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Sample records for advanced medullary thyroid

  1. Management of advanced medullary thyroid cancer.

    PubMed

    Hadoux, Julien; Pacini, Furio; Tuttle, R Michael; Schlumberger, Martin

    2016-01-01

    Medullary thyroid cancer arises from calcitonin-producing C-cells and accounts for 3-5% of all thyroid cancers. The discovery of a locally advanced medullary thyroid cancer that is not amenable to surgery or of distant metastases needs careful work-up, including measurement of serum calcitonin and carcinoembryonic antigen (and their doubling times), in addition to comprehensive imaging to determine the extent of the disease, its aggressiveness, and the need for any treatment. In the past, cytotoxic chemotherapy was used for treatment but produced little benefit. For the past 10 years, tyrosine kinase inhibitors targeting vascular endothelial growth factor receptors and RET (rearranged during transfection) have been used when a systemic therapy is indicated for large tumour burden and documented disease progression. Vandetanib and cabozantinib have shown benefits on progression-free survival compared with placebo in this setting, but their toxic effect profiles need thorough clinical management in specialised centres. This Review describes the management and treatment of patients with advanced medullary thyroid cancer with emphasis on current targeted therapies and perspectives to improve patient care. Most treatment responses are transient, emphasising that mechanisms of resistance need to be better understood and that the efficacy of treatment approaches should be improved with combination therapies or other drugs that might be more potent or target other pathways, including immunotherapy. PMID:26608066

  2. Treatment of advanced medullary thyroid cancer.

    PubMed

    Smit, Johannes

    2013-03-14

    Therapy decisions in advanced medullary thyroid carcinoma should be guided by a critical appraisal of the natural disease course (slowly progressive vs. aggressive) and benefits and side effects of therapy. Therapy goals should be distinguished between curative and palliative. Local treatments are mainly palliative and may add to quality of life. The advent of novel systemic therapies opens promising perspectives but its place in the therapeutic arsenal must be further determined. PMID:23514632

  3. Thyroid cancer - medullary carcinoma

    MedlinePlus

    Thyroid - medullary carcinoma; Cancer - thyroid (medullary carcinoma); MTC; Thyroid nodule - medullary ... The cause of medullary carcinoma of the thyroid (MTC) is unknown. ... and adults. Unlike other types of thyroid cancer, MTC is less ...

  4. Medullary carcinoma of thyroid

    MedlinePlus

    Thyroid - medullary carcinoma; Cancer - thyroid (medullary carcinoma); MTC ... The cause of medullary carcinoma of the thyroid (MTC) is unknown. Unlike other types of thyroid cancer, MTC is less likely to be caused by radiation therapy to the neck given ...

  5. Pediatric Medullary Thyroid Carcinoma

    PubMed Central

    Starenki, Dmytro; Park, Jong-In

    2016-01-01

    Medullary thyroid carcinoma (MTC), which originates from thyroid parafollicular C cells, accounts for 3 to 5% of thyroid malignancies. MTC occurs either sporadically or in an inherited autosomal dominant manner. Hereditary MTC occurs as a familial MTC or as a part of multiple endocrine neoplasia (MEN) type 2A and B syndromes. A strong genotype-phenotype correlation has been observed between hereditary MTC and germ-line “gain of function” mutations of the RET proto-oncogene. Most cases of pediatric MTC are hereditary whereas sporadic MTC is rare in children and is usually diagnosed in adults. Therefore, MTC in children is most often diagnosed in the course of a familial genetic investigation. The standard treatment of MTC mainly requires surgery involving total thyroidectomy and central neck node dissection before extrathyroidal extension occurs. To prevent MTC development in hereditary syndromes, prophylactic thyroidectomy is performed in presymptomatic patients. An appropriate age at which the surgery should take place is determined based upon the data from genotyping, serum calcitonin measurements, and ultrasonography. For the treatment of advanced MTC cases, the broad spectrum receptor tyrosine kinase inhibitors vandetanib and cabozantinib, which also inhibit RET, are used although they are not always effective. PMID:27014708

  6. [Medullary thyroid carcinoma].

    PubMed

    Niccoli-Sire, P; Conte-Devolx, B

    2007-10-01

    Medullary thyroid carcinoma (MTC) is developed from thyroid C cells that secrete calcitonin (CT). MTC represents 5-10% of thyroid cancers with a 1-2% incidence in nodular thyroid diseases. Diagnosis is usually made by a solitary nodule often associated to nodal metastasis and confirmed by a high basal CT level which represents its biological marker. MTC may present as a sporadic form and in about 30% of case as a familial form as a part of multiple endocrine neoplasia syndrome, an hereditary dominant inherited disease related to germline mutation of the proto-oncogene RET. Both biological (CT) and genetic (RET) markers allows the optimal diagnosis and treatment of MTC; the former allows screening and early diagnosis of MTC by routinely CT measurements in nodular thyroid diseases that make the adequate and complete surgery required to be performed. The former leads to diagnose familial MTC and to identify at risk subjects in whom early or prophylactic surgery may be performed. Treatment of MTC is based on the complete surgical resection: total thyroidectomy associated to central and laterocervical nodal dissection. For locally advanced or metastatic MTC, complete cervical surgery is required and needs to be associated to other systemic treatments: as chemotherapy is not very efficient, radioimmunotherapy and RET target gene therapy (mainly tyrosine kinase inhibitors) appears as possible valuable therapeutic options for the future. Prognosis of MTC is mainly related to both the stage of the disease and the extend of the initial surgery. Ten-year survival is about 80% when the patients are not surgically cured and reaches 95% when the biological marker CT is normalized after surgery. PMID:17572372

  7. Medullary Thyroid Carcinoma: Imaging.

    PubMed

    Delorme, Stefan; Raue, Friedhelm

    2015-01-01

    Imaging plays an important role in early detection and staging of medullary thyroid carcinoma (MTC) as well as in follow-up to localize early recurrence. MTC is a rare, calcitonin-secreting thyroid malignancy often diagnosed by ultrasound and calcitonin screening as part of the routine workup for any thyroid nodule. If calcitonin is elevated, imaging studies are needed for preoperative staging, which dictates surgical management. This can be done by ultrasound of the neck and abdomen. Computed tomography (CT) or magnetic resonance imaging (MRI) studies for more distant disease are done preoperatively if calcitonin levels are higher than 500 pg/ml. Neither FDG-PET/CT nor F-DOPA-PET/CT are used routinely for preoperative staging but may contribute in doubtful individual cases. Postoperative elevated calcitonin is related to persistence or recurrence of MTC. Imaging studies to localize tumor tissue during postoperative follow-up include ultrasound, CT, MRI as well as PET studies. They should be used wisely, however, since treatment consequences are often limited, and even patients with persistent disease may survive long enough to accumulate significant radiation doses. Imaging studies are also useful for diagnosis of associated components of the hereditary MTC such as pheochromocytoma and primary hyperparathyroidism (pHPT). PMID:26494385

  8. Medullary thyroid cancer.

    PubMed

    Clayman, Gary L; el-Baradie, Tarek S

    2003-02-01

    Medullary thyroid cancer is a rare neoplasm that arises from the parafollicular C cells. It occurs in a sporadic form, or less commonly as a hereditary form, as part of multiple endocrine neoplasia syndromes types 2A and 2B. The RET proto-oncogene is currently the primary factor that is implicated in the hereditary forms of this neoplasm. The knowledge about the genetic makeup of the neoplasm impacts upon management as it allows for screening, early detection, and prophylactic treatment. Surgery is the main modality that offers a cure. This entails a total thyroidectomy and vigilant management and surveillance of the neck. Prognosis of patients with MTC is variable, but the more constant factors that affect it are the stage of disease and the age of the patient. The emerging molecular genetic understanding of this malignancy will provide the foundation for prognostic and therapeutic decision-making in the future. Interdisciplinary management by surgeons, endocrinologists, pathologists, radiotherapists, radiologists, and medical oncologists should be sought. PMID:12803011

  9. Management of hereditary medullary thyroid carcinoma.

    PubMed

    Pappa, Theodora; Alevizaki, Maria

    2016-07-01

    Hereditary medullary thyroid carcinoma (MTC) represents up to one-third of MTC cases and includes multiple endocrine neoplasia syndrome type 2A (and its variant familial MTC) and 2B. The aim of this paper is to provide an overview of the disease focusing on the management of hereditary MTC patients, who have already developed tumor, as well as discuss the recommended approach for asymptomatic family members carrying the same mutation. A PubMed search was performed to review recent literature on diagnosis, genetic testing, and surgical and medical management of hereditary MTC. The wide use of genetic testing for RET mutations has markedly influenced the course of hereditary MTC. Prophylactic thyroidectomy of RET carriers at an early age eliminates the risk of developing MTC later in life. Pre-operative staging is a strong prognostic factor in patients, who have developed MTC. The use of recently approved tyrosine kinase inhibitors (vandetanib, cabozantinib) holds promising results for the treatment of unresectable, locally advanced, and progressive metastatic MTC. Genetic testing of the RET gene is a powerful tool in the diagnosis and prognosis of MTC. Ongoing research is expected to add novel treatment options for patients with advanced, progressive disease. PMID:26839093

  10. Esophageal recurrence of medullary thyroid carcinoma.

    PubMed

    Muñoz de Nova, Jose Luis; Dworzynska, Agnieszka; Lorente-Poch, Leyre; Sancho, Juan Jose; Sitges-Serra, Antonio

    2015-12-01

    Medullary thyroid carcinoma (MTC) metastasizes to the regional lymph nodes and to the lungs, liver and bones. Only one case of recurrence of MTC involving the upper gastrointestinal tract has been reported so far. We describe the case of a 38-year-old woman with MTC, who developed an upper esophageal submucosal recurrence after two previous local recurrences treated surgically and one ethanol injection. After resection of the right lateral esophageal wall, calcitonin dropped by 60% and showed a doubling time >1 year. We cannot rule out the role of deep ethanol injection in the involvement of the cervical esophagus wall. PMID:26645011

  11. Esophageal recurrence of medullary thyroid carcinoma

    PubMed Central

    Dworzynska, Agnieszka; Lorente-Poch, Leyre; Sancho, Juan Jose; Sitges-Serra, Antonio

    2015-01-01

    Medullary thyroid carcinoma (MTC) metastasizes to the regional lymph nodes and to the lungs, liver and bones. Only one case of recurrence of MTC involving the upper gastrointestinal tract has been reported so far. We describe the case of a 38-year-old woman with MTC, who developed an upper esophageal submucosal recurrence after two previous local recurrences treated surgically and one ethanol injection. After resection of the right lateral esophageal wall, calcitonin dropped by 60% and showed a doubling time >1 year. We cannot rule out the role of deep ethanol injection in the involvement of the cervical esophagus wall. PMID:26645011

  12. Hypercalcitoninemia is not Pathognomonic of Medullary Thyroid Carcinoma

    PubMed Central

    Toledo, Sergio PA; Lourenço, Delmar M; Santos, Marcelo Augusto; Tavares, Marcos R; Toledo, Rodrigo A; de Menezes Correia-Deur, Joya Emilie

    2009-01-01

    Hypercalcitoninemia has frequently been reported as a marker for medullary thyroid carcinoma. Currently, calcitonin measurements are mostly useful in the evaluation of tumor size and progression, and as an index of biochemical improvement of medullary thyroid carcinomas. Although measurement of calcitonin is a highly sensitive method for the detection of medullary thyroid carcinoma, it presents a low specificity for this tumor. Several physiologic and pathologic conditions other than medullary thyroid carcinoma have been associated with increased levels of calcitonin. Several cases of thyroid nodules associated with increased values of calcitonin are not medullary thyroid carcinomas, but rather are related to other conditions, such as hypercalcemias, hypergastrinemias, neuroendocrine tumors, renal insufficiency, papillary and follicular thyroid carcinomas, and goiter. Furthermore, prolonged treatment with omeprazole (> 2–4 months), beta-blockers, glucocorticoids and potential secretagogues, have been associated with hypercalcitoninemia. An association between calcitonin levels and chronic auto-immune thyroiditis remains controversial. Patients with calcitonin levels >100 pg/mL have a high risk for medullary thyroid carcinoma (~90%–100%), whereas patients with values from 10 to 100 pg/mL (normal values: <8.5 pg/mL for men, < 5.0 pg/mL for women; immunochemiluminometric assay) have a <25% risk for medullary thyroid carcinoma. In multiple endocrine neoplasia type 2 (MEN2), RET mutation analysis is the gold-standard for the recommendation of total preventive thyroidectomy to relatives at risk of harboring a germline RET mutation (50%). False-positive calcitonin results within MEN2 families have led to incorrect indications of preventive total thyroidectomy to RET mutation negative relatives. In this review, we focus on the differential diagnosis of hypercalcitoninemia, underlining its importance for the avoidance of misdiagnosis of medullary thyroid carcinoma and

  13. Beneficial Effects of the mTOR Inhibitor Everolimus in Patients with Advanced Medullary Thyroid Carcinoma: Subgroup Results of a Phase II Trial

    PubMed Central

    Schneider, T. C.; de Wit, D.; Links, T. P.; van Erp, N. P.; van der Hoeven, J. J. M.; Gelderblom, H.; van Wezel, T.; van Eijk, R.; Morreau, H.; Guchelaar, H. J.; Kapiteijn, E.

    2015-01-01

    Objective. Until recently, advanced medullary thyroid cancer (MTC) had few treatment options except surgery. The mTOR inhibitor everolimus has shown encouraging results in neuroendocrine tumors. As part of a prospective phase II study, we analyzed the safety and efficacy of everolimus in advanced MTC. Methods. Seven patients with per RECIST 1.1 documented advanced MTC were included and received everolimus 10 mg daily. The primary objective was determining treatment efficacy. Secondary endpoints included progression-free survival (PFS), overall survival (OS), toxicity, and pharmacokinetics (PK). Results. Median follow-up duration was 28 weeks (17–147). Five patients (71%) showed SD, of which 4 (57%) showed SD >24 weeks. Median PFS and OS were 33 (95%CI: 8–56) and 30 (95%CI: 15–45) weeks, respectively. Toxicity was predominantly grade 1/2 and included mucositis (43%), fatigue (43%), and hypertriglyceridemia (43%). Four MTCs harbored the somatic RET mutation c.2753T>C, p.Met918Thr. The best clinical response was seen in a MEN2A patient. PK characteristics were consistent with phase I data. One patient exhibited extensive toxicity accompanying elevated everolimus plasma concentrations. Conclusions. This study suggests that everolimus exerts clinically relevant antitumor activity in patients with advanced MTC. Given the high level of clinical benefit and the relatively low toxicity profile, further investigation of everolimus in these patients is warranted. PMID:26294908

  14. Medical Management of Metastatic Medullary Thyroid Cancer

    PubMed Central

    Maxwell, Jessica E.; Sherman, Scott K.; O’Dorisio, Thomas M.; Howe, James R.

    2014-01-01

    Medullary thyroid cancer (MTC) is an aggressive form of thyroid cancer, which occurs in both heritable and sporadic forms. Discovery that mutations in the RET protooncogene predispose to familial cases of this disease has allowed for presymptomatic identification of gene carriers and prophylactic surgery to improve the prognosis of these patients. A significant number of patients with the sporadic type of MTC and even with familial disease, still present with nodal or distant metastases, making surgical cure difficult. Over the past several decades, many different types of therapy for metastatic disease have been attempted, with limited success. Improved understanding of the molecular defects and pathways involved in both familial and sporadic MTC has resulted in new hope for these patients with the development of drugs targeting the specific alterations responsible. This new era of targeted therapy with kinase inhibitors represents a significant step forward from previous trials of chemotherapy, radiotherapy, and hormonal therapy. Although much progress has been made, additional agents and strategies are needed to achieve durable, long-term responses in patients with metastatic MTC. This article reviews the history and results of medical management for metastatic MTC from the early 1970s up until the present day. PMID:24942936

  15. Sporadic Medullary Thyroid Carcinoma: Clinical Data From A University Hospital

    PubMed Central

    Correia-Deur, Joya Emilie M.; Toledo, Rodrigo A.; Imazawa, Alice T.; Lourenço, Delmar M.; Ezabella, Marilza C. L.; Tavares, Marcos R.; Toledo, Sergio P. A.

    2009-01-01

    INTRODUCTION: Medullary thyroid carcinoma may occur in a sporadic (s-medullary thyroid carcinoma, 75%) or in a multiple endocrine neoplasia type 2 form (MEN2, 25%). These clinical forms differ in many ways, as s-medullary thyroid carcinoma cases are RET-negative in the germline and are typically diagnosed later than medullary thyroid carcinoma in MEN2 patients. In this study, a set of cases with s-medullary thyroid carcinoma are documented and explored. PURPOSE: To document the phenotypes observed in s-medullary thyroid carcinoma cases from a university group and to attempt to improve earlier diagnosis of s-medullary thyroid carcinoma. Some procedures for diagnostics are also recommended. METHOD: Patients (n=26) with apparent s-medullary thyroid carcinoma were studied. Their clinical data were reviewed and peripheral blood was collected and screened for RET germline mutations. RESULTS: The average age at diagnosis was 43.9 years (± 10.82 SD) and did not differ between males and females. Calcitonin levels were increased in all cases. Three patients presented values that were 100-fold greater than the normal upper limit. Most (61.54%) had values that were 20-fold below this limit. Carcinoembryonic antigen levels were high in 70.6% of cases. There was no significant association between age at diagnosis, basal calcitonin levels or time of disease onset with thyroid tumor size (0.6–15 cm). Routine thyroid cytology yielded disappointing diagnostic accuracy (46.7%) in this set of cases. After total thyroidectomy associated with extensive cervical lymph node resection, calcitonin values remained lower than 5 pg/mL for at least 12 months in eight of the cases (30.8%). Immunocyto- and histochemistry for calcitonin were positive in all analyzed cases. None of the 26 cases presented germline mutations in the classical hotspots of the RET proto-oncogene. CONCLUSION: Our cases were identified late. The basal calcitonin measurements and immunostaining for calcitonin were

  16. Uptake of I-131 MIBG by medullary thyroid cancer

    SciTech Connect

    Endo, K.; Koizumi, M.; Sakahara, H.; Nakashima, T.; Ohta, H.; Kasagi, K.; Konishi, J.; Miyauchi, A.; Kuma, K.; Torizuka, K.

    1985-05-01

    I-131 MIBG scans are useful for the localization of pheochromocytoma and neuroblastoma with high catecholamine levels. Recently the authors have found that medullary thyroid cancer also showed an uptake of I-131 MIBG in both primary neck tumors and metastatic sites. Up to now scintigraphic studies were performed in 5 patients with medullary thyroid cancer. Scintigraphy was done at 24 and 48 hours after the administration of 0.5 mCi of I-131 MIBG, thyroid uptake of dissociated I-131 being prevented by Lugol's solution. Four out of 5 cases were familial type and uptake of I-131 MIBG was similarly observed in medullary thyroid cancer as well as in pheochromocytoma. Bone metastasis of medullary thyroid cancer was also detected with I-131 MIBG. However, one case of sporadic form was negative with I-131 MIBG, whereas there was a high uptake of Tc(V)-99m dimercaptosuccinic acid: a newly developed radiopharmaceutical for medullary thyroid cancer, visualizing a different uptake mechanism of both reagents (J Nucl Med 25: 323-325, 1984). After adrenalectomy high uptake of I-131 MIBG was still observed in medullary thyroid cancer, in spite of normal catecholamine levels. The tumor to blood ratio was estimated in vivo to be about several hundreds at 24 hours after the administration. These cells are of neural crest origin and the mechanism of uptake of I-131 MIBG may not be related to the catechamine uptake mechanism. This paper concludes that I-131 MIBG is useful not only for the localization but also for the treatment of medullary thyroid cancer, as preliminary performed in pheochromocytoma and neuroblastoma.

  17. Primary thyroid paraganglioma mimicking medullary thyroid carcinoma: A case report

    PubMed Central

    YU, XING; WANG, YONG; WANG, PING; JI, CAI-HONG; MIAO, CHUN-DI; ZHENG, SHU

    2015-01-01

    Primary thyroid paraganglioma (TP) is an uncommon tumor, and in rare cases, this disease tends to mimic medullary thyroid carcinoma (MTC). The present study reports a rare case of primary TP mimicking thyroid carcinoma, accompanied by hyperthyroidism. A 30-year-old female presented with an anterior cervical mass. Pre-operative radiological studies and operative frozen section analysis indicated an atypical MTC. Primary TP was finally diagnosed by pathology and immunohistochemical staining. Laboratory examinations (thyroid hormones tests) and Tc99m emission computed tomography revealed hyperthyroidism. Gene analysis of TP-associated gene mutations was negative. Surgical resection was performed as a curative approach and there is currently no metastasis after 36 months of follow-up. Surgeons must be aware of this disease in order to ensure a correct diagnosis and to prevent them from performing unnecessary procedures. The current study presents a case of primary TP mimicking MTC, discusses the radiographic results and histological characteristics, and provides a review of the associated literature. PMID:26622613

  18. Peptide Receptor Radionuclide Therapy (PRRT) of Medullary and Nonmedullary Thyroid Cancer Using Radiolabeled Somatostatin Analogues.

    PubMed

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

    2016-05-01

    As therapeutic options in advanced medullary and non-iodine avid differentiated (nonmedullary) thyroid cancers are limited and associated with significant toxicity, targeting of somatostatin receptors (SSTRs) for internal radiation therapy provides a promising option. Theranostics (therapy and diagnosis) using radiolabeled somatostatin analogues has proved to be a milestone in the management of SSTR-expressing tumors. Peptide receptor radionuclide therapy using (177)Lu-labeled or (90)Y-labeled somatostatin analogues may have a significant role in the management of medullary and nonmedullary thyroid cancers in those patients where PET/CT with (68)Ga-labeled somatostatin analogues demonstrates significant SSTR expression. PMID:27067502

  19. Use of Vandetanib in Metastatic Medullary Carcinoma of Thyroid in a Pediatric Patient With Multiple Endocrine Neoplasia 2B.

    PubMed

    Narayanan, Vidya K; Ronghe, Milind; MacGregor, Fiona B; Bradshaw, Nicola; Davidson, Rosemarie; Welbury, Richard; Reed, Nicholas; Shaikh, Mohamad G

    2016-03-01

    We describe a child with advanced, metastatic, inoperable medullary carcinoma of thyroid associated with multiple endocrine neoplasia 2B and rearranged during transfection mutation with a positive response to vandetanib treatment. He responded well with a fall in calcitonin levels and a reduction in size of the thyroid malignancy, lymph nodes, and pulmonary metastases. He has been on vandetanib for 4 years with good clinical and biochemical response. Vandetanib has a role in the treatment of patients including children with inoperable locally advanced and metastatic medullary carcinoma of thyroid. More information is needed on its use in children and long-term outcome. PMID:26479990

  20. New drugs for medullary thyroid cancer: new promises?

    PubMed

    Spitzweg, Christine; Morris, John C; Bible, Keith C

    2016-06-01

    Medullary thyroid cancer (MTC) is a rare tumor arising from the calcitonin-producing parafollicular C cells of the thyroid gland, occurring either sporadically or alternatively in a hereditary form based on germline RET mutations in approximately one-third of cases. Historically, patients with advanced, metastasized MTC have had a poor prognosis, partly due to limited response to conventional chemotherapy and radiation therapy. In the past decade, however, considerable progress has been made in identifying key genetic alterations and dysregulated signaling pathways paving the way for the evaluation of a series of multitargeted kinase inhibitors that have started to meaningfully impact clinical practice. Two drugs, vandetanib and cabozantinib, are now approved in the US and EU for use in advanced, progressive MTC, with additional targeted agents also showing promise or awaiting results from clinical trials. However, the potential for toxicities with significant reduction in quality of life and lack of curative outcomes has to be carefully weighed against potential for benefit. Despite significant PFS prolongation observed in randomized clinical trials, most patients even with metastatic disease enjoy indolent courses with slow progression observed over years, wherein watchful waiting is still the preferred strategy. As advanced, progressive MTC is a rare and complex disease, a multidisciplinary approach centered in specialized centers providing interdisciplinary expertise in the individualization of available therapeutic options is preferred. In this review, we summarize current concepts of the molecular pathogenesis of advanced MTC and discuss results from clinical trials of targeted agents and also cytotoxic chemotherapy in the context of clinical implications and future perspectives. PMID:27185870

  1. Pazopanib Hydrochloride in Treating Patients With Advanced Thyroid Cancer

    ClinicalTrials.gov

    2016-08-31

    Recurrent Thyroid Gland Carcinoma; Stage III Differentiated Thyroid Gland Carcinoma; Stage III Thyroid Gland Medullary Carcinoma; Stage IVA Differentiated Thyroid Gland Carcinoma; Stage IVA Thyroid Gland Medullary Carcinoma; Stage IVA Thyroid Gland Undifferentiated (Anaplastic) Carcinoma; Stage IVB Differentiated Thyroid Gland Carcinoma; Stage IVB Thyroid Gland Medullary Carcinoma; Stage IVB Thyroid Gland Undifferentiated (Anaplastic) Carcinoma; Stage IVC Differentiated Thyroid Gland Carcinoma; Stage IVC Thyroid Gland Medullary Carcinoma; Stage IVC Thyroid Gland Undifferentiated (Anaplastic) Carcinoma; Thyroid Gland Undifferentiated (Anaplastic) Carcinoma

  2. Malignant melanoma arising in melanin-producing medullary thyroid carcinoma

    PubMed Central

    Hirokawa, Mitsuyoshi; Miyauchi, Akira; Otsuru, Minoru; Daa, Tsutomu

    2016-01-01

    Introduction We report a case of malignant melanoma arising in medullary thyroid carcinoma that has not yet been described. Presentation of case A 66-year-old woman presented with a mass in her thyroid. The resected mass was black in color, and was composed of a mixture of classic medullary thyroid carcinoma and pleomorphic atypical cells containing melanin pigments. The pleomorphic atypical cells were morphologically consistent with malignant melanoma, and expressed Melan-A, HMB-45, and S-100 protein as determined by immunohistochemistry. Some of these cells were also positive for calcitonin and chromogranin A. Although the malignant melanoma metastasized to the lymph nodes, the patient remained free from local recurrence and distant metastasis and the primary malignant melanoma lesion was not identified for up to 11 years after the thyroidectomy. Discussion 11 melanin-producing MTC cases have been reported to date. In the reported cases, the term “malignant melanoma” was not used, likely because the melanin-containing carcinoma cells were not morphologically consistent with malignant melanoma, but with medullary carcinoma. Conclusion Malignant melanoma arising in MTC may have a favorable prognosis. PMID:26852361

  3. Somatostatin receptors and somatostatin content in medullary thyroid carcinomas

    SciTech Connect

    Reubi, J.C.; Chayvialle, J.A.; Franc, B.; Cohen, R.; Calmettes, C.; Modigliani, E. )

    1991-04-01

    Human medullary thyroid carcinomas from 19 patients were analyzed for their content in somatostatin (SRIF) receptors using receptor autoradiography with a SRIF-28 analogue and the SRIF octapeptide (Tyr3)-SMS 201-995 as iodinated radioligands. Four out of 19 cases were SRIF receptor positive with the SRIF octapeptide radioligand. These cases as well as four additional tumors were also positive with the SRIF-28 radioligand 125I-(Leu8, D-Trp22, Tyr25)-SRIF-28. High affinity binding sites pharmacologically specific for bioactive SRIF analogues, specifically located on tumor tissue, were identified. In some cases the SRIF receptors were distributed in a non-homogeneous pattern, with labelling occurring preferentially in highly differentiated tumor regions. Numerous cases were shown to have a high tumoral SRIF content measured by radioimmunoassay or immunohistochemical technique. However, there was no correlation between SRIF receptor status and tumor levels of endogenous SRIF. No correlation was seen between the clinical outcome or the survival of the patients and their tumoral SRIF receptor content. Whereas some medullary thyroid carcinomas seem to be a target for SRIF, the SRIF function in these tumors remains unclear. SRIF receptors in a group of medullary thyroid carcinomas may be useful morphological marker of these tumors and of potential interest for their in vivo localization.

  4. Putative BRAF activating fusion in a medullary thyroid cancer

    PubMed Central

    Kasaian, Katayoon; Wiseman, Sam M.; Walker, Blair A.; Schein, Jacqueline E.; Hirst, Martin; Moore, Richard A.; Mungall, Andrew J.; Marra, Marco A.; Jones, Steven J.M.

    2016-01-01

    Medullary thyroid cancer (MTC) is a malignancy of the calcitonin-producing parafollicular cells of the thyroid gland. Surgery is the only curative treatment for this cancer. External beam radiation therapy is reserved for adjuvant treatment of MTC with aggressive features. Targeted therapeutics vandetanib and cabozantinib are approved for the treatment of aggressive and metastatic tumors that are not amenable to surgery. The use of these multikinase inhibitors are supported by the observed overactivation of the RET oncoprotein in a large subpopulation of MTCs. However, not all patients carry oncogenic alterations of this kinase. Hence, there is still a need for comprehensive molecular characterization of MTC utilizing whole-genome and transcriptome-sequencing methodologies with the aim of identifying targetable mutations. Here, we describe the genomic profiles of two medullary thyroid cancers and report the presence of a putative oncogenic BRAF fusion in one. Such alterations, previously observed in other malignancies and known targets of available drugs, can benefit patients who currently have no treatment options. PMID:27148585

  5. Putative BRAF activating fusion in a medullary thyroid cancer.

    PubMed

    Kasaian, Katayoon; Wiseman, Sam M; Walker, Blair A; Schein, Jacqueline E; Hirst, Martin; Moore, Richard A; Mungall, Andrew J; Marra, Marco A; Jones, Steven J M

    2016-03-01

    Medullary thyroid cancer (MTC) is a malignancy of the calcitonin-producing parafollicular cells of the thyroid gland. Surgery is the only curative treatment for this cancer. External beam radiation therapy is reserved for adjuvant treatment of MTC with aggressive features. Targeted therapeutics vandetanib and cabozantinib are approved for the treatment of aggressive and metastatic tumors that are not amenable to surgery. The use of these multikinase inhibitors are supported by the observed overactivation of the RET oncoprotein in a large subpopulation of MTCs. However, not all patients carry oncogenic alterations of this kinase. Hence, there is still a need for comprehensive molecular characterization of MTC utilizing whole-genome and transcriptome-sequencing methodologies with the aim of identifying targetable mutations. Here, we describe the genomic profiles of two medullary thyroid cancers and report the presence of a putative oncogenic BRAF fusion in one. Such alterations, previously observed in other malignancies and known targets of available drugs, can benefit patients who currently have no treatment options. PMID:27148585

  6. Revised American Thyroid Association Guidelines for the Management of Medullary Thyroid Carcinoma

    PubMed Central

    Asa, Sylvia L.; Dralle, Henning; Elisei, Rossella; Evans, Douglas B.; Gagel, Robert F.; Lee, Nancy; Machens, Andreas; Moley, Jeffrey F.; Pacini, Furio; Raue, Friedhelm; Frank-Raue, Karin; Robinson, Bruce; Rosenthal, M. Sara; Santoro, Massimo; Schlumberger, Martin; Shah, Manisha; Waguespack, Steven G.

    2015-01-01

    Introduction: The American Thyroid Association appointed a Task Force of experts to revise the original Medullary Thyroid Carcinoma: Management Guidelines of the American Thyroid Association. Methods: The Task Force identified relevant articles using a systematic PubMed search, supplemented with additional published materials, and then created evidence-based recommendations, which were set in categories using criteria adapted from the United States Preventive Services Task Force Agency for Healthcare Research and Quality. The original guidelines provided abundant source material and an excellent organizational structure that served as the basis for the current revised document. Results: The revised guidelines are focused primarily on the diagnosis and treatment of patients with sporadic medullary thyroid carcinoma (MTC) and hereditary MTC. Conclusions: The Task Force developed 67 evidence-based recommendations to assist clinicians in the care of patients with MTC. The Task Force considers the recommendations to represent current, rational, and optimal medical practice. PMID:25810047

  7. FNAC diagnosis of medullary carcinoma thyroid: A report of three cases with review of literature

    PubMed Central

    Mehdi, Ghazala; Maheshwari, Veena; Ansari, Hena A; Sadaf, Lubna; Khan, Mohammad Amanullah

    2010-01-01

    Medullary carcinoma of the thyroid is an unusual neoplasm, which is associated with specific supportive diagnostic markers. Despite this, its cytological diagnosis is often difficult. We report herewith three cases of medullary thyroid carcinoma. The diagnosis was established on fine-needle aspiration cytology. Plasmacytoid cell pattern was observed in two cases and spindle cell pattern in the third case. PMID:21157553

  8. RET mutation and increased angiogenesis in medullary thyroid carcinomas.

    PubMed

    Verrienti, Antonella; Tallini, Giovanni; Colato, Chiara; Boichard, Amélie; Checquolo, Saula; Pecce, Valeria; Sponziello, Marialuisa; Rosignolo, Francesca; de Biase, Dario; Rhoden, Kerry; Casadei, Gian Piero; Russo, Diego; Visani, Michela; Acquaviva, Giorgia; Ferdeghini, Marco; Filetti, Sebastiano; Durante, Cosimo

    2016-08-01

    Advanced medullary thyroid cancers (MTCs) are now being treated with drugs that inhibit receptor tyrosine kinases, many of which involved in angiogenesis. Response rates vary widely, and toxic effects are common, so treatment should be reserved for MTCs likely to be responsive to these drugs. RET mutations are common in MTCs, but it is unclear how they influence the microvascularization of these tumors. We examined 45 MTCs with germ-line or somatic RET mutations (RETmut group) and 34 with wild-type RET (RETwt). Taqman Low-Density Arrays were used to assess proangiogenic gene expression. Immunohistochemistry was used to assess intratumoral, peritumoral and nontumoral expression levels of VEGFR1, R2, R3, PDGFRa, PDGFB and NOTCH3. We also assessed microvessel density (MVD) and lymphatic vessel density (LVD) based on CD31-positive and podoplanin-positive vessel counts, respectively, and vascular pericyte density based on staining for a-smooth muscle actin (a-SMA), a pericyte marker. Compared with RETwt tumors, RETmut tumors exhibited upregulated expression of proangiogenic genes (mRNA and protein), especially VEGFR1, PDGFB and NOTCH3. MVDs and LVDs were similar in the two groups. However, microvessels in RETmut tumors were more likely to be a-SMA positive, indicating enhanced coverage by pericytes, which play key roles in vessel sprouting, maturation and stabilization. These data suggest that angiogenesis in RETmut MTCs may be more intense and complete than that found in RETwt tumors, a feature that might increase their susceptibility to antiangiogenic therapy. Given their increased vascular pericyte density, RETmut MTCs might also benefit from combined or preliminary treatment with PDGF inhibitors. PMID:27402614

  9. Iodine 131 metaiodobenzylguanidine scintigraphy of medullary carcinoma of the thyroid

    SciTech Connect

    Skowsky, W.R.; Wilf, L.H. )

    1991-05-01

    We have presented a case of sporadic medullary carcinoma of the thyroid with documentation of localization of tracer {sup 131}I-MIBG within the primary neoplasm. A review of the nuclear medicine literature of localization techniques for MCT demonstrates that {sup 131}I-MIBG, while an excellent choice for diagnosis of pheochromocytoma and neuroblastoma, produces low yield and unpredictable concentration in other neural crest apudomas, including MCT. A low incidence of true-positive results with {sup 131}I-MIBG uptake and a high incidence of false-negative results make this radiopharmaceutical a suboptimal choice for diagnostic studies, but a potentially promising one as a therapeutic agent.33 references.

  10. Characterisation of thyroid medullary carcinoma TT cell line.

    PubMed

    Zabel, M; Grzeszkowiak, J

    1997-01-01

    TT cell line is the best known stabilized cell line derived from the human medullary thyroid carcinoma. The ultrastructural characteristics of these cells include well developed rough endoplasmic reticulum, a prominent Golgi apparatus and a considerable number of secretory granules. Numerous hormones were immunocytochemically demonstrated in TT cells of which calcitonin and calcitonin gene-related peptide (CGRP) are the products of the same gene but an alternative RNA processing. TT cells were found to produce some other hormones as well, namely ACTH, neurotensin, enkephalin, PTHrP, gastrin-releasing peptide (GRP), serotonin but also functional proteins of the chromogranin group, synaptophysin, NSE, calbindin and tyrosine hydroxylase. Some marker proteins have been detected in the cytosol (CEA) and in the cytoskeleton (alpha-tubulin, cytokeratin). The influence of numerous factors on the secretory activity of these cells has been demonstrated so far, including effects of 1,25-dihydroxycholecalciferol, glucocorticoids, sex steroids, cAMP, gastrin-releasing peptide, sodium butyrate, phorbol esters, ionomycin and forskolin. The investigators performed on the TT cell line demonstrate that this is the most reliable model system for the human parafollicular cells developed so far, in comparison to other cell lines derived from the medullary carcinoma of the thyroid. PMID:9046062

  11. Diarrhoea associated with medullary carcinoma of the thyroid 1

    PubMed Central

    Bernier, J. J.; Rambaud, J. C.; Cattan, D.; Prost, A.

    1969-01-01

    Diarrhoea, which is present in roughly one third of cases of medullary carcinoma of the thyroid, was investigated in five cases. Excessive loss of water and electrolytes in the stools was the major factor. Steatorrhoea was mild or absent, and intestinal absorption of glucose and vitamin B12 was normal; the histological appearance of the small intestinal mucosa was normal or subnormal. Water and sodium diarrhoea seems to be linked to a sometimes considerable increase in the rate of transit through the small intestine and colon, and may be relieved by codeine or codethyline. The frequent increase in the maximum blood sugar level during an oral tolerance test should not be interpreted as evidence of a paradiabetic condition. In fact, the intravenous glucose tolerance test is usually normal and the excessive rise in blood sugar after oral administration seems to be the consequence of the increased rate of transit through the small intestine. The link between the tumour and the disordered motility seems definite in view of certain cases in which removal of the tumour caused the diarrhoea to disappear immediately. Production by the tumour of serotonin or other derivatives of tryptophan or of kallikrein, which activates bradykinin, is rare. With regard to prostaglandins, high concentrations have been observed in the tumours and in the venous blood draining the tumours, but their presence in systemic blood is inconstant. The only hormonal substance, concentration of which seems to be definitely increased in the systemic blood of patients with a medullary carcinoma of the thyroid, is thyrocalcitonin but this hormone does not seem to have any effect on the motor activity of the digestive tract. PMID:5366278

  12. 18F-DOPA PET/CT in Orbital Metastasis From Medullary Thyroid Carcinoma.

    PubMed

    Ruiz, Jean-Baptiste; Orré, Mathieu; Cazeau, Anne-Laure; Henriques de Figueiredo, Bénédicte; Godbert, Yann

    2016-06-01

    A 53-year-old-woman is being followed up for a sporadic medullary thyroid carcinoma that was initially treated surgically. Nine years later, a progressive increase in calcitonin levels along with headaches was observed. An orbital metastasis from medullary thyroid carcinoma was diagnosed by performing an F-DOPA PET/CT. The orbital lesion was treated by an external beam radiation. Four months later, an MRI revealed a global morphological stability and a reduction in calcitonin levels. PMID:27055131

  13. Treatment of advanced thyroid cancer: role of molecularly targeted therapies.

    PubMed

    Covell, Lorinda L; Ganti, Apar Kishor

    2015-09-01

    Advanced thyroid cancer is not amenable to therapy with conventional cytotoxic chemotherapy. However, newer advances in the understanding of the molecular pathogenesis of different subtypes of thyroid cancer have provided new opportunities for the evaluation of molecularly targeted therapies. This has led to multiple clinical trials using various multi-kinase inhibitors and the subsequent US FDA approval of sorafenib for differentiated thyroid cancer and vandetanib and cabozantinib for medullary thyroid carcinoma. This review provides a summary of the current literature for the treatment of advanced thyroid carcinoma and future directions in this disease. PMID:26335853

  14. Negative predictive value of procalcitonin in medullary thyroid carcinoma.

    PubMed

    Lim, Soo Kyung; Guéchot, Jérôme; Vaubourdolle, Michel

    2016-01-01

    Calcitonin (CT), the major biochemical marker in medullary thyroid carcinoma (MTC) is prone to in vitro instability and suffers from scarcity of clinical laboratory platforms. Procalcitonin (PCT), the precursor of CT, free of these shortcomings, has been reported as a potential MTC marker. The aim of this study was to assess the negative predictive value (NPV) of PCT as a first-line marker in MTC. 476 serum samples referred to our laboratory for CT measurements were analyzed for PCT. NPVs of PCT were assessed at 3 cut-offs (0.05, 0.10 and 0.15 ng/mL) and the diagnosis of MTC was based on CT levels. PCT and CT levels were correlated (r=0.7554 for CT levels above 10 pg/mL, n=66). Accepting the CT cut-off based on the upper reference limit the NPV of PCT were 98.1% (0.05 ng/mL), 96.3% (0.10 ng/mL) and 95.4% (0.15 ng/mL) respectively. For a CT cut-off of 100 pg/mL the NPVs of PCT were 100% for all PCT thresholds. Serum PCT has a strong NPV and could be a good candidate for a first-line screening test to exclude MTC in patients with suspicious thyroid nodules or suggestive symptoms. Larger prospective studies are necessary to confirm our results. PMID:26806393

  15. Cytologic aspects of an interesting case of medullary thyroid carcinoma coexisting with Hashimoto's thyroiditis

    PubMed Central

    Patel, Bidish K; Roy, Arun; Badhe, Bhawana A; Siddaraju, Neelaiah

    2016-01-01

    Among primary thyroid neoplasms, papillary thyroid carcinoma (PTC) and primary thyroid lymphoma (PTL) are known to coexist and are pathogenetically linked with Hashimoto's thyroiditis (HT). However, HT occurring in association with medullary thyroid carcinoma (MTC) is rarely documented. We report here an interesting case. A 34-year-old female with a solitary thyroid nodule underwent fine needle aspiration cytology (FNAC) that was interpreted as “MTC with admixed reactive lymphoid cells, derived possibly from a pretracheal lymph node.” Total thyroidectomy specimen showed “MTC with coexisting HT.” At a later stage, a follow-up FNAC from the recurrent thyroid swelling showed features consistent with HT. As an academic exercise, the initial smears on which a diagnosis of MTC was offered were reviewed to look for evidence of coexisting HT that showed scanty and patchy aggregates of reactive lymphoid cells without Hürthle cells. Our case highlights an unusual instance of MTC in concurrence with HT that can create a tricky situation for cytopathologists. PMID:27279687

  16. cabozantinib (COMETRIQ⁰). In medullary thyroid cancer: more harmful than beneficial, as is vandetanib.

    PubMed

    2016-01-01

    Surgery is the mainstay of treatment for medullary thyroid cancer. Cytotoxic chemotherapy is generally ineffective in patients with progressive, inoperable, advanced-stage or metastatic tumours. Vandetanib is also authorised in this setting, but it has more harms than benefits. Cabozantinib, like vandetanib, inhibits several tyrosine kinases involved in angiogenesis. Cabozantinib has been authorised in the European Union for use in this setting. In a randomised, placebo-controlled trial in 330 patients, adding cabozantinib to tailored symptomatic treatment did not prolong survival or improve symptoms, despite a favourable effect on tumour imaging and certain laboratory parameters. On the contrary, cabozantinib appeared to undermine quality of life and aggravate diarrhoea. The known adverse effects of cabozantinib are numerous and often severe: diarrhoea, hand-foot syndrome, hypertension, venous and arterial thrombosis, bleeding and fistulae. Deaths unrelated to tumour progression were more frequent with cabozantinib than with placebo. Cabozantinib carries a risk of multiple pharmacokinetic interactions by interfering with cytochrome P450 isoenzyme CYP3A4 and P-glycoprotein. In animals, cabozantinib is teratogenic and also impairs male and female fertility. Contraception is required for women, and also for the partners of treated men, who must use condoms. These precautions must be maintained for at least 4 months after the end of treatment. In practice, in mid-2015, cabozantinib, like vandetanib, has an unfavourable harm-benefit balance in medullary thyroid cancer. The focus should remain on tailored symptomatic care. PMID:26942253

  17. Results of Surgical Therapy in Patients with Medullary Thyroid Carcinoma.

    PubMed

    Vlad, Mihaela; Zosin, Ioana; Timar, Bogdan; Lazar, Fulger; Vlad, Adrian; Timar, Romulus; Cornianu, Marioara

    2016-08-01

    Medullary thyroid carcinoma (MTC) is a rare form of malignancy, having an intermediate prognosis. Controversies exist regarding the best surgical approach. The aim of the study was to analyze the outcome in a group of patients with MTC, diagnosed and followed up in a single care center. We performed a retrospective analysis of all the patients diagnosed with MTC in the Department of Endocrinology from the County Emergency Hospital Timisoara between 1992 and 2012. The study group included 19 patients, 6 men (31.6 %), mean age 41.2 ± 12.5 years (20-72 years). The preoperative diagnosis was based on the protocol for nodular thyroid disease. Total or near-total thyroidectomy was performed in 10 out of 16 patients who could be operated. Postoperative follow-up included repeated measurements of serum calcitonin and imaging investigations. Nine out of the total of 19 (47.3 %) patients had hereditary forms of MTC. Most of the cases (84.2 %) were submitted to surgery. The median duration of follow-up was 84 months. The pTNM staging indicated that the majority of the patients with hereditary MTC were diagnosed in an earlier stage. Disease remission was achieved in 7 cases (43.8 %). Four patients, all with sporadic forms, died. Survival rates at 1, 5 and 10 years were significantly higher (p = 0.048) in patients with hereditary MTC. An early diagnosis of MTC allows a better surgical approach and an improved survival rate. We support the general recommendation that modified radical neck dissection is not necessary for all the patients with MTC. PMID:27574350

  18. Long-Term Follow-up in Medullary Thyroid Carcinoma.

    PubMed

    Raue, Friedhelm; Frank-Raue, Karin

    2015-01-01

    After surgery, patients with medullary thyroid carcinoma (MTC) should be assessed regarding the presence of residual disease, the localization of metastases, and the identification of progressive disease. Postoperatively, patients with MTC are staged to separate those at low risk from those at high risk of recurrence. The TNM staging system is based on tumor size, extra-thyroidal invasion, nodal metastasis, and distant spread of cancer. In addition, the number of lymph-node metastases, the number of compartments involved, and the postoperative calcitonin (CTN) and carcinoembryonic antigen (CEA) levels should be documented. The postoperative normalization of the serum CTN level is associated with a favorable outcome. When patients have basal serum CTN levels less than 150 pg/ml after a thyroidectomy, any persistent or recurrent disease is nearly always confined to lymph nodes in the neck. When the postoperative serum CTN level exceeds 150 pg/ml, patients should be evaluated with imaging procedures, including computed tomography (CT) of the neck and chest, contrast-enhanced magnetic resonance imaging (MRI) and ultrasound (US) of the liver, bone scintigraphy, MRI of the bone, and positron emission tomography (PET)/CT. One can estimate the growth rate of MTC metastases by quantifying increases in tumor size over time from sequential imaging studies analyzed with response evaluation criteria in solid tumors (RECIST), and by determining the tumor marker doubling time from sequential measures of serum CTN or CEA levels over multiple time points. One of the main challenges remains to find effective adjuvant and palliative options for patients with metastatic disease. Patients with persistent or recurrent MTC localized to the neck following thyroidectomy are candidates for neck operations, depending on the tumor extension. Once metastases appear, the clinician must decide which patients require therapy. This requires a balance between the (often) slow rate of tumor

  19. Hereditary Medullary Thyroid Cancer Genotype-Phenotype Correlation.

    PubMed

    Frank-Raue, Karin; Raue, Friedhelm

    2015-01-01

    During the last two decades, there has been a marked expansion of our knowledge of both the basic and clinical aspects of multiple endocrine neoplasia type 2 (MEN2). There are two clinically distinct types of MEN2 syndrome, termed MEN2A and MEN2B. Within MEN2A, there are four variants: (i) classical MEN2A, represented by the uniform presence of MTC and the less frequent occurrence of pheochromocytoma, or primary hyperparathyroidism, or both; (ii) MEN2A with cutaneous lichen amyloidosis; (iii) MEN2A with Hirschsprung's disease; and (iv) familial medullary thyroid carcinoma (FMTC), i.e., families or individuals with only MTC. MEN2B is associated with MTC, pheochromocytoma, and mucosal neuromas. Hereditary MTC is caused by autosomal dominant gain of function mutations in the RET proto-oncogene. Specific RET mutations may suggest a predilection toward a particular phenotype and clinical course with a strong genotype-phenotype correlation. Based upon these genotype-phenotype correlations, RET mutations are now stratified into three risk levels, i.e., highest, high, and moderate risk, based on the penetrance and aggressiveness of the MTC. Children in the highest risk category should undergo thyroidectomy in their first year of life, and perhaps even in their first months of life. Children in the high-risk category should have ultrasound of the neck and calcitonin (CTN) measurement performed prior to thyroidectomy. Thyroidectomy should typically be performed at the age of 5 or earlier, depending on the presence of elevated serum CTN levels. However, heterogeneity in disease expression and progression within these groups varies considerably. To personalize disease management, the decision regarding the age of prophylactic thyroidectomy is no longer based upon genotype alone but is currently driven by additional clinical data, the most important being serum CTN levels; specifically, the decision to perform thyroidectomy should err on the safe side if the CTN level is

  20. Histopathological and immunohistochemical findings of primary and metastatic medullary thyroid carcinoma in a young dog

    PubMed Central

    Vieson, Miranda D.; Ramos-Vara, José A.; Moon-Larson, Martha; Saunders, Geoffrey

    2014-01-01

    This report describes the gross, histological, and immunohistochemical features of medullary thyroid carcinoma (MTC) with pulmonary metastases in a young dog. Sheets of pleomorphic cells supported by fibrous stroma characterized the primary mass, while metastatic nodules had a neuroendocrine pattern. Despite differing histologic features, all masses showed marked immunoreactivity against calcitonin and multiple neuroendocrine markers consistent with MTC. Although MTC is a well-recognized entity, it may be difficult to distinguish this mass from other thyroid neoplasms, necessitating immunohistochemical characterization. PMID:24690600

  1. Charting a course through the CEAs: diagnosis and management of medullary thyroid cancer.

    PubMed

    Rowe, Christopher W; Bendinelli, Cino; McGrath, Shaun

    2016-09-01

    Medullary thyroid cancer (MTC) is an uncommon thyroid cancer that requires a high index of suspicion to facilitate diagnosis of early-stage disease amenable to surgical cure. The challenges of diagnosis, as well as management in the setting of persistent disease, are explored in the context of a case presenting with the incidental finding of elevated carcinoembryonic antigen (CEA) and an (18) F-fluorodeoxyglucose positron emission tomography ((18) F-FDG-PET)-positive thyroid incidentaloma detected following treatment of colorectal cancer. Strategies to individualize prognosis, and emerging PET-based imaging modalities, particularly the potential role of (18) F-DOPA-PET in staging, are reviewed. PMID:27230389

  2. A Genomic Alternative to Identify Medullary Thyroid Cancer Preoperatively in Thyroid Nodules with Indeterminate Cytology

    PubMed Central

    Monroe, Robert J.; Traweek, S. Thomas; Lanman, Richard B.; Kennedy, Giulia C.

    2016-01-01

    Background: The use of calcitonin screening for the rare medullary thyroid cancer (MTC) is controversial due to questions of efficacy, accuracy, and cost-effectiveness. This study reports the results of a large prospective validation using a machine-trained algorithm (MTC Classifier) to preoperatively identify MTC in fine-needle aspiration biopsies in lieu of calcitonin measurements. Methods: Cytology analysis on a prospective consecutive series of 50,430 thyroid nodule biopsies yielded a total of 7815 indeterminate (Bethesda categories III/IV) cases, which were tested with the MTC classifier. A prospective, consecutively submitted series of 2673 Bethesda III–VI cases with cytology determined locally was also evaluated. RNA was isolated and tested for the MTC Classifier using microarrays. Results: Forty-three cases were positive by the MTC Classifier among 10,488 tested nodules (0.4%), consistent with the low prevalence of MTC. Of these, all but one was histologically or biochemically confirmed as MTC, yielding a positive predictive value (PPV) of 98%. Of the positive cases, only 19 (44%) had been specifically suspected of MTC by cytology, highlighting the limitations of light microscopy to detect this disease. Three surgically confirmed MTC cases that were detected by the MTC Classifier had low basal serum calcitonin values, indicating these would have been missed by traditional calcitonin screening methods. A pooled analysis of three independent validation sets demonstrates high test sensitivity (97.9%), specificity (99.8%), PPV (97.9%), and negative predictive value (99.8%). Conclusions: A clinical paradigm is proposed, whereby cytologically indeterminate thyroid nodules being tested for common malignancies using gene expression can be simultaneously tested for MTC using the same genomic assay at no added cost. PMID:26992356

  3. [Metastatic medullary thyroid carcinoma in a child with multiple endocrine neoplasia 2B. Efficiency of medium-term treatment with vandetanib without thyroid surgery].

    PubMed

    Segura, D; Dupuis, C; Chabre, O; Piolat, C; Durand, C; Plantaz, D

    2016-08-01

    Medullary thyroid carcinoma (MTC) is a rare cancer during childhood. MTC is sporadic in approximately 80% of cases and hereditary in 20%. When hereditary, it can be associated with other endocrine neoplasias and/or typical nonendocrine diseases, thus configuring the multiple endocrine neoplasia (MEN) syndromes. Children with clinically obvious MTC belong to MEN 2A or 2B families, related to RET mutations. The standard treatment is total thyroidectomy and central neck dissection. However, treatment of advanced MTC has not yet been standardized, even if a new tyrosine kinase inhibitor specific to RET mutation has changed the outcome of such patients. Vandetanib plays a role in the treatment of children with metastatic, locally advanced and nonoperable MTC, with good tolerance. We report the 5-year treatment of an 11-year-old patient, with vandetanib and without thyroid surgery. PMID:27345554

  4. 2012 European Thyroid Association Guidelines for Genetic Testing and Its Clinical Consequences in Medullary Thyroid Cancer

    PubMed Central

    Elisei, R.; Alevizaki, M.; Conte-Devolx, B.; Frank-Raue, K.; Leite, V.; Williams, G.R.

    2013-01-01

    Twenty-five percent of medullary thyroid cancers (MTC) are familial and inherited as an autosomal dominant trait. Three different phenotypes can be distinguished: multiple endocrine neoplasia (MEN) types 2A and 2B, in which the MTC is associated with other endocrine neoplasias, and familial MTC (FMTC), which occurs in isolation. The discovery that germline RET oncogene activating mutations are associated with 95–98% of MEN 2/FMTC syndromes and the availability of genotyping to identify mutations in affected patients and their relatives has revolutionized the diagnostic and therapeutic strategies available for the management of these patients. All patients with MTC, both those with a positive familial history and those apparently sporadic, should be submitted to RET genetic screening. Once an RET mutation has been confirmed in an index patient, first-degree relatives should be screened rapidly to identify the 50% who inherited the mutation and are therefore at risk for development of MTC. Relatives in whom no RET mutation is identified can be reassured and discharged from further follow-up, whereas RET-positive subjects (i.e. gene carriers) must be investigated and a therapeutic strategy initiated. These guideline recommendations are derived from the most recent studies identifying phenotype-genotype correlations following the discovery of causative RET gene mutations in MEN 2 eighteen years ago. Three major points will be discussed: (a) identification of patients and relatives who should have genetic screening for RET mutations, (b) management of asymptomatic gene carriers, and (c) ethics. PMID:24783025

  5. Advances in the management of thyroid cancer.

    PubMed

    Shaha, Ashok R

    2005-01-01

    The incidence of thyroid cancer is rapidly increasing in the United States. A large number of incidentalomas are found during routine head and neck evaluations. The diagnostic workup still revolves around fine needle aspiration biopsy. Ultrasound guided fine needle aspiration biopsy is likely to yield the best results. Surgical resection offers the best treatment choice. Controversy continues in relation to total versus less than total thyroidectomy. The incidence of complications is inversely proportional to the extent of surgery and obviously related to the experience of the operating surgeon. The decision regarding the extent of thyroidectomy should be based on prognostic factors and risk groups. Prognostic factors are well defined, such as age, grade of the tumor, extrathyroidal extension, size, distant metastasis, and histology. Nodal metastasis has minimal implications. Based on prognostic factors, thyroid cancer can be divided into low, intermediate and high risk groups. In the high risk group and in selected intermediate risk patients, radioactive iodine dosimetry and ablation should be considered after total thyroidectomy. PET scanning and the use of recombinant TSH have been major advances in follow-up care for patients with thyroid cancer. Thyroglobulin appears to be a very good tumor marker for follow-up. No major breakthrough is noted in the management of anaplastic thyroid cancer, however, identification of RET mutation has been extremely helpful in evaluating the family members of the patient with medullary thyroid cancer with strong consideration given to total thyroidectomy. PMID:17462286

  6. Horner's Syndrome Incidental to Medullary Thyroid Carcinoma Excision: Case Report and Brief Literature Review

    PubMed Central

    Mastronikolis, Nicholas S.; Spiliopoulou, Sofia P.; Zolota, Vassiliki; Papadas, Theodoros A.

    2016-01-01

    Horner's syndrome is characterized by a combination of ipsilateral miosis, blepharoptosis, enophthalmos, facial anhidrosis, and iris heterochromia in existence of congenital lesions. The syndrome results from a disruption of the ipsilateral sympathetic innervation of the eye and ocular adnexa at different levels. Though rare, thyroid and neck surgery could be considered as possible causes of this clinical entity. We present a case of Horner's syndrome in a patient after total thyroidectomy and neck dissection for medullary thyroid cancer with neck nodal disease and attempt a brief review of the relevant literature. PMID:27200201

  7. Horner's Syndrome Incidental to Medullary Thyroid Carcinoma Excision: Case Report and Brief Literature Review.

    PubMed

    Mastronikolis, Nicholas S; Spiliopoulou, Sofia P; Zolota, Vassiliki; Papadas, Theodoros A

    2016-01-01

    Horner's syndrome is characterized by a combination of ipsilateral miosis, blepharoptosis, enophthalmos, facial anhidrosis, and iris heterochromia in existence of congenital lesions. The syndrome results from a disruption of the ipsilateral sympathetic innervation of the eye and ocular adnexa at different levels. Though rare, thyroid and neck surgery could be considered as possible causes of this clinical entity. We present a case of Horner's syndrome in a patient after total thyroidectomy and neck dissection for medullary thyroid cancer with neck nodal disease and attempt a brief review of the relevant literature. PMID:27200201

  8. Overview and Management of Dermatologic Events Associated with Targeted Therapies for Medullary Thyroid Cancer

    PubMed Central

    Ciccolini, Kathryn; Kloos, Richard T.; Agulnik, Mark

    2014-01-01

    Background: Treatment options for patients with advanced or metastatic medullary thyroid cancer (MTC) have, in recent years, expanded with the approval of two tyrosine kinase inhibitors (TKIs): vandetanib and cabozantinib. Other agents, including TKIs, are under clinical investigation for MTC. Although patients treated with TKIs are at risk of developing dermatologic adverse events (AE), these untoward events may be mitigated through AE-driven algorithms. Summary: AE-driven algorithms combine effective nonpharmaceutical and pharmaceutical treatment modalities implemented by a multidisciplinary effort that incorporates nursing interventions, patient education, and referrals to pain-management specialists, podiatrists, and dermatologists, as appropriate. Effective AE prevention and management reduce the need for dose interruptions and modifications, allowing patients the opportunity to derive the maximal benefit from TKI therapy, while maintaining quality of life. Conclusions: Optimal use of targeted therapies in the treatment of MTC depends on careful patient selection, interdisciplinary communication, and patient education and encouragement to enhance compliance and safety, optimize consistent dosing, and maximize the use of effective therapies. PMID:24902006

  9. Chromosome 10 and RET gene copy number alterations in hereditary and sporadic Medullary Thyroid Carcinoma.

    PubMed

    Ciampi, Raffaele; Romei, Cristina; Cosci, Barbara; Vivaldi, Agnese; Bottici, Valeria; Renzini, Giulia; Ugolini, Clara; Tacito, Alessia; Basolo, Fulvio; Pinchera, Aldo; Elisei, Rossella

    2012-01-01

    About 30% of hereditary Medullary Thyroid Carcinoma (MTC) have been demonstrated to harbour imbalance between mutant and wild-type RET alleles. We studied the RET copy number alterations (RET CNA) in 65 MTC and their correlation with RET mutation and patients' outcome. Fluorescence in situ Hybridization and Real-time PCR revealed RET CNA in 27.7% MTC but only in a variable percentage of cells. In sporadic MTC, RET CNA were represented by chromosome 10 aneuploidy while in hereditary MTC by RET amplification. A significant higher prevalence of RET CNA was observed in RET mutated MTC (P=0.003). RET CNA was also associated to a poorer outcome (P=0.005). However, the multivariate analysis revealed that only RET mutation and advanced clinical stage correlated with the worst outcome. In conclusion, 30% MTC harbour RET CNA in variable percentage of cells suggesting cell heterogeneity. RET CNA can be considered a poor prognostic factor potentiating the poor prognostic role of RET mutation. PMID:21867742

  10. Medullary thyroid carcinoma: a review on ethical considerations in treatment of children.

    PubMed

    Nozhat, Zahra; Hedayati, Mehdi

    2016-06-01

    Thyroid carcinoma is the most common malignancy of the endocrine system and it accounts approximately 1%-3% of all human cancers. Among the three subtypes of thyroid cancers, medullary thyroid carcinoma (MTC) is the most common cause of death in patients with multiple endocrine neoplasia (MEN) type 2A (MEN2A), MEN type 2B (MEN2B) and familial medullary thyroid carcinoma (FMTC). Generally, MTC accounts for up to 10% of all types of thyroid cancers. It is one of the aggressive forms of thyroid carcinoma which is manifested in childhood ages more than adults, and it comprises about 17% of all pediatric thyroid cancer. Like the other cancers, prevention of MTC is easier than its cure. In the recent decades (from 1993) the diagnosis of asymptomatic child carrying RET mutations in the affected families by MTC, has been provided by genetic screening, and prophylactic thyroidectomy is an efficacy therapeutic procedure. On the one hand, according to near the complete penetrance of the disease and its onset in the early years of life, it is required to accelerate the protection of at-risk children with relative affected by MTC and on the other hand, there are several obstructions to MTC treatment including: 1) the proband's refusal to disclose the RET mutation genetic testing results, 2) children's vulnerability because of their inability to participate in the informed consent, and 3) the existence of conflict between physicians and children's guardian. In this review article, the recommendations and ethical issues of MTC treatment in asymptomatic and at-risk children have been summarized. PMID:26974132

  11. Targeting mTOR in RET mutant medullary and differentiated thyroid cancer cells

    PubMed Central

    Gild, Matti L; Landa, Iñigo; Ryder, Mabel; Ghossein, Ronald A; Knauf, Jeffrey A; Fagin, James A

    2015-01-01

    Inhibitors of RET, a tyrosine kinase receptor encoded by a gene that is frequently mutated in medullary thyroid cancer, have emerged as promising novel therapies for the disease. Rapalogs and other mammalian target of rapamycin (mTOR) inhibitors are effective agents in patients with gastroenteropancreatic neuroendocrine tumors, which share lineage properties with medullary thyroid carcinomas. The objective of this study was to investigate the contribution of mTOR activity to RET-induced signaling and cell growth and to establish whether growth suppression is enhanced by co-targeting RET and mTOR kinase activities. Treatment of the RET mutant cell lines TT, TPC-1, and MZ-CRC-1 with AST487, a RET kinase inhibitor, suppressed growth and showed profound and sustained inhibition of mTOR signaling, which was recapitulated by siRNA-mediated RET knockdown. Inhibition of mTOR with INK128, a dual mTORC1 and mTORC2 kinase inhibitor, also resulted in marked growth suppression to levels similar to those seen with RET blockade. Moreover, combined treatment with AST487 and INK128 at low concentrations suppressed growth and induced apoptosis. These data establish mTOR as a key mediator of RET-mediated cell growth in thyroid cancer cells and provide a rationale for combinatorial treatments in thyroid cancers with oncogenic RET mutations. PMID:23828865

  12. Molecular mechanisms of medullary thyroid carcinoma: current approaches in diagnosis and treatment.

    PubMed

    Boikos, S A; Stratakis, C A

    2008-01-01

    Medullary thyroid carcinoma is the most common cause of death among patients with multiple endocrine neoplasia (MEN) 2. Dominant-activating mutations in the RET proto-oncogene have been shown to have a central role in the development of MEN 2 and sporadic medullary thyroid cancer (MTC): about half of sporadic MTCs are caused by somatic genetic changes of the RET oncogene. Inactivating mutations of the same gene lead to Hirschprung disease and other developmental defects. Thus, RET genetic changes lead to phenotypes that largely depend on their location in the gene and the function and timing of developmental expression of the RET protein. The reproducibility of the phenotype caused by each RET genotype led to MEN 2/MTC being among the first conditions in Medicine where a drastic measure is applied to prevent cancer, following genetic testing: thyroidectomy is currently routinely done in young children that are carriers of MTC-predisposing RET mutations. RET inhibitors have been also developed recently and are used in various types of thyroid and other cancers. This report reviews the RET involvement in the etiology of MEN 2 and MTC and updates the therapeutic approach in preclinical and clinical studies. PMID:17952863

  13. Suberoylanilide Hydroxamic Acid in Treating Patients With Metastatic and/or Locally Advanced or Locally Recurrent Thyroid Cancer

    ClinicalTrials.gov

    2014-07-23

    Insular Thyroid Cancer; Recurrent Thyroid Cancer; Stage II Follicular Thyroid Cancer; Stage II Papillary Thyroid Cancer; Stage IV Follicular Thyroid Cancer; Stage IV Papillary Thyroid Cancer; Thyroid Gland Medullary Carcinoma

  14. Medullary thyroid carcinoma with a paraganglioma-like pattern and melanin production: a case report with ultrastructural and immunohistochemical studies.

    PubMed

    Ikeda, T; Satoh, M; Azuma, K; Sawada, N; Mori, M

    1998-06-01

    We report a case of medullary thyroid carcinoma with a paraganglioma-like pattern and melanin production. Macroscopically, a rectangular black area within a gray-white background was seen on the cut surface of the tumor. Histologically, the tumor was found to have a trabecular or nestlike architecture with many pigmented dendritic cells, resembling the "sustentacular cells" of paraganglioma, scattered among nonpigmented polygonal tumor cells. Fontana-Masson staining and bleaching with potassium permanganate and oxalic acid revealed that this pigment was melanin, which was also confirmed by electron microscopy. Immunohistochemically, pigmented dendritic cells were positive for calcitonin, as were the surrounding typical medullary thyroid carcinoma cells. These cells were also positive for S100 protein but not for HMB-45, compatible with sustentacular cells. These findings suggest that this tumor could be considered to bridge the gap between two variants of medullary thyroid carcinoma, the melanin-producing (pigmented) type and the paraganglioma-like type. PMID:9625426

  15. Prognostic Value of Serum Tumor Markers in Medullary Thyroid Cancer Patients Undergoing Vandetanib Treatment

    PubMed Central

    Werner, R.A.; Schmid, J.S.; Muegge, D.O.; Lückerath, K.; Higuchi, T.; Hänscheid, H.; Grelle, I.; Reiners, C.; Herrmann, K.; Buck, A.K.; Lapa, C.

    2015-01-01

    Abstract Tyrosine kinase inhibitors (TKIs) such as vandetanib have shown clinical effectiveness in advanced medullary thyroid cancer (MTC). During TKI treatment, fluctuations in the tumor markers carcinoembryonic antigen (CEA) and calcitonin (CTN) are frequently observed. Their role for treatment monitoring and the decision-making process has not been fully elucidated yet. Twenty-one patients (male, 16, female, 5; mean age, 49 ± 13 years) with progressive MTC receiving vandetanib (300 mg orally per day) were considered. Tumor restaging was performed every 3 months including contrast-enhanced computed tomography (CT). Response was assessed according to recent criteria (Response Evaluation Criteria in Solid Tumors, RECIST 1.1). Additionally, CEA and CTN were measured at the day of CT imaging and alterations observed in tumor markers were compared to respective imaging findings (partial response, PR; stable disease, SD; progressive disease, PD). During long-term follow-up (510 ± 350 days [range, 97–1140 days]), CTN and CEA levels initially dropped in 71.4% and 61.9% of the patients followed by fluctuations in serum marker levels. A rise in CTN ≥39.5% between 2 subsequent measurements (defined by ROC analysis) had a sensitivity of 70.6% and a specificity of 83.2% in predicting PD with an accuracy of 82.0% (area under the curve (AUC), 0.76). Oscillations in CEA levels were not predictive for PD. Whereas tumor marker fluctuations in MTC patients undergoing TKI treatment are a frequent phenomenon, a significant rise in CTN ≥40% turns out to as an early indicator of tumor progression. PMID:26559299

  16. Lymph node metastases and elevated postoperative calcitonin: Predictors of poor survival in medullary thyroid carcinoma.

    PubMed

    Siironen, Päivi; Hagström, Jaana; Mäenpää, Hanna O; Louhimo, Johanna; Arola, Johanna; Haglund, Caj

    2016-03-01

    Background Total thyroidectomy is the treatment of choice for medullary thyroid carcinoma (MTC), but the extent of neck dissection is controversial. Lymph node metastases, distant metastases, and old age are known predictors of poor survival. Patients Patients treated for primary MTC at Helsinki University Hospital from 1990 to 2009 were included (n = 54). Their clinical characteristics, treatment, and outcome were analysed retrospectively, these patients were followed until death or their last follow-up date. Results At last follow-up (3.4-23 years), of 54 MTC patients, 19 (35%) were disease-free, 17 (32%) were alive with disease, and 12 (22%) had died of MTC; six patients died of unrelated causes (11%). All disease-free patients were node negative and had normal postoperative calcitonin level. Of 19 disease-free patients, only four (21%) had undergone lymph node dissection. All patients who died of MTC were Stage IV at diagnosis and died with distant metastases. Disease-specific five-and 10-year survival was 84% and 76.2%. Advanced T-stage (p = 0.004), lymph node metastases (p < 0.001), distant metastases (p < 0.001), stage (p < 0.001), and elevated postoperative calcitonin (p < 0.001) significantly associated with survival. Conclusions Lymph node metastasis and elevated postoperative calcitonin are important prognostic factors. Patients with lymph node metastasis and/or elevated postoperative calcitonin with present treatments cannot become disease-free, but most of them can live a long life with metastasis. PMID:26339947

  17. Medullary thyroid carcinoma (MTC) treated with 177Lu-DOTATATE PRRT: a report of two cases.

    PubMed

    Makis, William; McCann, Karey; McEwan, Alexander J B

    2015-05-01

    Two patients diagnosed with metastatic medullary thyroid carcinoma (MTC) were referred for peptide receptor radionuclide therapy (PRRT) with Lu-[DOTA,Tyr]octreotate (DOTATATE). Each patient was treated with 4 doses of Lu-DOTATATE given 2 months apart. One patient achieved stable disease for 10 months then chose to pursue surgery, and the other achieved stable disease for 9 months on imaging; however, calcitonin continued to rise. The use of Lu-DOTATATE PRRT therapy in the management of MTC warrants further research. PMID:25674858

  18. Increased incidence of medullary carcinoma of the thyroid in rural regions in Greece.

    PubMed

    Alevizaki, M; Papapetrou, P; Georgouli, P; Alevizaki, C C; Papadodima, H; Souvatzoglou, A; Koutras, D

    1995-03-01

    A role of environmental factors for the development of Medullary Carcinoma of the Thyroid (MTC) has been shown for animals, but has only been speculated for humans. In the present study we analyzed our registry of 58 sporadic MTCs for the place of origin and place of residence and compared these with 408 other thyroid carcinomas of different histology who are attending the same Endocrine Clinics in the Athens area. Clustering of sporadic MTCs was observed in the Ionian islands, where an increased incidence of familial cases has previously been observed. Patients with sporadic MTCs originated more frequently from rural areas (p = 0.0006), where the main occupation is agriculture. No important differences were observed concerning the place of residence. We speculate that exposure to sunshine, which is greater in rural areas, may be one factor which, through vitamin D, could be involved in the development of C-cell tumors in predisposed individuals. PMID:7615908

  19. Surgery for lymph node metastases of medullary thyroid carcinoma: A review.

    PubMed

    Jin, Linda X; Moley, Jeffrey F

    2016-02-01

    Medullary thyroid carcinoma (MTC) is a neuroendocrine malignancy of the thyroid C cells that occurs in hereditary and sporadic clinical settings. Metastatic spread commonly occurs to cervical and mediastinal lymph nodes. MTC cells do not concentrate radioactive iodine and are not sensitive to hormonal manipulation, and therefore surgery is the most effective option for curative therapy, reduction in tumor burden, or effective palliation. In patients undergoing preventative surgery for hereditary MTC, central lymph node dissection should be considered if the calcitonin level is elevated. Preservation of parathyroid function in these young patients is of paramount importance. In patients with established primary tumors, systematic surgical removal of lymph node basins (compartmental dissection) should be guided by ultrasound mapping of lymph node metastases and level of serum calcitonin. A "berry-picking" approach is discouraged. Newly approved targeted molecular therapies offer wider treatment options for patients with progressive or metastatic disease. PMID:26539937

  20. 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

  1. Retrospective analysis of 140 cases of medullary thyroid carcinoma followed-up in a single institution

    PubMed Central

    SIMÕES-PEREIRA, JOANA; BUGALHO, MARIA JOÃO; LIMBERT, EDWARD; LEITE, VALERIANO

    2016-01-01

    Familial cases of medullary thyroid carcinoma (MTC) may be diagnosed by genetic screening, while in sporadic tumors the diagnosis relies mainly on fine-needle aspiration cytology. The aim of the present study was to determine the demographic, clinical and pathological characteristics of MTC patients followed-up at the Portuguese Institute of Oncology Francisco Gentil (Lisbon, Portugal). For that purpose, a retrospective analysis of 140 MTC patients diagnosed between 1990 and 2010 was performed. The results indicated that patients with hereditary MTC (11.4%) were significantly younger than patients with sporadic MTC. Of the latter, 34.3% had no clinical suspicion of MTC prior to surgery. The sensitivity of cytology and calcitonin (CT) assay in diagnosing MTC were 51.3 and 98.7%, respectively. All familial index cases and 69.0% of sporadic cases presented with advanced stage disease at the time of diagnosis, while 73.0% of familial MTC detected by genetic/pentagastrin screening were diagnosed at the early stage of the disease. Biochemical cure (BC) was achieved in 39.7% of patients and, of these, only 6.5% relapsed. The 5 and 10-year survival rates were 79.3 and 73.6%, respectively. Age >45 years (P=0.026), advanced stage at diagnosis (P<0.001) and absence of BC (P<0.001) were predictors of a worse prognosis on univariate analysis. However, when the patients detected by genetic/pentagastrin screening were excluded from the analysis, age was no longer a prognostic factor, although disease stage remained a significant prognostic factor. On multivariate analysis, BC was the only factor with a significant impact on prognosis (P=0.031). In addition, the present study confirmed that the majority of patients were diagnosed at advanced stages, and CT determination was observed to be more sensitive than cytology to diagnose MTC. Patients at early stages were more prone to achieve BC, which was a favorable prognostic factor. To the best of our knowledge, the present study

  2. Ectopic ACTH Production Leading to Diagnosis of Underlying Medullary Thyroid Carcinoma

    PubMed Central

    Matheny, Leslee N.; Wilson, Jessica R.; Baum, Howard B. A.

    2016-01-01

    Medullary thyroid carcinoma (MTC) has been described as a source of ectopic ACTH secretion in patients with Cushing’s syndrome. This is an infrequent association, occurring in less than 1% of MTC cases. Among these, it is even more unusual for an initial diagnosis of hypercortisolism to lead to the discovery of underlying MTC. Here we present a case of a patient with weakness, diarrhea, and hypokalemia who was found first to have Cushing’s syndrome and later diagnosed with metastatic MTC. The patient was treated initially with oral agents to control his hypercortisolism, then with an etomidate infusion after experiencing intestinal perforation. He also received vandetanib therapy targeting his underlying malignancy, as this has been shown to reverse clinical signs of Cushing’s syndrome in patients with MTC and subsequent ectopic ACTH secretion. Bilateral adrenalectomy was ultimately required. Medullary thyroid carcinoma should be considered in patients presenting with Cushing’s syndrome due to ectopic ACTH secretion, and a multimodality treatment approach is often required. PMID:27141514

  3. Interferon alpha and rapamycin inhibit the growth of carcinoid and medullary thyroid cancer in vitro.

    PubMed

    Motylewska, Ewelina; Lawnicka, Hanna; Kowalewicz-Kulbat, Magdalena; Sicinska, Paulina; Niedziela, Agata; Melen-Mucha, Gabriela; Stepien, Henryk

    2014-08-01

    Neuroendocrine tumors (NETs) are highly vascularized neoplasms characterized by rising incidence. Moreover, the neuroendocrine cells were shown to express vascular endothelial growth factor (VEGF) and VEGF receptors. Therefore, angiomodulators could be potentially a new group of drugs enhancing still unsatisfactory effectiveness of NET therapy. The aim of this study was to assess the direct influence of angiomodulators: VEGF and five endogenous and exogenous antiangiogenic compounds (endostatin, interferon alpha [IFNα], rapamycin, JV1-36, semaxinib [SU5416]) on the growth of two NET cell lines: lung carcinoid H727 cell line and medullary thyroid cancer TT cell line in vitro. IFNα and rapamycin induced the inhibitory effect on H727 and TT cell viability and proliferation, increasing apoptosis and arresting the cell cycle. Also semaxinib (10(-5)M) inhibited proliferation of both cell lines. VEGF and endostatin did not influence the growth of H727 and TT cells. The inhibitory effect of IFNα, rapamycin and semaxinib on carcinoid and medullary thyroid cancer growth was revealed in our in vitro study, although some other antiangiogenic agents did not directly influence H727 and TT cell growth. Thus, IFNα and mTOR inhibitors as multidirectionally acting drugs with antiangiogenic effect could be potentially efficient in treatment of neuroendocrine tumors and are worth further studies. PMID:24948064

  4. Type 2 Iodothyronine Deiodinase Is Highly Expressed in Medullary Thyroid Carcinoma

    PubMed Central

    Meyer, Erika L Souza; Goemann, Iuri M; Dora, José Miguel; Maia, Ana Luiza

    2008-01-01

    Summary Type II deiodinase (D2) plays a critical role in controlling intracellular T3 concentration and early studies indicated a follicular but not a parafollicular C-cell origin of D2 activity in the thyroid gland. Here, we show that D2 is highly expressed in human medullary thyroid carcinoma (MTC), a tumour that arises from the C-cells. D2 transcripts were detected in all MTC samples obtained from 12 unselected MTC patients and the levels of D2 activity were comparable to those found in surrounding normal follicular tissue (0.41±0.10 vs 0.43±0.41 fmol.min.mg.protein, P=0.91). Additional analysis in the TT cells, a human MTC cell line, demonstrated that the D2 expression is down regulated by thyroid hormones and enhanced by cAMP analogs and dexamethasone. The thyroid hormone receptor α1 and β isoforms were also detected in all MTC samples and in TT cells, thus suggesting a potential role of T3 locally produced by D2 in this neoplastic tissue. PMID:18514391

  5. Cutaneous metastasis of medullary carcinoma thyroid masquerading as subcutaneous nodules anterior chest and mandibular region.

    PubMed

    Mannan, Rahul; Kaur, Jasmine; Kaur, Jasleen; Piplani, Sanjay; Kaur, Harjot; Kaur, Harleen

    2014-01-01

    Cutaneous metastasis of underlying primary malignancies can present to dermatologist with chief complaints of cutaneous lesions. The underlying malignancy is generally diagnosed much later after a complete assessment of the concerned case. Medullary carcinoma thyroid (MCT) is a relatively uncommon primary neoplasia of the thyroid. Very few cases presenting as cutaneous metastases of MCT have been reported in the literature. Most of the cases which have been reported are of the papillary and the follicular types. We here report a case of a patient who presented in the dermatology clinic with the primary complaint of multiple subcutaneous nodules in anterior chest wall and left side of body of mandible. By systematic application of clinical and diagnostic skills these nodules were diagnosed as cutaneous metastasis of MCT bringing to the forefront a history of previously operated thyroid neoplasm. So clinically, the investigation of a flesh coloured subcutaneous nodule, presenting with a short duration, particularly in scalp, jaw, or anterior chest wall should include possibility of metastastic deposits. A dermatologist should keep a possibility of an internal organ malignancy in patients while investigating a case of flesh coloured subcutaneous nodules, presenting with short duration. A systematic application of clinical and diagnostic skills will eventually lead to such a diagnosis even when not suspected clinically at its primary presentation. A prompt and an emphatic diagnosis and treatment will have its bearing on the eventual outcome in all these patients. PMID:25478248

  6. Clinical management and outcomes of papillary, follicular and medullary thyroid cancer surgery.

    PubMed

    Rahmani, Nasrin; Abbas Hashemi, Seyyed; Fazli, Mehran; Raisian, Mohammad

    2013-02-01

    The clinical characteristics, pathological subtypes and patients' survival in 40 patients with thyroid carcinoma between March 2007 and March 2012 were evaluated. This study included 33 (82.5 %) females and seven (17.5%) males (female to male ratio of 4.7:1). The median age of patients was 47.5 (range; 24-64). Papillary carcinoma was the commonest pathological subtype (23 patients, 57.5%), followed by follicular carcinoma (14 patients, 35%) and medullary carcinoma (3 cases, 7.5%). Total thryoidectomy was performed in 30 (75%), lobectomy in six (15%), subtotal and multifocal thryoidectomy in two (5%) patients. The median time of follow up was 3 years with range of 1-5 years. After ive years 34 (85%) patients were alive and six (15%) were dead. The overall 5-year actuarial survival was 85%, for papillary carcinoma 91.3%, for follicular carcinoma 85.7% and for medullary carcinoma it was 33.3%. The results suggest that total thryoidectomy had better outcome in comparison with other surgeries. PMID:23348184

  7. Targeted therapy for genetic cancer syndromes: Fanconi anemia, medullary thyroid cancer, tuberous sclerosis, and RASopathies.

    PubMed

    Agarwal, Rishi; Liebe, Sarah; Turski, Michelle L; Vidwans, Smruti J; Janku, Filip; Garrido-Laguna, Ignacio; Munoz, Javier; Schwab, Richard; Rodon, Jordi; Kurzrock, Razelle; Subbiah, Vivek

    2015-02-01

    With the advent of genomics-based treatment in recent years, the use of targeted therapies in the treatment of various malignancies has increased exponentially. Though much data is available regarding the efficacy of targeted therapies for common malignancies, genetic cancer syndromes remain a somewhat unexplored topic with comparatively less published literature. This review seeks to characterize targeted therapy options for the following genetic cancer syndromes: Fanconi anemia, inherited medullary thyroid cancer, tuberous sclerosis, and RASopathies. By understanding the pathophysiology of these conditions as well as available molecularly targeted therapies, oncologists, in collaboration with geneticists and genetic counsellors, can begin to develop effective clinical management options and therapy regimens for the patients with these genetic syndromes that they may encounter in their practice. PMID:25725224

  8. Association of urothelial carcinoma of the renal pelvis with papillary and medullary thyroid carcinomas. A new sporadic neoplastic syndrome?

    PubMed

    Albores-Saavedra, Jorge; Dorantes-Heredia, Rita; Chablé-Montero, Fredy; Córdova-Ramón, Juan Carlos; Henson, Donald E

    2014-10-01

    We describe 2 adult women (72 and 54 years), 1 with a low-grade noninvasive papillary urothelial carcinoma of the renal pelvis, who 14 years later developed a papillary carcinoma in 1 thyroid lobe and a medullary carcinoma in the contralateral lobe. Both neoplasms were similar in size and appeared symmetrical. Despite its small size, the medullary carcinoma metastasized in multiple cervical lymph nodes. The second patient had a high-grade invasive papillary urothelial carcinoma of the renal pelvis that infiltrated the renal parenchyma and metastasized in one of the lungs. Five months later, a papillary carcinoma was discovered in the thyroid gland. The 2 papillary thyroid carcinomas were of the follicular variant. Adjacent to 1 papillary carcinoma, there was a dominant nodule of a colloid and adenomatous goiter. The medullary carcinoma contained stromal amyloid and was immunoreactive for calcitonin and carcinoembryonic antigen. There was no C-cell hyperplasia (medullary carcinoma in situ). The 2 patients are alive, 1 is living with pulmonary metastasis from the high-grade urothelial carcinoma. Twelve cases of this neoplastic association were registered in the Survey, Epidemiology, and End Results Program from 1980 to 2009. We believe that the combination of these unusual neoplasms in the same patient may represent a new sporadic neoplastic syndrome. PMID:25175810

  9. Serum calcitonin negative medullary thyroid carcinoma: a systematic review of the literature.

    PubMed

    Trimboli, Pierpaolo; Giovanella, Luca

    2015-09-01

    Generally, calcitonin (CT) values below the upper reference limit rule-out medullary thyroid carcinoma (MTC) with very high accuracy. However, sparse cases of serum-calcitonin-negative MTC (CT-NEG-MTC) have been reported. Here we reviewed CT-NEG-MTC reported in literature, discussed the potential causes and proposed a practical laboratory and clinical approach. A comprehensive literature search was conducted by using the terms "medullary thyroid carcinoma" AND "non-secreting calcitonin" OR "undetectable calcitonin". The search was updated until December 2014. Original articles that described CT-NEG-MTC were eligible for inclusion. Only MTC cases with preoperative CT below the upper reference limit were included in the present review. Eleven papers with 18 CT-NEG-MTC cases (age 50 years, size 26 mm) were retrieved. Four patients with poorly differentiated MTC died within 3 years. Different CT assays were employed and different reference values were adopted. Preoperative serum CT values were below the institution cut-off levels in all cases, and undetectable in four patients. In some papers negative CT results were confirmed by additional tests. Further laboratory investigations were performed in some of the included studies. In patients with well founded suspicious of MTC and within the reference limits/undetectable CT other laboratory investigations [carcinoembryonic antigen (CEA), procalcitonin, CT stimulation, CT in washout of nodule's aspiration] have to be performed. Surgical approach to CT-NEG-MTC does not differ from those secreting CT. Postoperative follow-up of these rare cases should include periodical imaging and measurement of all potential markers. Patients with poorly differentiated MTC are at higher risk of disease-related death, and require more aggressive follow-up strategy. PMID:25781697

  10. PI3K/Akt/mTOR: A promising therapeutic target for non-medullary thyroid carcinoma.

    PubMed

    Petrulea, Mirela S; Plantinga, Theo S; Smit, Jan W; Georgescu, Carmen E; Netea-Maier, Romana T

    2015-09-01

    Thyroid carcinoma (TC) is the most common endocrine malignancy. The pathogenesis of TC is complex and involves multiple genetic events that lead to activation of oncogenic pathways such as the MAP kinase (MAPK) pathway and the PI3K/Akt/mTOR pathway. The PI3K/Akt pathway has emerged as an important player in the pathogenesis of TC, particularly in follicular and advanced anaplastic or poorly differentiated TC. Because these patients have a poor prognosis, particularly when their tumors become resistant to the conventional treatment with radioactive iodine, efforts have been made to identify possible targets for therapy within these pathways. Orally available drugs targeting the PI3K/Akt/mTOR pathway are being used with success in treatment of several types of malignant tumors. There is an increasing amount of preclinical and clinical data supporting that this pathway may represent a promising target for systemic therapy in TC. The present review focuses on the most recent developments on the role of the PI3K/Akt pathway in the pathogenesis of non-medullary TC and will provide insight into how this pathway can be targeted either alone or in the context of multimodal therapeutic strategies for treatment of advanced TC. PMID:26138515

  11. Differential expression of cell cycle regulators in CDK5-dependent medullary thyroid carcinoma tumorigenesis.

    PubMed

    Pozo, Karine; Hillmann, Antje; Augustyn, Alexander; Plattner, Florian; Hai, Tao; Singh, Tanvir; Ramezani, Saleh; Sun, Xiankai; Pfragner, Roswitha; Minna, John D; Cote, Gilbert J; Chen, Herbert; Bibb, James A; Nwariaku, Fiemu E

    2015-05-20

    Medullary thyroid carcinoma (MTC) is a neuroendocrine cancer of thyroid C-cells, for which few treatment options are available. We have recently reported a role for cyclin-dependent kinase 5 (CDK5) in MTC pathogenesis. We have generated a mouse model, in which MTC proliferation is induced upon conditional overexpression of the CDK5 activator, p25, in C-cells, and arrested by interrupting p25 overexpression. Here, we identify genes and proteins that are differentially expressed in proliferating versus arrested benign mouse MTC. We find that downstream target genes of the tumor suppressor, retinoblastoma protein, including genes encoding cell cycle regulators such as CDKs, cyclins and CDK inhibitors, are significantly upregulated in malignant mouse tumors in a CDK5-dependent manner. Reducing CDK5 activity in human MTC cells down-regulated these cell cycle regulators suggesting that CDK5 activity is critical for cell cycle progression and MTC proliferation. Finally, the same set of cell cycle proteins was consistently overexpressed in human sporadic MTC but not in hereditary MTC. Together these findings suggest that aberrant CDK5 activity precedes cell cycle initiation and thus may function as a tumor-promoting factor facilitating cell cycle protein expression in MTC. Targeting aberrant CDK5 or its downstream effectors may be a strategy to halt MTC tumorigenesis. PMID:25900242

  12. Late liver metastasis of medullary thyroid cancer with low calcitonin levels - successfully cured by radiofrequency.

    PubMed

    Al-Salameh, Abdallah; Baudry, Camille; Gautier, Jean François; Toubert, Marie-Elisabeth; Bihan, Hélène; Cohen, Régis

    2016-01-01

    A 28-year-old female consulted in 1994 for a left thyroid nodule known for two years with documented progression. Left lobe resection was performed initially followed by total thyroidectomy without lymph node dissection in September 1994. Pathological examination concluded on unilateral 10 × 40 mm medullary thyroid carcinoma (MTC). RET mutation was negative. Basal and pentagastrin-stimulated CT levels had been normal from 1994 to 2008 when her CT level was found to be elevated at 33 ng/L and increased subsequently to 111 ng/L in 2010. In accordance with guidelines, cervical ultrasound was performed repeatedly with negative results. After discussion in a multidisciplinary meeting and with patient's consent, an F-Dopa PET scan was proposed in disagreement with guidelines. This scan showed unique uptake in liver segment VI, which was confirmed by MRI. CT levels reached to 253 ng/L when she finally accepted treatment. In February 2013 we performed radiofrequency ablation of the lesion, which allowed normalisation of CT levels. This observation highlights the possibility of late recurrence of MTC. We could propose that for MTC patients with low-calcitonin levels-recurrences F-DOPA-PET/CT is a good diagnostic tool to use in case of repeatedly negative US neck studies. (Endokrynol Pol 2016; 67 (3): 326-329). PMID:26884307

  13. Targeted DNA Sequencing Detects Mutations Related to Susceptibility among Familial Non-medullary Thyroid Cancer

    PubMed Central

    Yu, Yang; Dong, Li; Li, Dapeng; Chuai, Shaokun; Wu, Zhigang; Zheng, Xiangqian; Cheng, Yanan; Han, Lei; Yu, Jinpu; Gao, Ming

    2015-01-01

    Some studies have demonstrated that familial non-medullary thyroid cancer (FNMTC) has a more aggressive clinical behavior compared to sporadic NMTC (SNMTC). However, FNMTC is difficult to differentiate from SNMTC by the morphology and immunohistochemistry. Although genes responsible for FNMTC were unclear, screening for rare germline mutations on known important tumor suppressor genes might offer more insights on predicting susceptibility to FNMTC. Here, a customized panel was designed to capture all exons of 31 cancer susceptive genes possibly related to FNMTC. Using next-generation sequencing we performed deep sequencing to achieve 500× coverage of the targeted regions. At the end 45 variants were identified in 29 of 47 familial patients and 6 of 16 sporadic patients. Notably, several germline mutations were found matching between paired FNMTC patients from the same family, including APC L292F and A2778S, BRAF D22N, MSH6 G355S and A36V, MSH2 L719F, MEN1 G508D, BRCA1 SS955S, BRCA2 G2508S, and a GNAS inframe insertion. We demonstrated a novel approach to help diagnose and elucidate the genetic cause of the FNMTC patients, and assess whether their family members are exposed to a higher genetic risk. The findings would also provide insights on monitoring the potential second cancers for thyroid cancer patients. PMID:26530882

  14. Antiproliferative and pro-apoptotic effects of Uncaria tomentosa in human medullary thyroid carcinoma cells.

    PubMed

    Rinner, Beate; Li, Zeng Xia; Haas, Helga; Siegl, Veronika; Sturm, Sonja; Stuppner, Hermann; Pfragner, Roswitha

    2009-11-01

    Medullary thyroid carcinoma (MTC), a rare calcitonin-producing tumor, is derived from parafollicular C-cells of the thyroid and is characterized by constitutive Bcl-2 overexpression. The tumor is relatively insensitive to radiation therapy as well as conventional chemotherapy. To date, the only curative treatment is the early and complete surgical removal of all neoplastic tissue. In this study, the antiproliferative and pro-apoptotic effects of fractions obtained from Uncaria tomentosa (Willd.) DC, commonly known as uña de gato or cat's claw were investigated. Cell growth of MTC cells as well as enzymatic activity of mitochondrial dehydrogenase was markedly inhibited after treatment with different fractions of the plant. Furthermore, there was an increase in the expressions of caspase-3 and -7 and poly(ADP-ribose) polymerase (PARP) fraction, while bcl-2 overexpression remained constant. In particular, the alkaloids isopterpodine and pteropodine of U. tomentosa exhibited a significant pro-apoptotic effect on MTC cells, whereas the alkaloid-poor fraction inhibited cell proliferation but did not show any pro-apoptotic effects. These promising results indicate the growth-restraining and apoptotic potential of plant extracts against neuroendocrine tumors, which may add to existing therapies for cancer. PMID:20032400

  15. Molecular Basis of Medullary Thyroid Carcinoma: The Role of RET Polymorphisms

    PubMed Central

    Ceolin, Lucieli; Siqueira, Débora R.; Romitti, Mírian; Ferreira, Carla V.; Maia, Ana Luiza

    2012-01-01

    Medullary thyroid carcinoma is a rare malignant tumor originating in parafollicular C cells. It accounts for 5 to 8% of all thyroid cancers. MTC develops in either sporadic (75%) or hereditary form (25%). Genetic and molecular studies have demonstrated the involvement of the RET proto-oncogene in hereditary MTC and, less often, in its sporadic form. Although a strong genotype-phenotype correlation has been described, wide clinical heterogeneity is observed among families with the same RET mutation or even in carriers of the same kindred. In recent years, several single nucleotide polymorphisms of the RET gene have been described in the general population as well as in patients with MTC. Some studies have reported associations between the presence of polymorphisms and development or progression of MTC. Nonetheless, other studies failed to demonstrate any effect of the RET variants. Differences in the genetic background of distinct populations or methodological approaches have been suggested as potential reasons for the conflicting results. Here, we review current knowledge concerning the molecular pathogenesis of sporadic and hereditary MTC. In particular, we analyze the role of RET polymorphisms in the clinical presentation and prognosis of MTC based on the current literature. PMID:22312249

  16. Evolving molecularly targeted therapies for advanced-stage thyroid cancers.

    PubMed

    Bible, Keith C; Ryder, Mabel

    2016-07-01

    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 cancer (MTC), and two agents (sorafenib and lenvatinib) for the treatment of radioactive- iodine refractory differentiated thyroid cancer (DTC) in both the USA and in the EU. The effects of these and other therapies on overall survival and quality of life among patients with thyroid cancer, however, remain to be more-clearly defined. When applied early in the disease course, intensive multimodality therapy seems to improve the survival outcomes of patients with anaplastic thyroid cancer (ATC), but salvage therapies for ATC are of uncertain benefit. Additional innovative, rationally designed therapeutic strategies are under active development both for patients with DTC and for patients with ATC, with multiple phase II and phase III randomized clinical trials currently ongoing. Continued effort is being made to identify further signalling pathways with potential therapeutic relevance in thyroid cancers, as well as to elaborate on the complex interactions between signalling pathways, with the intention of translating these discoveries into effective and personalized therapies. Herein, we summarize the progress made in molecular medicine for advanced-stage thyroid cancers of different histotypes, analyse how these developments have altered - and might further refine - patient care, and identify open questions for future research. PMID:26925962

  17. Contribution of different scintigraphic techniques to the management of medullary thyroid carcinoma

    SciTech Connect

    Sandrock, D.; Blossey, H.C.; Steinroeder, M.; Munz, D.L.

    1989-01-01

    We compared three different scintigraphic techniques for the localization of neck recurrences and metastases in seven patients with medullary thyroid carcinoma one month to eight years after the first surgical intervention. Three successive scintigraphic studies were performed in five patients (6 x 3 studies) within two weeks using 201Tl chloride, 111In-labeled F(ab')2 fragments of the anti-carcinoembryonic antigen (anti-CEA) monoclonal antibody (MoAb) BW 431/31, and 131I meta-iodo-benzylguanidine (MIBG). Additionally, 11 studies were performed with the 111In-labeled MoAb fragment BW 431/31 (seven studies) or the 99mTc-labeled intact anti-CEA MoAb BW 431/26 (four studies). The gold standards for classifying scintigraphic results were biopsy, histology, surgery, and cytology. Six regions were classified as positive or negative in each study: thyroid region, four quadrants (lymph node regions) around the thyroid, and the region of the upper mediastinum. Of 36 sites, 201Tl was true positive (TP) in seven sites, false-positive (FP) in one site, true negative (TN) in 22 sites, and false-negative (FN) in six sites, resulting in a sensitivity of 54% and a specificity of 96%. 131I MIBG was TP in four sites, FP in none of the sites, TN in 23 sites, and FN in nine sites, with a sensitivity of 31% and a specificity of 100%. Immunoscintigraphy (102 sites overall) was TP in 16 sites, FP in five sites, TN in 77 sites, and FN in four sites, resulting in a sensitivity of 80% and a specificity of 94%. Immunoscintigraphy with 111In/99mTc anti-CEA F(ab')2 fragment/intact antibody is superior to scintigraphy with 201Tl and 131I MIBG.

  18. Postoperative Nomogram for Predicting Cancer-Specific Mortality in Medullary Thyroid Cancer

    PubMed Central

    Ho, Allen S.; Wang, Lu; Palmer, Frank L.; Yu, Changhong; Toset, Arnbjorn; Patel, Snehal; Kattan, Michael W.; Tuttle, R. Michael; Ganly, Ian

    2016-01-01

    Background Medullary thyroid cancer (MTC) is a rare thyroid cancer accounting for 5 % of all thyroid malignancies. The purpose of our study was to design a predictive nomogram for cancer-specific mortality (CSM) utilizing clinical, pathological, and biochemical variables in patients with MTC. Methods MTC patients managed entirely at Memorial Sloan-Kettering Cancer Center between 1986 and 2010 were identified. Patient, tumor, and treatment characteristics were recorded, and variables predictive of CSM were identified by univariable analyses. A multivariable competing risk model was then built to predict the 10-year cancer specific mortality of MTC. All predictors of interest were added in the starting full model before selection, including age, gender, pre- and postoperative serum calcitonin, pre- and postoperative CEA, RET mutation status, perivascular invasion, margin status, pathologic T status, pathologic N status, and M status. Stepdown method was used in model selection to choose predictive variables. Results Of 249 MTC patients, 22.5 % (56/249) died from MTC, whereas 6.4 % (16/249) died secondary to other causes. Mean follow-up period was 87 ± 67 months. The seven variables with the highest predictive accuracy for cancer specific mortality included age, gender, postoperative calcitonin, perivascular invasion, pathologic T status, pathologic N status, and M status. These variables were used to create the final nomogram. Discrimination from the final nomogram was measured at 0.77 with appropriate calibration. Conclusions We describe the first nomogram that estimates cause-specific mortality in individual patients with MTC. This predictive nomogram will facilitate patient counseling in terms of prognosis and subsequent clinical follow up. PMID:25366585

  19. Procalcitonin: A New Biomarker for Medullary Thyroid Cancer? A Systematic Review.

    PubMed

    Karagiannis, Apostolos K A; Girio-Fragkoulakis, Constantine; Nakouti, Theodora

    2016-08-01

    Medullary thyroid cancer (MTC) is a rare but aggressive thyroid malignancy. The gold-standard biomarker for its diagnosis and follow-up is calcitonin (CT); however, it has a variable half-life dependent on its circadian variability. It has been suggested that a more stable hormone, procalcitonin (PCT), may overcome these problems and its introduction to routine practice may give more accurate results in the diagnosis and follow-up of MTC. We systematically reviewed Pubmed, Scopus, Biosis Previews and Embase databases up to March 2016. A total of 15 out of 184 articles were retrieved and analyzed. Of these 15 studies, 3 were case reports. In these 15 studies, the values of CT and PCT were assessed in both patients with MTC and patients that were either healthy volunteers or with benign/malignant thyroid nodular disease or with bacterial infection. Our search suggests that PCT seems to be a useful biomarker for the diagnosis and follow-up of MTC when used in conjunction with CT, particularly in a small proportion of tumors that are CT-negative or secrete low levels of CT. So far, there has not been enough data to suggest a specific threshold for normal PCT. However, most studies indicate a value of 0.1 ng/ml as an acceptable cut-off in everyday clinical practice. At present, CT should continue to be the primary biomarker in MTC with the addition of PCT in some patient groups. Nevertheless, larger patient series need to be conducted in order to provide safer and more accurate results. PMID:27466480

  20. Diversity of mutations in the RET proto-oncogene and its oncogenic mechanism in medullary thyroid cancer.

    PubMed

    Hedayati, Mehdi; Zarif Yeganeh, Marjan; Sheikholeslami, Sara; Afsari, Farinaz

    2016-08-01

    Thyroid cancer is the most common endocrine malignancy and accounts for nearly 1% of all of human cancer. Thyroid cancer has four main histological types: papillary, follicular, medullary, and anaplastic. Papillary, follicular, and anaplastic thyroid carcinomas are derived from follicular thyroid cells, whereas medullary thyroid carcinoma (MTC) originates from the neural crest parafollicular cells or C-cells of the thyroid gland. MTC represents a neuroendocrine tumor and differs considerably from differentiated thyroid carcinoma. MTC is one of the aggressive types of thyroid cancer, which represents 3-10% of all thyroid cancers. It occurs in hereditary (25%) and sporadic (75%) forms. The hereditary form of MTC has an autosomal dominant mode of inheritance. According to the present classification, hereditary MTC is classified as a multiple endocrine neoplasi type 2 A & B (MEN2A & MEN2B) and familial MTC (FMTC). The RET proto-oncogene is located on chromosome 10q11.21. It is composed of 21 exons and encodes a transmembrane receptor tyrosine kinase. RET regulates a complex network of signal transduction pathways during development, survival, proliferation, differentiation, and migration of the enteric nervous system progenitor cells. Gain of function mutations in RET have been well demonstrated in MTC development. Variants of MTC result from different RET mutations, and they have a good genotype-phenotype correlation. Various MTC related mutations have been reported in different exons of the RET gene. We proposed that RET genetic mutations may be different in distinct populations. Therefore, the aim of this study was to find a geographical pattern of RET mutations in different populations. PMID:26678667

  1. Calcitonin doubling time in medullary thyroid carcinoma after the detection of distant metastases keenly predicts patients' carcinoma death.

    PubMed

    Ito, Yasuhiro; Miyauchi, Akira; Kihara, Minoru; Kudo, Takumi; Miya, Akihiro

    2016-07-30

    Therapy using tyrosine-kinase inhibitors (TKIs) is now available for recurring or advanced medullary thyroid carcinoma (MTC). Here we investigated the calcitonin doubling time (Ct-DT) of MTC patients with distant recurrence postoperatively and for those with distant metastasis at the initial surgery. Of the 13 patients, six died due to the MTC at 5-93 months after the detection of distant metastasis. Their Ct-DTs were ≤ 1.58 years. The remaining seven patients have been alive for 73-123 months after the detection of metastasis, and their Ct-DTs were low at -4, -2.25 years and 9.17-33.92 years. Similar results were obtained by analyzing the value of 1/Ct-DT to avoid discontinuity in the DT values among the patients with increasing serum Ct values over time and those with decreasing Ct values over time. These findings suggest that it is appropriate to use TKIs only for patients with a short Ct-DT and a large 1/Ct-DT with a cutoff at around 1.5 years and 0.67/year, respectively, even if they have distant metastases. PMID:27097545

  2. The Oncogenic Activity of RET Point Mutants for Follicular Thyroid Cells May Account for the Occurrence of Papillary Thyroid Carcinoma in Patients Affected by Familial Medullary Thyroid Carcinoma

    PubMed Central

    Melillo, Rosa Marina; Cirafici, Anna Maria; De Falco, Valentina; Bellantoni, Marie; Chiappetta, Gennaro; Fusco, Alfredo; Carlomagno, Francesca; Picascia, Antonella; Tramontano, Donatella; Tallini, Giovanni; Santoro, Massimo

    2004-01-01

    Activating germ-line point mutations in the RET receptor are responsible for multiple endocrine neoplasia type 2-associated medullary thyroid carcinoma (MTC), whereas somatic RET rearrangements are prevalent in papillary thyroid carcinomas (PTCs). Some rare kindreds, carrying point mutations in RET, are affected by both cancer types, suggesting that, under specific circumstances, point mutations in RET can drive the generation of PTC. Here we describe a family whose siblings, affected by both PTC and MTC, carried a germ-line point mutation in the RET extracellular domain, converting cysteine 634 into serine. We tested on thyroid follicular cells the transforming activity of RET(C634S), RET(K603Q), another mutant identified in a kindred with both PTC and MTC, RET(C634R) a commonly isolated allele in MEN2A, RET(M918T) responsible for MEN2B and also identified in kindreds with both PTC and MTC, and RET/PTC1 the rearranged oncogene that characterizes bona fide PTC in patients without MTC. We show that the various RET point mutants, but not wild-type RET, scored constitutive kinase activity and exerted mitogenic effects for thyroid PC Cl 3 cells, albeit at significantly lower levels compared to RET/PTC1. The low mitogenic activity of RET point mutants paralleled their reduced kinase activity compared to RET/PTC. Furthermore, RET point mutants maintained a protein domain, the intracellular juxtamembrane domain, that exerted negative effects on the mitogenic activity. In conclusion, RET point mutants can behave as dominant oncogenes for thyroid follicular cells. Their transforming activity, however, is rather modest, providing a possible explanation for the rare association of MTC with PTC. PMID:15277225

  3. Differential gene expression of medullary thyroid carcinoma reveals specific markers associated with genetic conditions.

    PubMed

    Maliszewska, Agnieszka; Leandro-Garcia, Luis J; Castelblanco, Esmeralda; Macià, Anna; de Cubas, Aguirre; Goméz-López, Gonzalo; Inglada-Pérez, Lucía; Álvarez-Escolá, Cristina; De la Vega, Leticia; Letón, Rocío; Gómez-Graña, Álvaro; Landa, Iñigo; Cascón, Alberto; Rodríguez-Antona, Cristina; Borrego, Salud; Zane, Mariangela; Schiavi, Francesca; Merante-Boschin, Isabella; Pelizzo, Maria R; Pisano, David G; Opocher, Giuseppe; Matias-Guiu, Xavier; Encinas, Mario; Robledo, Mercedes

    2013-02-01

    Medullary thyroid carcinoma accounts for 2% to 5% of thyroid malignancies, of which 75% are sporadic and the remaining 25% are hereditary and related to multiple endocrine neoplasia type 2 syndrome. Despite a genotype-phenotype correlation with specific germline RET mutations, knowledge of pathways specifically associated with each mutation and with non-RET-mutated sporadic MTC remains lacking. Gene expression patterns have provided a tool for identifying molecular events related to specific tumor types and to different clinical features that could help identify novel therapeutic targets. Using transcriptional profiling of 49 frozen MTC specimens classified as RET mutation, we identified PROM1, LOXL2, GFRA1, and DKK4 as related to RET(M918T) and GAL as related to RET(634) mutation. An independent series of 19 frozen and 23 formalin-fixed, paraffin-embedded (FFPE) MTCs was used for validation by RT-qPCR. Two tissue microarrays containing 69 MTCs were available for IHC assays. According to pathway enrichment analysis and gene ontology biological processes, genes associated with the MTC(M918T) group were involved mainly in proliferative, cell adhesion, and general malignant metastatic effects and with Wnt, Notch, NFκB, JAK/Stat, and MAPK signaling pathways. Assays based on silencing of PROM1 by siRNAs performed in the MZ-CRC-1 cell line, harboring RET(M918T), caused an increase in apoptotic nuclei, suggesting that PROM1 is necessary for survival of these cells. This is the first report of PROM1 overexpression among primary tumors. PMID:23201134

  4. Ursolic acid from Trailliaedoxa gracilis induces apoptosis in medullary thyroid carcinoma cells

    PubMed Central

    AGUIRIANO-MOSER, VICTOR; SVEJDA, BERNHARD; LI, ZENG-XIA; STURM, SONJA; STUPPNER, HERMANN; INGOLIC, ELISABETH; HÖGER, HARALD; SIEGL, VERONIKA; MEIER-ALLARD, NATHALIE; SADJAK, ANTON; PFRAGNER, ROSWITHA

    2015-01-01

    Medullary thyroid carcinoma (MTC) originates from the C-cells of the thyroid and is not sensitive to radiation or chemotherapy. Therefore, surgical removal of the tumor tissue in its entirety is the only curative treatment for MTC. The present study aimed to examine the potential mechanisms of action of extracts of Trailliaedoxa gracilis (TG; WW Smith & Forrest), a plant from the province of Sichuan, China, and of ursolic acid (UA), a pentacyclic triterpen present in TG, on the MTC-SK MTC cell line. A total of 13 TG fractions and UA were examined in vitro for their effects on cell morphology, cell number, proliferation and rates of apoptosis. Reverse transcription-quantitative polymerase chain reaction of nuclear factor-κB essential modifier (NEMO) was performed to delineate the role of the apoptotic pathway following treatment with UA. TG and UA were examined in vivo in xenotransplanted MTC-bearing severe combined immunodeficient mice. The TG fractions exhibited antiproliferative effects, with inhibition of mitochondrial activity in the tumor cells at concentrations, which caused no impairment of the normal control cells. The apoptotic rates of the MTC-SK cells treated with the TG fractions and UA were determined, in which no marked tumor inhibition was observed in the treated MTC-mice, and no change in the expression of NEMO was detected in the treated MTC-SK cells. The observation of early-onset activation of caspase 8 suggested that the responsible factor was linked to NEMO, an anti-apoptotic protein. However, no differences in the mRNA transcription levels of NEMO were detected in MTC-SK cells treated with UA, suggesting that this protein was not associated with the signal transducer and activator of transcription 3 pathway. PMID:26151624

  5. Scintigraphy and treatment of medullary carcinoma of the thyroid with iodine-131 metaiodobenzylguanidine

    SciTech Connect

    Clarke, S.E.; Lazarus, C.R.; Edwards, S.; Murby, B.; Clarke, D.G.; Roden, T.M.; Fogelman, I.; Maisey, M.N.

    1987-12-01

    We report our experience using (/sup 131/I)metaiodobenzylguanidine (MIBG) to image nine patients with proven medullary carcinoma of the thyroid (MCT). Positive uptake was seen in four patients, equivocal uptake in one patient, and no uptake in four patients. Data are presented to demonstrate the pharmacokinetics of (/sup 131/I)MIBG in three of the patients studied. Two patients, with diarrhea and severe pain from known bone metastases and positive uptake on (/sup 131/I)MIBG diagnostic scanning, subsequently received therapeutic doses of (/sup 131/I)MIBG, with marked improvement in both pain and diarrhea, but no evidence of significant biochemical response. Iodine-131 MIBG uptake in patients with MCT is variable, and gives a higher false-negative rate than is found when using (/sup 131/I)MIBG to image other neuroectodermally derived tumors. The therapeutic potential of (/sup 131/I)MIBG in patients with MCT warrants further evaluation, in view of the symptomatic relief experienced following therapy doses in two patients with extensive disease.

  6. Tumor suppressor role of Notch3 in Medullary Thyroid Carcinoma revealed by genetic and pharmacological induction

    PubMed Central

    Jaskula-Sztul, Renata; Eide, Jacob; Tesfazghi, Sara; Dammalapati, Ajitha; Harrison, April D.; Yu, Xiao-Min; Scheinebeck, Casi; Winston-McPherson, Gabrielle; Kupcho, Kevin R.; Robers, Matthew B.; Hundal, Amrit K.; Tang, Weiping; Chen, Herbert

    2014-01-01

    Notch1-3 are transmembrane receptors that appear to be absent in Medullary Thyroid Cancer (MTC). Previous research has shown that induction of Notch1 has a tumor suppressor effect in MTC cell lines, but little is known about the biological consequences of Notch3 activation for the progression of the disease. We elucidate the role of Notch3 in MTC by genetic (doxycycline inducible Notch3 intracellular domain) and pharmacological (AB3, novel HDAC inhibitor) approaches. We find that overexpression of Notch3 leads to the dose dependent reduction of neuroendocrine tumor markers. In addition, Notch3 activity is required to suppress MTC cell proliferation, and the extent of growth repression depends on the amount of Notch3 protein expressed. Moreover, activation of Notch3 induces apoptosis. The translational significance of this finding is highlighted by our observation that MTC tumors lack active Notch3 protein and reinstitution of this isoform could be a therapeutic strategy to treat patients with MTC. We demonstrate, for the first time, that overexpression of Notch3 in MTC cells can alter malignant neuroendocrine phenotype in both in vitro and in vivo models. In addition, our study provides a strong rationale for using Notch3 as a therapeutic target to provide novel pharmacological treatment options for MTC. PMID:25512616

  7. Dynamic risk stratification for medullary thyroid cancer according to the response to initial therapy.

    PubMed

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

    2016-07-01

    Detecting persistent/recurrent disease of medullary thyroid carcinoma (MTC) is important. The tumor-node-metastasis (TNM) staging system is useful for predicting disease-specific mortality, but is a static system and does not include postoperative serum calcitonin levels. We have focused on the clinical usefulness of dynamic risk stratification (DRS) using the best response to the initial therapy in MTC patients. A total of 120 MTC patients were classified into three DRS groups based on their responses to initial therapy. Clinical outcomes were assessed according to TNM staging and DRS. In the DRS, 70, 23 and 7 % of the MTC patients were classified into excellent, biochemical incomplete, or structural incomplete response groups, respectively. On TNM staging, 37, 16, 13 and 35 % of patients were stages I-IV, respectively. There were significant differences in survivals according to TNM staging (p = 0.03) and DRS (p = 0.005). During the median follow-up of 6.2 years, 75 patients (63 %) demonstrated no evidence of disease (NED). About 60 and 17 % of patients in stages III and IV were NED, respectively. DRS predicted NED better than TNM staging according to the proportion of variance explained (PVE) (49.1 vs. 28.7 %, respectively). At the final follow-up, 88, 4 and 0 % of patients in excellent, biochemical incomplete, and structural incomplete response groups attained NED, respectively. DRS based on the best response to the initial therapy can provide useful prognostic information in addition to initial TNM staging for predicting of mortality, as well as the likelihood of NED in MTC patients. PMID:26754662

  8. High-throughput mutation profiling improves diagnostic stratification of sporadic medullary thyroid carcinomas.

    PubMed

    Simbolo, Michele; Mian, Caterina; Barollo, Susi; Fassan, Matteo; Mafficini, Andrea; Neves, Diogo; Scardoni, Maria; Pennelli, Gianmaria; Rugge, Massimo; Pelizzo, Maria Rosa; Cavedon, Elisabetta; Fugazzola, Laura; Scarpa, Aldo

    2014-07-01

    Sporadic medullary thyroid carcinoma (MTC) harbors RET gene somatic mutations in up to 50 % of cases, and RAS family gene mutations occur in about 10 %. A timely and comprehensive characterization of molecular alterations is needed to improve MTC diagnostic stratification and design-tailored therapeutic approaches. Twenty surgically resected sporadic MTCs, previously analyzed for RET mutations by Sanger sequencing using DNA from formalin-fixed paraffin-embedded samples, were investigated for intragenic mutations in 50 cancer-associated genes applying a multigene Ion AmpliSeq next-generation sequencing (NGS) technology. Thirteen (65 %) MTCs harbored a RET mutation; 10 were detected at both Sanger and NGS sequencing, while 3 undetected by Sanger were revealed by NGS. One of the 13 RET-mutated cases also showed an F354L germline mutation in STK11. Of the seven RET wild-type MTCs, four cases (57.1 %) harbored a RAS mutation: three in HRAS (all Q61R) and one in KRAS (G12R). The three remaining MTCs (15 %) resulted as wild-type for all the 50 cancer-related genes. Follow-up was available in all but one RET-mutated case. At the end of follow-up, 7 of 12 (58 %) RET-mutated patients had relapsed, while the 4 RAS-mutated MTC patients were disease-free. Two of the three patients with MTC wild-type for all 50 genes relapsed during the follow-up period. Detection of mutations by NGS has the potential to improve the diagnostic stratification of sporadic MTC. PMID:24828033

  9. Prognostic significance and optimal cutoff of age in medullary thyroid cancer

    PubMed Central

    Wang, Yu-long; Li, Duan-shu; Wang, Yu; Huang, Cai-ping; Ji, Qing-hai

    2016-01-01

    Age has been found to correlate with the prognosis for medullary thyroid cancer (MTC). This study was conducted to investigate whether age can predict long-term unfavorable prognosis and evaluate its predictive accuracy associated with TNM staging, using data of patients diagnosed with MTC between 2000 and 2010 from Surveillance, Epidemiology and End Results database. The relationship between the patients’ age at diagnosis and cancer-specific survival (CSS) was evaluated using multivariate Cox regression analysis. Age stratifications were combined into a nomogram model to predict the CSS of MTC. The X-tile program determined 49 and 69 as optimal age cutoff values for CSS. On multivariate analysis, independent factors for survival were age (50–69 years, HR 2.853, 95% CI 1.631–4.991; ≥70 years, HR 5.804, 95% CI 2.91–11.555), race (white, HR 0.344, 95% CI 0.188–0.630), T (T3/4, HR 3.931, 95% CI 2.093–7.381), N (N1a, HR 3.269, 95% CI 1.386–7.710) and M (M1, HR 3.998, 95% CI 2.419–6.606). The C-index for CSS prediction with TNM, age (cutoff of 45)/sex/race/TNM and age (cutoff of 49 and 69)/sex/race/TNM were 0.832 (95% CI 0.763–0.901), 0.863 (95% CI 0.799–0.928), and 0.876 (95% CI 0.817–0.935), respectively. Subgroup multivariate analyses also showed that age significantly increased the risk for CSS in females, non-Hispanic white patients, and those with stage IV MTC. In conclusion, CSS was independently associated with ages between 49 and 69 years, which might be applied for risk stratification in MTC patients. PMID:26910117

  10. Loss of heterozygosity suggests multiple genetic alterations in pheochromocytomas and medullary thyroid carcinomas.

    PubMed Central

    Khosla, S; Patel, V M; Hay, I D; Schaid, D J; Grant, C S; van Heerden, J A; Thibodeau, S N

    1991-01-01

    Loss of heterozygosity (LOH) at specific loci may help localize tumor suppressor genes involved in the formation of various familial and sporadic tumors. In addition, the genetic loci for a number of familial tumor syndromes have been mapped by linkage analysis. To explore the possible role of tumor suppressor genes in endocrine tumors, we tested 41 pheochromocytomas (34 sporadic and 7 familial) and 11 medullary thyroid cancers (MTC) (10 sporadic and 1 familial) for LOH near a variety of potentially important genetic loci: (a) the multiple endocrine neoplasia type 2A (MEN 2A) locus on chromosome 10; (b) the von Hippel-Lindau locus on 3p; and (c) the p53 and neurofibromatosis 1 loci on 17. We also examined chromosomes 1p and 22q because previous studies in a small number of pheochromocytomas and MTCs suggested LOH in these regions. Background rates for LOH were assessed using several "random" probes. Finally, we examined a number of clinical and histologic characteristics of these tumors for possible correlations with specific genetic alterations. LOH in the region of the MEN 2A locus was uncommon (0% for MTCs, 5% for pheochromocytomas). However, we found significant allelic losses in pheochromocytomas on chromosomes 1p (42%), 3p (16%), 17p (24%), and 22q (31%). We also noted a correlation between LOH on 1p and urinary excretion of metanephrine by these patients (P = 0.02). LOH on 1p, 3p, and 17p also appeared to be associated with increased tumor volume. Analysis of the smaller number of MTCs demonstrated allelic losses on chromosomes 1p and 22q. Our results suggest that tumor formation and/or progression in pheochromocytomas and MTCs involves multiple genes, analogous with the model proposed for colon carcinoma. Images PMID:2022740

  11. Preclinical testing of selective Aurora kinase inhibitors on a medullary thyroid carcinoma-derived cell line.

    PubMed

    Tuccilli, Chiara; Baldini, Enke; Prinzi, Natalie; Morrone, Stefania; Sorrenti, Salvatore; Filippini, Angelo; Catania, Antonio; Alessandrini, Stefania; Rendina, Roberta; Coccaro, Carmela; D'Armiento, Massimino; Ulisse, Salvatore

    2016-05-01

    Deregulated expression of the Aurora kinases (Aurora-A, B, and C) is thought to be involved in cell malignant transformation and genomic instability in several cancer types. Over the last decade, a number of small-molecule inhibitors of Aurora kinases have been developed, which have proved to efficiently restrain malignant cell growth and tumorigenicity. Regarding medullary thyroid carcinoma (MTC), we previously showed the efficacy of a pan-Aurora kinase inhibitor (MK-0457) in impairing growth and survival of the MTC-derived cell line TT. In the present study, we sought to establish if one of the Aurora kinases might represent a preferential target for MTC therapy. The effects of selective inhibitors of Aurora-A (MLN8237) and Aurora-B (AZD1152) were analyzed on TT cell proliferation, apoptosis, cell cycle, and ploidy. The two inhibitors reduced TT cell proliferation in a time- and dose-dependent manner, with IC50 of 19.0 ± 2.4 nM for MLN8237 and 401.6 ± 44.1 nM for AZD1152. Immunofluorescence experiments confirmed that AZD1152 inhibited phosphorylation of histone H3 (Ser10) by Aurora-B, while it did not affect Aurora-A autophosphorylation. MLN8237 inhibited Aurora-A autophosphorylation as expected, but at concentrations required to achieve the maximum antiproliferative effects it also abolished H3 (Ser10) phosphorylation. Cytofluorimetry experiments showed that both inhibitors induced accumulation of cells in G2/M phase and increased the subG0/G1 fraction and polyploidy. Finally, both inhibitors triggered apoptosis. We demonstrated that inhibition of either Aurora-A or Aurora-B has antiproliferative effects on TT cells, and thus it would be worthwhile to further investigate the therapeutical potential of Aurora kinase inhibitors in MTC treatment. PMID:26215279

  12. A novel RET inhibitor with potent efficacy against medullary thyroid cancer in vivo

    PubMed Central

    Samadi, Abbas K.; Mukerji, Ridhwi; Shah, Anuj; Timmermann, Barbara N.; Cohen, Mark S.

    2010-01-01

    Background Most medullary thyroid carcinomas (MTC) recur or progress despite optimal surgical resection. Current targeted-therapies show promise but lack durable efficacy and tolerability. The purpose of this study was to build upon previous in vitro work and evaluate Withaferin A (WA), a novel RET inhibitor, in a metastatic murine model of MTC. Methods 5 million DRO-81-1 human MTC-cells injected in the left posterior neck of Nu/Nu mice uniformly generated metastases to the liver, spleen, and/or lungs. Treatment with WA (8mg/kg/day i.p.×21 days) was started for tumors >100 mm3. Endpoints were survival, tumor>1500 mm3, decreased bodyweight, or body score (all measured thrice weekly). Results All controls (saline; n=5) died or deteriorated from metastatic disease by 7 weeks post injection. All treated animals were alive,(WA; n=5), having tumor regression and growth-delay without toxicity or weight-loss at 6 wks post treatment; p<0.01. Tumor cells treated with WA demonstrated inhibition of total and phospho-RET levels by Western-Blot analysis in a dose-dependent manner (almost complete inhibition with 5uM WA treatment) as well as potent inhibition of phospho-ERK and phospho-AKT levels. Conclusions Withaferin A is a novel natural-product RET-inhibitor with efficacy in a metastatic murine model of MTC. Further long-term efficacy/toxicity studies are warranted to evaluate this compound for clinical translation. PMID:21134556

  13. Identification of Driving ALK Fusion Genes and Genomic Landscape of Medullary Thyroid Cancer

    PubMed Central

    Yun, Jae Won; Lee, Hyun-Woo; Kim, DeokGeun; Ji, Yongick; Kim, Duk-Hwan; Park, Woong-Yang; Shin, Hyun-Tae; Kim, Kyoung-Mee; Ahn, Myung-Ju; Park, Keunchil; Sun, Jong-Mu

    2015-01-01

    The genetic landscape of medullary thyroid cancer (MTC) is not yet fully understood, although some oncogenic mutations have been identified. To explore genetic profiles of MTCs, formalin-fixed, paraffin-embedded tumor tissues from MTC patients were assayed on the Ion AmpliSeq Cancer Panel v2. Eighty-four sporadic MTC samples and 36 paired normal thyroid tissues were successfully sequenced. We discovered 101 hotspot mutations in 18 genes in the 84 MTC tissue samples. The most common mutation was in the ret proto-oncogene, which occurred in 47 cases followed by mutations in genes encoding Harvey rat sarcoma viral oncogene homolog (N = 14), serine/threonine kinase 11 (N = 11), v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (N = 6), mutL homolog 1 (N = 4), Kiesten rat sarcoma viral oncogene homolog (N = 3) and MET proto-oncogene (N = 3). We also evaluated anaplastic lymphoma kinase (ALK) rearrangement by immunohistochemistry and break-apart fluorescence in situ hybridization (FISH). Two of 98 screened cases were positive for ALK FISH. To identify the genomic breakpoint and 5’ fusion partner of ALK, customized targeted cancer panel sequencing was performed using DNA from tumor samples of the two patients. Glutamine:fructose-6-phosphate transaminase 1 (GFPT1)-ALK and echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusions were identified. Additional PCR analysis, followed by Sanger sequencing, confirmed the GFPT1-ALK fusion, indicating that the fusion is a result of intra-chromosomal translocation or deletion. Notably, a metastatic MTC case harboring the EML4-ALK fusion showed a dramatic response to an ALK inhibitor, crizotinib. In conclusion, we found several genetic mutations in MTC and are the first to identify ALK fusions in MTC. Our results suggest that the EML4-ALK fusion in MTC may be a potential driver mutation and a valid target of ALK inhibitors. Furthermore, the GFPT1-ALK fusion may be a potential candidate for molecular target

  14. Advances in thyroid cancer treatment: latest evidence and clinical potential

    PubMed Central

    Alonso-Gordoa, T.; Díez, J.J.; Durán, M.

    2015-01-01

    Advanced thyroid carcinoma is an infrequent tumor entity with limited treatment possibilities until recently. The extraordinary improvement in the comprehension of genetic and molecular alterations involving the RAS/RAF/mitogen-activated protein kinase and phosphatidylinositide 3-kinase/Akt/mammalian target of rapamycin signaling and interacting pathways that are involved in tumor survival, proliferation, differentiation, motility and angiogenesis have been the rationale for the development of new effective targeted therapies. Data coming from phase II clinical trials have confirmed the efficacy of those targeted agents against receptors in cell membrane and cytoplasmic molecules. Moreover, four of those investigational drugs, vandetanib, cabozantinib, sorafenib and lenvatinib, have reached a phase III clinical trial with favorable results in progression-free survival and overall survival in medullary thyroid carcinoma and differentiated thyroid carcinoma. Further analysis for an optimal approach has been conducted according to mutational profile and tumor subtypes. However, consistent results are still awaited and the research for adequate prognostic and predictive biomarkers is ongoing. The following report offers a comprehensive review from the rationale to the basis of targeted agents in the treatment of thyroid carcinoma. In addition, current and future therapeutic developments by the inhibition of further molecular targets are discussed in this setting. PMID:25553081

  15. Thyroid nodule

    MedlinePlus

    ... 2016:chap 14. Read More Chronic thyroiditis (Hashimoto disease) Laryngeal nerve damage Multiple endocrine neoplasia (MEN) II Thyroid cancer Thyroid cancer - medullary carcinoma Thyroid gland removal Patient Instructions Thyroid gland ...

  16. Acute coronary syndrome: a rare case of multiple endocrine neoplasia syndromes with pheochromocytoma and medullary thyroid carcinoma.

    PubMed

    Maloberti, Alessadro; Meani, Paolo; Pirola, Roberto; Varrenti, Marisa; Boniardi, Marco; De Biase, Anna Maria; Vallerio, Paola; Bonacina, Edgardo; Mancia, Giuseppe; Loli, Paola; Giannattasio, Cristina

    2015-09-01

    Pheochromocytoma is a tumor arising from neuroectodermal chromaffin tissues in the adrenal gland or extra-adrenal paraganglia (paragangliomas). The prevalence of the tumor is 0.1%-0.6% in the hypertensive population, of which 10%-20% are malignant. Pheochromocytoma produces, stores, and secretes catecholamines, as well as leads to hypertensive crisis, arrhythmia, angina, and acute myocardial infarction without coronary artery diseases. We report a case of acute coronary syndrome (ACS) with a final diagnosis of multiple endocrine neoplasia with pheochromocytoma and medullary thyroid carcinoma (MTC). PMID:26487970

  17. Acute coronary syndrome: a rare case of multiple endocrine neoplasia syndromes with pheochromocytoma and medullary thyroid carcinoma

    PubMed Central

    Maloberti, Alessadro; Meani, Paolo; Pirola, Roberto; Varrenti, Marisa; Boniardi, Marco; De Biase, Anna Maria; Vallerio, Paola; Bonacina, Edgardo; Mancia, Giuseppe; Loli, Paola; Giannattasio, Cristina

    2015-01-01

    Pheochromocytoma is a tumor arising from neuroectodermal chromaffin tissues in the adrenal gland or extra-adrenal paraganglia (paragangliomas). The prevalence of the tumor is 0.1%-0.6% in the hypertensive population, of which 10%-20% are malignant. Pheochromocytoma produces, stores, and secretes catecholamines, as well as leads to hypertensive crisis, arrhythmia, angina, and acute myocardial infarction without coronary artery diseases. We report a case of acute coronary syndrome (ACS) with a final diagnosis of multiple endocrine neoplasia with pheochromocytoma and medullary thyroid carcinoma (MTC). PMID:26487970

  18. Effects of tamoxifen and somatostatin analogue on growth of human medullary, follicular, and papillary thyroid carcinoma cell lines: tissue culture and nude mouse xenograft studies.

    PubMed

    Weber, C J; Marvin, M; Krekun, S; Koschitzky, T; Karp, F; Benson, M; Feind, C R

    1990-12-01

    The knowledge that (1) the normal thyroid contains somatostatin, (2) polypeptide growth factors influence thyroid cell function, and (3) thyroid cells contain steroid hormone receptors prompted us to add somatostatin analogue No. 201-995 (SMS) (5 ng/ml) and/or tamoxifen citrate (TAM) (5 mumol/L) to 7-day monolayer cultures (50,000 cells/well) of three separate human thyroid carcinoma cell lines: DR081 (medullary), WR082 (follicular), and NPA'87 (papillary). Results, tabulated as cell numbers/well (X10(5) on day 7, revealed that TAM inhibited growth of medullary and follicular cells and that TAM plus SMS inhibited growth of papillary cells. In vivo studies of subcutaneous tumor cell xenografts in nude mice have documented that TAM (5 mg subcutaneous pellet) significantly inhibits the growth of medullary implants. Flow cytometric DNA studies of medullary cell cultures demonstrated a reduced G2 + M phase with TAM treatment. For papillary cell implants, TAM plus SMS (5 micrograms subcutaneously, twice daily) did not suppress tumor growth. All three cell lines were negative for estrogen receptor; addition of estradiol (5 ng/ml) to medullary cell cultures neither stimulated replication nor reversed the inhibitory effects of TAM in vitro. We conclude that (1) TAM slowed the growth of a cell line of human medullary carcinoma, both in vitro and in vivo; (2) this effect was not reversed by estradiol; (3) TAM plus SMS inhibited replication of a papillary carcinoma cell line in vitro, but not in vivo; and (4) TAM alone and TAM plus SMS inhibited replication of cultures of a human follicular thyroid carcinoma cell line. TAM and SMS may be useful in treatment of some human thyroid carcinomas. PMID:1978945

  19. Radioimmunoimaging of metastatic medullary carcinoma of the thyroid gland using an indium-111-labeled monoclonal antibody to CEA

    SciTech Connect

    Edington, H.D.; Watson, C.G.; Levine, G.; Tauxe, W.N.; Yousem, S.A.; Unger, M.; Kowal, C.D.

    1988-12-01

    Elevated levels of carcinoembryonic antigen (CEA) or calcitonin after surgical therapy for medullary carcinoma of the thyroid gland (MCT) indicate the presence of residual or metastatic disease. CEA elevations appear to be prognostically more reliable in patients with metastatic disease and suggest a more virulent tumor. Attempts to stage the disease with use of conventional imaging techniques are usually inadequate, as is the therapy for disseminated or recurrent MCT. An indium-111-labeled anti-CEA monoclonal antibody (ZCE-025) was used to image metastases in a patient with MCT. Potential applications of monoclonal antibody technology in the management of MCT would include (1) preoperative differentiation of unicentric from multicentric thyroid gland involvement, (2) detection of regional or distant metastases or both, (3) measurement of response to systemic therapy, and (4) the facilitation of radionuclide immunoconjugate therapy.

  20. RREB-1, a novel zinc finger protein, is involved in the differentiation response to Ras in human medullary thyroid carcinomas.

    PubMed Central

    Thiagalingam, A; De Bustros, A; Borges, M; Jasti, R; Compton, D; Diamond, L; Mabry, M; Ball, D W; Baylin, S B; Nelkin, B D

    1996-01-01

    An activated ras oncogene induces a program of differentiation in the human medullary thyroid cancer cell line TT. This differentiation process is accompanied by a marked increase in the transcription of the human calcitonin (CT) gene. We have localized a unique Ras-responsive transcriptional element (RRE) in the CT gene promoter. DNase I protection indicates two domains of protein-DNA interaction, and each domain separately can confer Ras-mediated transcriptional inducibility. This bipartite RRE was also found to be Raf responsive. By affinity screening, we have cloned a cDNA coding for a zinc finger transcription factor (RREB-1) that binds to the distal RRE. The consensus binding site for this factor is CCCCAAACCACCCC. RREB-1 is expressed ubiquitously in human tissues outside the adult brain. Overexpression of RREB-1 protein in TT cells confers the ability to mediate increased transactivation of the CT gene promoter-reporter construct during Ras- or Raf-induced differentiation. These data suggest that RREB-1 may play a role in Ras and Raf signal transduction in medullary thyroid cancer and other cells. PMID:8816445

  1. RET mutation screening in MEN2 patients and discovery of a novel mutation in a sporadic medullary thyroid carcinoma.

    PubMed

    Jhiang, S M; Fithian, L; Weghorst, C M; Clark, O H; Falko, J M; O'Dorisio, T M; Mazzaferri, E L

    1996-04-01

    RET germline mutations were found to predispose to the development of three variants of multiple endocrine neoplasia type 2, MEN2A, MEN2B, and familial medullary thyroid carcinoma (FMTC). We have screened for RET mutations at exons 10, 11, 13, and 16 in leukocyte DNA extracted from 37 individuals, and have identified RET germline mutations in 12 affected individuals from 9 unrelated families. No RET germline mutation was found in 19 individuals with apparent sporadic diseases. We have also screened for RET mutations at exons 10, 11, and 16 in tumor DNA extracted from 13 freshly frozen medullary thyroid carcinomas (MTC). RET mutation was detected in every tumor, either inherited or sporadic, indicating that RET plays an important role in the development of both inherited and sporadic MTC. We initially screened for RET mutations by direct DNA sequencing of the genomic PCR products amplified from patients' leukocyte or tumor DNA. Recently, we utilized the "Cold SSCP" method, nonradioactive single-stranded conformation polymorphism analysis, to screen for RET mutations and have identified a novel mutation, a 6-bp deletion preceding the cysteine-634, in a sporadic MTC. PMID:8733882

  2. Comparison of metabolic and receptor imaging in recurrent medullary thyroid carcinoma with histopathological findings.

    PubMed

    Adams, S; Baum, R P; Hertel, A; Schumm-Draeger, P M; Usadel, K H; Hör, G

    1998-09-01

    Early diagnosis of metastases of medullary thyroid carcinoma (MTC) provides the optimal condition for curative outcome. The aim of this study was to appraise the detection of metastases in patients with recurrent MTC using [111In-DTPA-d-Phe1]-pentetreotide and pentavalent technetium-99m dimercaptosuccinic acid [99mTc(V)-DMSA] in comparison with histopathological findings. Eighteen MTC patients with persistently elevated tumour marker (calcitonin, carcinoembryonic antigen) levels underwent somatostatin receptor scintigraphy using [111In-DTPA-d-Phe1]-pentetreotide (222 MBq) with early (4 h after injection) and delayed (24 h) whole-body scans and single-photon emission tomography (SPET) imaging. Metabolic whole-body and SPET imaging using 500 MBq 99mTc(V)-DMSA was performed 4 h after injection. Metabolic and receptor imaging revealed 51 sites of focal accumulation in the 18 patients investigated. Comparison with histological findings revealed that metabolic and receptor imaging had a sensitivity of 84% for the diagnosis of MTC. Using [111In-DTPA-d-Phe1]-pentetreotide, SPET discovered four lymph node metastases in two patients in whom planar views had previously identified only one lymph node metastasis, and provided no new information in the other 16 patients. In comparison, SPET studies [using 99mTc(V)-DMSA] additionally localized eight lymph node metastases in four patients and confirmed the diagnosis of hepatic metastases (n=5) in another patient in whom conventional imaging modalities and planar views had previously detected only three liver metastases. Overall, lesion detection sensitivities for 99mTc(V)-DMSA and [111In-DTPA-D-Phe1]-pentetreotide were 69% and 29%, respectively. Five surgically removed foci were adjudged false-positive with respect to MTC metastases. False-positve results were caused by lymphadenitis, an enchondroma and a pheochromocytoma (histologically proven). The smallest lesion identified by metabolic imaging was a 6 mm in diameter lymph node

  3. Distribution of RET Mutations and Evaluation of Treatment Approaches in Hereditary Medullary Thyroid Carcinoma in Turkey

    PubMed Central

    Aydoğan, Berna İmge; Yüksel, Bağdagül; Tuna, Mazhar Müslüm; Navdar Başaran, Mehtap; Akkurt Kocaeli, Ayşen; Ertörer, Melek Eda; Aydın, Kadriye; Güldiken, Sibel; Şimşek, Yasin; Cihan Karaca, Züleyha; Yılmaz, Merve; Aktürk, Müjde; Anaforoğlu, İnan; Kebapçı, Nur; Duran, Cevdet; Taşlıpınar, Abdullah; Kulaksızoğlu, Mustafa; Gürsoy, Alptekin; Dağdelen, Selçuk; Erdoğan, Murat Faik

    2016-01-01

    Objective: This retrospective multicenter study, centrally conducted and supported by the Society of Endocrinology and Metabolism of Turkey, aimed to evaluate the impact of free RET proto-oncogene testing in medullary thyroid carcinoma (MTC) patients. Surgical timing, adequacy of the treatment, and frequency of prophylactic thyroidectomy (PTx) in mutation carriers were also assessed. Methods: Genetic testing for MTC and pheochromocytoma was conducted between July 2008 and January 2012 in 512 patients. Application forms and RET mutation analyses of these patients whose blood samples were sent from various centers around Turkey were assessed retrospectively. An evaluation form was sent to the physicians of the eligible 319 patients who had confirmed sporadic MTC, familial MTC (FMTC), multiple endocrine neoplasia type 2 (MEN2), or who were mutation carriers. Physicians were asked to give information about the surgical history, latest calcitonin levels, morbidity, mortality, genetic screening, and PTx among family members. Twenty-five centers responded by filling in the forms of 192 patients. Results: Among the 319 patients, RET mutation was detected in 71 (22.3%). Cys634Arg mutation was the most prevalent mutation (43.7%), followed by Val804Met in 18 patients (25.4%), and Cys634Tyr in 6 patients (8.5%). Among 192 MTC patients, the diagnosis was sporadic MTC in 146 (76.4%), FMTC in 14 (7.3%), MEN2A in 15 patients (7.9%), and MEN2B in one patient. The number of mutation carriers among 154 apparently sporadic MTC patients was 8 (5.2%). Ten patients were submitted to PTx out of twenty-four mutation carriers at a mean age of 35±19 years. Conclusion: Turkish people have a similar RET proto-oncogene mutation distribution when compared to other Mediterranean countries. Despite free RET gene testing, the number of the PTx in Turkey is limited and relatively late in the life span of the carriers. This is mainly due to patient and family incompliance and incomplete family

  4. Advances in the management of patients with thyroid disease.

    PubMed

    Dworkin, H J; Meier, D A; Kaplan, M

    1995-07-01

    Discoveries related to thyroid immunology, especially concerning the thyroid-stimulating hormone (TSH) receptor, may facilitate new immunologic approaches to the therapy of Graves' disease and the thyroiditis syndromes. Advances in genetics are being applied to the thyroid hormone resistance syndromes and papillary and medullary carcinomas. The development of ever more sensitive TSH assays has led to the detection of subclinical thyroid disease, which has special implications for the sick and elderly patients. Sensitive TSH assays also allow more precise titration of levothyroxine (T4) dosages, especially for patients with a past history of thyroid cancer. Evidence continues to accumulate suggesting that postmenopausal women on T4 doses that suppress the TSH level below 0.1 ulU/mL have lower bone mineral density than matched patients with healthy TSH levels. Also, pregnant hypothyroid women need higher T4 doses to normalize the TSH levels. In the evaluation of thyroid nodules, fine-needle aspiration biopsy is the single most definitive modality in selecting the patients for surgery. Scintigraphy provides a complimentary role, especially in defining autonomously functioning thyroid adenomas (AFTA), because these should not be treated with T4 suppression. Ultrasound-guided needle biopsy is occasionally helpful with nodules that are difficult to palpate. Concern for possible tracheal compression after treatment of toxic multinodular goiter with large doses of radioactive iodine (I-131) in the range of 50 to 150 mCi (1.85 to 5.5 GBq) does not seem warranted. Work, primarily out of Italy, suggests AFTA can be ablated with repeat ethanol injections. Residual tissues after thyroidectomy for differentiated carcinoma can be "stunned" by tracer doses of 131I greater than 3.0 mCi (111 MBq), which diminishes the uptake and effectiveness of a subsequent therapy dose. Positron emission tomograph, imaging with thallium-201, and Technetium 99m Sestamibi can identify a small number

  5. Great cervical venous tumoral thrombosis of melanotic medullary carcinoma thyroid: Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography enabled diagnosis and radiotherapy planning

    PubMed Central

    Chigurupati, Mohana Vamsy; Madiraju, Vidya; Chigurupati, Namrata; Shinkar, Pawan Gulabrao; Dhagam, Snehalatha; Prabhakar Rao, Vatturi Venkata Satya

    2016-01-01

    The authors report an extremely rare occurrence of a massive tumor thrombus involving right internal and external jugular veins extending into superior vena cava from a still rarer melanotic medullary carcinoma thyroid in the postoperative follow-up. The case was managed by hypofractionated intensity modulated radiotherapy technique with gratifying results. PMID:26917895

  6. Recurrent spinal metastasis of a sporadic medullary carcinoma of the thyroid after radiation therapy: a case report and review of the literature.

    PubMed

    Munoz-Bendix, Christopher; Santacroce, Antonio; Gierga, Kristin; Floeth, Frank W; Steiger, Hans-Jakob; Penalonzo, Marco Antonio; Eicker, Sven Oliver

    2016-01-01

    Sporadic Medullary Carcinoma of the Thyroid is a relatively uncommon entity and at the time of diagnosis, most already present loco-regional metastasis. Therapy should be aggressive to reduce recurrence and mortality. Follow-up period should continue lifelong and should also include calcium/pentagastrin infusion test, as well as 6-month interval diagnostic imaging. PMID:26783427

  7. Simultaneous presentation of giant pheochromocytoma, primary hyperparathyroidism, and mixed-medullary-papillary thyroid cancer in MEN 2A.

    PubMed

    Gupta, Vishal

    2013-07-01

    The aim of this study was to describe a young man with probably the largest pheochromocytoma associated with MEN 2A, described till date. The patient, a non-vegetarian, fifth of eight siblings, married, having five children, presented with episodes of difficult-to-control hypertension requiring over five antihypertensives. He was referred to us with an abdominal CT scan that revealed a 16 cm left-sided adrenal mass. Biochemical testing confirmed a catecholamine secreting pathology. Histopathology confirmed the mass as a pheochromocytoma weighing 1.8 kg. Further evaluation suggested a parathormone-dependent hypercalcemia and a left-sided thyroid mass. Histopathology confirmed parathyroid hyperplasia and medullary carcinoma of the thyroid mixed with papillary carcinoma of thyroid. Putting all the findings together showed that the patient was suffering from multiple endocrine neoplasia 2. Multiple endocrine neoplasia 2A is a rare syndrome. The case is unique in the way it presented, with all the three tumors at the same time. The management was bold and addressed all the three lesions in the same hospital admission. We are also reporting the largest described case of pheochromocytoma from India. PMID:23961501

  8. Mild to moderate increase of serum calcitonin levels only in presence of large medullary thyroid cancer deposits.

    PubMed

    Pelizzo, M R; Torresan, F; Da Roit, A; Merante Boschin, I; Chondrogiannis, S; Rampin, L; Colletti, P M; Vinjamury, S; Perkins, A J; Rubello, D

    2015-01-01

    Many open questions remain to be elucidated about the diagnosis, treatment and prognosis of medullary thyroid cancer (MTC). The most intriguing concerns the outcome of MTC patients after surgery. Great importance is usually given to serum calcitonin (Ct) and carcinoembryonic (CEA) levels. It is commonly believed that the higher are the levels of these tumor markers and their kinetics (double time and velocity of markers levels) the worst is the prognosis. However, this is not the rule, as there are huge MTC metastatic deposits characterized by low serum Ct and CEA levels, and this condition is not closely related to the outcome of the disease during post-surgical follow-up. A series is reported here of patients who have these characteristics, as well as a description of their prognosis and clinical outcome. PMID:26420439

  9. Can the Serum Level of Myostatin be Considered as an Informative Factor for Cachexia Prevention in Patients with Medullary Thyroid Cancer?

    PubMed

    Hedayati, Mehdi; Nozhat, Zahra; Hannani, Masoomeh

    2016-01-01

    Thyroid cancer, the most common endocrine neoplasia, consists of four main types of carcinomas: papillary, follicular, and anaplastic, all with thyroid follicular origin, and medullary thyroid cancer (MTC) related to para-follicular cells. Cronic diseases such as diverse cancers may be associated with cachexia, especially at advanced stage. Cancer-induced cachexia is associated with diminished quality of life, functional performance, reduced response to antitumor therapy, and increased morbidity and mortality. Myostatin (Mst) is one of the outstanding molecules in the skeletal muscle loss process in cancer and it may be released by both skeletal muscle and cachexia-inducing tumors. Recently changes in serum levels of Mst have been identified as an important factor of cancer-induced cachexia. The goal of this study was to assessserum Mst levels in MTC patients. In this descriptive and case-control study, 90 participants were selected, comprising 45 MTC patients (20 males, 29±13.9 years, 25 females, 29±14.5 years) and 45 control individuals (25 males, 23.1±11.6 years, 20 females, 31.5±14.4 years). Serum Mst was determined using an ELISA kit and body mass index (BMI) was calculated by weight and height measurements. The Kolmogorov Simonov test showed a normal distribution for log transformed Mst serum levels in both case and control groups. Geometric means were 5.9 and 8.2 ng/ml respectively, and a significant difference was found according to the independent t-test results (P<0.01) . There was also a significant difference mean of Mst between females in control and MTC groups, but not for the males. Pearson correlation test showed no correlation between age and BMI with Mst serum levels. The findings of this study support the hypothesis that Mst serum levels may have a potential ability for early diagnosis of cachexia in MTC patients, especially in females. PMID:27165248

  10. Genetic and epigenetic background and protein expression profiles in relation to telomerase activation in medullary thyroid carcinoma

    PubMed Central

    Wang, Na; Kjellin, Hanna; Sofiadis, Anastasios; Fotouhi, Omid; Juhlin, C. Christofer; Bäckdahl, Martin; Zedenius, Jan; Xu, Dawei; Lehtiö, Janne; Larsson, Catharina

    2016-01-01

    Medullary thyroid carcinomas (MTCs) exhibit telomerase activation in strong association with shorter patient survival. To understand the background of telomerase activation we quantified TERT copy numbers and TERT promoter methylation in 42 MTCs and normal thyroid references. Gain of TERT was demonstrated by quantitative PCR in 5/39 sporadic MTC. Increased methylation index (MetI) for CpG methylation at the TERT promoter was found in sporadic MTCs (P < 0.0001) and in MEN 2 associated MTCs (P = 0.011) vs. normal thyroid tissues. MetI correlated positively with TERT gene expression (r = 0.432, P = 0.006) and negatively with telomere length (r = −0.343, P = 0.032). MTC cases with MetI above the median of 52% had shorter survival as compared to cases with lower MetI (P = 0.005 for overall survival and P = 0.007 for disease-related survival). Protein expression profiles obtained by mass spectrometry were then studied in relation to telomerase activation in MTCs. Comparing protein levels between tumors defined by telomerase activity status, 240 proteins were associated with telomerase activity. Among telomerase activation positive cases a set of proteins was found to discriminate between MTCs with high and low TERT gene expression with enrichment for proteins involved in telomerase regulation. XRCC5 mRNA expression was found increased in MTCs vs. normal thyroid (P = 0.007). In conclusion the findings suggest a role for TERT copy number gain, TERT promoter methylation and XRCC5 expression in telomerase activation and telomere maintenance of MTC. PMID:26870890

  11. Germline ESR2 mutation predisposes to medullary thyroid carcinoma and causes up-regulation of RET expression.

    PubMed

    Smith, Joel; Read, Martin L; Hoffman, Jon; Brown, Rachel; Bradshaw, Beth; Campbell, Christopher; Cole, Trevor; Navas, Johanna Dieguez; Eatock, Fiona; Gundara, Justin S; Lian, Eric; Mcmullan, Dom; Morgan, Neil V; Mulligan, Lois; Morrison, Patrick J; Robledo, Mercedes; Simpson, Michael A; Smith, Vicki E; Stewart, Sue; Trembath, Richard C; Sidhu, Stan; Togneri, Fiona S; Wake, Naomi C; Wallis, Yvonne; Watkinson, John C; Maher, Eamonn R; McCabe, Christopher J; Woodward, Emma R

    2016-05-01

    Familial medullary thyroid cancer (MTC) and its precursor, C cell hyperplasia (CCH), is associated with germline RET mutations causing multiple endocrine neoplasia type 2. However, some rare families with apparent MTC/CCH predisposition do not have a detectable RET mutation. To identify novel MTC/CCH predisposition genes we undertook exome resequencing studies in a family with apparent predisposition to MTC/CCH and no identifiable RET mutation. We identified a novel ESR2 frameshift mutation, c.948delT, which segregated with histological diagnosis following thyroid surgery in family members and demonstrated loss of ESR2-encoded ERβ expression in the MTC tumour. ERα and ERβ form heterodimers binding DNA at specific oestrogen-responsive elements (EREs) to regulate gene transcription. ERβ represses ERα-mediated activation of the ERE and the RET promoter contains three EREs. In vitro, we showed that ESR2 c.948delT results in unopposed ERα mediated increased cellular proliferation, activation of the ERE and increased RET expression. In vivo, immunostaining of CCH and MTC using an anti-RET antibody demonstrated increased RET expression. Together these findings identify germline ESR2 mutation as a novel cause of familial MTC/CCH and provide important insights into a novel mechanism causing increased RET expression in tumourigenesis. PMID:26945007

  12. Advanced thyroid cancers: new era of treatment.

    PubMed

    Mohammed, Amrallah A; El-Shentenawy, Ayman

    2014-07-01

    Since chemotherapy has been shown to be unsuccessful in case of advanced thyroid carcinomas, the research for new therapies is fundamental. Clinical trials of many tyrosine kinase inhibitors as well as anti-angiogenic inhibitors suggest that patients with thyroid cancer could have an advantage with new target therapy. Recently, Food and Drug Administration approved two targeted therapies, vandetanib and cabozantinib for the treatment of metastatic thyroid carcinomas with acceptable outcome. We summarized the results and the toxic effects associated with these treatments reported in clinical trials. Future trials should aim at combinations of targeted agents with or without other treatment modalities to obtain a more effective result in thyroid carcinoma treatment. PMID:24908065

  13. New Treatment of Medullary and Papillary Human Thyroid Cancer: Biological Effects of Hyaluronic Acid Hydrogel Loaded With Quercetin Alone or in Combination to an Inhibitor of Aurora Kinase.

    PubMed

    Quagliariello, Vincenzo; Armenia, Emilia; Aurilio, Caterina; Rosso, Francesco; Clemente, Ottavia; de Sena, Gabriele; Barbarisi, Manlio; Barbarisi, Alfonso

    2016-08-01

    The aim of this paper is based on the use of a hyaluronic acid hydrogel of Quercetin tested alone and in combination to an inhibitor of Aurora Kinase type A and B (SNS-314) on human medullary and papillary thyroid cancer cells. Biological investigations were focused on the cellular uptake of the hydrogel, cell viability, antioxidant, and cytokines secretion studies. Quercetin delivered from hydrogel show a time and CD44 dependent interaction with both cell lines with significant anti-inflammatory effects. Combination of Quercetin and SNS-314 leads to a synergistic cytotoxic effect on medullary TT and papillary BCPAP cell lines with a significant reduction of the IC50 value. These results, highlights the importance of synergistic effect of the hyaluronic acid hydrogel of Quercetin with SNS-314 in the regulation of human thyroid cancer cell proliferation and emphasize the anti-tumor activity of these molecules. J. Cell. Physiol. 231: 1784-1795, 2016. © 2015 Wiley Periodicals, Inc. PMID:26660542

  14. Are there disparities in the presentation, treatment and outcomes of patients diagnosed with medullary thyroid cancer?—An analysis of 634 patients from the California Cancer Registry

    PubMed Central

    Cox, Christine; Chen, Yingjia; Cress, Rosemary; Semrad, Alison M.; Semrad, Thomas; Gosnell, Jessica E.

    2016-01-01

    Background Race, gender and socioeconomic disparities have been suggested to adversely influence stage at presentation, treatment options and outcomes in patients with cancer. Underserved minorities and those with a low socioeconomic status (SES) present with more advanced disease and have worse outcomes for differentiated thyroid cancer, but this relationship has never been evaluated for medullary thyroid cancer (MTC). Methods We used the California Cancer Registry (CCR) to evaluate disparities in the presentation, treatment and outcomes of patients diagnosed with MTC. Results We identified 634 patients with MTC diagnosed between 1988 and 2011. Almost everyone (85%) underwent thyroidectomy with 50% having a central lymph node dissection (CLND). There were no statistically significant differences by age, race or SES in mean tumor size or the proportion of patients diagnosed with localized disease, but men were diagnosed with larger tumors than women and were less likely to be diagnosed at a localized stage. Younger patients and women were more likely to be treated with a thyroidectomy. There were no statistically significant differences in surgical treatment by race or SES. Patients in the highest SES category had a better overall survival, but not disease specific survival, than those in the lowest SES (HR =0.3, CI =0.1–0.7). Patients treated with thyroidectomy had a better overall and cause specific survival, but the effect of CLND was not statistically significant after adjustment for other factors. Conclusions In MTC, we did not find that race, gender or SES influenced the presentation, treatment or outcomes of patients with MTC. Men with MTC present with larger tumors and are less likely to have localized disease. Half of the MTC patients in California do not undergo a CLND at the time of thyroidectomy, which may suggest a lack appropriate care across a range of healthcare systems. PMID:27563561

  15. RET mutation p.S891A in a Chinese family with familial medullary thyroid carcinoma and associated cutaneous amyloidosis binding OSMR variant p.G513D

    PubMed Central

    Qi, Xiao-Ping; Zhao, Jian-Qiang; Chen, Zhen-Guang; Cao, Jin-Lin; Du, Juan; Liu, Nai-Fang; Li, Feng; Sheng, Mao; Fu, Er; Guo, Jian; Jia, Hong; Zhang, Yi-Ming; Ma, Ju-Ming

    2015-01-01

    There are no reports on the relationship between familial medullary thyroid carcinoma (FMTC) associated with cutaneous amyloidosis (CA) and RET or OSMR/IL31RA gene mutations. In this study, we investigated a Chinese family with FMTC/CA and found a recurrent RET c.2671T>G (p.S891A) mutation in six of 17 family members. Three of the six p.S891A mutation carriers presented with medullary thyroid carcinoma (MTC). Of them, three (two with and one without MTC) were diagnosed as having combined lichen/macular biphasic CA. We also identified a novel RET variant, c.1573C>T (p.R525W) in five members. Of them, three carriers had no evidence of thyroid/skin or basal serum/stimulated calcitonin abnormalities. In vitro cell proliferation assay indicated that oncogenic activity of RET p.S891A was slightly enhanced by p.R525W, whereas p.R525W alone had no effect on cell proliferation. Meanwhile, we identified a novel OSMR variant, c.1538G>A (p.G513D) in seven members. We noticed that three OSMR p.G513D carriers presenting with CA also had the RET p.S891A mutation. Our investigation indicated that the RET p.S891A mutation combined with OSMR p.G513D may underlie a novel phenotype manifesting as FMTC and CA. PMID:26356818

  16. RET mutation p.S891A in a Chinese family with familial medullary thyroid carcinoma and associated cutaneous amyloidosis binding OSMR variant p.G513D.

    PubMed

    Qi, Xiao-Ping; Zhao, Jian-Qiang; Chen, Zhen-Guang; Cao, Jin-Lin; Du, Juan; Liu, Nai-Fang; Li, Feng; Sheng, Mao; Fu, Er; Guo, Jian; Jia, Hong; Zhang, Yi-Ming; Ma, Ju-Ming

    2015-10-20

    There are no reports on the relationship between familial medullary thyroid carcinoma (FMTC) associated with cutaneous amyloidosis (CA) and RET or OSMR/IL31RA gene mutations. In this study, we investigated a Chinese family with FMTC/CA and found a recurrent RET c.2671T>G (p.S891A) mutation in six of 17 family members. Three of the six p.S891A mutation carriers presented with medullary thyroid carcinoma (MTC). Of them, three (two with and one without MTC) were diagnosed as having combined lichen/macular biphasic CA. We also identified a novel RET variant, c.1573C>T (p.R525W) in five members. Of them, three carriers had no evidence of thyroid/skin or basal serum/stimulated calcitonin abnormalities. In vitro cell proliferation assay indicated that oncogenic activity of RET p.S891A was slightly enhanced by p.R525W, whereas p.R525W alone had no effect on cell proliferation. Meanwhile, we identified a novel OSMR variant, c.1538G>A (p.G513D) in seven members. We noticed that three OSMR p.G513D carriers presenting with CA also had the RET p.S891A mutation. Our investigation indicated that the RET p.S891A mutation combined with OSMR p.G513D may underlie a novel phenotype manifesting as FMTC and CA. PMID:26356818

  17. Comprehensive assessment of the disputed RET Y791F variant shows no association with medullary thyroid carcinoma susceptibility

    PubMed Central

    Toledo, Rodrigo A; Hatakana, Roxanne; Lourenço, Delmar M; Lindsey, Susan C; Camacho, Cleber P; Almeida, Marcio; Lima, José V; Sekiya, Tomoko; Garralda, Elena; Naslavsky, Michel S; Yamamoto, Guilherme L; Lazar, Monize; Meirelles, Osorio; Sobreira, Tiago J P; Lebrao, Maria Lucia; Duarte, Yeda A O; Blangero, John; Zatz, Mayana; Cerutti, Janete M; Maciel, Rui M B; Toledo, Sergio P A

    2015-01-01

    Accurate interpretation of germline mutations of the rearranged during transfection (RET) proto-oncogene is vital for the proper recommendation of preventive thyroidectomy in medullary thyroid carcinoma (MTC)-prone carriers. To gain information regarding the most disputed variant of RET, ATA-A Y791F, we sequenced blood DNA samples from a cohort of 2904 cancer-free elderly individuals (1261 via Sanger sequencing and 1643 via whole-exome/genome sequencing). We also accessed the exome sequences of an additional 8069 individuals from non-cancer-related laboratories and public databanks as well as genetic results from the Catalogue of Somatic Mutations in Cancer (COSMIC) project. The mean allelic frequency observed in the controls was 0.0031, with higher occurrences in Central European populations (0.006/0.008). The prevalence of RET Y791F in the control databases was extremely high compared with the 40 known RET pathogenic mutations (P=0.00003), while no somatic occurrence has been reported in tumours. In this study, we report new, unrelated Brazilian individuals with germline RET Y791F-only: two tumour-free elderly controls; two individuals with sporadic MTC whose Y791F-carrying relatives did not show any evidence of tumours; and a 74-year-old phaeochromocytoma patient without MTC. Furthermore, we showed that the co-occurrence of Y791F with the strong RET C634Y mutation explains the aggressive MTC phenotypes observed in a large affected family that was initially reported as Y791F-only. Our literature review revealed that limited analyses have led to the misclassification of RET Y791F as a probable pathogenic variant and, consequently, to the occurrence of unnecessary thyroidectomies. The current study will have a substantial clinical influence, as it reveals, in a comprehensive manner, that RET Y791F only shows no association with MTC susceptibility. PMID:25425582

  18. Selective Mitochondrial Uptake of MKT-077 Can Suppress Medullary Thyroid Carcinoma Cell Survival In Vitro and In Vivo

    PubMed Central

    Starenki, Dmytro

    2015-01-01

    Background Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor mainly caused by mutations in the rearranged during transfection (RET) proto-oncogene. Not all patients with progressive MTC respond to current therapy inhibiting RET, demanding additional therapeutic strategies. We recently demonstrated that disrupting mitochondrial metabolism using a mitochondria-targeted agent or by depleting a mitochondrial chaperone effectively suppressed human MTC cells in culture and in mouse xenografts by inducing apoptosis and RET downregulation. These observations led us to hypothesize that mitochondria are potential therapeutic targets for MTC. This study further tests this hypothesis using1-ethyl-2-[[3-ethyl-5-(3-methylbenzothiazolin-2-yliden)]-4-oxothiazolidin-2-ylidenemethyl] pyridinium chloride (MKT-077), a water-soluble rhodocyanine dye analogue, which can selectively accumulate in mitochondria. Methods The effects of MKT-077 on cell proliferation, survival, expression of RET and tumor protein 53 (TP53), and mitochondrial activity were determined in the human MTC lines in culture and in mouse xenografts. Results MKT-077 induced cell cycle arrest in TT and MZ-CRC-1. Intriguingly, MKT-077 also induced RET downregulation and strong cell death responses in TT cells, but not in MZ-CRC-1 cells. This discrepancy was mainly due to the difference between the capacities of these cell lines to retain MKT-077 in mitochondria. The cytotoxicity of MKT-077 in TT cells was mainly attributed to oxidative stress while being independent of TP53. MKT-077 also effectively suppressed tumor growth of TT xenografts. Conclusion MKT-077 can suppress cell survival of certain MTC subtypes by accumulating in mitochondria and interfering with mitochondrial activity although it can also suppress cell proliferation via other mechanisms. These results consistently support the hypothesis that mitochondrial targeting has therapeutic potential for MTC. PMID:26485469

  19. Detection rate of recurrent medullary thyroid carcinoma using fluorine-18 fluorodeoxyglucose positron emission tomography: a meta-analysis.

    PubMed

    Treglia, Giorgio; Villani, Maria Felicia; Giordano, Alessandro; Rufini, Vittoria

    2012-12-01

    Several studies evaluated the diagnostic performance of fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET), and positron emission tomography/computed tomography (PET/CT) in detecting recurrent medullary thyroid carcinoma (MTC) with conflicting results. Aim of our study is to meta-analyze published data about this topic. A comprehensive computer literature search of studies published in PubMed/MEDLINE, Scopus, and Embase databases through December 2011 and regarding FDG PET or PET/CT in patients with suspected recurrent MTC was carried out. Pooled detection rate (DR) on a per patient-based analysis was calculated to measure the diagnostic performance of FDG PET and PET/CT in this setting. A sub-analysis considering PET device used, serum calcitonin, carcino-embryonic antigen (CEA), calcitonin doubling time (CTDT), and CEA doubling time (CEADT) values was also performed. Twenty-four studies comprising 538 patients with suspected recurrent MTC were included. DR of FDG PET or PET/CT in suspected recurrent MTC on a per patient-based analysis was 59 % (95 % confidence interval: 54-63 %). Heterogeneity between the studies was revealed. DR increased in patients with serum calcitonin ≥ 1,000 ng/L (75 %), CEA ≥ 5 ng/ml (69 %), CTDT <12 months (76 %), and CEADT <24 months (91 %). In patients with suspected recurrent MTC FDG PET and PET/CT are associated with a non-optimal DR since about 40 % of suspected recurrent MTC remain usually unidentified. However, FDG PET and PET/CT could modify the patient management in a certain number of recurrent MTC because these methods are often performed after negative conventional imaging studies. DR of FDG PET and PET/CT increases in patients with higher calcitonin and CEA values and lower CTDT and CEADT values, suggesting that these imaging methods could be very helpful in patients with more aggressive disease. PMID:22527889

  20. Treatment of advanced thyroid cancer with targeted therapies: ten years of experience.

    PubMed

    Viola, David; Valerio, Laura; Molinaro, Eleonora; Agate, Laura; Bottici, Valeria; Biagini, Agnese; Lorusso, Loredana; Cappagli, Virginia; Pieruzzi, Letizia; Giani, Carlotta; Sabini, Elena; Passannati, Paolo; Puleo, Luciana; Matrone, Antonio; Pontillo-Contillo, Benedetta; Battaglia, Valentina; Mazzeo, Salvatore; Vitti, Paolo; Elisei, Rossella

    2016-04-01

    Thyroid cancer is rare, but it is the most frequent endocrine malignancy. Its prognosis is generally favorable, especially in cases of well-differentiated thyroid cancers (DTCs), such as papillary and follicular cancers, which have survival rates of approximately 95% at 40 years. However, 15-20% of cases became radioiodine refractory (RAI-R), and until now, no other treatments have been effective. The same problems are found in cases of poorly differentiated (PDTC) and anaplastic (ATC) thyroid cancers and in at least 30% of medullary thyroid cancer (MTC) cases, which are very aggressive and not sensitive to radioiodine. Tyrosine kinase inhibitors (TKIs) represent a new approach to the treatment of advanced cases of RAI-R DTC, MTC, PDTC, and, possibly, ATC. In the past 10 years, several TKIs have been tested for the treatment of advanced, progressive, and RAI-R thyroid tumors, and some of them have been recently approved for use in clinical practice: sorafenib and lenvatinib for DTC and PDTC and vandetanib and cabozantinib for MTC. The objective of this review is to present the current status of the treatment of advanced thyroid cancer with the use of innovative targeted therapies by describing both the benefits and the limits of their use based on the experiences reported so far. A comprehensive analysis and description of the molecular basis of these therapies, as well as new therapeutic perspectives, are reported. Some practical suggestions are given for both the choice of patients to be treated and their management, with particular regard to the potential side effects. PMID:27207700

  1. Reference values of serum calcitonin with calcium stimulation tests by electrochemiluminescence immunoassay before/after total thyroidectomy in Japanese patients with thyroid diseases other than medullary thyroid carcinoma.

    PubMed

    Kihara, Minoru; Miyauchi, Akira; Kudo, Takumi; Hirokawa, Mitsuyoshi; Miya, Akihiro

    2016-07-30

    Calcitonin is a very sensitive tumor marker of medullary thyroid carcinoma (MTC). MTC patients usually have very high values of serum calcitonin that can be used to diagnose the disease. To improve the diagnostic sensitivity in family members with small MTCs and to evaluate the postoperative biochemical cure status, a calcium stimulation test is widely used. Serum calcitonin has been measured using several methods, but in Japan, only an electrochemiluminescence immunoassay (ECLIA) is currently performed to determine serum calcitonin. Reference values for the calcium stimulation test using an ECLIA have not been reported. Here we conducted a calcium stimulation tests in 26 patients without MTC before and after total thyroidectomy. Preoperatively, the basal calcitonin values of all patients were within normal limits and increased to a mean of 14.4 pg/mL after calcium stimulation. We transformed the peak values before total thyroidectomy to a logarithmic distribution and calculated the normalized mean ± 1.96× standard deviation; the reference upper limit was thus expressed. In the female patients with non-MTC, the reference upper limit was 67.6 pg/mL. In all patients, the calcium stimulation test results after total thyroidectomy showed undetectable basal and stimulated calcitonin values (<0.5 pg/mL). This is the first study to determine reference values to be used for the calcium stimulation test along with an ECLIA in non-MTC patients. We propose that female patients are regarded as biochemically cured or normal when the stimulated calcitonin values by ECLIA are <67.6 pg/mL before surgery and <0.5 pg/mL after total thyroidectomy. PMID:27097651

  2. 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

  3. Development of medullary thyroid carcinoma in transgenic mice expressing the RET protooncogene altered by a multiple endocrine neoplasia type 2A mutation

    PubMed Central

    Michiels, Francine-Marie; Chappuis, Sophie; Caillou, Bernard; Pasini, Andrea; Talbot, Monique; Monier, Roger; Lenoir, Gilbert M.; Feunteun, Jean; Billaud, Marc

    1997-01-01

    Multiple endocrine neoplasia type 2 (MEN 2) is a dominantly inherited cancer syndrome that comprises three clinical subtypes: MEN type 2A (MEN-2A), MEN type 2B (MEN-2B), and familial medullary thyroid carcinoma (FMTC). Medullary thyroid carcinoma (MTC), a malignant tumor arising from calcitonin-secreting thyroid C cells, is the cardinal disease feature of this syndrome, and mortality in affected MEN-2 patients is mainly caused by this malignancy. Germ-line mutations of the RET protooncogene, which encodes a receptor tyrosine kinase, are responsible for these three neoplastic-prone disorders. MEN2 mutations convert the RET protooncogene in a dominantly acting oncogene as a consequence of the ligand-independent activation of the tyrosine kinase. The majority of MEN2A and FMTC mutations are located in the extracellular domain and cause the replacement of one of five juxtamembrane cysteines by a different amino acid. To examine whether expression of a MEN2A allele of RET results in transformation of C cells, we have used the transgenic approach. Expression of the RET gene altered by a MEN2A mutation was targeted in C cells by placing the transgene under the control of the calcitonin gene-related peptide/calcitonin promoter. Animals of three independent transgenic mouse lines, which expressed the transgene in the thyroid, displayed overt bilateral C cell hyperplasia as early as 3 weeks of age and subsequently developed multifocal and bilateral MTC. Moreover, these tumors were morphologically and biologically similar to human MTC which afflicts MEN- 2 individuals. These findings provide evidence that the MEN2A mutant form of RET is oncogenic in parafollicular C cells and suggest that these transgenic mice should prove a valuable animal model for hereditary MTC. PMID:9096393

  4. Pathophysiological study of diarrhoea in a patient with medullary thyroid carcinoma. Evidence against a secretory mechanism and for the role of shortened colonic transit time.

    PubMed Central

    Rambaud, J C; Jian, R; Flourié, B; Hautefeuille, M; Salmeron, M; Thuillier, F; Ruskoné, A; Florent, C; Chaoui, F; Bernier, J J

    1988-01-01

    Intubation techniques and scintigraphic studies were used to determine the origin and mechanism of diarrhoea in a patient with medullary thyroid carcinoma, high plasma immunoreactive calcitonin and normal circulating serotonin, substance P and prostaglandins E2 and F2 alpha. Normal function of the small intestine was found for the following: (a) absorption tests; (b) water and electrolyte absorption in the proximal jejunum; (c) 24 hour flow rate and composition of fluid entering the colon and (d) gastric emptying rate and small intestinal progression of a normal meal. By contrast, colonic function was markedly impaired in three ways: (a) water absorption was decreased by half; (b) as the main excreted solutes were organic acids, a large electrolyte gap was recorded in faecal water, and (c) colonic transit time of the meal marker was very short, and was in agreement with the rapid transit of ingested radioopaque markers. These data strongly suggest that decreased absorption in the colon secondary to a motor disturbance is the main mechanism of diarrhoea in this case of medullary thyroid carcinoma, while calcitonin induced small intestinal fluid secretion suggested earlier is either non-existent, or only of minor importance. PMID:3371722

  5. In silico and in vitro analysis of rare germline allelic variants of RET oncogene associated with medullary thyroid cancer.

    PubMed

    Cosci, B; Vivaldi, A; Romei, C; Gemignani, F; Landi, S; Ciampi, R; Tacito, A; Molinaro, E; Agate, L; Bottici, V; Cappagli, V; Viola, D; Piaggi, P; Vitti, P; Pinchera, A; Elisei, R

    2011-10-01

    Germline and somatic RET oncogene mutations are found in 98% hereditary and 40% sporadic medullary thyroid carcinomas. Our aim was to analyse by in silico and in vitro assays the transforming activity of six rare RET mutations (T338I, V648I, M918V, A883T, S904F and M848T). Six known RET mutations were used as controls. The in silico analysis showed the highest score value (i.e. 65) for S904F, M848T, M918T and C634R, whereas L790F, G691S, T338I and V648I had 0 score. Intermediate score values were obtained by A883T (score=55), M918V, V804M and Y791F (score=15). The in vitro focus formation assay showed that cells transfected with S904F, M918T, M848T or C634R generated the largest number of focus formation units (FFU). Intermediate numbers of FFU were observed in cells transfected with M918V, V804M, Y791F or A883T, while cells transfected with L790F, G691S, T338I or V648I showed a number of FFU similar to control cells. A positive correlation between the in silico score and in vitro FFU was found (P=0.0005). Only cells transfected with M918T or C634R grew faster and generated higher number of colonies in soft agar than control cells. However, the cells that were transfected with V804M produced an intermediate number of colonies. In conclusion, two of the six rare RET mutations, S904F and M848T possessed a relatively high transforming activity but a low aggressiveness; the other four mutations T338I, V648I, M918V and A883T were low or non-transforming, and their ability to induce tumoural transformation might be related to particular genetic conditions. PMID:21810974

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

    ClinicalTrials.gov

    2016-06-17

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

  7. Sunitinib Malate in Treating Patients With Iodine-Refractory Recurrent or Metastatic Thyroid Cancer

    ClinicalTrials.gov

    2015-09-28

    Recurrent Thyroid Cancer; Stage IVA Follicular Thyroid Cancer; Stage IVA Papillary Thyroid Cancer; Stage IVB Follicular Thyroid Cancer; Stage IVB Papillary Thyroid Cancer; Stage IVC Follicular Thyroid Cancer; Stage IVC Papillary Thyroid Cancer; Thyroid Gland Medullary Carcinoma

  8. [Expression of the MDR1 gene in five human cell lines of medullary thyroid cancer and reversion of the resistance to doxorubicine by ciclosporin A and verapamil].

    PubMed

    Massart, C; Gibassier, J; Lucas, C; Pourquier, P; Robert, J

    1996-01-01

    Medullary thyroid carcinoma (MTC) is frequently resistant to chemotherapy. Multidrug resistance (MDR) is one of the involved mechanisms. In this work we have studied the MDR1 gene expression in five MTC human cell lines that we have isolated and we have compared this expression to that of normal thyroid tissue. We have also tried to reverse the resistance to doxorubicin with verapamil (VRP) and ciclosporin A (CSA). MDR1 ARNm expression was studied and quantified by polymerase chain reaction (PCR) in normal and pathological thyroid tissues. The doxorubicin-induced cytotoxicity was evaluated with the 3,-4,5 dimethylthiazol-2,5 diphenyl tetrazolium bromide (MTT) test, the neutral red (NR) uptake and with total glutathione (GSH) or intracellular lactate dehydrogenase (LDH) measurements. We found an increase of MDR1 ARNm in MTC as compared with normal tissues. Doxorubicin was cytotoxic after a 48-h coincubation with the cells. Three microM CSA and 10 microM VRP reversed the doxorubicin resistance only after a 48-h coincubation, generally followed with a 24 h-post-incubation. In these conditions, the GSH levels were decreased only by VRP in all the five cell lines. In conclusion, a chemoresistance related to the MDR1 gene overexpression was found in the five human MTC lines tested. VRP and CSA reversed the resistance to doxorubicin in all the MTC cell lines tested. PMID:8672855

  9. Cervix carcinoma and incidental finding of medullary thyroid carcinoma by 18F-FDG PET/CT--clinical case.

    PubMed

    Chaushev, Borislav; Bochev, Pavel; Klisarova, Anelia; Yordanov, Kaloyan; Encheva, Elitsa; Dancheva, Jivka; Yordanova, Cvetelina; Hristozov, Kiril; Krasnaliev, Ivan; Radev, Radoslav; Nenkov, Rumen

    2014-01-01

    Thyroid nodules are encountered in clinical practice during the diagnostic procedures or patients' follow-up due to other diseases quite far from the thyroid gland with prevalence 4-50% in general population, depending on age, diagnostic method and race. The prevalence of thyroid nodules increases with age and their clarification should be done for their adequate treatment. An 18F-FDG PET/CT was done with a PET/CT scanner (Philips Gemini TF), consisting of dedicated lutetium orthosilicate full ring PET scanner and 16 slice CT. The PET/CT scan of the whole-body revealed on the CT portion a hypodense nodular lesion in the left lobe of the thyroid gland with increased uptake of 18F-FDG on the PET with SUVmax 10.3 and demonstrated a complete response to the induction therapy of the main oncological disease of the patient--squamous cell carcinoma. This clinical case demonstrates that whole-body 18F-FDG-PET/CT has an increasingly important role in the early evaluation of thyroid cancer as a second independent malignant localization. Focal thyroid lesion with high risk of thyroid malignancy was incidentally found on 18F-FDG PET/CT. PMID:25088110

  10. Medullary carcinoma of the thyroid, pancreatic nesidioblastosis and microadenosis, and pancreatic polypeptide hypersecretion: a new association and clinical and hormonal responses to long-acting somatostatin analog SMS 201-995.

    PubMed

    Jerkins, T W; Sacks, H S; O'Dorisio, T M; Tuttle, S; Solomon, S S

    1987-06-01

    We describe a 63-yr-old man with disseminated medullary carcinoma of the thyroid and pancreatic nesidioblastosis and microadenosis with pancreatic polypeptide (PP) hypersecretion. His major symptoms were watery diarrhea, flushing, and abdominal bloating; these and the elevated plasma PP levels did not change after resection of the distal two thirds of the pancreas, which contained a 2-cm mass of nesidioblastotic tissue. Postoperatively, a long-acting somatostatin analog, SMS 201-995 (100 micrograms/day), normalized PP secretion acutely and chronically (7 months) and ameliorated his symptoms. The analog had no side-effects and did not alter glucose tolerance, calcitonin hypersecretion, or growth of the medullary carcinoma, but it did inhibit GH secretion. After withdrawal from therapy for 1 month, PP hypersecretion and all symptoms except diarrhea recurred. The coexistence of medullary carcinoma of the thyroid and PP cell nesidioblastosis represents a new variant of the overlap syndromes between multiple endocrine neoplasia types I and II. Patients with medullary carcinoma and unexplained watery diarrhea should have fasting gastroenteropancreatic hormone assays done to screen for a potential gastrointestinal or pancreatic origin for the diarrhea. PMID:2883196

  11. Predicting Malignancy in Thyroid Nodules: Molecular Advances

    PubMed Central

    Melck, Adrienne L.; Yip, Linwah

    2016-01-01

    Over the last several years, a clearer understanding of the genetic alterations underlying thyroid carcinogenesis has developed. This knowledge can be utilized to tackle one of the greatest challenges facing thyroidologists: management of the indeterminate thyroid nodule. Despite the accuracy of fine needle aspiration cytology, many patients undergo invasive surgery in order to determine if a follicular or Hurthle cell neoplasm is malignant, and better diagnostic tools are required. A number of biomarkers have recently been studied and show promise in this setting. In particular, BRAF, RAS, PAX8-PPARγ, microRNAs and loss of heterozygosity have each been demonstrated as useful molecular tools for predicting malignancy and can thereby guide decisions regarding surgical management of nodular thyroid disease. This review summarizes the current literature surrounding each of these markers and highlights our institution’s prospective analysis of these markers and their subsequent incorporation into our management algorithms for thyroid nodules. PMID:21818817

  12. Cholecystokinin-B/Gastrin receptor-targeting peptides for staging and therapy of medullary thyroid cancer and other cholecystokinin-B receptor-expressing malignancies.

    PubMed

    Behr, Thomas M; Béhé, Martin P

    2002-04-01

    The high sensitivity of the pentagastrin stimulation test in detecting primary or metastatic medullary thyroid cancer (MTC) suggests a widespread expression of the corresponding receptor type on human MTC. Indeed, autoradiographic studies demonstrated cholecystokinin (CCK)-B/gastrin receptors not only in more than 90% of MTCs, but also in a high percentage of small-cell lung cancers, stromal ovarian tumors, and potentially a variety of other tumors, including gastrointestinal adenocarcinomas, neuroendocrine tumors, and malignant glioma. The aim of our work was to develop and systematically optimize suitable radioligands for targeting CCK-B receptors in vivo and to investigate their role in the staging and therapy of MTC and other CCK-B receptor expressing malignancies. For this purpose, a variety of CCK/gastrin-related peptides, all having in common the C-terminal CCK-receptor binding tetrapeptide sequence-Trp-Met-Asp-PheNH(2) or derivatives thereof, were investigated. They were members of the gastrin or cholecystokinin families or possessed characteristics of both, which differ by the intramolecular position of a tyrosyl moiety. Their stability and affinity were studied and optimized in vitro and in vivo; their biodistribution and therapeutic efficacy were tested in preclinical models. Best tumor uptake and tumor to nontumor ratios were obtained with members of the gastrin family, because of their superior selectivity and affinity for the CCK-B receptor subtype. Radiometal-labeled derivates of minigastrin showed excellent targeting of CCK-B receptor expressing tissues in animals and healthy human volunteers. Preclinical therapy experiments in MTC-bearing animals showed significant antitumor efficacy. In a subsequent clinical study, 45 MTC patients with metastatic MTC were investigated; 23 had known and 22 had occult disease. CCK-B receptor scintigraphy was performed with (111)In-diethylenetriamine pentaacetic acid-d-Glu(1)-minigastrin. The normal organ uptake was

  13. Expression of Tenascin C, EGFR, E-Cadherin, and TTF-1 in Medullary Thyroid Carcinoma and the Correlation with RET Mutation Status

    PubMed Central

    Steiner, Florian; Hauser-Kronberger, Cornelia; Rendl, Gundula; Rodrigues, Margarida; Pirich, Christian

    2016-01-01

    Tenascin C expression correlates with tumor grade and indicates worse prognosis in several tumors. Epidermal growth factor receptor (EGFR) plays an important role in driving proliferation in many tumors. Loss of E-cadherin function is associated with tumor invasion and metastasis. Thyroid transcription factor-1 (TTF-1) is involved in rearranged during transfection (RET) transcription in Hirschsprung’s disease. Tenascin C, EGFR, E-cadherin, TTF-1-expression, and their correlations with RET mutation status were investigated in 30 patients with medullary thyroid carcinoma (MTC) (n = 26) or C-cell hyperplasia (n = 4). Tenascin C was found in all, EGFR in 4/26, E-cadherin in 23/26, and TTF-1 in 25/26 MTC. Tenascin C correlated significantly with tumor proliferation (overall, r = 0.61, p < 0.005; RET-mutated, r = 0.81, p < 0.01). E-cadherin showed weak correlation, whereas EGFR and TTF-1 showed no significant correlation with tumor proliferation. EGFR, E-cadherin, and TTF-1 showed weak correlation with proliferation of RET-mutated tumors. Correlation between TTF-1 and tenascin C, E-cadherin, and EGFR was r = −0.10, 0.37, and 0.21, respectively. In conclusion, MTC express tenascin C, E-cadherin, and TTF-1. Tenascin C correlates significantly with tumor proliferation, especially in RET-mutated tumors. EGFR is low, and tumors expressing EGFR do not exhibit higher proliferation. TTF-1 does not correlate with RET mutation status and has a weak correlation with tenascin C, E-cadherin, and EGFR expression. PMID:27409604

  14. Expression of Tenascin C, EGFR, E-Cadherin, and TTF-1 in Medullary Thyroid Carcinoma and the Correlation with RET Mutation Status.

    PubMed

    Steiner, Florian; Hauser-Kronberger, Cornelia; Rendl, Gundula; Rodrigues, Margarida; Pirich, Christian

    2016-01-01

    Tenascin C expression correlates with tumor grade and indicates worse prognosis in several tumors. Epidermal growth factor receptor (EGFR) plays an important role in driving proliferation in many tumors. Loss of E-cadherin function is associated with tumor invasion and metastasis. Thyroid transcription factor-1 (TTF-1) is involved in rearranged during transfection (RET) transcription in Hirschsprung's disease. Tenascin C, EGFR, E-cadherin, TTF-1-expression, and their correlations with RET mutation status were investigated in 30 patients with medullary thyroid carcinoma (MTC) (n = 26) or C-cell hyperplasia (n = 4). Tenascin C was found in all, EGFR in 4/26, E-cadherin in 23/26, and TTF-1 in 25/26 MTC. Tenascin C correlated significantly with tumor proliferation (overall, r = 0.61, p < 0.005; RET-mutated, r = 0.81, p < 0.01). E-cadherin showed weak correlation, whereas EGFR and TTF-1 showed no significant correlation with tumor proliferation. EGFR, E-cadherin, and TTF-1 showed weak correlation with proliferation of RET-mutated tumors. Correlation between TTF-1 and tenascin C, E-cadherin, and EGFR was r = -0.10, 0.37, and 0.21, respectively. In conclusion, MTC express tenascin C, E-cadherin, and TTF-1. Tenascin C correlates significantly with tumor proliferation, especially in RET-mutated tumors. EGFR is low, and tumors expressing EGFR do not exhibit higher proliferation. TTF-1 does not correlate with RET mutation status and has a weak correlation with tenascin C, E-cadherin, and EGFR expression. PMID:27409604

  15. Autophagy activity is associated with membranous sodium iodide symporter expression and clinical response to radioiodine therapy in non-medullary thyroid cancer.

    PubMed

    Plantinga, Theo S; Tesselaar, Marika H; Morreau, Hans; Corssmit, Eleonora P M; Willemsen, Brigith K; Kusters, Benno; van Engen-van Grunsven, A C H; Smit, Johannes W A; Netea-Maier, Romana T

    2016-07-01

    Although non-medullary thyroid cancer (NMTC) generally has a good prognosis, 30-40% of patients with distant metastases develop resistance to radioactive iodine (RAI) therapy due to tumor dedifferentiation. For these patients, treatment options are limited and prognosis is poor. In the present study, expression and activity of autophagy was assessed in large sets of normal, benign and malignant tissues and was correlated with pathology, SLC5A5/hNIS (solute carrier family 5 member 5) protein expression, and with clinical response to RAI ablation therapy in NMTC patients. Fluorescent immunostaining for the autophagy marker LC3 was performed on 100 benign and 80 malignant thyroid tissues. Semiquantitative scoring was generated for both diffuse LC3-I intensity and number of LC3-II-positive puncta and was correlated with SLC5A5 protein expression and clinical parameters. Degree of diffuse LC3-I intensity and number of LC3-II-positive puncta scoring were not discriminative for benign vs. malignant thyroid lesions. Interestingly, however, in NMTC patients significant associations were observed between diffuse LC3-I intensity and LC3-II-positive puncta scoring on the one hand and clinical response to RAI therapy on the other hand (odds ratio [OR] = 3.13, 95% confidence interval [CI] =1.91-5.12, P = 0.01; OR = 5.68, 95%CI = 3.02-10.05, P = 0.002, respectively). Mechanistically, the number of LC3-II-positive puncta correlated with membranous SLC5A5 expression (OR = 7.71, 95%CI = 4.15-11.75, P<0.001), number of RAI treatments required to reach remission (P = 0.014), cumulative RAI dose (P = 0.026) and with overall remission and recurrence rates (P = 0.031). In conclusion, autophagy activity strongly correlates with clinical response of NMTC patients to RAI therapy, potentially by its capacity to maintain tumor cell differentiation and to preserve functional iodide uptake. PMID:27105307

  16. Usefulness of Serum Calcitonin in Patients Without a Suspicious History of Medullary Thyroid Carcinoma and with Thyroid Nodules Without an Indication for Fine-Needle Aspiration or with Benign Cytology.

    PubMed

    Rosario, P W; Calsolari, M R

    2016-06-01

    This study evaluated the usefulness of serum calcitonin (Ctn) in subjects without a suspicious history of medullary thyroid carcinoma (MTC) and with nodular thyroid disease without an indication for fine-needle aspiration (FNA) or with benign cytology. This was a prospective study that evaluated 421 patients with nodular disease without an indication for FNA and 602 patients with benign cytology. Patients with basal Ctn>10 pg/ml were submitted to calcium stimulation testing. Patients with stimulated Ctn>100 pg/ml were submitted to total thyroidectomy. Basal Ctn was<10 pg/ml in 1001 patients (97.8%). Among patients with basal Ctn>10 pg/ml, 16/22 exhibited stimulated Ctn>100 pg/ml. Two of these 16 patients had MTC. The 2 patients with MTC had undetectable basal Ctn 6 months after surgery. Using a cut-off of 30 pg/ml in women and 60 pg/ml in men for basal Ctn, the 2 cases of MTC of our series would have been identified and there would have been no false-positive case. It should be noted that 14/16 patients with stimulated Ctn>100 pg/ml were false-positive cases. Although uncommon, even subjects without a suspicious history and with nodular thyroid disease without an indication for FNA or with benign cytology can have MTC. The measurement of Ctn permits the diagnosis of these cases. Our results favor the hypothesis that basal Ctn could be superior to stimulated Ctn. PMID:27203410

  17. High Affinity Pharmacological Profiling of Dual Inhibitors Targeting RET and VEGFR2 in Inhibition of Kinase and Angiogeneis Events in Medullary Thyroid Carcinoma.

    PubMed

    Dunna, Nageswara Rao; Kandula, Venkatesh; Girdhar, Amandeep; Pudutha, Amareshwari; Hussain, Tajamul; Bandaru, Srinivas; Nayarisseri, Anuraj

    2015-01-01

    Clinical evidence shows that dual inhibition of kinases as well angiogenesis provides ideal therapeutic option in the treatment of medullary thyroid carcinoma (MTC) than inhibiting either of these with the events separately. Although treatment with dual inhibitors has shown good clinical responses in patients with MTC, it has been associated with serious side effects. Some inhibitors are active agents for both angiogenesis or kinase activity. Owing to narrow therapeutic window of established inhibitors, the present study aims to identify high affinity dual inhibitors targeting RET and VEGFR2 respectively for kinase and angiogenesis activity. Established inhibitors like Vandetanib, Cabozantinib, Motesanib, PP121, RAF265 and Sunitinib served as query parent compounds for identification of structurally similar compounds by Tanimoto-based similarity searching with a threshold of 95% against the PubChem database. All the parent inhibitors and respective similar compounds were docked against RET and VEGFR2 in order to retrieve high affinity compounds with these two proteins. AGN-PC-0CUK9P PubCID: 59320403 a compound related to PPI21 showed almost equal affinity for RET and VEGFR2 and unlike other screened compounds with no apparent bias for either of the receptors. Further, AGN- PC-0CUK9P demonstrated appreciable interaction with both RET and VEGFR2 and superior kinase activity in addition to showed optimal ADMET properties and pharmacophore features. From our in silico investigation we suggest AGN-PC-0CUK9P as a superior dual inhibitor targeting RET and VEGFR2 with high efficacy which should be proposed for pharmacodynamic and pharmacokinetic studies for improved treatment of MTC. PMID:26514495

  18. Effect of 3′UTR RET Variants on RET mRNA Secondary Structure and Disease Presentation in Medullary Thyroid Carcinoma

    PubMed Central

    Ceolin, Lucieli; Romitti, Mirian; Rodrigues Siqueira, Débora; Vaz Ferreira, Carla; Oliboni Scapineli, Jessica; Assis-Brazil, Beatriz; Vieira Maximiano, Rodolfo; Dias Amarante, Tauanne; de Souza Nunes, Miriam Celi; Weber, Gerald; Maia, Ana Luiza

    2016-01-01

    Background The RET S836S variant has been associated with early onset and increased risk for metastatic disease in medullary thyroid carcinoma (MTC). However, the mechanism by which this variant modulates MTC pathogenesis is still open to discuss. Of interest, strong linkage disequilibrium (LD) between RET S836S and 3'UTR variants has been reported in Hirschsprung's disease patients. Objective To evaluate the frequency of the RET 3’UTR variants (rs76759170 and rs3026785) in MTC patients and to determine whether these variants are in LD with S836S polymorphism. Methods Our sample comprised 152 patients with sporadic MTC. The RET S836S and 3’UTR (rs76759170 and rs3026785) variants were genotyped using Custom TaqMan Genotyping Assays. Haplotypes were inferred using the phase 2.1 program. RET mRNA structure was assessed by Vienna Package. Results The mean age of MTC diagnosis was 48.5±15.5 years and 57.9% were women. The minor allele frequencies of RET polymorphisms were as follows: S836S, 5.6%; rs76759170, 5.6%; rs3026785, 6.2%. We observed a strong LD among S836S and 3’UTR variants (|D’| = -1, r2 = 1 and |D’| = -1, r2 = 0,967). Patients harboring the S836S/3’UTR variants presented a higher percentage of lymph node and distant metastasis (P = 0.013 and P<0.001, respectively). Accordingly, RNA folding analyses demonstrated different RNA secondary structure predictions for WT(TCCGT), S836S(TTCGT) or 3’UTR(GTCAC) haplotypes. The S836S/3’UTR haplotype presented a greater number of double helices sections and lower levels of minimal free energy when compared to the wild-type haplotype, suggesting that these variants provides the most thermodynamically stable mRNA structure, which may have functional consequences on the rate of mRNA degradation. Conclusion The RET S836S polymorphism is in LD with 3’UTR variants. In silico analysis indicate that the 3’UTR variants may affect the secondary structure of RET mRNA, suggesting that these variants might play a

  19. Thyroid

    MedlinePlus

    Thyroid is used to treat the symptoms of hypothyroidism (a condition where the thyroid gland does not produce enough thyroid hormone). Symptoms of hypothyroidism include lack of energy, depression, constipation, weight gain, ...

  20. Thyroiditis

    MedlinePlus

    ... Hashimoto’s thyroiditis is the most common cause of hypothyroidism in the United States. Postpartum thyroiditis, which causes ... hormone levels in the blood) followed by temporary hypothyroidism, is a common cause of thyroid problems after ...

  1. Update on external beam radiation therapy in thyroid cancer.

    PubMed

    Brierley, James D

    2011-08-01

    Surgery is the mainstay of treatment for thyroid cancer. The role for external beam radiotherapy (EBRT) as an adjuvant to surgery or as the primary therapy is established in anaplastic thyroid cancer but is controversial in differentiated thyroid cancer and uncertain in medullary thyroid cancer. This update reviews the recent reported success of combining EBRT with taxanes in anaplastic thyroid cancer. Also discussed are the recent reports from large single institutions that support the recommendations of the American and British Thyroid Associations on the use of EBRT in high-risk differentiated thyroid cancer. Further evidence on the role of EBRT in MTC is discussed. The important advances in the delivery of EBRT using intensity-modulated radiation and image-guided radiation that result in more accurate and potentially more effective radiation therapy with less toxicity are also discussed. PMID:21816795

  2. Presentation of points of general discussion and voting among the speakers of the European Thyroid Association-Cancer Research Network (ETA-CRN) meeting in Lisbon, 2009, entitled ”European comments to ATA medullary thyroid cancer guidelines”

    PubMed Central

    2013-01-01

    The main subjects of discussion, held online within the ETA-CRN board invited 16 expert-panelists are shown. The ad hoc emerged ETA-CRN panel of experts (EPE) first congratulated Professor Kloos and the ATA Taskforce for the extensive work on medullary thyroid cancer, and appreciated discussing the ATA guidelines during the ETA-CRN meeting. As it was not possible for all experts to visit the meeting, they enclosed their comments in the online ETA forum. The overall intention was to evaluate certain discrepancies between the ATA guidelines and were biased European clinical practice. All discussants were aware that the ATA guidelines had followed evidence based medicine rules; however, it was intended to reach an European consensus in this matter. The results of online voting among the EPE are shown. We received answers from nine experts. The particular ATA guidelines devoted to the management of MTC ranged in agreement in 0/9 to 4/9. This did not reflect the general, good assessment of the guidelines, as of votes a set of questions. The strongest discrepancies were found in assessment of the usefulness of pentagastrin (Peptavlon®) stimulated calcitonin secretion. The majority of the EPE (5/9) chose an option: “the increase of the basal Ct >100 ng/L means the substantial risk of MTC. However, there should also have been a recommendation for the grey zone 10-100 ng/L, where stimulation with pentagastrin is useful. The cut-off to perform stimulation test at ≤ 15-20 ng/L and values >100 ng/L means a significant suspicion of MTC”. Similarly, attention from the EPE was raised towards the surgical procedures in MTC, particularly the extent and indications for lymph node surgical intervention. Four questions were related to the indications to lymphadenectomy and extent of surgery. The equal number (4/8) of EPE agreed with the ATA R61 and half of the ETA-CRN panel of experts disagreed because the indications to lymphadenectomy (Lx) depended in their opinion on the

  3. Recent Advances in Molecular Biology of Thyroid Cancer and Their Clinical Implications

    PubMed Central

    Xing, Mingzhao

    2009-01-01

    Synopsis Thyroid cancer is the most common endocrine malignancy with a rapid rising incidence in recent years. Novel efficient management strategies are increasingly needed for this cancer. Remarkable advances have occurred in recent years in understanding the molecular biology of thyroid cancer. This is reflected in several major biological areas of thyroid cancer, including the molecular alterations for the loss of radioiodine avidity of thyroid cancer, the pathogenic role of the MAP kinase and PI3K/Akt pathways and their related genetic alterations, and the aberrant methylation of functionally important genes in thyroid tumorigenesis and pathogenesis. These exciting advances in molecular biology of thyroid cancer provide unprecedented opportunities for the development of molecular-based novel diagnostic, prognostic, and therapeutic strategies for this cancer. PMID:19040974

  4. Role of External Beam Radiotherapy in Patients With Advanced or Recurrent Nonanaplastic Thyroid Cancer: Memorial Sloan-Kettering Cancer Center Experience

    SciTech Connect

    Terezakis, Stephanie A. Lee, Kyungmouk S.; Ghossein, Ronald A.; Rivera, Michael; Tuttle, Robert M.; Wolden, Suzanne L.; Zelefsky, Michael J.; Wong, Richard J.; Patel, Snehal G.; Pfister, David G.; Shaha, Ashok R.; Lee, Nancy Y.

    2009-03-01

    Purpose: External beam radiotherapy (EBRT) plays a controversial role in the management of nonanaplastic thyroid cancer. We reviewed our institution's outcomes in patients treated with EBRT for advanced or recurrent nonanaplastic thyroid cancer. Methods and Materials: Between April 1989 and April 2006, 76 patients with nonanaplastic thyroid cancer were treated with EBRT. The median follow-up for the surviving patients was 35.3 months (range, 4.2-178.4). The lesions were primarily advanced and included Stage T2 in 5 (7%), T3 in 5 (7%), and T4 in 64 (84%) patients. Stage N1 disease was present in 60 patients (79%). Distant metastases before EBRT were identified in 27 patients (36%). The median total EBRT dose delivered was 6,300 cGy. The histologic features examined included medullary in 12 patients (16%) and nonmedullary in 64 (84%). Of the 76 patients, 71 (93%) had undergone surgery before RT, and radioactive iodine treatment was used in 56 patients (74%). Results: The 2- and 4-year overall locoregional control rate for all histologic types was 86% and 72%, respectively, and the 2- and 4-year overall survival rate for all patients was 74% and 55%, respectively. No significant differences were found in locoregional control, overall survival, or distant metastases-free survival for patients with complete resection, microscopic residual disease, or gross residual disease. Grade 3 acute mucositis and dysphagia occurred in 14 (18%) and 24 (32%) patients, respectively. Late adverse toxicity was notable for percutaneous endoscopic gastrostomy tube use in 4 patients (5%). Conclusion: The results of our study have shown that EBRT is effective for locoregional control of selected locally advanced or recurrent nonanaplastic thyroid malignancies, with acceptable acute toxicity.

  5. Thyroid cancer in childhood

    SciTech Connect

    Gorlin, J.B.; Sallan, S.E. )

    1990-09-01

    The incidence, clinical presentation, and types of thyroid cancers presenting in childhood are reviewed. The role of antecedent radiation in papillary and follicular thyroid cancers and genetics of medullary thyroid carcinoma are discussed. Unique aspects of therapy and prognosis for the pediatric patient with thyroid carcinoma are addressed as well as a diagnostic approach to the child who presents with a neck mass.59 references.

  6. Tyrosine kinase inhibitors and the thyroid.

    PubMed

    Sherman, Steven I

    2009-12-01

    Protein tyrosine kinase inhibitors (TKIs) have emerged as significant targets for novel cancer therapies. For patients with differentiated or medullary carcinomas unresponsive to conventional treatments, multiple novel therapies primarily targeting angiogenesis have entered clinical trials. Partial response rates up to 30% have been reported in single-agent studies, but prolonged disease stabilisation is more commonly seen. The most successful agents target the vascular endothelial growth factor receptors. Sorafenib and sunitinib have had promising preliminary results reported and are being used selectively for patients who do not qualify for clinical trials. Treatment for patients with metastatic or advanced thyroid carcinoma now emphasises clinical trial opportunities for novel agents with considerable promise. Adverse effects on thyroid function and thyroid hormone metabolism have also been seen with several TKIs, necessitating prospective thyroid function testing for all patients starting therapy. PMID:19942148

  7. Novel molecular targeted therapies for refractory thyroid cancer.

    PubMed

    Perez, Cesar A; Santos, Edgardo S; Arango, Belisario A; Raez, Luis E; Cohen, Ezra E W

    2012-05-01

    The incidence of thyroid cancer continues to increase and this neoplasia remains the most common endocrine malignancy. No effective systemic treatment currently exists for iodine-refractory differentiated or medullary thyroid carcinoma, but recent advances in the pathogenesis of these diseases have revealed key targets that are now being evaluated in the clinical setting. RET (rearranged during transfection)/PTC (papillary thyroid carcinoma) gene rearrangements, B-Raf gene mutations, and vascular endothelial growth factor receptor 2 (VEGFR-2) angiogenesis pathways are some of the known genetic alterations playing a crucial role in the development of thyroid cancer. Several novel agents have demonstrated promising responses. Of the treatments studied, multi-kinase inhibitors such as axitinib, sorafenib, motesanib, and XL-184 have shown to be the most effective by inducing clinical responses and stabilizing the disease process. Randomized clinical trials are currently evaluating these agents, results that may soon change the management of thyroid cancer. PMID:21544895

  8. Advances in the management of differentiated thyroid cancer with follicular cell strain.

    PubMed

    Ben Slimène, Faouzi; Mhiri, Aida; Ben Ali, Moez; Slimène, Hédia; Ben Raies, Nouzha; Karboua, Esma; Schlumberger, Martin

    2016-03-01

    The management of nodules and thyroid cancer is evolving. The aim is to individualize the treatment, decreasing aggression in the forms low risk and instead seeking new therapeutic options in advanced disease. This update shows the main recent advances in this field. PMID:27575497

  9. Medullary Sponge Kidney

    MedlinePlus

    ... Association of Kidney Patients National Kidney Foundation MedlinePlus Kidney and Urologic Disease Organizations Many organizations provide support ... PDF, 345 KB)​​​​​ Alternate Language URL Medullary Sponge Kidney Page Content On this page: What is Medullary ...

  10. 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.

  11. A Founding Locus within the RET Proto-Oncogene May Account for a Large Proportion of Apparently Sporadic Hirschsprung Disease and a Subset of Cases of Sporadic Medullary Thyroid Carcinoma

    PubMed Central

    Borrego, Salud; Wright, Fred A.; Fernández, Raquel M.; Williams, Nita; López-Alonso, Manuel; Davuluri, Ramana; Antiñolo, Guillermo; Eng, Charis

    2003-01-01

    Hirschsprung disease (HSCR) is a common congenital disorder characterized by aganglionosis of the gut. The seemingly unrelated multiple endocrine neoplasia type 2 (MEN 2) is an autosomal dominant disorder characterized by medullary thyroid carcinoma (MTC), pheochromocytoma, and hyperparathyroidism. Yet, germline mutations in the RET proto-oncogene are associated with both MEN 2 and HSCR. In the former, gain-of-function mutations in a limited set of codons is found, whereas, in the latter, loss-of-function mutations are found. However, germline RET mutation is associated with only 3% of a population-based series of isolated HSCR, and little is known about susceptibility to sporadic MTC. We have found previously that specific haplotypes comprising RET coding single-nucleotide polymorphisms (SNPs) comprising exon 2 SNP A45A were strongly associated with HSCR, whereas haplotypes associated with exon 14 SNP S836S were associated with MTC. In this study, we describe three novel intron 1 SNPs, and, together with the coding SNP haplotypes, the data suggest the presence of distinct ancestral haplotypes for HSCR and sporadic MTC in linkage disequilibrium with a putative founding susceptibility locus/loci. The data are consistent with the presence of a very ancient, low-penetrance founder locus ∼20–30 kb upstream of SNP A45A, but the failure of the SNPs to span the locus presents challenges in modeling mode of transmission or ancestry. We postulate that this founding locus is germane to both isolated HSCR and MTC but also that different mutations in this locus would predispose to one or the other. PMID:12474140

  12. [Advances in thyroglobulin assays and their impact on the management of differentiated thyroid cancers].

    PubMed

    d'Herbomez, Michèle; Lion, Georges; Béron, Amandine; Wémeau, Jean-Louis; DoCao, Christine

    2016-01-01

    Thyroglobulin (Tg) is a high molecular weight glycoprotein located mainly in thyroid follicles, where thyroid hormones are synthesized and stored. In patients with differentiated thyroid cancer of follicular origin, serum Tg levels become undetectable following total thyroidectomy and iodine-131 remnant ablation. It is a key biomarker to follow-up patients with differentiated thyroid cancer, in combination with neck ultrasound monitoring. The measurement of Tg in the wash-out of the needle used for fine needle aspiration biopsy is a valuable aid to the diagnosis of lymph node metastasis. The presence of anti-thyroglobulin antibodies affects reliability of Tg results measured in serum or plasma. Systematic investigation of such antibodies is required to validate any Tg assay. Elevated or rising levels of anti-thyroglobulin antibodies can in turn be used as a surrogate tumor marker of thyroid cancer. The development of second-generation Tg assay (automated, highly sensitive) has enabled significant advances in the management of differentiated thyroid cancer: early detection of persistent or recurrent disease and follow-up care simplified in low-risk patients. Testing of serum Tg can also be useful in evaluating other clinical situations such as congenital hypothyroidism, endemic goiter and thyrotoxicosis factitia. PMID:26711165

  13. Preclinical pharmacokinetics, biodistribution, radiation dosimetry and toxicity studies required for regulatory approval of a phase I clinical trial with 111In-CP04 in medullary thyroid carcinoma patients

    PubMed Central

    Maina, Theodosia; Konijnenberg, Mark W.; KolencPeitl, Petra; Garnuszek, Piotr; Nock, Berthold A.; Kaloudi, Aikaterini; Kroselj, Marko; Zaletel, Katja; Maecke, Helmut; Mansi, Rosalba; Erba, Paola; von Guggenberg, Elisabeth; Hubalewska-Dydejczyk, Alicja; Mikolajczak, Renata; Decristoforo, Clemens

    2016-01-01

    Introduction From a series of radiolabelled cholecystokinin (CCK) and gastrin analogues, 111In-CP04 (111In-DOTA-(DGlu)6-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2) was selected for further translation as a diagnostic radiopharmaceutical towards a first-in-man study in patients with medullary thyroid carcinoma (MTC). A freeze-dried kit formulation for multicentre application has been developed. We herein report on biosafety, in vivo stability, biodistribution and dosimetry aspects of 111In-CP04 in animal models, essential for the regulatory approval of the clinical trial. Materials and methods Acute and extended single dose toxicity of CP04 was tested in rodents, while the in vivo stability of 111In-CP04 was assessed by HPLC analysis of mouse blood samples. The biodistribution of 111In-CP04 prepared from a freeze-dried kit was studied in SCID mice bearing double A431-CCK2R(±) xenografts at 1, 4 and 24 h pi. Further 4-h animal groups were either additionally treated with the plasma expander gelofusine or injected with 111In-CP04 prepared by wet-labelling. Pharmacokinetics in healthy mice included the 30 min, 1, 4, 24, 48 and 72 h time points pi. Dosimetric calculations were based on extrapolation of mice data to humans adopting two scaling models. Results CP04 was well-tolerated by both mice and rats, with an LD50 > 178.5 μg/kg body weight for mice and a NOAEL (no-observed-adverse-effect-level) of 89 μg/kg body weight for rats. After labelling, 111In-CP04 remained >70% intact in peripheral mouse blood at 5 min pi. The uptake of 111In-CP04 prepared from the freeze-dried kit and by wet-labelling were comparable in the A431-CCK2R(+)-xenografts (9.24 ± 1.35%ID/g and 8.49 ± 0.39%ID/g, respectively; P > 0.05). Gelofusine-treated mice exhibited significantly reduced kidneys values (1.69 ± 0.15%ID/g vs. 5.55 ± 0.94%ID/g in controls, P < 0.001). Dosimetry data revealed very comparable effective tumour doses for the two scaling models applied, of 0.045 and 0.044 m

  14. Thyroid nodules.

    PubMed

    Niedziela, Marek

    2014-03-01

    According to the literature, thyroid nodules (TNs) are quite rare in the first two decades of life and are predominantly non-cancerous, although cancerous TNs are more common in the first two decades of life than in adults. Therefore, it is important for clinicians to distinguish benign from malignant lesions preoperatively because the latter require a total thyroidectomy with or without neck lymph node dissection. A careful work-up and a fine-needle aspiration biopsy (FNAB) are mandatory to improve the preoperative diagnosis. High-resolution thyroid ultrasound and real-time elastosonography are adjuvant presurgical tools in selecting patients for surgery, particularly those with indeterminate or non-diagnostic cytology. Elevated thyroid-stimulating hormone (TSH) level in a patient with a thyroid nodule is a new laboratory predictor of thyroid cancer risk. The majority of thyroid carcinomas derive from the follicular cell, whereas medullary thyroid carcinoma (MTC) derives from calcitonin-producing cells. Patients with MTC are screened for germ-line RET mutations to detect carriers and identify family members for prophylactic or therapeutic thyroidectomy. PMID:24629865

  15. Can Thyroid Cancer Be Prevented?

    MedlinePlus

    ... look for the gene mutations found in familial medullary thyroid cancer (MTC). Because of this, most of the familial cases of MTC can be prevented or treated early by removing the thyroid gland. Once the disease is discovered in a family, the rest of ...

  16. High-mobility group box 1 inhibits HCO(3)(-) absorption in medullary thick ascending limb through a basolateral receptor for advanced glycation end products pathway.

    PubMed

    Good, David W; George, Thampi; Watts, Bruns A

    2015-10-15

    High-mobility group box 1 (HMGB1) is a damage-associated molecule implicated in mediating kidney dysfunction in sepsis and sterile inflammatory disorders. HMGB1 is a nuclear protein released extracellularly in response to infection or injury, where it interacts with Toll-like receptor 4 (TLR4) and other receptors to mediate inflammation. Previously, we demonstrated that LPS inhibits HCO(3)(-) absorption in the medullary thick ascending limb (MTAL) through a basolateral TLR4-ERK pathway (Watts BA III, George T, Sherwood ER, Good DW. Am J Physiol Cell Physiol 301: C1296-C1306, 2011). Here, we examined whether HMGB1 could inhibit HCO(3)(-) absorption through the same pathway. Adding HMGB1 to the bath decreased HCO(3)(-) absorption by 24% in isolated, perfused rat and mouse MTALs. In contrast to LPS, inhibition by HMGB1 was preserved in MTALs from TLR4(-/-) mice and was unaffected by ERK inhibitors. Inhibition by HMGB1 was eliminated by the receptor for advanced glycation end products (RAGE) antagonist FPS-ZM1 and by neutralizing anti-RAGE antibody. Confocal immunofluorescence showed expression of RAGE in the basolateral membrane domain. Inhibition of HCO(3)(-) absorption by HMGB1 through RAGE was additive to inhibition by LPS through TLR4 and to inhibition by Gram-positive bacterial molecules through TLR2. Bath amiloride, which selectively prevents inhibition of MTAL HCO(3)(-) absorption mediated through Na⁺/H⁺ exchanger 1 (NHE1), eliminated inhibition by HMGB1. We conclude that HMGB1 inhibits MTAL HCO(3)(-) absorption through a RAGE-dependent pathway distinct from TLR4-mediated inhibition by LPS. These studies provide new evidence that HMGB1-RAGE signaling acts directly to impair the transport function of renal tubules. They reveal a novel paradigm for sepsis-induced renal tubule dysfunction, whereby exogenous pathogen-associated molecules and endogenous damage-associated molecules act directly and independently to inhibit MTAL HCO(3)(-) absorption through

  17. [Thyroid cancer].

    PubMed

    Nagayama, Yuji

    2012-03-01

    The thyroid glands are a vulnerable organ to ionizing radiation. Indeed the epidemiological studies have revealed an increase in the incidences of thyroid cancer among atomic bomb survivors in Hiroshima and Nagasaki and radiation casualties in Chernobyl. The carcinogenic risk for the thyroids is dependent on radiation dose, and higher in younger people. Recent advances in molecular biology contribute to clarify the mechanisms for thyroid carcinogenesis at genetic and molecular levels. Here radiation-induced thyroid carcinogenesis is reviewed from epidemiological data to basic research. PMID:22514922

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

    PubMed Central

    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. PMID:26316818

  19. Renal Medullary Interstitial Cells

    NASA Astrophysics Data System (ADS)

    Rao, Reena; Hao, Chuan-Ming; Breyer, Matthew D.

    2007-04-01

    Renal medullary interstitial cells (RMICs) are specialized fibroblast-like cells that reside in the renal medulla among the vasa recta, the thin limbs of Henle's loop, and medullary collecting ducts. These cells are characterized by abundant lipid droplets in the cytoplasm. The lipid droplets are composed of triglycerides, cholesterol esters and free long-chain fatty acids, including arachidonic acid. RMICs are also a major site of cyclooxygenase2 (COX-2) expression, and thus a major site of COX-2 derived prostanoid biosynthesis. RMICs are also a potential target of hormones such as angiotensin II and endothelin. The RMIC COX-2 expression and the abundance of lipid droplets change with salt and water intake. These properties of RMICs are consistent with an important role of these cells in modulating physiologic and pathologic processes of the kidney.

  20. Thyroid cancer in children and adolescents

    SciTech Connect

    Ceccarelli, C.; Pacini, F.; Lippi, F.; Elisei, R.; Arganini, M.; Miccoli, P.; Pinchera, A.

    1988-12-01

    We report on 49 patients younger than 18 years at diagnosis, of 776 patients with thyroid cancer, seen in our institution in the last 17 years. Female/male ratio was 2.2:1. Histologic type was papillary in 44, follicular in 4, and medullary in 1. Initial treatment was near-total thyroidectomy with or without neck dissection. Surgical complications (vocal cord palsy, permanent hypoparathyroidism, or both) were found in 25 patients and were usually associated with more advanced primary tumors. At surgery, node metastases were present in 73% of the patients and lung metastases, detected by chest x ray films, in 6%. Patients were treated with thyroid suppressive therapy and, except the one with medullary cancer, with radioiodine (131I) therapy. After a mean follow-up of 7.7 +/- 4.4 years (range, 1 to 17 years), one patient with lung metastases died of respiratory failure. Of 36 patients who have been followed up more than 4 years, 22 (61.1%) are now cured, and 14 have metastases (to lymph nodes, 2; to nodes and lung, 10; and to lung, 2). Since 1977 serum thyroglobulin (Tg) was used routinely as a tumor marker for differentiated thyroid cancer. After operation, Tg was elevated in all patients both not receiving (mean +/- SE, 902 +/- 380 ng/ml) and receiving (44 +/- 15 ng/ml) suppressive therapy; after 131I treatment, serum Tg dropped to 104 +/- 50 and 7.3 +/- 1.7 ng/ml, without and with suppressive therapy, respectively. Of 11 patients with lung metastases treated with 131I, respiratory function, as assessed by means of spirometry, was normal in three, mildly reduced in six, and severely impaired in two (including the one who died). In conclusion, our study indicates that thyroid cancer in young patients is rather advanced at initial examination and usually associated with node and, less frequently, lung metastases.

  1. Detecting and Treating Thyroid Nodules and Cancer Before, During, and After Pregnancy

    MedlinePlus

    ... cancer have their own risk factors. For instance, “medullary” thyroid cancer (an uncommon type) can run in ... most common to least common, are papillary, follicular, medullary, and anaplastic. (See the Hormone Health Network’s Thyroid ...

  2. Targeted molecular therapies in thyroid carcinoma.

    PubMed

    Romagnoli, Serena; Moretti, Sonia; Voce, Pasquale; Puxeddu, Efisio

    2009-12-01

    Thyroid cancer incidence has significantly increased in the last three decades and many patients seek medical attention for its treatment every year. Among follicular cell-derived tumors, the majority are differentiated thyroid carcinomas (DTC), whose prognosis is very good with only 15% of the cases presenting disease persistence or recurrence after initial treatment. Medullary thyroid carcinoma has a worse prognosis, especially in patients with diffused cancers at the time of initial surgery. Traditional treatment options for persistent or recurrent disease include additional surgery, radioiodine treatment and TSH-suppression in DTC patients; external beam radiotherapy, and cytotoxic chemotherapy, often have low efficacy and many patients with advanced disease ultimately die. In the last two decades many of the molecular events involved in cancer formation have been uncovered. This knowledge has prompted the development of novel therapeutic strategies mainly based on the inhibition of key molecular mediators of the tumorigenic process. In particular the class of small-molecule tyrosine kinase inhibitors was enriched by many compounds that have reached clinical trials and in some cases have had approval for clinical use in specific cancers. Many of these compounds entered clinical trials also for locally advanced or metastatic thyroid carcinomas showing very promising results. PMID:20126863

  3. The thyroid hormone receptor gene (c-erbA alpha) is expressed in advance of thyroid gland maturation during the early embryonic development of Xenopus laevis.

    PubMed Central

    Banker, D E; Bigler, J; Eisenman, R N

    1991-01-01

    The c-erbA proto-oncogene encodes the thyroid hormone receptor, a ligand-dependent transcription factor which plays an important role in vertebrate growth and development. To define the role of the thyroid hormone receptor in developmental processes, we have begun studying c-erbA gene expression during the ontogeny of Xenopus laevis, an organism in which thyroid hormone has well-documented effects on morphogenesis. Using polymerase chain reactions (PCR) as a sensitive assay of specific gene expression, we found that polyadenylated erbA alpha RNA is present in Xenopus cells at early developmental stages, including the fertilized egg, blastula, gastrula, and neurula. By performing erbA alpha-specific PCR on reverse-transcribed RNAs from high-density sucrose gradient fractions prepared from early-stage embryos, we have demonstrated that these erbA transcripts are recruited to polysomes. Therefore, erbA is expressed in Xenopus development prior to the appearance of the thyroid gland anlage in tailbud-stage embryos. This implies that erbA alpha/thyroid hormone receptors may play ligand-independent roles during the early development of X. laevis. Quantitative PCR revealed a greater than 25-fold range in the steady-state levels of polyadenylated erbA alpha RNA across early stages of development, as expressed relative to equimolar amounts of total embryonic RNA. Substantial increases in the levels of erbA alpha RNA were noted at stages well after the onset of zygotic transcription at the mid-blastula transition, with accumulation of erbA alpha transcripts reaching a relative maximum in advance of metamorphosis. We also show that erbA alpha RNAs are expressed unequally across Xenopus neural tube embryos. This differential expression continues through later stages of development, including metamorphosis. This finding suggests that erbA alpha/thyroid hormone receptors may play roles in tissue-specific processes across all of Xenopus development. Images PMID:1656222

  4. Lenvatinib: Role in thyroid cancer and other solid tumors.

    PubMed

    Cabanillas, Maria E; Habra, Mouhammed Amir

    2016-01-01

    Despite recent breakthroughs in treatment of advanced thyroid cancers, prognoses remain poor. Treatment of advanced, progressive disease remains challenging, with limited treatment options. Small-molecule tyrosine kinase inhibitors, including vandetanib, cabozantinib, sorafenib, and lenvatinib, which are now FDA-approved for thyroid cancer, have shown clinical benefit in advanced thyroid cancer. Lenvatinib is approved for treatment of locally recurrent or metastatic, progressive, radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC). It has been studied in phase II and III trials for treatment of advanced RAI-refractory DTC, and in a phase II trial for medullary thyroid cancer (MTC). Lenvatinib targets vascular endothelial growth factor receptors 1-3 (VEGFR1-3), fibroblast growth factor receptors 1-4 (FGFR-1-4), RET, c-kit, and platelet-derived growth factor receptor α (PDGFRα). Its antitumor activity may be due to antiangiogenic properties and direct antitumor effects. Lenvatinib has demonstrated antitumor activity in a variety of solid tumors, including MTC, in phase I and II clinical trials. In a phase II study in advanced RAI-refractory DTC, lenvatinib-treated patients achieved a 50% response rate (RR), with median progression-free survival (PFS) of 12.6 months. In a phase III trial in RAI-refractory DTC, median PFS in lenvatinib-treated patients was 18.3 months, with a 65% overall RR, versus 3.6 months in placebo-treated patients, with a 2% RR. Adverse events occurring in >50% of patients included hypertension, diarrhea, fatigue/asthenia, and decreased appetite. Lenvatinib is a promising new agent for treatment of patients with advanced thyroid cancer. PMID:26678514

  5. Thyroid cancer in children.

    PubMed

    Rivera, Gabriel; Lugo-Vicente, Humberto

    2014-01-01

    Cancer of the thyroid gland in pediatric patients is rare and if left untreated spreads and become lethal. Thyroid nodules in pediatric patients are four times more likely being malignant than adult nodules. The incidence of thyroid cancer in children increases with age, sex, race and nodule size. Exposures to low level of head and neck irradiation at young age, cancer survivors, family history of thyroid cancer and iodine deficiency are specific risk factors to develop thyroid cancer. Thyroid cancer is subdivided into papillary, follicular and medullary thyroid cancer varying in histological characteristics. Children who present with thyroid nodules should undergo ultrasound and fine needle aspiration biopsy to evaluate malignant potential. If biopsy results are positive for malignancy best option is complete surgical resection of the thyroid gland with central lymph node dissection followed by radioactive iodine treatment. Surgeons need to take certain precaution to avoid postoperative complications like hypoparathyroidism or recurrent laryngeal nerve damage. Follow-up is essential in order to evaluate remission or recurrence. An excellent prognosis in pediatric patients is the result of such an aggressive approach that can be supported by the low complications rate and low recurrence rate following surgery. PMID:25470911

  6. Thyroid cancer in children.

    PubMed

    Rivera, Gabriel; Lugo-Vicente, Humberto

    2014-01-01

    Cancer of the thyroid gland in pediatric patients is rare and if left untreated spreads and become lethal. Thyroid nodules in pediatric patients are four times more likely being malignant than adult nodules. The incidence of thyroid cancer in children increases with age, sex, race and nodule size. Exposures to low level of head and neck irradiation at young age, cancer survivors, family history of thyroid cancer and iodine deficiency are specific risk factors to develop thyroid cancer. Thyroid cancer is subdivided into papillary, follicular and medullary thyroid cancer varying in histological characteristics. Children who present with thyroid nodules should undergo ultrasound and fine needle aspiration biopsy to evaluate malignant potential. If biopsy results are positive for malignancy best option is complete surgical resection of the thyroid gland with central lymph node dissection followed by radioactive iodine treatment. Surgeons need to take certain precaution to avoid postoperative complications like hypoparathyroidism or recurrent laryngeal nerve damage. Follow-up is essential in order to evaluate remission or recurrence. An excellent prognosis in pediatric patients is the result of such an aggressive approach that can be supported by the low complications rate and low recurrence rate following surgery. PMID:25508538

  7. [Current Advances and Future Development of Thyroid Ultrasound Examination--Steps toward State-of-the-Art Laboratory Medicine in Fukushima].

    PubMed

    Shimura, Hiroki

    2015-03-01

    Since the accidents at the Fukushima Daiichi Nuclear Power Plant after the Great East Japan Earthquake on March 11, 2011, large quantities of radionuclides have leaked into the surrounding environment. Fukushima Prefecture started the Fukushima Health Management Survey Project including Thyroid Ultrasound Examination to screen for thyroid cancer in all residents aged 0 to 18 years at the time of the nuclear accident. This accident also led to increased interest in thyroid ultrasound examination in Japan. This article reviews the studies to establish ultrasound diagnostic criteria for thyroid nodules and the clinical guidelines of thyroid nodule management, both of which are fundamental to Thyroid Ultrasound Examination in Fukushima. This article also reviews a study designed to clarify the actual frequency of sonographically detected thyroid nodular lesions among Japanese children, which will become appropriate reference data to interpret the results from Thyroid Ultrasound Examination. Further advances in the screening and management of thyroid diseases are important responsibilities of clinicians and researchers in Fukushima. PMID:26524862

  8. Post-laryngectomy voice rehabilitation with a voice prosthesis in a young girl with advanced thyroid cancer.

    PubMed

    Fukuhara, Takahiro; Miyoshi, Masayuki; Fujii, Taihei; Miyake, Naritomo; Taira, Kenkichiro; Koyama, Satoshi; Taguchi, Daizo; Fujiwara, Kazunori; Kataoka, Hideyuki; Kitano, Hiroya; Takeuchi, Hiromi

    2016-10-01

    The aim of this report is to evaluate the effects of voice rehabilitation with a voice prosthesis in a young patient with thyroid cancer. A 17-year-old girl underwent voice restoration with a voice prosthesis after laryngectomy to treat thyroid cancer. She completed voice-related questionnaires (the Voice Handicap Index-10 and Voice-Related Quality Of Life Survey) at ages 17 and 21 and underwent phonetic functional evaluation. The sound spectrograms of her phonation using the voice prosthesis showed low frequency sounds without an obvious basic frequency. She was ashamed of her hoarse voice and did not use her voice prosthesis during high school. However, after beginning to work at age 20, she used her voice to communicate in the workplace. At age 21, her questionnaire scores, especially those related to the physical and functional domains, improved compared with those at age 17. Voice restoration with a voice prosthesis is recommended for young patients who undergo laryngectomy for advanced thyroid cancer. The advantages of voice restoration with a voice prosthesis may increase when the patient reaches working age, and it may improve post-laryngectomy quality of life considerably. PMID:26960746

  9. Thyroid cancer

    MedlinePlus

    ... cancer is a cancer that starts in the thyroid gland. The thyroid gland is located inside the front of your lower ... thyroid cells that are normally present in the thyroid gland. This form of thyroid cancer tends to occur ...

  10. Sorafenib treatment of radioiodine-refractory advanced thyroid cancer in daily clinical practice: a cohort study from a single center.

    PubMed

    Gallo, Marco; Michelon, Federica; Castiglione, Anna; Felicetti, Francesco; Viansone, Alessandro Adriano; Nervo, Alice; Zichi, Clizia; Ciccone, Giovannino; Piovesan, Alessandro; Arvat, Emanuela

    2015-08-01

    Treatment options for recurrent or metastatic differentiated thyroid cancer (DTC) refractory to radioactive iodine (RAI) are inadequate. Multitargeted kinase inhibitors have recently shown promising results in phase 2-3 studies. This retrospective study aimed to document our clinical experience on the effects of sorafenib in the setting of daily clinical practice. Retrospective study evaluating the efficacy and safety of sorafenib in a cohort of patients consecutively treated with sorafenib at a single center. Twenty patients with advanced RAI-refractory thyroid carcinoma were enrolled (March 2011-March 2014). Patients generally started with 400 mg of sorafenib twice daily, tapering the dose in case of side effects. Radiological response and toxicity were measured during follow-up, together with safety parameters. CT scans were performed by a single experienced radiologist every 3-4 months. Five patients stopped sorafenib within 90 days due to severe toxicities. Median progression-free survival was 248 days. Five patients had a partial response (PR), achieved in all cases within 3 months, whereas 5 had stable disease (SD) at 12 months. Durable response rate (PR plus SD) for at least 6 months was 50 %, among those who received sorafenib for at least 3 months. Commonest adverse events included skin toxicity, gastrointestinal and constitutional symptoms. In our cohort of patients with advanced RAI-refractory thyroid carcinoma, sorafenib confirmed antitumor activity leading to SD or PR in the majority of cases, at the expense of clinically relevant side effects. More effective and tolerable agents are still needed in the treatment of RAI-refractory DTC. PMID:25414068

  11. Sorafenib in the treatment of thyroid cancer.

    PubMed

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

    2015-01-01

    Sorafenib has been evaluated in several Phase II and III studies in patients with locally advanced/metastatic radioactive iodine-refractory differentiated thyroid carcinomas (DTCs), reporting partial responses, stabilization of the disease and improvement of progression-free survival. Best responses were observed in lung metastases and minimal responses in bone lesions. On the basis of these studies, sorafenib was approved for the treatment of metastatic DTC in November 2013. Few studies suggested that reduction of thyroglobulin levels, or of average standardized uptake value at the fluorodeoxyglucose-PET, could be helpful for the identification of responding patients; but further studies are needed to confirm these results. Tumor genetic marker levels did not have any prognostic or predictive role in DTC patients.The most common adverse events observed included skin toxicity and gastrointestinal and constitutional symptoms. Encouraging results have also been observed in patients with medullary thyroid cancer. Many studies are ongoing to evaluate the long-term efficacy and tolerability of sorafenib in DTC patients. PMID:26152651

  12. Thyroid storm

    MedlinePlus

    Thyrotoxic storm; Hyperthyroid storm; Accelerated hyperthyroidism; Thyroid crisis; Thyrotoxicosis - thyroid storm ... thyroid storm can be caused by treatment of hyperthyroidism with radioiodine therapy.

  13. Thyroid scan

    MedlinePlus

    ... Read More Anaplastic thyroid cancer Cancer Goiter - simple Hyperthyroidism Multiple endocrine neoplasia (MEN) II PET scan Skin ... A.M. Editorial team. Related MedlinePlus Health Topics Hyperthyroidism Hypothyroidism Nuclear Scans Thyroid Cancer Thyroid Diseases Thyroid ...

  14. Thyroid scan

    MedlinePlus

    ... is done to: Check for thyroid cancer Evaluate thyroid nodules or goiter Find the cause of an overactive ... the thyroid appears lighter, it could be a thyroid problem. Nodules that are darker can be overactive and may ...

  15. Postpartum Thyroiditis

    MedlinePlus

    ... high thyroid hormone levels in the blood) and hypothyroidism (low thyroid hormone levels in the blood). In postpartum thyroiditis, thyrotoxicosis occurs first followed by hypothyroidism. What causes postpartum thyroiditis? The exact cause is ...

  16. Thyroid Tests

    MedlinePlus

    ... calories and how fast your heart beats. Thyroid tests check how well your thyroid is working. They ... thyroid diseases such as hyperthyroidism and hypothyroidism. Thyroid tests include blood tests and imaging tests. Blood tests ...

  17. Thyroid nodule

    MedlinePlus

    ... other thyroid blood tests Thyroid ultrasound Thyroid scan (nuclear medicine) Fine needle aspiration biopsy of the nodule or ... Guidelines for Clinical Practice for the Diagnosis and Management of Thyroid Nodules. Endocr Pract. 2010;16(suppl ...

  18. Diagnosis and Management of Hereditary Thyroid Cancer.

    PubMed

    Bano, Gul; Hodgson, Shirley

    2016-01-01

    Thyroid cancers are largely divided into medullary (MTC) and non-medullary (NMTC) cancers , depending on the cell type of origin. Familial non-medullary thyroid cancer (FNMTC) comprises about 5-15% of NMTC and is a heterogeneous group of diseases, including both non-syndromic and syndromic forms. Non-syndromic FNMTC tends to manifest papillary thyroid carcinoma , usually multifocal and bilateral . Several high-penetrance genes for FNMTC have been identified, but they are often confined to a few or single families, and other susceptibility loci appear to play a small part, conferring only small increments in risk. Familial susceptibility is likely to be due to a combination of genetic and environmental influences. The current focus of research in FNMTC is to characterise the susceptibility genes and their role in carcinogenesis. FNMTC can also occur as a part of multitumour genetic syndromes such as familial adenomatous polyposis , Cowden's disease , Werner's syndrome and Carney complex . These tend to present at an early age and are multicentric and bilateral with distinct pathology. The clinical evaluation of these patients is similar to that for most patients with a thyroid nodule. Medullary thyroid cancer (MTC) arises from the parafollicular cells of the thyroid which release calcitonin. The familial form of MTC accounts for 20-25% of cases and presents as a part of the multiple endocrine neoplasia type 2 (MEN 2) syndromes or as a pure familial MTC (FMTC). They are caused by germline point mutations in the RET oncogene on chromosome 10q11.2. There is a clear genotype-phenotype correlation, and the aggressiveness of FMTC depends on the specific genetic mutation, which should determine the timing of surgery. PMID:27075347

  19. Efficacy and safety of vascular endothelial growth factor receptor tyrosine kinase inhibitors in the treatment of advanced thyroid cancer: a meta-analysis of randomized controlled trials

    PubMed Central

    Yimaer, Wufuer; Abudouyimu, Aizizi; Tian, Ye; Magaoweiya, Sailike; Bagedati, Duman; Wen, Hao

    2016-01-01

    Background We performed a systematic review and meta-analysis to determine the efficacy and safety of the US Food and Drug Administration approved vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) in the treatment of advanced thyroid cancer. Patients and methods We included prospective randomized controlled trials that compared VEGFR-TKIs with placebo for advanced thyroid cancer. The endpoints included safety (fatal adverse events [FAEs], treatment discontinuation, and any severe [grade 3 or 4] adverse events [AEs]) and efficacy (objective response rate, progression-free survival, and overall survival). The pooled relative risk (RR) or hazard ratio (HR) was calculated by using either random-effects or fixed-effects models according to the heterogeneity of included studies. Results A total of 1,614 advanced thyroid cancer patients from five randomized controlled trials were identified for analysis. Compared with placebo alone, VEGFR-TKIs significantly increased the risk of treatment discontinuation (RR: 3.80, 95% confidence interval [CI]: 2.56–5.65, P<0.001) and any severe AEs (RR: 2.63, 95% CI: 1.72–4.03, P<0.001), but not of FAEs (RR: 1.24, 95% CI: 0.65–2.39, P=0.52). The use of VEGFR-TKIs in advanced thyroid cancer was associated with a significant improvement in objective response rate (RR: 8.73, 95% CI: 1.72–44.4, P=0.009) and progression-free survival (HR: 0.41, 95% CI: 0.27–0.61, P<0.001), with a tendency to improve overall survival (HR: 0.83, 95% CI: 0.68–1.01, P=0.06). Conclusion The use of small-molecule VEGFR-TKIs in advanced thyroid cancer did significantly increase the risk of treatment discontinuation and any severe AEs, but not of FAEs, compared with placebo alone. It is important for physicians to weigh the risk of toxicities as well as the potential survival benefits associated with VEGFR-TKI treatment in advanced thyroid cancer patients. PMID:27022276

  20. Thyrotoxicosis followed by Hypothyroidism due to Suppurative Thyroiditis Caused by Nocardia brasiliensis in a Patient with Advanced Acquired Immunodeficiency Syndrome.

    PubMed

    Teckie, G2; Bhana, S A; Tsitsi, J M L; Shires, R

    2014-03-01

    Acute thyroiditis is an extremely rare complication of nocardiosis. We report a patient with hyperthyroidism due to suppurative thyroiditis caused by Nocardia brasiliensis. A 38-year-old Black male presented with features of thyrotoxicosis, sepsis and airway obstruction. He had no evidence of underlying thyroid disease, but was severely immunocompromised as a result of acquired immunodeficiency syndrome. He had previously been diagnosed with pulmonary nocardiosis and also had nocardial abscesses on his anterior chest wall. Investigations revealed thyrotoxicosis, with a FT4 of 43.2 pmol/l and a suppressed TSH <0.01 mIU/l. Serum anti-thyroperoxidase and anti-thyroglobulin antibodies were absent. Computed tomography scan showed a large abscess in the anterior neck involving the left lobe and isthmus, as well as inhomogeneous changes in the right lobe of the thyroid. The radioisotopic scan showed absent uptake of tracer in keeping with thyroiditis. Although the initial presentation was that of hyperthyroidism, destruction of the gland later resulted in sustained hypothyroidism, necessitating thyroid hormone supplementation. The hyperthyroidism can be explained by the release of presynthesized and stored thyroid hormone into the circulation as a result of inflammation and disruption of the thyroid follicles, and the subsequent hypothyroidism by the fact that much of the gland was destroyed by the abscess and the extensive inflammatory process. This is the first documented case of hyperthyroidism in a patient with acute suppurative thyroiditis caused by Nocardia. PMID:24847469

  1. Laboratory evaluation of anatomic disorders of the thyroid

    SciTech Connect

    Kabadi, U.M.

    1983-11-01

    Thyroid function tests, radioiodine uptake and scintiscanning, and antithyroid antibody titers are the main laboratory tests useful in the management of goiter. Scintiscanning and ultrasonography aid in differentiating a functioning adenoma from a ''cold'' solid nodule--a crucial distinction since the incidence of cancer in a cold nodule is 20 percent. Radioiodine scanning and serum thyroglobulin help in the diagnosis of a well-differentiated thyroid cancer. Serum calcitonin serves as a reliable tumor marker for medullary carcinoma.

  2. Thyroid Tests

    MedlinePlus

    ... Organizations (PDF, 269 KB). Alternate Language URL Thyroid Tests Page Content On this page: What is the ... Top ] Why do health care providers perform thyroid tests? Health care providers perform thyroid tests to assess ...

  3. Thyroid Surgery

    MedlinePlus

    ... thyroid surgery, requiring treatment with thyroid hormone (see Hypothyroidism brochure ). This is especially true if you had ... Nodules Goiter Graves’ Disease Hashimoto’s Thyroiditis Hyperthyroidism (Overactive) Hypothyroidism (Underactive) Iodine Deficiency Low Iodine Diet Radioactive Iodine ...

  4. Silent thyroiditis

    MedlinePlus

    ... gland. The disorder can cause hyperthyroidism, followed by hypothyroidism. The thyroid gland is located in the neck, ... Later symptoms may be of an underactive thyroid ( hypothyroidism ), including fatigue and cold intolerance, until the thyroid ...

  5. Ultrasonography in the diagnosis of Hashimoto's thyroiditis.

    PubMed

    Wu, Guihua; Zou, Dazhong; Cai, Haiyun; Liu, Yajun

    2016-01-01

    Hashimoto's thyroiditis is a type of autoimmune thyroid disease with an increasing prevalence in past decades. Its diagnosisis mostly based on ultrasonography. Ultrasonography is a useful and essential tool to make this diagnosis based on the characteristics of the disease. In the differential diagnosis of thyroid nodules, ultrasound-guided fine-needle biopsy is an effective method to distinguish Hashimoto's thyroiditis from other thyroid disorders. One exciting and recent advance is that non-invasive ultrasound-based methods have supplemented fine-needle aspiration to diagnose Hashimoto's thyroiditis under more complex conditions. In this review, we discuss the recent advantages of ultrasonography in the diagnosis of Hashimoto's thyroiditis. PMID:27100487

  6. Thyroid Diseases Tests

    MedlinePlus

    ... of thyroiditis and identify autoimmune thyroid conditions Thyroid peroxidase (TPO) antibody—a marker for autoimmune thyroid disease; ... for thyroid gland abnormalities and to evaluate thyroid function (for iodine) in different areas of the thyroid ...

  7. Calcitonin-negative neuroendocrine tumor of thyroid gland mimicking anaplastic carcinoma: an unusual entity

    PubMed Central

    Arpaci, Rabia Bozdogan; Berkesoglu, Mustafa; Dag, Ahmet; Sezer, Emel; Bal, Kemal Koray; Vayısoğlu, Yusuf

    2015-01-01

    Medullary thyroid cancer is the neuroendocrine tumor (NET) of thyroid with mostly both secreting calcitonin and immunohistochemically showing calcitonin positivity. Occasionally; NETs of thyroid may have little or no calcitonin expression. We present a case of serum calcitonin negative and immunohistochemically calcitonin-negative staining tumor with positive reaction to neuroendocrine markers synaptophysin and chromogranin-A. The patient’s right vocal cord was paralytic and thyroid mass was huge with descending to thorax till hilar region. We discussed diagnostic difficulties and way of treatment about NETs of thyroid with the light of current literature with this case. PMID:26312221

  8. Genetics Home Reference: medullary cystic kidney disease type 1

    MedlinePlus

    ... disease type 1 medullary cystic kidney disease type 1 Enable Javascript to view the expand/collapse boxes. ... Close All Description Medullary cystic kidney disease type 1 (MCKD1) is an inherited condition that affects the ...

  9. Recovery of Dysphagia in Lateral Medullary Stroke

    PubMed Central

    Gupta, Hitesh; Banerjee, Alakananda

    2014-01-01

    Lateral medullary stroke is typically associated with increased likelihood of occurrence of dysphagia and exhibits the most severe and persistent form. Worldwide little research exists on dysphagia in brainstem stroke. An estimated 15% of all patients admitted to stroke rehabilitation units experience a brainstem stroke out of which about 47% suffer from dysphagia. In India, a study showed that 22.3% of posterior circulation stroke patients develop dysphagia. Dearth of literature on dysphagia and its outcome in brainstem stroke particularly lateral medullary stroke motivated the author to present an actual case study of a patient who had dysphagia following a lateral medullary infarct. This paper documents the severity and management approach of dysphagia in brainstem stroke, with traditional dysphagia therapy and VitalStim therapy. Despite being diagnosed with a severe form of dysphagia followed by late treatment intervention, the patient had complete recovery of the swallowing function. PMID:25045555

  10. Radioiodine and radiotherapy in the management of thyroid cancers

    SciTech Connect

    Simpson, W.J. )

    1990-06-01

    Radioiodine is an important adjuvant treatment in the management of resectable papillary and follicular thyroid cancers in all patients except those with the best prognostic features. External radiation is also an important adjuvant therapy in these patients, especially those with tumors that extend beyond the thyroid gland and invade the trachea, esophagus, nerves, and blood vessels; it is especially important in treating patients whose tumors do not concentrate radioiodine. Radioiodine may be curative in patients with microscopic distant metastases demonstrated by radioiodine scanning. Even unresectable primary papillary and follicular cancers may be eradicated by combined therapy with radioiodine and radiotherapy. Radioiodine plays no significant role in the treatment of medullary or anaplastic thyroid cancers, but external radiation may eradicate microscopic thyroid bed or nodal disease when persistent disease is indicated by elevated calcitonin levels in medullary thyroid cancer patients. Anaplastic thyroid cancers are usually unresectable and are not eradicated by conventional radiotherapy or by any of the novel radiation techniques, with or without chemotherapy. In all types of thyroid cancer, external radiotherapy may produce beneficial palliative results in patients with distant metastases, but the use of radioiodine should always be explored in papillary and follicular thyroid cancer patients. 30 references.

  11. Thyroid Cancer

    MedlinePlus

    ... are here Home > Types of Cancer > Thyroid Cancer Thyroid Cancer This is Cancer.Net’s Guide to Thyroid Cancer. Use the menu below to choose the ... social workers, and patient advocates. Cancer.Net Guide Thyroid Cancer Overview Statistics Medical Illustrations Risk Factors Symptoms ...

  12. Thyroid pathologies accompanying primary hyperparathyroidism: a high rate of papillary thyroid microcarcinoma

    PubMed Central

    Kutlutürk, Koray; Otan, Emrah; Yağcı, Mehmet Ali; Usta, Sertaç; Aydın, Cemalettin; Ünal, Bülent

    2014-01-01

    Objective: Thyroid pathologies and non-medullary thyroid cancer often accompany primary hyperparathyroidism (PHPT). The purpose of this study was to examine the association between thyroid diseases, especially micropapillary thyroid cancer, with PHPT. Material and Methods: Data regarding 46 patients who were operated on with a diagnosis of PHPT at Inonu University Faculty of Medicine, General Surgery Clinic between June 2009 and March 2013 were retrospectively analyzed. Age, gender, levels of preoperative calcium, parathyroid hormone and phosphorus, and the histopathological results of the removed parathyroid and thyroid tissues were evaluated. All of the patients had a preoperative diagnosis of PHPT and there was no history of radiation to the head and neck region in any of the patients. Results: Out of the 46 patients who were operated on for PHPT, 39 were female and 7 were male. The mean age was 52.8 years (25–76). Simultaneous thyroidectomy was performed in 35 patients (76.1%) due to an accompanying thyroid disorder. Papillary microcarcinoma was detected in 5 of these 35 (10.9%) patients who underwent thyroidectomy, two of which (40%) were multifocal tumors. The benign thyroid pathologies detected in the remaining 30 (65.2%) cases included lymphocytic thyroiditis in 3, Hashimoto thyroiditis in 1, follicular adenoma in 3 (two of which was Hurtle cell), and nodular colloidal goiter in 23 patients. The preoperative serum phosphate level was significantly higher in the group with papillary thyroid microcarcinoma (p=0.013). Conclusion: In regions where goiter is endemic, thyroid diseases and thyroid papillary microcarcinoma occur in association with PHPT at a higher rate compared to the normal population. Therefore, we believe that patients who are planned for surgery due to PHPT should be thoroughly investigated for the presence of any concomitant malignant thyroid pathologies in the preoperative period. It should also be kept in mind that patients with high

  13. Thyroid cancer: a lethal endocrine neoplasm

    SciTech Connect

    Robbins, J.; Merino, M.J.; Boice, J.D. Jr.; Ron, E.; Ain, K.B.; Alexander, H.R.; Norton, J.A.; Reynolds, J.

    1991-07-15

    This conference focuses on the controversies about managing thyroid cancer, emphasizing the possibility that the treatment of patients with potentially fatal thyroid cancer may be improved. Although the mortality rate from thyroid cancer is low, it is the highest among cancers affecting the endocrine glands (excluding the ovary). Exposure to radiation during childhood in the 1930s and 1940s increased the incidence of but not the mortality from thyroid cancer, because these tumors are mainly papillary cancers developing in young adults. These rates may change as the exposed cohort ages. Risk factors that increase mortality include older patient age and the growth characteristics of the tumor at diagnosis, the presence of distant metastases, and cell type (for example, the tall-cell variants of papillary cancer, follicular cancer (to be distinguished from the more benign follicular variant of papillary cancer), medullary cancer, and anaplastic cancer). Local metastases in lymph nodes do not seem to increase the risk for death from papillary cancer, but they do increase the risk for death from follicular and medullary cancer. In the latter, mortality is decreased by the early detection and treatment of patients with the familial multiple endocrine neoplasia syndrome 2a. There are excellent tumor markers for differentiated cancer of the parafollicular and of the follicular cells. Measuring the calcitonin level allows early diagnosis of familial medullary cancer, whereas measuring the thyroglobulin level, although useful only after total thyroidectomy, allows early recognition of recurrence or metastases of papillary or follicular cancer. Initial surgery, protocols for follow-up, and the use of radioiodine for the ablation of any residual thyroid and the treatment of metastatic cancer are discussed.128 references.

  14. Diagnostic Dilemma in a Thyroid Incidentaloma: Second Primary versus Metastatic Nodule?

    PubMed Central

    Mirza, Abid Ali; Srinivas, Kodaganur Gopinath; Amarendra, Shankarappa; Gopinath, K.S

    2016-01-01

    With the increasing use of 18F-Fluro-Deoxyglucose (FDG) Positron Emission Tomography (PET) the number of thyroid incidentalomas is on the rise. Focal thyroid incidentalomas identified by FDG-PET have been reported to have a high incidence of malignancy. Neuroendocrine tumours of the thyroid are rare entities. The most common neuroendocrine tumour of the thyroid is medullary carcinoma. A thyroid nodule in a patient with a known neuroendocrine tumour must be differentiated from a primary medullary carcinoma which can present as a diagnostic challenge to the clinician. A 65-year-old female patient was referred for thyroidectomy for a FNAC diagnosed follicular neoplasm of the left lobe of the thyroid, detected on FDG PET follow up. She was a known case of neuroendocrine tumour of the pancreas with no features suggestive of familial Multiple Endocrine Neoplasia (MEN) syndrome. The patient had undergone Whipple’s procedure elsewhere, 5 years back. Following total thyroidectomy, the final histopathology report was suggestive of a primary neuroendocrine tumour. We present this case to highlight the clinical dilemma in diagnosing a thyroid incidentaloma as a second primary neuroendocrine tumour versus a solitary metastatic nodule in the background of metastatic gastroentero pancreatic neuroendocrine tumour. Although clinically, a metastatic nodule should have been the obvious diagnosis, the histopathological and immunohistochemical features were in favour of a primary non-medullary Neuroendocrine Tumor (NET) of the thyroid. PMID:27504349

  15. Selective use of vandetanib in the treatment of thyroid cancer

    PubMed Central

    Fallahi, Poupak; Di Bari, Flavia; Ferrari, Silvia Martina; Spisni, Roberto; Materazzi, Gabriele; Miccoli, Paolo; Benvenga, Salvatore; Antonelli, Alessandro

    2015-01-01

    Vandetanib is a once-daily orally available tyrosine kinase inhibitor that works by blocking RET (REarranged during Transfection), vascular endothelial growth factor receptor (VEGFR-2, VEGFR-3), and epidermal growth factor receptor and to a lesser extent VEGFR-1, which are important targets in thyroid cancer (TC). It is emerging as a potentially effective option in the treatment of advanced medullary thyroid cancer (MTC) and in dedifferentiated papillary thyroid cancer not responsive to radioiodine. The most important effect of vandetanib in aggressive MTC is a prolongation of progression-free survival and a stabilization of the disease. Significant side effects have been observed with the vandetanib therapy (as fatigue, hypertension, QTc prolongation, cutaneous rash, hand-and-foot syndrome, diarrhea, etc), and severe side effects can require the suspension of the drug. Several studies are currently under way to evaluate the long-term efficacy and tolerability of vandetanib in MTC and in dedifferentiated papillary TC. The efficacy of vandetanib in patients with MTC in long-term treatments could be overcome by the resistance to the drug. However, the effectiveness of the treatment could be ameliorated by the molecular characterization of the tumor and by the possibility to test the sensitivity of primary TC cells from each subject to different tyrosine kinase inhibitor. Association studies are evaluating the effect of the association of vandetanib with other antineoplastic agents (such as irinotecan, bortezomib, etc). Further research is needed to determine the ideal therapy to obtain the best response in terms of survival and quality of life. PMID:26170630

  16. Veliparib, Capecitabine, and Temozolomide in Patients With Advanced, Metastatic, and Recurrent Neuroendocrine Tumor

    ClinicalTrials.gov

    2016-07-10

    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

  17. Thyroid Disease

    MedlinePlus

    ... base of your neck, just below your Adam's apple. This gland makes thyroid hormone that travels in ... base of your neck, just below your Adam's apple. This gland makes thyroid hormone that travels in ...

  18. Thyroid Cancer

    MedlinePlus

    ... body work normally. There are several types of cancer of the thyroid gland. You are at greater ... imaging tests, and a biopsy to diagnose thyroid cancer. Treatment depends on the type of cancer you ...

  19. Thyroid cancer

    MedlinePlus

    ... known prevention. Awareness of risk (such as previous radiation therapy to the neck) can allow earlier diagnosis and treatment. Sometimes, people with family histories and genetic mutations related to thyroid cancer will have their thyroid ...

  20. Thyroid ultrasound

    MedlinePlus

    ... to: Cysts Enlargement of the thyroid gland ( goiter ) Thyroid nodules Your doctor can use these results and the results of other tests to direct your care. Additional conditions ... Multiple endocrine neoplasia (MEN) II Papillary carcinoma of ...

  1. Thyroid Problems

    MedlinePlus

    ... treated differently. Common thyroid disorders and problems include: Hypothyroidism Hypothyroidism is a disorder in which your thyroid doesn’ ... normal after you get better. If you have hypothyroidism, however, the levels of T4 in your blood ...

  2. Thyroid Antibodies

    MedlinePlus

    ... blocking production of thyroid hormones and resulting in hypothyroidism . TBII is not routinely tested, but TSI is ... autoimmune disease . A low level of thyroid hormones ( hypothyroidism ) can cause symptoms, such as: Weight gain Fatigue ...

  3. Silent thyroiditis

    MedlinePlus

    ... of the thyroid gland. The disorder can cause hyperthyroidism , followed by hypothyroidism . ... earliest symptoms result from an overactive thyroid gland (hyperthyroidism). These symptoms may last for up to 3 ...

  4. Thyroid storm

    MedlinePlus

    Thyrotoxic storm; Hyperthyroid storm; Accelerated hyperthyroidism ... Thyroid storm occurs in people with untreated hyperthyroidism. It is usually brought on by a major stress such as trauma, heart attack, or infection. Thyroid storm is very rare.

  5. Thyroid disease

    SciTech Connect

    Falk, S.

    1990-01-01

    Presenting a multidisciplinary approach to the diagnosis and treatment of thyroid disease, this volume provides a comprehensive picture of current thyroid medicine and surgery. The book integrates the perspectives of the many disciplines that deal with the clinical manifestations of thyroid disorders. Adding to the clinical usefulness of the book is the state-of-the-art coverage of many recent developments in thyroidology, including the use of highly sensitive two-site TSH immunoradionetric measurements to diagnose thyroid activity; thyroglobulin assays in thyroid cancer and other diseases; new diagnostic applications of MRI and CT; treatment with radionuclides and chemotherapy; new developments in thyroid immunology, pathology, and management of hyperthyroidism; suppressive treatment with thyroid hormone; and management of Graves' ophthalmopathy. The book also covers all aspects of thyroid surgery, including surgical treatment of hyperthyroidism; papillary, follicular, and other carcinomas; thyroidectomy; and prevention and management of complications.

  6. Thyroid Tests

    MedlinePlus

    ... the pituitary decreases TSH production. [ Top ] Why do health care providers perform thyroid tests? Health care providers perform ... Hyperthyroidism and Hypothyroidism . [ Top ] What blood tests do health care providers use to check a person’s thyroid function? ...

  7. Thyroid Emergencies.

    PubMed

    Leung, Angela M

    2016-01-01

    Myxedema coma and thyroid storm are thyroid emergencies associated with increased mortality. Prompt recognition of these states-which represent the severe, life-threatening conditions of extremely reduced or elevated circulating thyroid hormone concentrations, respectively-is necessary to initiate treatment. Management of myxedema coma and thyroid storm requires both medical and supportive therapies and should be treated in an intensive care unit setting. PMID:27598067

  8. Clinicopathological significance of gastric poorly differentiated medullary carcinoma.

    PubMed

    Hirai, Hideaki; Yoshizawa, Tadashi; Morohashi, Satoko; Haga, Toshihiro; Wu, Yunyan; Ota, Rie; Takatsuna, Masafumi; Akasaka, Harue; Hakamada, Kenichi; Kijima, Hiroshi

    2016-01-01

    Poorly differentiated gastric adenocarcinoma of solid type is known to show a clinicopathological diversity, but its morphological characteristics have rarely been investigated. In this study, we defined poorly differentiated medullary carcinoma indicating the following three characteristics: (i) more than 90% of the entire tumor were composed of poorly differentiated adenocarcinoma in a medullary growth, (ii) the tumor exhibited an expansive growth at the tumor margin, and (iii) special types such as an α-fetoprotein-producing carcinoma, neuroendocrine carcinoma, and carcinoma with lymphoid stroma were excluded. Based on the definition, we subclassified the poorly differentiated gastric adenocarcinoma of solid type into the two groups: medullary carcinoma and non-medullary carcinoma, and clinicopathologically analyzed 23 cases of medullary carcinomas and 38 cases of non-medullary carcinomas. The medullary carcinomas less frequently displayed lymphatic invasion, venous invasion, and lymph node metastasis, compared with the non-medullary carcinoma (P < 0.001, P = 0.002, and P < 0.001, respectively). The patients with medullary carcinomas significantly showed better disease-free survival (P = 0.017). This is the first study to demonstrate that poorly differentiated adenocarcinoma of solid type can be subclassified into tumors with low and high malignant potentials. Gastric poorly differentiated medullary carcinoma is considered to be a novel histological type predicting good patients' prognosis. PMID:27108877

  9. Differential Expression of Aquaporins and Its Diagnostic Utility in Thyroid Cancer

    PubMed Central

    Niu, Dongfeng; Kondo, Tetsuo; Nakazawa, Tadao; Kawasaki, Tomonori; Yamane, Tetsu; Mochizuki, Kunio; Kato, Yohichiro; Matsuzaki, Toshiyuki; Takata, Kuniaki; Katoh, Ryohei

    2012-01-01

    Background Aquaporin3 (AQP3) and Aquaporin4 (AQP4) play a major role in transcellular and transepithelial water movement as water channel membrane proteins. Little is known of their expression and significance in human thyroid tissues. Thus, we examined the expression of AQP3 and AQP4 in normal, hyperplastic and neoplastic thyroid tissues in conjunction with human thyroid cancer cell lines. Methods and Results Immunohistochemical analyses demonstrated AQP3 in the cytoplasmic membrane of normal C cells, but not in follicular cells. In contrast, AQP4 was not found in C cells but was identified in normal follicular cells. AQP4 was positive in 92% of Graves’ disease thyroids and 97% of multinodular goiters, and we failed to demonstrate AQP3 in these hyperplastic tissues. In neoplastic thyroid lesions, we observed AQP3 in 91% of medullary thyroid carcinomas but in no other follicular cell tumors. AQP4 was demonstrated in 100% of follicular adenomas, 90% of follicular carcinomas, and 85% of papillary carcinomas, while it was negative in all medullary carcinomas and undifferentiated carcinomas. Reverse transcriptase polymerase chain reaction (RT-PCR) analyses revealed AQP3 mRNA expression only in medullary carcinomas and AQP4 mRNA expression in follicular cell-derived tumors except for undifferentiated carcinomas. In thyroid cancer cell lines, using RT-PCR and western blotting, AQP3 mRNA and protein were only identified in the TT cell line (human medullary carcinoma cell line) and AQP4 in the other cell lines. In addition, AQP3 mRNA expression was up-regulated by FBS and calcium administration in both a dose and time dependent manner in TT cells. Conclusion The differential expressions of AQP3 and AQP4 may reflect the biological nature and/or function of normal, hyperplastic, and neoplastic thyroid cells and additionally may have value in determining differential diagnoses of thyroid tumors. PMID:22808259

  10. Incidental Detection of Oxyphilic Papillary Thyroid Carcinoma by 18F-Fluorocholine PET/CT.

    PubMed

    Lalire, Paul; Zalzali, Mohamed; Garbar, Christian; Bruna-Muraille, Claire; Morland, David

    2016-06-01

    A 70-year-old man with prostate cancer and increased prostate-specific antigen level of 55 ng/mL underwent staging F-fluorocholine PET/CT, which demonstrated the primary prostate tumor and a focal area corresponding to a 2-cm hypodense nodule in the left thyroid lobe. Fine-needle aspiration and subsequent total thyroidectomy with central lymph node dissection showed an oxyphilic papillary thyroid carcinoma and a medullary microcarcinoma. Oxyphilic tumors represent a significant proportion of the few case reports of incidental focal thyroid fluorocholine thyroid uptake. PMID:26914574

  11. 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

  12. [Thyroid diseases in sub-Saharan Africa].

    PubMed

    Sidibé, El Hassane

    2007-01-01

    hyperthyroidism has tripled, now accounting for 18.5% of all such operations. This disorder is found today in subjects older than 50 years, mainly from rural areas, and caused most often by Graves disease (25 of 51 cases). Graves disease in young women can cause serious problems during pregnancy; in such cases assessment of the minimal effective dose of antithyroid agents is essential. Carbimazole leads to remission in 61% of cases of Graves disease. Hypothyroidism can be auto-immune and often in patent forms because of insufficient screening in Africa: 24 cases in Dakar (1984) and 37 others noticed by us (1998). Single-nodule tumors were assessed in 89 patients in Khartoum: they were found to be simple goiters in 72% of cases, follicular adenoma in 13.5%, cancer in 13.5% (with 6 of the 12 cases follicular, 5 papillary, and 1 anaplastic). The sex ratio for thyroid cancer in Ouagadougou is 0.22, thus mainly women. It affects mainly women in their 30s. Thyroid cancer at Ibadan was found to be papillary carcinoma in 45.3% of cases; follicular forms were seen in 44.5% and this series includes 5% of medullary cancers (7 cases), with a mean age of 34 years. Already 4 other cases from Francophone sub-Saharan Africa have been noticed. Iodine deficiency is suggested to play a role because follicular cancer in southern Africa accounts for up to 55% of thyroid cancers. Thyroid cancers in Algeria are associated with low socioeconomic status and characterized by a high prevalence of cancers discovered at an advanced stage and of anaplastic carcinomas. Oral potassium iodate is recommended: 30 mg of iodate a month or 8 mg every two weeks. Iodized oil has been recommended by some authors, as well as a combination of iodine and sugar, and the iodation of drinking water; these are in addition to the proposed methods of opening up areas by new infrastructure). In conclusion, thyroid disease is due predominantly to iodine deficiency and goitrogenic products, but we also note the increasing emergence

  13. Medullary thymic epithelium expresses a ligand for CTLA4 in situ and in vitro

    SciTech Connect

    Nelson, A.J.; Hosier, S.; Farr, A.G. ); Brady, W.; Linsley, P.S. )

    1993-09-01

    A fusion protein consisting of the extracellular domain of CTLA4 and an Ig C[gamma]1 chain (CTLA4-Ig) was used to examine the distribution of the ligands for CTLA4 within the murine thymus and to characterize the nature of these ligands. Two-color immunofluorescence of thymus tissue revealed binding of the fusion protein to medullary thymic epithelial cells and dendritic cells within the corticomedullary and medullary areas of the thymus. Medullary cells binding the fusion protein also expressed MHC class II products and ICAM-1. Thymus tissue sections treated with cross-linking fixatives, such as glutaraldehyde, paraformaldehyde, or 1-ethyl-3(d dimethylaminopropyl)-carbodiimide no longer bound the CTLA4 fusion protein, indicating that binding was very sensitive to the tertiary structure of the tissue ligand. The ability of thymic tissue to bind the fusion protein was developmentally regulated. At day 14 of gestation, only scattered single cells were labeled. Clusters of labeled cells, which were detected by day 16 of gestation, increased in frequency with advancing gestational age. Consistent with the in situ labeling studies. CTLA4-lg also labeled several thymic epithelial cell lines previously shown to have a medullary phenotype. Polymerase chain reaction analysis of mRNA extracted from these cells indicated they contained mRNA for B7, a known counter receptor for CTLA4 and CD28. Immunoprecipitation of [sup 125]I-labeled thymic epithelial cells with the CTLA4-Ig detected a M[sub r] 65,000 to 70,000 species under reducing conditions, consistent with previous studies of B7. These data suggest that the ligand for CTLA4 expressed by thymic epithelial cells in vitro is B7 and that the expression of this ligand in situ is largely restricted to the medullary compartment and is associated with epithelial cells and dendritic cells.

  14. [Advances in the research of BRAF(V600E) gene mutation correlated with papillary thyroid carcinoma].

    PubMed

    Xu, X Q; Wang, X H; Jing, J X

    2016-08-01

    The increase in the incidence of papillary thyroid carcinoma (PTC) is a serious threat to public health. V-raf murine sarcoma viral oncogene homolog B(BRAF)(V600E) gene mutation is not only the common genetics factors, but also is the early event in process of thyroid carcinogenesis. We mainly illustrate the mechanism of BRAF(V600E) gene in genesis and development of PTC and the correlation of BRAF(V600E) gene mutation and the clinicopathological characteristics of PTC. Finally, we briefly summarize some scientific achievements about tyrosine kinase inhibitors targeted for BRAF(V600E) gene and their clinical prospect in terms of translation medicine concept. In summary, BRAF(V600E) gene is expected to be a new molecular marker of PTC, which will take a new hope for individualized precise treatment for patients with PTC. PMID:27625138

  15. Application of Metabolomics in Thyroid Cancer Research

    PubMed Central

    Wojakowska, Anna; Chekan, Mykola; Widlak, Piotr; Pietrowska, Monika

    2015-01-01

    Thyroid cancer is the most common endocrine malignancy with four major types distinguished on the basis of histopathological features: papillary, follicular, medullary, and anaplastic. Classification of thyroid cancer is the primary step in the assessment of prognosis and selection of the treatment. However, in some cases, cytological and histological patterns are inconclusive; hence, classification based on histopathology could be supported by molecular biomarkers, including markers identified with the use of high-throughput “omics” techniques. Beside genomics, transcriptomics, and proteomics, metabolomic approach emerges as the most downstream attitude reflecting phenotypic changes and alterations in pathophysiological states of biological systems. Metabolomics using mass spectrometry and magnetic resonance spectroscopy techniques allows qualitative and quantitative profiling of small molecules present in biological systems. This approach can be applied to reveal metabolic differences between different types of thyroid cancer and to identify new potential candidates for molecular biomarkers. In this review, we consider current results concerning application of metabolomics in the field of thyroid cancer research. Recent studies show that metabolomics can provide significant information about the discrimination between different types of thyroid lesions. In the near future, one could expect a further progress in thyroid cancer metabolomics leading to development of molecular markers and improvement of the tumor types classification and diagnosis. PMID:25972898

  16. A review on thyroid cancer during pregnancy: Multitasking is required.

    PubMed

    Khaled, Hussein; Al Lahloubi, Nasr; Rashad, Noha

    2016-07-01

    Thyroid cancer is the second most common cancer diagnosed during pregnancy after breast cancer. The goal of management is to control malignancy and prevent maternal and fetal complications as a result of maternal hypothyroidism. The role of female sex hormones as an etiologic factor was investigated, with no clear association. Pregnancy can cause an increase in size of a previously existed thyroid nodule through the structural similarity between TSH and BHCG, and the normally expressed estrogen receptors on thyroid gland cells. Effect of pregnancy on development and prognosis of differentiated thyroid malignancies (papillary and follicular) has also been studied. The prognosis of thyroid cancer is not worse in patients diagnosed during pregnancy or those who got pregnant after curative treatment. Termination of pregnancy is not indicated at all, surgery can be delayed till after delivery except in rapidly growing aggressive tumors. While radioactive iodine ablation is absolutely contra-indicated, the new systemic therapies are not well studied during pregnancy. However, almost all these new agents are classified as FDA category C or D and are better to be avoided. The effect of pregnancy on other types of thyroid cancer (medullary and anaplastic thyroid tumors) is not well studied because of very low incidence with pregnancy. The endocrinological management of thyroid cancer during pregnancy is of utmost importance. The hypothyroidism after total thyroidectomy can cause fetal hypothyroidism. Therefore, the management of thyroid cancer related to pregnancy needs a multidisciplinary team. PMID:27408758

  17. Current Concepts in the Molecular Genetics and Management of Thyroid Cancer: An Update for Radiologists.

    PubMed

    Kelil, Tatiana; Keraliya, Abhishek R; Howard, Stephanie A; Krajewski, Katherine M; Braschi-Amirfarzan, Marta; Hornick, Jason L; Ramaiya, Nikhil H; Tirumani, Sree Harsha

    2016-01-01

    Substantial improvement in the understanding of the oncogenic pathways in thyroid cancer has led to identification of specific molecular alterations, including mutations of BRAF and RET in papillary thyroid cancer, mutation of RAS and rearrangement of PPARG in follicular thyroid cancer, mutation of RET in medullary thyroid cancer, and mutations of TP53 and in the phosphatidylinositol 3'-kinase (PI3K)/AKT1 pathway in anaplastic thyroid cancer. Ultrasonography (US) and US-guided biopsy remain cornerstones in the initial workup of thyroid cancer. Surgery is the mainstay of treatment, with radioactive iodine (RAI) therapy reserved for differentiated subtypes. Posttreatment surveillance of thyroid cancer is done with US of the thyroid bed as well as monitoring of tumor markers such as serum thyroglobulin and serum calcitonin. Computed tomography (CT), magnetic resonance imaging, and fluorine 18 fluorodeoxyglucose positron emission tomography/CT are used in the follow-up of patients with negative iodine 131 imaging and elevated tumor markers. Certain mutations, such as mutations of BRAF in papillary thyroid carcinoma and mutations in RET codons 883, 918, and 928, are associated with an aggressive course in medullary thyroid carcinoma, and affected patients need close surveillance. Treatment options for metastatic RAI-refractory thyroid cancer are limited. Currently, Food and Drug Administration-approved molecularly targeted therapies for metastatic RAI-refractory thyroid cancer, including sorafenib, lenvatinib, vandetanib, and cabozantinib, target the vascular endothelial growth factor receptor and RET kinases. Imaging plays an important role in assessment of response to these therapies, which can be atypical owing to antiangiogenic effects. A wide spectrum of toxic effects is associated with the molecularly targeted therapies used in thyroid cancer and can be detected at restaging scans. (©)RSNA, 2016. PMID:27618325

  18. Radionuclide bone scanning of medullary chondrosarcoma

    SciTech Connect

    Hudson, T.M.; Chew, F.S.; Manaster, B.J.

    1982-12-01

    /sup 99m/Tc methylene diphosphonate bone scans of 18 medullary chondrosarcomas of bone were correlated with pathologic macrosections of the resected tumors. There was increased scan uptake by all 18 tumors, and the uptake in 15 scans corresponded accurately to the anatomic extent of the tumors. Only three scans displayed increased uptake beyond the true tumor margins; thus, the extended pattern of uptake beyond the true tumor extent is much less common in medullary chondrosarcomas than in many other primary bone tumors. Therefore, increased uptake beyond the apparent radiographic margin of the tumor suggests possible occult tumor spread. Pathologically, there was intense reactive new bone formation and hyperemia around the periphery of all 18 tumors, and there were foci of enchondral ossification, hyperemia, or calcification within the tumor itself in nearly every tumor. Three scans displayed less uptake in the center of the tumors than around their peripheries. One of these tumors was necrotic in the center, but the other two were pathologically no different from tumors that displayed homogeneous uptake on the scan.

  19. [Radiotherapy for Thyroid Cancer].

    PubMed

    Jingu, Keiichi; Maruoka, Shin; Umezawa, Rei; Takahashi, Noriyoshi

    2015-06-01

    Radioactive 131I therapy for differentiated thyroid cancer has been used since the 1940s and is an established and effective treatment. In contrast, external beam radiotherapy (EBRT) was considered to be effective for achieving local control but not for prolonging survival. Although clinicians were hesitant to administer EBRT owing to the potential radiation-induced adverse effects of 2 dimensional (2D)-radiotherapy until 2000, it is expected that adverse effects will be reduced and treatment efficacy improved through the introduction of more advanced techniques for delivering radiation (eg, 3D-radiotherapy and intensity modulated radiotherapy [IMRT]). The prognosis of undifferentiated thyroid cancer is known to be extremely bad, although in very rare cases, multimodality therapy (total or subtotal resection, chemotherapy, and radiotherapy) has allowed long-term survival. Here, we report the preliminary results of using hypofractionated radiotherapy for undifferentiated thyroid cancer in our institution. PMID:26199238

  20. Diagnosis and management of carcinoma of the thyroid

    SciTech Connect

    Block, M.A.

    1987-06-01

    Thyroid nodules are a frequent finding but engender concern primarily because of a large size or, occasionally, as a manifestation of a carcinoma. Needle biopsy permits a definite diagnosis in the majority of cases. Well-differentiated thyroid carcinoma is treated by surgery, the extent of which would be based on the gross evidence of the extent of the disease, the histologic features of the lesion, the patient's age and overall medical status, and the need to avoid postoperative complications. The appropriate care after surgery is also based on the individual patient. Medullary thyroid carcinoma is best treated by total thyroidectomy with cervical lymph node dissection on the side of a palpable nodule. Serum calcitonin determinations provide diagnostic and some prognostic data. Anaplastic carcinoma is usually best treated by radiation therapy. The outlook is good for most thyroid carcinoma recognized reasonably early.

  1. Lingual thyroid

    PubMed Central

    Kumar, L. K. Surej; Kurien, Nikhil Mathew; Jacob, M. M.; Menon, P. Varun; Khalam, Sherin A.

    2015-01-01

    Lingual thyroid is an abnormal mass of ectopic thyroid tissue seen in base of tongue caused due to embryological aberrancy in development of thyroid gland. Most of the ectopic tissue is seen in the tongue. Their identification and proper management is essential since they may be the only functioning thyroid tissue occurring in the body. We report a case of lingual thyroid in a 40 year old female patient who was hypothyroid with posterior swelling of tongue. Tc-99 scintigraphy confirmed the clinical diagnosis and surgical excision of entire tissue was done by midline mandibular split osteotomy and patient was placed under lifelong thyroxine replacement. Follow up showed excellent results with minimum patient discomfort. PMID:26389046

  2. Remote access thyroid surgery

    PubMed Central

    Bhatia, Parisha; Mohamed, Hossam Eldin; Kadi, Abida; Walvekar, Rohan R.

    2015-01-01

    Robot assisted thyroid surgery has been the latest advance in the evolution of thyroid surgery after endoscopy assisted procedures. The advantage of a superior field vision and technical advancements of robotic technology have permitted novel remote access (trans-axillary and retro-auricular) surgical approaches. Interestingly, several remote access surgical ports using robot surgical system and endoscopic technique have been customized to avoid the social stigma of a visible scar. Current literature has displayed their various advantages in terms of post-operative outcomes; however, the associated financial burden and also additional training and expertise necessary hinder its widespread adoption into endocrine surgery practices. These approaches offer excellent cosmesis, with a shorter learning curve and reduce discomfort to surgeons operating ergonomically through a robotic console. This review aims to provide details of various remote access techniques that are being offered for thyroid resection. Though these have been reported to be safe and feasible approaches for thyroid surgery, further evaluation for their efficacy still remains. PMID:26425450

  3. Follicular cell-derived thyroid cancer.

    PubMed

    Dralle, Henning; Machens, Andreas; Basa, Johanna; Fatourechi, Vahab; Franceschi, Silvia; Hay, Ian D; Nikiforov, Yuri E; Pacini, Furio; Pasieka, Janice L; Sherman, Steven I

    2015-01-01

    Follicular cell-derived thyroid cancers are derived from the follicular cells in the thyroid gland, which secrete the iodine-containing thyroid hormones. Follicular cell-derived thyroid cancers can be classified into papillary thyroid cancer (80-85%), follicular thyroid cancer (10-15%), poorly differentiated thyroid cancer (<2%) and undifferentiated (anaplastic) thyroid cancer (<2%), and these have an excellent prognosis with the exception of undifferentiated thyroid cancer. The advent and expansion of advanced diagnostic techniques has driven and continues to drive the epidemic of occult papillary thyroid cancer, owing to overdiagnosis of clinically irrelevant nodules. This transformation of the thyroid cancer landscape at molecular and clinical levels calls for the modification of management strategies towards personalized medicine based on individual risk assessment to deliver the most effective but least aggressive treatment. In thyroid cancer surgery, for instance, injuries to structures outside the thyroid gland, such as the recurrent laryngeal nerve in 2-5% of surgeries or the parathyroid glands in 5-10% of surgeries, negatively affect quality of life more than loss of the expendable thyroid gland. Furthermore, the risks associated with radioiodine ablation may outweigh the risks of persistent or recurrent disease and disease-specific mortality. Improvement in the health-related quality of life of survivors of follicular cell-derived thyroid cancer, which is decreased despite the generally favourable outcome, hinges on early tumour detection and minimization of treatment-related sequelae. Future opportunities include more widespread adoption of molecular and clinical risk stratification and identification of actionable targets for individualized therapies. PMID:27188261

  4. Thyroid function tests

    MedlinePlus

    ... free T4 (the main thyroid hormone in your blood) TSH (the hormone from the pituitary gland that stimulates the thyroid to produce T4) T3 (also included sometimes) Other thyroid tests include: T3 resin uptake Thyroid scan

  5. Multiple medullary venous malformations decreasing cerebral blood flow: Case report

    SciTech Connect

    Tomura, N.; Inugami, A.; Uemura, K.; Hadeishi, H.; Yasui, N. )

    1991-02-01

    A rare case of multiple medullary venous malformations in the right cerebral hemisphere is reported. The literature review yielded only one case of multiple medullary venous malformations. Computed tomography scan showed multiple calcified lesions with linear contrast enhancement representing abnormal dilated vessels and mild atrophic change of the right cerebral hemisphere. Single-photon emission computed tomography using N-isopropyl-p-({sup 123}I) iodoamphetamine demonstrated decreased cerebral blood flow in the right cerebral hemisphere.

  6. Imaging diagnosis--Medullary tibial infarction in a horse.

    PubMed

    Sánchez, Jesus; Gonzalo-Orden, José M; Ginja, Mário M D; Oliveira, Paula A; Reyes, Luis E; Serantes, Alicia E; Orden, Maria A

    2010-01-01

    An Andalusian Stallion with left hind limb lameness had a radiolucent lesion in the medullary cavity of distal tibial metaphysis. After euthanasia for other disease, the tibia was examined with magnetic resonance (MR). The MR imaging sequences were characterized by a double line sign, although showing quite different lesion area intensities. Histologically, the lesion was compatible with medullary infarction being characterized by normal spongy bone, areas of abundant fibrous tissue and numerous necrotic adipocytes in various stages of destruction. PMID:20402402

  7. Robotic surgery for thyroid disease.

    PubMed

    Lee, C R; Chung, W Y

    2015-10-01

    While conventional open thyroidectomy techniques are the most widely performed thyroid operation, they produce an anterior neck scar that may be difficult to conceal. The endoscopic thyroidectomy was developed to decrease the cosmetic impact on the patient and has the advantage of reducing the incidence of anterior neck hypoesthesia and paresthesia. However, this procedure has some drawbacks, which motivated surgeons to develop a new operation method. Robotic thyroidectomy is a relatively new approach for treating differentiated thyroid cancer. Over the last few years, robotic thyroidectomies have become more common. Robotic thyroidectomies are a feasible, safe alternative for managing thyroid disease that has remarkable functional benefits beyond those of conventional open methods. The applications for robotic thyroidectomy have expanded to include increasingly advanced cases, which will consequently change the thyroid surgery paradigm in the future. PMID:26149523

  8. Effect of Advanced Glycation End Products on Human Thyroglobulin's Antigenicity as Identified by the Use of Sera from Patients with Hashimoto's Thyroiditis and Gestational Diabetes Mellitus

    PubMed Central

    Hatzioannou, A.; Kanistras, I.; Mantzou, E.; Anastasiou, E.; Peppa, M.; Sarantopoulou, V.; Lymberi, P.; Alevizaki, M.

    2015-01-01

    Advanced glycation end products (AGEs) are formed on proteins after exposure to high concentrations of glucose and modify protein's immunogenicity. Herein, we investigated whether the modification of thyroglobulin (Tg) by AGEs influences its antigenicity and immunogenicity. Human Tg was incubated in vitro with increasing concentrations of D-glucose-6-phosphate in order to produce Tgs with different AGE content (AGE-Tg). Native Tg and AGE-Tgs were used in ELISA to assess the serum antibody reactivity of two patient groups, pregnant women with gestational diabetes (GDM), and patients with Hashimoto's thyroiditis (HT). We produced in vitro AGE-Tg with low and high AGE content, 13 and 49 AGE units/mg Tg, respectively. All HT patients' sera presented the same antibody reactivity profile against native Tg and AGE-Tgs, indicating that the modification of Tg by AGEs did not alter its antigenicity. Similarly, the GDM patients' sera did not discriminate among the two forms of Tg, native or artificially glycated, suggesting that the modification of Tg by AGEs might not alter its immunogenicity. The modification of Tg by AGEs has no obvious effect on neither its antigenicity nor, most likely, its immunogenicity. It seems that other Tg modifications might account for the production of aTgAbs in patients with GDM. PMID:26229534

  9. Update of Thyroid Developmental Genes.

    PubMed

    Stoupa, Athanasia; Kariyawasam, Dulanjalee; Carré, Aurore; Polak, Michel

    2016-06-01

    Thyroid dysgenesis (TD) is the most common cause of congenital hypothyroidism in iodine-sufficient regions and includes a spectrum of developmental anomalies. The genetic components of TD are complex. Although a sporadic disease, advances in developmental biology have revealed monogenetic forms of TD. Inheritance is not based on a simple Mendelian pattern and additional genetic elements might contribute to the phenotypic spectrum. This article summarizes the key steps of normal thyroid development and provides an update on responsible genes and underlying mechanisms of TD. Up-to-date technologies in genetics and biology will allow us to advance in our knowledge of TD. PMID:27241962

  10. Renal pericytes: regulators of medullary blood flow

    PubMed Central

    Kennedy-Lydon, T M; Crawford, C; Wildman, S S P; Peppiatt-Wildman, C M

    2013-01-01

    Regulation of medullary blood flow (MBF) is essential in maintaining normal kidney function. Blood flow to the medulla is supplied by the descending vasa recta (DVR), which arise from the efferent arterioles of juxtamedullary glomeruli. DVR are composed of a continuous endothelium, intercalated with smooth muscle-like cells called pericytes. Pericytes have been shown to alter the diameter of isolated and in situ DVR in response to vasoactive stimuli that are transmitted via a network of autocrine and paracrine signalling pathways. Vasoactive stimuli can be released by neighbouring tubular epithelial, endothelial, red blood cells and neuronal cells in response to changes in NaCl transport and oxygen tension. The experimentally described sensitivity of pericytes to these stimuli strongly suggests their leading role in the phenomenon of MBF autoregulation. Because the debate on autoregulation of MBF fervently continues, we discuss the evidence favouring a physiological role for pericytes in the regulation of MBF and describe their potential role in tubulo-vascular cross-talk in this region of the kidney. Our review also considers current methods used to explore pericyte activity and function in the renal medulla. PMID:23126245

  11. Molecular Targeted Therapies of Aggressive Thyroid Cancer

    PubMed Central

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

    2015-01-01

    Differentiated thyroid carcinomas (DTCs) that arise from follicular cells account >90% of thyroid cancer (TC) [papillary thyroid cancer (PTC) 90%, follicular thyroid cancer (FTC) 10%], while medullary thyroid cancer (MTC) accounts <5%. Complete total thyroidectomy is the treatment of choice for PTC, FTC, and MTC. Radioiodine is routinely recommended in high-risk patients and considered in intermediate risk DTC patients. DTC cancer cells, during tumor progression, may lose the iodide uptake ability, becoming resistant to radioiodine, with a significant worsening of the prognosis. The lack of specific and effective drugs for aggressive and metastatic DTC and MTC leads to additional efforts toward the development of new drugs. Several genetic alterations in different molecular pathways in TC have been shown in the past few decades, associated with TC development and progression. Rearranged during transfection (RET)/PTC gene rearrangements, RET mutations, BRAF mutations, RAS mutations, and vascular endothelial growth factor receptor 2 angiogenesis pathways are some of the known pathways determinant in the development of TC. Tyrosine kinase inhibitors (TKIs) are small organic compounds inhibiting tyrosine kinases auto-phosphorylation and activation, most of them are multikinase inhibitors. TKIs act on the aforementioned molecular pathways involved in growth, angiogenesis, local, and distant spread of TC. TKIs are emerging as new therapies of aggressive TC, including DTC, MTC, and anaplastic thyroid cancer, being capable of inducing clinical responses and stabilization of disease. Vandetanib and cabozantinib have been approved for the treatment of MTC, while sorafenib and lenvatinib for DTC refractory to radioiodine. These drugs prolong median progression-free survival, but until now no significant increase has been observed on overall survival; side effects are common. New efforts are made to find new more effective and safe compounds and to personalize the therapy in

  12. Unclassified Renal Cell Carcinoma With Medullary Phenotype Versus Renal Medullary Carcinoma: Lessons From Diagnosis in an Italian Man Found to Harbor Sickle Cell Trait

    PubMed Central

    Colombo, Piergiuseppe; Smith, Steven C.; Massa, Simona; Renne, Salvatore L.; Brambilla, Simona; Peschechera, Roberto; Graziotti, Pierpaolo; Roncalli, Massimo; Amin, Mahul B.

    2015-01-01

    Medullary carcinoma is a rare malignant tumor of the kidney. It affects individuals of African descent and all cases reported show evidence of sickle cell trait. We reviewed an unusual carcinoma arising in a white man, the ninth in the literature. The tumor demonstrated features associated with renal medullary carcinoma, or unclassified renal cell carcinoma, medullary phenotype as recently described; the presence of sickle cell trait confirmed the diagnosis of medullary carcinoma. This case is helpful in the differential diagnosis with non-sickle cell associated “renal cell carcinoma, unclassified with medullary phenotype,” and study of this spectrum of tumors is ongoing. PMID:26793557

  13. Conus Medullaris Teratoma with Utilization of Fiber Tractography: Case Report

    PubMed Central

    Alkherayf, Fahad; Arab, Abdullah Faisal; Tsai, Eve

    2015-01-01

    Objective Conus medullaris teratomas are very rare tumors. Traditional preoperative diagnosis depended on the findings from magnetic resonance imaging (MRI). Tractography is a novel technique that has recently been utilized to diagnose spinal cord lesions. This case report shows that fiber tractography has great potential in preoperative diagnosis and postoperative follow-up of teratomas of the conus medullaris. Methods A 50-year-old man with a conus medullaris teratoma underwent tractography with the aim of visualizing the tumor in relation to the white matter tracts. The patient underwent a T12–L2 laminectomy, and the lesion was resected. The histopathology diagnosis was of a mature teratoma. Study Design Case report. Results Diffusion tensor imaging (DTI) and tractography provide more details about the white matter tracts in relation to space-occupying lesions that may be more sensitive than conventional MRI and have recently been utilized in spinal cord lesions. Fiber tracking has the ability to visualize the integrity of the white matter tracts at the level of the conus medullaris in relation to the lesion. The tracts appeared to be displaced by the lesion at the conus medullaris. Tractography also showed no white matter tracts within the lesion. Such findings are consistent with the characteristics of a benign lesion. Exploiting tractography in this case was helpful in predicting the nature of the lesion preoperatively and in planning the surgical intervention. Conclusions Conus medullaris teratomas mostly affect adults. Patients generally present with a long history of clinical symptoms prior to diagnosis. Surgery is required for diagnosis, and the goal should be complete tumor excision without sacrificing any neurologic functions. The use of DTI and tractography, in addition to conventional MRI, has the potential to be very valuable for the diagnosis, surgical planning, and follow-up of patients with conus medullaris teratomas. PMID:26251802

  14. [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. PMID:26486481

  15. Bone loss in thyroid disease: role of low TSH and high thyroid hormone.

    PubMed

    Abe, Etsuko; Sun, Li; Mechanick, Jeffrey; Iqbal, Jameel; Yamoah, Kosj; Baliram, Ramkumarie; Arabi, Ario; Moonga, Baljit S; Davies, Terry F; Zaidi, Mone

    2007-11-01

    More than 10% of postmenopausal women in the United States receive thyroid hormone replacement therapy and up to 20% of these women are over-replaced inducing subclinical hyperthyroidism. Because hyperthyroidism and post menopausal osteoporosis overlap in women of advancing age, it is urgent to understand the effect of thyroid hormone excess on bone. We can now provide results that not thyroid hormones but also TSH itself has an equally important role to play in bone remodeling. PMID:18083940

  16. Robotic transaxillary thyroid surgery.

    PubMed

    Rabinovics, Naomi; Aidan, Patrick

    2015-10-01

    Recent technological advances have led to a rapid progress in endocrine surgery. With the advent of minimally invasive techniques in thyroid surgery, robot-assisted transaxillary thyroid surgery (RATS) has emerged as one of the most promising approaches. Its main advantages are improved cosmetic outcome, avoiding cervical incisions, increased patient satisfaction, improved visualization, arms articulations, eliminating surgeon's natural tremor, thereby increasing precision. The main disadvantages are longer operative time, and increased cost compared to conventional thyroidectomy, as well as potential injuries to the brachial plexus, skin flap, esophagus, and trachea. Large-scale studies, mainly from South-Korea, have proved that in skilled hands, RATS is a safe alternative to conservative thyroidectomy and should be presented to patients with aesthetic concerns. As with any new emerging technique, careful patient selection is crucial, and further evidence must be sought to confirm its indications. PMID:26425452

  17. Robotic facelift thyroid surgery

    PubMed Central

    Bomeli, Steven R.; Duke, William S.

    2015-01-01

    Techniques for thyroid surgery have advanced dramatically over the past two decades, driven by a better understanding of thyroid physiology, anatomy, and perioperative management strategies. Improvements in surgical technology have permitted surgeons to perform minimally invasive surgery associated with less dissection, decreased pain, smaller anterior cervical incisions, and most importantly a faster recovery. The advent of robotic surgical technology has allowed the development of remote access thyroidectomy for select patients who wish to avoid a visible cervical incision completely. The robotic facelift thyroidectomy (RFT) approach also offers the advantage of outpatient surgery without the need for postoperative drainage. A growing body of evidence supports the safety and efficacy of the approach, and as a result the technique is now being performed at several centers around the world. PMID:26425453

  18. Thyroid function in pregnancy☆

    PubMed Central

    Leung, Angela M.

    2014-01-01

    Iodine is required for the production of thyroid hormones. Normal thyroid function during pregnancy is important for both the mother and developing fetus. This review discusses the changes in thyroid physiology that occur during pregnancy, the significance of thyroid function tests and thyroid antibody titers assessed during pregnancy, and the potential obstetric complications associated with maternal hypothyroidism. PMID:22658718

  19. The role of surgery in the management of thyroid cancer.

    PubMed Central

    Mustard, R. A.

    1975-01-01

    This is a review of one surgeon's personal experience with 85 patients with thyroid cancer treated over a 20-year period. The data confirm that for papillary thyroid tumours, with rare exceptions, the prognosis is excellent. Anaplastic lesions, however, are consistently lethal. Follicular carcinoma and medullary carcinoma fall between these extremes. A simple clinical classification is offered as a guide to operative management and a reliable index of prognosis. Patients with clinically apparent, "manifest cancer" have serious, life-threatening disease; many such patients die of their disease. Patients with "neck lumps not yet diagnosed" usually have papillary carcinoma; their prognosis is excellent. Patients whose thyroid tumours fall into the category of "malignant nodule" or "pathologist's cancer" are particularly fortunate: in this series no such patient has died. The importance of age in relation to thyroid cancer is also confirmed: non of the patients first treated before the age of 40 years has died of cancer. For young patients with favourable disease the author recommends conservative surgical treatment, which avoids cosmetic deformity or functional disability, to be followed by administration of levothyroxine to suppress production of thyroid=stimulating hormone. For patients with "unfavourable" thyroid cancer valuable palliation can often be achieved by a combination of surgery and irradiation. Survival rates for the total series are 76% at 5 years and 60% at 10 years. PMID:1139493

  20. An Association of Chronic Hyperaldosteronism with Medullary Nephrocalcinosis

    PubMed Central

    Mittal, Kartik; Anandpara, Karan; Dey, Amit K.; Sharma, Rajaram; Thakkar, Hemangini; Hira, Priya; Deshmukh, Hemant

    2015-01-01

    Summary Background An association between chronic hyperaldosteronism and medullary nephrocalcinosis has rarely been made, with only a handful of cases described in literature. Case Report We describe five cases of hyperaldosteronism with a long- standing history in whom associated medullary nephrocalcinosis was established. Conclusions We infer that a chronic hyperaldosteronic status, whether primary or secondary, is a causal factor in the etiopathogenesis of medullary nephrocalcinosis. This article illustrates and summarizes various postulated theories that support our proposed association between hyperaldosteronism and nephrocalcinosis. We conclude that chronic hyperaldosteronism should be included as one of the causes of nephrocalcinosis and that our case series emphasizes the need of a well-organized retrospective study to prove it further. PMID:26413177

  1. What Is Thyroid Cancer?

    MedlinePlus

    ... Having too much thyroid hormone (a condition called hyperthyroidism ) can cause a rapid or irregular heartbeat, trouble ... nodules make too much thyroid hormone and cause hyperthyroidism. Nodules that produce increased thyroid hormone are almost ...

  2. Retrosternal thyroid surgery

    MedlinePlus

    The thyroid gland is normally located at the front of the neck. A retrosternal thyroid refers to the abnormal location of all or part of the thyroid gland below the breastbone (sternum). This article discusses ...

  3. Chronic thyroiditis (Hashimoto disease)

    MedlinePlus

    ... determine thyroid function include: Free T4 test Serum TSH T3 Thyroid autoantibodies Imaging studies are generally not ... signs of mild thyroid failure (such as elevated TSH). This condition is also known as subclinical hypothyroidism. ...

  4. Chronic thyroiditis (Hashimoto disease)

    MedlinePlus

    ... gland that often results in reduced thyroid function ( hypothyroidism ). Causes Chronic thyroiditis or Hashimoto disease is a ... TSH). This condition is also known as subclinical hypothyroidism. If there is no evidence of thyroid hormone ...

  5. Thyroid gland biopsy (image)

    MedlinePlus

    ... a sample of cells is needed from the thyroid gland a fine needle biopsy can be performed. During ... procedure, a skinny needle is inserted into the thyroid gland, and a sample of thyroid cells and fluid ...

  6. Stages of Thyroid Cancer

    MedlinePlus

    ... glands make hormones. The thyroid uses iodine , a mineral found in some foods and in iodized salt, ... Fine-needle aspiration biopsy of the thyroid : The removal of thyroid tissue using a thin needle. The ...

  7. A phase 2 trial of lenvatinib (E7080) in advanced progressive radioiodine-refractory differentiated thyroid cancer: a clinical outcomes and biomarker assessment

    PubMed Central

    Cabanillas, Maria E.; Schlumberger, Martin; Jarzab, Barbara; Martins, Renato G.; Pacini, Furio; Robinson, Bruce; McCaffrey, Judith C.; Shah, Manisha H.; Bodenner, Donald L.; Topliss, Duncan; Andresen, Corina; O'Brien, James P.; Ren, Min; Funahashi, Yasuhiro; Allison, Roger; Elisei, Rossella; Newbold, Kate; Licitra, Lisa F.; Sherman, Steven I.; Ball, Douglas W.

    2016-01-01

    Background Lenvatinib is an oral, multitargeted tyrosine kinase inhibitor of VEGFR1–3, FGFR1–4, PDGFRα, RET, and KIT signaling networks implicated in tumor angiogenesis. Positive phase 1 results in solid tumors prompted a phase 2 trial in advanced radioiodine-refractory differentiated thyroid cancer (RR-DTC). Methods Fifty-eight patients with RR-DTC and disease progression during the prior 12 months were administered lenvatinib 24-mg once daily in 28-day cycles until disease progression, unmanageable toxicity, withdrawal, or death. Prior VEGFR-targeted therapy was permitted. The primary endpoint was objective response rate (ORR) based upon independent imaging review (IIR). Secondary endpoints included progression-free survival (PFS) and safety. Serum levels of 51 circulating cytokines and angiogenic factors were also assessed. Results After ≥14 months of follow-up, patients had ORR of 50% (95% confidence interval [CI] 37–63) with only partial responses reported. Median time to response was 3.6 months; median duration of response was 12.7 months; median PFS was 12.6 months (95% CI 9.9–16.1). ORR for patients with prior VEGF therapy (n=17) was 59% (95% CI 33–82). Lower baseline levels of angiopoietin-2 were suggestive of tumor response and longer PFS. Grade 3/4 treatment-emergent adverse events regardless of relation to treatment occurred in 72% of patients, most frequently weight loss (12%), hypertension (10%), proteinuria (10%), and diarrhea (10%). Conclusion In patients with and without prior exposure to VEGF therapy, the encouraging response rates, median time to response, and PFS for lenvatinib have prompted further investigation in a phase 3 trial. PMID:25913680

  8. Efficacy of pazopanib in progressive, radioiodine-refractory, metastatic differentiated thyroid cancers: results of a phase 2 consortium study

    PubMed Central

    Bible, Keith C; Suman, Vera J; Molina, Julian R; Smallridge, Robert C; Maples, William J; Menefee, Michael E; Rubin, Joseph; Sideras, Kostandinos; Morris, John C; McIver, Bryan; Burton, Jill K; Webster, Kevin P; Bieber, Carolyn; Traynor, Anne M; Flynn, Patrick J; Goh, Boon Cher; Tang, Hui; Ivy, Susan Percy; Erlichman, Charles

    2011-01-01

    . Interpretation Pazopanib seems to represent a promising therapeutic option for patients with advanced differentiated thyroid cancers. The correlation of the patient’s response and pazopanib concentration during the first cycle might indicate that treatment can be individualised to achieve optimum outcomes. Assessment of pazopanib in an expanded cohort of patients with differentiated thyroid cancer, as well as in cohorts of patients with medullary and anaplastic thyroid cancers, is presently being done. Funding National Cancer Institute, supported in part by NCI CA15083 and CM62205. PMID:20851682

  9. Thyroid Imaging in Infants.

    PubMed

    Goldis, Marina; Waldman, Lindsey; Marginean, Otilia; Rosenberg, Henrietta Kotlus; Rapaport, Robert

    2016-06-01

    Congenital hypothyroidism is the most common preventable cause of mental retardation. It is important to know the cause of each patient's thyroid dysfunction to foresee the course of therapy and outcomes. Imaging methods, such as ultrasound and thyroid scan, help determine the anatomy and function of the thyroid gland. Although thyroid scan is considered superior in detecting ectopic thyroid tissue, ultrasound is able to detect the presence of thyroid tissue not otherwise visualized in 15% of patients. PMID:27241963

  10. A Calcitonin-Negative Neuroendocrine Tumor Derived from Follicular Lesions of the Thyroid

    PubMed Central

    Kim, Ga Young; Park, Chul Yun; Cho, Chang Ho; Park, June Sik; Jung, Eui Dal

    2015-01-01

    Neuroendocrine lesions of the thyroid are rare. The most common types are medullary thyroid carcinomas (MTCs) and C-cell hyperplasia. MTCs originate from thyroid parafollicular cells that secrete calcitonin which serves as a serum marker of MTCs. Here, the rare case of a calcitonin-negative neuroendocrine tumor (NET) derived from follicular lesions of the thyroid is described. A 34-year-old man presented at our hospital for the surgical management of an incidental thyroid nodule that was observed on an ultrasound sonography (USG) of the neck. Initially, USG-guided aspiration cytology was performed, and a MTC was suspected. The expressions of thyroglobulin and thyroid transcription factor-1, which are thyroid follicular cell markers, and synaptophysin and chromogranin A, which are neuroendocrine markers, was confirmed following surgical pathology. However, the staining of calcitonin, a marker of MTCs, was not observed. A nonmedullary NET of the thyroid is uncommon, and the distinction between calcitonin-negative NETs and MTCs of the thyroid may be important due to differences in their clinical courses and management. PMID:25491784

  11. Glucagon-like-peptide-1 receptor expression in normal and diseased human thyroid and pancreas.

    PubMed

    Waser, Beatrice; Blank, Annika; Karamitopoulou, Eva; Perren, Aurel; Reubi, Jean C

    2015-03-01

    Glucagon-like-peptide-1 (GLP1) analogs may induce thyroid or pancreatic diseases in animals, raising questions about their use in diabetic patients. There is, however, controversy regarding expression of GLP1 receptors (GLP1R) in human normal and diseased thyroid and pancreas. Here, 221 human thyroid and pancreas samples were analyzed for GLP1R immunohistochemistry and compared with quantitative in vitro GLP1R autoradiography. Neither normal nor hyperplastic human thyroids containing parafollicular C cells express GLP1R with either method. Papillary thyroid cancer do not, and medullary thyroid carcinomas rarely express GLP1R. Insulin- and somatostatin-producing cells in the normal pancreas express a high density of GLP1R, whereas acinar cells express them in low amounts. Ductal epithelial cells do not express GLP1R. All benign insulinomas express high densities of GLP1R, whereas malignant insulinomas rarely express them. All ductal pancreatic carcinomas are GLP1R negative, whereas 6/20 PanIN 1/2 and 0/12 PanIN 3 express GLP1R. Therefore, normal thyroid, including normal and hyperplastic C cells, or papillary thyroid cancer are not targets for GLP1 analogs in humans. Conversely, all pancreatic insulin- and somatostatin-producing cells are physiological GLP1 targets, as well as most acini. As normal ductal epithelial cells or PanIN 3 or ductal pancreatic carcinomas do not express GLP1R, it seems unlikely that GLP1R is related to neoplastic transformation in pancreas. GLP1R-positive medullary thyroid carcinomas and all benign insulinomas are candidates for in vivo GLP1R targeting. PMID:25216224

  12. Sorafenib in locally advanced or metastatic, radioactive iodine-refractory, differentiated thyroid cancer: a randomized, double-blind, phase 3 trial

    PubMed Central

    Brose, Marcia S; Nutting, Christopher M; Jarzab, Barbara; Elisei, Rossella; Siena, Salvatore; Bastholt, Lars; de la Fouchardiere, Christelle; Pacini, Furio; Paschke, Ralf; KeeShong, Young; Sherman, Steven I; Smit, Johannes WA; Chung, John; Kappeler, Christian; Pena, Carol; Molnár, István; Schlumberger, Martin J

    2015-01-01

    Background Patients with radioactive iodine (131I, RAI)-refractory locally advanced or metastatic differentiated thyroid cancer (DTC) have a poor prognosis due to the lack of effective treatment options. Methods This multicentre, randomized (1:1), double-blind, placebo-controlled, phase 3 study (DECISION; NCT00984282) investigated sorafenib (400 mg orally twice-daily) in patients with RAI-refractory locally advanced or metastatic DTC progressing within the past 14 months. The primary endpoint was progression-free survival (PFS) by central independent review. Patients receiving placebo could crossover to open-label sorafenib upon progression. Archival tumour tissue was examined for BRAF and RAS mutations. Serum thyroglobulin was measured at baseline and each visit. Findings A total of 417 patients were randomized to sorafenib (n=207) or placebo (n=210). Sorafenib treatment significantly improved PFS compared with placebo (hazard ratio, 0·59; 95% confidence interval, 0·45–0·76; P<0·0001; median 10·8 vs. 5·8 months, respectively). PFS improvement was seen in all pre-specified clinical and genetic biomarker subgroups irrespective of mutation status. There was no statistically significant difference in overall survival (hazard ratio, 0·80; 95% confidence interval, 0·54–1·19; P=0·14); median overall survival had not been reached and 150 (71%) patients receiving placebo crossed over to sorafenib upon progression. Response rates (all partial responses) were 12·2% (24/196; sorafenib) and 0·5% (1/201; placebo; p<0·0001). Median thyroglobulin levels increased in the placebo group, and decreased, then paralleled treatment responses in the sorafenib group. Most adverse events were grade 1 or 2. The most common treatment-emergent adverse events in the sorafenib arm were hand–foot skin reaction (76·3%), diarrhoea (68·6%), alopecia (67·1%), and rash/desquamation (50·2%). Interpretation Sorafenib significantly improved PFS compared with placebo in patients

  13. Role of metallothioneins in benign and malignant thyroid lesions

    PubMed Central

    2012-01-01

    Recent findings in the past two decades have brought many insights into the biology of thyroid benign and malignant lesions, in particular the papillary and follicular thyroid cancers. Although, much progress have been made, thyroid cancers still pose diagnostic problems regarding differentiation of follicular lesions in relation to their aggressiveness and the treatment of advanced and undifferentiated thyroid cancers. Metallothioneins (MTs) were shown to induce cancer cells proliferation, mediate resistance to apoptosis, certain chemotherapeutics and radiotherapy. Therefore, MTs may be of utility in diagnosis and management of patients with benign and malignant lesions of the thyroid. PMID:23273222

  14. Thyroid and parathyroid imaging

    SciTech Connect

    Sandler, M.P.; Patton, J.A.; Partain, C.L.

    1986-01-01

    This book describes the numerous modalities currently used in the diagnosis and treatment of both thyroid and parathyroid disorders. Each modality is fully explained and then evaluated in terms of benefits and limitations in the clinical context. Contents: Production and Quality Control of Radiopharmaceutics Used for Diagnosis and Therapy in Thyroid and Parathyroid Disorders. Basic Physics. Nuclear Instrumentation. Radioimmunoassay: Thyroid Function Tests. Quality Control. Embryology, Anatomy, Physiology, and Thyroid Function Studies. Scintigraphic Thyroid Imaging. Neonatal and Pediatric Thyroid Imaging. Radioiodine Thyroid Uptake Measurement. Radioiodine Treatment of Thyroid Disorders. Radiation Dosimetry of Diagnostic Procedures. Radiation Safety Procedures for High-Level I-131 Therapies. X-Ray Fluorescent Scanning. Thyroid Sonography. Computed Tomography in Thyroid Disease. Magnetic Resonance Imaging in Thyroid Disease. Parathyroid Imaging.

  15. Quadruple Cancers of Non-producing Multiple Myeloma, Cholangiocellular Carcinoma, and Two Different Thyroid Cancers.

    PubMed

    Mizutani, Shinsuke; Kuroda, Junya; Sasaki, Nana; Kiyota, Miki; Tatekawa, Shotaro; Tsukamoto, Taku; Maegawa, Saori; Chinen, Yoshiaki; Shimura, Yuji; Nagoshi, Hisao; Kobayashi, Tsutomu; Horiike, Shigeo; Tando, So; Fushiki, Shinji; Taniwaki, Masafumi

    2016-01-01

    We report the case of a 72-year-old man who presented with non-producing multiple myeloma (MM) with three additional concomitant solid tumors that were identified by postmortem autopsy. The disease was refractory to anti-MM therapy including bortezomib and lenalidomide, and he finally died of bacterial pneumonia with diffuse alveolar damage 8 months after the diagnosis. An autopsy revealed that he was also affected by three other solid cancers, cholangiocellular carcinoma, medullary thyroid cancer and papillary thyroid cancer that were clinically asymptomatic and remained undiagnosed before death. A review of the literature suggests that primary quadruple cancers including MM are extremely rare. PMID:27150876

  16. Early diagnosis of and surgical strategy for adrenal medullary disease in MEN II gene carriers

    SciTech Connect

    Jansson, S.; Tisell, L.E.; Fjaelling, M.L.; Lindberg, S.; Jacobsson, L.; Zachrisson, B.F.

    1988-01-01

    Sixteen multiple endocrine neoplasia type II (MEN II) gene carriers--12 who had undergone thyroidectomy because of medullary carcinoma of the thyroid and 4 whose thyroid glands had been removed because of C cell hyperplasia--were examined for the presence of pheochromocytomas. No patient had sought medical advice for pheochromocytoma symptoms. Fourteen patients had MEN IIa syndromes, one patient had a MEN IIb and another patient had a mixed syndrome of von Recklinghausen's neurofibromatosis and MEN II. Eight patients had undergone unilateral adrenalectomy for pheochromocytoma 11 +/- 4 years before. The patients underwent clinical examination, determination of the urinary excretion of catecholamines and metabolites, and /sup 131/I-metaiodobenzylguanidine (/sup 131/I-MIBG) and CAT scans. /sup 131/I-MIBG scanning was performed with images 1, 4, and 7 days after the radionuclide injection. In seven of eight patients who had undergone unilateral adrenalectomies, the /sup 131/I-MIBG scans showed accumulation of the radionuclide in the remaining adrenal gland. Bilateral adrenal accumulation of the radionuclide was demonstrated in seven of eight MEN IIa gene carriers who had not undergone adrenalectomy. Five patients, two of whom had undergone adrenalectomy, were found to have unilateral pheochromocytomas less than 2 cm in diameter. Only one of these five patients had an elevated excretion of urinary catecholamines. Between day 4 and day 7 after /sup 131/I-MIBG injection, adrenal glands with pheochromocytomas increased their relative accumulation of the radionuclide significantly more (p less than 0.02) than did adrenal glands without any demonstrable pheochromocytomas. All the pheochromocytomas were viewed by means of CAT scans.

  17. Pathophysiology of radiocontrast nephropathy: a role for medullary hypoxia.

    PubMed

    Heyman, S N; Reichman, J; Brezis, M

    1999-11-01

    Recent experimental data underlies the role of hypoxic tubular injury in the pathophysiology of radiocontrast nephropathy. Although systemic transient hypoxemia, increased blood viscosity, and a leftward shift of the oxygen-hemoglobin dissociation curve may all contribute to intrarenal hypoxia, imbalance between oxygen demand and supply plays a major role in radiocontrast-induced outer medullary hypoxic damage. Low oxygen tension normally exists in this renal region, reflecting the precarious regional oxygen supply and a high local metabolic rate and oxygen requirement, resulting from active salt reabsorption by medullary thick ascending limbs of Henle's loop. Radiologic contrast agents markedly aggravate outer medullary physiologic hypoxia. This results from enhanced metabolic activity and oxygen consumption (as a result of osmotic diuresis and increased salt delivery to the distal nephron) because the regional blood flow and the oxygen supply actually increase. The latter effect may result in part from the activation of various regulatory mediators of outer medullary blood flow to ensure maximal regional oxygen supply. Low-osmolar radiocontrast agents may be less nephrotoxic because of the smaller osmotic load and vasomotor alterations. Experimental radiocontrast-induced renal failure requires preconditioning of animals with various insults (for example, congestive heart failure, reduced renal mass, salt depletion, or inhibition of nitric oxide and prostaglandin synthesis). In all these perturbations, which resemble clinical conditions that predispose to contrast nephropathy, outer medullary hypoxic injury results from insufficiency or inactivation of mechanisms designed to preserve regional oxygen balance. This underlines the importance of identifying and ameliorating predisposing factors in the prevention of this iatrogenic disease. PMID:10548380

  18. Anaplastic thyroid cancer

    MedlinePlus

    ... or MRI of the neck may show a tumor growing from the thyroid gland. A thyroid biopsy makes the diagnosis. An examination ... the thyroid Images ... Saunders; 2016:chap 226. Lai SY, Mandel SJ, Weber RS. Management of thyroid neoplasms. In: Flint PW, Haughey BH, Lund LJ, et ...

  19. Management of thyroid disorders

    PubMed Central

    Premawardhana, L D K E; Lazarus, J H

    2006-01-01

    Autoimmune thyroid disease is the predominant form of thyroid dysfunction in the developed world. Although its precise cause is currently unclear, principles of management have been established. There is a vigorous debate about the management of the increasingly commonly recognised subclinical forms of thyroid dysfunction despite recent recommendations. Nodular thyroid disease and thyroid carcinoma have received wide attention. The effects of drugs and pregnancy on thyroid function have also been investigated widely. This short review attempts to give an overview and clarify the current management of common thyroid disorders. PMID:16954449

  20. Influence of thyroid hormones on maturation of rat cerebellar astrocytes.

    PubMed

    Manzano, Jimena; Bernal, Juan; Morte, Beatriz

    2007-05-01

    Thyroid hormone influences brain maturation through interaction with nuclear receptors and regulation of gene expression. Their role on astrocyte maturation remains unclear. We have analyzed the role of thyroid hormone in rat cerebellar astrocyte maturation by comparing the sequential patterns of intermediate filament expression in normal and hypothyroid animals. During normal development astroglial cells sequentially express nestin, vimentin, and glial fibrillary acidic protein. Differentiated astrocytes appeared in the superior medullary vellum by postnatal day 2 and reached the white mater and internal granular layer by postnatal day 4. Intermediate filament marker expression was transiently lost from postnatal days 6 to 8 in anterior lobes, without an increased apoptosis. Vimentin expression was replaced by glial fibrillary acidic protein between postnatal days 10 and 32. The differentiated astrocytes were evenly distributed throughout the cerebellar slices, including the internal granular layer. Differences between normal and hypothyroid rats were observed starting from postnatal day 4, with lack of differentiated astrocytes in the internal granular layer. The transient decrease of astrocyte markers immunoreactivity in the anterior lobe did not take place in hypothyroid rats. The vimentin-glial fibrillary acidic protein transition was delayed and most differentiated astrocytes remained confined to the white matter. The results indicate that thyroid hormone deficiency induces a delay and a partial arrest of astrocyte differentiation. Astrocytes express thyroid hormone receptor alpha and beta subtypes suggesting that astrocytes are direct target cells of thyroid hormones. PMID:17408906

  1. Thyroid carcinoma

    SciTech Connect

    Friedman, M.; Skolnik, E.M.; Baim, H.M.; Becker, S.P.; Katz, A.H.; Mantravadi, R.V.

    1980-12-01

    Differentiated thyroid carcinoma was studied with regard to mode of presentation, initial findings, treatment and survival. The classic signs, symptoms, physical and scan findings were found to be present in approximately 70% of the patients. Prognosis was found to be dependent on age of presentation more than any other factor. Patients with prior exposure to radiation were found to have more extensive disease and require more extensive surgery but ultimately had the same prognosis for 15-year cure. Treatment for distant metastatic disease by surgery, radioactive iodine and external radiation all resulted in long-term survival in certain cases.

  2. Mitochondrial Energy Metabolism and Thyroid Cancers.

    PubMed

    Lee, Junguee; Chang, Joon Young; Kang, Yea Eun; Yi, Shinae; Lee, Min Hee; Joung, Kyong Hye; Kim, Kun Soon; Shong, Minho

    2015-06-01

    Primary thyroid cancers including papillary, follicular, poorly differentiated, and anaplastic carcinomas show substantial differences in biological and clinical behaviors. Even in the same pathological type, there is wide variability in the clinical course of disease progression. The molecular carcinogenesis of thyroid cancer has advanced tremendously in the last decade. However, specific inhibition of oncogenic pathways did not provide a significant survival benefit in advanced progressive thyroid cancer that is resistant to radioactive iodine therapy. Accumulating evidence clearly shows that cellular energy metabolism, which is controlled by oncogenes and other tumor-related factors, is a critical factor determining the clinical phenotypes of cancer. However, the role and nature of energy metabolism in thyroid cancer remain unclear. In this article, we discuss the role of cellular energy metabolism, particularly mitochondrial energy metabolism, in thyroid cancer. Determining the molecular nature of metabolic remodeling in thyroid cancer may provide new biomarkers and therapeutic targets that may be useful in the management of refractory thyroid cancers. PMID:26194071

  3. New technologies in thyroid cancer surgery.

    PubMed

    Dhepnorrarat, Rataphol Chris; Witterick, Ian J

    2013-07-01

    Several new technologies have advanced the practice of thyroid surgery in recent years, with some centers implementing substantial changes in the way thyroid surgery is performed. As many thyroid cancers are diagnosed at an early stage the treatment is quite effective, and the prognosis is good for most patients with differentiated thyroid cancer. With excellent long term survival, advancements in the treatment of patients with thyroid cancers are focusing on reducing complications of surgery, improving quality-of-life and delivering care in a cost-effective way. The LigaSure electrothermal bipolar vessel sealing system and Harmonic scalpel have been designed to aid in dissection with less thermal spread than conventional electrocautery. Alternative access approaches to the thyroid allow for improved cosmetic outcomes and potentially improve the view of the surgical field. The intraoperative use of gamma-probe for the localization of metastases and sentinel lymph nodes are being increasingly reported on. Surgeon performed ultrasound is promoted for improving the detection of disease, and intraoperative nerve monitoring is now widespread, aiding in laryngeal nerve detection and protection. The assay of parathyroid hormone is also in common use for predicting patients at risk for developing postoperative hypocalcemia. This article reviews the current literature on new technologies for thyroid surgery and discusses some of the implications for the future of this field of surgery. PMID:23578371

  4. Incidental Finding of Papillary Thyroid Carcinoma in the Patients with Primary Hyperparathyroidism

    PubMed Central

    Yazici, Pinar; Mihmanli, Mehmet; Bozdag, Emre; Aygun, Nurcihan; Uludag, Mehmet

    2015-01-01

    Objective: The relationship between primary hyperparathyroidism (pHPT) and papillary thyroid cancer (PTC) still remains unclear. We aimed to investigate the incidence of the co-existence of pHPT and PTC. Materials and Methods: Between 2010 and 2013, all patients with pHPT were retrospectively reviewed and those undergoing concomitant thyroid surgery were recorded. Of these, patients with a pathological result showing papillary or micro-papillary thyroid cancer were included into the study. A chart review of 228 patients who underwent surgery for pHPT revealed 86 (37.7%) patients with concurrent thyroid disease requiring surgical treatment. Results: Thyroid cancer was noted in six female patients (6.9%) undergoing thyroid resection, and 2.6% of all patients with pHPT. Four patients underwent total thyroidectomy while lobectomy was applied in the remaining two. None of the cases with lobectomy required a completion thyroidectomy. Conclusion: We demonstrated the concurrence of PTC and pHPT at a rate of 2.6% which appeared as a coincidental pathology; however, thyroid disorders, seen in one of three patients with pHPT, were not uncommon. Further research is still needed to develop a reliable explanation for relationship between pHPT and non-medullary thyroid cancer. PMID:26644769

  5. Thyroiditis: an integrated approach.

    PubMed

    Sweeney, Lori B; Stewart, Christopher; Gaitonde, David Y

    2014-09-15

    Thyroiditis is a general term that encompasses several clinical disorders characterized by inflammation of the thyroid gland. The most common is Hashimoto thyroiditis; patients typically present with a nontender goiter, hypothyroidism, and an elevated thyroid peroxidase antibody level. Treatment with levothyroxine ameliorates the hypothyroidism and may reduce goiter size. Postpartum thyroiditis is transient or persistent thyroid dysfunction that occurs within one year of childbirth, miscarriage, or medical abortion. Release of preformed thyroid hormone into the bloodstream may result in hyperthyroidism. This may be followed by transient or permanent hypothyroidism as a result of depletion of thyroid hormone stores and destruction of thyroid hormone-producing cells. Patients should be monitored for changes in thyroid function. Beta blockers can treat symptoms in the initial hyperthyroid phase; in the subsequent hypothyroid phase, levothyroxine should be considered in women with a serum thyroid-stimulating hormone level greater than 10 mIU per L, or in women with a thyroid-stimulating hormone level of 4 to 10 mIU per L who are symptomatic or desire fertility. Subacute thyroiditis is a transient thyrotoxic state characterized by anterior neck pain, suppressed thyroid-stimulating hormone, and low radioactive iodine uptake on thyroid scanning. Many cases of subacute thyroiditis follow an upper respiratory viral illness, which is thought to trigger an inflammatory destruction of thyroid follicles. In most cases, the thyroid gland spontaneously resumes normal thyroid hormone production after several months. Treatment with high-dose acetylsalicylic acid or nonsteroidal anti-inflammatory drugs is directed toward relief of thyroid pain. PMID:25251231

  6. Radiological and surgical management of thyroid neoplasms.

    PubMed

    Takami, H; Ikeda, Y; Miyabe, R; Okinaga, H; Kameyama, K; Fukunari, N

    2004-01-01

    Recent advances in the radiological diagnosis in thyroid neoplasms have been achieved by high-resolution ultrasonography and color-Doppler, and the ultrasound-guided fine-needle aspiration biopsy and ultrasound-guided percutaneous ethanol injection therapy have been developed on the basis of these modalities. Ultrasonography and ultrasound-guided fine-needle aspiration biopsy have made minimally invasive thyroid surgery possible. The surgical procedures are classified into three main categories according to the approach, and each approach has its own advantages and disadvantages. Surgeons have to select the most suitable approach from one of these categories of approaches for each patient with a thyroid neoplasm. PMID:15271417

  7. Advanced bone formation in mice with a dominant-negative mutation in the thyroid hormone receptor β gene due to activation of Wnt/β-catenin protein signaling.

    PubMed

    O'Shea, Patrick J; Kim, Dong Wook; Logan, John G; Davis, Sean; Walker, Robert L; Meltzer, Paul S; Cheng, Sheue-yann; Williams, Graham R

    2012-05-18

    Thyroid hormone (T(3)) acts in chondrocytes and bone-forming osteoblasts to control bone development and maintenance, but the signaling pathways mediating these effects are poorly understood. Thrb(PV/PV) mice have a severely impaired pituitary-thyroid axis and elevated thyroid hormone levels due to a dominant-negative mutant T(3) receptor (TRβ(PV)) that cannot bind T(3) and interferes with the actions of wild-type TR. Thrb(PV/PV) mice have accelerated skeletal development due to unknown mechanisms. We performed microarray studies in primary osteoblasts from wild-type mice and Thrb(PV/PV) mice. Activation of the canonical Wnt signaling in Thrb(PV/PV) mice was confirmed by in situ hybridization analysis of Wnt target gene expression in bone during postnatal growth. By contrast, T(3) treatment inhibited Wnt signaling in osteoblastic cells, suggesting that T(3) inhibits the Wnt pathway by facilitating proteasomal degradation of β-catenin and preventing its accumulation in the nucleus. Activation of the Wnt pathway in Thrb(PV/PV) mice, however, results from a gain of function for TRβ(PV) that stabilizes β-catenin despite the presence of increased thyroid hormone levels. These studies demonstrate novel interactions between T(3) and Wnt signaling pathways in the regulation of skeletal development and bone formation. PMID:22442145

  8. Evaluation of thyroid tissue by Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Teixeira, C. S. B.; Bitar, R. A.; Santos, A. B. O.; Kulcsar, M. A. V.; Friguglietti, C. U. M.; Martinho, H. S.; da Costa, R. B.; Martin, A. A.

    2010-02-01

    Thyroid gland is a small gland in the neck consisting of two lobes connected by an isthmus. Thyroid's main function is to produce the hormones thyroxine (T4), triiodothyronine (T3) and calcitonin. Thyroid disorders can disturb the production of these hormones, which will affect numerous processes within the body such as: regulating metabolism and increasing utilization of cholesterol, fats, proteins, and carbohydrates. The gland itself can also be injured; for example, neoplasias, which have been considered the most important, causing damage of to the gland and are difficult to diagnose. There are several types of thyroid cancer: Papillary, Follicular, Medullary, and Anaplastic. The occurrence rate, in general is between 4 and 7%; which is on the increase (30%), probably due to new technology that is able to find small thyroid cancers that may not have been found previously. The most common method used for thyroid diagnoses are: anamnesis, ultrasonography, and laboratory exams (Fine Needle Aspiration Biopsy- FNAB). However, the sensitivity of those test are rather poor, with a high rate of false-negative results, therefore there is an urgent need to develop new diagnostic techniques. Raman spectroscopy has been presented as a valuable tool for cancer diagnosis in many different tissues. In this work, 27 fragments of the thyroid were collected from 18 patients, comprising the following histologic groups: goitre adjacent tissue, goitre nodular tissue, follicular adenoma, follicular carcinoma, and papillary carcinoma. Spectral collection was done with a commercial FTRaman Spectrometer (Bruker RFS100/S) using a 1064 nm laser excitation and Ge detector. Principal Component Analysis, Cluster Analysis, and Linear Discriminant Analysis with cross-validation were applied as spectral classification algorithm. Comparing the goitre adjacent tissue with the goitre nodular region, an index of 58.3% of correct classification was obtained. Between goitre (nodular region and

  9. Anaplastic Thyroid Carcinoma, Version 2.2015

    PubMed Central

    Haddad, Robert I.; Lydiatt, William M.; Ball, Douglas W.; Busaidy, Naifa Lamki; Byrd, David; Callender, Glenda; Dickson, Paxton; Duh, Quan-Yang; Ehya, Hormoz; Haymart, Megan; Hoh, Carl; Hunt, Jason P.; Iagaru, Andrei; Kandeel, Fouad; Kopp, Peter; Lamonica, Dominick M.; McCaffrey, Judith C.; Moley, Jeffrey F.; Parks, Lee; Raeburn, Christopher D.; Ridge, John A.; Ringel, Matthew D.; Scheri, Randall P.; Shah, Jatin P.; Smallridge, Robert C.; Sturgeon, Cord; Wang, Thomas N.; Wirth, Lori J.; Hoffmann, Karin G.; Hughes, Miranda

    2016-01-01

    This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Thyroid Carcinoma focuses on anaplastic carcinoma because substantial changes were made to the systemic therapy recommendations for the 2015 update. Dosages and frequency of administration are now provided, docetaxel/doxorubicin regimens were added, and single-agent cisplatin was deleted because it is not recommended for patients with advanced or metastatic anaplastic thyroid cancer. PMID:26358798

  10. Microsurgical anatomy of the arterial basket of the conus medullaris.

    PubMed

    Martirosyan, Nikolay L; Kalani, M Yashar S; Lemole, G Michael; Spetzler, Robert F; Preul, Mark C; Theodore, Nicholas

    2015-06-01

    OBJECT The arterial basket of the conus medullaris (ABCM) consists of 1 or 2 arteries arising from the anterior spinal artery (ASA) and circumferentially connecting the ASA and the posterior spinal arteries (PSAs). The arterial basket can be involved in arteriovenous fistulas and arteriovenous malformations of the conus. In this article, the authors describe the microsurgical anatomy of the ABCM with emphasis on its morphometric parameters and important role in the intrinsic blood supply of the conus medullaris. METHODS The authors performed microsurgical dissections on 16 formalin-fixed human spinal cords harvested within 24 hours of death. The course, diameter, and branching angles of the arteries comprising the ABCM were then identified and measured. In addition, histological sections were obtained to identify perforating vessels arising from the ABCM. RESULTS The ASA tapers as it nears the conus medullaris (mean preconus diameter 0.7 ± 0.12 mm vs mean conus diameter 0.38 ± 0.08 mm). The ASA forms an anastomotic basket with the posterior spinal artery (PSA) via anastomotic branches. In most of the specimens (n= 13, 81.3%), bilateral arteries formed connections between the ASA and PSA. However, in the remaining specimens (n= 3, 18.7%), a unilateral right-sided anastomotic artery was identified. The mean diameter of the right ABCM branch was 0.49 ± 0.13 mm, and the mean diameter of the left branch was 0.53 ± 0.14 mm. The mean branching angles of the arteries forming the anastomotic basket were 95.9° ± 36.6° and 90° ± 34.3° for the right- and left-sided arteries, respectively. In cases of bilateral arterial anastomoses between the ASA and PSA, the mean distance between the origins of the arteries was 4.5 ± 3.3 mm. Histological analysis revealed numerous perforating vessels supplying tissue of the conus medullaris. CONCLUSIONS The ABCM is a critical anastomotic connection between the ASA and PSA, which play an important role in the intrinsic blood supply

  11. Key Statistics for Thyroid Cancer

    MedlinePlus

    ... cancer? Next Topic Thyroid cancer risk factors Key statistics for thyroid cancer How common is thyroid cancer? ... remains very low compared with most other cancers. Statistics on survival rates for thyroid cancer are discussed ...

  12. Neurotoxicity of Thyroid Disrupting Contaminants

    EPA Science Inventory

    Thyroid hormones playa critical role in the normal development ofthe mammalian brain. Thyroid disrupting chemicals (TDCs) are environmental contaminants that alter the structure or function ofthe thyroid gland, alter regulatory enzymes associated with thyroid hormone (TH) homeost...

  13. Thyroid autoimmunity in pregnant Nigerians

    PubMed Central

    Kayode, Oluwatosin O.; Odeniyi, Ifedayo A.; Iwuala, Sandra; Olopade, Oluwarotimi B.; Fasanmade, Olufemi A.; Ohwovoriole, Augustine E.

    2015-01-01

    Context: Thyroid autoimmunity is a recognized disorder in pregnancy and is associated with a number of adverse pregnancy outcomes. Aim: This study set out to determine the relationship between pregnancy and thyroid autoimmunity in Nigerian women. Settings and Design: This was an analytical cross-sectional study carried out in a tertiary hospital in South Western Nigeria with a total study population of 108 pregnant and 52 nonpregnant women. Subjects and Methods: Serum thyroid stimulating hormone, free thyroxine and thyroid peroxidase antibodies (TPO-Ab) were quantitatively determined using enzyme linked immuno-assays. Pregnant women were grouped into three categories (<14 weeks, 14–28 weeks and > 28 weeks). The relationship between pregnancy and thyroid autoimmunity was determined using Spearman correlation. Analysis of variance was used in comparison of means, Chi-square test used in analyzing proportions while P ≤ 0.05 was considered as significant. Results: The mean age of the pregnant women was 30.4 ± 6.0 years while the mean gestational age of all pregnant women was 20.6 ± 9.6 weeks. The mean TPO-Ab of 11.58 IU/ml in the pregnant was significantly higher than that of the controls of 7.23 IU/ml (P < 0.001). Out of 108 pregnant women, 27 (25%) had elevated TPO-Ab as against about 2% of the nonpregnant women levels P < 0.001. The number of pregnant women with elevated TPO-Ab levels decreased from 33.3% in the first group to 25.6% and 15.2% in the second and third groups. Conclusion: Thyroid autoimmunity expressed by the presence of TPO-Ab is high among pregnant Nigerian women and the frequency of autoimmunity appears to decline with advancing gestational age. PMID:26425470

  14. A Novel Orthotopic Mouse Model of Human Anaplastic Thyroid Carcinoma

    PubMed Central

    Nucera, Carmelo; Nehs, Matthew A.; Mekel, Michal; Zhang, Xuefeng; Hodin, Richard; Lawler, Jack; Nose, Vânia

    2009-01-01

    Background Orthotopic mouse models of human cancer represent an important in vivo tool for drug testing and validation. Most of the human thyroid carcinoma cell lines used in orthotopic or subcutaneous models are likely of melanoma and colon cancer. Here, we report and characterize a novel orthotopic model of human thyroid carcinoma using a unique thyroid cancer cell line. Methods We used the cell line 8505c, originated from a thyroid tumor histologically characterized by anaplastic carcinoma cell features. We injected 8505c cells engineered using a green fluorescent protein–positive lentiviral vector orthotopically into the thyroid of severe combined immunodeficient mice. Results Orthotopic implantation with the 8505c cells produced thyroid tumors after 5 weeks, showing large neck masses, with histopathologic features of a high-grade neoplasm (anaplasia, necrosis, high mitotic and proliferative indexes, p53 positivity, extrathyroidal invasion, lymph node and distant metastases) and immunoprofile of follicular thyroid cell origin with positivity for thyroid transcription factor-1 and PAX8, and for cytokeratins. Conclusions Here we describe a novel orthotopic thyroid carcinoma model using 8505c cells. This model can prove to be a reliable and useful tool to investigate in vivo biological mechanisms determining thyroid cancer aggressiveness, and to test novel therapeutics for the treatment of refractory or advanced thyroid cancers. PMID:19772429

  15. Imaging of rare medullary adrenal tumours in adults.

    PubMed

    Maciel, C A; Tang, Y Z; Coniglio, G; Sahdev, A

    2016-05-01

    Although adrenal medullary tumours are rare, they have important clinical implications. They form a heterogeneous group of tumours, ranging from benign, non-secretory, incidental masses to hormonally active tumours presenting acutely, or malignant tumours with disseminated disease and a poor prognosis. Increasingly, benign masses are incidentally detected due to the widespread use of imaging and routine medical check-ups. This review aims to illustrate the multimodality imaging appearances of rare adrenal medullary tumours, excluding the more common phaeochromocytomas, with clues to the diagnosis and to summarise relevant epidemiological and clinical data. Careful correlation of clinical presentation, hormone profile, and various imaging techniques narrow the differential diagnosis. Image-guided percutaneous adrenal biopsy can provide a definitive diagnosis, allowing for conservative management in selected cases. A close collaboration between the radiologist, endocrinologist, and surgeon is of the utmost importance in the management of these tumours. PMID:26944698

  16. Effect of Space Flight on Adrenal Medullary Function

    NASA Technical Reports Server (NTRS)

    Lelkes, Peter I.

    1999-01-01

    We hypothesize that microgravity conditions during space flight alter the expression and specific activities of the adrenal medullary CA synthesizing enzymes (CASE). Previously, we examined adrenals from six rats flown for six days aboard STS 54 and reported that microgravity induced a decrease in the expression and specific activity of rat adrenal medullary tyrosine hydroxylase, the rate limiting enzyme of CA synthesis, without affecting the expression of other CASE. In the past, we analyzed some of the > 300 adrenals from two previous Space Shuttle missions (PARE 03 and SLS 2). The preliminary results (a) attest to the good state of tissue preservation, thus proving the feasibility of subsequent large-scale evaluation, and (b) confirm and extend our previous findings. With this grant we will be able to expeditiously analyze all our specimens and to complete our studies in a timely fashion.

  17. Discharge properties of dorsal medullary inspiratory neurons in newborn pigs.

    PubMed

    Sica, A L; Donnelly, D F; Steele, A M; Gandhi, M R

    1987-04-01

    The discharges of medullary inspiratory neurons were recorded in newborn pigs. They were classified by discharge pattern; response to lung inflation; synaptic relation to phrenic motoneurons. Our results showed: these neurons have similar discharge patterns and responses to lung inflation as adult cats; most neurons do not project to phrenic motoneurons. It is suggested that our sampled population of neurons is involved in integrating pulmonary afferent inputs. PMID:3594209

  18. A registry-based study of thyroid paraganglioma: histological and genetic characteristics.

    PubMed

    von Dobschuetz, Ernst; Leijon, Helena; Schalin-Jäntti, Camilla; Schiavi, Francesca; Brauckhoff, Michael; Peczkowska, Mariola; Spiazzi, Giovanna; Demattè, Serena; Cecchini, Maria Enrica; Sartorato, Paola; Krajewska, Jolanta; Hasse-Lazar, Kornelia; Roszkowska-Purska, Katarzyna; Taschin, Elisa; Malinoc, Angelica; Akslen, Lars A; Arola, Johanna; Lange, Dariusz; Fassina, Ambrogio; Pennelli, Gianmaria; Barbareschi, Mattia; Luettges, Jutta; Prejbisz, Aleksander; Januszewicz, Andrzej; Strate, Tim; Bausch, Birke; Castinetti, Frederic; Jarzab, Barbara; Opocher, Giuseppe; Eng, Charis; Neumann, Hartmut P H

    2015-04-01

    The precise diagnosis of thyroid neoplasias will guide surgical management. Primary thyroid paraganglioma has been rarely reported. Data on prevalence, immunohistochemistry (IHC), and molecular genetics in a systematic series of such patients are pending. We performed a multinational population-based study on thyroid paraganglioma and analyzed prevalence, IHC, and molecular genetics. Patients with thyroid paraganglioma were recruited from the European-American-Head-and-Neck-Paraganglioma-Registry. Demographic and clinical data were registered. Histopathology and IHC were re-investigated. All patients with thyroid paraganglioma underwent molecular genetic analyses of the SDHA, SDHB, SDHC, SDHD, SDHAF2, VHL, RET, TMEM127, and MAX genes. Analyses included Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA) for detection of large rearrangements. Of 947 registrants, eight candidates were initially identified. After immunohistochemical analyses of these eight subjects, 5 (0.5%) were confirmed to have thyroid paraganglioma. IHC was positive for chromogranin, synaptophysin, and S-100 and negative for calcitonin in all five thyroid paragangliomas, whereas the three excluded candidate tumors stained positive for pan-cytokeratin, a marker excluding endocrine tumors. Germline variants, probably representing mutations, were found in four of the five confirmed thyroid paraganglioma cases, two each in SDHA and SDHB, whereas the excluded cases had no mutations in the tested genes. Thyroid paraganglioma is a finite entity, which must be differentiated from medullary thyroid carcinoma, because medical, surgical, and genetic management for each is different. Notably, approximately 80% of thyroid paragangliomas are associated with germline variants, with implications for additional tumors and a potential risk for the family. As opposed to sporadic tumors, surgical management and extent of resection are different for heritable tumors, each guided by the

  19. Neurobrucellosis presenting as an intra-medullary spinal cord abscess

    PubMed Central

    Vajramani, Girish V; Nagmoti, Mahantesh B; Patil, Chidanand S

    2005-01-01

    Background Of the diverse presentation of neurobrucellosis, intra-medullary spinal cord abscess is extremely rare. Only four other cases have been reported so far. We present a case of spinal cord intra-medullary abscess due to Brucella melitensis. Case presentation A forty-year-old female presented with progressive weakness of both lower limb with urinary incontinence of 6 months duration. She was febrile. Neurological examination revealed flaccid areflexic paraplegia with T10 below sensory impairment including perianal region. An intramedullary mass was diagnosed on Magnetic Resonance Image (MRI) scan extending from T12 to L2. At surgery, a large abscess was encountered at the conus medullaris, from which Brucella melitensis was grown on culture. She was started on streptomycin and doxycycline for 1 month, followed by rifampicin and doxycycline for 1 month. At 2-year follow-up, she had recovered only partially and continued to have impaired bladder function. Conclusion Neurobrucellosis, if not treated early, can result in severe neurological morbidity and sequale, which may be irreversible. Hence it is important to consider the possibility of neurobrucellosis in endemic region and treat aggressively. PMID:16168059

  20. Imaging medullary cystic kidney disease with magnetic resonance.

    PubMed

    Meier, Pascal; Farres, Maria Teresa; Mougenot, Béatrice; Jacob, Laurent; Le Goas, Françoise; Antignac, Corinne; Ronco, Pierre

    2003-07-01

    Medullary cystic kidney disease is characterized by multiple renal cysts at the corticomedullary boundary area, by autosomal dominant inheritance, and by onset of chronic renal failure in the third decade of life. Its clinical manifestations are often insignificant and nonspecific. Furthermore, its diagnosis may be difficult in sporadic forms where genetic linkage analysis cannot be performed. The authors report the case of a patient presenting with a sporadic form of medullary cystic kidney disease whose diagnosis was confirmed using computerized tomography with 3-dimensional reconstruction at the nephrography-excretion time and magnetic resonance imaging (MRI) with magnetic resonance angiography and urography after the injection of gadolinium, a nonnephrotoxic compound. Both imaging techniques showed normal-sized, normal-shaped kidneys containing multiple cysts from 1 to 30 mm in diameter in the medulla and at the corticomedullary junction. A characteristic medullary nephrogram appeared after injection of iodinated contrast medium or gadolinium corresponding to contrast-filled dilated collecting ducts. This report shows that MRI with gadolinium injection can substitute for computerized tomography in azotemic patients. MRI seems particularly promising for the diagnosis of cystic diseases of the kidney and must also be considered when investigating a patient with chronic renal failure of unknown origin. PMID:12830488

  1. A medullary inhibitory region for trigeminal motoneurons in the cat.

    PubMed

    Castillo, P; Pedroarena, C; Chase, M H; Morales, F R

    1991-05-24

    The present report describes the effects on trigeminal motoneurons of stimulation of a circumscribed site within the parvocellular region of the medullary reticular formation. This medullary site was selected because anatomical studies have shown that premotor interneurons project from this site to the trigeminal motorpool. Electrical stimulation of this site induced IPSPs (PcRF-IPSPs) in jaw-closer motoneurons. A population of these IPSPs, recorded contralateral to the site of stimulation, exhibited latencies shorter than 1.5 ms (mean 1.16 +/- 0.08 SD). Their mean amplitude was 1.72 mV +/- 1.13 SD and their mean duration was 3.52 ms +/- 2.15 SD. We believe that these PcRF-IPSPs arose as the result of activation of a monosynaptic pathway. A comparable inhibitory input from this site to ipsilateral jaw-closer motoneurons and to both contra and ipsilateral digastric motoneurons was also observed. We therefore conclude that this medullary PcRF site contains premotor interneurons that are capable of postsynaptically inhibiting motoneurons that innervate antagonistic jaw muscles. PMID:1884229

  2. Thyroid Hemiagenesis Associated with Hashimoto's Thyroiditis

    PubMed Central

    Nsame, D.; Chadli, A.; Hallab, L.; El Aziz, S.; El Ghomari, H.; Farouqi, A.

    2013-01-01

    Thyroid hemiagenesis is a rare congenital anomaly resulting from failure of one thyroid lobe development. We report a 23-year-old female presented with Hashimoto's thyroiditis in left lobe, associated with hemiagenesis of right lobe and isthmus which was previously diagnosed as Graves' hyperthyroidism, but developed further into Hashimoto's thyroiditis after being treated with antithyroid drugs. The symptoms of hyperthyroidism in the current case led to the diagnostic confirmation by scintiscanning of an absent lobe. The antithyroid pharmacotherapy by thiamazole was used. However, due to symptoms of hypothyroidism, it was discontinued two months later, so thyroid hormone substitution was reintroduced. Antithyroid antibody studies and ultrasonography documented the presence of Hashimoto's thyroiditis. PMID:24198979

  3. Fine needle aspiration of secondary synovial sarcoma of the thyroid gland.

    PubMed

    Murro, Diana; Slade, Jamie Macagba; Syed, Sahr; Gattuso, Paolo

    2015-11-01

    Synovial sarcomas (SS) of the head and neck region are extremely rare and arise in only 5% of cases. We present a case of secondary SS of the thyroid originally diagnosed as medullary carcinoma on fine needle aspiration (FNA). A 41-year-old man presented with several weeks of dysphonia and a left thyroid mass. FNA of the thyroid nodule showed a cellular smear composed of loosely cohesive oval to spindle-shaped cells with irregular nuclear borders, finely granular chromatin, and inconspicuous nucleoli. The patient was diagnosed with medullary carcinoma and underwent a total thyroidectomy. Intro-operatively, the mass was found to arise from the tracheoesophageal groove with spread to the left thyroid. Microscopic examination of the thyroid tumor revealed a dense spindle cell proliferation with abundant mitoses, scant cords and nests of epithelial cells and foci of necrosis. The spindle cells were positive for bcl2 and vimentin and the epithelial cells were positive for cytokeratin 8/18 and epithelial membrane antigen (EMA). Both spindle and epithelial cells were negative for thyroglobulin, calcitonin, synaptophysin and chromogranin. Fluorescence in situ hybridization (FISH) demonstrated translocation (X;18)(p11;q11), confirming the diagnosis of SS. The patient underwent a total laryngopharyngoesophagectomy with subsequent adjuvant therapy and is currently disease free. Only 6 cases of histologically confirmed primary SS of the thyroid have been reported. To the best of our knowledge, this is the first case of FISH-confirmed secondary SS of the thyroid and also the first case of SS arising from the tracheoesophageal groove. PMID:26304470

  4. Unusual CNS presentation of thyroid cancer.

    PubMed

    Heery, Christopher R; Engelhard, Herbert H; Slavin, Konstantin V; Michals, Edward A; Villano, J Lee

    2012-09-01

    As advanced therapies allow cancer patients to live longer, disease failure in the central nervous system increases from limited therapeutic penetration. Primary thyroid malignancies rarely metastasize to the brain and have a small number of investigations in literature on the subject. The majority of brain metastases involve the brain parenchyma, reflecting the mass and blood distribution within the brain and central nervous system. Here, we report two cases of the most common differentiated thyroid cancers; follicular thyroid cancer having brain involvement from extra-axial growth and papillary thyroid cancer having brain involvement from a single intraventricular metastasis, presumed as metastasis from the vascular choroid plexus. Both of our cases had widespread systemic involvement. For our follicular thyroid cancer, brain involvement was a result of extra-axial growth from cavarial bone, and our papillary thyroid cancer had brain involvement from a single intraventricular metastasis that was initially resected and nearly a year later developed extensive brain involvement. Unlike the usual gray-white junction metastases seen in the majority of metastatic brain tumors, including thyroid, our cases are uncommon. They reflect differences in tumor biology that allows for spread and growth in the brain. Although there is growing genetic knowledge on tumors that favor brain metastases, little is known about tumors that rarely involve the brain. PMID:22296651

  5. Thyroid dysfunction and subfertility

    PubMed Central

    2015-01-01

    The thyroid hormones act on nearly every cell in the body. Moreover, the thyroid gland continuously interacts with the ovaries, and the thyroid hormones are involved in almost all phases of reproduction. Thyroid dysfunctions are relatively common among women of reproductive age, and can affect fertility in various ways, resulting in anovulatory cycles, high prolactin levels, and sex hormone imbalances. Undiagnosed and untreated thyroid disease can be a cause of subfertility. Subclinical hypothyroidism (SCH), also known as mild thyroid failure, is diagnosed when peripheral thyroid hormone levels are within the normal reference laboratory range, but serum thyroid-stimulating hormone levels are mildly elevated. Thyroid autoimmunity (TAI) is characterized by the presence of anti-thyroid antibodies, which include anti-thyroperoxidase and anti-thyroglobulin antibodies. SCH and TAI may remain latent, asymptomatic, or even undiagnosed for an extended period. It has also been demonstrated that controlled ovarian hyperstimulation has a significant impact on thyroid function, particularly in women with TAI. In the current review, we describe the interactions between thyroid dysfunctions and subfertility, as well as the proper work-up and management of thyroid dysfunctions in subfertile women. PMID:26816871

  6. Thyroid spindle epithelial tumor with thymus-like differentiation (SETTLE): is cytopathological diagnosis possible?

    PubMed

    Kloboves-Prevodnik, Veronika; Jazbec, Janez; Us-Krasovec, Marija; Lamovec, Janez

    2002-05-01

    Spindle epithelial tumor with thymus-like differentiation (SETTLE) is a rare tumor of the thyroid gland which occurs predominantly in children, adolescents, and young adults. It usually presents as a painless neck or thyroid mass and only exceptionally as a diffusely enlarged thyroid gland, without metastatic disease at diagnosis. We report on the case of 12-yr-old girl who had diffusely enlarged thyroid gland for about 1 yr and was initially treated for thyroiditis. Fine-needle aspiration biopsy (FNAB) was performed 8 mo after the first admission. Cytological examination of smears showed unusual morphological features. FNAB smears were cellular, with dissociated cells, naked oval nuclei, aggregates, and groups. Three main cell types were observed: spindle, epithelioid, and epithelial. These cells were uniform, cytologically bland, with few mitotic figures. The distinction between these cells was not always unequivocal. In the background of the smears abundant red extracellular material in the form of fine, dust-like granules and irregular patches were present. It was also observed in some aggregates and groups of tumor cells. Spindle and epithelioid cells were immunocytochemically diffusely pan-cytokeratin-positive. In the differential diagnosis, medullary thyroid carcinoma and SETTLE were suggested. The final histological diagnosis was SETTLE. In cases of SETTLE presented as a diffuse thyromegaly the correct diagnosis may be delayed because clinically and ultrasonographically thyroiditis is suspected. To avoid such a delay, FNAB should be used preoperatively. It can provide specific cytological diagnosis based on morphological features and certain immunocytochemical characteristics of the tumor. PMID:11992375

  7. 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.

  8. Thyroid Involvement in Two Patients with Bannayan-Riley-Ruvalcaba Syndrome

    PubMed Central

    Peiretti, Valentina; Mussa, Alessandro; Feyles, Francesca; Tuli, Gerdi; Santanera, Arianna; Molinatto, Cristina; Ferrero, Giovanni Battista; Corrias, Andrea

    2013-01-01

    Bannayan-Riley-Ruvalcaba syndrome (BRRs) is an overgrowth disorder characterized by macrocephaly, pigmented maculae of the glans penis, and benign mesodermal hamartomas (primarily subcutaneous and visceral lipomas, multiple hemangiomas, and intestinal polyps). Dysmorphic features as well as delayed neuropsychomotor development can also be present. These patients have also a higher risk of developing tumors, as the gene involved in BRRs is phosphatase and tensin homologue (PTEN), and up to 30% of the patients have thyroid involvement consistent with multinodular goiter, thyroid adenoma, differentiated non-medullary thyroid cancer, or Hashimoto’s thyroiditis. Here, we report two cases of BRRs at opposite ends of its phenotypic spectrum: clinical manifestations of the first patient were more severe, while the second one showed only few signs and had no family history of the disease. Both cases developed thyroid disorders detected by thyroid ultrasound screening. We believe that it is important for clinicians, specifically pediatric endocrinologists, to know that this syndrome can appear in very subtle ways and also to be aware that thyroid nodules and intestinal polyps seem to be its most frequently encountered features. Conflict of interest:None declared. PMID:24379037

  9. Child thyroid anatomy (image)

    MedlinePlus

    The thyroid is a gland located in the neck. It is a part of the endocrine (hormone) system, and ... a major role in regulating the body's metabolism. Thyroid disorders are more common in older children and ...

  10. Retrosternal thyroid surgery

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/007558.htm Retrosternal thyroid surgery To use the sharing features on this page, please enable JavaScript. The thyroid gland is normally located at the front of ...

  11. Thyroid gland removal

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/002933.htm Thyroid gland removal To use the sharing features on this page, please enable JavaScript. Thyroid gland removal is surgery to remove all or ...

  12. Chemotherapy for Thyroid Cancer

    MedlinePlus

    ... cancer Next Topic Targeted therapy for thyroid cancer Chemotherapy for thyroid cancer Chemotherapy (chemo) uses anti-cancer drugs that are injected ... vein or muscle, or are taken by mouth. Chemotherapy is systemic therapy, which means that the drug ...

  13. Thyroid Disorders (For Kids)

    MedlinePlus

    ... of thyroid disorder or thyroid disease. Hyperthyroidism (say: hi-per-THYE-roy-diz-em) happens when the ... Kids with the opposite problem have hypothyroidism (say: hi-po-THYE-roy-diz-em). In this case, ...

  14. Thyroid gland removal - discharge

    MedlinePlus

    ... surgery to remove part or all of your thyroid gland. This operation is called thyroidectomy . You probably ... in just a few weeks. If you had thyroid cancer, you may need to have radioactive iodine ...

  15. Thyroid preparation overdose

    MedlinePlus

    Thyroid preparations are medicines used to treat thyroid gland disorders. Overdose occurs when someone takes more than the normal or recommended amount of this medicine. This can be by accident or ...

  16. Pregnancy and Thyroid Disease

    MedlinePlus

    ... Disease Organizations (PDF, 269 KB). Alternate Language URL Pregnancy and Thyroid Disease Page Content On this page: ... responds by decreasing TSH production. [ Top ] How does pregnancy normally affect thyroid function? Two pregnancy-related hormones— ...

  17. Thyroid Hormone Treatment

    MedlinePlus

    ... is to closely replicate normal thyroid functioning. Pure, synthetic thyroxine (T4) works in the same way as ... needing thyroid hormone replacement (see Hypothyroidism brochure ). Pure synthetic thyroxine (T4), taken once daily by mouth, successfully ...

  18. Thyroid Function Tests

    MedlinePlus

    ... problem that is directly affecting the thyroid (primary hypothyroidism). The opposite situation, in which the TSH level ... making enough TSH to stimulate the thyroid (secondary hypothyroidism). In most healthy individuals, a normal TSH value ...

  19. Thyroid Disorders Overview

    MedlinePlus

    ... the amount of hormones produced by the thyroid. Hypothyroidism Hypothyroidism is a thyroid disorder that occurs when the ... irregularities Depression Dry skin and hair Sluggishness Constipation Hypothyroidism is often caused by Hashimoto's disease, an autoimmune ...

  20. Thyroid preparation overdose

    MedlinePlus

    ... a person takes too much of the medicine: Levothyroxine Liothyronine Liotrix Other thyroid medicine Other thyroid preparations ... found in these medicines with these brand names: Levothyroxine ... Liothyronine (Cytomel) Liotrix (Thyrolar, Euthyroid) Other ...

  1. Technological Innovations in Surgical Approach for Thyroid Cancer

    PubMed Central

    Lang, Brian Hung-Hin; Lo, Chung-Yau

    2010-01-01

    Over the last decade, surgeons have witnessed dramatic changes in surgical practice as a result of the introduction of new technological advancement. Some of these changes include refinement of techniques in thyroid cancer surgery. The development of various endoscopic thyroidectomy techniques, the addition of the da Vinci robot, and the use of operative adjuncts in thyroid surgery, such as intraoperative neuromonitoring and quick intraoperative parathyroid hormone, have made thyroid cancer surgery not only safer and better accepted by patients with thyroid cancer but also offer them more surgical treatment options. PMID:20798772

  2. Thyroid Disease Definitions

    MedlinePlus

    ... How Can I Help a Friend Who Cuts? Thyroid Disease Definitions KidsHealth > For Teens > Thyroid Disease Definitions Print A A A Text Size ... sweat, mucous, and tears. goiter: This is a thyroid gland that is enlarged to the point that ...

  3. Thyroid and menopause.

    PubMed

    del Ghianda, S; Tonacchera, M; Vitti, P

    2014-06-01

    Thyroid dysfunction is common in the general population especially in women. All thyroid diseases are in fact more common in women than in men and may interfere with the reproductive system. Thyroid function and the gonadal axes are related throughout the woman's fertile period. The relationship between the two glands is mutual. In particular, thyroid hormones affect the reproductive function both directly and indirectly through several actions. Studies on the relationship between menopause and thyroid function are few and do not allow to clarify whether menopause has an effect on the thyroid regardless of aging. With aging, the main changes regarding thyroid physiology and function are: a reduction of thyroid iodine uptake, free thyroxine and free triiodothyronine synthesis and catabolism of free thyroxine while reverse triiodothyronine increases; the level of thyroid stimulating hormone remains normal with sometimes a tendency to higher limits. These changes are present in both sexes without distinction between males and females. The complexity of the relationships can be summarized in three aspects: thyroid status does not influence significantly the climacteric syndrome; menopause may modify the clinical expression of some thyroid diseases, particularly the autoimmune ones; thyroid function is not directly involved in the pathogenesis of the complications of menopause. However, coronary atherosclerosis and osteoporosis may be aggravated in the presence of hyperthyroidism or hypothyroidism. The effects of postmenopausal estrogen replacement on thyroxine requirements in women with hypothyroidism should be considered. PMID:23998691

  4. Cixutumumab, Everolimus, and Octreotide Acetate in Treating Patients With Advanced Low to Intermediate Grade Neuroendocrine Carcinoma

    ClinicalTrials.gov

    2016-07-14

    Gastrin-Producing Neuroendocrine Tumor; Lung Carcinoid Tumor; Metastatic Digestive System Neuroendocrine Tumor G1; Pancreatic Glucagonoma; Pancreatic Insulinoma; Pancreatic Polypeptide Tumor; Paraganglioma; Recurrent Digestive System Neuroendocrine Tumor G1; Recurrent Merkel Cell Carcinoma; Recurrent Pancreatic Neuroendocrine Carcinoma; Regional Digestive System Neuroendocrine Tumor G1; Somatostatin-Producing Neuroendocrine Tumor; Stage III Merkel Cell Carcinoma; Stage IV Merkel Cell Carcinoma; Thyroid Gland Medullary Carcinoma

  5. Expression and function of CXCL12/CXCR4/CXCR7 in thyroid cancer

    PubMed Central

    ZHU, XIAOLI; BAI, QIANMING; LU, YONGMING; LU, YIQIONG; ZHU, LINLIN; ZHOU, XIAOYAN; WU, LIJING

    2016-01-01

    The contribution of CXCL12/CXCR4/CXCR7 axis to cancer progression has been increasingly recognized. However, its role in thyroid cancer development remains unclear. The present study aimed to examine the expression and function of CXCL12 and its receptors in thyroid cancer. The expression of CXCL12/CXCR4/CXCR7 in human tissue specimens of papillary, follicular, medullary, and anaplastic thyroid carcinoma, follicular adenoma, Hashimoto's thyroiditis and nodular goiter were examined by immunohistochemistry using a tissue microarray. CXCR4 and CXCR7 were over-expressed in human thyroid cancer cells K1 by transduction of recombinant lentivirus. The effect of overexpression of CXCR4 and CXCR7 on K1 cell proliferation and invasion and the molecular mechanism underlying the effect were investigated. CXCL12 was exclusively expressed in papillary thyroid carcinoma tissue but absent in other types of thyroid malignancies and benign lesions. CXCR7 was widely expressed in the endothelial cells of all types of malignancy but only occasionally detected in benign lesions. CXCR4 was expressed in 62.5% of papillary thyroid carcinoma tissue specimens and in 30–40% of other types of malignancy, and it was either absent or weakly expressed in benign lesions. CXCL12 stimulated the invasion and migration of K1 cells overexpressing CXCR4, but did not affect K1 cells overexpressing CXCR7. K1 cell proliferation was not affected by overexpression of CXCR4 or CXCR7. Overexpression of CXCR4 in K1 cells significantly increased AKT and ERK phosphorylation and markedly induced the expression and activity of matrix metalloproteinase-2 (MMP-2). Thus, CXCL12 may be an effective diagnostic marker for papillary thyroid carcinoma, and CXCL12/CXCR4/CXCR7 axis may contribute to thyroid cancer development by regulating cancer cell migration and invasion via AKT and ERK signaling and MMP-2 activation. PMID:27082011

  6. Expression and function of CXCL12/CXCR4/CXCR7 in thyroid cancer.

    PubMed

    Zhu, Xiaoli; Bai, Qianming; Lu, Yongming; Lu, Yiqiong; Zhu, Linlin; Zhou, Xiaoyan; Wu, Lijing

    2016-06-01

    The contribution of CXCL12/CXCR4/CXCR7 axis to cancer progression has been increasingly recognized. However, its role in thyroid cancer development remains unclear. The present study aimed to examine the expression and function of CXCL12 and its receptors in thyroid cancer. The expression of CXCL12/CXCR4/CXCR7 in human tissue specimens of papillary, follicular, medullary, and anaplastic thyroid carcinoma, follicular adenoma, Hashimoto's thyroiditis and nodular goiter were examined by immunohistochemistry using a tissue microarray. CXCR4 and CXCR7 were over-expressed in human thyroid cancer cells K1 by transduction of recombinant lentivirus. The effect of overexpression of CXCR4 and CXCR7 on K1 cell proliferation and invasion and the molecular mechanism underlying the effect were investigated. CXCL12 was exclusively expressed in papillary thyroid carcinoma tissue but absent in other types of thyroid malignancies and benign lesions. CXCR7 was widely expressed in the endothelial cells of all types of malignancy but only occasionally detected in benign lesions. CXCR4 was expressed in 62.5% of papillary thyroid carcinoma tissue specimens and in 30-40% of other types of malignancy, and it was either absent or weakly expressed in benign lesions. CXCL12 stimulated the invasion and migration of K1 cells overexpressing CXCR4, but did not affect K1 cells overexpressing CXCR7. K1 cell proliferation was not affected by overexpression of CXCR4 or CXCR7. Overexpression of CXCR4 in K1 cells significantly increased AKT and ERK phosphorylation and markedly induced the expression and activity of matrix metalloproteinase-2 (MMP‑2). Thus, CXCL12 may be an effective diagnostic marker for papillary thyroid carcinoma, and CXCL12/CXCR4/CXCR7 axis may contribute to thyroid cancer development by regulating cancer cell migration and invasion via AKT and ERK signaling and MMP-2 activation. PMID:27082011

  7. The use of SPECT-CT improves accuracy of post-radioiodine therapy imaging and changes the management strategy in a case of advanced follicular thyroid carcinoma.

    PubMed

    Wong, T H; Amir Hassan, S Z

    2015-12-01

    This is a case of follicular thyroid carcinoma with extensive lung, bone and brain metastases. Multi-modality treatments including total thyroidectomy, modified radical neck dissection, cranial radiotherapy and Iodine-131 (RAI) therapy were instituted. Post RAI therapy planar whole body scan showed RAI avid metastases in the skull, cervical spine, bilateral lungs and abdomen. With the use of SPECTCT imaging, rare adrenal metastasis and additional rib metastasis were identified. Besides, management strategy was altered due to detection of non-RAI avid brain and lung metastatic lesions. PMID:26988209

  8. Thyroglossal Duct Papillary Thyroid Carcinoma and Synchronous Lingual Thyroid Atypia

    PubMed Central

    Yoo, Timothy; Kim, Yohanan; Simental, Alfred; Inman, Jared C.

    2016-01-01

    Thyroglossal duct and lingual thyroid ectopic lesions are exceedingly rare synchronous findings. Papillary thyroid carcinoma of these ectopic thyroid sites is well understood but still a rare finding. This case points to some management nuances in regard to ectopic thyroid screening with imaging and also shows the effectiveness of minimally invasive transoral robotic surgery for lingual thyroid. PMID:27119036

  9. Bilateral medial medullary syndrome secondary to Takayasu arteritis.

    PubMed

    Deshpande, Anirudda; Chandran, Vijay; Pai, Aparna; Rao, Suryanarayana; Shetty, Ranjan

    2013-01-01

    Medial medullary syndrome (MMS) is a rare type of stroke which results due to occlusion of the anterior spinal artery or vertebral artery or its branches. In this case report we present a patient who developed MMS secondary to Takayasu arteritis (TA). TA is a chronic inflammatory arteritis primarily involving the arch of aorta and its branches, which in our patient resulted in occlusion of subclavian arteries as well as infarction of the medial medulla bilaterally. To our knowledge this is the first time that MMS has been found to occur secondary to TA. PMID:23943806

  10. Secondary SUNCT syndrome caused by dorsolateral medullary infarction.

    PubMed

    Jin, Di; Lian, Ya-Jun; Zhang, Hai-Feng

    2016-12-01

    Short-lasting unilateral neuralgiform headaches with conjunctival injection and tearing (SUNCT) is a rare headache syndrome which belongs to trigeminal autonomic cephalalgias. Though the majority of SUNCT syndrome is idiopathic, more and more cases of secondary SUNCT syndrome have been reported recently. In this study, we present a case of symptomatic SUNCT syndrome caused by acute dorsolateral medullary infarction which was verified by brain MRI(magnetic resonance imaging). Up to now, there is not absolutely effective treatment for SUNCT syndrome. However, in our case, SUNCT was completely resolved after conventional treatment for cerebral infarction without specific drug intervention. PMID:26885826

  11. Adrenal imaging (Part 2): Medullary and secondary adrenal lesions

    PubMed Central

    Dhamija, Ekta; Panda, Ananya; Das, Chandan J.; Gupta, A. K.

    2015-01-01

    Adrenal malignancies can be either primary adrenal tumors or secondary metastases, with metastases representing the most common malignant adrenal lesion. While imaging cannot always clearly differentiate between various adrenal malignancies, presence of certain imaging features, in conjunction with appropriate clinical background and hormonal profile, can suggest the appropriate diagnosis. The second part of the article on adrenal imaging describes adrenal medullary tumors, secondary adrenal lesions, bilateral adrenal lesions, adrenal incidentalomas and provides an algorithmic approach to adrenal lesions based on current imaging recommendations. PMID:25593821

  12. Treatment modalities of thyroid related orbitopathy

    PubMed Central

    Ahn, Eric S; Subramanian, Prem S

    2014-01-01

    Aims: The aim was to highlight recent advances in the treatment of thyroid eye disease. Settings and Design: Review article. Materials and Methods: Existing literature and the authors’ experience was reviewed. Results: Thyroid ophthalmopathy is a disfiguring and vision-threatening complication of autoimmune thyroid disease that may develop or persist even in the setting of well-controlled systemic thyroid status. Treatment response can be difficult to predict, and optimized algorithms for disease management do not exist. Thyroid ophthalmopathy should be graded for both severity and disease activity before choosing a treatment modality for each patient. The severity of the disease may not correlate directly with the activity; medical treatment is most effective in active disease, and surgery is usually reserved for quiescent disease with persistent proptosis and/or eyelid changes. Conclusions: Intravenous pulsed corticosteroids, orbital radiotherapy, and orbital surgical techniques form the mainstay of current management of thyroid ophthalmopathy. Immunosuppressive and biologic agents may have a role in treating active disease although additional safety and efficacy studies are needed. PMID:25449934

  13. [Trabecular hyalinizing adenoma of the thyroid (HAT): A report of two cases].

    PubMed

    Román-González, Alejandro; Simón-Duque, Carlos; Camilo-Pérez, Juan; Vélez-Hoyo, Alejandro

    2016-01-01

    The hyalinizing trabecular adenoma is a rare lesion of the thyroid. There is controversy in the literature about the correct name for this disease. Dr. Carney defended the benign nature of this condition and therefore continues calling it adenoma, the World Health Organization calls for the potential of tumor malignancy, and others qualify it as a variant of papillary carcinoma based on the presence of rearranged in transformation/papillary thyroid carcinoma (RET/PTC) rearrangements. In Latin America there are few reported cases. Two cases of hyalinizing trabecular adenoma are reported. The first is a 40-year-old woman with a thyroid nodule of 3x3 cm. The immunohistochemistry was positive for thyroglobulin and calcitonin and negative for cytokeratin 19 and chromogranin. The second case is a 36-year-old patient with a thyroid nodule of 4x4 cm with an immunohistochemical pattern identical to the first case. Trabecular hyalinizing adenoma is a benign disease, easily confused with papillary or medullary thyroid carcinoma. Awareness of this entity will allow a better classification and management of thyroid conditions. PMID:26927651

  14. Comparison of mathematical models for red marrow and blood absorbed dose estimation in the radioiodine treatment of advanced differentiated thyroid carcinoma

    NASA Astrophysics Data System (ADS)

    Miranti, A.; Giostra, A.; Richetta, E.; Gino, E.; Pellerito, R. E.; Stasi, M.

    2015-02-01

    Metastatic and recurrent differentiated thyroid carcinoma is preferably treated with 131I, whose administered activity is limited by red marrow (RM) toxicity, originally correlated by Benua to a blood absorbed dose higher than 2 Gy. Afterward a variety of dosimetric approaches has been proposed. The aim of this work is to compare the results of the Benua formula with the ones of other three blood and RM absorbed dose formulae. Materials and methods have been borrowed by the dosimetric protocol of the Italian Internal Dosimetry group and adapted to the routine of our centre. Wilcoxon t-tests and percentage differences have been applied for comparison purposes. Results are significantly different (p < 0.05) from each other, with an average percentage difference between Benua versus other results of -22%. The dosimetric formula applied to determine blood or RM absorbed dose may contribute significantly to increase heterogeneity in absorbed dose and dose-response results. Standardization should be a major objective.

  15. Renal medullary changes in renal allograft recipients with raised serum creatinine

    PubMed Central

    Sis, B; Sarioglu, S; Celik, A; Kasap, B; Yildiz, S; Kavukcu, S; Gulay, H; Camsari, T

    2006-01-01

    Objective To test the hypothesis that the renal medulla may reflect rejection related changes and thus have a predictive value in the assessment of acute renal allograft rejection or chronic graft damage. Methods 75 post‐transplant biopsies from 57 patients were scored according to the Banff 1997 scheme. The biopsies with adequate cortical and medullary tissue (n = 23) were selected and medullary tissues were reviewed for rejection related lesions except intimal arteritis. Chronic damage was determined by image analysis depending on periodic acid‐methenamine silver (PAMS)‐Masson trichrome (MT) staining. Medullary and cortical changes were compared. Results Interstitial inflammation and tubulitis were more frequent and severe in the cortex (p<0.001). Medullary tubulitis was associated with intimal arteritis (p = 0.003, r = 0.598). Medullary interstitial inflammation (n = 8) and tubulitis (n = 4) were associated with cortical borderline changes (n = 5) or allograft rejection (n = 3). The sensitivity, specificity, and positive and negative predictive values of medullary inflammatory changes in predicting cortical allograft rejection were 43%, 69%, 37%, and 73%, respectively. A significant association was observed between medullary MT‐SAP and cortical PAMS‐SAP values (p = 0.02, R2 = 0.23). Conclusions Acute rejection related lesions are more common and severe in the cortex, and the renal medulla does not sufficiently reflect cortical rejection. The positive and negative predictive values of medullary changes for allograft rejection are low, and medullary inflammation is not a reliable indicator of allograft rejection. Increased medullary fibrosis is correlated with chronic cortical damage. PMID:16461569

  16. Fine needle aspiration of the thyroid

    MedlinePlus

    Thyroid nodule fine needle aspirate biopsy; Biopsy - thyroid - skinny-needle; Skinny-needle thyroid biopsy ... cleaned. A thin needle is inserted into the thyroid, and a sample of thyroid cells and fluid ...

  17. Treatment Option Overview (Thyroid Cancer)

    MedlinePlus

    ... glands make hormones. The thyroid uses iodine , a mineral found in some foods and in iodized salt, ... Fine-needle aspiration biopsy of the thyroid : The removal of thyroid tissue using a thin needle. The ...

  18. Ectopic goitrous submandibular thyroid with goitrous orthotopic thyroid gland.

    PubMed

    Bhardwaj, Avinash Kumar; Mani, Vinayaga; Dixit, Rashmi; Garg, Anju

    2016-01-01

    Ectopic thyroid is a rare developmental anomaly with lingual thyroid accounting for majority of the cases. The presence of ectopic thyroid tissue lateral to the midline is very rare, and very few cases located in the submandibular region have been reported. The simultaneous finding of submandibular ectopic thyroid tissue and a functional orthotopic thyroid gland is even rarer. In the differential diagnosis of an ectopic submandibular thyroid, it is fundamental to exclude a metastasis from well-differentiated thyroid cancer, even when primary thyroid carcinoma is not demonstrable. PMID:27413274

  19. Ectopic goitrous submandibular thyroid with goitrous orthotopic thyroid gland

    PubMed Central

    Bhardwaj, Avinash Kumar; Mani, Vinayaga; Dixit, Rashmi; Garg, Anju

    2016-01-01

    Ectopic thyroid is a rare developmental anomaly with lingual thyroid accounting for majority of the cases. The presence of ectopic thyroid tissue lateral to the midline is very rare, and very few cases located in the submandibular region have been reported. The simultaneous finding of submandibular ectopic thyroid tissue and a functional orthotopic thyroid gland is even rarer. In the differential diagnosis of an ectopic submandibular thyroid, it is fundamental to exclude a metastasis from well-differentiated thyroid cancer, even when primary thyroid carcinoma is not demonstrable. PMID:27413274

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

    PubMed Central

    Iype, Elizabeth Mathew; Jagad, Vijay; Varghese, Bipin T.; Sebastian, Paul

    2016-01-01

    Introduction Intraoperative management of thyroid gland in laryngeal and hypopharyngeal cancer is controversial. Aim The objectives of this study were to determine the incidence of thyroid gland invasion in patients undergoing surgery for laryngeal or hypopharyngeal carcinoma, to assess predictive factors and to assess the prognosis in patients with and without thyroid gland invasion. Materials and Methods One hundred and thirty-three patients who underwent surgery for carcinoma larynx and hypopharynx from 2006 to 2010 were reviewed retrospectively. Surgical specimens were examined to determine the incidence of thyroid gland invasion and predictive factors were analysed. The recurrence rate and the survival in patients with and without thyroid gland invasion were also analysed. Results Out of the 133 patients with carcinoma larynx and hypopharynx who underwent surgery, histological thyroid gland invasion was observed in 28/133 (21%) patients. Significant relationship was found between histological thyroid gland invasion and preoperative evidence of thyroid cartilage erosion by CT scan and also when gross thyroid gland involvement observed during surgery. There is significant association between thyroid gland invasion when there is upper oesophageal or subglottic involvement. Conclusion After analysing the retrospective data from our study, we would like to suggest that thyroid gland need not be removed routinely in all laryngectomies, unless there is advanced disease with thyroid cartilage erosion and gross thyroid gland involvement or disease with significant subglottic or oesophageal involvement. PMID:27042568

  1. Synthetic gene network restoring endogenous pituitary–thyroid feedback control in experimental Graves’ disease

    PubMed Central

    Saxena, Pratik; Charpin-El Hamri, Ghislaine; Folcher, Marc; Zulewski, Henryk; Fussenegger, Martin

    2016-01-01

    Graves’ disease is an autoimmune disorder that causes hyperthyroidism because of autoantibodies that bind to the thyroid-stimulating hormone receptor (TSHR) on the thyroid gland, triggering thyroid hormone release. The physiological control of thyroid hormone homeostasis by the feedback loops involving the hypothalamus–pituitary–thyroid axis is disrupted by these stimulating autoantibodies. To reset the endogenous thyrotrophic feedback control, we designed a synthetic mammalian gene circuit that maintains thyroid hormone homeostasis by monitoring thyroid hormone levels and coordinating the expression of a thyroid-stimulating hormone receptor antagonist (TSHAntag), which competitively inhibits the binding of thyroid-stimulating hormone or the human autoantibody to TSHR. This synthetic control device consists of a synthetic thyroid-sensing receptor (TSR), a yeast Gal4 protein/human thyroid receptor-α fusion, which reversibly triggers expression of the TSHAntag gene from TSR-dependent promoters. In hyperthyroid mice, this synthetic circuit sensed pathological thyroid hormone levels and restored the thyrotrophic feedback control of the hypothalamus–pituitary–thyroid axis to euthyroid hormone levels. Therapeutic plug and play gene circuits that restore physiological feedback control in metabolic disorders foster advanced gene- and cell-based therapies. PMID:26787873

  2. Synthetic gene network restoring endogenous pituitary-thyroid feedback control in experimental Graves' disease.

    PubMed

    Saxena, Pratik; Charpin-El Hamri, Ghislaine; Folcher, Marc; Zulewski, Henryk; Fussenegger, Martin

    2016-02-01

    Graves' disease is an autoimmune disorder that causes hyperthyroidism because of autoantibodies that bind to the thyroid-stimulating hormone receptor (TSHR) on the thyroid gland, triggering thyroid hormone release. The physiological control of thyroid hormone homeostasis by the feedback loops involving the hypothalamus-pituitary-thyroid axis is disrupted by these stimulating autoantibodies. To reset the endogenous thyrotrophic feedback control, we designed a synthetic mammalian gene circuit that maintains thyroid hormone homeostasis by monitoring thyroid hormone levels and coordinating the expression of a thyroid-stimulating hormone receptor antagonist (TSHAntag), which competitively inhibits the binding of thyroid-stimulating hormone or the human autoantibody to TSHR. This synthetic control device consists of a synthetic thyroid-sensing receptor (TSR), a yeast Gal4 protein/human thyroid receptor-α fusion, which reversibly triggers expression of the TSHAntag gene from TSR-dependent promoters. In hyperthyroid mice, this synthetic circuit sensed pathological thyroid hormone levels and restored the thyrotrophic feedback control of the hypothalamus-pituitary-thyroid axis to euthyroid hormone levels. Therapeutic plug and play gene circuits that restore physiological feedback control in metabolic disorders foster advanced gene- and cell-based therapies. PMID:26787873

  3. Thyroid hormone testing in the 21st century.

    PubMed

    Singh, Ravinder J; Kaur, Parmpreet

    2016-08-01

    Thyroid dysfunction and treatment follow up require accurate measurement of thyroid hormones. Most thyroid disease is treated on an outpatient basis; thus, assays have to be rapid and cost effective for optimal patient care. There are no rapid or point-of-care thyroid tests yet available, which could replace centralized automated thyroid testing. With the high population of thyroid dysfunction, it is important for thyroid assays to be available widely and locally. Immunoassays are most commonly used due to their ease and availability, but are limited in their accuracy. MS assays are much more specific, but are laborious with a high machine cost. Many hospitals may not be able to afford the machines and lack technical expertise. Sensitivity, specificity and standardization issues still result in substantial differences between various tests currently used for this population. To address these issues, new performance standards are being established by the professional organizations and technological advancements are being undertaken by instrument manufacturers. Automation solution is provided by various manufacturers and offers a choice for the hospital labs to select a platform which helps in their workflow and other chemistry testing. This has also resulted in decentralization and easy access to the thyroid testing. Even with these advancements, it is understandably confusing for clinicians to choose an assay for various clinical scenarios (20). As it becomes more available and standardized, LC-MS will continue to demonstrate its superiority to immunoassay. PMID:27329994

  4. Nodular thyroid disease in children and adolescents: a high incidence of carcinoma

    SciTech Connect

    McHenry, C.; Smith, M.; Lawrence, A.M.; Jarosz, H.; Paloyan, E.

    1988-07-01

    Over a period of 32 years from 1954 to 1986, 65 patients under the age of 21 years, 52 girls and 13 boys, were operated for nodular thyroids: the overall incidence of carcinoma was 37 per cent. It was 46 per cent in those patients presenting with a solitary nodule. Among the 24 patients with a malignancy, the carcinoma was of the papillary variety in 63 per cent, follicular in 25 per cent and medullary in 12 per cent. Two thirds of the patients had metastatic disease at the time of presentation. All patients with thyroid carcinoma were treated with total thyroidectomy. Other measures included neck dissection and radioactive iodine. When the eight patients with a history of head and neck irradiation and the three patients with medullary carcinoma were excluded, the incidence of carcinoma was 28 per cent. In summary, in spite of the decline in radiation associated cases, the incidence of carcinoma in nodular thyroid disease in the population under 21 years, remains at the relatively high figure of 28 per cent.

  5. Thyroid and parathyroid imaging.

    PubMed

    Freitas, J E; Freitas, A E

    1994-07-01

    With the advent of better thyroid function tests, a tumor marker, and fine-needle aspiration, the role of thyroid imaging studies in the evaluation of the patients with thyroid disease has diminished. Although multimodality thyroid imaging had improved our understanding of thyroid disease, current indications for thyroid imaging are the solitary or dominant thyroid nodule, an upper mediastinal mass, differentiation of hyperthyroidism, detection and staging of postoperative thyroid cancer, neonatal hypothyroidism, thyroid developmental anomalies, and the thyroid mass post-thyroidectomy for benign disease. To provide optimal, cost-effective, care for the thyroid patient, the physician must understand the advantages and disadvantages of each imaging modality--scintigraphy, real-time sonography (RTS), computed tomography, and magnetic resonance--in specific clinical settings. Similarly, preoperative noninvasive localization of hyperfunctioning parathyroid tissue in patients with primary hyperparathyroidism undergoing their initial neck exploration usually is not warranted. In this situation, the best localization procedure is to enlist the services of an experienced parathyroid surgeon. However, if this is not feasible because of local constraints, both sestamibi methoxy isobutyl isonitrile (MIBI) scintigraphy and magnetic resonance imaging (MRI) provide excellent localization (< 90%) of juxta-thyroidal and ectopic parathyroid adenomas. Hyperplastic glands are more difficult to detect because of their smaller size, and tandem studies (MIBI and MRI) should provide higher sensitivity before initial exploration, especially in patients with ectopic glands. In patients with persistent or recurrent disease, multimodality imaging with MIBI, MR, computed tomography and RTS in a sequential fashion is warranted to optimize two-test, site-specific localization. PMID:7973759

  6. Thyroid calcifications: a pictorial essay.

    PubMed

    Lacout, Alexis; Chevenet, Carole; Thariat, Juliette; Marcy, Pierre Yves

    2016-05-01

    Incidental diagnosis of thyroid nodules is very common on adult neck ultrasonography examination. Thyroid calcifications are encountered in benign thyroid nodules and goiters as well as in thyroid malignancy. Depiction and characterization of such calcifications within a thyroid nodule may be a key element in the thyroid nodule diagnosis algorithm. The goal of this paper is to display typical radio-pathological correlations of various thyroid pathologies of benign and malignant conditions in which the calcification type diagnosis can play a key role in the final diagnosis of the thyroid nodule. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 44:245-251, 2016. PMID:26891122

  7. Autoimmune Thyroid Diseases in Children

    PubMed Central

    Cappa, Marco; Bizzarri, Carla; Crea, Francesca

    2011-01-01

    The two major autoimmune thyroid diseases (ATDs) include Graves' disease (GD) and autoimmune thyroiditis (AT); both of which are characterized by infiltration of the thyroid by T and B cells reactive to thyroid antigens, by the production of thyroid autoantibodies and by abnormal thyroid function (hyperthyroidism in GD and hypothyroidism in AT). While the exact etiology of thyroid autoimmunity is not known, it is believed to develop when a combination of genetic susceptibility and environmental encounters leads to breakdown of tolerance. It is important to recognize thyroid dysfunction at an early stage by maintaining an appropriate index of suspicion. PMID:21209713

  8. Thyroid cancer around Chernobyl

    SciTech Connect

    Beral, V.

    1997-03-01

    The author`s presentation on thyroid cancer around Chernobyl will focus on four different things. First will be the time trends, or the pattern of thyroid cancer occurrence before and after the accident. It is now very well known that the increase in thyroid cancer in children in several areas has been unprecedented. Second, the author discusses thyroid cancer in general and patterns of thyroid cancer around the world before the Chernobyl accident, including differences by age and pathology. Third, the author presents relatively crude analyses of risk according to dose to the thyroid gland. And last, the author attempts to contrast the findings for thyroid cancer in relation to the internal radioiodine dose in Chernobyl studies with analyses of the effects of external dose on thyroid cancer incidence. The bottom line to be developed is similar to that presented by Elaine Ron with regard to effects of external dose on thyroid cancer. The similarities between the childhood finding from Chernobyl studies and external radiation studies appear more remarkable than the differences.

  9. Rhythm generation in organotypic medullary cultures of newborn rats.

    PubMed

    Baker, R E; Ballantyne, D; Bingmann, D; Jones, D; Widman, G

    1995-12-01

    Organotypic transverse medullary slices (obex level) from six-day-old rats, cultured for two to four weeks in chemically defined medium contained rhythmically discharging neurones which were activated by CO2 and H+. The mechanisms underlying this rhythmicity and the spread of excitation and synaptic transmission within this organotypic tissue were examined by modifying the composition of the external solution. Our findings showed that (1) Exposure to tetrodotoxin (0.2 microM) or to high magnesium (6 mM) and low calcium (0.2 mM) concentrations abolished periodic activity. (2) Neither the blockade of GABAergic potentials with bicuculline methiodide (200 microM) and/or hydroxysaclofen (200 microM) nor the blockade of glycinergic potentials with strychnine hydrochloride (100 microM) abolished rhythmicity. (3) While atropine sulphate (5 microM) was ineffective in modulating periodic discharges nicotine (100 microM) - like CO2-shortened the intervals between the periodic events; hexamethonium (50-100 microM) reduced both periodic and aperiodic activity. (4) Exposure to the NMDA antagonist 2-aminophosphonovaleric acid (50 microM) suppressed periodic events only transiently. In the presence of 2-aminophosphonovaleric acid rhythmicity recovered. However, the AMPA-antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (10-50 microM), abolished periodic activity reversibly within less than 5 min. When 6-cyano-7-nitroquinoxaline-2,3-dione and nicotine were administered simultaneously periodic events persisted for up to 10 min. These findings indicate that synaptic excitatory drive is a prerequisite for the generation of rhythmic discharges of medullary neurones in this preparation. This drive may activate voltage-dependent channels or it may facilitate endogenous cellular mechanisms which initiate oscillations of intracellular calcium concentration. To test the latter possibility (5) calcium antagonists were added to the bath saline. The organic calcium antagonists verapamil and

  10. Myeloma bone and extra-medullary disease: Role of PET/CT and other whole-body imaging techniques.

    PubMed

    Rubini, Giuseppe; Niccoli-Asabella, Artor; Ferrari, Cristina; Racanelli, Vito; Maggialetti, Nicola; Dammacco, Francesco

    2016-05-01

    Multiple myeloma (MM) is the second most common hematological malignancy. Although it can affect different organs, the bone compartment stands out both in terms of prevalence and clinical impact. Despite the striking advances in MM therapy, bone disease can remarkably affect the patient's quality of life. The occurrence and extension of bone marrow and extra-medullary involvement should be carefully assessed to confirm the diagnosis, to locate and whenever possible prevent dreadful complications such as pathological fractures and spinal cord compression, and to establish suitable therapeutic measures. Many imaging techniques have been proposed for the detection of MM skeletal involvement. With the development of more sophisticated imaging tools, it is time to use the right technique at the right time. Based on the review of the literature and our own experience, this article discusses advantages and disadvantages of the different imaging methods in the work-up of MM patients, with particular emphasis on the role that PET/CT can play. It is emphasized that whole body low-dose computed tomography should be the preferred imaging technique at baseline. However, bone marrow infiltration and extra-medullary manifestations are better detected by whole body magnetic resonance imaging. Positron emission tomography/computed tomography, on the other hand, combines the benefits of the two mentioned imaging procedures and is particularly useful not only for the detection of osteolytic lesions unrevealed by conventional X-ray, but also in the assessment of prognosis and therapeutic response. PMID:26997302

  11. Imaging of the thyroid in benign and malignant disease.

    PubMed

    Intenzo, Charles M; Dam, Hung Q; Manzone, Timothy A; Kim, Sung M

    2012-01-01

    expert opinion and retrospective analysis with inherent bias. With a growing trend not to ablate low-risk patients, so that a PTS cannot be performed, some thyroid carcinoma patients may never have radioiodine imaging. In routine clinical practice, however, imaging plays a critical role in patient management both before and after treatment. Moreover, as evidenced by the robust flow of publications concerning WBS and PTS, planar imaging of thyroid carcinoma remains a topic of great interest in this modern age of rapidly advancing cross sectional and hybrid imaging with single-photon emission computed tomography, single-photon emission computed tomography/CT, and positron emission tomography/CT. PMID:22117813

  12. Thyroid Growth and Cancer.

    PubMed

    Williams, Dillwyn

    2015-09-01

    It is proposed that most papillary thyroid cancers originate in infancy and childhood, based on the early rise in sporadic thyroid carcinoma incidence, the pattern of radiation-induced risk (highest in those exposed as infants), and the high prevalence of sporadic papillary thyroid cancers in children and adolescents (ultrasound screening after the Fukushima accident). The early origin can be linked to the growth pattern of follicular cells, with a high mitotic rate in infancy falling to very low replacement levels in adult life. The cell of origin of thyroid cancers, the differentiated follicular cell, has a limited growth potential. Unlike cancers originating in stem cells, loss of the usually tight link between differentiation and replicative senescence is required for immortalisation. It is suggested that this loss distinguishes larger clinically significant papillary thyroid cancers from micro-papillary thyroid cancers of little clinical significance. Papillary carcinogenesis can then be divided into 3 stages: (1) initiation, the first mutation in the carcinogenic cascade, for radiation-induced papillary thyroid cancers usually a RET rearrangement, (2) progression, acquisition of the additional mutations needed for low-grade malignancy, and (3) escape, further mutations giving immortality and a higher net growth rate. Most papillary thyroid cancers will not have achieved full immortality by adulthood, and remain as so-called micro-carcinomas with a very low growth rate. The use of the term 'cancer' to describe micro-papillary thyroid cancers in older patients encourages overtreatment and alarms patients. Invasive papillary thyroid tumours show a spectrum of malignancy, which at its lowest poses no threat to life. The treatment protocols and nomenclature for small papillary carcinomas need to be reconsidered in the light of the new evidence available, the continuing discovery of smaller lesions, and the model of thyroid carcinogenesis proposed. PMID:26558233

  13. Thyroid Growth and Cancer

    PubMed Central

    Williams, Dillwyn

    2015-01-01

    It is proposed that most papillary thyroid cancers originate in infancy and childhood, based on the early rise in sporadic thyroid carcinoma incidence, the pattern of radiation-induced risk (highest in those exposed as infants), and the high prevalence of sporadic papillary thyroid cancers in children and adolescents (ultrasound screening after the Fukushima accident). The early origin can be linked to the growth pattern of follicular cells, with a high mitotic rate in infancy falling to very low replacement levels in adult life. The cell of origin of thyroid cancers, the differentiated follicular cell, has a limited growth potential. Unlike cancers originating in stem cells, loss of the usually tight link between differentiation and replicative senescence is required for immortalisation. It is suggested that this loss distinguishes larger clinically significant papillary thyroid cancers from micro-papillary thyroid cancers of little clinical significance. Papillary carcinogenesis can then be divided into 3 stages: (1) initiation, the first mutation in the carcinogenic cascade, for radiation-induced papillary thyroid cancers usually a RET rearrangement, (2) progression, acquisition of the additional mutations needed for low-grade malignancy, and (3) escape, further mutations giving immortality and a higher net growth rate. Most papillary thyroid cancers will not have achieved full immortality by adulthood, and remain as so-called micro-carcinomas with a very low growth rate. The use of the term ‘cancer’ to describe micro-papillary thyroid cancers in older patients encourages overtreatment and alarms patients. Invasive papillary thyroid tumours show a spectrum of malignancy, which at its lowest poses no threat to life. The treatment protocols and nomenclature for small papillary carcinomas need to be reconsidered in the light of the new evidence available, the continuing discovery of smaller lesions, and the model of thyroid carcinogenesis proposed. PMID

  14. Medullary Sponge Kidney and Urinary Calculi Aeromedical Concerns

    NASA Technical Reports Server (NTRS)

    Jones, Jeffrey A.; Cherian, Sebastian F.; Barr, Yael R.; Stocco, Amber

    2008-01-01

    Medullary Sponge Kidney (MSK) is a benign disorder associated with renal stones in 60% of patients. Patients frequently have episodic painless hematuria but are otherwise asymptomatic unless renal calculi or infections complicate the disease. Nephrolithiasis is a relative, but frequently enforced, contraindication to space or other high performance flight. Two case reports of asymptomatic NASA flight crew with MSK and three cases of military aviators diagnosed with MSK are reviewed, all cases resulted in waiver and return to flight status after treatment and a vigorous follow up and prophylaxis protocol. MSK in aviation and space flight necessitates a highly case-by-case dependent evaluation and treatment process to rule out other potential confounding factors that might also contribute to stone formation and in order to re-qualify the aviator for flight duties.

  15. Detrusor function with lesions of the conus medullaris.

    PubMed

    Beric, A; Light, J K

    1992-07-01

    Conventional urodynamic evaluation is unable to distinguish between a pure conus lesion and one with concomitant cauda equina involvement. Lumbosacral evoked potentials to tibial nerve stimulation assesses the sensory root and dorsal horn interneurons of the L5 to S2 spinal cord segments. This allows for the diagnosis of a pure lesion of the conus medullaris with preservation of the sensory root response (R wave) with absence of the dorsal horn gray matter response (S wave). Urodynamic evaluation in 5 patients with a conus lesion showed a variety of detrusor responses ranging from hyperreflexia through areflexia with decreased compliance to areflexia with normal compliance. The ability to diagnose a pure conus lesion may have prognostic significance as newer modalities of treatment emerge, all of which require intact gray matter of the spinal cord. PMID:1613846

  16. Lateral medullary stroke in patient with granulomatous polyangiitis.

    PubMed

    Taraschenko, Olga D; Amory, Colum F; Waldman, Jonathan; Hanspal, Era K; Bernardini, Gary L

    2014-01-01

    Granulomatous polyangiitis (GPA), also known as Wegener granulomatosis, is a systemic antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis that infrequently affects the central nervous system. We report a 41-year-old man with lateral medullary infarction who developed rapidly progressive renal failure. He was diagnosed with GPA based on positive serum c-ANCA and antiproteinase 3 antibodies and demonstration of pauci-immune crescentic glomerulonephritis on kidney biopsy. He was treated with Coumadin, pulse steroids, cyclophosphamide, and plasmapheresis. He had resolution of his neurologic deficits and improvement in renal function. This case report highlights the importance to consider GPA vasculitis in the differential diagnosis of stroke in patients with development of acute kidney injury. PMID:24128976

  17. Decitabine in Treating Patients With Metastatic Papillary Thyroid Cancer or Follicular Thyroid Cancer Unresponsive to Iodine I 131

    ClinicalTrials.gov

    2014-08-20

    Recurrent Thyroid Cancer; Stage IVA Follicular Thyroid Cancer; Stage IVA Papillary Thyroid Cancer; Stage IVB Follicular Thyroid Cancer; Stage IVB Papillary Thyroid Cancer; Stage IVC Follicular Thyroid Cancer; Stage IVC Papillary Thyroid Cancer

  18. [Psychotic episode due to Hashimoto's thyroiditis].

    PubMed

    Nazou, M; Parlapani, E; Nazlidou, E-I; Athanasis, P; Bozikas, V P

    2016-01-01

    Thyroid hormones are crucial in adult brain metabolic activity. As a result, abnormal thyroid gland function and in particular hypofunction, might cause principally depression and neurocognitive dysfunction. Psychosis, presented mainly with thought disorders and perceptual disturbances, is a much rarer manifestation of hypothyreoidism. A correlation between hypothyreoidism and psychosis has been described since 1888, especially in cases of advanced hypothyreoidism. A few years later (1949), Asher first added the terminology "myxedema madness" to the literature. Psychotic symptoms typically appear after the onset of physical symptoms, usually with a delay of months or years. The case of a female patient who presented a psychotic episode as a first manifestation of hypothyroidism will be described. NE, a 48 yearold female patient, was admitted for the first time to an inpatient mental health care unit due to delusions of persecution and reference, as well as auditory hallucinations that appeared a few weeks ago. After the patient admission, routine laboratory examination was conducted. In order to relieve the patient from her sense of discomfort and while awaiting laboratory results, olanzapine, 5 mg/day, was administered. Neurological examination and cranial computed tomography scan were unremarkable. Hormonal laboratory tests though revealed severe low thyroid hormone levels. Thyroid antibody testing certified Hashimoto's thyroiditis. Olanzapine was discontinued and the patient received thyroid hormone substitution, levothyroxine 75 μg/day, instead. The patient was discharged showing a significant improvement of psychotic symptoms after a 12-day hospitalization. A month later the patient was reevaluated. She had fully recovered from the psychotic episode. A year later, the patient continues to remain free from psychiatric symptoms, while thyroid hormone levels have been restored within normal range. The patient continues receiving only thyroid hormone substitution

  19. Letrozole inhibits the osteogenesis of medullary bone in prelay pullets.

    PubMed

    Deng, Y-F; Chen, X-X; Zhou, Z-L; Hou, J-F

    2010-05-01

    This study was performed to investigate the effect of letrozole, an aromatase inhibitor, on osteogenesis of medullary bone in prelay pullets. Three hundred fifteen 95-d-old ISA prelay pullets were used. After 10 d of adaptation in the cages, 15 pullets were selected randomly to collect the serum and bone samples and the rest were randomly assigned to 2 groups with 3 replicates each. One group was control and the other was letrozole-treated, fed 0.5 mg of letrozole per prelay pullet per day for 18 d. The serum and bone samples from these birds were collected during the experiment. Estradiol and testosterone in serum were assayed using commercial RIA kits. The serum alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP), Ca, and inorganic P were measured by an automatic biochemistry analyzer with commercial kits. The periosteum perimeter, endosteum perimeter, cortical bone index, cortical width, cortical bone area, and cortical area ratios of tibia were measured by transmitted scanner and a computer-assisted image analyzer. Our results showed that relative to the control-fed pullet, letrozole-fed pullets had reduced serum estrogen (57.5%), Ca (33.2%), ALP (33.6%), and TRAP (24.2%) and that values of serum estrogen, Ca, estrogen receptor expression, tibia radiographic density, serum ALP, and TRAP were all reduced (P < 0.05) and the serum P had a degressive trend in letrozole-treated groups. By contrast, the serum androgen and the tibia cortical bone index values were higher in the letrozole-treated group (P < 0.05). No differences were observed in the periosteum perimeter, endosteum perimeter, cortical width, and cortical area ratios of tibia between the 2 groups. The results showed that letrozole can inhibit the development of bone and medullary osteogenesis by inhibiting the synthesis of estrogen and its receptor in prelay pullets. PMID:20371843

  20. Syntaxin specificity of aquaporins in the inner medullary collecting duct.

    PubMed

    Mistry, Abinash C; Mallick, Rickta; Klein, Janet D; Weimbs, Thomas; Sands, Jeff M; Fröhlich, Otto

    2009-08-01

    Proper targeting of the aquaporin-2 (AQP2) water channel to the collecting duct apical plasma membrane is critical for the urine concentrating mechanism and body water homeostasis. However, the trafficking mechanisms that recruit AQP2 to the plasma membrane are still unclear. Snapin is emerging as an important mediator in the initial interaction of trafficked proteins with target soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP) receptor (t-SNARE) proteins, and this interaction is functionally important for AQP2 regulation. We show that in AQP2-Madin-Darby canine kidney cells subjected to adenoviral-mediated expression of both snapin and syntaxins, the association of AQP2 with both syntaxin-3 and syntaxin-4 is highly enhanced by the presence of snapin. In pull-down studies, snapin detected AQP2, syntaxin-3, syntaxin-4, and SNAP23 from the inner medullary collecting duct. AQP2 transport activity, as probed by AQP2's urea permeability, was greatly enhanced in oocytes that were coinjected with cRNAs of SNARE components (snapin+syntaxin-3+SNAP23) over those injected with AQP2 cRNA alone. It was not enhanced when syntaxin-3 was replaced by syntaxin-4 (snapin+syntaxin-4+SNAP23). On the other hand, the latter combination significantly enhanced the transport activity of the related AQP3 water channel while the presence of syntaxin-3 did not. This AQP-syntaxin interaction agrees with the polarity of these proteins' expression in the inner medullary collecting duct epithelium. Thus our findings suggest a selectivity of interactions between different aquaporin and syntaxin isoforms, and thus in the regulation of AQP2 and AQP3 activities in the plasma membrane. Snapin plays an important role as a linker between the water channel and the t-SNARE complex, leading to the fusion event, and the pairing with specific t-SNAREs is essential for the specificity of membrane recognition and fusion. PMID:19515809

  1. Everolimus and Vatalanib in Treating Patients With Advanced Solid Tumors

    ClinicalTrials.gov

    2016-04-18

    Gastrinoma; Glucagonoma; Insulinoma; Metastatic Gastrointestinal Carcinoid Tumor; Metastatic Pheochromocytoma; Pancreatic Polypeptide Tumor; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Islet Cell Carcinoma; Recurrent Melanoma; Recurrent Neuroendocrine Carcinoma of the Skin; Recurrent Non-small Cell Lung Cancer; Recurrent Pheochromocytoma; Recurrent Renal Cell Cancer; Somatostatinoma; Stage III Neuroendocrine Carcinoma of the Skin; Stage IV Melanoma; Stage IV Non-small Cell Lung Cancer; Stage IV Renal Cell Cancer; Thyroid Gland Medullary Carcinoma; Unspecified Adult Solid Tumor, Protocol Specific

  2. [Ultrasound of the Thyroid].

    PubMed

    Dietrich, C F; Bojunga, J

    2016-02-01

    Thyroid nodules and thyroid abnormalities are common findings in the general population. Ultrasonography is the most important imaging tool for diagnosing thyroid disease. In the majority of cases a correct diagnosis can already be made in synopsis of the sonographic together with clinical findings and basal thyroid hormone parameters and an appropriate therapy can be initiated thereafter. A differentiation of hormonally active vs. inactive nodes, and in particular benign vs. malignant nodules is sonographically, however, not reliably possible. In this context, radioscanning has its clinical significance predominantly in diagnosing hormonal activity of thyroid nodules. Efforts of the past years aimed to improve sonographic risk stratification to predict malignancy of thyroid nodules through standardized diagnostic assessment of evaluated risk factors in order to select patients, who need further diagnostic work up. According to the "Breast Imaging Reporting and Data System" (BI-RADS), "Thyroid Imaging Reporting and Data Systems" (TI-RADS) giving standardized categories with rates of malignancy were evaluated as a basis for further clinical management. Recent technological developments, such as elastography, also showpromising data and could gain entrance into clinical practice. The ultrasound-guided fineneedle aspiration is the key element in the diagnosis of sonographically suspicious thyroid nodules and significantly contributes to the diagnosis of malignancy versus benignity. PMID:26859730

  3. Thyroid imaging studies

    SciTech Connect

    Drew, H.H.; LaFrance, N.D.; Chen, J.J.S.

    1987-06-01

    This is the second in a series of Continuing Education articles related to functional/quantitative imaging techniques. After reading this article, the reader should be able to: 1) discuss the clinical applications of thyroid imaging; 2) understand the relationship of related thyroid tests; and 3) recognize the pitfalls and problems associated with this procedure.

  4. Thyroid ultrasound (image)

    MedlinePlus

    ... is a sound wave picture of the thyroid gland taken by a hand-held instrument and translated to a 2-dimensional picture on a monitor. It is used in diagnosis of tumors, cysts or goiters of the thyroid, and is a painless, no-risk procedure.

  5. Thyroid Function and Obesity

    PubMed Central

    Laurberg, Peter; Knudsen, Nils; Andersen, Stig; Carlé, Allan; Pedersen, Inge Bülow; Karmisholt, Jesper

    2012-01-01

    Important interaction exists between thyroid function, weight control, and obesity. Several mechanisms seem to be involved, and in studies of groups of people the pattern of thyroid function tests depends on the balance of obesity and underlying thyroid disease in the cohort studied. Obese people with a normal thyroid gland tend to have activation of the hypothalamic-pituitary-thyroid axis with higher serum TSH and thyroid hormones in serum. On the other hand, small differences in thyroid function are associated with up to 5 kg difference in body weight. The weight loss after therapy of overt hypothyroidism is caused by excretion of water bound in tissues (myxoedema). Many patients treated for hyperthyroidism experience a gain of more weight than they lost during the active phase of the disease. The mechanism for this excessive weight gain has not been fully elucidated. New studies on the relation between L-T3 therapy and weight control are discussed. The interaction between weight control and therapy of thyroid disease is important to many patients and it should be studied in more detail. PMID:24783015

  6. Thyroid function and obesity.

    PubMed

    Laurberg, Peter; Knudsen, Nils; Andersen, Stig; Carlé, Allan; Pedersen, Inge Bülow; Karmisholt, Jesper

    2012-10-01

    Important interaction exists between thyroid function, weight control, and obesity. Several mechanisms seem to be involved, and in studies of groups of people the pattern of thyroid function tests depends on the balance of obesity and underlying thyroid disease in the cohort studied. Obese people with a normal thyroid gland tend to have activation of the hypothalamic-pituitary-thyroid axis with higher serum TSH and thyroid hormones in serum. On the other hand, small differences in thyroid function are associated with up to 5 kg difference in body weight. The weight loss after therapy of overt hypothyroidism is caused by excretion of water bound in tissues (myxoedema). Many patients treated for hyperthyroidism experience a gain of more weight than they lost during the active phase of the disease. The mechanism for this excessive weight gain has not been fully elucidated. New studies on the relation between L-T3 therapy and weight control are discussed. The interaction between weight control and therapy of thyroid disease is important to many patients and it should be studied in more detail. PMID:24783015

  7. [Pregnancy and thyroid disorders].

    PubMed

    Bricaire, L; Groussin, L

    2015-03-01

    Thyroid disorders are frequent among women, with a few specificities during pregnancy. Recent guidelines from the Endocrine Society concerning the management of thyroid disorders during pregnancy have been published, one year after the guidelines published by the American Thyroid Association. Iodine deficiency in France can increase the development of thyroid disorders during pregnancy. Hypothyroidism during pregnancy must be correctly substituted to avoid fetal complications. Maternal hyperthyroidism should be explored and monitored following a specific defined modality to discuss the necessity of a treatment and to prevent maternal and fetal complications. In case of thyroid nodes or cancer, the follow-up will not differ from non-pregnant women. However in most of cases, involvement of a multidisciplinay team might be necessary. PMID:25194220

  8. Autoimmunity against thyroid hormones.

    PubMed

    Sakata, S

    1994-01-01

    The presence of thyroid hormone autoantibodies (THAA) is a common phenomenon. More than 270 cases have been reported by the end of 1993 involving not only thyroidal but also nonthyroidal disorders. Clinically, THAA in a patient's serum produces variation in thyroid hormone metabolism and, in particular, may interfere with the radioimmunoassay (RIA) results of total or free thyroid hormone measurements, which can cause unusually high or low values of the hormones depending on the B/F separation method used. This in vitro interference can give clinicians confusing information about the patient's thyroid state. As a result, the patient may receive inappropriate treatment from physicians who are unaware of this disorder. The presence of THAA has been reported not only in humans but also in dogs, chickens, and rats. In this review article, clinical features of THAA and the mechanism of autoantibody production are discussed. PMID:7535535

  9. [Osteoporosis in thyroid diseases].

    PubMed

    Kosińska, Agnieszka; Syrenicz, Anhelli; Kosiński, Bogusław; Garanty-Bogacka, Barbara; Syrenicz, Małgorzata; Gromniak, Elwira

    2005-01-01

    Thyroid hormones play the essential role in the regulation of metabolism and bone remodeling in physiological conditions and in the course of thyroid dysfunction. Introduction of densitometry to the diagnostics of osteoporosis has made possible the evaluation of influence of both hyperthyroidism and hypothyroidism and their treatment on bone mineral density. Moreover it became possible to estimate the influence of treatment with exogenous thyroid hormones on the skeletal system. Authors presented mechanisms of the thyroid hormones action on bone tissue and analysed current state of knowledge concerning the influence of the thyroxine treatment with replacement and suppressive doses on the bone mineral density. The influence of thyroid hormones on the skeletal system with respect to premenopausal and postmenopausal period was also discussed. Great discrepancies in literature data and its reasons were underlined. PMID:16335687

  10. Mutation Profile of Well-Differentiated Thyroid Cancer in Asians

    PubMed Central

    Song, Young Shin; Lim, Jung Ah

    2015-01-01

    Recent advances in molecular diagnostics have led to significant insights into the genetic basis of thyroid tumorigenesis. Among the mutations commonly seen in thyroid cancers, the vast majority are associated with the mitogen-activated protein kinase pathway. B-Raf proto-oncogene (BRAF) mutations are the most common mutations observed in papillary thyroid cancers (PTCs), followed by RET/PTC rearrangements and RAS mutations, while follicular thyroid cancers are more likely to harbor RAS mutations or PAX8/peroxisome proliferator-activated receptor γ (PPARγ) rearrangements. Beyond these more common mutations, alterations in the telomerase reverse transcriptase (TERT) promoter have recently been associated with clinicopathologic features, disease prognosis, and tumorigenesis in thyroid cancer. While the mutations underlying thyroid tumorigenesis are well known, the frequency of these mutations is strongly associated with geography, with clear differences reported between Asian and Western countries. Of particular interest is the prevalence of BRAF mutations, with Korean patients exhibiting the highest rate of BRAF-associated thyroid cancers in the world. Here, we review the prevalence of each of the most common mutations in Asian and Western countries, and identify the characteristics of well-differentiated thyroid cancer in Asians. PMID:26435130

  11. The Role of Thyroid Hormone in Testicular Development and Function

    PubMed Central

    Wagner, Márcia Santos; Wajner, Simone Magagnin; Maia, Ana Luiza

    2009-01-01

    Thyroid hormone is a critical regulator of growth, development and metabolism in virtually all tissues, and altered thyroid status affects many organs and systems. Although for many years testis has been regarded as a thyroid hormone unresponsive organ, it is now evident that thyroid hormone plays an important role in testicular development and function. A considerable amount of data shows that thyroid hormone influences steroidogenesis as well as spermatogenesis. The involvement of triiodothyronine (T3) in the control of Sertoli cell proliferation and functional maturation is widely accepted, as well as its role in postnatal Leydig cell differentiation and steroidogenesis. The presence of thyroid hormone receptors in testicular cells throughout development and in adulthood implies that T3 may act directly on these cells to bring about its effects. Several recent studies have employed different methodologies and techniques in an attempt to understand the mechanisms underlying thyroid hormone effects on testicular cells. The current review aims at presenting an updated picture of the recent advances made regarding the role of thyroid hormones in male gonadal function. PMID:18728126

  12. Correlation of normal thyroid ultrasonography with thyroid tests

    PubMed Central

    Kaya, Cafer; Üçler, Rıfkı; Dirikoç, Ahmet; Ersoy, Reyhan; Çakır, Bekir

    2015-01-01

    Background Thyroid disorders are frequently seen in the community. Thyroid ultrasonography (US) is commonly used in the diagnosis of thyroid diseases. The relationship between heterogeneous echogenicity of thyroid gland and thyroid tests are well known. Methods The aim of this study is to evaluate the correlation of normal US with the thyroid tests. A total of 681 individuals were enrolled in the study. Individuals were separated into two groups as normal (group 1) and hypoechoic (group 2) according to the echogenicity in US. Subjects with nodular thyroid lesions were excluded from the study. Thyroid stimulating hormone (TSH), free T4 (fT4), thyroid peroxidase antibody (TPOAb) and anti-thyroglobulin antibody (TgAb) values were recorded in both groups and thyroid stimulating hormone receptor antibody (TRAb) was recorded in individuals with low TSH. Results 86.1% of individuals in group 1 had normal TSH, 93.7% had normal thyroid antibodies and in 77.6% of individuals, all thyroid tests performed were normal. In the 6.9% of the group 2, all reviewed thyroid tests were normal (P<0.001). Conclusions Our study shows that US is correlated with normal thyroid function tests and is a valuable tool in the prediction of normal thyroid function. PMID:26435920

  13. Thyroid cancer detected by ultrasound-guided fine-needle aspiration biopsy.

    PubMed

    Yokozawa, T; Fukata, S; Kuma, K; Matsuzuka, F; Kobayashi, A; Hirai, K; Miyauchi, A; Sugawara, M

    1996-09-01

    A greater percentage of thyroid cancers can be detected by ultrasound-guided fine-needle aspiration biopsy (UG-FNAB) than by ordinary FNAB. A group of 678 patients were selected sequentially as having been diagnosed with benign nodules by the conventional FNAB method. We reexamined these patients by UG-FNAB and investigated the types of thyroid cancer that were missed by the conventional FNAB. Of the 678 patients diagnosed with benign nodules (using conventional FNAB), 571 (84.2%) demonstrated the same diagnosis when UG-FNAB was used. The remaining 107 patients (15.8%) studied were suspected of having a malignancy after UG-FNAB had been performed. Surgical specimen histology proved thyroid cancer in 99 of the 107 patients: 93 had papillary carcinoma, 4 had follicular carcinoma, 1 had medullary carcinoma and 1 had anaplastic carcinoma. Two drawbacks were noted when conventional FNAB was used: (1) cancer lesions difficult to palpate (n = 55) (e.g., small cancers with or without benign lesions or cancers associated with Hashimoto's thyroiditis or Graves' disease); and (2) palpable cancers with insufficient cell material for analysis (n = 44) (e.g., cystic carcinoma and cancers with calcified lesions. UG-FNAB is a powerful technique for detecting microcancers, cystic carcinomas, cancers associated with benign nodules, Hashimoto's thyroiditis, or coarse calcifications. PMID:8678961

  14. Pediatric thyroid disease: when is surgery necessary, and who should be operating on our children?

    PubMed

    Breuer, Christopher; Tuggle, Charles; Solomon, Daniel; Sosa, Julie Ann

    2013-01-01

    Surgical diseases of the thyroid in the pediatric population represent a diverse set of both benign and malignant conditions. Overall, incidence is rare. Benign conditions include Graves' disease, toxic adenomas, congenital hyperthyroidism, and goiter. Differentiated thyroid cancer (DTC) and medullary thyroid carcinoma (MTC), with its related familial cancer syndromes, are the most common malignancies. Near-total or total thyroidectomy is the appropriate surgery for thyroid cancer, with/out central lymph node dissection. Emerging practice guidelines from professional societies are helpful, although they generally have not addressed surgical management of the pediatric patient. Thyroidectomy in children is associated with a higher rate of complications, such as recurrent laryngeal nerve injury and hypoparathyroidism, as compared to the surgery in adults. Therefore, it is essential that pediatric thyroidectomy be performed by high-volume thyroid surgeons, regardless of specialty. Case volume to support surgical expertise usually must be borrowed from the adult experience, given the relative paucity of pediatric thyroidectomies at an institutional level. These surgeons should work as part of a multidisciplinary team that includes pediatric endocrinologists and anesthesiologists, pediatricians, nuclear medicine physicians, and pathologists to afford children the best clinical outcomes. PMID:23149389

  15. Association of RET codon 691 polymorphism in radiation-induced human thyroid tumours with C-cell hyperplasia in peritumoural tissue

    PubMed Central

    Bounacer, A; Du Villard, J A; Wicker, R; Caillou, B; Schlumberger, M; Sarasin, A; Suárez, H G

    2002-01-01

    The RET proto-oncogene encodes a protein structurally related to transmembrane receptors with an intracellular tyrosine kinase domain. In human thyroid gland, the RET proto-oncogene is normally expressed in parafollicular C-cells. Thyroid C-cell hyperplasia is associated with inherited medullary thyroid carcinomas and is considered as a pre-neoplastic stage of C-cells disease. It has also been observed in thyroid tissues adjacent to follicular and papillary carcinomas. In order to study the relationship between a misfunctioning of the RET proto-oncogene and the presence of C-cell hyperplasia, we compared a series of thyroid glands presenting sporadic or radiation-associated tumours, as well as samples of unrelated normal thyroid tissues, for alteration in exons 10 and 11 of the gene and for the presence or absence of C-cell hyperplasia. Here we report a significantly higher frequency of C-cell hyperplasia present in peritumoural thyroid tissues of radiation-induced epithelial thyroid tumours, than in peritumoural of sporadic thyroid tumours or in control normal thyroid tissues (P=0.001). A G691S RET polymorphism was present with a higher frequency in radiation-induced epithelial thyroid tumours (55%) than in sporadic tumours (20%) and in control normal thyroid tissues (15%). Interestingly, this polymorphism was associated in the majority (88%) of radiation-induced tumours with a C-cell hyperplasia in the peritumoural tissues. Several explanations for this association are discussed. British Journal of Cancer (2002) 86, 1929–1936. doi:10.1038/sj.bjc.6600371 www.bjcancer.com © 2002 Cancer Research UK PMID:12085189

  16. Thyroid diseases in elderly.

    PubMed

    Faggiano, A; Del Prete, M; Marciello, F; Marotta, V; Ramundo, V; Colao, A

    2011-09-01

    Thyroid diseases are the commonest endocrine disorders in the general population. In most of the cases, they are consistent with benign conditions which may be asymptomatic or affect people at a variable extent. Since they often represent chronic conditions their prevalence increases by age and reaches in elderly the highest rates. Thyroid nodules are a common clinical finding. Most subjects with thyroid nodules have few or no symptoms. Thyroid nodules are more commonly non-functioning. However, in elderly, toxic multinodular goiter is the most frequent cause of spontaneous hyperthyroidism and often, it emerges insidiously from nontoxic multinodular goiter. Although autoimmune thyroiditis is the most common cause of hypothyroidism in elderly subjects, other causes, such as drugs, neck radiotherapy, thyroidectomy or radioiodine therapy, are frequently observed among these subjects. A small subset of medications including dopamine agonists, glucocorticoids and somatostatin analogs affect thyroid function through suppression of TSH. Other medications that may affect TSH levels are metformin, antiepileptic medications, lithium carbonate and iodine-containing medications. Other drugs can alter T4 absorption, T4 and T3 transport in serum and metabolism of T4 and T3, such as proton-pump inhibitors and antacids, estrogens, mitotane and fluorouracil, phenobarbital and rifampin. Amiodarone administration is associated with thyrotoxicosis or hypothyroidism. Thyroid cancer has similar characteristics in elderly as in general population, however the rate of aggressive forms such as the anaplastic histotype, is higher in older than younger subjects. Diagnosis of thyroid diseases includes a comprehensive medical history and physical examination and appropriate laboratory tests. A correct diagnosis of thyroid diseases in the elderly is crucial for proper treatment, which consists in the removal of medications that may alter thyroid function, in the use of levo-thyroxine in case of

  17. Total lymphoid irradiation leads to transient depletion of the mouse thymic medulla and persistent abnormalities among medullary stromal cells

    SciTech Connect

    Adkins, B.; Gandour, D.; Strober, S.; Weissman, I.

    1988-05-15

    Mice given multiple doses of sublethal irradiation to both the thymus and the peripheral lymphoid tissues showed major transient, and some persistent disruptions in general thymic architecture and in thymic stromal components. At 2 wk after total lymphoid irradiation (TLI), the thymus lacked identifiable medullary regions by immunohistochemical analyses. Medullary stromal cells expression MHC Ag or a medullary epithelial cell Ag, as well as medullary macrophages, were undetectable. Instead, the processes of cortical epithelial cells were observed throughout the entire thymus. Strikingly, thymocyte subsets with mature phenotypes (CD4+CD8- and CD4-CD8+) were present in the apparent absence of a medulla. This early, gross effect was rapidly reversed such that by 1 to 2 mo after TLI, medullary areas with MHC Ag-positive cells were evident. However, abnormalities in a subset of medullary stromal cells appeared to be more persistent. Medullary epithelial cells, identified by the MD1 mAb, were greatly reduced in number and abnormally organized for at least 4 mo after TLI. In addition, macrophages containing endogenous peroxidase activity, normally abundant in medullary regions, were undetectable at all times examined after TLI. Therefore, this irradiation regimen induced both transient and long term effects in the thymus, primarily in medullary regions. These results suggest that TLI may be used as an experimental tool for studying the impact of selective depletion of medullary stromal cells on the development of specific T cell functions.

  18. Fatal pulmonary embolization after reaming of the femoral medullary cavity in sclerosing osteomyelitis: a case report.

    PubMed

    Pape, H C; Krettek, C; Maschek, H; Regel, G; Tscherne, H

    1996-01-01

    Reaming of the medullary may be used in cases of sclerosing osteomyelitis (type Garré), refractory to other methods. We report a case of fatal intraoperative complication related to this procedure. An otherwise healthy young patient died during reaming using a machine-driven reamer of the femoral medullary canal due to pulmonary bone embolism. The technique and the indication for this procedure as well as the intraoperative monitoring options are discussed. PMID:8854322

  19. Reactive oxygen species as important determinants of medullary flow, sodium excretion, and hypertension

    PubMed Central

    Abe, Michiaki; Mori, Takefumi; O'Connor, Paul M.; Ohsaki, Yusuke; Zheleznova, Nadezhda N.

    2014-01-01

    The physiological evidence linking the production of superoxide, hydrogen peroxide, and nitric oxide in the renal medullary thick ascending limb of Henle (mTAL) to regulation of medullary blood flow, sodium homeostasis, and long-term control of blood pressure is summarized in this review. Data obtained largely from rats indicate that experimentally induced elevations of either superoxide or hydrogen peroxide in the renal medulla result in reduction of medullary blood flow, enhanced Na+ reabsorption, and hypertension. A shift in the redox balance between nitric oxide and reactive oxygen species (ROS) is found to occur naturally in the Dahl salt-sensitive (SS) rat model, where selective reduction of ROS production in the renal medulla reduces salt-induced hypertension. Excess medullary production of ROS in SS rats emanates from the medullary thick ascending limbs of Henle [from both the mitochondria and membrane NAD(P)H oxidases] in response to increased delivery and reabsorption of excess sodium and water. There is evidence that ROS and perhaps other mediators such as ATP diffuse from the mTAL to surrounding vasa recta capillaries, resulting in medullary ischemia, which thereby contributes to hypertension. PMID:25354941

  20. Thyroid Hormone and Cardioprotection.

    PubMed

    Gerdes, Anthony Martin; Ojamaa, Kaie

    2016-01-01

    The heart is a major target of thyroid hormones, with maintenance of euthyroid hormone balance critical for proper function. In particular, chronic low thyroid function can eventually lead to dilated heart failure with impaired coronary blood flow. New evidence also suggests that heart diseases trigger a reduction in cardiac tissue thyroid hormone levels, a condition that may not be detectible using serum hormone assays. Many animal and clinical studies have demonstrated a high prevalence of low thyroid function in heart diseases with worse outcomes from this condition. Animal and human studies have also demonstrated many benefits from thyroid hormone treatment of heart diseases, particularly heart failure. Nonetheless, this potential treatment has not yet translated to patients due to a number of important concerns. The most serious concern involves the potential of accidental overdose leading to increased arrhythmias and sudden death. Several important clinical studies, which actually used excessive doses of thyroid hormone analogs, have played a major role in convincing the medical community that thyroid hormones are simply too dangerous to be considered for treatment in cardiac patients. Nonetheless, this issue has not gone away due primarily to overwhelmingly positive evidence for treatment benefits and a new understanding of the cellular and molecular mechanisms underlying those benefits. This review will first discuss the clinical evidence for the use of thyroid hormones as a cardioprotective agent and then provide an overview of the cellular and molecular mechanisms underlying beneficial changes from thyroid hormone treatment of heart diseases. © 2016 American Physiological Society. Compr Physiol 6:1199-1219, 2016. PMID:27347890

  1. Cementless porous-coated anatomic medullary locking total hip prostheses.

    PubMed

    Kim, Y H; Kim, V E

    1994-06-01

    The authors studied 50 consecutive and nonselected patients (52 hips) who were followed for a minimum of 7 years (range, 84-89 months) after they had a primary total hip arthroplasty with an uncemented Anatomic Medullary Locking (DePuy, Warsaw, IN) hip system. The average age of the patients at operation was 47.6 years (range, 19-88 years). The operative diagnoses were: avascular necrosis of the femoral head in 18 hips (34%), osteoarthritis in 16 (31%), fracture of the femoral neck in 14 (27%), and miscellaneous in 4 (8%). The average preoperative Harris hip score was 59 points (range, 6-67 points) that improved to 91 points (range, 69-100 points) at the 7-year follow-up examination. To assess the adequacy of intramedullary fit, the fit of the stem at the proximal canal and isthmus level was evaluated. Forty-one hips (79%) had a good press-fit at both the proximal canal and isthmus level, five hips (10%) had a good press-fit at the proximal canal only, and the remaining six hips (11%) had a poor fit at both the proximal canal and isthmus level. Of the 46 hips that had a good press-fit at the proximal canal and/or isthmus level or proximal canal only, 32 (70%) had bone ingrowth and 14 (30%) had stable fibrous tissue ingrowth. Of the remaining six hips with a poor press-fit at both the proximal canal and isthmus level, three (6%) had stable fibrous tissue ingrowth and another three (6%) were unstable. Of the three hips (6%) with femoral component loosening, one was revised and the other two were asymptomatic. There was an alarmingly high incidence of perioprosthetic osteolysis in our series: 16 hips (31%) had acetabular and femoral osteolysis and 13 hips (25%) had femoral osteolysis only. Also, there was a strikingly high incidence of polyethylene-liner wear (12 hips or 23%). Although the incidence of component loosening was low, a high incidence of periprosthetic osteolysis and excessive wear in the polyethylene linear remain challenging problems after insertion of

  2. Dynamical model for thyroid

    NASA Astrophysics Data System (ADS)

    Rokni Lamooki, Gholam Reza; Shirazi, Amir H.; Mani, Ali R.

    2015-05-01

    Thyroid's main chemical reactions are employed to develop a mathematical model. The presented model is based on differential equations where their dynamics reflects many aspects of thyroid's behavior. Our main focus here is the well known, but not well understood, phenomenon so called as Wolff-Chaikoff effect. It is shown that the inhibitory effect of intake iodide on the rate of one single enzyme causes a similar effect as Wolff-Chaikoff. Besides this issue, the presented model is capable of revealing other complex phenomena of thyroid hormones homeostasis.

  3. Thyroid function and obesity.

    PubMed

    Longhi, Silvia; Radetti, Giorgio

    2013-01-01

    Nowadays, childhood obesity is one of the biggest health emergencies in the developed countries. Obesity leads to multiple metabolic alterations which increase the risk of developing diabetes and cardiovascular diseases. Thyroid function has been often described as altered in obese children, however, it is not clear whether the altered thyroid function is the cause or the consequence of fat excess. On the other hand, thyroid structure seems also to be affected. Nevertheless, both functional and structural alterations seem to improve after weight loss and therefore no treatment is needed. PMID:23149391

  4. Transoral robotic thyroid surgery

    PubMed Central

    Clark, James H.; Kim, Hoon Yub

    2015-01-01

    There is currently significant demand for minimally invasive thyroid surgery; however the majority of proposed surgical approaches necessitate a compromise between minimal tissue dissection with a visible cervical scar or extensive tissue dissection with a remote, hidden scar. The development of transoral endoscopic thyroid surgery however provides an approach which is truly minimally invasive, as it conceals the incision within the oral cavity without significantly increasing the amount of required dissection. The transoral endoscopic approach however presents multiple technical challenges, which could be overcome with the incorporation of a robotic operating system. This manuscript summarizes the literature on the feasibility and current clinical experience with transoral robotic thyroid surgery. PMID:26425456

  5. Destabilizing RET in targeted treatment of thyroid cancers

    PubMed Central

    Gild, M L; Bullock, M; Pon, C K; Robinson, B G; Clifton-Bligh, R J

    2015-01-01

    Metastatic differentiated thyroid cancers (DTC) are resistant to traditional chemotherapy. Kinase inhibitors have shown promise in patients with progressive DTC, but dose-limiting toxicity is commonplace. HSP90 regulates protein degradation of several growth-mediating kinases such as RET, and we hypothesized that HSP90 inhibitor (AUY922) could inhibit RET-mediated medullary thyroid cancer (MTC) as well as papillary thyroid cancer (PTC) cell growth and also radioactive iodine uptake by PTC cells. Studies utilized MTC cell lines TT (C634W) and MZ-CRC-1 (M918T) and the PTC cell line TPC-1 (RET/PTC1). Cell viability was assessed with MTS assays and apoptosis by flow cytometry. Signaling target expression was determined by western blot and radioiodine uptake measured with a gamma counter. Prolonged treatment of both MTC cell lines with AUY922 simultaneously inhibited both MAPK and mTOR pathways and significantly induced apoptosis (58.7 and 78.7% reduction in MZ-CRC-1 and TT live cells respectively, following 1 μM AUY922; P<0.02). Similarly in the PTC cell line, growth and signaling targets were inhibited, and also a 2.84-fold increase in radioiodine uptake was observed following AUY922 administration (P=0.015). AUY922 demonstrates in vitro activity against MTC and PTC cell lines. We observed a potent dose-dependent increase in apoptosis in MTC cell lines following drug administration confirming its anti-tumorigenic effects. Western blots confirm inhibition of pro-survival proteins including AKT suggesting this as the mechanism of cell death. In a functional study, we observed an increase in radioiodine uptake in the PTC cell line following AUY922 treatment. We believe HSP90 inhibition could be a viable alternative for treatment of RET-driven chemo-resistant thyroid cancers. PMID:26574568

  6. TSH (Thyroid-Stimulating Hormone) Test

    MedlinePlus

    ... symptoms of a thyroid disorder , including hyperthyroidism or hypothyroidism . TSH is produced by the pituitary gland , a ... thyroid Monitor thyroid replacement therapy in people with hypothyroidism Monitor anti-thyroid treatment in people with hyperthyroidism ...

  7. Medullary carcinoma of the colon: a distinct morphology reveals a distinctive immunoregulatory microenvironment.

    PubMed

    Friedman, Kenneth; Brodsky, Alexander S; Lu, Shaolei; Wood, Stephanie; Gill, Anthony J; Lombardo, Kara; Yang, Dongfang; Resnick, Murray B

    2016-05-01

    Medullary carcinoma of the colon is a unique histologic subtype of microsatellite unstable colorectal carcinoma but little is known regarding its tumor-immunoregulatory microenvironment. The aims of this study were to characterize the immune environment of medullary carcinoma and compare it with other microsatellite unstable and microsatellite stable colorectal carcinomas. An initial gene expression microarray analysis of six cases of medullary carcinoma was used to detect potentially differentially expressed genes. We extended this analysis utilizing genomic data from the Cancer Genome Atlas to compare eight cases of medullary carcinoma with other microsatellite unstable and stable carcinomas. Finally, we evaluated expression of key immune pathway proteins and lymphocyte subsets via immunohistochemistry of a large group of medullary carcinomas (n=105) and compared these findings with three other groups: poorly differentiated, microsatellite unstable well-differentiated and microsatellite stable well-differentiated carcinomas. Microarray and the Cancer Genome Atlas data analysis identified significant upregulation of several immunoregulatory genes induced by IFNγ including IDO-1, WARS (tRNA(trp)), GBP1, GBP4, GBP5, PDCD1 (PD-1), and CD274 (PD-L1) in medullary carcinoma compared with other microsatellite unstable and microsatellite stable tumors. By immunohistochemistry, IDO-1 was expressed in 64% of medullary carcinomas compared with 19% (9/47) of poorly differentiated carcinomas, 14% (3/22) of microsatellite unstable, and 7% (2/30) of the microsatellite stable well-differentiated carcinomas (P<0.0001). tRNA(trp) was overexpressed in 81% (84/104) of medullary carcinomas, 19% (9/47) of poorly differentiated, 32% (7/22) of microsatellite unstable, and 3% (1/30) of microsatellite stable well-differentiated carcinomas (P<0.0001). Medullary carcinoma had higher mean CD8+ and PD-L1+ tumor-infiltrating lymphocytes compared with all other groups (P<0.0001). This study

  8. Incidental and non-incidental thyroid microcarcinoma

    PubMed Central

    KALISZEWSKI, KRZYSZTOF; WOJTCZAK, BEATA; STRUTYŃSKA-KARPIŃSKA, MARTA; ŁUKIEŃCZUK, TADEUSZ; FORKASIEWICZ, ZDZISŁAW; DOMOSŁAWSKI, PAWEŁ

    2016-01-01

    There is no clear therapeutic approach for thyroid microcarcinoma (TMC). This may be as a consequence of recent observations that have reported biologically different types of TMC, which should be treated differently. The objective of the present study was to compare incidental TMC (ITMC) and non-incidental TMC (NITMC) in order to assess the differences in the incidence, diagnostic results, clinicopathological characteristics and surgical treatment. The study consisted of a retrospective chart review of 3,218 patients consecutively admitted and surgically treated in a single institution due to thyroid pathology. A total of 246 (7.64%) patients presented with a thyroid malignancy, and 97 (39.43%) of these individuals were diagnosed with TMC; 37 (38.14%) patients exhibited ITMC and 60 (61.86%) exhibited NITMC. All 37 (100.00%) patients with ITMC exhibited a papillary type of cancer. In the NITMC group, 1 (1.67%) patient presented with follicular microcarcinoma, 1 (1.67%) individual with papillary- and follicular-type microcarcinoma, 1 (1.67%) individual with medullary microcarcinoma, and the remaining 57 (95.00%) patients presented with papillary microcarcinoma. The number of younger patients (<45 years old) was higher in the NITMC group, but this difference was not significant (P=0.205). In all patients with ITMC, ultrasound-guided fine-needle aspiration biopsy did not reveal malignant processes. In the NITMC group, the number of larger tumors (>5 mm) was significantly higher compared with that in the ITMC group (P<0.001). ITMC was significantly associated with multinodular goiter (MNG) (P<0.001). Amongst the NITMC group, 18.33% of patients presented with cervical lymph node involvement (P<0.001). Overall, the incidence of TMC is high, and consists of ITMC and NITMC, although the prevalence of NITMC is higher than that of ITMC. The majority of ITMCs and NITMCs are composed of a papillary type of cancer. The majority of ITMCs have dimensions ≤5 mm in diameter and

  9. Differential O-glycosylation in cortical and medullary thymocytes.

    PubMed

    Alvarez, Georgina; Lascurain, Ricardo; Hernández-Cruz, Pedro; Tetaert, Daniel; Degand, Pierre; Gorocica, Patricia; Espinosa, Blanca; Zenteno, Edgar; Chávez, Raúl

    2006-08-01

    Differentiation of T lymphocytes is characterized by variable expression of CD8/CD4 co-receptor molecules and changes in the glycosylation pattern. In this work, O-glycosylation was analyzed in microsomes from murine thymocytes purified with the PNA and Amaranthus leucocarpus (ALL) lectins, specific for the T antigen (Gal beta1,3GalNAc1,0 Ser/Thr) in cortical and medullary thymocytes, respectively. Three peptides were used as acceptors for UDP-N-acetylgalactosamine: polypeptide N-acetylgalactosaminyl-transferase (GalNAc transferase); the peptide motif TTSAPTTS was the best glycosylated one. Cortical ALL-PNA+ thymocytes showed two-fold higher GalNAc transferase activity than ALL+PNA- thymocytes; however, capillary electrophoresis showed a higher proportion of di- versus mono-glycosylated peptides for ALL+PNA- than for ALL-PNA+. We compared the GalNAc transferase activity of thymocytes from dexamethasone-treated mice versus control mice. GalNAc transferase activity was six-fold higher in thymocytes from control mice than from dexamethasone-treated mice; the rate of di-glycosylated peptides for dexamethosone-resistant ALL+ was two-fold higher than for ALL- thymocytes. Our results confirm an upregulated biosynthesis of O-glycosidically linked glycans on T cell surface glycoproteins, and suggest that the modification of GalNAc transferase activity plays a relevant role during the maturation process of thymic cells. PMID:16762509

  10. Hormonal regulation of medullary bone metabolism in the laying hen

    SciTech Connect

    Harrison, J.R.

    1987-01-01

    A new organ culture system for the study of bone formation has been developed using medullary bone, a non-structural, metabolically active form of bone which is found in the marrow cavities of egg-laying birds. In the presence of fetal calf serum, bone explants were viable in culture by morphological criteria, and retained large numbers of osteoblasts and osteoclasts. Incorporation of /sup 3/H-proline into collagenase-digestible protein (CDP) and non-collagen protein (NCP) was determined using purified bacterial collagenase. Collagen accounted for over 10% of the total protein labeled. The calcium-regulating hormones, parathyroid hormone and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), caused a dose-dependent inhibition of /sup 3/H-proline incorporation into CDP. The effective dose range of 1,25(OH)2D3 was 0.1 nM to 100 nM, while that of PTH was 1.0 nM to 100 nM. The effect of both hormones was specific for collagen, since /sup 3/H-proline incorporation into NCP was unaffected. Hydroxyproline analysis of bone explants and culture medium revealed that both hormones decreased the total hydroxyroline content of the cultures, suggesting that the inhibition of /sup 3/H-proline incorporation into DCP is due to inhibition of collagen synthesis.

  11. [Postpartum thyroiditis. A review].

    PubMed

    Hurtado-Hernández, Z; Segura-Domínguez, A

    2013-01-01

    Postpartum thyroiditis (PPT) is a transient thyroid dysfunction of autoimmune origin that can occur in the first year postpartum in women who have not been previously diagnosed with thyroid disease. It may start with clinical thyrotoxicosis followed by hypothyroidism and the subsequent recovery of thyroid function, or may just appear as isolated thyrotoxicosis or hypothyroidism. PPT recurs in high percentage of patients after subsequent pregnancies. Many women develop permanent hypothyroidism sometime during the 3 to 10 year period after an episode of PPT. It is important for family physicians to be familiar with this disease, due to its high prevalence in order to make a correct diagnosis and therapeutic intervention. Family doctors also play a crucial role in the monitoring of these patients, given the negative implications of established hypothyroidism on reproduction in the female population during their reproductive years. This article reviews the principle characteristics of PPT along with its diagnosis and treatment. PMID:23834978

  12. Thyroid Disease (for Parents)

    MedlinePlus

    ... change over just a few months. previous continue 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 ...

  13. Thyroid Disease and Teens

    MedlinePlus

    ... change over just a few months. previous continue 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 ...

  14. Thyroid cancer - papillary carcinoma

    MedlinePlus

    ... some noncancerous childhood conditions Radiation exposure from nuclear plant disasters Radiation given through a vein (through an IV) during medical tests and treatments does not increase the risk of developing thyroid cancer.

  15. Idiopathic thyroid abscess

    PubMed Central

    Cawich, Shamir O.; Hassranah, Dale; Naraynsingh, Vijay

    2014-01-01

    INTRODUCTION Thyroid abscesses are uncommon because the gland is relatively resistant to developing infection due to its rich blood supply, well-developed capsule and high iodine content. However, clinicians must be aware of this differential to make an early diagnosis. PRESENTATION OF CASE We present the case of a patient who required urgent operative resection as definitive treatment for a thyroid abscess secondary to infection with Staphylococcus aureus. DISCUSSION Although this is rare, a thyroid abscess left untreated can lead to serious morbidity. Therefore, clinicians must be aware of the presenting features and therapeutic options. CONCLUSION Thyroid abscess is an uncommon diagnosis but can lead to significant morbidity. Therefore clinicians must be aware of the diagnosis in order to institute early aggressive management. PMID:24981167

  16. American Thyroid Association

    MedlinePlus

    ... learn more Meetings ATA meeting dates, information, and education. learn more Publications Thyroid, Clinical Thyroidology and VideoEndocrinology. ... learn more DEDICATED TO SCIENTIFIC INQUIRY, CLINICAL EXCELLENCE, EDUCATION AND COLLABORATION August 23, 2016 10 Clinical Thyroidology ...

  17. Pediatric Thyroid Cancer

    MedlinePlus

    ... isthmus). The thyroid secretes three main hormones: 1) Thyroxine, that contains iodine, needed for growth and metabolism; ... also contains iodine and similar in function to Thyroxine; and 3) Calcitonin, which decreases the concentration of ...

  18. Thyroid cancer - papillary carcinoma

    MedlinePlus

    ... non-cancerous childhood conditions Radiation exposure from nuclear plant disasters Radiation given through a vein (through an IV) during medical tests and treatments does not increase the risk of developing thyroid cancer.

  19. AZD1480 blocks growth and tumorigenesis of RET- activated thyroid cancer cell lines.

    PubMed

    Couto, Joana P; Almeida, Ana; Daly, Laura; Sobrinho-Simões, Manuel; Bromberg, Jacqueline F; Soares, Paula

    2012-01-01

    Persistent RET activation is a frequent event in papillary thyroid carcinoma (PTC) and medullary thyroid carcinoma (MTC). In these cancers, RET activates the ERK/MAPK, the PI3K/AKT/mTOR and the JAK/STAT3 pathways. Here, we tested the efficacy of a JAK1/2- inhibitor, AZD1480, in the in vitro and in vivo growth of thyroid cancer cell lines expressing oncogenic RET. Thyroid cancer cell lines harboring RET/PTC1 (TPC-1), RET M918T (MZ-CRC1) and RET C634W (TT) alterations, as well as TPC-1 xenografts, were treated with JAK inhibitor, AZD1480. This inhibitor led to growth inhibition and/or apoptosis of the thyroid cancer cell lines in vitro, as well as to tumor regression of TPC-1 xenografts, where it efficiently blocked STAT3 activation in tumor and stromal cells. This inhibition was associated with decreased proliferation, decreased blood vessel density, coupled with increased necrosis. However, AZD1480 repressed the growth of STAT3- deficient TPC-1 cells in vitro and in vivo, demonstrating that its effects in this cell line were independent of STAT3 in the tumor cells. In all cell lines, the JAK inhibitor reduced phospho-Y1062 RET levels, and mTOR effector phospho-S6, while JAK1/2 downregulation by siRNA did not affect cell growth nor RET and S6 activation. In conclusion, AZD1480 effectively blocks proliferation and tumor growth of activated RET- thyroid cancer cell lines, likely through direct RET inhibition in cancer cells as well as by modulation of the microenvironment (e.g. via JAK/phospho-STAT3 inhibition in endothelial cells). Thus, AZD1480 should be considered as a therapeutic agent for the treatment of RET- activated thyroid cancers. PMID:23056499

  20. Hashimoto's thyroiditis following Graves' disease.

    PubMed

    Umar, Husaini; Muallima, Nur; Adam, John M F; Sanusi, Harsinen

    2010-01-01

    Both Graves' disease and chronic thyroiditis (Hashimoto's thyroiditis) are autoimmune diseases of thyroid gland. Graves' disease is caused by stimulation of TSH receptor located on the thyroid gland by an antibody, which is known as TSH receptor antibody (TRAb). Furthermore, this may lead to hyperplasia and hyperfunction of the thyroid gland. On the contrary, the cause of Hashimoto's thyroiditis is thought due to a TSH stimulation-blocking antibody (TSBAb) which blocks the action of TSH hormone and subsequently brings damage and atrophy to thyroid gland. Approximately 15-20% of patients with Graves' disease had been reported to have spontaneous hypothyroidism resulting from the chronic thyroiditis (Hashimoto's disease). Pathogenesis for chronic thyroiditis following anti-thyroid drug treatment in patients with Graves' disease remains unclear. It has been estimated that chronic thyroiditis or Hashimoto's disease, which occurs following the Graves' disease episode is due to extended immune response in Graves' disease. It includes the immune response to endogenous thyroid antigens, i.e. thyroid peroxidase and thyroglobulin, which may enhance lymphocyte infiltration and finally causes Hashimoto's thyroiditis. We report four cases of chronic thyroiditis (Hashimoto's disease) in patients who have been previously diagnosed with Graves' hyperthyroidism. In three cases, Hashimoto's thyroiditis occurs in 7 to 25 years after the treatment of Grave's disease; while the other case has it only after few months of Grave's disease treatment. The diagnosis of Hashimoto's disease (chronic thyroiditis) was based on clinical manifestation, high TSHs level, positive thyroid peroxidase antibody and thyroglobulin antibody, and supported by positive results of fine needle aspiration biopsy. Moreover, the result of histopathological test has also confirmed the diagnosis in two cases. All cases have been successfully treated by levothyroxine treatment. PMID:20305330

  1. Thyroid function and postmenopause.

    PubMed

    Schindler, A E

    2003-02-01

    There is an increasing prevalence of high levels of thyroid stimulating hormone (TSH) with age - particularly in postmenopausal women - which are higher than in men. The incidence of thyroid disease in a population of postmenopausal women is as follows: clinical thyroid disease, about 2.4%; subclinical thyroid disease, about 23.2%. Among the group with subclinical thyroid disease, 73.8% are hypothyroid and 26.2% are hyperthyroid. The rate of thyroid cancer increases with age. The symptoms of thyroid disease can be similar to postmenopausal complaints and are clinically difficult to differentiate. There can also be an absence of clinical symptoms. It is of importance that even mild thyroid failure can have a number of clinical effects such as depression, memory loss, cognitive impairment and a variety of neuromuscular complaints. Myocardial function has been found to be subtly impaired. There is also an increased cardiovascular risk, caused by increased serum total cholesterol and low-density lipoprotein cholesterol as well as reduced levels of high-density lipoprotein. These adverse effects can be improved or corrected by L-thyroxine replacement therapy. Such treatment has been found to be cost-effective. With time, overt hypothyroidism can develop. Therefore, routine screening of thyroid function in the climacteric period to determine subclinical thyroid disease is recommended. Hormone replacement therapy (HRT) in women with hypothyroidism treated with thyroxine causes changes in free thyroxine and TSH. Increased binding of thyroxine to elevated thyroxine-binding globulin causes an elevation of TSH by feedback. Since adaptation is insufficient, there is an increased need for thyroxine in these women taking HRT. TSH levels should be controlled at 12 weeks after the beginning of therapy. At higher age the need for iodine and thyroxine is decreased. Therefore, therapy has to be controlled. For bone metabolism thyroid hormones play a dominant role. While there are

  2. Thyroid transplantation developing autoimmune thyroiditis following thymectomy and irradiation.

    PubMed Central

    Ahmed, S A; Penhale, W J

    1981-01-01

    Post-irradiation transplantation of normal thyroids under the renal capsule of syngenetic thymectomized and irradiated (Tx-X) rats leads to the development of thyroiditis in the ectopic grafted thyroids. A close correlation was observed between the extent of the lesions in the grafted and recipient's own thyroid. The histopathology of both grafted and recipient thyroid was similar and was characterized by infiltration with mononuclear cells together with some plasma cells. Conversely, grafting of affected thyroids from Tx-X rats to normal animals resulted in the regression of the lesion in the graft and no evidence thyroiditis was observed in either the graft or the recipient's thyroid when these were examined 60 days post-grafting. Thyroids derived from normal animals grafted to syngenetic normal rats were found to remain healthy and intact over a 60-day period. In contrast to normal animals, Tx-X rats were unable to reject totally in transplanted allogeneic thyroids by 28 days post-grafting, suggesting that some impairment of cell-mediated immunity follows this treatment. These findings indicate that the pathological change occurring in the thyroid gland of Tx-X rats is not attributable to the local effect of irradiation of the thyroids and adds further support to the concept that the process is immunologically mediated by thyroid-specific circulating components in the absence of normal immune regulatory function. Images Fig. 1 Fig. 3 Fig. 4 PMID:6896018

  3. Clinical and laboratory assessment of thyroid abnormalities

    SciTech Connect

    Kaplan, M.M.

    1985-09-01

    Clinical assessment of the patient with suspected thyroid disease remains an important part of the workup. Available laboratory tests of thyroid function include measurements of serum thyroid hormones and thyroid-stimulating hormone, titers of autoantibodies involved with Graves' disease and thyroiditis, and thyroid imaging and uptake techniques. The usefulness and limitations of each of these tests are reviewed.

  4. [Thyroid Adenomas in Children].

    PubMed

    Morozov, D A; Pimenova, E S; Mirokova, E D

    2015-01-01

    According to the papers thyroid nodules are quite rare in the first two decades of life. However, there are some exceptions, relating to areas with an iodine deficiency or affected by radioactive fallout, where the risk of nodules and carcinomas is increased. Therefore, it is a great challenge for the physician to distinguish between benign and malignant lesions preoperatively, and not only in these areas of greater risk. The authors analyzed current works, which are devoted to diagnostics and treatment of adenomas of thyroid gland in children. This literature review is based on works dedicated to epidemiology, histotypes study, and methods of diagnostics, surgical treatment, prognosis and complications of this pathology. The current tendencies in surgical approaches, intraoperative monitoring of recurrent laryngeal nerve are also discussed. The actuality of this problem is connected with last decade increase of adenomas in structure of thyroid gland nodules, increase of number of patients with multiple adenomas and with polypathias: adenomas with nodular goiter, autoimmune thyroiditis and cancer in children. The difficulties of diagnostic of adenomas are related to the similar clinical symptoms, cytogenetic characteristics of growth of benign and malignant lesions of thyroid gland. Additionally there is no systematic review about thyroid adenomas in children recent years. PMID:26846075

  5. Postpartum thyroiditis: an autoimmune thyroid disorder which predicts future thyroid health

    PubMed Central

    Keely, Erin Joanne

    2011-01-01

    Postpartum thyroiditis is a potentially destructive lymphocytic thyroiditis occurring in approximately 8% of the pregnant population, making it the most common endocrine disorder associated with pregnancy. This autoimmune thyroid disorder is precipitated by the postpartum immunological rebound that follows the partial immunosuppression of pregnancy, in individuals already at risk of autoimmune thyroid disease. The manifestations of postpartum thyroiditis are usually not present at the six-week postpartum visit and thus it is important that all physicians be aware of the risks, presentation and intervention required for this common disorder. Postpartum thyroiditis is a strong predictor of future thyroid health and it is essential that women with a history of postpartum thyroiditis be screened regularly, especially prior to a future pregnancy. Selenium supplementation has recently been identified as a potential means to prevent postpartum thyroiditis in women at risk but further studies are required before recommendations for its use can be made.

  6. Bladder urine oxygen tension for assessing renal medullary oxygenation in rabbits: experimental and modeling studies.

    PubMed

    Sgouralis, Ioannis; Kett, Michelle M; Ow, Connie P C; Abdelkader, Amany; Layton, Anita T; Gardiner, Bruce S; Smith, David W; Lankadeva, Yugeesh R; Evans, Roger G

    2016-09-01

    Oxygen tension (Po2) of urine in the bladder could be used to monitor risk of acute kidney injury if it varies with medullary Po2 Therefore, we examined this relationship and characterized oxygen diffusion across walls of the ureter and bladder in anesthetized rabbits. A computational model was then developed to predict medullary Po2 from bladder urine Po2 Both intravenous infusion of [Phe(2),Ile(3),Orn(8)]-vasopressin and infusion of N(G)-nitro-l-arginine reduced urinary Po2 and medullary Po2 (8-17%), yet had opposite effects on renal blood flow and urine flow. Changes in bladder urine Po2 during these stimuli correlated strongly with changes in medullary Po2 (within-rabbit r(2) = 0.87-0.90). Differences in the Po2 of saline infused into the ureter close to the kidney could be detected in the bladder, although this was diminished at lesser ureteric flow. Diffusion of oxygen across the wall of the bladder was very slow, so it was not considered in the computational model. The model predicts Po2 in the pelvic ureter (presumed to reflect medullary Po2) from known values of bladder urine Po2, urine flow, and arterial Po2 Simulations suggest that, across a physiological range of urine flow in anesthetized rabbits (0.1-0.5 ml/min for a single kidney), a change in bladder urine Po2 explains 10-50% of the change in pelvic urine/medullary Po2 Thus, it is possible to infer changes in medullary Po2 from changes in urinary Po2, so urinary Po2 may have utility as a real-time biomarker of risk of acute kidney injury. PMID:27385734

  7. 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

  8. Relb acts downstream of medullary thymic epithelial stem cells and is essential for the emergence of RANK(+) medullary epithelial progenitors.

    PubMed

    Baik, Song; Sekai, Miho; Hamazaki, Yoko; Jenkinson, William E; Anderson, Graham

    2016-04-01

    Thymic epithelial cells (TECs) provide essential signals for αβT-cell development, and medullary TECs (mTECs) control T-cell tolerance through both negative selection and Foxp3(+) regulatory T (Treg) cell development. Although heterogeneity within the mTEC compartment is well studied, the molecular regulators of specific stages of mTEC development are still poorly understood. Given the importance of the RANK-RANKL axis in thymus medulla formation, we have used RANK Venus reporter mice to analyze the ontogeny of RANK(+) TECs during development and correlated RANK expression with mTEC stem cells defined by SSEA-1. In addition, we have investigated how requirements for the key regulators Foxn1 and Relb map to specific stages of mTEC development. Here, we show SSEA-1(+) mTEC stem cells emerge prior to RANK expression and are present in both nude and Relb(-/-) mice, providing direct evidence that mTEC lineage specification occurs independently of Foxn1 and Relb. In contrast, we show that Relb is necessary for the effective production of downstream RANK(+) mTEC progenitors. Collectively, our work defines stage-specific requirements for critical TEC regulators during medulla development, including the timing of Relb dependency, and provides new information on mechanisms controlling mTEC specification. PMID:26806881

  9. Management of Differentiated Thyroid Cancer in Children: Focus on the American Thyroid Association Pediatric Guidelines.

    PubMed

    Parisi, Marguerite T; Eslamy, Hedieh; Mankoff, David

    2016-03-01

    First introduced in 1946, radioactive iodine (I-131) produces short-range beta radiation with a half-life of 8 days. The physical properties of I-131 combined with the high degree of uptake in the differentiated thyroid cancers (DTCs) led to the use of I-131 as a therapeutic agent for DTC in adults. There are two indications for the potential use of I-131 therapy in pediatric thyroid disorders: nonsurgical treatment of hyperthyroidism owing to Graves' disease and the treatment of children with intermediate- and high-risk DTC. However, children are not just miniature adults. Not only are children and the pediatric thyroid gland more sensitive to radiation than adults but also the biologic behavior of DTC differs between children and adults as well. As opposed to adults, children with DTC typically present with advanced disease at diagnosis; yet, they respond rapidly to therapy and have an excellent prognosis that is significantly better than that in adult counterparts with advanced disease. Unfortunately, there are also higher rates of local and distant disease recurrence in children with DTC compared with adults, mandating lifelong surveillance. Further, children have a longer life expectancy during which the adverse effects of I-131 therapy may become manifest. Recognizing the differences between adults and children with DTC, the American Thyroid Association commissioned a task force of experts who developed and recently published a guideline to address the unique issues related to the management of thyroid nodules and DTC in children. This article reviews the epidemiology, diagnosis, staging, treatment, therapy-related effects, and suggestions for surveillance in children with DTC, focusing not only on the differences between adults and children with this disease but also on the latest recommendations from the inaugural pediatric management guidelines of the American Thyroid Association. PMID:26897719

  10. Occupation and Thyroid Cancer

    PubMed Central

    Aschebrook-Kilfoy, Briseis; Ward, Mary H.; Valle, Curt T. Della; Friesen, Melissa C.

    2014-01-01

    Objectives Numerous occupational and environmental exposures have been shown to disrupt thyroid hormones, but much less is known about their relationships with thyroid cancer. Here we review the epidemiology studies of occupations and occupational exposures and thyroid cancer incidence to provide insight into preventable risk factors for thyroid cancer. Methods The published literature was searched using the Web of Knowledge database for all articles through August 2013 that had in their text “occupation” “job” ”employment” or “work” and “thyroid cancer”. After excluding 10 mortality studies and 4 studies with less than 5 exposed incident cases, we summarized the findings of 30 articles that examined thyroid cancer incidence in relation to occupations or occupational exposure. The studies were grouped by exposure/occupation category, study design, and exposure assessment approach. Where available, gender stratified results are reported. Results The most studied (19 of 30 studies) and the most consistent associations were observed for radiation-exposed workers and health care occupations. Suggestive, but inconsistent, associations were observed in studies of pesticide-exposed workers and agricultural occupations. Findings for other exposures and occupation groups were largely null. The majority of studies had few exposed cases and assessed exposure based on occupation or industry category, self-report, or generic (population-based) job exposure matrices. Conclusion The suggestive, but inconsistent findings for many of the occupational exposures reviewed here indicate that more studies with larger numbers of cases and better exposure assessment are necessary, particularly for exposures known to disrupt thyroid homeostasis. PMID:24604144

  11. Overexpression of NDRG2 Increases Iodine Uptake and Inhibits Thyroid Carcinoma Cell Growth In Situ and In Vivo.

    PubMed

    Yin, Anqi; Wang, Chengguo; Sun, Jiachen; Gao, Jianjun; Tao, Liang; Du, Xilin; Zhao, Huadong; Yang, Jiandong; Li, Yan

    2016-01-01

    Medullary thyroid carcinoma (MTC) is an uncommon and highly aggressive tumor of the neuroendocrine system, which derives from the neuroendocrine C cells of the thyroid gland. Except for surgical resection, there are not very many effective systemic treatment options for MTC. N-Myc downstream-regulated gene 2 (NDRG2) had a significantly lower expression in MTC compared with normal thyroid tissue. However, the function of NDRG2 in MTC oncogenesis is largely unknown. In this study, we found that overexpression of NDRG2 inhibited the proliferation of TT cells (human medullary thyroid carcinoma cells) in vitro and suppressed the development of MTC in a nude mouse xenograft model. Further analysis revealed that NDRG2 arrested the cell cycle G0/G1 phase progression and induced TT cell apoptosis. Moreover, NDRG2 overexpression may mediate the antiproliferative effect by reducing cyclin D1 and cyclin E protein levels. We also found aberrant NDRG2-mitigated TT cell migration and invasion in vitro. Sodium/iodide symporter (NIS) mediates active I(-) transport into the thyroid follicular cells, and radionuclide treatment is a promising therapy for MTC. Our current data revealed that NDRG2 overexpression enhanced NIS level in TT cells and increased their iodine uptake in vitro. Furthermore, (99m)TcO4(-) radionuclide imaging of the xenograft tumors indicated that NDRG2 could promote NIS-mediated radionuclide transport. In conclusion, the present study suggested that NDRG2 is a critical molecule in the regulation of MTC biological behavior and a potential promoter in radioactive iodine therapy. PMID:26802650

  12. Drugs Approved for Thyroid Cancer

    MedlinePlus

    ... Ask about Your Treatment Research Drugs Approved for Thyroid Cancer This page lists cancer drugs approved by ... that are not listed here. Drugs Approved for Thyroid Cancer Cabozantinib-S-Malate Caprelsa (Vandetanib) Cometriq (Cabozantinib-S-Malate) ...

  13. General Information about Thyroid Cancer

    MedlinePlus

    ... Research Thyroid Cancer Treatment (PDQ®)–Patient Version General Information About Thyroid Cancer Go to Health Professional Version ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  14. Genetics Home Reference: Hashimoto thyroiditis

    MedlinePlus

    ... is the most common cause of thyroid underactivity (hypothyroidism) in the United States. Related Information What information ... However, some people with thyroid antibodies never develop hypothyroidism or experience any related signs or symptoms. People ...

  15. Thyroid Hormone and Wound Healing

    PubMed Central

    Safer, Joshua D.

    2013-01-01

    Although thyroid hormone is one of the most potent stimulators of growth and metabolic rate, the potential to use thyroid hormone to treat cutaneous pathology has never been subject to rigorous investigation. A number of investigators have demonstrated intriguing therapeutic potential for topical thyroid hormone. Topical T3 has accelerated wound healing and hair growth in rodents. Topical T4 has been used to treat xerosis in humans. It is clear that the use of thyroid hormone to treat cutaneous pathology may be of large consequence and merits further study. This is a review of the literature regarding thyroid hormone action on skin along with skin manifestations of thyroid disease. The paper is intended to provide a context for recent findings of direct thyroid hormone action on cutaneous cells in vitro and in vivo which may portend the use of thyroid hormone to promote wound healing. PMID:23577275

  16. Thyroid dysfunction: an autoimmune aspect.

    PubMed

    Khan, Farah Aziz; Al-Jameil, Noura; Khan, Mohammad Fareed; Al-Rashid, May; Tabassum, Hajera

    2015-01-01

    Auto immune thyroid disease (AITD) is the common organ specific autoimmune disorder, Hashimoto thyroiditis (HT) and Grave's disease (GD) are its well-known sequelae. It occurs due to loss of tolerance to autoantigens thyroid peroxidase (TPO), thyroglobulin (Tg), thyroid stimulating hormone receptor (TSH-R) which leads to the infiltration of the gland. T cells in chronic autoimmune thyroiditis (cAIT) induce apoptosis in thyroid follicular cells and cause destruction of the gland. Presences of TPO antibodies are common in HT and GD, while Tg has been reported as an independent predictor of thyroid malignancy. Cytokines are small proteins play an important role in autoimmunity, by stimulating B and T cells. Various cytokines IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, IL-14, TNF-α and IFN-γ are found in thyroid follicular cells which enhance inflammatory response with nitric oxide (NO) and prostaglandins. PMID:26221205

  17. Colon cancer metastasis to the thyroid gland: report of a case with unique molecular profile.

    PubMed

    Roloff, Gregory W; Yang, Zhiming; Wood, Lauren V; Neychev, Vladimir K

    2016-06-01

    A high index of suspicion is needed when a patient presents with thyroid mass in the settings of an advanced CRC. Secondary thyroid malignancy should be considered unless proven otherwise. reatment should be determined considering extent of CRC metastasis, patient's general condition, and presence of local symptoms. PMID:27398194

  18. Neural control of adrenal medullary and cortical blood flow during hemorrhage

    SciTech Connect

    Breslow, M.J.; Jordan, D.A.; Thellman, S.T.; Traystman, R.J.

    1987-03-01

    Hemorrhagic hypotension produces an increase in adrenal medullary blood flow and a decrease in adrenal cortical blood flow. To determine whether changes in adrenal blood flow during hemorrhage are neurally mediated, the authors compared blood flow responses following adrenal denervation (splanchnic nerve section) with changes in the contralateral, neurally intact adrenal. Carbonized microspheres labeled with /sup 153/Gd, /sup 114/In, /sup 113/Sn, /sup 103/Ru, /sup 95/Nb or /sup 46/Se were used. Blood pressure was reduced and maintained at 60 mmHg for 25 min by hemorrhage into a pressurized bottle system. Adrenal cortical blood flow decreased to 50% of control with hemorrhage in both the intact and denervated adrenal. Adrenal medullary blood flow increased to four times control levels at 15 and 25 min posthemorrhage in the intact adrenal, but was reduced to 50% of control at 3, 5, and 10 min posthemorrhage in the denervated adrenal. In a separate group of dogs, the greater splanchnic nerve on one side was electrically stimulated at 2, 5, or 15 Hz for 40 min. Adrenal medullary blood flow increased 5- to 10-fold in the stimulated adrenal but was unchanged in the contralateral, nonstimulated adrenal. Adrenal cortical blood flow was not affected by nerve stimulation. They conclude that activity of the splanchnic nerve profoundly affects adrenal medullary vessels but not adrenal cortical vessels and mediates the observed increase in adrenal medullary blood flow during hemorrhagic hypotension.

  19. Stat3 Signaling Promotes Survival And Maintenance Of Medullary Thymic Epithelial Cells

    PubMed Central

    Bolner, Michelle; Reeh, Kaitlin A. G.; Kang, Rhea; Reddy, Madhava C.; DiGiovanni, John; Richie, Ellen R.

    2016-01-01

    Medullary thymic epithelial cells (mTECs) are essential for establishing central tolerance by expressing a diverse array of self-peptides that delete autoreactive thymocytes and/or divert thymocytes into the regulatory T cell lineage. Activation of the NFκB signaling pathway in mTEC precursors is indispensable for mTEC maturation and proliferation resulting in proper medullary region formation. Here we show that the Stat3-mediated signaling pathway also plays a key role in mTEC development and homeostasis. Expression of a constitutively active Stat3 transgene targeted to the mTEC compartment increases mTEC cellularity and bypasses the requirement for signals from positively selected thymocytes to drive medullary region formation. Conversely, conditional deletion of Stat3 disrupts medullary region architecture and reduces the number of mTECs. Stat3 signaling does not affect mTEC proliferation, but rather promotes survival of immature MHCIIloCD80lo mTEC precursors. In contrast to striking alterations in the mTEC compartment, neither enforced expression nor deletion of Stat3 affects cTEC cellularity or organization. These results demonstrate that in addition to the NFkB pathway, Stat3-mediated signals play an essential role in regulating mTEC cellularity and medullary region homeostasis. PMID:26789196

  20. Requirement of Stat3 Signaling in the Postnatal Development of Thymic Medullary Epithelial Cells.

    PubMed

    Satoh, Rumi; Kakugawa, Kiyokazu; Yasuda, Takuwa; Yoshida, Hisahiro; Sibilia, Maria; Katsura, Yoshimoto; Levi, Ben; Abramson, Jakub; Koseki, Yoko; Koseki, Haruhiko; van Ewijk, Willem; Hollander, Georg A; Kawamoto, Hiroshi

    2016-01-01

    Thymic medullary regions are formed in neonatal mice as islet-like structures, which increase in size over time and eventually fuse a few weeks after birth into a continuous structure. The development of medullary thymic epithelial cells (TEC) is dependent on NF-κB associated signaling though other signaling pathways may contribute. Here, we demonstrate that Stat3-mediated signals determine medullary TEC cellularity, architectural organization and hence the size of the medulla. Deleting Stat3 expression selectively in thymic epithelia precludes the postnatal enlargement of the medulla retaining a neonatal architecture of small separate medullary islets. In contrast, loss of Stat3 expression in cortical TEC neither affects the cellularity or organization of the epithelia. Activation of Stat3 is mainly positioned downstream of EGF-R as its ablation in TEC phenocopies the loss of Stat3 expression in these cells. These results indicate that Stat3 meditated signal via EGF-R is required for the postnatal development of thymic medullary regions. PMID:26789017

  1. Stat3 Signaling Promotes Survival And Maintenance Of Medullary Thymic Epithelial Cells.

    PubMed

    Lomada, Dakshayani; Jain, Manju; Bolner, Michelle; Reeh, Kaitlin A G; Kang, Rhea; Reddy, Madhava C; DiGiovanni, John; Richie, Ellen R

    2016-01-01

    Medullary thymic epithelial cells (mTECs) are essential for establishing central tolerance by expressing a diverse array of self-peptides that delete autoreactive thymocytes and/or divert thymocytes into the regulatory T cell lineage. Activation of the NFκB signaling pathway in mTEC precursors is indispensable for mTEC maturation and proliferation resulting in proper medullary region formation. Here we show that the Stat3-mediated signaling pathway also plays a key role in mTEC development and homeostasis. Expression of a constitutively active Stat3 transgene targeted to the mTEC compartment increases mTEC cellularity and bypasses the requirement for signals from positively selected thymocytes to drive medullary region formation. Conversely, conditional deletion of Stat3 disrupts medullary region architecture and reduces the number of mTECs. Stat3 signaling does not affect mTEC proliferation, but rather promotes survival of immature MHCIIloCD80lo mTEC precursors. In contrast to striking alterations in the mTEC compartment, neither enforced expression nor deletion of Stat3 affects cTEC cellularity or organization. These results demonstrate that in addition to the NFkB pathway, Stat3-mediated signals play an essential role in regulating mTEC cellularity and medullary region homeostasis. PMID:26789196

  2. Requirement of Stat3 Signaling in the Postnatal Development of Thymic Medullary Epithelial Cells

    PubMed Central

    Satoh, Rumi; Kakugawa, Kiyokazu; Yasuda, Takuwa; Yoshida, Hisahiro; Sibilia, Maria; Katsura, Yoshimoto; Levi, Ben; Abramson, Jakub; Koseki, Yoko; Koseki, Haruhiko; van Ewijk, Willem; Hollander, Georg A.; Kawamoto, Hiroshi

    2016-01-01

    Thymic medullary regions are formed in neonatal mice as islet-like structures, which increase in size over time and eventually fuse a few weeks after birth into a continuous structure. The development of medullary thymic epithelial cells (TEC) is dependent on NF-κB associated signaling though other signaling pathways may contribute. Here, we demonstrate that Stat3-mediated signals determine medullary TEC cellularity, architectural organization and hence the size of the medulla. Deleting Stat3 expression selectively in thymic epithelia precludes the postnatal enlargement of the medulla retaining a neonatal architecture of small separate medullary islets. In contrast, loss of Stat3 expression in cortical TEC neither affects the cellularity or organization of the epithelia. Activation of Stat3 is mainly positioned downstream of EGF-R as its ablation in TEC phenocopies the loss of Stat3 expression in these cells. These results indicate that Stat3 meditated signal via EGF-R is required for the postnatal development of thymic medullary regions. PMID:26789017

  3. GABA Signaling and Neuroactive Steroids in Adrenal Medullary Chromaffin Cells

    PubMed Central

    Harada, Keita; Matsuoka, Hidetada; Fujihara, Hiroaki; Ueta, Yoichi; Yanagawa, Yuchio; Inoue, Masumi

    2016-01-01

    Gamma-aminobutyric acid (GABA) is produced not only in the brain, but also in endocrine cells by the two isoforms of glutamic acid decarboxylase (GAD), GAD65 and GAD67. In rat adrenal medullary chromaffin cells only GAD67 is expressed, and GABA is stored in large dense core vesicles (LDCVs), but not synaptic-like microvesicles (SLMVs). The α3β2/3γ2 complex represents the majority of GABAA receptors expressed in rat and guinea pig chromaffin cells, whereas PC12 cells, an immortalized rat chromaffin cell line, express the α1 subunit as well as the α3. The expression of α3, but not α1, in PC12 cells is enhanced by glucocorticoid activity, which may be mediated by both the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR). GABA has two actions mediated by GABAA receptors in chromaffin cells: it induces catecholamine secretion by itself and produces an inhibition of synaptically evoked secretion by a shunt effect. Allopregnanolone, a neuroactive steroid which is secreted from the adrenal cortex, produces a marked facilitation of GABAA receptor channel activity. Since there are no GABAergic nerve fibers in the adrenal medulla, GABA may function as a para/autocrine factor in the chromaffin cells. This function of GABA may be facilitated by expression of the immature isoforms of GAD and GABAA receptors and the lack of expression of plasma membrane GABA transporters (GATs). In this review, we will consider how the para/autocrine function of GABA is achieved, focusing on the structural and molecular mechanisms for GABA signaling. PMID:27147972

  4. GABA Signaling and Neuroactive Steroids in Adrenal Medullary Chromaffin Cells.

    PubMed

    Harada, Keita; Matsuoka, Hidetada; Fujihara, Hiroaki; Ueta, Yoichi; Yanagawa, Yuchio; Inoue, Masumi

    2016-01-01

    Gamma-aminobutyric acid (GABA) is produced not only in the brain, but also in endocrine cells by the two isoforms of glutamic acid decarboxylase (GAD), GAD65 and GAD67. In rat adrenal medullary chromaffin cells only GAD67 is expressed, and GABA is stored in large dense core vesicles (LDCVs), but not synaptic-like microvesicles (SLMVs). The α3β2/3γ2 complex represents the majority of GABAA receptors expressed in rat and guinea pig chromaffin cells, whereas PC12 cells, an immortalized rat chromaffin cell line, express the α1 subunit as well as the α3. The expression of α3, but not α1, in PC12 cells is enhanced by glucocorticoid activity, which may be mediated by both the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR). GABA has two actions mediated by GABAA receptors in chromaffin cells: it induces catecholamine secretion by itself and produces an inhibition of synaptically evoked secretion by a shunt effect. Allopregnanolone, a neuroactive steroid which is secreted from the adrenal cortex, produces a marked facilitation of GABAA receptor channel activity. Since there are no GABAergic nerve fibers in the adrenal medulla, GABA may function as a para/autocrine factor in the chromaffin cells. This function of GABA may be facilitated by expression of the immature isoforms of GAD and GABAA receptors and the lack of expression of plasma membrane GABA transporters (GATs). In this review, we will consider how the para/autocrine function of GABA is achieved, focusing on the structural and molecular mechanisms for GABA signaling. PMID:27147972

  5. Robotic thyroidectomy and cervical neck dissection for thyroid cancer.

    PubMed

    Paek, Se Hyun; Kang, Kyung Ho

    2016-06-01

    A robotic approach for thyroid surgery was developed to overcome the limitations of endoscopic thyroidectomy and provide many technical advantages. This approach facilitates the surgeon's control through a magnified three-dimensional view, decreased tremor, and freedom of motion with articulated instruments. Robotic thyroidectomy is safe and technically feasible in patients with well-differentiated, low-risk thyroid cancer. Furthermore, robotic thyroidectomy may become a good surgical alternative option for patients with more advanced thyroid cancer. Our modified bilateral axillo-breast approach (BABA) for central and lateral cervical neck lymph node (LN) dissection has yielded excellent surgical outcomes as an open procedure. The incorporation of robotics in thyroid cancer surgery will continue to evolve, and the surgical indications for robotic thyroidectomy will continue to expand. Further analyses that include long-term outcomes and randomized comparative trials remain important. PMID:27294043

  6. Robotic thyroidectomy and cervical neck dissection for thyroid cancer

    PubMed Central

    Paek, Se Hyun

    2016-01-01

    A robotic approach for thyroid surgery was developed to overcome the limitations of endoscopic thyroidectomy and provide many technical advantages. This approach facilitates the surgeon’s control through a magnified three-dimensional view, decreased tremor, and freedom of motion with articulated instruments. Robotic thyroidectomy is safe and technically feasible in patients with well-differentiated, low-risk thyroid cancer. Furthermore, robotic thyroidectomy may become a good surgical alternative option for patients with more advanced thyroid cancer. Our modified bilateral axillo-breast approach (BABA) for central and lateral cervical neck lymph node (LN) dissection has yielded excellent surgical outcomes as an open procedure. The incorporation of robotics in thyroid cancer surgery will continue to evolve, and the surgical indications for robotic thyroidectomy will continue to expand. Further analyses that include long-term outcomes and randomized comparative trials remain important. PMID:27294043

  7. Is thyroid surgery performed too often in Germany?

    PubMed

    Verburg, Frederik A

    2015-01-01

    Thyroid surgery is one of the more common surgical procedures in Germany. This is in contrast with the situation in some other countries, where this procedure is performed comparatively rarely. In this paper the number of thyroid surgeries in Germany is compared with other western countries (Netherlands, USA, England). In contrast to e. g. the USA and England the number of thyroid surgeries in Germany is declining, however with approximately 109/100,000/year in 2012 is still elevated (Netherlands: 16/100,000/year, USA: at least 42/100,000/year, England: at least 27/100,000/year). Possible contributing factors to this higher number of thyroid surgeries in Germany are explored. These factors include iodine deficiency, the frequent use of advanced diagnostics such as ultrasound, insufficient use of preoperative diagnostic measures such as fine needle biopsy and the practice of "defensive medicine". How much each of these factors contributes is however unclear. PMID:26105718

  8. Cardiovascular effects of thyroid disease.

    PubMed

    Sangster, Jodi K; Panciera, David L; Abbott, Jonathan A

    2013-07-01

    Thyroid hormones have many effects on cardiovascular function, and deficiency or excess of thyroid hormones can result in cardiac dysfunction. Abnormalities of the cardiovascular system are often identified during examination of hyperthyroid and hypothyroid patients. This article addresses the effects of thyroid hormones on the cardiovascular system and the clinical relevance of the cardiovascular response to thyroid dysfunction. In addition, treatment recommendations are presented. PMID:23677842

  9. On the Origin of Cells and Derivation of Thyroid Cancer: C Cell Story Revisited.

    PubMed

    Nilsson, Mikael; Williams, Dillwyn

    2016-07-01

    We will highlight and put into perspective new lineage tracing data from genetic studies in mice indicating that the genuine progenitors to C cells arise in the endoderm germ layer. This overturns the current concept of a neural crest origin of thyroid C cells referred to in every textbook and dedicated paper to this very day. As will become apparent, except for a single experiment, the neural crest theory has little or no support when the evolution and development of calcitonin-producing cells in the entire chordate family are considered. Instead, a unifying origin of all cells of the ultimobranchial bodies reopens questions on the histogenesis of certain thyroid pathologies previously difficult to explain. On this aspect, medullary thyroid cancer shows a stronger connection to gut neuroendocrine tumours than previously recognized. It is envisaged that novel factors implicated in C cell-derived tumour growth and progression will be discovered as the mechanisms that regulate lineage expansion of embryonic C cell precursors from pharyngeal endoderm are uncovered. We will not discuss why C cells go to the bother of burying themselves in the thyroid - this remains a mystery. PMID:27493881

  10. Predictors of Regional Lymph Node Recurrence after Initial Thyroidectomy in Patients with Thyroid Cancer

    PubMed Central

    Sharifi, Amirsina; Shojaeifard, Abolfazl; Soroush, Ahmadreza; Jafari, Mehdi; Abdehgah, Ali Ghorbani; Mahmoudzade, Hossein

    2016-01-01

    Background. Regional lymph node recurrence (RLNR) is common in patients with thyroid cancer but clinicopathological predictors are unclear. We aimed to clarify these predictors and identify patients who would benefit from prophylactic lymph node dissection the most. Method. 343 patients with different types of thyroid cancer were analyzed retrospectively. All patients underwent total thyroidectomy between 2007 and 2013. Results. The median ± interquartile range of patients' age was 40 ± 25 years. 245 (71.4%) patients were female. Regarding the risk of regional lymph node recurrence, we found that male gender, age ≥45 years, non-PTC (i.e., medullary, follicular, and anaplastic types) histopathology, T3 (i.e., tumor size >4 cm in the greatest dimension limited to the thyroid or any tumor with minimal extrathyroid extension), stage IVa, and isolated cervical lymphadenopathy as initial manifestation (ICL) are significant risk factors. T3 (p < 0.001; odds ratio = 156.41, 95% CI [55.72–439.1]) and ICL (p < 0.001; odds ratio = 77.79, 95% CI [31.55–191.81]) were the strongest predictors of regional lymph node recurrence. Conclusion. We found easily achievable risk factors for RLNR in thyroid cancers patients. We suggested that patients with specific clinicopathological features like male gender, age ≥45 years, larger tumor size, and extrathyroidal extension be considered as prophylactic lymphadenectomy candidates. PMID:27403370

  11. Evaluation of the thyroid nodule

    SciTech Connect

    Cannon, C.R.

    1986-05-01

    Evaluation of thyroid nodules challenges the most astute clinician. The history and the physical examination often identify those patients who require immediate surgical management. In other patients, time-honored thyroid function studies and thyroid scanning are helpful. Fine needle aspiration and computed tomography are also valuable in the diagnostic work-up.

  12. Thyroid Function in Down Syndrome.

    ERIC Educational Resources Information Center

    Pueschel, Siegfried M.; And Others

    1991-01-01

    This study investigated the thyroid function of 181 patients (mean age 14 years) with Down's syndrome and found more thyroid dysfunctions than in the general population. Periodic thyroid hormone function tests are recommended for Down's syndrome individuals, especially as they get older. (Author/DB)

  13. Corticosteroid therapy in Riedel's thyroiditis.

    PubMed

    Vaidya, B; Harris, P E; Barrett, P; Kendall-Taylor, P

    1997-12-01

    We report a case of Riedel's thyroiditis presenting with a systemic illness, life-threatening stridor and a stony hard goitre. Diagnosis was confirmed by open thyroid biopsy. Treatment with corticosteroid resulted in a dramatic improvement. A possible autoimmune mechanism in the pathogenesis of Riedel's thyroiditis is discussed. PMID:9497955

  14. [Thyroid dysfunction during pregnancy].

    PubMed

    Díez, Juan J; Iglesias, Pedro; Donnay, Sergio

    2015-10-21

    Recent clinical practice guidelines on thyroid dysfunction and pregnancy have changed health care provided to pregnant women, although their recommendations are under constant revision. Trimester- and area-specific reference ranges for serum thyroid-stimulating hormone are required for proper diagnosis of hypothyroidism and hyperthyroidism. There is no doubt on the need of therapy for overt hypothyroidism, while therapy for subclinical hypothyroidism is controversial. Further research is needed to settle adverse effects of isolated hypothyroxinemia and thyroid autoimmunity. Differentiation between hyperthyroidism due to Graves' disease and the usually self-limited gestational transient thyrotoxicosis is critical. It is also important to recognize risk factors for postpartum thyroiditis. Supplementation with iodine is recommended to maintain adequate iodine nutrition during pregnancy and avoid serious consequences in offspring. Controversy remains about universal screening for thyroid disease during pregnancy or case-finding in high-risk women. Opinions of some scientific societies and recent cost-benefit studies favour universal screening. Randomized controlled studies currently under development should reduce the uncertainties that still remain in this area. PMID:25433782

  15. Thyroid hormone resistance.

    PubMed

    Olateju, Tolulope O; Vanderpump, Mark P J

    2006-11-01

    Resistance to thyroid hormone (RTH) is a rare autosomal dominant inherited syndrome of reduced end-organ responsiveness to thyroid hormone. Patients with RTH have elevated serum free thyroxine (FT4) and free triiodothyronine (FT3) concentrations and normal or slightly elevated serum thyroid stimulating hormone (TSH) level. Despite a variable clinical presentation, the common characteristic clinical features are goitre but an absence of the usual symptoms and metabolic consequences of thyroid hormone excess. Patients with RTH can be classified on clinical grounds alone into either generalized resistance (GRTH), pituitary resistance (PRTH) or combined. Mutations in the thyroid hormone receptor (TR) beta gene are responsible for RTH and 122 different mutations have now been identified belonging to 300 families. With the exception of one family found to have complete deletion of the TRbeta gene, all others have been demonstrated to have minor alterations at the DNA level. The differential diagnosis includes a TSH-secreting pituitary adenoma and the presence of endogenous antibodies directed against thyroxine (T4) and triiodothyronine (T3). Failure to differentiate RTH from primary thyrotoxicosis has resulted in the inappropriate treatment of nearly one-third of patients. Although occasionally desirable, no specific treatment is available for RTH; however, the diagnosis allows appropriate genetic counselling. PMID:17132274

  16. Expression of p63 and Bcl-2 in Malignant Thyroid Tumors and their Correlation with other Diagnostic Immunocytochemical Markers

    PubMed Central

    Jain, Shyama; Khurana, Nita; Kakar, Arun Kumar

    2016-01-01

    Introduction Bcl-2 is a marker recently studied in thyroid tumours and proposed to have prognostic significance. p63 is expressed in a proportion of papillary thyroid carcinoma cases and may have a role in tumour progression. Aim To study expression of Bcl2 and p63 in thyroid tumours and correlation of Bcl-2 with diagnostic markers including Thyroglobulin, Calcitonin and Carcinoembryonic antigen. Materials and Methods Cytology smears of 35 cases of thyroid cancer were studied over a period of 18 months. In 20 cases histopathology was available. Immunocytochemistry for Bcl-2 and p63 was done, and diagnostic markers were applied as and when required. Results p63 showed focal nuclear expression in 46.1% of papillary thyroid carcinoma cases, and was negative in all other tumours. Bcl-2 was positive in 88.9% of follicular carcinomas, 100% of papillary carcinomas and 83.3% of medullary carcinoma cases, and showed focal weak expression in 40% of Anaplastic Carcinoma (ATC) cases, thereby signifying down regulation (p-value = 0.001). There was significant down regulation of Thyroglobulin (Tg) in ATC vs well differentiated follicular derived tumours (p-value ≤ 0.016). Positive correlation was noted between expression of Bcl-2 and Calcitonin (0.93) and Bcl-2 and Carcinoembryonic Antigen (CEA) (0.89), and weak positive correlation (0.65) between Tg and Bcl-2. Conclusion Bcl-2 is downregulated in anaplastic carcinomas as compared to well differentiated thyroid tumours, and shows correlation with differentiation associated tumour antigens. Thus, loss of Bcl-2 was associated with loss of differentiation in thyroid tumours. Anaplastic carcinoma as such is associated with worse prognosis and loss of Bcl-2 may be partly responsible for the same. p63 is specific but less sensitive marker for PTC. Further studies are required to determine the role of Bcl-2 and p63 in thyroid tumours.

  17. Chemistry and Biology in the Biosynthesis and Action of Thyroid Hormones.

    PubMed

    Mondal, Santanu; Raja, Karuppusamy; Schweizer, Ulrich; Mugesh, Govindasamy

    2016-06-27

    Thyroid hormones (THs) are secreted by the thyroid gland. They control lipid, carbohydrate, and protein metabolism, heart rate, neural development, as well as cardiovascular, renal, and brain functions. The thyroid gland mainly produces l-thyroxine (T4) as a prohormone, and 5'-deiodination of T4 by iodothyronine deiodinases generates the nuclear receptor binding hormone T3. In this Review, we discuss the basic aspects of the chemistry and biology as well as recent advances in the biosynthesis of THs in the thyroid gland, plasma transport, and internalization of THs in their target organs, in addition to the deiodination and various other enzyme-mediated metabolic pathways of THs. We also discuss thyroid hormone receptors and their mechanism of action to regulate gene expression, as well as various thyroid-related disorders and the available treatments. PMID:27226395

  18. [Thyroid dysfunction: a topic of constant review for the gynaecologist, for its frequency in women].

    PubMed

    Zárate, Arturo; Basurto, Lourdes; Saucedo, Renata; Hernández Valencia, Marcelino

    2009-02-01

    Thyroid dysfunction is more common in women than in men due to the hormone changes which are functional in proper stages such as puberty, pregnancy and menopause. It seems that the interrelationship between the endocrine and immunologic systems may be responsible of the incidence of thyroid dysfunction. The development of precise techniques for the measurement of thyroid hormones as well as the advancement in imagenology studies have contributed to proper diagnosis and therapeutic modalities. Thyroid diseases during pregnancy are now better treated and no harm has been observed in neonates. Fine needle-aspiration biopsy for the diagnosis of thyroid cancer is considered the best diagnostic procedure, but remains in controversy the extension of surgery of the gland. There are still some controversial points regarding TSH universal screening, the adequate treatment of hyperthyroidism and the management of non-cancerous thyroid nodules. PMID:19365951

  19. Adrenocortical hemorrhagic necrosis: the role of catecholamines and retrograde medullary-cell embolism

    SciTech Connect

    Szabo, S.; McComb, D.J.; Kovacs, K.; Huettner, I.

    1981-10-01

    We investigated the pathogenesis of adrenal necrosis using animal models of the disease (induced by administration of acrylonitrile, cysteamine, or pyrazole) and human cases. Results of electron-microscopic and histochemical time-response studies with rat models revealed an early, retrograde embolization of medullary cells and cell fragments in the cortical capillaries that showed prominent endothelial injury. The experimental adrenal lesions were prevented by surgical removal of the medulla one month before administration of adrenocorticolytic chemicals, or by the administration of the alpha-adrenergic antagonist phenoxybenzamine hydrochloride. Histochemical staining for medullary (argyrophil) granules in human cases of adrenal necrosis demonstrated tissue fragments that stained positively for silver in vascular cortical spaces in nine of ten autopsy specimens and in all four surgical cases we reviewed. Thus, catecholamines released from the adrenal medulla and from the retrograde medullary emboli in the cortex may have a role in the pathogenesis of adrenocortical necrosis.

  20. Malignant astrocytoma of the cervico-medullary junction masquerading as Guillain-Barré syndrome.

    PubMed

    Beards, S C; Robertson, L J; Jackson, A; Lipman, J

    1994-07-01

    Brainstem gliomas are rare primary brain tumours which most commonly occur in the midbrain and pons. Malignant gliomas and tumours at the cervico-medullary junction are particularly unusual. The diagnosis of tumours at this site is particularly difficult using computed tomographic (CT) scanning owing to artifacts around the base of the skull. Intrinsic tumours of the cervico-medullary junction may lead to a dissociated motor deficit and the onset of symptoms can be rapid. We describe a patient in whom an isolated ascending motor deficit in association with a raised cerebrospinal fluid protein and a normal CT scan led to an erroneous diagnosis of Guillain-Barré syndrome. The patient was treated on the intensive care unit for an 8-week period before further investigation demonstrated a malignant glioma of the cervico-medullary junction. We recommend confirmation of the diagnosis of polyradiculopathy by nerve conduction studies wherever possible. PMID:7937428

  1. Effect of medullary cavity in cancellous bone on two-wave phenomenon

    NASA Astrophysics Data System (ADS)

    Hachiken, Takuma; Nakanishi, Shoko; Matsukawa, Mami

    2016-07-01

    Osteoporotic patients have a larger medullary cavity in their cancellous bone than healthy people. In this study, the effect of the medullary cavity on the two-wave phenomenon was experimentally investigated using a cancellous bone model and a radius bone model. In the cancellous bone model, with the increase in hole (medullary cavity) diameter, the amplitudes of the fast waves became smaller, whereas the amplitudes of the slow waves became larger. In the radius bone model, the fast wave overlapped with the circumferential wave. The slow wave became larger with increasing hole diameter. The analysis of the slow wave thus seems to be useful for the in vivo diagnosis of the degree of osteoporosis.

  2. Solitary thyroid nodule. 1. Clinical characteristics

    SciTech Connect

    Mazzaferri, E.L.

    1981-07-01

    The approach to management of an isolated thyroid nodule requires some understanding of the natural history of thyroid cancer and other forms of nodular thyroid disease. The histologic classification of thyroid cancer is an important determinant of survival, as are the size of the primary tumor, presence of thyroid capsule invasion, and presence of distant metastases. Therapeutic radiation and radioactive fallout increase the risk that a thyroid nodule is malignant. Autonomously functioning thyroid nodules are usually benign follicular adenomas and may cause thyrotoxicosis.

  3. Metastatic ductal carcinoma of the breast to the thyroid gland diagnosed with fine needle aspiration: A case report with emphasis on morphologic and immunophenotypic features.

    PubMed

    Magers, Martin J; Dueber, Julie C; Lew, Madelyn; Pang, Judy C; Davenport, Robertson D

    2016-06-01

    Metastases to the thyroid are uncommon [<0.2% of thyroid fine needle aspirations (FNA)]. Of metastases to the thyroid, breast carcinoma is relatively common. The diagnosis of metastasis to the thyroid has important therapeutic and prognostic implications. To our knowledge, a morphologic and immunophenotypic comparison of metastatic ductal carcinoma of the breast and primary thyroid carcinomas has not been reported. Here, we report the case of a 37-year-old female with a history of metastatic ductal carcinoma of the breast (modified Bloom-Richardson grade 2; ER+, PgR+, HER2+) diagnosed 6 years prior. She developed hoarseness, prompting a CT scan. Multiple thyroid nodules were found, including a 1.5 cm hypoechoic, solid, irregularly-shaped nodule. On FNA, cells were arranged singly and in crowded groups, varied in size and degree of pleomorphism, and exhibited rare nuclear grooves, inconspicuous nucleoli, and rare intracytoplasmic lumina with no nuclear pseudoinclusions or colloid (Figs. 1A and B). These findings raised the differential of papillary thyroid carcinoma (Fig. 1C), follicular neoplasm (Fig. 1D), medullary carcinoma (Fig. 1E), parathyroid (Fig. 1F), and metastatic breast carcinoma. Immunostaining for GATA-3 (+), ER (+), PAX-8 (-), and TTF-1 (-) was consistent with metastatic breast carcinoma (Fig. 2). We conclude that metastatic breast carcinoma to the thyroid may morphologically mimic primary thyroid carcinoma on FNA; a panel of immunomarkers, such as GATA-3, hormonal marker(s), PAX-8, and TTF-1, may be useful in some cases. GATA-3 immunostaining for metastatic breast carcinoma was helpful in our case and has not been previously reported in a thyroid metastasis sampled by FNA. Diagn. Cytopathol. 2016;44:530-534. © 2016 Wiley Periodicals, Inc. PMID:26932153

  4. Amiodarone-induced thyroid dysfunction.

    PubMed

    Danzi, Sara; Klein, Irwin

    2015-05-01

    Amiodarone is an effective medication for the treatment of cardiac arrhythmias. Originally developed for the treatment of angina, it is now the most frequently prescribed antiarrhythmia drug despite the fact that its use is limited because of potential serious side effects including adverse effects on the thyroid gland and thyroid hormones. Although the mechanisms of action of amiodarone on the thyroid gland and thyroid hormone metabolism are poorly understood, the structural similarity of amiodarone to thyroid hormones, including the presence of iodine moieties on the inner benzene ring, may play a role in causing thyroid dysfunction. Amiodarone-induced thyroid dysfunction includes amiodarone-induced thyrotoxicosis (AIT) and amiodarone-induced hypothyroidism (AIH). The AIT develops more commonly in iodine-deficient areas and AIH in iodine-sufficient areas. The AIT type 1 usually occurs in patients with known or previously undiagnosed thyroid dysfunction or goiter. The AIT type 2 usually occurs in normal thyroid glands and results in destruction of thyroid tissue caused by thyroiditis. This is the result of an intrinsic drug effect from the amiodarone itself. Mixed types are not uncommon. Patients with cardiac disease receiving amiodarone treatment should be monitored for signs of thyroid dysfunction, which often manifest as a reappearance of the underlying cardiac disease state. When monitoring patients, initial tests should include the full battery of thyroid function tests, thyroid-stimulating hormone, thyroxine, triiodothyronine, and antithyroid antibodies. Mixed types of AIT can be challenging both to diagnose and treat and therapy differs depending on the type of AIT. Treatment can include thionamides and/or glucocorticoids. The AIH responds favorably to thyroid hormone replacement therapy. Amiodarone is lipophilic and has a long half-life in the body. Therefore, stopping the amiodarone therapy usually has little short-term benefit. PMID:24067547

  5. [Thyroid gland and fertility].

    PubMed

    Andreeva, P

    2014-01-01

    It is well-known that the thyroid hormones are associated with a number of aspects of the human reproduction. Both states, hyperthyroidism and hypothyroidism, have significant effect on the estrogen and androgen metabolism, the menstrual function and on fertility. The role of thyroid hormones (TH) during infertility has been little exploited. Interesting facts are that TH deficiency is more common in women with polycystic ovary syndrome (PCOS) and in certain cases with unexplained infertility. There are very few studies on the effect and paracrine regulation of TH and its receptors in the female reproductive tract. This report provides an overview of the most common thyroid disorders and their impact on ovarian function and reproductive performance in women as well as in cases with infertility and the implementation of assisted reproductive technologies (ART). PMID:25675618

  6. [Therapy of thyroid nodules].

    PubMed

    Schott, Matthias

    2015-04-01

    Thyroid nodules are frequent in Germany. In about every fourth person thyroid nodules can be detected. Most of them are benign. Signs for malignancy are hypoechogenicity, microcalcifications, an unregular margin and increased blood perfusion. There is no strict indication for the treatment of benign nodules. In most cases iodine supplementation is sufficient. A combination therapy with levothyroxine and iodine is more efficient for the treatment of larger nodules. Subclinical hyperthyroidism caused by an adenoma does not necessarily need to be treated, whereas manifest hyperthyroidism needs to treated in most cases with antithyroid drug therapy. Radioiodine therapy is the classical indication for the treatment of unifocal autonomous adenomas. A largely increased thyroid gland with and without uni- / multifocal adenomas are often operated. PMID:25831118

  7. Systemic Pregabalin Attenuates Sensorimotor Responses and Medullary Glutamate Release in Inflammatory Tooth Pain Model

    PubMed Central

    Narita, Noriyuki; Kumar, Naresh; Cherkas, Pavel S.; Chiang, Chen Yu; Dostrovsky, Jonathan O.; Coderre, Terence J.; Sessle, Barry J.

    2012-01-01

    Our previous studies have demonstrated that application to the tooth pulp of the inflammatory irritant mustard oil (MO) induces medullary glutamate release and central sensitization in the rat medullary dorsal horn (MDH), as well as nociceptive sensorimotor responses in craniofacial muscles in rats. There is recent evidence that anticonvulsant drugs such as pregabalin that influence glutamatergic neurotransmission are effective in several pain states. The aim of this study was to examine whether systemic administration of pregabalin attenuated glutamate release in the medulla as well as these nociceptive effects reflected in increased electromyographic (EMG) activity induced by MO application to the tooth pulp. Male adult rats were anesthetized with isofluorane (1.0~1.2 %), and jaw and tongue muscle EMG activities were recorded by needle electrodes inserted bilaterally into masseter and anterior digastric muscles and into the genioglossus muscle, and also the medullary release of glutamate was assessed by in vivo microdialysis. Pregabalin or vehicle control (isotonic saline) was administered 30 min before the pulpal application of MO or vehicle control (mineral oil). Application of mineral oil to the maxillary first molar tooth pulp produced no change in baseline EMG activity and glutamate release. However, application of MO to the pulp significantly increased both the medullary release of glutamate and EMG activity in the jaw and tongue muscles for several minutes. In contrast, pre-medication with pregabalin, but not vehicle control, significantly and dose-dependently attenuated the medullary glutamate release and EMG activity in these muscles after MO application to the tooth pulp (ANOVA, p<0.05). These results suggest that pregabalin may attenuate the medullary release of glutamate and associated nociceptive sensorimotor responses in this acute inflammatory pulpal pain model, and that it may prove useful for the treatment of orofacial inflammatory pain states

  8. Systemic pregabalin attenuates sensorimotor responses and medullary glutamate release in inflammatory tooth pain model.

    PubMed

    Narita, N; Kumar, N; Cherkas, P S; Chiang, C Y; Dostrovsky, J O; Coderre, T J; Sessle, B J

    2012-08-30

    Our previous studies have demonstrated that application of inflammatory irritant mustard oil (MO) to the tooth pulp induces medullary glutamate release and central sensitization in the rat medullary dorsal horn (MDH), as well as nociceptive sensorimotor responses in craniofacial muscles in rats. There is recent evidence that anticonvulsant drugs such as pregabalin that influence glutamatergic neurotransmission are effective in several pain states. The aim of this study was to examine whether systemic administration of pregabalin attenuated glutamate release in the medulla as well as these nociceptive effects reflected in increased electromyographic (EMG) activity induced by MO application to the tooth pulp. Male adult rats were anesthetized with isofluorane (1.0-1.2%), and jaw and tongue muscle EMG activities were recorded by needle electrodes inserted bilaterally into masseter and anterior digastric muscles and into the genioglossus muscle, and also the medullary release of glutamate was assessed by in vivo microdialysis. Pregabalin or vehicle control (isotonic saline) was administered 30 min before the pulpal application of MO or vehicle control (mineral oil). Application of mineral oil to the maxillary first molar tooth pulp produced no change in baseline EMG activity and glutamate release. However, application of MO to the pulp significantly increased both the medullary release of glutamate and EMG activity in the jaw and tongue muscles for several minutes. In contrast, pre-medication with pregabalin, but not vehicle control, significantly and dose-dependently attenuated the medullary glutamate release and EMG activity in these muscles after MO application to the tooth pulp (analysis of variance (ANOVA), p<0.05). These results suggest that pregabalin may attenuate the medullary release of glutamate and associated nociceptive sensorimotor responses in this acute inflammatory pulpal pain model, and that it may prove useful for the treatment of orofacial

  9. Do egg-laying crocodilian (Alligator mississippiensis) archosaurs form medullary bone?

    PubMed

    Schweitzer, M H; Elsey, R M; Dacke, C G; Horner, J R; Lamm, E-T

    2007-04-01

    It is beyond question that Mesozoic dinosaurs, like Aves and Crocodylia, are archosaurs. However, within the archosaurian clade, the origin and distribution of some major features are less clear, particularly with respect to reproductive physiology. Medullary bone, a highly mineralized, bony reproductive tissue present in the endosteal cavities of all extant egg-laying birds thus far examined, has recently been reported in Tyrannosaurus rex. Its presence or absence in extant crocodilians, therefore, may shed light on the timing of its evolutionary appearance. If medullary bone is present in all three taxa, it arose before the three lineages diverged. However, if medullary bone arose after this divergence, it may be present in both extinct dinosaurs and birds, or in birds only. If present in extinct dinosaurs and birds, but not crocodilians, it would indicate that it arose in the common ancestor of this clade, thus adding support to the closer phylogenetic relationship of dinosaurs and birds relative to crocodilians. Thus, the question of whether the crocodilian Alligator mississippiensis forms medullary bone during the production of eggs has important evolutionary significance. Our examination of long bones from several alligators (two alligators with eggs in the oviducts, one that had produced eggs in the past but was not currently in reproductive phase, an immature female and an adult male) shows no differences on the endosteal surfaces of the long bones, and no evidence of medullary bone, supporting the hypothesis that medullary bone first evolved in the dinosaur-bird line, after the divergence of crocodilians from this lineage. PMID:17223615

  10. Integrating Molecular Testing in the Diagnosis and Management of Children with Thyroid Lesions.

    PubMed

    Ballester, Leomar Y; Sarabia, Stephen F; Sayeed, Hadi; Patel, Nimesh; Baalwa, Joshua; Athanassaki, Ioanna; Hernandez, Jose A; Fang, Erica; Quintanilla, Norma M; Roy, Angshumoy; López-Terrada, Dolores H

    2016-01-01

    Thyroid nodules occur in 1-2% of children, and identifying which nodules are malignant is often challenging. Cytologic evaluation facilitates the diagnosis of thyroid lesions (TLs), but in 10-40% of cases the interpretation is indeterminate. Patients with indeterminate diagnoses are often treated with hemithyroidectomy followed by completion thyroidectomy, if cancer is found in the initial specimen. Exposing patients to multiple surgeries increases costs and morbidity. The American Thyroid Association states that a combination of molecular markers is likely to optimize the management of patients with indeterminate cytology. However, few studies have addressed the molecular alterations present in pediatric TL. Twenty-seven thyroid carcinomas from patients 10 to 19 years of age were tested for alterations common in adult TL, including BRAF V600E mutation, RET fusions, and TERT promoter mutations. Mutation-negative cases were subsequently analyzed with a next-generation sequencing (NGS) mutation panel to search for additional targets. Histologic diagnoses included 12 classic papillary thyroid carcinomas (PTCs), 13 follicular variant PTCs, 1 medullary thyroid carcinoma, and 1 follicular carcinoma. Fourteen cases showed lymph node involvement, and 13 cases demonstrated lymphovascular invasion. The BRAF V600E mutation was detected in 10/27 cases, and RET fusions were detected in 6/27 cases. No TERT promoter mutations were identified in any of the cases. The NGS panel revealed additional RET and CTNNB1 pathogenic missense mutations. Our results demonstrate that molecular abnormalities are common in pediatric TLs and suggest that incorporation of molecular testing will be helpful in optimizing patient management. PMID:26366474

  11. Thyroid Disease and the Heart.

    PubMed

    Klein, Irwin; Danzi, Sara

    2016-02-01

    Thyroid hormones have an intimate relationship with cardiac function. Some of the most significant clinical signs and symptoms of thyroid disease are the cardiac manifestations. In both hypothyroidism and hyperthyroidism, the characteristic physiological effects of thyroid hormone can be understood from the actions at the molecular and cellular level. Here we explore topics from the metabolism and cellular effects of thyroid hormone to special considerations related to statin and amiodarone therapy for the alterations in thyroid hormone metabolism that accompany heart disease. PMID:26792255

  12. Rapid alterations of avian medullary bone material during the daily egg-laying cycle.

    PubMed

    Kerschnitzki, Michael; Zander, Thomas; Zaslansky, Paul; Fratzl, Peter; Shahar, Ron; Wagermaier, Wolfgang

    2014-12-01

    Bone is a dynamic tissue which is continuously adapting not only to external mechanical stimuli but also to internal metabolic calcium demands. During normal bone remodeling, bone-resorbing osteoclasts release calcium from the bone and digest the collagenous bone matrix, after which bone-depositing osteoblasts form unmineralized collagen matrix, which subsequently mineralizes. The detailed mechanism by which calcium is deposited at the site of mineralization and removed from it during bone resorption is largely unknown. Experimental studies are difficult to conduct because in adult bone only a small fraction of bone tissue is remodeled at any moment in time. Thus, one promising approach is to study mineral deposition and resorption in model systems in which a large fraction of the bone mineral is mobilized in a relatively short period of time. We investigated the microscopic and nanoscopic alterations of avian medullary bone architecture during the egg-laying (oviposition) cycle of hens. Medullary bone forms a labile calcium reservoir for eggshell production and is characterized by an extremely rapid and high-flux calcium metabolism. It thus, provides the unique opportunity to study processes of bone remodeling in their most intensive form. We used a combination of synchrotron X-ray tomography together with small angle X-ray scattering (SAXS), wide angle X-ray diffraction (WAXD) and X-ray fluorescence (XRF) to correlate microscopic medullary bone attributes such as the mineral content, medullary bone volume fraction and medullary bone trabecular thickness with nanoscopic alterations in the mineral particle size (thickness parameter T and length parameter L) during the oviposition cycle. To identify the timing of the different stages of the cycle, ionic calcium, phosphorus and PTH concentrations in the blood of the layers were monitored. We found that the microscopic and nanoscopic architecture of avian medullary bone material changes rapidly during the oviposition

  13. Thyroid cell lines in research on goitrogenesis.

    PubMed

    Gerber, H; Peter, H J; Asmis, L; Studer, H

    1991-12-01

    Thyroid cell lines have contributed a lot to the understanding of goitrogenesis. The cell lines mostly used in thyroid research are briefly discussed, namely the rat thyroid cell lines FRTL and FRTL-5, the porcine thyroid cell lines PORTHOS and ARTHOS, The sheep thyroid cell lines OVNIS 5H and 6H, the cat thyroid cell lines PETCAT 1 to 4 and ROMCAT, and the human thyroid cell lines FTC-133 and HTh 74. Chinese hamster ovary (CHO) cells and COS-7 cells, stably transfected with TSH receptor cDNA and expressing a functional TSH receptor, are discussed as examples for non-thyroidal cells, transfected with thyroid genes. PMID:1726925

  14. Vaccine Therapy With or Without Sargramostim in Treating Patients With Advanced or Metastatic Cancer

    ClinicalTrials.gov

    2013-01-24

    Adenocarcinoma of the Colon; Adenocarcinoma of the Gallbladder; Adenocarcinoma of the Pancreas; Adenocarcinoma of the Rectum; Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Gallbladder; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Male Breast Cancer; Mixed Adenocarcinoma of the Stomach; Ovarian Endometrioid Adenocarcinoma; Paget Disease of the Breast With Intraductal Carcinoma; Paget Disease of the Breast With Invasive Ductal Carcinoma; Recurrent Adult Primary Liver Cancer; Recurrent Breast Cancer; Recurrent Colon Cancer; Recurrent Gallbladder Cancer; Recurrent Gastric Cancer; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Recurrent Salivary Gland Cancer; Salivary Gland Adenocarcinoma; Stage II Malignant Testicular Germ Cell Tumor; Stage II Pancreatic Cancer; Stage III Colon Cancer; Stage III Gastric Cancer; Stage III Malignant Testicular Germ Cell Tumor; Stage III Pancreatic Cancer; Stage III Rectal Cancer; Stage III Salivary Gland Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IV Breast Cancer; Stage IV Colon Cancer; Stage IV Gastric Cancer; Stage IV Pancreatic Cancer; Stage IV Rectal Cancer; Stage IV Salivary Gland Cancer; Thyroid Gland Medullary Carcinoma; Unresectable Gallbladder Cancer

  15. What Causes Thyroid Cancer?

    MedlinePlus

    ... not yet known. Certain changes in a person’s DNA can cause thyroid cells to become cancerous. DNA is the chemical in each of our cells ... parents because they are the source of our DNA. But DNA affects more than just how we ...

  16. Cancer of the Thyroid

    MedlinePlus

    ... at a Glance Show More At a Glance Estimated New Cases in 2016 64,300 % of All New Cancer Cases 3.8% Estimated Deaths in 2016 1,980 % of All Cancer ... of This Cancer : In 2013, there were an estimated 637,115 people living with thyroid cancer in ...

  17. Thyroid Cancer Risk Factors

    MedlinePlus

    ... and radiation fallout from power plant accidents or nuclear weapons. Having had head or neck radiation treatments in childhood is a risk factor for ... should be done using the lowest dose of radiation that still provides a clear ... from nuclear weapons or power plant accidents. For instance, thyroid ...

  18. Pregnancy and Thyroid Disease

    MedlinePlus

    ... to make thyroid hormone, iodine is an important mineral for a mother during pregnancy. During pregnancy, the baby gets iodine from the mother’s diet. Women need more iodine when they are pregnant—about 250 micrograms a day. In the United States, about 7 percent of pregnant women may not ...

  19. Overview of the 2015 American Thyroid Association guidelines for managing thyroid nodules and differentiated thyroid cancer.

    PubMed

    Matti, Bashar; Cohen-Hallaleh, Ruben

    2016-01-01

    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. PMID:27607088

  20. Celecoxib, a cyclooxygenase-2 inhibitor, potentiates the chemotherapic effect of vinorelbine in the medullary thyroid cancer TT cell line.

    PubMed

    Vivaldi, A; Ciampi, R; Tacito, A; Molinaro, E; Agate, L; Bottici, V; Pinchera, A; Collecchi, P; Elisei, R

    2012-05-15

    We analyzed the in vitro effects of celecoxib, a COX-2 inhibitor, and determined if celecoxib can sensitize a human MTC-derived cell line (TT) to chemotherapeutics. We found that celecoxib induced apoptosis in TT cells and decreased drug efflux by reducing the expression of MDR-1 mRNA, which codes for the drug efflux pump P-gp. We also observed that TT cells were 10-fold more resistant to doxorubicin than to vinorelbine, mimicking what can be observed in clinical practice. In addition, we found that the combination of celecoxib and vinorelbine, but not doxorubicin, induced a significant reduction in cell viability and a significant increase in apoptosis. In conclusion, we showed that celecoxib was able to enhance the chemotherapeutic effect of vinorelbine. A clinical trial exploring the in vivo activities of celecoxib in MTC patients who cannot benefit from available treatments would be desirable, taking into account the possible risks of cardiovascular effects of this drug. PMID:22305971

  1. Morphological ultrasound microimaging of thyroid in living mice.

    PubMed

    Mancini, Marcello; Vergara, Emilia; Salvatore, Giuliana; Greco, Adelaide; Troncone, Giancarlo; Affuso, Andrea; Liuzzi, Raffaele; Salerno, Paolo; Scotto di Santolo, Maria; Santoro, Massimo; Brunetti, Arturo; Salvatore, Marco

    2009-10-01

    The objective of the study was to explore high-frequency ultrasound (HFUS) for noninvasive microimaging of thyroid in living mice. Thyroid examination was performed by HFUS in 10 normal C57BL/6 mice, eight mice treated by propylthiouracil, and 22 Tg-TRK-T1 transgenic mice. The dimension of the gland and the presence of nodules were evaluated. Nodules were classified as malignant (hypoechogenicity, poorly defined margins, internal microcalcification, irregular shapes, and extra glandular extension) or not, and the findings were compared with histological data. Thyroid images were successfully obtained in all the animals analyzed. Normal thyroid reached a volume of 4.92 microl (range 2.11-4.92 microl). Mice with propylthiouracil-induced goiter showed diffuse thyroid enlargement (median volume 6.67 microl, range 4.09-8.82 microl). In 19 of 22 Tg-TRK-T1 mice (86%), HFUS identified a nodular process (the smallest detected nodule had a diameter of 0.46 mm). Eleven nodules were classified as malignant and eight as benign. Compared with histological analysis, HFUS showed a sensitivity of 100% in the detection of thyroid nodules and a specificity of 60% (two of the nodules identified by HFUS were not confirmed at the histology). The specificity and sensitivity of HFUS in predicting the malignancy of the thyroid nodules were 83 and 91%, respectively. Thus, HFUS is an accurate imaging modality that can potentially replace more invasive techniques, and, therefore, it represents a significant advancement in phenotypic assessment of mouse models of thyroid cancer. PMID:19589864

  2. Chemical contamination and the thyroid.

    PubMed

    Duntas, Leonidas H

    2015-02-01

    Industrial chemical contaminants have a variable impact on the hypothalamic-pituitary-thyroid axis, this depending both on their class and on confounding factors. Today, mounting evidence is pointing to the role of environmental factors, and specifically EDCs, in the current distressing upsurge in the incidence of thyroid disease. The unease is warranted. These substances, which are nowadays rife in our environments (including in foodstuffs), have been shown to interfere with thyroid hormone action, biosynthesis, and metabolism, resulting in disruption of tissue homeostasis and/or thyroid function. Importantly, based on the concept of the "nonmonotonic dose-response curve", the relationship between dose and effect has often been found to be nonlinear. Thus, small doses can induce unpredictable, adverse effects, one case being polychlorinated biphenyls (PCBs), of which congener(s) may centrally inhibit the hypothalamic-pituitary-thyroid axis, or dissociate thyroid receptor and selectively affect thyroid hormone signaling and action. This means that PCBs can act as agonists or antagonists at the receptor level, underlining the complexity of the interaction. This review highlights the multifold activity of chemicals demonstrated to cause thyroid disruption. It also represents a call to action among clinicians to undertake systematic monitoring of thyroid function and registering of the classes of EDs and additionally urges broader scientific collaborations to clarify these chemicals' molecular mechanisms of action, substances whose prevalence in our environments is disrupting not only the thyroid but all life on earth. PMID:25294013

  3. Thyroid, spermatogenesis, and male infertility.

    PubMed

    Rajender, Singh; Monica, Marie Gray; Walter, Lee; Agarwal, Ashok

    2011-01-01

    Since the identification of thyroid hormone receptors on the testes, thyroid has been suggested to have a significant impact on the male reproductive tract, spermatogenesis, and male fertility. Several research articles on the role of thyroid in spermatogenesis or male infertility have been published in the last three decades. We conducted an exhaustive literature search was conducted in order to create an up-to-date review of literature. This review aims to discuss the impact of thyroid on testicular development, spermatogenesis, hypo- or hyper- thyroidism and male infertility, and the management of thyroid related abnormal semen profile. The literature revealed that thyroid significantly impacts testicular development and that abnormal thyroid profile affects semen quality and male fertility by compromising testicular size, sperm motility and ejaculate volume. A clear link exists between thyroid hormones, testicular development and spermatogenesis. Thyroid disease negatively affects spermatogenesis and consequently may cause male infertility. In such cases, infertility is reversible, but more studies need to be conducted, especially in post-pubertal males to cement the current findings. PMID:21622096

  4. Malignant histiocytosis (histiocytic medullary reticulosis) with spindle cell differentiation and tumour formation.

    PubMed Central

    Macgillivray, J B; Duthie, J S

    1977-01-01

    Malignant histiocytosis (histiocytic medullary reticulosis) in a 45-year-old white man is described. Unusual features were presentation as a surgical emergency with signs of obstruction and peritonitis due to an ileal tumour and extensive spindle cell differentiation. Problems in the differential diagnosis of malignant histiocytosis are briefly discussed. Images PMID:845260

  5. CCR4 promotes medullary entry and thymocyte-dendritic cell interactions required for central tolerance.

    PubMed

    Hu, Zicheng; Lancaster, Jessica N; Sasiponganan, Chayanit; Ehrlich, Lauren I R

    2015-10-19

    Autoimmunity results from a breakdown in central or peripheral tolerance. To establish central tolerance, developing T cells must enter the thymic medulla, where they scan antigen-presenting cells (APCs) displaying a diverse array of autoantigens. If a thymocyte is activated by a self-antigen, the cell undergoes either deletion or diversion into the regulatory T cell (T reg) lineage, thus maintaining self-tolerance. Mechanisms promoting thymocyte medullary entry and interactions with APCs are incompletely understood. CCR4 is poised to contribute to central tolerance due to its expression by post-positive selection thymocytes, and expression of its ligands by medullary thymic dendritic cells (DCs). Here, we use two-photon time-lapse microscopy to demonstrate that CCR4 promotes medullary entry of the earliest post-positive selection thymocytes, as well as efficient interactions between medullary thymocytes and DCs. In keeping with the contribution of thymic DCs to central tolerance, CCR4 is involved in regulating negative selection of polyclonal and T cell receptor (TCR) transgenic thymocytes. In the absence of CCR4, autoreactive T cells accumulate in secondary lymphoid organs and autoimmunity ensues. These studies reveal a previously unappreciated role for CCR4 in the establishment of central tolerance. PMID:26417005

  6. Placental Insufficiency Associated with Loss of Cited1 Causes Renal Medullary Dysplasia

    PubMed Central

    Sparrow, Duncan B.; Boyle, Scott C.; Sams, Rebecca S.; Mazuruk, Bogdan; Zhang, Li; Moeckel, Gilbert W.; Dunwoodie, Sally L.; de Caestecker, Mark P.

    2009-01-01

    A number of studies have shown that placental insufficiency affects embryonic patterning of the kidney and leads to a decreased number of functioning nephrons in adulthood; however, there is circumstantial evidence that placental insufficiency may also affect renal medullary growth, which could account for cases of unexplained renal medullary dysplasia and for abnormalities in renal function among infants who had experienced intrauterine growth retardation. We observed that mice with late gestational placental insufficiency associated with genetic loss of Cited1 expression in the placenta had renal medullary dysplasia. This was not caused by lower urinary tract obstruction or by defects in branching of the ureteric bud during early nephrogenesis but was associated with decreased tissue oxygenation and increased apoptosis in the expanding renal medulla. Loss of placental Cited1 was required for Cited1 mutants to develop renal dysplasia, and this was not dependent on alterations in embryonic Cited1 expression. Taken together, these findings suggest that renal medullary dysplasia in Cited1 mutant mice is a direct consequence of decreased tissue oxygenation resulting from placental insufficiency. PMID:19297558

  7. CCR4 promotes medullary entry and thymocyte–dendritic cell interactions required for central tolerance

    PubMed Central

    Hu, Zicheng; Lancaster, Jessica N.; Sasiponganan, Chayanit

    2015-01-01

    Autoimmunity results from a breakdown in central or peripheral tolerance. To establish central tolerance, developing T cells must enter the thymic medulla, where they scan antigen-presenting cells (APCs) displaying a diverse array of autoantigens. If a thymocyte is activated by a self-antigen, the cell undergoes either deletion or diversion into the regulatory T cell (T reg) lineage, thus maintaining self-tolerance. Mechanisms promoting thymocyte medullary entry and interactions with APCs are incompletely understood. CCR4 is poised to contribute to central tolerance due to its expression by post-positive selection thymocytes, and expression of its ligands by medullary thymic dendritic cells (DCs). Here, we use two-photon time-lapse microscopy to demonstrate that CCR4 promotes medullary entry of the earliest post-positive selection thymocytes, as well as efficient interactions between medullary thymocytes and DCs. In keeping with the contribution of thymic DCs to central tolerance, CCR4 is involved in regulating negative selection of polyclonal and T cell receptor (TCR) transgenic thymocytes. In the absence of CCR4, autoreactive T cells accumulate in secondary lymphoid organs and autoimmunity ensues. These studies reveal a previously unappreciated role for CCR4 in the establishment of central tolerance. PMID:26417005

  8. Thyroid dysfunction and pregnancy outcomes

    PubMed Central

    Nazarpour, Sima; Ramezani Tehrani, Fahimeh; Simbar, Masoumeh; Azizi, Fereidoun

    2015-01-01

    Background: Pregnancy has a huge impact on the thyroid function in both healthy women and those that have thyroid dysfunction. The prevalence of thyroid dysfunction in pregnant women is relatively high. Objective: The objective of this review was to increase awareness and to provide a review on adverse effect of thyroid dysfunction including hyperthyroidism, hypothyroidism and thyroid autoimmune positivity on pregnancy outcomes. Materials and Methods: In this review, Medline, Embase and the Cochrane Library were searched with appropriate keywords for relevant English manuscript. We used a variety of studies, including randomized clinical trials, cohort (prospective and retrospective), case-control and case reports. Those studies on thyroid disorders among non-pregnant women and articles without adequate quality were excluded. Results: Overt hyperthyroidism and hypothyroidism has several adverse effects on pregnancy outcomes. Overt hyperthyroidism was associated with miscarriage, stillbirth, preterm delivery, intrauterine growth retardation, low birth weight, preeclampsia and fetal thyroid dysfunction. Overt hypothyroidism was associated with abortion, anemia, pregnancy-induced hypertension, preeclampsia, placental abruption, postpartum hemorrhage, premature birth, low birth weight, intrauterine fetal death, increased neonatal respiratory distress and infant neuro developmental dysfunction. However the adverse effect of subclinical hypothyroidism, and thyroid antibody positivity on pregnancy outcomes was not clear. While some studies demonstrated higher chance of placental abruption, preterm birth, miscarriage, gestational hypertension, fetal distress, severe preeclampsia and neonatal distress and diabetes in pregnant women with subclinical hypothyroidism or thyroid autoimmunity; the other ones have not reported these adverse effects. Conclusion: While the impacts of overt thyroid dysfunction on feto-maternal morbidities have been clearly identified and its long

  9. Thyroid diseases and female reproduction.

    PubMed

    Mintziori, G; Anagnostis, P; Toulis, K A; Goulis, D G

    2012-02-01

    Thyroid diseases are very common in women of reproductive age. The aim of this study was to review the current evidence on physiology, pathophysiology, diagnosis and management of women with thyroid disorders that are currently seeking fertility, undergoing assisted reproduction technologies (ART) or being pregnant. Normal thyroid function is essential for normal function of the gonadal axis, thus important in maintaining normal reproductive capacity. On the contrary, any type of thyroid dysfunction may reduce the likelihood of pregnancy; the latter can be restored to normal after appropriate treatment. Over eight million children have been born as a result of assisted reproduction techniques (ART) since 1978. As these procedures are becoming more common in clinical practice, the exact impact of thyroid status on reproductive outcomes as well as that of drugs used in ART on thyroid function has to be fully elucidated. Maternal thyroid function is crucial, especially during the first weeks of gestation, for offspring's wellness and brain development. On the other hand, normal physiological mechanisms during gestation can have a major impact on maternal thyroid function. As human chorionic gonadotropin (hCG) has a thyroid stimulating hormone (TSH)-like effect, high hCG concentrations are associated with thyroid stimulation, both functionally (lower serum TSH concentrations) and anatomically (increased thyroid volume). Although the association between maternal hypothyroidism and increased perinatal morbidity has been described for over a century, more recently, even the presence of anti-thyroid antibodies has been associated with adverse pregnancy outcomes, such as recurrent abortions and placental abruption. This is of major clinical significance, as anti-thyroid antibodies are surprisingly prevalent in pregnancy, especially during the first two trimesters. PMID:22278068

  10. Thyroid disrupting chemicals in plastic additives and thyroid health.

    PubMed

    Andra, Syam S; Makris, Konstantinos C

    2012-01-01

    The globally escalating thyroid nodule incidence rates may be only partially ascribed to better diagnostics, allowing for the assessment of environmental risk factors on thyroid disease. Endocrine disruptors or thyroid-disrupting chemicals (TDC) like bisphenol A, phthalates, and polybrominated diphenyl ethers are widely used as plastic additives in consumer products. This comprehensive review studied the magnitude and uncertainty of TDC exposures and their effects on thyroid hormones for sensitive subpopulation groups like pregnant women, infants, and children. Our findings qualitatively suggest the mixed, significant (α = 0.05) TDC associations with natural thyroid hormones (positive or negative sign). Future studies should undertake systematic meta-analyses to elucidate pooled TDC effect estimates on thyroid health indicators and outcomes. PMID:22690712

  11. The age- and shorter telomere-dependent TERT promoter mutation in follicular thyroid cell-derived carcinomas.

    PubMed

    Liu, T; Wang, N; Cao, J; Sofiadis, A; Dinets, A; Zedenius, J; Larsson, C; Xu, D

    2014-10-16

    Telomerase activation through induction of its catalytic component telomerase reverse transcriptase (TERT) expression is essential for malignant transformation. TERT promoter mutations namely C228T and C250T that stimulate TERT transcription and telomerase activation have recently been identified in many human malignancies. We thus determined these mutations and their biological and clinical implications in thyroid carcinomas in the present study. The TERT promoter was sequenced in 10 thyroid cancer cell lines and 144 tumors from 20 patients with anaplastic thyroid carcinoma (ATC), 51 with papillary thyroid carcinoma (PTC), 36 with follicular thyroid carcinoma (FTC), and 37 with medullary thyroid carcinoma (MTC). We identified C228T or C250T mutation in 6/8 of ATC cell lines, as well as in tumor tissue from 10/20, 13/51, 8/36 and 0/37 patients with ATC, PTC, FTC and MTC, respectively. In PTC patients, these mutations were exclusively present in the group with age >45 years (P<0.0001), and highly correlated shorter telomeres (P<0.0001) and distant metastasis (P=0.028). The previous radioactivity exposure did not induce the mutation. The presence of C228T or C250T was an independent predictor associated with shorter disease-related survival (DRS) in the entire cohort (P<0.0001), as well as among patients >45 years (P=0.021). ATC patients carrying the mutation survived shorter than those without mutations, although not statistically significant (P=0.129). The TERT promoter mutation was associated with overall survival (P=0.038) and DRS (P=0.058) of FTC patients. Taken together, age- and shorter telomere-dependent TERT promoter mutations occur frequently in follicular cell-derived thyroid carcinoma (ATC, PTC and FTC) but not in parafollicular cell-originated MTC, and may serve as a marker for aggressive disease and poor outcome. PMID:24141777

  12. Thyroid disrupting chemicals: Mechanisms and mixtures

    EPA Science Inventory

    Environmental contaminants are known to act as thyroid disrupting chemicals (TDCs). Broadly defined, TDCs are xenobiotics that alter the structure or function of the thyroid gland, alter regulatory enzymes associated with thyroid hormone (TH) homeostasis, or change circulating o...

  13. Treatment Options by Stage (Thyroid Cancer)

    MedlinePlus

    ... glands make hormones. The thyroid uses iodine , a mineral found in some foods and in iodized salt, ... Fine-needle aspiration biopsy of the thyroid : The removal of thyroid tissue using a thin needle. The ...

  14. Fine needle aspiration of the thyroid

    MedlinePlus

    Thyroid nodule fine needle aspirate biopsy; Biopsy - thyroid - skinny-needle; Skinny-needle thyroid biopsy ... under your shoulders and your neck extended. The biopsy site is cleaned. A thin needle is inserted ...

  15. Medullary raphe neurones and baroreceptor modulation of the respiratory motor pattern in the cat

    PubMed Central

    Lindsey, B G; Arata, A; Morris, K F; Hernandez, Y M; Shannon, R

    1998-01-01

    Perturbations of arterial blood pressure change medullary raphe neurone activity and the respiratory motor pattern. This study sought evidence for actions of baroresponsive raphe neurones on the medullary respiratory network.Blood pressure was perturbed by intravenous injection of an α1-adrenergic receptor agonist, unilateral pressure changes in the carotid sinus, or occlusion of the descending aorta in thirty-six Dial-urethane-anaesthetized, vagotomized, paralysed, artificially ventilated cats. Neurones were monitored with microelectrode arrays in two or three of the following domains: nucleus raphe obscurus-nucleus raphe pallidus, nucleus raphe magnus, and rostral and caudal ventrolateral medulla. Data were analysed with cycle-triggered histograms, peristimulus time and cumulative sum histograms, cross-correlograms and spike-triggered averages of efferent phrenic nerve activity.Prolongation of the expiratory phase and decreased peak integrated phrenic amplitude were most frequently observed. Of 707 neurones studied, 310 had altered firing rates during stimulation; changes in opposite directions were monitored simultaneously in fifty-six of eighty-seven data sets with at least two baroresponsive neurones.Short time scale correlations were detected between neurones in 347 of 3388 pairs. Seventeen pairs of baroresponsive raphe neurones exhibited significant offset correlogram features indicative of paucisynaptic interactions. In correlated raphe-ventrolateral medullary neurone pairs with at least one baroresponsive neurone, six of seven ventrolateral medullary decrementing expiratory (E-Decr) neurones increased their firing rate during baroreceptor stimulation. Thirteen of fifteen ventrolateral medullary inspiratory neurones correlated with raphe cells decreased their firing rate during baroreceptor stimulation.The results support the hypothesis that raphe neuronal assemblies transform and transmit information from baroreceptors to neurones in the ventral

  16. AZD6244 in Treating Patients With Papillary Thyroid Cancer That Did Not Respond to Radioactive Iodine

    ClinicalTrials.gov

    2016-09-02

    Recurrent Thyroid Gland Carcinoma; Stage I Thyroid Gland Papillary Carcinoma; Stage II Thyroid Gland Papillary Carcinoma; Stage III Thyroid Gland Papillary Carcinoma; Stage IV Thyroid Gland Papillary Carcinoma

  17. Reproductive manifestations of thyroid disease.

    PubMed

    Johnson, C A

    1994-05-01

    Thyroid function and reproductive function have many interactions, the scope and mechanism of which are not fully understood. These functions are of greatest clinical importance for veterinarians working with breeders of purebred dogs. Thyroid dysfunction does not always result in clinical signs of reproductive disorders or in subfertility. It seems that animals with overt thyroid dysfunction are those most likely to manifest reproduction problems. PMID:8053110

  18. Thyroid Cancer and Tumor Collaborative Registry (TCCR).

    PubMed

    Shats, Oleg; Goldner, Whitney; Feng, Jianmin; Sherman, Alexander; Smith, Russell B; Sherman, Simon

    2016-01-01

    A multicenter, web-based Thyroid Cancer and Tumor Collaborative Registry (TCCR, http://tccr.unmc.edu) allows for the collection and management of various data on thyroid cancer (TC) and thyroid nodule (TN) patients. The TCCR is coupled with OpenSpecimen, an open-source biobank management system, to annotate biospecimens obtained from the TCCR subjects. The demographic, lifestyle, physical activity, dietary habits, family history, medical history, and quality of life data are provided and may be entered into the registry by subjects. Information on diagnosis, treatment, and outcome is entered by the clinical personnel. The TCCR uses advanced technical and organizational practices, such as (i) metadata-driven software architecture (design); (ii) modern standards and best practices for data sharing and interoperability (standardization); (iii) Agile methodology (project management); (iv) Software as a Service (SaaS) as a software distribution model (operation); and (v) the confederation principle as a business model (governance). This allowed us to create a secure, reliable, user-friendly, and self-sustainable system for TC and TN data collection and management that is compatible with various end-user devices and easily adaptable to a rapidly changing environment. Currently, the TCCR contains data on 2,261 subjects and data on more than 28,000 biospecimens. Data and biological samples collected by the TCCR are used in developing diagnostic, prevention, treatment, and survivorship strategies against TC. PMID:27168721

  19. Thyroid Cancer and Tumor Collaborative Registry (TCCR)

    PubMed Central

    Shats, Oleg; Goldner, Whitney; Feng, Jianmin; Sherman, Alexander; Smith, Russell B.; Sherman, Simon

    2016-01-01

    A multicenter, web-based Thyroid Cancer and Tumor Collaborative Registry (TCCR, http://tccr.unmc.edu) allows for the collection and management of various data on thyroid cancer (TC) and thyroid nodule (TN) patients. The TCCR is coupled with OpenSpecimen, an open-source biobank management system, to annotate biospecimens obtained from the TCCR subjects. The demographic, lifestyle, physical activity, dietary habits, family history, medical history, and quality of life data are provided and may be entered into the registry by subjects. Information on diagnosis, treatment, and outcome is entered by the clinical personnel. The TCCR uses advanced technical and organizational practices, such as (i) metadata-driven software architecture (design); (ii) modern standards and best practices for data sharing and interoperability (standardization); (iii) Agile methodology (project management); (iv) Software as a Service (SaaS) as a software distribution model (operation); and (v) the confederation principle as a business model (governance). This allowed us to create a secure, reliable, user-friendly, and self-sustainable system for TC and TN data collection and management that is compatible with various end-user devices and easily adaptable to a rapidly changing environment. Currently, the TCCR contains data on 2,261 subjects and data on more than 28,000 biospecimens. Data and biological samples collected by the TCCR are used in developing diagnostic, prevention, treatment, and survivorship strategies against TC. PMID:27168721

  20. The relevance of preoperative ultrasound cervical mapping in patients with thyroid cancer

    PubMed Central

    Kocharyan, Davit; Schwenter, Frank; Bélair, Manon; Nassif, Edgard

    2016-01-01

    Background Cervical lymph node involvement in thyroid cancer is associated with locoregional recurrence and decreased disease-free survival. Preoperative lymph node mapping helps in planning surgery for neck dissection and improves patient outcomes. We sought to perform a qualitative and quantitative analysis of ultrasound mapping for thyroid cancer and evaluate the clinical importance of this exam in terms of identifying the group of patients who would benefit most from subsequent surgical dissection. Methods We retrospectively reviewed the cases of 263 patients who underwent thyroid surgery between 2009 and 2013. We calculated the positive predictive values (PPVs) of ultrasound mapping of both the lateral and central compartments together and the lateral or central compartment individually. A quantitative analysis was performed by comparing the number of positive lymph nodes at ultrasound imaging with histopathologic evaluation. Results A total of 136 cases of thyroid cancer in 120 patients met the inclusion criteria for ultrasound mapping analysis. The PPVs (and 95% confidence intervals) were 83.82 (0.76–0.89) for the lateral and central compartments, 85.39% (0.76–0.91) for the lateral compartment, and 80.48% (0.7–0.87) for the central compartment. When comparing the positive lymph nodes at ultrasound imaging with histopathologic evaluation, the result was χ2 = 10.33 (p = 0.006). Conclusion This single-institution study indicated that preoperative ultrasound mapping is an accurate imaging procedure for predicting lymphatic spread in differentiated and medullary thyroid cancer. Ultrasound mapping can be used as an efficient tool for surgical planning and prognosis determination, as well as for identifying the group of patients who would benefit most from subsequent surgical intervention. PMID:27007092

  1. Utility of a Histone Deacetylase Inhibitor (PXD101) for Thyroid Cancer Treatment

    PubMed Central

    Lin, Shu-Fu; Lin, Jen-Der; Chou, Ting-Chao; Huang, Yu-Yao; Wong, Richard J.

    2013-01-01

    Background We evaluated the therapeutic effects of the histone deacetylase inhibitor PXD101 alone and in combination with conventional chemotherapy in treating thyroid cancer. Methodology/Principal Findings We studied eight cell lines from four types of thyroid cancer (papillary, follicular, anaplastic and medullary). The cytotoxicity of PXD101 alone and in combination with three conventional chemotherapeutic agents (doxorubicin, paclitaxel and docetaxel) was measured using LDH assay. Western blot assessed expression of acetylation of histone H3, histone H4 and tubulin, proteins associated with apoptosis, RAS/RAF/ERK and PI3K/AKT/mTOR signaling pathways, DNA damage and repair. Apoptosis and intracellular reactive oxygen species (ROS) were measured by flow cytometry. Mice bearing flank anaplastic thyroid cancers (ATC) were daily treated with intraperitoneal injection of PXD101 for 5 days per week. PXD101 effectively inhibited thyroid cancer cell proliferation in a dose-dependent manner. PXD101 induced ROS accumulation and inhibited RAS/RAF/ERK and PI3K/mTOR pathways in sensitive cells. Double-stranded DNA damage and apoptosis were induced by PXD101 in both sensitive and resistant cell lines. PXD101 retarded growth of 8505C ATC xenograft tumors with promising safety. Combination therapy of PXD101with doxorubicin and paclitaxel demonstrated synergistic effects against four ATC lines in vitro. Conclusions PXD101 represses thyroid cancer proliferation and has synergistic effects in combination with doxorubicin and paclitaxel in treating ATC. These findings support clinical trials using PXD101 for patients with this dismal disease. PMID:24155971

  2. Thyroid scintigraphy in veterinary medicine.

    PubMed

    Daniel, Gregory B; Neelis, Dana A

    2014-01-01

    Thyroid scintigraphy is performed in cats and dogs and has been used to a limited degree in other species such as the horse. Thyroid scintigraphy is most commonly used to aid in the diagnosis and treatment management of feline hyperthyroidism but is also used in the evaluation of canine hypothyroidism and canine thyroid carcinoma. This article reviews the normal scintigraphic appearance of the thyroid in the cat, the dog, and the horse and the principles of interpretation of abnormal scan results in the cat and the dog. Radioiodine is the treatment of choice for feline hyperthyroidism, and the principles of its use in the cat are reviewed. PMID:24314043

  3. Viruses and thyroiditis: an update

    PubMed Central

    Desailloud, Rachel; Hober, Didier

    2009-01-01

    Viral infections are frequently cited as a major environmental factor involved in subacute thyroiditis and autoimmune thyroid diseases This review examines the data related to the role of viruses in the development of thyroiditis. Our research has been focused on human data. We have reviewed virological data for each type of thyroiditis at different levels of evidence; epidemiological data, serological data or research on circulating viruses, direct evidence of thyroid tissue infection. Interpretation of epidemiological and serological data must be cautious as they don't prove that this pathogen is responsible for the disease. However, direct evidence of the presence of viruses or their components in the organ are available for retroviruses (HFV) and mumps in subacute thyroiditis, for retroviruses (HTLV-1, HFV, HIV and SV40) in Graves's disease and for HTLV-1, enterovirus, rubella, mumps virus, HSV, EBV and parvovirus in Hashimoto's thyroiditis. However, it remains to determine whether they are responsible for thyroid diseases or whether they are just innocent bystanders. Further studies are needed to clarify the relationship between viruses and thyroid diseases, in order to develop new strategies for prevention and/or treatment. PMID:19138419

  4. Thyroid Cancer in Pediatrics.

    PubMed

    Machac, Josef

    2016-06-01

    Well differentiated thyroid cancer (DTC) in children is characterized by a high rate of response to treatment and low disease-specific mortality. Treatment of children with DTC has evolved toward a greater reliance on evaluation and monitoring with serial serum thyroglobulin measurements and ultrasound examinations. Radioiodine therapy is recommended for thyroid remnant ablation in high-risk patients, treatment of demonstrated radioiodine-avid local-regional disease not amenable to surgical resection, or distant radioiodine-avid metastatic disease. Sufficient time should be given for benefits of radioiodine therapy to be realized, with follow-up monitoring. Re-treatment with radioiodine can be deferred until progression of significant disease manifests. PMID:27241970

  5. Incidental thyroid nodules and thyroid cancer: considerations before determining management.

    PubMed

    Tufano, Ralph P; Noureldine, Salem I; Angelos, Peter

    2015-06-01

    The worldwide incidence of thyroid cancer is increasing substantially, almost exclusively attributable to small papillary thyroid cancers. Increased use of diagnostic imaging is considered the most likely explanation for this reported rise, but other factors may also be contributing. The increase in health care expenditures related to managing these presumably low-risk cancers, without a clear patient benefit, has resulted in a backlash against the early detection of thyroid cancer. Currently, there is no way to confidently predict which incidentally detected thyroid nodule may be the precursor to a more aggressive process. Predictions such as these would require more accurate characterization of the biology of individual thyroid cancers than is currently possible. With time, we might prove our ability to confidently differentiate low-risk from high-risk thyroid cancers, but until that happens, routine screening for thyroid cancer by imaging billed as a "health checkup" should not be performed. However, incidentally detected thyroid nodules should be reported, and a clear medical team management plan should be developed. Our ethical responsibility is to provide patients with objective, evidence-based information about their disease status, not to assume that we know what is best for them by selectively withholding information. In addition, providing patients with psychosocial assistance will help them process the information necessary to make informed decisions that will provide them with the most value when a small thyroid nodule or cancer is incidentally identified. Herein, we summarize the epidemiological data for disease incidence, discuss some controversies in disease management, and outline the key elements and ethical considerations of informed decision making as they apply to managing incidentally detected thyroid nodules and thyroid cancer. PMID:25928353

  6. 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

  7. Radiofrequency ablation for postsurgical thyroid removal of differentiated thyroid carcinoma.

    PubMed

    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 (99m)TcO4 (-) 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

  8. Tubercular thyroid abscess.

    PubMed

    Kumar, Awanish; Pahwa, Harvinder Singh; Srivastava, Rohit; Khan, Khursheed Alam

    2013-01-01

    We encountered a patient who presented with neck swelling, difficulty in swallowing, voice change along with systemic features such as evening rise of temperature, chronic cough and weight loss. Ultrasonography of the thyroid gland revealed two cystic swellings. An ultrasound guided fine needle aspiration cytology was suggestive of tubercular abscess. The patient responded well to antigravity aspiration of the swellings and antitubercular treatment. PMID:23814203

  9. Thyroid associated orbitopathy.

    PubMed

    Maheshwari, Rajat; Weis, Ezekiel

    2012-01-01

    Thyroid associated orbitopathy, also known as Graves' orbitopathy, is typically a self-limiting autoimmune process associated with dysthyroid states. The clinical presentation may vary from very mild disease to severe irreversible sight-threatening complications. Despite ongoing basic science and clinical research, the pathogenesis and highly effective therapeutic strategies remain elusive. The present article reviews the pathophysiology, clinical presentation, and management of this common, yet poorly understood disease, which remains a challenge to the ophthalmologist. PMID:22446901

  10. Chronic autoimmune thyroid disease.

    PubMed

    Litta Modignani, R; Barantani, E; Mazzolari, M; Pincetti Nervi, M; Macchi, R

    1991-01-01

    A total of 67 patients with chronic autoimmune thyroid disease were followed, mainly as outpatients, for a period of a few months to over 15 years. The diagnosis was euthyroidism (n = 16, 23.8%), subclinical hypothyroidism (n = 20, 29.8%), primary hypothyroidism (n = 28, 41.7%) or hashitoxicosis (n = 3, 4.47%). Patients with goiters fit Hashimoto's original description of "struma lymphomatosa". The diagnosis was made on clinical grounds and the usual laboratory hormonal tests. Histological examination was carried out at surgery or by fine needle aspiration in 35 patients (52.2%), and a clinical diagnosis was made in 32 (47.7%). Three patients had juvenile Hashimoto's thyroiditis. Most patients were in the fourth, fifth or sixth decade (64.8%), and of these 12 (18%) had subclinical hypothyroidism, which should be suspected when thyrotropin (TSH) is twice the upper normal limit. In these cases thyrotropin releasing hormone (TRH) testing and evaluation of anti-thyroglobulin antibodies (TgAb) and anti-microsomal antigen antibodies (MsAb) are mandatory. Hypothyroidism with few symptoms develops insidiously in young or elderly patients; the most sensitive test is TSH assay in conjunction with tests for TgAb and MsAb. L-thyroxine administration may be harmful in older patients with late diagnosed primary hypothyroidism. Thyroid supplementation is suggested for patients with subclinical hypothyroidism if TSH values are above 10 mU/L; otherwise they should be followed up annually, as should patients with positive thyroid autoantibodies who are still euthyroid. PMID:1804288

  11. Early clinical studies of novel therapies for thyroid cancers.

    PubMed

    Sherman, Steven I

    2008-06-01

    Historically, systemic therapies for advanced, metastatic thyroid carcinomas have been poorly effective. However, as a result of a confluence of increasing knowledge of the biologic basis for thyroid cancer development and progression, identification of therapeutic agents that could target these biologic abnormalities, and enthusiasm for research by both funding agencies as well as patients, multiple clinical trials have been initiated and successfully completed during the past several years. This article focuses on findings from key studies that reflect the new paradigms for treatment. PMID:18502340

  12. Geospatial and Temporal Analysis of Thyroid Cancer Incidence in a Rural Population

    PubMed Central

    Hanley, John P.; Jackson, Erin; Morrissey, Leslie A.; Rizzo, Donna M.; Sprague, Brian L.; Sarkar, Indra Neil

    2015-01-01

    Background: The increasing incidence of thyroid cancer has resulted in the rate tripling over the past 30 years. Reasons for this increase have not been established. Geostatistics and geographic information system (GIS) tools have emerged as powerful geospatial technologies to identify disease clusters, map patterns and trends, and assess the impact of ecological and socioeconomic factors (SES) on the spatial distribution of diseases. In this study, these tools were used to analyze thyroid cancer incidence in a rural population. Methods: Thyroid cancer incidence and socio-demographic factors in Vermont (VT), United States, between 1994 and 2007 were analyzed by logistic regression and geospatial and temporal analyses. Results: The thyroid cancer age-adjusted incidence in Vermont (8.0 per 100,000) was comparable to the national level (8.4 per 100,000), as were the ratio of the incidence of females to males (3.1:1) and the mortality rate (0.5 per 100,000). However, the estimated annual percentage change was higher (8.3 VT; 5.7 U.S.). Incidence among females peaked at 30–59 years of age, reflecting a significant rise from 1994 to 2007, while incidence trends for males did not vary significantly by age. For both females and males, the distribution of tumors by size did not vary over time; ≤1.0 cm, 1.1–2.0 cm, and >2.0 cm represented 38%, 22%, and 40%, respectively. In females, papillary thyroid cancer (PTC) accounted for 89% of cases, follicular (FTC) 8%, medullary (MTC) 2%, and anaplastic (ATC) 0.6%, while in males PTC accounted for 77% of cases, FTC 15%, MTC 1%, and ATC 3%. Geospatial analysis revealed locations and spatial patterns that, when combined with multivariate incidence analyses, indicated that factors other than increased surveillance and access to healthcare (physician density or insurance) contributed to the increased thyroid cancer incidence. Nine thyroid cancer incidence hot spots, areas with very high normalized incidence, were identified

  13. Anatabine ameliorates experimental autoimmune thyroiditis.

    PubMed

    Caturegli, Patrizio; De Remigis, Alessandra; Ferlito, Marcella; Landek-Salgado, Melissa A; Iwama, Shintaro; Tzou, Shey-Cherng; Ladenson, Paul W

    2012-09-01

    Tobacco smoking favorably influences the course of Hashimoto thyroiditis, possibly through the antiinflammatory proprieties of nicotine. In this study we tested anatabine, another tobacco alkaloid, in a model of experimental autoimmune thyroiditis. Experimental autoimmune thyroiditis was induced by different doses of thyroglobulin, to produce a disease of low, moderate, or high severity, in 88 CBA/J female mice: 43 drank anatabine supplemented water and 45 regular water. Mice were bled after immunization and killed to assess thyroid histopathology, thyroglobulin antibodies, T(4), and thyroid RNA expression of 84 inflammatory genes. We also stimulated in vitro a macrophage cell line with interferon-γ or lipopolysaccharide plus or minus anatabine to quantitate inducible nitric oxide synthase and cyclooxygenase 2 protein expression. Anatabine reduced the incidence and severity of thyroiditis in the moderate disease category: only 13 of 21 mice (62%) developed thyroid infiltrates when drinking anatabine as compared with 22 of 23 (96%) controls (relative risk 0.59, P = 0.0174). The median thyroiditis severity was 0.5 and 2.0 in anatabine and controls, respectively (P = 0.0007 by Wilcoxon rank sum test). Anatabine also reduced the antibody response to thyroglobulin on d 14 (P = 0.029) and d 21 (P = 0.045) after immunization and improved the recovery of thyroid function on d 21 (P = 0.049). In the thyroid transcriptome, anatabine restored expression of IL-18 and IL-1 receptor type 2 to preimmunization levels. Finally, anatabine suppressed in a dose-dependent manner macrophage production of inducible nitric oxide synthase and cyclooxygenase 2. Anatabine ameliorates disease in a model of autoimmune thyroiditis, making the delineation of its mechanisms of action and potential clinical utility worthwhile. PMID:22807490

  14. Thyroid cancer following radiotherapy for Hodgkin's disease: a case report and review of the literature

    SciTech Connect

    Moroff, S.V.; Fuks, J.Z.

    1986-01-01

    Improved survival resulting from advances in therapy in patients with Hodgkin's disease is associated with long-term morbidity, including the potential for the development of a second solid malignancy. We report a 44-year-old man with an unusually aggressive course of thyroid carcinoma 15 years after treatment for Hodgkin's disease. In a review of the English-language literature, we found 21 cases of thyroid cancer following radiotherapy for Hodgkin's disease, with latency periods ranging from 6 to 48 years. The development of secondary thyroid cancer after high-dose neck irradiation may be related to hypothyroidism, itself a complication of radiotherapy. Thyroid function should be measured at least once a year in all patients given neck irradiation, with initiation of thyroid hormone replacement if there is evidence of sustained hypothyroidism.

  15. A Case of Painful Hashimoto Thyroiditis that Mimicked Subacute Thyroiditis.

    PubMed

    Seo, Hye Mi; Kim, Miyeon; Bae, Jaeseok; Kim, Jo-Heon; Lee, Jeong Won; Lee, Sang Ah; Koh, Gwanpyo; Lee, Dae Ho

    2012-04-01

    Hashimoto thyroiditis (HT) is an autoimmune thyroid disorder that usually presents as a diffuse, nontender goiter, whereas subacute thyroiditis (SAT) is an uncommon disease that is characterized by tender thyroid enlargement, transient thyrotoxicosis, and an elevated erythrocyte sedimentation rate (ESR). Very rarely, patients with HT can present with painful, tender goiter or fever, a mimic of SAT. We report a case of painful HT in a 68-year-old woman who presented with pain and tenderness in a chronic goiter. Her ESR was definitely elevated and her thyroid laboratory tests suggested subclinical hypothyroidism of autoimmune origin. (99m)Tc pertechnetate uptake was markedly decreased. Fine needle aspiration biopsy revealed reactive and polymorphous lymphoid cells and occasional epithelial cells with Hürthle cell changes. Her clinical symptoms showed a dramatic response to glucocorticoid treatment. She became hypothyroid finally and is now on levothyroxine therapy. PMID:22570820

  16. Breaking Tolerance to Thyroid Antigens: Changing Concepts in Thyroid Autoimmunity

    PubMed Central

    Rapoport, Basil

    2014-01-01

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

  17. Spastic Quadriparesis Caused by Anomalous Vertebral Artery Compression of Spinal Cord at the Cervico-Medullary Junction

    PubMed Central

    Rajesh, S; Adkatalwar, Vijayendra; Shiva, Meyyappan; Agrawal, Nitesh; Ramakrishnan, K G

    2015-01-01

    Vascular compression of medulla or spinal cord at the cervico-medullary junction has been commonly described in the literature and is often attributed to dolichoectasia of the vertebrobasilar arteries. We describe a case of anomalous course of the cervical segments of the bilateral vertebral arteries which were seen entering the spinal canal directly after exiting the transverse foramen of axis and causing significant cord compression at the cervico-medullary region leading to spastic quadriparesis. PMID:25924176

  18. Sensitivity and Specificity of Galectin-3 and Glypican-3 in Follicular-Patterned and Other Thyroid Neoplasms

    PubMed Central

    Younes, Sheren Fouad

    2016-01-01

    Introduction Diagnosing follicular-patterned thyroid neoplasm can be quiet challenging in some cases, where an immunohistochemical profiling becomes mandatory. Galectin-3 may be a helpful tool for classical PTC diagnosis, but it cannot be considered as a diagnostic marker of malignancy. Glypican-3, in contrast, is not thoroughly studied in thyroid neoplasms. Aim Determine the sensitivity and specificity of galectin-3 and glypican-3 in diagnosing thyroid carcinoma and follicular-patterned thyroid carcinoma. Materials and Methods A retrospective study was conducted on archival blocks diagnosed from pathology department between 2010 and 2012 including 17 cases of follicular adenoma, 16 cases of Classic Papillary Thyroid Carcinoma (PTC), 6 cases of Follicular Variant of Papillary Thyroid Carcinoma (FVPTC), 3 cases of follicular carcinoma, 5 cases of medullary carcinoma and 1 case of Hürthle cell carcinoma. The nearby non neoplastic (normal) thyroid follicles present in both adenoma and carcinoma cases were also evaluated. Study Design Evaluation of both galectin-3 and glypican-3 expression using standard immunohistochemical techniques. Statistical Analysis Used Descriptive analysis of the variables and statistical significances were calculated by non-parametric chi-square test using the Statistical Package for the Social Sciences version 12.0 (SPSS). Results Five (30%) and 4 (24%) out of the 17 studied follicular adenoma cases, were positively stained by galectin-3 and glypican-3 respectively, while 30 (97%) and 25 (81%) cases out of the studied 31 carcinoma cases were positively stained by galectin-3 and glypican-3 respectively. The sensitivity, specificity and diagnostic accuracy of galectin-3 vs. glypican-3 in discrimination between thyroid carcinoma and adenoma was 96.8%, 70.6%, and 87.5%vs. 81% 76.5% and 79% respectively. As for the discrimination between follicular-patterned thyroid carcinoma and follicular adenoma it was 90%, 71% and 78% vs. 90% 76.5% and 82

  19. Endocrinopathies. Thyroid and adrenal disorders.

    PubMed

    Merchant, S R; Taboada, J

    1997-11-01

    This article focuses on common adrenal and thyroid diseases in the geriatric patient consisting of hypothyroidism in the dog, hyperthyroidism in the cat, and hyperadrenocorticism in the dog to include clinical signs, diagnosis, and management. A brief section on hyperadrenocorticism in the cat, thyroid tumors in the dog, and pheochromocytoma in the dog and cat are also included. PMID:9348631

  20. SUPPORT FOR NCRP THYROID STUDY

    EPA Science Inventory

    The National Council on Radiation Protection and Measurements (NCRP) conducted an assessment of risks from radiation exposure of the thyroid. NCRP published the report “Risk to the Thyroid from Ionizing Radiation”, 159, in 2008. It is anticipated that results from this report ...

  1. SAHA-induced loss of tumor suppressor Pten gene promotes thyroid carcinogenesis in a mouse model.

    PubMed

    Zhu, Xuguang; Kim, Dong Wook; Zhao, Li; Willingham, Mark C; Cheng, Sheue-Yann

    2016-07-01

    Thyroid cancer is on the rise. Novel approaches are needed to improve the outcome of patients with recurrent and advanced metastatic thyroid cancers. FDA approval of suberoylanilide hydroxamic acid (SAHA; vorinostat), an inhibitor of histone deacetylase, for the treatment of hematological malignancies led to the clinical trials of vorinostat for advanced thyroid cancer. However, patients were resistant to vorinostat treatment. To understand the molecular basis of resistance, we tested the efficacy of SAHA in two mouse models of metastatic follicular thyroid cancer: Thrb(PV/PV) and Thrb(PV/PV)Pten(+/-) mice. In both, thyroid cancer is driven by overactivation of PI3K-AKT signaling. However, the latter exhibit more aggressive cancer progression due to haplodeficiency of the tumor suppressor, the Pten gene. SAHA had no effects on thyroid cancer progression in Thrb(PV/PV) mice, indicative of resistance to SAHA. Unexpectedly, thyroid cancer progressed in SAHA-treated Thrb(PV/PV)Pten(+/-) mice with accelerated occurrence of vascular invasion, anaplastic foci, and lung metastasis. Molecular analyses showed further activated PI3K-AKT in thyroid tumors of SAHA-treated Thrb(PV/PV)Pten(+/-) mice, resulting in the activated effectors, p-Rb, CDK6, p21(Cip1), p-cSrc, ezrin, and matrix metalloproteinases, to increase proliferation and invasion of tumor cells. Single-molecule DNA analysis indicated that the wild-type allele of the Pten gene was progressively lost, whereas carcinogenesis progressed in SAHA-treated Thrb(PV/PV)Pten(+/-) mice. Thus, this study has uncovered a novel mechanism by which SAHA-induced loss of the tumor suppressor Pten gene to promote thyroid cancer progression. Effectors downstream of the Pten loss-induced signaling may be potential targets to overcome resistance of thyroid cancer to SAHA. PMID:27267120

  2. Genetic determination of the hypothalamic-pituitary-thyroid axis: where do we stand?

    PubMed

    Medici, Marco; Visser, W Edward; Visser, Theo J; Peeters, Robin P

    2015-04-01

    For a long time it has been known that both hypo- and hyperthyroidism are associated with an increased risk of morbidity and mortality. In recent years, it has also become clear that minor variations in thyroid function, including subclinical dysfunction and variation in thyroid function within the reference range, can have important effects on clinical endpoints, such as bone mineral density, depression, metabolic syndrome, and cardiovascular mortality. Serum thyroid parameters show substantial interindividual variability, whereas the intraindividual variability lies within a narrow range. This suggests that every individual has a unique hypothalamus-pituitary-thyroid axis setpoint that is mainly determined by genetic factors, and this heritability has been estimated to be 40-60%. Various mutations in thyroid hormone pathway genes have been identified in persons with thyroid dysfunction or altered thyroid function tests. Because these causes are rare, many candidate gene and linkage studies have been performed over the years to identify more common variants (polymorphisms) associated with thyroid (dys)function, but only a limited number of consistent associations have been found. However, in the past 5 years, advances in genetic research have led to the identification of a large number of new candidate genes. In this review, we provide an overview of the current knowledge about the polygenic basis of thyroid (dys)function. This includes new candidate genes identified by genome-wide approaches, what insights these genes provide into the genetic basis of thyroid (dys)function, and which new techniques will help to further decipher the genetic basis of thyroid (dys)function in the near future. PMID:25751422

  3. Signaling Pathways in Thyroid Cancer and Their Therapeutic Implications

    PubMed Central

    Jin, Shan; Borkhuu, Oyungerel; Bao, Wuyuntu; Yang, Yun-Tian

    2016-01-01

    Thyroid cancer is a common malignancy of endocrine system, and has now become the fastest increasing cancer among all the malignancies. The development, progression, invasion, and metastasis are closely associated with multiple signaling pathways and the functions of related molecules, such as Src, Janus kinase (JAK)-signal transducers and activators of transcription (STAT), mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K)/Akt, NF-κB, thyroid stimulating hormone receptor (TSHR), Wnt-β-catenin and Notch signaling pathways. Each of the signaling pathways could exert its function singly or through network with other pathways. These pathways could cooperate, promote, antagonize, or interact with each other to form a complex network for the regulation. Dysfunction of this network could increase the development, progression, invasion, and metastasis of thyroid cancer. Inoperable thyroid cancer still has a poor prognosis. However, signaling pathway-related targeted therapies offer the hope of longer quality of meaningful life for this small group of patients. Signaling pathway-related targets provide unprecedented opportunities for further research and clinical development of novel treatment strategies for this cancer. In the present work, the advances in these signaling pathways and targeted treatments of thyroid cancer were reviewed. PMID:26985248

  4. Iodine and thyroid hormones during pregnancy and postpartum.

    PubMed

    Pérez-López, Faustino R

    2007-07-01

    Iodine is a trace element essential for synthesis of the thyroid hormones, triiodothyronine and thyroxine. These hormones play a vital role in the early growth and development stages of most organs, especially the brain. The World Health Organization (WHO) has declared that, after famine, iodine deficiency is the most avoidable cause of cerebral lesions including different degrees of mental retardation and cerebral paralysis. The main function of iodine in vertebrates is to interact with the thyroid hormones. During pregnancy sufficient quantities of iodine are required to prevent the appearance of hypothyroidism, trophoblastic and embryonic or fetal disorders, neonatal and maternal hypothyroidism, and permanent sequelae in infants. Thyroid hormone receptors and iodothyronine deiodinases are present in placenta and central nervous tissue of the fetus. A number of environmental factors influence the epidemiology of thyroid disorders, and even relatively small abnormalities and differences in the level of iodine intake in a population have profound effects on the occurrence of thyroid abnormalities. The prevalence of disorders related to iodine deficit during pregnancy and postpartum has increased. Iodine supplementation is an effective measure in the case of pregnant and lactating women. However, it is not implemented and the problem is still present even in societies with theoretically advanced health systems. During pregnancy and postpartum, the WHO recommends iodine intake be increased to at least 200 microg/day. Side-effects provoked by iodine supplementation are rare during pregnancy at the recommended doses. PMID:17701774

  5. Impact of nitric-oxide-mediated vasodilation and oxidative stress on renal medullary oxygenation: a modeling study.

    PubMed

    Fry, Brendan C; Edwards, Aurélie; Layton, Anita T

    2016-02-01

    The goal of this study was to investigate the effects of nitric oxide (NO)-mediated vasodilation in preventing medullary hypoxia, as well as the likely pathways by which superoxide (O2(-)) conversely enhances medullary hypoxia. To do so, we expanded a previously developed mathematical model of solute transport in the renal medulla that accounts for the reciprocal interactions among oxygen (O2), NO, and O2(-) to include the vasoactive effects of NO on medullary descending vasa recta. The model represents the radial organization of the vessels and tubules, centered around vascular bundles in the outer medulla and collecting ducts in the inner medulla. Model simulations suggest that NO helps to prevent medullary hypoxia both by inducing vasodilation of the descending vasa recta (thus increasing O2 supply) and by reducing the active sodium transport rate (thus reducing O2 consumption). That is, the vasodilative properties of NO significantly contribute to maintaining sufficient medullary oxygenation. The model further predicts that a reduction in tubular transport efficiency (i.e., the ratio of active sodium transport per O2 consumption) is the main factor by which increased O2(-) levels lead to hypoxia, whereas hyperfiltration is not a likely pathway to medullary hypoxia due to oxidative stress. Finally, our results suggest that further increasing the radial separation between vessels and tubules would reduce the diffusion of NO towards descending vasa recta in the inner medulla, thereby diminishing its vasoactive effects therein and reducing O2 delivery to the papillary tip. PMID:26831340

  6. Bone sialoprotein keratan sulfate proteoglycan (BSP-KSPG) and FGF-23 are important physiological components of medullary bone.

    PubMed

    Hadley, Jill A; Horvat-Gordon, Maria; Kim, Woo-Kyun; Praul, Craig A; Burns, Dennis; Leach, Roland M

    2016-04-01

    Medullary bone is a specialized bone found in the marrow cavity of laying birds. It provides a significant contribution to the calcium supply for egg shell formation. Medullary bone is distinguished from cortical bone by the presence of large amounts of a keratan sulfate proteoglycan (KSPG). The aims of the present experiment are to confirm the identity of the core protein of KSPG, identify a marker of medullary bone metabolism, and determine whether changes in keratan sulfate (KS) concentration in blood are associated with the egg-laying cycle. Using two different isolation techniques- one specific for bone and another for blood- we have identified bone sialoprotein (BSP) to be the core protein of this KSPG. We also determined that the amount of keratan sulfate (KS) in laying hen blood fluctuates in synchrony with the egg-laying cycle, and thus can serve as a specific marker for medullary bone metabolism. During the course of this investigation, we also found FGF-23 (phosphatonin) to be expressed in medullary bone, in synchrony with the egg-laying cycle. Western blotting was used to demonstrate the presence of this peptide in both laying hen blood and medullary bone extracts. The importance of FGF-23 (phosphatonin) and parathyroid hormone in normalizing the dramatic changes in plasma calcium and phosphorus during the 24h egg-laying cycle is discussed. PMID:26773479

  7. Methodology and dosimetry in adrenal medullary imaging with iodine-131 MIBG

    SciTech Connect

    Lindberg, S.; Fjaelling, M.J.; Jacobsson, L.; Jansson, S.; Tisell, L.E.

    1988-10-01

    Iodine-131 MIBG scans were performed in 59 patients in order to localize intra- or extra-adrenal pheochromocytomas (pheos), or to visualize hyperplastic adrenal medulla. Images were obtained from the pelvis to the base of the skull on Days 1, 4, and 7 after tracer injection. The 15 patients with histopathologic confirmation of adrenal medullary disease had positive scans. In three of these, the pheos were visible only on images obtained on Day 7. One scan was false negative. After excluding patients with a predisposition to adrenal medullary disease, nine subjects (28%) without verification of pheo displayed adrenal uptake of the radionuclide. Late images produce a low rate of false-negative scans; the background activity diminishes and even small pheos can be detected. In order to increase the quality of late images, 40 MBq (/sup 131/I)MIBG was used instead of 20 MBq. The dosimetric considerations are discussed.

  8. [Sliding centro-medullary nailing. Application to the treatment of severe forms of osteogenesis imperfecta].

    PubMed

    Metaizeau, J P

    1987-01-01

    In osteogenesis Imperfecta, the bowing of bones concures to increase their fragility. In order to avoid bowing of bones, Sofield, followed by Bailey have proposed centro medullary nailing. The pins used by Sofield do not expand and repeated changes are necessary. The expanding rods used by Bailey are to large and they can't be used in neonates. The author describe a new technique of bipolar centro medullary pinning. Two bowed K. Wires are introduced in the centromedullary canal, the first one through the proximal epiphysis, the second one through the distal epiphysis. During growth, each pin migrates distally and the osteosynthesis expand regularly. The technique can be used in the neonates and protects their bone from progressive bowing. PMID:3442930

  9. Nivolumab-induced thyroid dysfunction.

    PubMed

    Tanaka, Ryota; Fujisawa, Yasuhiro; Maruyama, Hiroshi; Nakamura, Yasuhiro; Yoshino, Koji; Ohtsuka, Mikio; Fujimoto, Manabu

    2016-06-01

    Nivolumab (ONO-4538) is an anti-programmed death-1 specific monoclonal antibody, which has become a standard treatment for metastatic malignant melanoma. Nivolumab induces autoimmune adverse events, defined as immune-related adverse events. Herein, we report a case of nivolumab-induced thyroid dysfunction in the clinical setting. Fourteen patients were treated with nivolumab at our institute, of which three developed thyroid dysfunction, an incidence higher than previously reported in the initial clinical trials. Interestingly, one patient achieved complete remission; suggesting that in some patients, the occurrence of immune-related adverse events, including thyroid dysfunction, might reflect the drug's antitumour efficacy. No patient died or discontinued nivolumab treatment owing to thyroid dysfunction. Although thyroid dysfunction first appeared to be asymptomatic, two of the three patients developed symptoms related to hypothyroidism soon after, requiring hormone replacement therapy. Another patient developed hyperthyroidism that was initially asymptomatic; the patient subsequently developed myalgia with fever >39.5°C after two additional courses of nivolumab. Treatment with nivolumab was therefore discontinued, and treatment with prednisolone was initiated. Symptoms resolved within a few days, and thyroid function normalized. Thyroid dysfunction is sometimes difficult to diagnose because its symptoms similar to those of many other diseases. In addition, thyroid-related immune-related adverse events may present with unique symptoms such as myalgia with high fever, abruptly worsening patients' quality of life. Consequently, thyroid dysfunction should be considered as a possible immune-related adverse event. Thus, it is important to test for thyroid dysfunction at baseline and before the administration of each nivolumab dose if possible. PMID:27012985

  10. Impact of renal medullary three-dimensional architecture on oxygen transport.

    PubMed

    Fry, Brendan C; Edwards, Aurélie; Sgouralis, Ioannis; Layton, Anita T

    2014-08-01

    We have developed a highly detailed mathematical model of solute transport in the renal medulla of the rat kidney to study the impact of the structured organization of nephrons and vessels revealed in anatomic studies. The model represents the arrangement of tubules around a vascular bundle in the outer medulla and around a collecting duct cluster in the upper inner medulla. Model simulations yield marked gradients in intrabundle and interbundle interstitial fluid oxygen tension (PO2), NaCl concentration, and osmolality in the outer medulla, owing to the vigorous active reabsorption of NaCl by the thick ascending limbs. In the inner medulla, where the thin ascending limbs do not mediate significant active NaCl transport, interstitial fluid composition becomes much more homogeneous with respect to NaCl, urea, and osmolality. Nonetheless, a substantial PO2 gradient remains, owing to the relatively high oxygen demand of the inner medullary collecting ducts. Perhaps more importantly, the model predicts that in the absence of the three-dimensional medullary architecture, oxygen delivery to the inner medulla would drastically decrease, with the terminal inner medulla nearly completely deprived of oxygen. Thus model results suggest that the functional role of the three-dimensional medullary architecture may be to preserve oxygen delivery to the papilla. Additionally, a simulation that represents low medullary blood flow suggests that the separation of thick limbs from the vascular bundles substantially increases the risk of the segments to hypoxic injury. When nephrons and vessels are more homogeneously distributed, luminal PO2 in the thick ascending limb of superficial nephrons increases by 66% in the inner stripe. Furthermore, simulations predict that owing to the Bohr effect, the presumed greater acidity of blood in the interbundle regions, where thick ascending limbs are located, relative to that in the vascular bundles, facilitates the delivery of O2 to support the

  11. [Medullary layer activity of the rat adrenals after a flight on the Kosmos-1129 biosatellite].

    PubMed

    Kvetnanský, R; Blazicek, P; Tigranian, R A

    1982-01-01

    After a 18.5-day space flight on Cosmos-1129 rat adrenals were investigated for the concentration of catecholamines and activity of enzymes involved in their synthesis, i.e. tyrosine hydroxylase, dopamine-beta-hydroxylase, and phenyl ethanol amine-N-methyl transferase. It was found that inflight the sympatho-adreno-medullary system of rats was not exposed to a prolonged or strong stressogenic effect. Postflight the rats showed an increased reactivity to the immobilization stress. PMID:7120908

  12. Corticotropin-releasing factor enhances locomotion and medullary neuronal firing in an amphibian.

    PubMed

    Lowry, C A; Rose, J D; Moore, F L

    1996-03-01

    Corticotropin-releasing factor (CRF) administration has been shown to act centrally to enhance locomotion in rats and amphibians. In the present study we used an amphibian, the roughskin newt (Taricha granulosa), to characterize changes in medullary neuronal activity associated with CRF-induced walking and swimming in animals chronically implanted with fine-wire microelectrodes. Neuronal activity was recorded from the raphe and adjacent reticular region of the rostral medulla. Under baseline conditions most of the recorded neurons showed low to moderate amounts of neuronal activity during periods of immobility and pronounced increases in firing that were time-locked with episodes of walking. These neurons sometimes showed further increases in discharge during swimming. Injections of CRF but not saline into the lateral ventricle produced a rapidly appearing increase in walking and pronounced changes (mostly increases) in firing rates of the medullary neurons. CRF produced diverse changes in patterns of firing in different neurons, but for these neurons as a group, the effects of CRF showed a close temporal association with the onset and expression of the peptide's effect on locomotion. In neurons that were active exclusively during movement prior to CRF treatment, the post-CRF increase in firing was evident during episodes of walking; in other neurons that also were spontaneously active during immobility prior to CRF infusion, post-CRF activity changes were evident during immobility as well as during episodes of locomotion. Thus, a principal effect of CRF was to potentiate the level of neuronal firing in a population of medullary neurons with locomotor-related properties. Due to the route of administration CRF may have acted on multiple central nervous system sites to enhance locomotion, but the results are consistent with neurophysiological effects involving medullary locomotion-regulating neurons. PMID:8724179

  13. Frequency of thyroid cancer in patients operated at Cantonal Hospital Zenica, Bosnia and Herzegovina, in the period 2007-2014.

    PubMed

    Hrnčić, Nermin; Goga, Amna; Hrnčić, Selma; Filipovska-Mušanović, Marijana; Hatibović, Haris; Hodžić, Ðenad

    2016-08-01

    Aim To determine frequency and type of thyroid cancer (TC) as well as gender and age distribution of patients operated at the Department of Ear, Nose and Throat (ENT), Cantonal Hospital Zenica, Bosnia and Herzegovina. Methods A retrospective analysis of data obtained from an operating protocol and disease history of patients operated in the eightyear period (2007- 2014) was made according to the frequency and type of thyroid cancer, as well as age and gender of the patients. χ2 test was used for statistical with p<0.05. Results A total of 818 surgeries of the thyroid gland were conducted, in 714 (87.29%) female and 104 (12.71%) male patients. Malignancies were diagnosed in 74 (9.05%) patients, of whom 64 (86.49%) were females and 10 (13.51%) were males, resulting in the gender prevalence of 8.96% and 9.62%, respectively. The most often presented type was papillary carcinoma, in 48(out of 74, 64.86%) patients, followed by follicular carcinoma in 10 (13.51%), medullary carcinoma in four (5.41%), Hurthle cell carcinoma in four (5.41%) patients, while anaplastic carcinoma was found in one (1.35%) patient. The number of diagnosed malignancy varied from 0% (in 2007) to 13.91% (in 2014) (p=0.05). Conclusion The prevalence of thyroid cancer is low, but has an increasing trend. A large number of unnecessary surgeries on thyroid gland was performed. Preoperative diagnostic procedures for diseases of the thyroid gland in Cantonal Hospital Zenica should be improved in order to avoid unessential surgeries. PMID:27313111

  14. Upregulation of long noncoding RNA LOC100507661 promotes tumor aggressiveness in thyroid cancer.

    PubMed

    Kim, Daham; Lee, Woo Kyung; Jeong, Seonhyang; Seol, Mi-Youn; Kim, Hyunji; Kim, Kyung-Sup; Lee, Eun Jig; Lee, Jandee; Jo, Young Suk

    2016-08-15

    Recent advances in next-generation sequencing have revealed a variety of long noncoding RNAs (lncRNAs). However, studies of lncRNAs are at a very early stage, our knowledge of the biological functions and clinical implications remains limited. To investigate the roles of lncRNAs in thyroid cancers, we verified 56 lncRNAs identified as potential cancer-promoting genes in a previous study that analyzed 2394 tumor SNP arrays from 12 types of cancer. Based on verified sequence information in NCBI and Ensembl, we ultimately selected three candidate lncRNAs for detailed analysis. One of the candidates, LOC100507661, was strongly upregulated in thyroid cancer tissues relative to paired contralateral normal tissue. LOC100507661 was easily detectable in papillary and anaplastic thyroid cancer cell lines such as TPC1, BCPAP, C643, and 8505C, but not in the follicular thyroid cancer cell line FTC133. Stable overexpression of LOC100507661 promoted cell proliferation, migration, and invasion of thyroid cancer cells. Lymph node metastasis and BRAF V600E mutations were more frequent in papillary thyroid cancers with high LOC100507661 expression. Our data demonstrate that LOC100507661 expression is elevated in human thyroid cancer and may play a critical role in thyroid carcinogenesis. PMID:27151833

  15. New Model Systems to Illuminate Thyroid Organogenesis. Part I: An Update on the Zebrafish Toolbox

    PubMed Central

    Opitz, Robert; Antonica, Francesco; Costagliola, Sabine

    2013-01-01

    Thyroid dysgenesis (TD) resulting from defects during embryonic thyroid development represents a major cause of congenital hypothyroidism. The pathogenetic mechanisms of TD in human newborns, however, are still poorly understood and disease-causing genetic variants have been identified in only a small percentage of TD cases. This limited understanding of the pathogenesis of TD is partly due to a lack of knowledge on how intrinsic factors and extrinsic signalling cues orchestrate the differentiation of thyroid follicular cells and the morphogenesis of thyroid tissue. Recently, embryonic stem cells and zebrafish embryos emerged as novel model systems that allow for innovative experimental approaches in order to decipher cellular and molecular mechanisms of thyroid development and to unravel pathogenic mechanisms of TD. Zebrafish embryos offer several salient properties for studies on thyroid organogenesis including rapid and external development, optical transparency, ease of breeding, relative short generation time and amenability for genome editing. In this review, we will highlight recent advances in the zebrafish toolkit to visualize cellular dynamics of organ development and discuss specific prospects of the zebrafish model for studies on vertebrate thyroid development and human congenital thyroid diseases. PMID:24783054

  16. Sonographic Elastography of the Thyroid Gland

    PubMed Central

    Menzilcioglu, Mehmet Sait; Duymus, Mahmut; Avcu, Serhat

    2016-01-01

    Summary Thyroid gland disorders include benign and malignant thyroid nodules and diffuse thyroid disorders. The incidence of malignant thyroid nodules is low and the prognosis is good. The diagnosis of thyroid cancer and diffuse parenchymal disorders is generally based on clinical manifestations and histopathological evaluation. Ultrasonography has its place in the diagnostics and follow-up of thyroid disorders. Ultrasonographic elastography is a new, developing method that shows increase in clinical practice. In this study, we aimed to review the data on thyroid ultrasound elastography. PMID:27103947

  17. Conus medullaris ganglioneuroma with syringomyelia radiologically mimicking ependymoma: A case report

    PubMed Central

    WANG, KAI; DAI, JIANPING

    2015-01-01

    Ganglioneuromas are rare, benign, well-differentiated tumors of the conus medullaris. Approximately 20 cases of spinal cord ganglioneuroma, and only 1 case of mixed chemodectoma-ganglioneuroma of the conus medullaris have been previously reported. The present study presents the case of a 38-year-old man with a histopathological diagnosis of conus medullaris ganglioneuroma. The patient presented with hypoesthesia in the lower limbs, muscle atrophy of the right lower limb and dysuria. Magnetic resonance imaging analysis led to a diagnosis of ependymoma. Histopathological analysis of the excised mass revealed typical, well-differentiated ganglion cells, consistent with a ganglioneuroma. The mass was associated with a neighboring syringomyelia. At an 18 month follow-up the patient had recovered, although some remaining difficulty in walking and urinating remained. The aim of the present report was to raise awareness that when ganglioneuromas present in unusual locations, analogous radiological findings may mislead investigators to consider more common pathologies and thus result in misdiagnosis. The present case demonstrates the importance of considering the potential differential diagnoses for neural tissue neoplasms. PMID:26788212

  18. Medullary nephrocalcinosis, distal renal tubular acidosis and polycythaemia in a patient with nephrotic syndrome

    PubMed Central

    2012-01-01

    Background Medullary nephrocalcinosis and distal renal tubular acidosis are closely associated and each can lead to the other. These clinical entities are rare in patients with nephrotic syndrome and polycythaemia is an unusual finding in such patients. We describe the presence of medullary nephrocalcinosis, distal renal tubular acidosis and polycythaemia in a patient with nephrotic syndrome due to minimal change disease. Proposed mechanisms of polycythaemia in patients with nephrotic syndrome and distal renal tubular acidosis include, increased erythropoietin production and secretion of interleukin 8 which in turn stimulate erythropoiesis. Case presentation A 22 year old Sri Lankan Sinhala male with nephrotic syndrome due to minimal change disease was investigated for incidentally detected polycythaemia. Investigations revealed the presence of renal tubular acidosis type I and medullary nephrocalcinosis. Despite extensive investigation, a definite cause for polycythaemia was not found in this patient. Treatment with potassium and bicarbonate supplementation with potassium citrate led to correction of acidosis thereby avoiding the progression of nephrocalcinosis and harmful effects of chronic acidosis. Conclusion The constellation of clinical and biochemical findings in this patient is unique but the pathogenesis of erythrocytosis is not clearly explained. The proposed mechanisms for erythrocytosis in other patients with proteinuria include increased erythropoietin secretion due to renal hypoxia and increased secretion of interleukin 8 from the kidney. This case illustrates that there may exist hitherto unknown connections between tubular and glomerular dysfunction in patients with nephrotic syndrome. PMID:22834973

  19. Medullary raphe midline is involved in production of expulsive expirations in anesthetized rabbits.

    PubMed

    Poliacek, I; Jakus, J; Knocikova, J; Barani, H; Halasova, E; Visnovcova, N

    2008-12-01

    Effects of kainic acid lesions in the medullary raphe midline on reflex expirations induced mechanically from the trachea were examined. Spontaneously breathing rabbits were anesthetized by ketamine and xylazine i.m., followed by pentobarbitone i.v. Excitatory neurotoxin kainic acid (2 mg/ml in artificial CSF, total volume of 55-100 nl) was pressure microinjected into the medullary midline, rostral to the obex (2 microinjections at 2 different depths). The lesion (mostly affected the obscurus and magnus raphe nuclei) reduced the number of reflex expirations by 80% and expiratory amplitudes of esophageal pressure, abdominal EMG moving averages, and abdominal EMG powers by 71%, 62%, and 57%, respectively (in all cases P<0.05). The duration of abdominal activity in post-lesion responses was not altered. Control microinjections of artificial CSF had no effect on the reflex responses. We conclude that in rabbits, the medullary raphe nuclei participate in the control of expiratory expulsions originating from the trachea. PMID:19218686

  20. Etiopathogenetic factors, thyroid functions and thyroid autoimmunity in melasma patients

    PubMed Central

    Özcan, Nimet; Kılıç, Arzu; Koparal, Suha; Artüz, Ferda; Çakmak, Atıl; Köse, Kenan

    2015-01-01

    Introduction Melasma is a common chronic, acquired pigmentation disorder with a significant impact on the quality of life of patients. Aim To investigate the etiopathogenetic factors, thyroid functions and thyroid autoimmunity in patients with melasma. Material and methods Forty-five women with melasma and 45 age-matched healthy women were included in the study group. A detailed history was taken from the patients including triggering factors of melasma. Serum free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), anti-thyroglobulin (AbTG) and anti-thyroid peroxidase (Ab-TPO) were measured and thyroid ultrasonography was performed for each subject. Results In 26.7% of patients, pregnancy, in 17.8%, oral contraceptive use and in 13.3%, intense sunlight exposure were the triggering factors. 17.8% of patients had a family history of melasma. FT4, TSH and AbTG levels were significantly higher in the patient group. Conclusions The results suggest that a combination of factors including pregnancy, oral contraceptive use, sunlight and genetic factors often trigger melasma. Thyroid hormones and thyroid autoimmunity may also play a role in the pathogenesis which needs to be proven by further studies. PMID:26759539