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Sample records for recurrent medullary thyroid

  1. 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

  2. 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

  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. 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

  6. 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

  7. 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

  8. [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

  9. 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

  10. 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

  11. 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

  12. 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

  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. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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.

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  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. 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.

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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.

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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.

  3. 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

  4. 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.

  5. 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

  6. 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

  7. 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

  8. 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

  9. Recurrent thyroid cancer with changing histologic features

    PubMed Central

    Konduri, Kartik; Harshman, Leeanne K.; Welch, Brian J.; O'Brien, John C.

    2010-01-01

    We present the case of a 57-year-old woman diagnosed with breast cancer and a thyroid mass that was suspicious for cancer. The breast cancer was estrogen and progesterone receptor negative, HER2/neu borderline, with a high proliferative index. Treatment of this cancer took precedence. Nine months later, a total thyroidectomy was done for papillary thyroid cancer with metastases to 2 of 8 perithyroid lymph nodes. Postoperative radioactive iodine ablation was given. Recurrent thyroid disease was found in the right neck 1 year later and was resected; no radioactive iodine was given at that time. After 2½ years, the cancer recurred as a more highly aggressive, undifferentiated anaplastic thyroid carcinoma. Treatment is discussed. PMID:21240322

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. Aflibercept in Treating Patients With Recurrent and/or Metastatic Thyroid Cancer That Did Not Respond to Radioactive Iodine Therapy

    ClinicalTrials.gov

    2015-06-01

    Recurrent Thyroid Gland Carcinoma; Stage III Thyroid Gland Follicular Carcinoma; Stage III Thyroid Gland Papillary Carcinoma; Stage IV Thyroid Gland Follicular Carcinoma; Stage IV Thyroid Gland Papillary Carcinoma

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. Trametinib in Increasing Tumoral Iodine Incorporation in Patients With Recurrent or Metastatic Thyroid Cancer

    ClinicalTrials.gov

    2016-06-30

    Poorly Differentiated Thyroid Gland Carcinoma; Recurrent Thyroid Gland Carcinoma; Stage IVA Thyroid Gland Follicular Carcinoma; Stage IVA Thyroid Gland Papillary Carcinoma; Stage IVB Thyroid Gland Follicular Carcinoma; Stage IVB Thyroid Gland Papillary Carcinoma; Stage IVC Thyroid Gland Follicular Carcinoma; Stage IVC Thyroid Gland Papillary Carcinoma

  10. Iodine I-131 With or Without Selumetinib in Treating Patients With Recurrent or Metastatic Thyroid Cancer

    ClinicalTrials.gov

    2016-07-12

    Poorly Differentiated Thyroid Gland Carcinoma; Recurrent Thyroid Gland Carcinoma; Stage IVA Thyroid Gland Follicular Carcinoma; Stage IVA Thyroid Gland Papillary Carcinoma; Stage IVB Thyroid Gland Follicular Carcinoma; Stage IVB Thyroid Gland Papillary Carcinoma; Stage IVC Thyroid Gland Follicular Carcinoma; Stage IVC Thyroid Gland Papillary Carcinoma

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. Radiofrequency Ablation of Benign Thyroid Nodules and Recurrent Thyroid Cancers: Consensus Statement and Recommendations

    PubMed Central

    Na, Dong Gyu; Lee, Jeong Hyun; Jung, So Lyung; Kim, Ji-hoon; Sung, Jin Yong; Shin, Jung Hee; Kim, Eun-Kyung; Lee, Joon Hyung; Kim, Dong Wook; Park, Jeong Seon; Kim, Kyu Sun; Baek, Seon Mi; Lee, Younghen; Chong, Semin; Sim, Jung Suk; Huh, Jung Yin; Bae, Jae-Ik; Kim, Kyung Tae; Han, Song Yee; Bae, Min Young; Kim, Yoon Suk

    2012-01-01

    Thermal ablation using radiofrequency is a new, minimally invasive modality employed as an alternative to surgery in patients with benign thyroid nodules and recurrent thyroid cancers. The Task Force Committee of the Korean Society of Thyroid Radiology has developed recommendations for the optimal use of radiofrequency ablation for thyroid nodules. These recommendations are based on a comprehensive analysis of the current literature, the results of multicenter studies, and expert consensus. PMID:22438678

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  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. 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

  11. 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.

  12. Contemporary Management of Recurrent Nodal Disease in Differentiated Thyroid Carcinoma.

    PubMed

    Na'ara, Shorook; Amit, Moran; Fridman, Eran; Gil, Ziv

    2016-01-01

    Differentiated thyroid carcinoma (DTC) comprises over 90% of thyroid tumors and includes papillary and follicular carcinomas. Patients with DTC have an excellent prognosis, with a 10-year survival rate of over 90%. However, the risk of recurrent tumor ranges between 5% and 30% within 10 years of the initial diagnosis. Cervical lymph node disease accounts for the majority of recurrences and in most cases is detected during follow-up by ultrasound or elevated levels of serum thyroglobulin. Recurrent disease is accompanied by increased morbidity. The mainstay of treatment of nodal recurrence is surgical management. We provide an overview of the literature addressing surgical management of recurrent or persistent lymph node disease in patients with DTC. PMID:26886954

  13. Contemporary Management of Recurrent Nodal Disease in Differentiated Thyroid Carcinoma

    PubMed Central

    Na’ara, Shorook; Amit, Moran; Fridman, Eran; Gil, Ziv

    2016-01-01

    Differentiated thyroid carcinoma (DTC) comprises over 90% of thyroid tumors and includes papillary and follicular carcinomas. Patients with DTC have an excellent prognosis, with a 10-year survival rate of over 90%. However, the risk of recurrent tumor ranges between 5% and 30% within 10 years of the initial diagnosis. Cervical lymph node disease accounts for the majority of recurrences and in most cases is detected during follow-up by ultrasound or elevated levels of serum thyroglobulin. Recurrent disease is accompanied by increased morbidity. The mainstay of treatment of nodal recurrence is surgical management. We provide an overview of the literature addressing surgical management of recurrent or persistent lymph node disease in patients with DTC. PMID:26886954

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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 ...

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. [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

  11. 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

  12. Recurrence of papillary thyroid cancer after optimized surgery

    PubMed Central

    2015-01-01

    Recurrence of papillary thyroid cancer (PTC) after optimized surgery requires a full understanding of the disease, especially as it has changed in the last 15 years, what comprises optimized surgery, and the different types and implications of disease relapse that can be encountered. PTC has evolved to tumors that are much smaller than previously seen, largely due to various high quality imaging studies obtained for different reasons, but serendipitously identifying thyroid nodules that prove to be papillary thyroid microcarcinomas (PTMC). With rare exception, these cancers are cured by conservative surgery without additional therapy, and seldom result in recurrent disease. PTC is highly curable in 85% of cases because of its rather innocent biologic behavior. Therefore, the shift in emphasis from disease survival to recurrence is appropriate. As a result of three technologic advances—high-resolution ultrasound (US), recombinant TSH, and highly sensitive thyroglobulin (Tg)—disease relapse can be discovered when it is subclinical. Endocrinologists who largely control administration of radioactive iodine have used it to ablate barely detectable or even biochemically apparent disease, hoping to reduce recurrence and perhaps improve survival. Surgeons, in response to this new intense postoperative surveillance that has uncovered very small volume disease, have responded by utilizing US preoperatively to image this disease, and incorporated varying degrees of lymphadenectomy into their initial treatment algorithm. Bilateral thyroid resection—either total or near-total thyroidectomy—remains the standard for PTC >1 cm, although recent data has re-emphasized the value of unilateral lobectomy in treating even some PTC measuring 1-4 cm. Therapeutic lymphadenectomy has universal approval, but when lymph nodes in the central neck are not worrisome to the surgeon’s intraoperative assessment, although that judgment in incorrect up to 50%, whether they should be excised

  13. 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

  14. 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

  15. Lymph Node Ratio Predicts Recurrence in Papillary Thyroid Cancer

    PubMed Central

    Mazeh, Haggi; Chen, Herbert; Sippel, Rebecca S.

    2013-01-01

    Background. Lymph node metastasis occurs in 20%–50% of patients presenting for initial treatment of papillary thyroid cancer (PTC). The significance of lymph node metastases remains controversial, and the aim of this study is to determine how the lymph node ratio (LNR) may predict the likelihood of disease recurrence. Methods. We conducted a retrospective review of patients undergoing total thyroidectomy for PTC at our institution from 2005 to 2010. A total LNR (positive nodes to total nodes) and central lymph node ratio (cLNR) was calculated. Regression was used to determine a threshold LNR that best predicted recurrence. Multivariate logistic regression then determined the influence of LNR on recurrence while accounting for other known predictors of recurrence. Kaplan-Meier analysis and the log-rank test were used to compare differences in disease-free survival. Results. Of the 217 patients undergoing total thyroidectomy for PTC, 69 patients had concomitant neck dissections. Sixteen (23.2%) patients developed disease recurrence. When disease-free survival functions were compared, we found that patients with a total LNR ≥0.7 (p < .01) or a cLNR ≥0.86 (p = .04) had significantly worse disease-free survival rates than patients with ratios below these threshold values. Considering other known predictors of recurrence, we found that LNR was significantly associated with recurrence (odds ratio: 19.5, 95% confidence interval: 4.1–22.9; p < .01). Conclusions. Elevated total LNR and cLNR are strongly associated with recurrence of PTC after initial operation. LNR in PTC is a tool that can be used to determine the likelihood of the patient developing recurrent disease and inform postoperative follow-up. PMID:23345543

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  1. Iodine I 131 and Pazopanib Hydrochloride in Treating Patients With Recurrent and/or Metastatic Thyroid Cancer Previously Treated With Iodine I 131 That Cannot Be Removed By Surgery

    ClinicalTrials.gov

    2015-11-04

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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. Risk Factors for Recurrence in Filipinos with Well-Differentiated Thyroid Cancer

    PubMed Central

    Canto, Abigail Uy; Maningat, Patricia Deanna D.

    2015-01-01

    Background The incidence of well-differentiated thyroid cancer (WDTC) has increased in recent years. Despite its excellent prognosis, increasing morbidity from recurrent diseases continues to affect long-term outcomes. Among at-risk populations, Filipinos have the highest incidence of thyroid cancer worldwide, characterized by a highly aggressive and recurrent form of disease. Here, we sought to identify risk factors associated with disease recurrence among Filipinos with WDTC. Methods This retrospective cohort study examined 723 patients diagnosed with WDTC seen at Philippine General Hospital. Affected individuals were classified based on the presence or absence of disease recurrence. Multivariate logistic regression analyses were used to determine significant predictors of recurrence. Results Multiple risk factors, including age >45 years (odds ratio [OR], 1.44), multifocality of cancer (OR, 1.43), nodal involvement (OR, 4.0), and distant metastases at presentation (OR, 2.78), were significantly associated with a recurrence of papillary thyroid cancer (PTC). In contrast, follicular variant histology (OR, 0.60) and postsurgical radioactive iodine therapy (OR, 0.31) were protective for PTC recurrence. Distant metastases at presentation (OR, 19.4) and postsurgical radioactive iodine therapy (OR, 0.41) were associated with follicular thyroid cancer (FTC) recurrence. Conclusion Lymph node metastases at presentation was the strongest predictor of recurrence in PTC, whereas distant metastases at presentation was the strongest for FTC recurrence. Among Filipinos, stratification of WDTC patients based on recurrence risk factors identified in this study will be helpful in guiding the intensity of treatment strategies and long-term thyroid cancer surveillance. PMID:26485470

  9. 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

  10. 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

  11. 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

  12. 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

  13. [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

  14. 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.

  15. Laser-induced interstitial thermotherapy in treatment of recurrent nodular goiter and thyroid cancer

    NASA Astrophysics Data System (ADS)

    Seliverstov, Oleg V.; Privalov, Valeriy A.; Lappa, Alexander V.; Demidov, A. K.; Faizrakhmanov, Alexey B.; Yarovoy, Nicolay N.

    2001-10-01

    Laser-induced interstitial thermotherapy was performed in 29 patients with recurrent nodular and multinodular goiter, and in 3 patients with recurrent inoperable thyroid cancer. There were used transcutaneous puncture under ultrasonic control, diode lasers with wavelength 805, 980, and 1060 nm, quartz monofibers, special computerized thermometer with microthermocouples. Disappearance or significant reduction of nodes in the most goiter cases, and regress of tumor in the cancer cases were marked during observation period (0.5 - 2.5 years).

  16. 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

  17. 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

  18. 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

  19. 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

  20. Recurrent Episodes of Thyrotoxicosis in a Man following Pregnancies of his Spouse with Hashimoto's Thyroiditis

    PubMed Central

    Belokovskaya, Regina; Levine, Alice C.

    2015-01-01

    Over an 8-year period, a male patient presented three times to an endocrinologist with strikingly similar presentations, including palpitations, anxiety, and tremors. Each of his presentations occurred following either the birth of one of his two children or his wife's late termination of pregnancy. This patient's illness followed the typical time course of silent thyroiditis: hyperthyroidism, followed by euthyroidism, a late hypothyroid phase, and then a complete resolution of symptoms and normalization of thyroid function tests over a period of several months. We discuss the curious clinical presentation, diagnostic evaluation, and a literature review of alternate explanations for this patient's condition, including a discussion of the impact of seasonal shift, spousal's autoimmune disease, stress, and evolutionary changes in males postpartum. Although the differential diagnosis is broad in this case and the thyrotoxicosis could have coincidentally followed pregnancies of the patient's wife, documented hormonal changes in men during postpartum period in conjunction with the timeline of the patient's condition are suggestive of recurrent “sympathetic” postpartum thyroiditis. To our knowledge, this is the first case report of recurrent painless thyroiditis in a man following pregnancies of his wife with Hashimoto's thyroiditis. PMID:26421199

  1. Recurrent Episodes of Thyrotoxicosis in a Man following Pregnancies of his Spouse with Hashimoto's Thyroiditis.

    PubMed

    Belokovskaya, Regina; Levine, Alice C

    2015-01-01

    Over an 8-year period, a male patient presented three times to an endocrinologist with strikingly similar presentations, including palpitations, anxiety, and tremors. Each of his presentations occurred following either the birth of one of his two children or his wife's late termination of pregnancy. This patient's illness followed the typical time course of silent thyroiditis: hyperthyroidism, followed by euthyroidism, a late hypothyroid phase, and then a complete resolution of symptoms and normalization of thyroid function tests over a period of several months. We discuss the curious clinical presentation, diagnostic evaluation, and a literature review of alternate explanations for this patient's condition, including a discussion of the impact of seasonal shift, spousal's autoimmune disease, stress, and evolutionary changes in males postpartum. Although the differential diagnosis is broad in this case and the thyrotoxicosis could have coincidentally followed pregnancies of the patient's wife, documented hormonal changes in men during postpartum period in conjunction with the timeline of the patient's condition are suggestive of recurrent "sympathetic" postpartum thyroiditis. To our knowledge, this is the first case report of recurrent painless thyroiditis in a man following pregnancies of his wife with Hashimoto's thyroiditis. PMID:26421199

  2. TERT Promoter Mutations and Tumor Persistence/Recurrence in Papillary Thyroid Cancer

    PubMed Central

    Myung, Jae Kyung; Kwak, Byung Kuk; Lim, Jung Ah; Lee, Myung-Chul; Kim, Min Joo

    2016-01-01

    Purpose A telomerase reverse transcriptase (TERT) promoter mutation was identified in thyroid cancer. This TERT promoter mutation is thought to be a prognostic molecular marker, because its association with tumor aggressiveness, persistence/recurrence, and disease-specific mortality in papillary thyroid carcinoma (PTC) has been reported. In this study, we attempted to determine whether the impact of the TERT promoter mutation on PTC persistence/recurrence is independent of clinicopathological parameters. Materials and Methods Using propensity score matching, 39 patients with PTC persistence or recurrence were matched with 35 patients without persistence or recurrence, with a similar age, sex, tumor size, multifocality, bilaterality, extrathyroidal extension, and lymph node metastasis. The TERT promoter and the BRAF V600E mutations were identified from PTC samples. Results The TERT promoter mutation was detected in 18% of PTC patients (13/74). No significant difference in the frequency of the TERT promoter mutation was observed between the persistence/recurrence group and the non-recurrence group. Conclusion These results suggest that the prognostic implications of the TERT promoter mutation are dependent on clinicopathological parameters. PMID:26727717

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. Primary squamous cell carcinoma of thyroid gland with local recurrence: ultrasonographic and computed tomographic findings

    PubMed Central

    2014-01-01

    Primary squamous cell carcinoma of the thyroid gland (PSCCT) is a rare malignancy that presents with advanced disease and poor prognosis. It is difficult to diagnose PSCCT in its early stage because of its rarity and lack of typical imaging findings. We experienced an elderly woman with PSCCT confirmed by surgery. Although preoperative fine-needle aspiration revealed no malignancy, surgical resection was performed because the ultrasonogram showed diffuse microcalcifications, which suggested malignancy, and clinically, the mass grew rapidly to compress the trachea. Local tumor recurrence was noted at 3 months after surgery. Surgical resection or repeat biopsy should be considered if a cytologically benign thyroid mass shows imaging or clinical features of malignancy. PMID:24936508

  9. Evaluation of thyroid function in dogs suffering from recurrent flank alopecia.

    PubMed Central

    Daminet, S; Paradis, M

    2000-01-01

    Thyroid function was assessed in euthyroid dogs (n = 20), dogs suffering from canine recurrent flank alopecia (CRFA, n = 18), and hypothyroid dogs (n = 21). Blood samples obtained from all dogs in each group were assayed for total thyroxine (TT4), thyrotropin (TSH), and thyroglobulin autoantibody (TgAA) serum concentrations. Total T4 and TSH serum concentrations were significantly decreased and increased, respectively, in the hypothyroid group compared with the other 2 groups. No significant differences in TT4 and TSH serum values were found between the euthyroid and CRFA groups. Thyroglobulin autoantibodies were detected in 10, 11.1, and 61.9% of euthyroid dogs, dogs with CRFA, and hypothyroid dogs, respectively. In conclusion, dogs suffering from CRFA have a normal thyroid function, and the determination of TT4 and TSH serum concentrations allows differentiation of these dogs from dogs with hypothyroidism, in most cases. Occasionally, the 2 diseases can be concomitant. PMID:10992988

  10. Recurrent Thyrotoxicosis due to Both Graves' Disease and Hashimoto's Thyroiditis in the Same Three Patients.

    PubMed

    Schaffer, Ashley; Puthenpura, Vidya; Marshall, Ian

    2016-01-01

    Hashimoto's thyroiditis (HT) and Graves' disease (GD) are the 2 most common autoimmune disease processes affecting the thyroid gland. The relationship between the two is complex and not clearly understood. It has been theorized that HT and GD are 2 separate disease processes due to unique genetic differences demonstrated by genome studies. On the other hand, based on occurrence of both HT and GD in monozygotic twins and within the same family, they have been regarded to represent 2 ends of the same spectrum. This case report describes 3 patients who presented with thyrotoxicosis due to both GD and HT. The initial presentation was thyrotoxicosis due to GD treated with antithyroid medication followed by temporary resolution. They all subsequently experienced recurrence of thyrotoxicosis in the form of Hashitoxicosis due to HT, and then eventually all developed thyrotoxicosis due to GD, requiring radioablation therapy. PMID:27340576

  11. Recurrent Thyrotoxicosis due to Both Graves' Disease and Hashimoto's Thyroiditis in the Same Three Patients

    PubMed Central

    Schaffer, Ashley; Puthenpura, Vidya

    2016-01-01

    Hashimoto's thyroiditis (HT) and Graves' disease (GD) are the 2 most common autoimmune disease processes affecting the thyroid gland. The relationship between the two is complex and not clearly understood. It has been theorized that HT and GD are 2 separate disease processes due to unique genetic differences demonstrated by genome studies. On the other hand, based on occurrence of both HT and GD in monozygotic twins and within the same family, they have been regarded to represent 2 ends of the same spectrum. This case report describes 3 patients who presented with thyrotoxicosis due to both GD and HT. The initial presentation was thyrotoxicosis due to GD treated with antithyroid medication followed by temporary resolution. They all subsequently experienced recurrence of thyrotoxicosis in the form of Hashitoxicosis due to HT, and then eventually all developed thyrotoxicosis due to GD, requiring radioablation therapy. PMID:27340576

  12. 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

  13. Percutaneous Irreversible Electroporation for Recurrent Thyroid Cancer--A Case Report.

    PubMed

    Meijerink, Martijn R; Scheffer, Hester J; de Bree, Remco; Sedee, Robert-Jan

    2015-08-01

    A 74-year-old man presented with a small locoregional, histopathologically proven, fluorodeoxyglucose positron emission tomography/computed tomography-avid recurrence of follicular thyroid carcinoma in the left subglottic space after extensive surgical resection, adjuvant radioactive iodine therapy, and external beam radiation therapy. Because all established focal therapies were contraindicated, percutaneous irreversible electroporation was performed without complications. Follow-up imaging at 7 months showed a small ablation scar without signs for residual vital tumor tissue. Irreversible electroporation may be a viable treatment option for selected cases of recurring head and neck tumors that are unsuitable for other local treatments. PMID:26210244

  14. Recurrent EZH1 mutations are a second hit in autonomous thyroid adenomas.

    PubMed

    Calebiro, Davide; Grassi, Elisa S; Eszlinger, Markus; Ronchi, Cristina L; Godbole, Amod; Bathon, Kerstin; Guizzardi, Fabiana; de Filippis, Tiziana; Krohn, Knut; Jaeschke, Holger; Schwarzmayr, Thomas; Bircan, Rifat; Gozu, Hulya Iliksu; Sancak, Seda; Niedziela, Marek; Strom, Tim M; Fassnacht, Martin; Persani, Luca; Paschke, Ralf

    2016-09-01

    Autonomous thyroid adenomas (ATAs) are a frequent cause of hyperthyroidism. Mutations in the genes encoding the TSH receptor (TSHR) or the Gs protein α subunit (GNAS) are found in approximately 70% of ATAs. The involvement of other genes and the pathogenesis of the remaining cases are presently unknown. Here, we performed whole-exome sequencing in 19 ATAs that were paired with normal DNA samples and identified a recurrent hot-spot mutation (c.1712A>G; p.Gln571Arg) in the enhancer of zeste homolog 1 (EZH1) gene, which codes for a catalytic subunit of the polycomb complex. Targeted screening in an independent cohort confirmed that this mutation occurs with high frequency (27%) in ATAs. EZH1 mutations were strongly associated with known (TSHR, GNAS) or presumed (adenylate cyclase 9 [ADCY9]) alterations in cAMP pathway genes. Furthermore, functional studies revealed that the p.Gln571Arg EZH1 mutation caused increased histone H3 trimethylation and increased proliferation of thyroid cells. In summary, this study revealed that a hot-spot mutation in EZH1 is the second most frequent genetic alteration in ATAs. The association between EZH1 and TSHR mutations suggests a 2-hit model for the pathogenesis of these tumors, whereby constitutive activation of the cAMP pathway and EZH1 mutations cooperate to induce the hyperproliferation of thyroid cells. PMID:27500488

  15. The Delayed Risk Stratification System in the Risk of Differentiated Thyroid Cancer Recurrence

    PubMed Central

    Walczyk, Agnieszka; Pałyga, Iwona; Gąsior-Perczak, Danuta; Gadawska-Juszczyk, Klaudia; Szymonek, Monika; Trybek, Tomasz; Lizis-Kolus, Katarzyna; Szyska-Skrobot, Dorota; Mikina, Estera; Hurej, Stefan; Słuszniak, Janusz; Mężyk, Ryszard; Góźdź, Stanisław

    2016-01-01

    Context There has been a marked increase in the detection of differentiated thyroid carcinoma (DTC) over the past few years, which has improved the prognosis. However, it is necessary to adjust treatment and monitoring strategies relative to the risk of an unfavourable disease course. Materials and Methods This retrospective study examined data from 916 patients with DTC who received treatment at a single centre between 2000 and 2013. The utility of the American Thyroid Association (ATA) and the European Thyroid Association (ETA) recommended systems for early assessment of the risk of recurrent/persistent disease was compared with that of the recently recommended delayed risk stratification (DRS) system. Results The PPV and NPV for the ATA (24.59% and 95.42%, respectively) and ETA (24.28% and 95.68%, respectively) were significantly lower than those for the DRS (56.76% and 98.5%, respectively) (p<0.0001). The proportion of variance for predicting the final outcome was 15.8% for ATA, 16.1% for ETA and 56.7% for the DRS. Recurrent disease was rare (1% of patients), and was nearly always identified in patients at intermediate/high risk according to the initial stratification (9/10 cases). Conclusions The DRS showed a better correlation with the risk of persistent disease than the early stratification systems and allows personalisation of follow-up. If clinicians plan to alter the intensity of surveillance, patients at intermediate/high risk according to the early stratification systems should remain within the specialized centers; however, low risk patients can be referred to endocrinologists or other appropriate practitioners for long-term follow-up, as these patients remained at low risk after risk re-stratification. PMID:27078258

  16. 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

  17. Aberrant Expression of COT Is Related to Recurrence of Papillary Thyroid Cancer

    PubMed Central

    Lee, Jandee; Jeong, Seonhyang; Park, Jae Hyun; Lee, Cho Rok; Ku, Cheol Ryong; Kang, Sang-Wook; Jeong, Jong Ju; Nam, Kee-Hyun; Shin, Dong Yeob; Lee, Eun Jig; Chung, Woong Youn; Jo, Young Suk

    2015-01-01

    Abstract Aberrant expression of Cancer Osaka Thyroid Oncogene mitogen-activated protein kinase kinase kinase 8 (COT) (MAP3K8) is a driver of resistance to B-RAF inhibition. However, the de novo expression and clinical implications of COT in papillary thyroid cancer (PTC) have not been investigated. The aim of this study is to investigate the expression of A-, B-, C-RAF, and COT in PTC (n = 167) and analyze the clinical implications of aberrant expression of these genes. Quantitative polymerase chain reaction (qPCR) and immunohistochemical staining (IHC) were performed on primary thyroid cancers. Expression of COT was compared with clinicopathological characteristics including recurrence-free survival. Datasets from public repository (NCBI) were subjected to Gene Set Enrichment Analysis (GSEA). qPCR data showed that the relative mRNA expression of A-, B-, C-RAF and COT of PTC were higher than normal tissues (all P < 0.01). In addition, the expression of COT mRNA in PTC showed positive correlation with A- (r = 0.4083, P < 0.001), B- (r = 0.2773, P = 0.0003), and C-RAF (r = 0.5954, P < 0.001). The mRNA expressions of A-, B,- and C-RAF were also correlated with each other (all P < 0.001). In IHC, the staining intensities of B-RAF and COT were higher in PTC than in normal tissue (P < 0.001). Interestingly, moderate-to-strong staining intensities of B-RAF and COT were more frequent in B-RAFV600E-positive PTC (P < 0.001, P = 0.013, respectively). In addition, aberrant expression of COT was related to old age at initial diagnosis (P = 0.045) and higher recurrence rate (P = 0.025). In multivariate analysis, tumor recurrence was persistently associated with moderate-to-strong staining of COT after adjusting for age, sex, extrathyroidal extension, multifocality, T-stage, N-stage, TNM stage, and B-RAFV600E mutation (odds ratio, 4.662; 95% confidence interval 1.066 − 21.609; P = 0.045). Moreover, moderate

  18. Aberrant expression of COT is related to recurrence of papillary thyroid cancer.

    PubMed

    Lee, Jandee; Jeong, Seonhyang; Park, Jae Hyun; Lee, Cho Rok; Ku, Cheol Ryong; Kang, Sang-Wook; Jeong, Jong Ju; Nam, Kee-Hyun; Shin, Dong Yeob; Lee, Eun Jig; Chung, Woong Youn; Jo, Young Suk

    2015-02-01

    Aberrant expression of Cancer Osaka Thyroid Oncogene mitogen-activated protein kinase kinase kinase 8 (COT) (MAP3K8) is a driver of resistance to B-RAF inhibition. However, the de novo expression and clinical implications of COT in papillary thyroid cancer (PTC) have not been investigated.The aim of this study is to investigate the expression of A-, B-, C-RAF, and COT in PTC (n = 167) and analyze the clinical implications of aberrant expression of these genes.Quantitative polymerase chain reaction (qPCR) and immunohistochemical staining (IHC) were performed on primary thyroid cancers. Expression of COT was compared with clinicopathological characteristics including recurrence-free survival. Datasets from public repository (NCBI) were subjected to Gene Set Enrichment Analysis (GSEA).qPCR data showed that the relative mRNA expression of A-, B-, C-RAF and COT of PTC were higher than normal tissues (all P < 0.01). In addition, the expression of COT mRNA in PTC showed positive correlation with A- (r = 0.4083, P < 0.001), B- (r = 0.2773, P = 0.0003), and C-RAF (r = 0.5954, P < 0.001). The mRNA expressions of A-, B,- and C-RAF were also correlated with each other (all P < 0.001). In IHC, the staining intensities of B-RAF and COT were higher in PTC than in normal tissue (P < 0.001). Interestingly, moderate-to-strong staining intensities of B-RAF and COT were more frequent in B-RAF-positive PTC (P < 0.001, P = 0.013, respectively). In addition, aberrant expression of COT was related to old age at initial diagnosis (P = 0.045) and higher recurrence rate (P = 0.025). In multivariate analysis, tumor recurrence was persistently associated with moderate-to-strong staining of COT after adjusting for age, sex, extrathyroidal extension, multifocality, T-stage, N-stage, TNM stage, and B-RAF mutation (odds ratio, 4.662; 95% confidence interval 1.066 - 21.609; P = 0.045). Moreover, moderate-to-strong COT expression in PTC

  19. Analysis of Risk Factors Contributing to Recurrence of Papillary Thyroid Carcinoma in Chinese Patients Who Underwent Total Thyroidectomy

    PubMed Central

    Zhang, Wei; Jiao, De; Liu, Baoguo; Sun, Shanping

    2016-01-01

    Background Thyroid cancer is a very common endocrine malignancy, with a rate of total thyroidectomy reported to be up to 27.8%. However, studies analyzing the risk factors that contribute to recurrence of papillary thyroid carcinoma (PTC) after total thyroidectomy in China are still scarce. Material/Methods A total of 536 patients with PTC who underwent total thyroidectomy were retrospectively analyzed. Patients were divided into 2 groups: patients with no recurrent tumor were included in group 1 and patients with tumor recurrence were included in group 2. Results Of 536 patients, 65 patients (12.1%) developed a recurrence of PTC, and 471 patients (87.9%) did not have a recurrence. Univariate analysis indicated that male sex, age ≥50 years, tumor ≥1 cm, poor differentiation, lymph node metastasis, bilaterality, and multifocality may be related to PTC recurrence. Additionally, the results of the logistic regression analysis indicated that male sex, age ≥50 years, primary tumor ≥1 cm, poor dedifferentiation of the tumor, lymph node metastasis, and multifocality may be independent factors contributing to PTC recurrence. Conclusions Male sex, age more than 50 years, primary tumor larger than 1 cm, poor dedifferentiation of the primary tumor, lymph node metastasis, and multifocality were found to increase the risk of PTC recurrence in patients who underwent total thyroidectomy. Additionally, it is necessary to use strictly aggressive and extensive surgery, as well as close monitoring, after the operation. PMID:27084873

  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. 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, ...

  2. Optimal Cut-Off Values of Lymph Node Ratio Predicting Recurrence in Papillary Thyroid Cancer

    PubMed Central

    Lee, Seul Gi; Ho, Joon; Choi, Jung Bum; Kim, Tae Hyung; Kim, Min Jhi; Ban, Eun Jeong; Lee, Cho Rok; Kang, Sang-Wook; Jeong, Jong Ju; Nam, Kee-Hyun; Jung, Sang Geun; Jo, Young Suk; Lee, Jandee; Chung, Woong Youn

    2016-01-01

    Abstract Regional lymph node (LN) metastasis has a significant impact for prediction of recurrence in patients with papillary thyroid cancers (PTC); however, the prognostic value of the lymph node ratio (LNR), which is defined as the ratio of the number of metastatic LNs to the total number of investigated LNs, is controversial. In this study, we determined the optimal cut-off values of LNRs for the prediction of recurrence in PTC patients. This large cohort study retrospectively evaluated 2294 patients who had undergone total thyroidectomy for PTC at a single institution from October 1985 to June 2009. The prediction probability of central LNR (cLNR, level VI) and total LNR (tLNR, levels II–VI) were estimated by binominal logistic regression analysis. Hazard ratios of the cut-off LNR values for cancer recurrence were calculated for relevant covariates using multivariate Cox regression analyses. Kaplan–Meier analyses were also utilized to assess the effects of estimated LNR cut-off values on recurrence-free survival (RFS). Of the 2294 patients, 138 (6.0%) presented cancer recurrence during the follow-up period (median duration = 107.1 months). The prediction probability indicated that LNRs of 0.4 and 0.5 for central LN and total LN, respectively, are optimal cut-off values for precise prediction with minimization of outliers. Multivariate Cox regression analyses revealed that cLNR ≥0.4 was independently predictive of recurrence in patients with N0 and N1a PTCs (hazard ratio [HR]: 7.016, 95% confidence interval [CI]: 3.72–12.986, P < 0.001) and that tLNR ≥0.5 indicated a significantly increased risk of recurrence in patients with N1b PTCs (HR: 2.372, 95% CI: 1.458–3.860, P < 0.001). In addition, Kaplan–Meier analyses clearly demonstrated that these LNR cut-off values are precisely operational in RFS estimation. The cut-off LNR values of 0.4 and 0.5 for cLNR and tLNR, respectively, were identified. Risk stratification combined with these LNR cut

  3. Optimal Cut-Off Values of Lymph Node Ratio Predicting Recurrence in Papillary Thyroid Cancer.

    PubMed

    Lee, Seul Gi; Ho, Joon; Choi, Jung Bum; Kim, Tae Hyung; Kim, Min Jhi; Ban, Eun Jeong; Lee, Cho Rok; Kang, Sang-Wook; Jeong, Jong Ju; Nam, Kee-Hyun; Jung, Sang Geun; Jo, Young Suk; Lee, Jandee; Chung, Woong Youn

    2016-02-01

    Regional lymph node (LN) metastasis has a significant impact for prediction of recurrence in patients with papillary thyroid cancers (PTC); however, the prognostic value of the lymph node ratio (LNR), which is defined as the ratio of the number of metastatic LNs to the total number of investigated LNs, is controversial. In this study, we determined the optimal cut-off values of LNRs for the prediction of recurrence in PTC patients.This large cohort study retrospectively evaluated 2294 patients who had undergone total thyroidectomy for PTC at a single institution from October 1985 to June 2009. The prediction probability of central LNR (cLNR, level VI) and total LNR (tLNR, levels II-VI) were estimated by binominal logistic regression analysis. Hazard ratios of the cut-off LNR values for cancer recurrence were calculated for relevant covariates using multivariate Cox regression analyses. Kaplan-Meier analyses were also utilized to assess the effects of estimated LNR cut-off values on recurrence-free survival (RFS).Of the 2294 patients, 138 (6.0%) presented cancer recurrence during the follow-up period (median duration = 107.1 months). The prediction probability indicated that LNRs of 0.4 and 0.5 for central LN and total LN, respectively, are optimal cut-off values for precise prediction with minimization of outliers. Multivariate Cox regression analyses revealed that cLNR ≥0.4 was independently predictive of recurrence in patients with N0 and N1a PTCs (hazard ratio [HR]: 7.016, 95% confidence interval [CI]: 3.72-12.986, P < 0.001) and that tLNR ≥0.5 indicated a significantly increased risk of recurrence in patients with N1b PTCs (HR: 2.372, 95% CI: 1.458-3.860, P < 0.001). In addition, Kaplan-Meier analyses clearly demonstrated that these LNR cut-off values are precisely operational in RFS estimation.The cut-off LNR values of 0.4 and 0.5 for cLNR and tLNR, respectively, were identified. Risk stratification combined with these LNR cut-off values may prove

  4. Human thyreoglobulin (HTG) for the diagnosis of recurrent differentiated thyroid carcinoma: Evaluation by ROC - analysis

    SciTech Connect

    Laubenbacher, C.; Schrafstetter, C.; Senekowitsch, R.

    1995-05-01

    The value of hTg-measurements are still discussed controversially. Also, there are no tables with sensitivity/specificity pairs for different cutoffs, since valuable information is lost by presenting only one sensitivity/specificity pair. Therefore, we wanted to determine these values for hTg by a ROC-analysis. Inclusion criteria were: (a) differentiated thyroid carcinoma (papillary or follicular), (b) no thyroid-rest after primary therapy (e.g. no detectable hTg and nc iodine accumulating foci in iodine-whole body scan), (c) no detectable hTg- antibodies, (d) an observation period of at least 1 year, hTg was determined by TG-RIA and hTg-antibodies by IMMUtest anti-Tg. Recurrence was proven by iodine-whole-body scans under maximal endogenous TSH-stimulation or by histology. Sensitivity and specificity were calculated for different hTg-cutoffs. During 10/80 and 10/89 93 patients met these criteria. There were 71 female and 22 male with a mean age of 48.6 {plus_minus} 16.3 years. 51 patients had papillary carcinomas, 42 patients follicular carcinomas. The observation period was 78.4 {plus_minus} 40.9 months. In these 93 patients there were 16 recurrences during the observation period. Sensitivity/specificity pairs for different cutoffs are given. These sensitivity/specificity pairs avoid the reduction of the original continuous data to a Yes/No decision. The knowledge of these data and of the ROC-curve could improve the intuitive rating of a laboratory result by the physician.

  5. F18-FDG-PET for recurrent differentiated thyroid cancer: a systematic meta-analysis

    PubMed Central

    Haslerud, Torjan; Brauckhoff, Katrin; Reisæter, Lars; Küfner Lein, Regina; Heinecke, Achim; Varhaug, Jan Erik

    2015-01-01

    Background Positron emission tomography (PET) with fluor-18-deoxy-glucose (FDG) is widely used for diagnosing recurrent or metastatic disease in patients with differentiated thyroid cancer (DTC). Purpose To assess the diagnostic accuracy of FDG-PET for DTC in patients after ablative therapy. Material and Methods A systematic search was conducted in Medline/PubMed, EMBASE, Cochrane Library, Web of Science, and Open Grey looking for all English-language original articles on the performance of FDG-PET in series of at least 20 patients with DTC having undergone ablative therapy including total thyroidectomy. Diagnostic performance measures were pooled using Reitsma’s bivariate model. Results Thirty-four publications between 1996 and 2014 met the inclusion criteria. Pooled sensitivity and specificity were 79.4% (95% confidence interval [CI], 73.9–84.1) and 79.4% (95% CI, 71.2–85.4), respectively, with an area under the curve of 0.858. Conclusion F18-FDG-PET is a useful method for detecting recurrent DTC in patients having undergone ablative therapy. PMID:26163534

  6. 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

  7. 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

  8. 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

  9. Metastatic Lymph Node Ratio of Central Neck Compartment Has Predictive Values for Locoregional Recurrence in Papillary Thyroid Microcarcinoma

    PubMed Central

    Choi, Sung Yong; Cho, Jae-Keun; Moon, Jeong Hwan; Son, Young-Ik

    2016-01-01

    Objectives This study aimed to evaluate the significance of metastatic lymph node ratio (the ratio between the metastatic lymph node and the harvested lymph nodes; MLNR) in the central neck for the prediction of locoregional recurrence in patients with papillary thyroid microcarcinoma. Methods After reviewing medical records of papillary thyroid microcarcinoma patients who received total thyroidectomy with central neck node dissection, 573 consecutive adult patients were enrolled in this study, with a follow-up period of more than 36 months. Regarding the risk of recurrence, multivariate analyses were performed with the following variables; sex, age, multiplicity of the primary tumor, presence of pathological extrathyroidal extension, the level of postoperative stimulated serum thyroglobulin, the number of harvested lymph nodes, the number of lymph node metastasis and MLNR. Results The MLNR showed a predictive significance for the locoregional recurrence (P<0.05). Most recurrences were occurred in the lateral neck (n=12, 80%) with a median interval of 20 months. The lowest cutoff value of the MLNR for a meaningful separation of disease recurrence was 0.44 (hazard ratio, 8.86; 95% confidence interval, 1.49 to 52.58; P=0.001). Conclusion When the MLNR is higher than 0.44, there is an increased risk of locoregional recurrence mostly in the lateral neck. Therefore, MLNR of the central neck in a permanent or frozen biopsy may be helpful in decision making in the extent of thyroidectomy and/or the need for contralateral central neck lymph nodes dissection. PMID:26976031

  10. Protective effect of intraoperative nerve monitoring against recurrent laryngeal nerve injury during re-exploration of the thyroid

    PubMed Central

    2013-01-01

    Background Previous thyroid or parathyroid surgery induces scarring or distorts anatomy, and increases the risk of recurrent laryngeal nerve (RLN) injury for a reoperation. The benefit of intraoperative nerve monitoring (IONM) for re-exploration (a second nerve exploration) and reoperation has not been established. Methods Two hundred and ten patients were given a thyroid or parathyroid reoperation at our hospital between 2001 and 2010. Using IONM, we re-explored 56 patients who had been operated on before June 2007. The injury rate in these patients was compared with that of the 15 patients re-explored without IONM between 2001 and 2006. Results Of the 70 nerves that were re-explored using IONM, only one was incidentally injured, significantly fewer than the three injured in the 15 nerves re-explored without using IONM (1.43% vs. 20%, P = 0.0164). Conclusions IONM helped prevent RLN damage when re-exploring nerves during thyroid and parathyroid surgery. We recommend the routine use of IONM in thyroid and parathyroid reoperations. PMID:23618223

  11. Cabozantinib-S-Malate in Treating Younger Patients With Recurrent, Refractory, or Newly Diagnosed Sarcomas, Wilms Tumor, or Other Rare Tumors

    ClinicalTrials.gov

    2016-08-15

    Adrenal Cortex Carcinoma; Adult Alveolar Soft Part Sarcoma; Adult Clear Cell Sarcoma of Soft Parts; Adult Hepatocellular Carcinoma; Adult Rhabdomyosarcoma; Adult Soft Tissue Sarcoma; Childhood Alveolar Soft Part Sarcoma; Childhood Central Nervous System Neoplasm; Childhood Clear Cell Sarcoma of Soft Parts; Childhood Hepatocellular Carcinoma; Childhood Rhabdomyosarcoma; Childhood Soft Tissue Sarcoma; Childhood Solid Neoplasm; Ewing Sarcoma; Hepatoblastoma; Hepatocellular Carcinoma; Recurrent Adrenal Cortex Carcinoma; Recurrent Adult Hepatocellular Carcinoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Alveolar Soft Part Sarcoma; Recurrent Childhood Central Nervous System Neoplasm; Recurrent Childhood Hepatocellular Carcinoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Ewing Sarcoma; Recurrent Hepatoblastoma; Recurrent Renal Cell Carcinoma; Recurrent Rhabdomyosarcoma; Relapsed Solid Neoplasm; Renal Cell Carcinoma; Thyroid Gland Medullary Carcinoma; Wilms Tumor

  12. 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.

  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. Identification alone versus intraoperative neuromonitoring of the recurrent laryngeal nerve during thyroid surgery: experience of 2034 consecutive patients

    PubMed Central

    2014-01-01

    Background The aim of this study was to evaluate the ability of intraoperative neuromonitoring in reducing the postoperative recurrent laryngeal nerve palsy rate by a comparison between patients submitted to thyroidectomy with intraoperative neuromonitoring and with routine identification alone. Methods Between June 2007 and December 2012, 2034 consecutive patients underwent thyroidectomy by a single surgical team. We compared patients who have had neuromonitoring and patients who have undergone surgery with nerve visualization alone. Patients in which neuromonitoring was not utilized (Group A) were 993, patients in which was utilized (group B) were 1041. Results In group A 28 recurrent laryngeal nerve injuries were observed (2.82%), 21 (2.11%) transient and 7 (0.7%) permanent. In group B 23 recurrent laryngeal nerve injuries were observed (2.21%), in 17 cases (1.63%) transient and in 6 (0.58%) permanent. Differences were not statistically significative. Conclusions Visual nerve identification remains the gold standard of recurrent laryngeal nerve management in thyroid surgery. Neuromonitoring helps to identify the nerve, in particular in difficult cases, but it did not decrease nerve injuries compared with visualization alone. Future studies are warranted to evaluate the benefit of intraoperative neuromonitoring in thyroidectomy, especially in conditions in which the recurrent nerve is at high risk of injury. PMID:24942225

  15. The effect of routine reversal of neuromuscular blockade on adequacy of recurrent laryngeal nerve stimulation during thyroid surgery.

    PubMed

    Marshall, S D; Boden, E; Serpell, J

    2015-07-01

    Testing of the integrity of the recurrent laryngeal nerve during thyroid surgery has become routine practice for many surgeons to aid dissection and minimise the chance of inadvertent nerve injury. We hypothesised that routine reversal of an intermediate-acting, non-depolarising neuromuscular blocking agent would improve conditions for stimulation of the recurrent laryngeal nerve. We conducted a single-centre, randomised, double-blind placebo-controlled trial of patients undergoing thyroid surgery by the same surgeon. After randomisation, the participants received either neostigmine 2.5 mg with glycopyrrolate 0.4 mg or placebo, at 30 minutes after induction of anaesthesia and administration of 0.4 mg/kg of atracurium. The primary outcome was the subjective assessment by the surgeon as to whether the neuromuscular function was adequate for stimulation of the recurrent laryngeal nerve using a neuromuscular integrity monitor (NIM). Time to NIM stimulation was 44.6 minutes in the placebo group and 41.4 minutes in the intervention group (P=0.268). Of the 21 patients who received the neuromuscular blockade reversal, 20 (95.2%) had adequate surgical conditions for NIM stimulation, compared to 9 out of 18 patients (50%) in the placebo group (P=0.002). Three of the ten patients (30%) with inadequate reversal showed no evidence of residual blockade assessed peripherally. The routine reversal of neuromuscular blockade at 30 minutes post induction appears to result in adequate surgical conditions for safe stimulation of the recurrent laryngeal nerve. Return of neuromuscular function at a peripheral site does not guarantee adequate laryngeal muscle function for use of the NIM. PMID:26099761

  16. 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 ...

  17. [Right non recurrent laryngeal nerve during thyroid surgery: one case report].

    PubMed

    Huang, Weipeng; Zhang, Qingfeng; She, Cuiping

    2015-12-01

    A 56 years old female was admitted to our department with complaint of a painless cervical mass. Clinical feature:there was a painless mass above left lobe of thyroid gland, which was about 3.0 cm x 2.5 cm in size, and could move with swallowing action. B-mode ultrasound features: there was a solid mass in left lobe of thyroid gland, which was about 3.2 cm. Nodule was found in isthmus, accompanied with lymphadenovarix on the left neck possibly be MCA. fT3: 4.64 pmol/L, fT4:16.56 pmol/L,TSH:3.74 mIU/L, anti-TG:17.75 U/ml, anti-TPO:40.77 U/ml. Pathological result of the neoplasm: papillocarcinoma. Clinical diagnosis: papillary thyroid carcinoma. PMID:27093826

  18. 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.

  19. Sorafenib Tosylate in Treating Younger Patients With Relapsed or Refractory Rhabdomyosarcoma, Wilms Tumor, Liver Cancer, or Thyroid Cancer

    ClinicalTrials.gov

    2015-05-14

    Childhood Hepatocellular Carcinoma; Papillary Thyroid Cancer; Previously Treated Childhood Rhabdomyosarcoma; Recurrent Childhood Liver Cancer; Recurrent Childhood Rhabdomyosarcoma; Recurrent Thyroid Cancer; Recurrent Wilms Tumor and Other Childhood Kidney Tumors

  20. 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

  1. [Monitoring of recurrent laryngeal nerve injury using an electromyographic endotracheal tube in thyroid and parathyroid surgery. Anesthetic aspects].

    PubMed

    Martín Jaramago, J; Tamarit Conejeros, M; Escudero Torrella, M; Solaz Roldán, C

    2013-12-01

    Recurrent laryngeal nerve injury remains one of the main complications in thyroid and parathyroid surgery. When this injury is bilateral, an acute upper airway obstruction may occur, leading to a potentially life-threatening situation for the patient. The visual identification of the nerve during surgery is the best way to preserve its integrity. However identification of the nerves by means of electromyographic stimuli through electrodes attached to endotracheal tubes could help in decreasing nerve injury. In these cases the experience and role of the anesthetist is essential to correctly place the electromyographic endotracheal tube and ensure that the electrodes are in touch with the vocal cords during the surgery. Moreover, the results of the electromyography can be affected by the neuromuscular blocking agents. Therefore, the choice and dose must be adapted, in order to ensure a suitable anesthetic depth, and adequate response. PMID:23886448

  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. Post-PET ultrasound improves specificity of 18F-FDG-PET for recurrent differentiated thyroid cancer while maintaining sensitivity

    PubMed Central

    Kråkenes, Jostein; Brauckhoff, Katrin; Haugland, Hans Kristian; Heinecke, Achim; Akslen, Lars A; Varhaug, Jan Erik; Brauckhoff, Michael

    2015-01-01

    Background Positron emission tomography (PET) using fluor-18-deoxyglucose (18F-FDG) with or without computed tomography (CT) is generally accepted as the most sensitive imaging modality for diagnosing recurrent differentiated thyroid cancer (DTC) in patients with negative whole body scintigraphy with iodine-131 (I-131). Purpose To assess the potential incremental value of ultrasound (US) over 18F-FDG-PET-CT. Material and Methods Fifty-one consecutive patients with suspected recurrent DTC were prospectively evaluated using the following multimodal imaging protocol: (i) US before PET (pre-US) with or without fine needle biopsy (FNB) of suspicious lesions; (ii) single photon emission computed tomography (≥3 GBq I-131) with co-registered CT (SPECT-CT); (iii) 18F-FDG-PET with co-registered contrast-enhanced CT of the neck; (iv) US in correlation with the other imaging modalities (post-US). Postoperative histology, FNB, and long-term follow-up (median, 2.8 years) were taken as composite gold standard. Results Fifty-eight malignant lesions were identified in 34 patients. Forty lesions were located in the neck or upper mediastinum. On receiver operating characteristics (ROC) analysis, 18F-FDG-PET had a limited lesion-based specificity of 59% at a set sensitivity of 90%. Pre-US had poor sensitivity and specificity of 52% and 53%, respectively, increasing to 85% and 94% on post-US, with knowledge of the PET/CT findings (P < 0.05 vs. PET and pre-US). Multimodal imaging changed therapy in 15 out of 51 patients (30%). Conclusion In patients with suspected recurrent DTC, supplemental targeted US in addition to 18F-FDG-PET-CT increases specificity while maintainin sensitivity, as non-malignant FDG uptake in cervical lesions can be confirmed. PMID:25770086

  4. Radioactive iodine ablation may not decrease the risk of recurrence in intermediate-risk papillary thyroid carcinoma.

    PubMed

    Kim, Seo Ki; Woo, Jung-Woo; Lee, Jun Ho; Park, Inhye; Choe, Jun-Ho; Kim, Jung-Han; Kim, Jee Soo

    2016-05-01

    The use of radioactive iodine (RAI) ablation in patients with intermediate-risk papillary thyroid carcinoma (PTC) who show microscopic extrathyroidal extension (ETE), regional lymph node (LN) metastasis, tumors with aggressive histology, or vascular invasion has been debated due to the lack of data regarding long-term prognosis in this risk group. Therefore, the purpose of this study was to resolve the controversy surrounding the prognostic benefit of RAI ablation, especially in intermediate-risk PTC patients. We retrospectively reviewed the medical records of 8297 intermediate-risk PTC patients who underwent primary total thyroidectomy with or without neck dissection at the Thyroid Cancer Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea, between January 1997 and June 2015. Of these 8297 patients, 7483 (90.2%) received RAI ablation. After adjusting for clinicopathological characteristics, RAI ablation did not significantly decrease the risk of loco-regional recurrence (LRR) (adjusted hazard ratio (HR) 0.852, P 0.413). Moreover, RAI ablation did not decrease the risk of LRR even in intermediate-risk PTC patients with aggressive features such as BRAF positivity (adjusted HR 0.729, P 0.137), tumor size >1 cm (adjusted HR 0.762, P 0.228), multifocality (adjusted HR 1.032, P 0.926), ETE (adjusted HR 0.870, P 0.541), and regional LN metastasis (adjusted HR 0.804, P 0.349). Furthermore, high-dose RAI ablation (>100 mCi) did not significantly decrease the risk of LRR (adjusted HR 0.942, P 0.843). Therefore, RAI ablation in intermediate-risk PTC patients should be considered on the basis of tailored risk restratification. PMID:26917553

  5. 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

  6. 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

  7. 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 ...

  8. Image-guided high-dose-rate interstitial brachytherapy – a valuable salvage treatment approach for loco-regional recurrence of papillary thyroid cancer

    PubMed Central

    Wu, Ning; Zhao, Hongfu; Han, Dongmei; Zhao, Zhipeng; Ge, Yuxin

    2016-01-01

    Purpose To report the treatment effect of image-guided high-dose-rate (HDR) interstitial brachytherapy for refractory recurrence of papillary thyroid cancer (PTC). Case report This 66-year-old female presented with recurrence 5 years after thyroidectomy for PTC. Despite external irradiation and radioactive 131I, the lesion expanded as 3.7 × 3.0 × 2.3 cm3 and 2.0 × 1.5 × 1.5 cm3. The locoregional recurrent tumor was treated with image-guided HDR interstitial brachytherapy. The total dose of 30 Gy in 6 fractions were delivered on the whole recurrent tumor. Results Removal of the recurrent tumor was securely achieved by HDR interstitial brachytherapy guided with ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI) scanning. The refractory tumor in the patients healed uneventfully after HDR interstitial brachytherapy without recurrence during the 14 months of follow-up. Conclusions The image-guided HDR interstitial brachytherapy may be a valuable salvage treatment approach for refractory recurrence of PTC. PMID:27257420

  9. Predictive factors for recurrence of differentiated thyroid cancer in patients under 21 years of age and a meta-analysis of the current literature.

    PubMed

    Qu, Ning; Zhang, Ling; Lu, Zhong-Wu; Ji, Qing-Hai; Yang, Shu-Wen; Wei, Wen-Jun; Zhang, Yan

    2016-06-01

    The influence of predictors for recurrence in relation to recurrence-free survival was analyzed retrospectively in differentiated thyroid cancer (DTC) patients under 21 years of age who underwent primary surgical treatment and who had a pathological diagnosis of DTC between 1983 and 2012 at Fudan University Cancer Hospital. Recurrences were retrospectively analyzed using a Cox regression model for the hazard ratio (HR) according to the clinicopathological features. A meta-analysis was performed with respect to the potential predictors for recurrence from current related studies. In the present study, there were 146 young patients aged from 7 to 20 years, with a female/male ratio of 2.65/1. Female gender was the only factor significantly associated with recurrence according to univariate (HR = 2.812, P = 0.037) and multivariate (HR = 4.107, P = 0.024) Cox regression analyses. Meta-analyses revealed that multifocality (HR = 1.91, P < 0.05) and presentation at diagnosis (HR = 1.39, P < 0.05) were highly associated with recurrence in young DTC patients. However, female gender and other factors, such as age (≤10 vs. 11-20 years), PTC (PTC vs. FTC), extrathyroidal extension, lymph node metastasis, total thyroidectomy (total vs. less than total), radioiodine therapy, and radiation history, were not associated with recurrence in young DTC patients. In conclusion, multifocality and presentation at diagnosis are strong predictive factors of recurrence in relation to recurrence-free survival. We recommend studies with larger sample sizes and longer follow-up to verify the influence of predictors for disease recurrence in young patients. PMID:26695148

  10. Intraoperative neuromonitoring of the recurrent laryngeal nerve in robotic thyroid surgery.

    PubMed

    Bae, Dong Sik; Kim, Su-jin

    2015-02-01

    This study evaluated the technical feasibility and efficacy of intraoperative neuromonitoring (IONM) of the recurrent laryngeal nerve (RLN) to aid its identification and preservation during robotic thyroidectomy (RoT). IONM of the RLN was evaluated in 30 consecutive patients undergoing RoT. All patients underwent an indirect laryngoscope examination to objectively assess vocal cord function. Their Voice Handicap Index-10 (VHI-10) was measured to subjectively assess vocal cord function preoperatively and at postoperative months 1 and 3. Of the 56 RLNs at risk in 30 patients undergoing RoT, all were visualized and identified by IONM. The IONM sensitivity for postoperative permanent RLN palsy was 100%, with a positive predictive value of 100%. The mean VHI-10 scores preoperatively and at postoperative months 1 and 3 were 0.20±0.66, 3.47±5.04, and 1.53±2.47, respectively (P<0.001). IONM of the RLN during RoT is technically feasible and effective for identifying this nerve. PMID:25238177

  11. Cediranib Maleate With or Without Lenalidomide in Treating Patients With Thyroid Cancer

    ClinicalTrials.gov

    2016-07-20

    Recurrent Thyroid Gland Carcinoma; Stage I Thyroid Gland Follicular Carcinoma; Stage I Thyroid Gland Papillary Carcinoma; Stage II Thyroid Gland Follicular Carcinoma; Stage II Thyroid Gland Papillary Carcinoma; Stage III Thyroid Gland Follicular Carcinoma; Stage III Thyroid Gland Papillary Carcinoma; Stage IVA Thyroid Gland Follicular Carcinoma; Stage IVA Thyroid Gland Papillary Carcinoma; Stage IVB Thyroid Gland Follicular Carcinoma; Stage IVB Thyroid Gland Papillary Carcinoma; Stage IVC Thyroid Gland Follicular Carcinoma; Stage IVC Thyroid Gland Papillary Carcinoma

  12. Risk Factors Associated with Disease Recurrence among Patients with Low-Risk Papillary Thyroid Cancer Treated at the University of the Philippines-Philippine General Hospital

    PubMed Central

    Buenaluz-Sedurante, Myrna; Jimeno, Cecilia Alegado

    2016-01-01

    Background The management of papillary thyroid carcinoma (PTC) in high-risk patients is well-standardized. However, this is not the case for low-risk patients. Filipinos show a high incidence of recurrence of thyroid cancer. Thus, the identification of risk factors for recurrence in this population could potentially identify individuals for whom radioactive iodine (RAI) therapy might be beneficial. Methods We reviewed the medical records of adult Filipinos with low-risk PTC who underwent near-total or total thyroidectomy at the University of the Philippines-Philippine General Hospital. Multivariate logistic regression analysis was used to determine risk factors for recurrence. Results Recurrence was documented in 51/145 of patients (35.17%) included in this study. Possible risk factors such as age, sex, family history, smoking history, tumor size, multifocality, prophylactic lymph node dissection, initial thyroglobulin (Tg) level, initial anti-thyroglobulin (anti-Tg) antibody concentration, suppression of thyroid stimulating hormone production, and RAI therapy were analyzed. Multivariate analysis revealed that a tumor diameter 2 to 4 cm (odds ratio [OR], 9.17; 95% confidence interval [CI], 1.62 to 51.88; P=0.012), a tumor diameter >4 cm (OR, 16.46; 95% CI, 1.14 to 237.31; P=0.04), and a family history of PTC (OR, 67.27; 95% CI, 2.03 to 2228.96; P=0.018) were significant predictors of recurrence. In addition, RAI therapy (OR, 0.026; 95% CI, 0.01 to 0.023; P≤0.005), an initial Tg level ≤2 ng/mL (OR, 0.049; 95% CI, 0.01 to 0.23; P≤0.005), and an anti-Tg antibody level ≤50 U/mL (OR, 0.087; 95% CI, 0.011 to 0.67; P=0.019) were significant protective factors. Conclusion A tumor diameter ≥2 cm and a family history of PTC are significant predictors of recurrence. RAI therapy and low initial titers of Tg and anti-Tg antibody are significant protective factors against disease recurrence among low-risk PTC patients. PMID:26676333

  13. 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.

  14. 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 ...

  15. Impact of Iymph node metastases identified on central neck dissection (CND) on the recurrence of papillary thyroid cancer: potential role of BRAFV600E mutation in defining CND

    PubMed Central

    Alzahrani, Ali S; Xing, Mingzhao

    2013-01-01

    The impact of metastasized cervical lymph nodes (CLN) identified on central neck dissection (CND) on the recurrence/persistence of papillary thyroid cancer (PTC) and the extent of CND needed to reduce recurrence/persistence have not been firmly established. To assess the impact of CLN metastasis and BRAF mutation on the recurrence/persistence of PTC and the potential of BRAF mutation in assisting CND, we analysed data of 379 consecutive patients with PTC who underwent thyroidectomy with (n=243) or without CND (n=136) at a tertiary-care academic hospital during the period 2001–2010 for their clinicopathological outcomes and BRAF mutation status. Increasingly aggressive tumor characteristics were found as the extent of CND was advanced following conventional risk criteria from non-CND to limited CND to formal CND. Disease recurrence/persistence rate also sharply rose from 4.7% to 15.7% and 40.5% in these CND settings respectively (P<0.0001). CLN metastasis rate rose from 18.0 to 77.3% from limited CND to formal CND (P<0.0001). An increasing rate of BRAF mutation was also found from less to more extensive CND. A strong association of CLN metastasis and BRAF mutation with disease recurrence/persistence was revealed on Kaplan– Meier analysis and BRAF mutation strongly predicted CLN metastasis. CLN metastases found on CND are closely associated with disease recurrence/persistence of PTC, which are both strongly predicted by BRAF mutation. Current selection of PTC patients for CND is appropriate but higher extent of the procedure, once selected, is needed to reduce disease recurrence, which may be defined by combination use of preoperative BRAF mutation testing and conventional risk factors of PTC. PMID:23132792

  16. Detection of Tumor Multifocality Is Important for Prediction of Tumor Recurrence in Papillary Thyroid Microcarcinoma: A Retrospective Study and Meta-Analysis

    PubMed Central

    Pyo, Jung-Soo; Sohn, Jin Hee; Kang, Guhyun

    2016-01-01

    Background: The clinicopathological characteristics and conclusive treatment modality for multifocal papillary thyroid microcarcinoma (mPTMC) have not been fully established. Methods: A retrospective study, systematic review, and meta-analysis were conducted to elucidate the clinicopathological significance of mPTMC. We investigated the multiplicity of 383 classical papillary thyroid microcarcinomas (PTMCs) and the clinicopathological significance of incidental mPTMCs. Correlation between tumor recurrence and multifocality in PTMCs was evaluated through a systematic review and meta-analysis. Results: Tumor multifocality was identified in 103 of 383 PTMCs (26.9%). On linear regression analysis, primary tumor diameter was significantly correlated with tumor number (R2=0.014, p=.021) and supplemental tumor diameter (R2=0.117, p=.023). Of 103 mPTMCs, 61 (59.2%) were non-incidental, with tumor detected on preoperative ultrasonography, and 42 (40.8%) were diagnosed (incidental mPTMCs) on pathological examination. Lymph node metastasis and higher tumor stage were significantly correlated with tumor multifocality. However, there was no difference in nodal metastasis or tumor stage between incidental and non-incidental mPTMCs. On meta-analysis, tumor multifocality was significantly correlated with tumor recurrence in PTMCs (odds ratio, 2.002; 95% confidence interval, 1.475 to 2.719, p<.001). Conclusions: Our results show that tumor multifocality in PTMC, regardless of manner of detection, is significantly correlated with aggressive tumor behavior. PMID:27271109

  17. Use of imaging tests after primary treatment of thyroid cancer in the United States: population based retrospective cohort study evaluating death and recurrence

    PubMed Central

    Banerjee, Mousumi; Wiebel, Jaime L; Guo, Cui; Gay, Brittany

    2016-01-01

    Objective To determine whether the use of imaging tests after primary treatment of differentiated thyroid cancer is associated with more treatment for recurrence and fewer deaths from the disease. Design Population based retrospective cohort study. Setting Surveillance Epidemiology and End Results-Medicare database in the United States. Participants 28 220 patients diagnosed with differentiated thyroid cancer between 1998 and 2011. The study cohort was followed up to 2013, with a median follow-up of 69 months. Main outcome measures Treatment for recurrence of differentiated thyroid cancer (additional neck surgery, additional radioactive iodine treatment, or radiotherapy), and deaths due to differentiated thyroid cancer. We conducted propensity score analyses to assess the relation between imaging (neck ultrasound, radioiodine scanning, or positron emission tomography (PET) scanning) and treatment for recurrence (logistic model) and death (Cox proportional hazards model). Results From 1998 until 2011, we saw an increase in incident cancer (rate ratio 1.05, 95% confidence interval 1.05 to 1.06), imaging (1.13, 1.12 to 1.13), and treatment for recurrence (1.01, 1.01 to 1.02); the change in death rate was not significant. In multivariable analysis, use of neck ultrasounds increased the likelihood of additional surgery (odds ratio 2.30, 95% confidence interval 2.05 to 2.58) and additional radioactive iodine treatment (1.45, 1.26 to 1.69). Radioiodine scans were associated with additional surgery (odds ratio 3.39, 95% confidence interval 3.06 to 3.76), additional radioactive iodine treatment (17.83, 14.49 to 22.16), and radiotherapy (1.89, 1.71 to 2.10). Use of PET scans was associated with additional surgery (odds ratio 2.31, 95% confidence interval 2.09 to 2.55), additional radioactive iodine treatment (2.13, 1.89 to 2.40), and radiotherapy (4.98, 4.52 to 5.49). Use of neck ultrasounds or PET scans did not significantly affect disease specific survival (hazard

  18. Cabozantinib-S-Malate in Treating Patients With Refractory Thyroid Cancer

    ClinicalTrials.gov

    2016-07-04

    Poorly Differentiated Thyroid Gland Carcinoma; Recurrent Thyroid Gland Carcinoma; Stage I Thyroid Gland Follicular Carcinoma; Stage I Thyroid Gland Papillary Carcinoma; Stage II Thyroid Gland Follicular Carcinoma; Stage II Thyroid Gland Papillary Carcinoma; Stage III Thyroid Gland Follicular Carcinoma; Stage III Thyroid Gland Papillary Carcinoma; Stage IVA Thyroid Gland Follicular Carcinoma; Stage IVA Thyroid Gland Papillary Carcinoma; Stage IVB Thyroid Gland Follicular Carcinoma; Stage IVB Thyroid Gland Papillary Carcinoma; Stage IVC Thyroid Gland Follicular Carcinoma; Stage IVC Thyroid Gland Papillary Carcinoma; Tall Cell Variant Thyroid Gland Papillary Carcinoma; Thyroid Gland Oncocytic Follicular Carcinoma

  19. 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

  20. Recurrent differentiated thyroid cancer: towards personalized treatment based on evaluation of tumor characteristics with PET (THYROPET Study): study protocol of a multicenter observational cohort study

    PubMed Central

    2014-01-01

    Background After initial treatment of differentiated thyroid carcinoma (DTC) patients are followed with thyroglobulin (Tg) measurements to detect recurrences. In case of elevated levels of Tg and negative neck ultrasonography, patients are treated 'blindly' with Iodine-131 (131I). However, in up to 50% of patients, the post-therapy scan reveals no 131I-targeting of tumor lesions. Such patients derive no benefit from the blind therapy but are exposed to its toxicity. Alternatively, iodine-124 (124I) Positron Emission Tomography/Computed Tomography (PET/CT) has become available to visualize DTC lesions and without toxicity. In addition to this, 18F-fluorodeoxyglucose (18F-FDG) PET/CT detects the recurrent DTC phenotype, which lost the capacity to accumulate iodine. Taken together, the combination of 124I and 18F-FDG PET/CT has potential to stratify patients for treatment with 131I. Methods/Design In a multicenter prospective observational cohort study the hypothesis that the combination of 124I and 18F-FDG PET/CT can avoid futile 131I treatments in patients planned for ‘blind’ therapy with 131I, is tested. One hundred patients planned for 131I undergo both 124I and 18F-FDG PET/CT after rhTSH stimulation. Independent of the outcome of the scans, all patients will subsequently receive, after thyroid hormone withdrawal, the 131I therapy. The post 131I therapeutic scintigraphy is compared with the outcome of the 124I and 18F-FDG PET/CT in order to evaluate the diagnostic value of the combined PET modalities. This study primary aims to reduce the number of futile 131I therapies. Secondary aims are the nationwide introduction of 124I PET/CT by a quality assurance and quality control (QA/QC) program, to correlate imaging outcome with histopathological features, to compare 124I PET/CT after rhTSH and after withdrawal of thyroid hormone, and to compare 124I and 131I dosimetry. Discussion This study aims to evaluate the potential value of the combination of 124I and 18F

  1. 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

  2. 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

  3. Recurrent Papillary Thyroid Carcinoma with Pleural Metastasis Diagnosed by Effusion Cytology: A Report of Cases with Clinicopathologic Correlation

    PubMed Central

    Sakamoto, Reid I; Sumida, Lauren C; Lum, Christopher AK

    2015-01-01

    Papillary thyroid carcinoma (PTC) is typically an indolent disease characterized by slow growth and a favorable prognosis. In rare instances, this disease may metastasize to the pleura and manifest as a malignant pleural effusion. We report 3 female patients of Japanese/Okinawan ancestry with a history of PTC who presented with hydrothorax. Cytologic examination in conjunction with immunohistochemical staining enabled a definitive diagnosis of metastatic PTC. Molecular analysis of the mitogen activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) pathways demonstrated the presence of the v-raf murine sarcoma viral oncogene homolog B (BRAF)V600E mutation in 2 of our 3 patients, with the absence of any other clinically significant mutations in all cases. Further investigation is necessary to elucidate the molecular and environmental mechanisms involved in this aggressive manifestation of PTC. PMID:25755913

  4. An unusual cause of hoarseness and recurrent laryngeal nerve palsy.

    PubMed

    Truong, Phat; Dickerson, Lisa

    2016-08-01

    Recurrent laryngeal nerve palsy and thyroid disease suggest locally invasive thyroid malignancy. In contrast, recurrent laryngeal nerve palsy caused by benign multinodular goiters or ectopic thyroid tissue accounts for only 1% of cases. This article describes an unusual case of recurrent laryngeal nerve palsy secondary to a benign ectopic retrosternal thyroid tissue mass. Recurrent laryngeal nerve palsy should be considered in the differential diagnosis of patients presenting with progressive voice weakness and hoarseness. PMID:27467296

  5. [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

  6. The treatment of metastatic thyroid disease

    SciTech Connect

    Lee, K.Y.; Lore, J.M. Jr. )

    1990-06-01

    Removal of all resectable disease commensurate with reasonable morbidity and mortality is the initial treatment of all thyroid carcinoma. Patients with no evidence of recurrent metastatic well-differentiated thyroid carcinoma should be placed on suppressive doses of Synthroid. {sup 131}I is utilized for nonresectable and for distant metastatic well-differentiated thyroid carcinoma. External radiation therapy and chemotherapy are utilized in recurrent or metastatic thyroid carcinomas that do not concentrate {sup 131}I. 49 references.

  7. 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 ...

  8. Classic Architecture with Multicentricity and Local Recurrence, and Absence of TERT Promoter Mutations are Correlates of BRAF (V600E) Harboring Pediatric Papillary Thyroid Carcinomas.

    PubMed

    Onder, Semen; Ozturk Sari, Sule; Yegen, Gulcin; Sormaz, Ismail Cem; Yilmaz, Ismail; Poyrazoglu, Sukran; Sanlı, Yasemin; Giles Senyurek, Yasemin; Kapran, Yersu; Mete, Ozgur

    2016-06-01

    This study is aimed to investigate the BRAF (V600E) and TERT promoter mutation profile of 50 pediatric papillary thyroid carcinomas (PTCs) to refine their clinicopathological correlates. The median age at the time of surgery was 16 years (range, 6-18). No TERT promoter mutations were identified in this series. The BRAF (V600E) mutation was present in 15 (30 %) tumors. From genotype-histologic variant correlation perspective, 13 of 24 classic variant PTCs and 2 of 7 diffuse sclerosing variant PTCs were found to harbor BRAF (V600E) mutation. One cribriform-morular variant, 3 solid variant, and 15 follicular variant PTCs were BRAF wild type. While tumors with distant metastasis were BRAF wild type, two of five tumors with extrathyroidal extension (ETE) harbored BRAF (V600E) mutation. Nine of 15 BRAF (V600E) harboring tumors had central lymph node metastases. There was no significant correlation with BRAF (V600E) mutation and age, gender, tumor size, ETE, central lymph node metastasis, the status of pT, pN1a-b, and distant metastasis. An adverse correlation between BRAF (V600E) mutation and disease-free survival (DFS) was noted in the entire cohort; however, the predictive value of BRAF (V600E) mutation disappeared within the group of tumors displaying classic architecture as well as classic variant PTCs. The present cohort identifies that the classic architecture with multicentricity and local recurrence are correlates of BRAF (V600E) harboring pediatric PTCs. While the small size of this cohort is one of the limitations, neither the BRAF mutation status nor the classic tumor architecture does seem to be an independent prognosticator of DFS in this series. Evidence also suggests that TERT promoter mutations do not seem to play a major role in the pathogenesis of pediatric PTCs. PMID:26951110

  9. 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

  10. 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.

  11. 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 ...

  12. 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 ...

  13. 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 ...

  14. 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 ...

  15. 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 ...

  16. 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

  17. 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

  18. Recurrent Takotsubo Cardiomyopathy Related to Recurrent Thyrotoxicosis

    PubMed Central

    Patel, Keval; Griffing, George T.; Hauptman, Paul J.

    2016-01-01

    Takotsubo cardiomyopathy, or transient left ventricular apical ballooning syndrome, is characterized by acute left ventricular dysfunction caused by transient wall-motion abnormalities of the left ventricular apex and mid ventricle in the absence of obstructive coronary artery disease. Recurrent episodes are rare but have been reported, and several cases of takotsubo cardiomyopathy have been described in the presence of hyperthyroidism. We report the case of a 55-year-old woman who had recurrent takotsubo cardiomyopathy, documented by repeat coronary angiography and evaluations of left ventricular function, in the presence of recurrent hyperthyroidism related to Graves disease. After both episodes, the patient's left ventricular function returned to normal when her thyroid function normalized. These findings suggest a possible role of thyroid-hormone excess in the pathophysiology of some patients who have takotsubo cardiomyopathy. PMID:27127432

  19. Recurrent Takotsubo Cardiomyopathy Related to Recurrent Thyrotoxicosis.

    PubMed

    Patel, Keval; Griffing, George T; Hauptman, Paul J; Stolker, Joshua M

    2016-04-01

    Takotsubo cardiomyopathy, or transient left ventricular apical ballooning syndrome, is characterized by acute left ventricular dysfunction caused by transient wall-motion abnormalities of the left ventricular apex and mid ventricle in the absence of obstructive coronary artery disease. Recurrent episodes are rare but have been reported, and several cases of takotsubo cardiomyopathy have been described in the presence of hyperthyroidism. We report the case of a 55-year-old woman who had recurrent takotsubo cardiomyopathy, documented by repeat coronary angiography and evaluations of left ventricular function, in the presence of recurrent hyperthyroidism related to Graves disease. After both episodes, the patient's left ventricular function returned to normal when her thyroid function normalized. These findings suggest a possible role of thyroid-hormone excess in the pathophysiology of some patients who have takotsubo cardiomyopathy. PMID:27127432

  20. Scans Not Worthwhile for Most Thyroid Cancers: Study

    MedlinePlus

    ... fullstory_160009.html Scans Not Worthwhile for Most Thyroid Cancers: Study Doctors found checking for recurrences with ... News) -- Having scans after treatment does not improve thyroid cancer patients' chances of survival, a new study ...

  1. 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

  2. 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

  3. Genome Haploidisation with Chromosome 7 Retention in Oncocytic Follicular Thyroid Carcinoma

    PubMed Central

    Corver, Willem E.; Ruano, Dina; Weijers, Karin; den Hartog, Wietske C. E.; van Nieuwenhuizen, Merlijn P.; de Miranda, Noel; van Eijk, Ronald; Middeldorp, Anneke; Jordanova, Ekaterina S.; Oosting, Jan; Kapiteijn, Ellen; Hovens, Guido; Smit, Jan; van Wezel, Tom; Morreau, Hans

    2012-01-01

    Background Recurrent non-medullary thyroid carcinoma (NMTC) is a rare disease. We initially characterized 27 recurrent NMTC: 13 papillary thyroid cancers (PTC), 10 oncocytic follicular carcinomas (FTC-OV), and 4 non-oncocytic follicular carcinomas (FTC). A validation cohort composed of benign and malignant (both recurrent and non-recurrent) thyroid tumours was subsequently analysed (n = 20). Methods Data from genome-wide SNP arrays and flow cytometry were combined to determine the chromosomal dosage (allelic state) in these tumours, including mutation analysis of components of PIK3CA/AKT and MAPK pathways. Results All FTC-OVs showed a very distinct pattern of genomic alterations. Ten out of 10 FTC-OV cases showed near-haploidisation with or without subsequent genome endoreduplication. Near-haploidisation was seen in 5/10 as extensive chromosome-wide monosomy (allelic state [A]) with near-haploid DNA indices and retention of especially chromosome 7 (seen as a heterozygous allelic state [AB]). In the remaining 5/10 chromosomal allelic states AA with near diploid DNA indices were seen with allelic state AABB of chromosome 7, suggesting endoreduplication after preceding haploidisation. The latter was supported by the presence of both near-haploid and endoreduplicated tumour fractions in some of the cases. Results were confirmed using FISH analysis. Relatively to FTC-OV limited numbers of genomic alterations were identified in other types of recurrent NMTC studied, except for chromosome 22q which showed alterations in 6 of 13 PTCs. Only two HRAS, but no mutations of EGFR or BRAF were found in FTC-OV. The validation cohort showed two additional tumours with the distinct pattern of genomic alterations (both with oncocytic features and recurrent). Conclusions We demonstrate that recurrent FTC-OV is frequently characterised by genome-wide DNA haploidisation, heterozygous retention of chromosome 7, and endoreduplication of a near-haploid genome. Whether normal gene

  4. Cancer Stem Cells in the Thyroid

    PubMed Central

    Nagayama, Yuji; Shimamura, Mika; Mitsutake, Norisato

    2016-01-01

    The cancer stem cell (CSC) model posits that CSCs are a small, biologically distinct subpopulation of cancer cells in each tumor that have self-renewal and multi-lineage potential, and are critical for cancer initiation, metastasis, recurrence, and therapy-resistance. Numerous studies have linked CSCs to thyroid biology, but the candidate markers and signal transduction pathways that drive thyroid CSC growth are controversial, the origin(s) of thyroid CSCs remain elusive, and it is unclear whether thyroid CSC biology is consistent with the original hierarchical CSC model or the more recent dynamic CSC model. Here, we critically review the thyroid CSC literature with an emphasis on research that confirmed the presence of thyroid CSCs by in vitro sphere formation or in vivo tumor formation assays with dispersed cells from thyroid cancer tissues or bona fide thyroid cancer cell lines. Future perspectives of thyroid CSC research are also discussed. PMID:26973599

  5. Cancer Stem Cells in the Thyroid.

    PubMed

    Nagayama, Yuji; Shimamura, Mika; Mitsutake, Norisato

    2016-01-01

    The cancer stem cell (CSC) model posits that CSCs are a small, biologically distinct subpopulation of cancer cells in each tumor that have self-renewal and multi-lineage potential, and are critical for cancer initiation, metastasis, recurrence, and therapy-resistance. Numerous studies have linked CSCs to thyroid biology, but the candidate markers and signal transduction pathways that drive thyroid CSC growth are controversial, the origin(s) of thyroid CSCs remain elusive, and it is unclear whether thyroid CSC biology is consistent with the original hierarchical CSC model or the more recent dynamic CSC model. Here, we critically review the thyroid CSC literature with an emphasis on research that confirmed the presence of thyroid CSCs by in vitro sphere formation or in vivo tumor formation assays with dispersed cells from thyroid cancer tissues or bona fide thyroid cancer cell lines. Future perspectives of thyroid CSC research are also discussed. PMID:26973599

  6. 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.

  7. 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 ...

  8. 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 ...

  9. 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 ...

  10. [CME: Radioactive iodine therapy in thyroid cancer].

    PubMed

    Steinert, Hans C; Aberle, Susanne

    2015-11-11

    Differentiated thyroid carcinomas represent about 90% of all thyroid tumors and are divided in papillary and follicular carcinomas. Their prognosis is good, however, recurrences are not rare. Their ability to accumulate iodine is used for the radioactive iodine treatment. The aim of the postoperative radioactive iodine ablation therapy is the complete elimination of remnant thyroid cells and sensitive staging (Fig. 1). The recurrence rate decreases after a complete thyroid ablation. Furthermore, thyroglobulin can be used as a sensitive tumor marker. Radioactive iodine treatment by itself describes the therapy of metastases. An exception is the papillary microcarcinoma, which in general is treated by a lobectomy alone. PMID:26558927

  11. 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 ...

  12. 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

  13. 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

  14. 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 ...

  15. 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

  16. 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.

  17. 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 ...

  18. 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

  19. 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

  20. [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

  1. 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

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

    PubMed

    Sidibé, El Hassane

    2007-01-01

    Thyroid gland diseases vary according to the environment. In sub-Saharan Africa, they are also influenced by population isolation and the absence of food self-sufficiency, both factors affecting the onset and persistence of iodine-deficiency goiters. More cosmopolitan diseases are now added to these thyroid disorders. Women are mainly affected (94.2%), most often with euthyroid goiters (54.7%), followed by Graves disease (13.1%), hypothyroidism (8.8%), thyroiditis (6.6%), toxic multinodular goiters (6.6 %) and unclassified goiters (10%) [Gabon]. The paucity of laboratories specializing in endocrinology and of nuclear medicine facilities, the delay in diagnosis that results in compressive or recurrent goiters, and endemic goiters are all typical in Africa. In children and adolescents, death rates increase with congenital or acquired thyroiditis as with delayed physical or mental development. In this environment, thyroiditis can also be pregnancy-related. Very recent surveys show a prevalence of endemic goiters of 28.6% in the community of Sekota, Ethiopia, 64-70% in Sahel-Sudan (population aged 10-20 years), 20-29% in KwaZulu-Natal (school children), 14.3-30.2% in Namibia (school children), 0.21% (congenital hypothyroidism or cretinism) in Plateau State, Nigeria, 55.2% at Zitenga, Burkina Faso (210 persons 0-45 years), and 10% in Hararé and Wedza, Zimbabwe (newborn TSH >10.1 microIU/mL). The prevalence of goiters is 43.6% in children emigrating from Ethiopia to Israel. Millet from semi-arid zones contains apigenin at a concentration of 150 mg/kg and luteolin at 350 mg/kg, both of which can interfere with thyroid function. The harmful effects of cassava (also known as manioc) are better known: milling cassava reduces its goitrogenic potential. In addition to iodine deficiency, selenium deficiency, and the effect of the thiocyanates in cassava, ion concentrations in soil and drinking water appear to play a role. The proportion of thyroid surgery indicated for

  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 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 ...

  5. 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 ...

  6. 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 ...

  7. 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? ...

  8. 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 ...

  9. 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 ...

  10. 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 ...