant volume and the iodine avidity, which were used to calculate the dose delivered to the remnant tissue. The success rate of I-131 ablation was assessed with four different criteria based on serum thyroglobulin (Tg) and USG with and without the utilization of I-131 diagnostic whole-body scintigraphy (DxWBS). Ablation was considered to be successful if patients fulfilled all of the following criteria. (a) Strict criteria based on three tests: (i) USG negative, (ii) no tracer uptake or less than twice the background activity in the thyroid bed on DxWBS and/or up to 0.2% RAIU, and (iii) Tg < 0.2 ng/ml; (b) lax criteria based on three tests: (i) USG negative, (ii) no tracer uptake or less than twice the background activity in the thyroid bed on DxWBS and/or ≤ 0.2% RAIU, and (iii) Tg < 2 ng/ml; (c) strict criteria based on two tests: (i) USG negative and (ii) Tg < 0.2 ng/ml; (d) lax criteria based on two test: (i) USG negative and (ii) Tg < 2 ng/ml. When three tests were used to define successful ablation, in group L, 32 out of 53 (60%) and 43 out of 53 (81%) patients were successfully treated versus 35 out of 55 (64%) and 42 out of 55 (76%) for group H on the basis of strict and lax criteria, respectively (P=NS). The differences were not statistically significant between the two groups when only two tests were used to define ablation success (62 vs. 69% with strict and 89 vs. 87% with lax criteria, respectively). Our findings suggest that remnant thyroid tissue in patients with low-risk, well-differentiated thyroid cancer after total thyroidectomy can be ablated with 800 MBq of I-131. The success rate is not different from that obtained with 3700 MBq I-131.

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.

Thyroid cancer characteristics in the population surrounding Three Mile Island.

PubMed

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

2012-06-01

To determine differences in disease characteristics between the thyroid cancer populations in the area around the Three Mile Island (TMI) nuclear power plant and the rest of the state of Pennsylvania. Retrospective cross-sectional study. Data from the Pennsylvania Cancer Registry from 1985 to 2008 were reviewed and information regarding age at diagnosis, sex, race, residential status, county of residence, thyroid pathology, thyroid surgery, and staging was recorded. Dauphin, Lancaster, and York counties were defined as the TMI area. Records of 26,357 thyroid cancer patients were reviewed, with 2,611 patients within the TMI area. A higher proportion of papillary thyroid cancer (P < .001) and lower proportion of follicular thyroid cancer (P < .001) were noted in the TMI area population. Thyroid cancer cases from the TMI area were found to be more likely to be diagnosed before the age of 65 years (P < .001), be Pennsylvania born (P < .001), be well differentiated (P < .001), be <10 mm in size (P < .001), and be localized without spread (P < .001). Although the TMI area shows a higher incidence of thyroid cancer as compared to the rest of the state, this was not statistically significant. The TMI population showed a higher proportion of papillary thyroid cancer and less aggressive pathology and earlier diagnosis compared to the rest of Pennsylvania. No statistically significant difference in thyroid cancer incidence was noted. Overall, the study does not show a clear link with more advanced thyroid cancer and proximity to the TMI nuclear reactors. Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.

Clinical significance of prophylactic central compartment neck dissection in the treatment of clinically node-negative papillary thyroid cancer patients.

PubMed

Gambardella, Claudio; Tartaglia, Ernesto; Nunziata, Anna; Izzo, Graziella; Siciliano, Giuseppe; Cavallo, Fabio; Mauriello, Claudio; Napolitano, Salvatore; Thomas, Guglielmo; Testa, Domenico; Rossetti, Gianluca; Sanguinetti, Alessandro; Avenia, Nicola; Conzo, Giovanni

2016-09-19

Lymph nodal involvement is very common in differentiated thyroid cancer, and in addition, cervical lymph node micrometastases are observed in up to 80 % of papillary thyroid cancers. During the last decades, the role of routine central lymph node dissection (RCLD) in the treatment of papillary thyroid cancer (PTC) has been an object of research, and it is now still controversial. Nevertheless, many scientific societies and referral authors have definitely stated that even if in expert hands, RCLD is not associated to higher morbidity; it should be indicated only in selected cases. In order to better analyze the current role of prophylactic neck dissection in the surgical treatment of papillary thyroid cancers, an analysis of the most recent literature data was performed. Prophylactic or therapeutic lymph node dissection, selective, lateral or central lymph node dissection, modified radical neck dissection, and papillary thyroid cancer were used by the authors as keywords performing a PubMed database research. Literature reviews, PTCs large clinical series and the most recent guidelines of different referral endocrine societies, inhering neck dissection for papillary thyroid cancers, were also specifically evaluated. A higher PTC incidence was nowadays reported in differentiated thyroid cancer (DTC) clinical series. In addition, ultrasound guided fine-needle aspiration citology allowed a more precocious diagnosis in the early phases of disease. The role of prophylactic neck dissection in papillary thyroid cancer management remains controversial especially regarding indications, approach, and surgical extension. Even if morbidity rates seem to be similar to those reported after total thyroidectomy alone, RCLD impact on local recurrence and long-term survival is still a matter of research. Nevertheless, only a selective use in high-risk cases is supported by more and more scientific data. In the last years, higher papillary thyroid cancer incidence and more precocious diagnoses were worldwide reported. Among endocrine and neck surgeons, there is agreement about indications to prophylactic treatment of node-negative "high-risk" patients. A recent trend toward RCLD avoiding radioactive treatment is still debated, but nevertheless, prophylactic dissections in low-risk cases should be avoided. Prospective randomized trials are needed to evaluate the benefits of different approaches and allow to drawn definitive conclusions.

A protocol for a Canadian prospective observational study of decision-making on active surveillance or surgery for low-risk papillary thyroid cancer.

PubMed

Sawka, Anna M; Ghai, Sangeet; Tomlinson, George; Rotstein, Lorne; Gilbert, Ralph; Gullane, Patrick; Pasternak, Jesse; Brown, Dale; de Almeida, John; Irish, Jonathan; Chepeha, Douglas; Higgins, Kevin; Monteiro, Eric; Jones, Jennifer M; Gafni, Amiram; Goldstein, David P

2018-04-12

Low-risk papillary thyroid cancer (PTC) is increasingly being diagnosed throughout the world; yet the mortality risk is low compared with other malignancies. Traditional management includes thyroid surgery, sometimes followed by radioactive iodine and thyroid hormone treatment. Active surveillance (AS) has been proposed as a means to reduce overtreatment of PTC. AS involves close disease follow-up, with the intention to intervene if the disease progresses, or on patient request. This is a multiphase prospective observational study. In the first phase of this study, consenting eligible adults with low-risk PTC, that is, <2 cm in maximal diameter, confined to the thyroid and not immediately adjacent to critical structures in the neck, are provided verbal and written information about PTC disease prognosis following surgery or AS. Questionnaires are administered at baseline and after the disease management decision on AS or surgery is finalised. Patients may choose either option (surgery or AS), and the primary outcome is the frequency with which either disease management option is chosen. Secondary outcomes include: rationale for the decision, role of the patient in decision-making and decision satisfaction. In the second phase of the study, consenting eligible adult patients who completed the first study phase may enrol in respective AS or surgery group follow-up studies. The following outcomes are examined 1 year after enrolment in the follow-up phase: decision regret about disease management choice (primary outcome), psychological distress, disease-specific quality of life, fear of disease progression, body image satisfaction, disease progression, crossover to surgery in the AS group, new chronic thyroid hormone use and healthcare resource utilisation. The University Health Network Research Ethics Board approved this study (ID 15-8942). The results will be published in an open access journal. NCT03271892; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Human herpes simplex viruses in benign and malignant thyroid tumours.

PubMed

Jensen, Kirk; Patel, Aneeta; Larin, Alexander; Hoperia, Victoria; Saji, Motoyasu; Bauer, Andrew; Yim, Kevin; Hemming, Val; Vasko, Vasyl

2010-06-01

To test the hypothesis that herpes viruses may have a role in thyroid neoplasia, we analysed thyroid tissues from patients with benign (44) and malignant (65) lesions for HSV1 and HSV2 DNA. Confirmatory studies included direct sequencing, analysis of viral gene expression, and activation of viral-inducible signalling pathways. Expression of viral entry receptor nectin-1 was examined in human samples and in cancer cell lines. In vitro experiments were performed to explore the molecular mechanisms underlying thyroid cancer cell susceptibility to HSV. HSV DNA was detected in 43/109 (39.4%) examined samples. HSV capsid protein expression correlated with HSV DNA status. HSV-positive tumours were characterized by activation of virus-inducible signalling such as interferon-beta expression and nuclear NFkappaB expression. Lymphocyte infiltration and oncocytic cellular features were common in HSV-positive tumours. HSV1 was detected with the same frequency in benign and malignant thyroid tumours. HSV2 was significantly associated with papillary thyroid cancer and the presence of lymph node metastases. The expression of HSV entry receptor nectin-1 was increased in thyroid tumours compared to normal thyroid tissue and further increased in papillary thyroid cancer. Nectin-1 expression was detected in all examined thyroid cancer cell lines. Nectin-1 expression in cancer cells correlated with their susceptibility to HSV. Inhibition of PI3K/AKT or MAPK/ERK signalling did not affect the level of nectin-1 expression but decreased thyroid cancer cell susceptibility to HSV. These findings showed that HSV is frequently detected in thyroid cancer. During tumour progression, thyroid cells acquire increased susceptibility to HSV due to increased expression of viral entry mediator nectin-1 and activation of mitogenic signalling in cancer cells.

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

Functioning and nonfunctioning thyroid adenomas involve different molecular pathogenetic mechanisms.

PubMed

Tonacchera, M; Vitti, P; Agretti, P; Ceccarini, G; Perri, A; Cavaliere, R; Mazzi, B; Naccarato, A G; Viacava, P; Miccoli, P; Pinchera, A; Chiovato, L

1999-11-01

The molecular biology of follicular cell growth in thyroid nodules is still poorly understood. Because gain-of-function (activating) mutations of the thyroid-stimulating hormone receptor (TShR) and/or Gs alpha genes may confer TSh-independent growth advantage to neoplastic thyroid cells, we searched for somatic mutations of these genes in a series of hyperfunctioning and nonfunctioning follicular thyroid adenomas specifically selected for their homogeneous gross anatomy (single nodule in an otherwise normal thyroid gland). TShR gene mutations were identified by direct sequencing of exons 9 and 10 of the TShR gene in genomic DNA obtained from surgical specimens. Codons 201 and 227 of the Gs alpha gene were also analyzed. At histology, all hyperfunctioning nodules and 13 of 15 nonfunctioning nodules were diagnosed as follicular adenomas. Two nonfunctioning thyroid nodules, although showing a prevalent microfollicular pattern of growth, had histological features indicating malignant transformation (a minimally invasive follicular carcinoma and a focal papillary carcinoma). Activating mutations of the TShR gene were found in 12 of 15 hyperfunctioning follicular thyroid adenomas. In one hyperfunctioning adenoma, which was negative for TShR mutations, a mutation in codon 227 of the Gs alpha gene was identified. At variance with hyperfunctioning thyroid adenomas, no mutation of the TShR or Gs alpha genes was detected in nonfunctioning thyroid nodules. In conclusion, our findings clearly define a different molecular pathogenetic mechanism in hyperfunctioning and nonfunctioning follicular thyroid adenomas. Activation of the cAMP cascade, which leads to proliferation but maintains differentiation of follicular thyroid cells, typically occurs in hyperfunctioning thyroid adenomas. Oncogenes other than the TShR and Gs alpha genes are probably involved in nonfunctioning follicular adenomas.

Thyroglossal duct cyst cancer most likely arises from a thyroid gland remnant.

PubMed

Rossi, Esther D; Martini, Maurizio; Straccia, Patrizia; Cocomazzi, Alessandra; Pennacchia, Ilaria; Revelli, Luca; Rossi, Armando; Lombardi, Celestino Pio; Larocca, Luigi M; Fadda, Guido

2014-07-01

Thyroglossal duct cancer is a rare entity, occurring in 1.5 % of all thyroglossal duct cysts (TDC). A definitive consensus about its neoplastic origin has not been established as two contrasting theories exist, one proposing an origin in extra-thyroid remnants and the other a metastatic localization of a primary thyroid cancer. We compare morphological and molecular characteristics of both thyroglossal and thyroid carcinomas in a case series from our institute. We evaluated histology of 80 TDC. In 12 cases, prior cytological evaluation had been performed by liquid-based cytology (LBC). The BRAF gene was examined for mutations, and the histology of both thyroglossal duct and synchronous thyroid carcinoma was reevaluated. In 9 out of 80 (11 %) TDC cases, a papillary thyroid cancer (PTC) was diagnosed. In five out of nine (56 %) thyroglossal carcinomas, a synchronous thyroid cancer was diagnosed: 3 PTC and 2 follicular variant PTC (FVPC). In five thyroglossal carcinomas, mutated BRAF (V600E) was found, three in PTC and in thyroglossal as well as in the synchronous tumor in the thyroid. All the patients are in a disease-free status and still alive. Our results suggest that the majority of thyroglossal carcinomas most likely develop as a primary malignancy from a thyroid remnant. Neither the presence of V600E BRAF mutations nor that of a well-differentiated thyroid carcinoma changed the outcome or disease-free survival. We suggest that a diagnosis of thyroglossal carcinoma should be followed by a detailed evaluation of the thyroid gland. In the absence of clinical and radiological thyroid alterations, follow-up as for thyroid cancer is the correct management.

An Advantageous Role of Spectral Doppler Sonography in the Evaluation of Thyroid Dysfunction During the Postpartum Period.

PubMed

Gaberšček, Simona; Osolnik, Jasna; Zaletel, Katja; Pirnat, Edvard; Hojker, Sergej

2016-07-01

To evaluate the diagnostic value of spectral Doppler sonography in women with thyroid dysfunction during the first postpartum year. This prospective observational clinical study included 83 consecutive untreated women: 32 with hyperthyroid postpartum thyroiditis, 32 with hypothyroid postpartum thyroiditis, and 19 with Graves disease, which first appeared within 12 months after delivery. Thyrotropin, free thyroid hormones, thyroid peroxidase antibodies, thyroglobulin antibodies, and thyrotropin receptor antibodies were measured. With a 7.5-MHz linear transducer, we measured the thyroid volume and peak systolic velocity (PSV) at the level of intrathyroid arteries. Hyperthyroid postpartum thyroiditis appeared significantly earlier (mean ± SD, 4.4 ± 1.9 months after delivery) than hypothyroid postpartum thyroiditis (6.5 ± 2.1 months) and Graves disease (7.2 ± 2.7 months; P< .001). The thyroid volume in hyperthyroid postpartum thyroiditis (9.7 ± 6.3 mL) was significantly lower than in hypothyroid postpartum thyroiditis (14.7 ± 10.2 mL; P = .030) and Graves disease (19.4 ± 10.2 mL; P< .001). The PSV in hyperthyroid postpartum thyroiditis (9.4 ± 3.4 cm/s) was significantly lower than in hypothyroid postpartum thyroiditis (14.4 ± 3.9 cm/s; P < .001) and Graves disease (19.8 ± 7.0 cm/s; P < .001). With a cutoff level of 15 cm/s, the sensitivity and specificity of the PSV as a predictor of the correct diagnosis in hyperthyroid postpartum women were 94.7% and 96.8%, respectively. A multinomial logistic regression revealed PSV and the time after delivery at which the disorders presented as independent predictors of the differentiation between hyperthyroid postpartum thyroiditis and Graves disease (P = .003; P = .022). Spectral Doppler sonography was shown to be a useful and accurate method for thyroid dysfunction evaluation during the postpartum period.

Hypokalemic Paralysis: A Hidden Card of Several Autoimmune Diseases

PubMed Central

Velarde-Mejía, Yelitza; Gamboa-Cárdenas, Rocío; Ugarte-Gil, Manuel; Asurza, César Pastor

2017-01-01

Acute hypokalemic paralysis is a rare and potentially fatal condition, with few related causes, one of which highlights distal renal tubular acidosis (dRTA). Distal renal tubular acidosis is a rare complication of several autoimmune diseases such as systemic lupus erythematosus, Sjögren’s syndrome, and Hashimoto thyroiditis. We report a case of a lupic patient who presented rapidly progressive quadriparesis in the context of active renal disease. Research revealed severe refractory hypokalemia, metabolic acidosis, and alkaline urine suggestive of dRTA. We diagnosed Sjögren’s syndrome based on sicca symptoms, an abnormal salivary glands’ nuclear scan and the presence of anti-Ro/SSA and anti-La/SSB. In addition, the finding of thyroid peroxidase, thyroglobulin antibodies, and hypothyroidism led us to the diagnosis of Hashimoto thyroiditis. Due to the active renal involvement on the context of systemic lupus erythematosus and Sjögren’s syndrome, the patient received immunosuppression with rituximab, resulting in a progressive and complete improvement. PMID:28839447

Why is the thyroid so prone to autoimmune disease?

PubMed

Saranac, L; Zivanovic, S; Bjelakovic, B; Stamenkovic, H; Novak, M; Kamenov, B

2011-01-01

The thyroid gland plays a major role in the human body; it produces the hormones necessary for appropriate energy levels and an active life. These hormones have a critical impact on early brain development and somatic growth. At the same time, the thyroid is highly vulnerable to autoimmune thyroid diseases (AITDs). They arise due to the complex interplay of genetic, environmental, and endogenous factors, and the specific combination is required to initiate thyroid autoimmunity. When the thyroid cell becomes the target of autoimmunity, it interacts with the immune system and appears to affect disease progression. It can produce different growth factors, adhesion molecules, and a large array of cytokines. Preventable environmental factors, including high iodine intake, selenium deficiency, and pollutants such as tobacco smoke, as well as infectious diseases and certain drugs, have been implicated in the development of AITDs in genetically predisposed individuals. The susceptibility of the thyroid to AITDs may come from the complexity of hormonal synthesis, peculiar oligoelement requirements, and specific capabilities of the thyroid cell's defense system. An improved understanding of this interplay could yield novel treatment pathways, some of which might be as simple as identifying the need to avoid smoking or to control the intake of some nutrients. Copyright © 2011 S. Karger AG, Basel.

Ex vivo imaging of human thyroid pathology using integrated optical coherence tomography and optical coherence microscopy

NASA Astrophysics Data System (ADS)

Zhou, Chao; Wang, Yihong; Aguirre, Aaron D.; Tsai, Tsung-Han; Cohen, David W.; Connolly, James L.; Fujimoto, James G.

2010-01-01

We evaluate the feasibility of optical coherence tomography (OCT) and optical coherence microscopy (OCM) for imaging of benign and malignant thyroid lesions ex vivo using intrinsic optical contrast. 34 thyroid gland specimens are imaged from 17 patients, covering a spectrum of pathology ranging from normal thyroid to benign disease/neoplasms (multinodular colloid goiter, Hashimoto's thyroiditis, and follicular adenoma) and malignant thyroid tumors (papillary carcinoma and medullary carcinoma). Imaging is performed using an integrated OCT and OCM system, with <4 μm axial resolution (OCT and OCM), and 14 μm (OCT) and <2 μm (OCM) transverse resolution. The system allows seamless switching between low and high magnifications in a way similar to traditional microscopy. Good correspondence is observed between optical images and histological sections. Characteristic features that suggest malignant lesions, such as complex papillary architecture, microfollicules, psammomatous calcifications, or replacement of normal follicular architecture with sheets/nests of tumor cells, can be identified from OCT and OCM images and are clearly differentiable from normal or benign thyroid tissues. With further development of needle-based imaging probes, OCT and OCM could be promising techniques to use for the screening of thyroid nodules and to improve the diagnostic specificity of fine needle aspiration evaluation.

Differential expression of glucose transporters in normal and pathologic thyroid tissue.

PubMed

Matsuzu, Kenichi; Segade, Fernando; Matsuzu, Utako; Carter, Aaron; Bowden, Donald W; Perrier, Nancy D

2004-10-01

Malignant cells demonstrate increased glucose uptake and utilization. Immunohistochemical studies have suggested that enhanced glucose uptake in cancer cells may be caused by the overexpression of glucose transporters (GLUTs), in most cases GLUT1 and/or GLUT3. The aim of this study was to examine in detail the expression pattern and levels of GLUT genes in normal and pathologic thyroid tissues and to evaluate the clinical significance of GLUT mRNA levels. One hundred fifty-two surgically resected thyroid tissue samples from 103 patients were evaluated. Samples included: normal thyroid tissue (n = 58), benign thyroid disease (n = 61), and thyroid carcinoma (n = 33). Expression of the GLUT1, GLUT2, GLUT3, GLUT4, and GLUT10 genes were examined by reverse transcription-polymerase chain reaction (RT-PCR) and mRNA levels were quantitated by real-time RT-PCR. All thyroid parenchymal cells expressed GLUT1, GLUT3, GLUT4, and GLUT10. GLUT1 showed increased expression in carcinoma cases (p < 0.0001) and also in comparison with paired normal tissue samples from the same patient (p < 0.0001). Other GLUTs were statistically unchanged in pathologic tissues. These results are consistent with the theory that GLUT1 is upregulated during carcinogenesis and may play a major role in enhanced glucose uptake in thyroid cancer cells.

Veliparib, Capecitabine, and Temozolomide in Patients With Advanced, Metastatic, and Recurrent Neuroendocrine Tumor

ClinicalTrials.gov

2017-09-26

Functional Pancreatic Neuroendocrine Tumor; Malignant Somatostatinoma; Merkel Cell Carcinoma; Metastatic Adrenal Gland Pheochromocytoma; Metastatic Carcinoid Tumor; Multiple Endocrine Neoplasia Type 1; Multiple Endocrine Neoplasia Type 2A; Multiple Endocrine Neoplasia Type 2B; Neuroendocrine Neoplasm; Non-Functional Pancreatic Neuroendocrine Tumor; Pancreatic Glucagonoma; Pancreatic Insulinoma; Recurrent Adrenal Cortex Carcinoma; Recurrent Adrenal Gland Pheochromocytoma; Recurrent Merkel Cell Carcinoma; Somatostatin-Producing Neuroendocrine Tumor; Stage III Adrenal Cortex Carcinoma; Stage III Thyroid Gland Medullary Carcinoma; Stage IIIA Merkel Cell Carcinoma; Stage IIIB Merkel Cell Carcinoma; Stage IV Adrenal Cortex Carcinoma; Stage IV Merkel Cell Carcinoma; Stage IVA Thyroid Gland Medullary Carcinoma; Stage IVB Thyroid Gland Medullary Carcinoma; Stage IVC Thyroid Gland Medullary Carcinoma; Thymic Carcinoid Tumor; VIP-Producing Neuroendocrine Tumor; Well Differentiated Adrenal Cortex Carcinoma; Zollinger Ellison Syndrome

The Natural History of Subclinical Hypothyroidism in the Elderly: The Cardiovascular Health Study

PubMed Central

Somwaru, Lily L.; Rariy, Chevon M.; Arnold, Alice M.

2012-01-01

Context: Studies of long-term outcomes of subclinical hypothyroidism have assessed only baseline thyroid function, despite natural transitions to euthyroidism and overt hypothyroidism over time. Objective: We provide estimates of persistence, resolution, and progression of subclinical hypothyroidism over 4 yr, stratified by baseline TSH, anti-thyroid peroxidase antibody (TPOAb) status, age, and sex. Design, Setting, and Participants: Participants were 3996 U.S. individuals at least 65 yr old enrolled in the Cardiovascular Health Study. Subclinical hypothyroidism was detected at baseline in 459 individuals not taking thyroid medication. Main Outcome Measure: Thyroid function was evaluated at 2 and 4 yr and initiation of thyroid medication annually. Results were stratified by baseline TSH, TPOAb status, age, and sex. Results: Persistence of subclinical hypothyroidism was 56% at 2 and 4 yr. At 2 yr, resolution was more common with a TSH of 4.5–6.9 mU/liter (46 vs. 10% with TSH 7–9.9 mU/liter and 7% with TSH ≥10 mU/liter; P < 0.001) and with TPOAb negativity (48 vs. 15% for positive; P < 0.001). Higher TSH and TPOAb positivity were independently associated with lower likelihood of reversion to euthyroidism (P < 0.05). TSH of 10 mU/liter or higher was independently associated with progression to overt hypothyroidism (P < 0.05). Transitions between euthyroidism and subclinical hypothyroidism were common between 2 and 4 yr. Age and sex did not affect transitions. Conclusions: Subclinical hypothyroidism persists for 4 yr in just over half of older individuals, with high rates of reversion to euthyroidism in individuals with lower TSH concentrations and TPOAb negativity. Future studies should examine the impact of transitions in thyroid status on clinical outcomes. PMID:22438233

Quality-of-Life Priorities in Patients with Thyroid Cancer: A Multinational European Organisation for Research and Treatment of Cancer Phase I Study.

PubMed

Singer, Susanne; Husson, Olga; Tomaszewska, Iwona M; Locati, Laura D; Kiyota, Naomi; Scheidemann-Wesp, Ulrike; Hofmeister, Dirk; Winterbotham, Melanie; Brannan, Christine; Araújo, Cláudia; Gamper, Eva M; Kulis, Dagmara; Rimmele, Harald; Andry, Guy; Licitra, Lisa

2016-11-01

The objectives of this study were to determine quality of life (QoL) issues that are relevant to thyroid cancer patients cross-culturally, and to identify those with highest relevance to them in addition to the more general issues covered by the core European Organisation for Research and Treatment of Cancer QoL questionnaire (EORTC QLQ-C30). A systematic literature search provided a list of potentially relevant QoL issues to supplement the core questionnaire EORTC QLQ-C30, which is widely used in research and in care and addresses QoL issues relevant to all groups of cancer patients. A panel of experts revised this list, and thyroid cancer patients rated the issues regarding their relevance for QoL by selecting the 25 issues that they would include in a thyroid cancer-specific QoL module. The literature search and expert discussion provided a list of 71 QoL issues that was rated by thyroid cancer patients (n = 110) from seven countries. All issues were of high priority to at least some of the patients. The most frequently selected issues were sudden attacks of tiredness, exhaustion, quality of sleep, employment, social support, fear of cancer progression, fear of second operation, difficulties swallowing, and globus sensation. Thyroid cancer patients cross-culturally rate fatigue-related issues as highly important for their QoL, calling for increased efforts to find successful treatments for this problem. Vocational rehabilitation is also highly relevant for them and should therefore be an important aim of multidisciplinary care. The third important area of concern is psychological issues, especially fear of progression and of additional treatments.

Exercise training versus T3 and T4 hormones treatment: The differential benefits of thyroid hormones on the parasympathetic drive of infarcted rats.

PubMed

Teixeira, Rayane Brinck; Zimmer, Alexsandra; de Castro, Alexandre Luz; Carraro, Cristina Campos; Casali, Karina Rabello; Dias, Ingrid Gonçalves Machuca; Godoy, Alessandra Eifler Guerra; Litvin, Isnard Elman; Belló-Klein, Adriane; da Rosa Araujo, Alex Sander

2018-03-01

This study aimed to investigate whether beneficial effects of thyroid hormones are comparable to those provided by the aerobic exercise training, to verify its applicability as a therapeutic alternative to reverse the pathological cardiac remodeling post-infarction. Male rats were divided into SHAM-operated (SHAM), myocardial infarction (MI), MI subjected to exercise training (MIE), and MI who received T3 and T4 treatment (MIH) (n = 8/group). MI, MIE and MIH groups underwent an infarction surgery while SHAM was SHAM-operated. One-week post-surgery, MIE and MIH groups started the exercise training protocol (moderate intensity on treadmill), or the T3 (1.2 μg/100 g/day) and T4 (4.8 μg/100 g/day) hormones treatment by gavage, respectively, meanwhile SHAM and MI had no intervention for 9 weeks. The groups were accompanied until 74 days after surgery, when all animals were anesthetized, left ventricle echocardiography and femoral catheterization were performed, followed by euthanasia and left ventricle collection for morphological, oxidative stress, and intracellular kinases expression analysis. Thyroid hormones treatment was more effective in cardiac dilation and infarction area reduction, while exercise training provided more protection against fibrosis. Thyroid hormones treatment increased the lipoperoxidation and decreased GSHPx activity as compared to MI group, increased the t-Akt2 expression as compared to SHAM group, and increased the vascular parasympathetic drive. Thyroid hormones treatment provided differential benefits on the LV function and autonomic modulation as compared to the exercise training. Nevertheless, the redox unbalance induced by thyroid hormones highlights the importance of more studies targeting the ideal duration of this treatment. Copyright © 2018 Elsevier Inc. All rights reserved.

Weight Changes in Patients with Differentiated Thyroid Carcinoma during Postoperative Long-Term Follow-up under Thyroid Stimulating Hormone Suppression

PubMed Central

Sohn, Seo Young; Joung, Ji Young; Cho, Yoon Young; Park, Sun Mi; Jin, Sang Man; Chung, Jae Hoon

2015-01-01

Background There are limited data about whether patients who receive initial treatment for differentiated thyroid cancer (DTC) gain or lose weight during long-term follow-up under thyroid stimulating hormone (TSH) suppression. This study was aimed to evaluate whether DTC patients under TSH suppression experience long-term weight gain after initial treatment. We also examined the impact of the radioactive iodine ablation therapy (RAIT) preparation method on changes of weight, comparing thyroid hormone withdrawal (THW) and recombinant human TSH (rhTSH). Methods We retrospectively reviewed 700 DTC patients who underwent a total thyroidectomy followed by either RAIT and levothyroxine (T4) replacement or T4 replacement alone. The control group included 350 age-matched patients with benign thyroid nodules followed during same period. Anthropometric data were measured at baseline, 1 to 2 years, and 3 to 4 years after thyroidectomy. Comparisons were made between weight and body mass index (BMI) at baseline and follow-up. Results Significant gains in weight and BMI were observed 3 to 4 years after initial treatment for female DTC but not in male patients. These gains among female DTC patients were also significant compared to age-matched control. Women in the THW group gained a significant amount of weight and BMI compared to baseline, while there was no increase in weight or BMI in the rhTSH group. There were no changes in weight and BMI in men according to RAIT preparation methods. Conclusion Female DTC patients showed significant gains in weight and BMI during long-term follow-up after initial treatment. These changes were seen only in patients who underwent THW for RAIT. PMID:26248858