Multiple endocrine neoplasia: the Chilean experience

Multiple endocrine neoplasia (MEN) types 1 and 2 are genetic diseases that are inherited as autosomal traits. The major clinical manifestations of multiple endocrine neoplasia type 1 include the so-called “3 P's”: parathyroid, pituitary, and pancreatic tumors, including gastroenteroneuroendocrine tumors. Genetic testing can be performed on patients and the potential carriers of the menin gene mutation, but the genotype-phenotype correlation in multiple endocrine neoplasia type 1 is less straightforward than multiple endocrine neoplasia type 2. Most likely, the main advantage of genetic testing in MEN1 is to exclude from further studies those who are negative for the genetic mutation if they belong to a family with a known history of MEN1. In Chile, we started with rearranged during transfection proto-oncogene genetic testing (MEN2) 15 years ago. We carried out a prophylactic total thyroidectomy to prevent medullary thyroid carcinoma in a three-year-old girl who presented with microscopic medullary thyroid carcinoma. More than 90% of the individuals who tested positive using a genetic test achieved a biochemical cure compared with only 27% of patients who receive a clinical diagnosis. Mutations are mainly located in exon 11; the most common is C634W, rather than C634R. Hypertensive crisis was the cause of death in three patients, and extensive distant metastases occurred in nine (including two patients with multiple endocrine neoplasia type 2B) of 14 patients. Earlier recognition of medullary thyroid carcinoma and the other features of the disease, especially pheochromocytoma, will improve the survival rate of patients with multiple endocrine neoplasia

Neoplasias endocrinas múltiples. desde el laboratorio al paciente

ResumenLas neoplasias endocrinas múltiples (NEM) tipo 1 y 2 son enfermedades genéticas heredadas en forma autosómica dominante. Las principales manifestaciones clínicas en NEM1 incluyen tumores paratiroideos, hipofisiarios y gastroenteropancreáticos. El test genético se puede realizar en los pacientes y potenciales portadores de mutaciones en el gen menin, pero la correlación genotipo-fenotipo es menos directa en comparación a NEM2. En la NEM2 el cáncer medular de tíroides (CMT) es común a los tres subtipos: NEM2A (feocromocitoma e hiperparatiroidismo), NEM2B (feocromocitoma y neuromas mucosos) y CMT familiar. A aquellos pacientes con mutación RET se les debe recomendar la realización de tiroidectomía profiláctica en la niñez, de acuerdo a la categoría de riesgo ATA. Algunos casos de CMT aparentemente esporádicos son actualmente NEM2 después de la realización del estudio genético para proto-oncogen RET, por lo tanto se recomienda la aplicación rutinaria de este estudio a todos los pacientes con CMT aparentemente esporádico.SummaryMultiple endocrine neoplasia (MEN) type 1 and 2, are genetic diseases heritage in an autosomal trait. The major clinical manifestations in MEN1 include parathyroid, pituitary and gastroenteropancreatic neuroendocrine tumors. Genetic testing can be done in patients and potential carrier of the menin gene mutation, but the genotype-phenotype correlation is less straightforward in comparison with MEN2. In MEN2 the medullary thyroid carcinoma (MTC) is common to the three subtypes: MEN2A (phechromocytoma and hyperparathyroidism), MEN2B (phechromocytoma and mucosal neuromas) and familial MTC. Those with the RET mutation should be advised to have prophylactic thyroidectomy in the childhood, according with the ATA risk level. Some cases of apparently sporadic MTC are actually MEN2 after RET proto-oncogene testing is done, therefore routine application of this test is recommended in all cases of apparently sporadic MTC

Recomendações da Sociedade Latino-Americana de Tireoide para diagnóstico e manejo do carcinoma diferenciado de tireoide

The aims of these recommendations were to develop clinical guidelines for evaluation and management of patients with differentiated thyroid cancer applicable to Latin American countries. The panel was composed by 13 members of the Latin American Thyroid Society (LATS) involved with research and management of thyroid cancer from different medical centers in Latin America. The recommendations were produced on the basis of the expert opinion of the panel with use of principles of Evidence-Based Medicine. Following a group meeting, a first draft based on evidences and the expert opinions of the panel was elaborated and, later, circulated among panel members, for further revision. After, this document was submitted to the LATS members, for commentaries and considerations, and, finally, revised and refined by the authors. The final recommendations presented in this paper represent the state of the art on management of differentiated thyroid cancer applied to all Latin American countries.Estas recomendações tiveram por objetivo o desenvolvimento de diretrizes para avaliação e manejo de pacientes com câncer diferenciado da tiroide em países latino-americanos. Um painel composto por 13 membros da Sociedade Latino-Americana de Tireoide (SLAT) - que estavam envolvidos em pesquisas, e eram peritos no cuidado do paciente com câncer da tiroide e provenientes de diferentes centros médicos latino-americanos - utilizou os princípios da Medicina Baseada em Evidências para produzir esse consenso. Após uma primeira reunião, um texto inicial foi elaborado, baseado em evidências e opiniões dos especialistas do painel e, posteriormente, circulado entre os membros do painel, para revisão. Após a revisão, o documento foi enviado aos membros da SLAT para comentários e considerações e, finalmente, revisado e refinado pelos autores. As recomendações finais aqui apresentadas demonstram o estado da arte no manejo do câncer diferenciado da tireoide aplicadas aos países latino-americanos.88488

Recomendações da Sociedade Latino-Americana de Tireoide no manejo de nódulos tireoideos

Several guidelines on diagnosis and treatment of thyroid nodules and cancer have recently been published. However, recommended practices are not always appropriate to different settings or countries. The aim of this consensus was to develop Clinical Guidelines for evaluation and management of patients with thyroid nodules applicable to Latin American countries. The panel was composed by 13 members of the Latin American Thyroid Society involved with research and management of thyroid nodules and cancer from different medical centers in Latin America. The consensus was produced based on the expert opinion of the panel with use of principles of evidence-based medicine. Following a group meeting, a first draft based on the expert opinion of the panel was elaborated and later circulated among panel members for further revision. After revision, this document was submitted to all LATS members for commentaries and considerations and finally revised and refined by the authors. The final recommendations represent state of the art on management of thyroid nodules applied to all Latin American countries.Vários consensos têm sido publicados acerca do diagnóstico e do tratamento de nódulos e câncer da tireoide. Entretanto, as recentes recomendações nem sempre são apropriadas para diferentes regiões ou países. O objetivo deste trabalho foi oferecer uma série de recomendações para a avaliação e conduta de pacientes portadores de nódulos tireoideos aplicáveis a todos os países da América Latina. O trabalho foi realizado por um comitê composto por 13 membros da Sociedade Latino-Americana de Tireoide envolvidos com pesquisa e manejo de pacientes portadores de nódulos e carcinoma diferenciado da tireoide, de diferentes centros médicos da América Latina. As recomendações foram estabelecidas, após consenso, utilizando as opiniões especializadas de cada membro e os princípios da medicina baseada em evidência. Após a primeira reunião do grupo, um primeiro documento foi elaborado e encaminhado a todos os membros para revisão. Posteriormente, o documento foi enviado aos membros da Sociedade Latino-Americana de Tireoide para avaliação, sugestões e comentários. A versão final, elaborada após refinada revisão de todos os autores, representa o estado da arte no diagnóstico e na conduta de nódulos tireoideos, aplicáveis a todos os países da América Latina

Recomendações da sociedade Latino-Americana de tireoide no manejo de nódulos tireoideos

Several guidelines on diagnosis and treatment of thyroid nodules and cancer have recently been published. However, recommended practices are not always appropriate to different settings or countries. The aim of this consensus was to develop Clinical Guidelines for evaluation and management of patients with thyroid nodules applicable to Latin American countries. The panel was composed by 13 members of the Latin American Thyroid Society involved with research and management of thyroid nodules and cancer from different medical centers in Latin America. The consensus was produced based on the expert opinion of the panel with use of principles of evidence-based medicine. Following a group meeting, a first draft based on the expert opinion of the panel was elaborated and later circulated among panel members for further revision. After revision, this document was submitted to all LATS members for commentaries and considerations and finally revised and refined by the authors. The final recommendations represent state of the art on management of thyroid nodules applied to all Latin American countries539Vários consensos têm sido publicados acerca do diagnóstico e do tratamento de nódulos e câncer da tireoide. Entretanto, as recentes recomendações nem sempre são apropriadas para diferentes regiões ou países. O objetivo deste trabalho foi oferecer uma série de recomendações para a avaliação e conduta de pacientes portadores de nódulos tireoideos aplicáveis a todos os países da América Latina. O trabalho foi realizado por um comitê composto por 13 membros da Sociedade Latino-Americana de Tireoide envolvidos com pesquisa e manejo de pacientes portadores de nódulos e carcinoma diferenciado da tireoide, de diferentes centros médicos da América Latina. As recomendações foram estabelecidas, após consenso, utilizando as opiniões especializadas de cada membro e os princípios da medicina baseada em evidência. Após a primeira reunião do grupo, um primeiro documento foi elaborado e encaminhado a todos os membros para revisão. Posteriormente, o documento foi enviado aos membros da Sociedade Latino-Americana de Tireoide para avaliação, sugestões e comentários. A versão final, elaborada após refinada revisão de todos os autores, representa o estado da arte no diagnóstico e na conduta de nódulos tireoideos, aplicáveis a todos os países da América Latin

Head and neck paragangliomas: clinical and molecular genetic classification

Head and neck paragangliomas are tumors arising from specialized neural crest cells. Prominent locations are the carotid body along with the vagal, jugular, and tympanic glomus. Head and neck paragangliomas are slowly growing tumors, with some carotid body tumors being reported to exist for many years as a painless lateral mass on the neck. Symptoms depend on the specific locations. In contrast to paraganglial tumors of the adrenals, abdomen and thorax, head and neck paragangliomas seldom release catecholamines and are hence rarely vasoactive. Petrous bone, jugular, and tympanic head and neck paragangliomas may cause hearing loss. The internationally accepted clinical classifications for carotid body tumors are based on the Shamblin Class I–III stages, which correspond to postoperative permanent side effects. For petrous-bone paragangliomas in the head and neck, the Fisch classification is used. Regarding the molecular genetics, head and neck paragangliomas have been associated with nine susceptibility genes: NF1, RET, VHL, SDHA, SDHB, SDHC, SDHD, SDHAF2 (SDH5), and TMEM127. Hereditary HNPs are mostly caused by mutations of the SDHD gene, but SDHB and SDHC mutations are not uncommon in such patients. Head and neck paragangliomas are rarely associated with mutations of VHL, RET, or NF1. The research on SDHA, SDHAF2 and TMEM127 is ongoing. Multiple head and neck paragangliomas are common in patients with SDHD mutations, while malignant head and neck paraganglioma is mostly seen in patients with SDHB mutations. The treatment of choice is surgical resection. Good postoperative results can be expected in carotid body tumors of Shamblin Class I and II, whereas operations on other carotid body tumors and other head and neck paragangliomas frequently result in deficits of the cranial nerves adjacent to the tumors. Slow growth and the tendency of hereditary head and neck paragangliomas to be multifocal may justify less aggressive treatment strategies

Latin American Thyroid Society Recommendations For The Management Of Thyroid Nodules [recomendações Da Sociedade Latino-americana De Tireoide No Manejo De Nódulos Tireoideos]

Several guidelines on diagnosis and treatment of thyroid nodules and cancer have recently been published. However, recommended practices are not always appropriate to different settings or countries. The aim of this consensus was to develop Clinical Guidelines for evaluation and management of patients with thyroid nodules applicable to Latin American countries. The panel was composed by 13 members of the Latin American Thyroid Society involved with research and management of thyroid nodules and cancer from different medical centers in Latin America. The consensus was produced based on the expert opinion of the panel with use of principles of evidence-based medicine. Following a group meeting, a first draft based on the expert opinion of the panel was elaborated and later circulated among panel members for further revision. After revision, this document was submitted to all LATS members for commentaries and considerations and finally revised and refined by the authors. The final recommendations represent state of the art on management of thyroid nodules applied to all Latin American countries. © ABE&M todos os direitos reservados.53911671175Villena, J., Pretell, E., Bocio nodular tóxico en pacientes de zonas yodo deficientes y de la costa (1991) Rev Méd Hered, 2 (4), pp. 149-155Villena, J., Ferrufino, J.C., Klinge, G., Nódulo tireoideo frio. Características clínicas y anatomopatológicas en pacientes migrantes de zonas con deficiencia de yodo y de la costa (1993) Rev Méd Hered, 4 (4), pp. 188-193Harach, H.R., Ceballos, G.A., Thyroid cancer, thyroiditis and dietary iodine: A review based on the Salta, Argentina model (2008) Endocr Pathol, 19 (4), pp. 209-220Pretell, E.A., Delange, F., Hostalek, U., Corigliano, S., Barreda, L., Higa, A.M., Iodine nutrition improves in Latin America (2004) Thyroid, 14 (8), pp. 595-604Harach, H.R., Franssila, K.O., Wasenius, V.M., Occult papillary carcinoma of the thyroid. A "normal" finding in Finland. A systematic autopsy study (1985) Cancer, 56 (3), pp. 531-538Rosai, J., Livolsi, V.A., Sobrinho-Simoes, M., Williams, E.D., Renaming papillary microcarcinoma of the thyroid gland: The Porto proposal (2003) Int J Surg Pathol, 11 (4), pp. 249-251Hay, I.D., Grant, C.S., van Heerden, J.A., Goellner, J.R., Ebersold, J.R., Bergstralh, E.J., Papillary thyroid microcarcinoma: A study of 535 cases observed in a 50-year period (1992) Surgery, 112 (6), pp. 1139-1146Jukkola, A., Bloigu, R., Ebeling, T., Salmela, P., Blanco, G., Prognostic factors in differentiated thyroid carcinomas and their implications for current staging classifications (2004) Endocr Relat Cancer, 11 (3), pp. 571-579Passler, C., Scheuba, C., Prager, G., Kaczirek, K., Kaserer, K., Zettinig, G., Prognostic factors of papillary and follicular thyroid cancer: Differences in an iodine-replete endemic goiter region (2004) Endocr Relat Cancer, 11 (1), pp. 131-139Rossi, R., Roti, E., Trasforini, G., Pansini, G., Cavazzini, L., Zatelli, M.C., Differentiated thyroid cancers 11-20 mm in diameter have clinical and histopathologic characteristics suggesting higher aggressiveness than those ≤ 10 mm (2008) Thyroid, 18 (3), pp. 309-315Curtis, R.E., Rowlings, P.A., Deeg, H.J., Shriner, D.A., Socie, G., Travis, L.B., Solid cancers after bone marrow transplantation (1997) N Engl J Med, 336 (13), pp. 897-904Sippel, R.S., Caron, N.R., Clark, O.H., An evidence-based approach to familial nonmedullary thyroid cancer: Screening, clinical management, and follow-up (2007) World J Surg, 31 (5), pp. 924-933Pacini, F., Pinchera, A., Giani, C., Grasso, L., Doveri, F., Baschieri, L., Serum thyroglobulin in thyroid carcinoma and other thyroid disorders (1980) J Endocrinol Invest, 3 (3), pp. 283-292Niccoli, P., Wion-Barbot, N., Caron, P., Henry, J.F., de Micco, C., Saint Andre, J.P., Interest of routine measurement of serum calcitonin: Study in a large series of thyroidectomized patients. The French Medullary Study Group (1997) J Clin Endocrinol Metab, 82 (2), pp. 338-341Gagel, R.F., Hoff, A.O., Cote, G.J., Medullary thyroid carcinoma (2005) Werner and Ingbar's the Thyroid: A Fundamental and Clinical Text, pp. 967-988. , In: Lewis E, Robert D, Sidney H, Sidney C, (Eds)., Philadelphia: Lippincott Williams and WilkinsPapini, E., Guglielmi, R., Bianchini, A., Crescenzi, A., Taccogna, S., Nardi, F., Risk of malignancy in nonpalpable thyroid nodules: Predictive value of ultrasound and color-Doppler features (2002) J Clin Endocrinol Metab, 87 (5), pp. 1941-1946Camargo, R.Y., Tomimori, E.K., Knobel, M., Medeiros-Neto, G., Preoperative assessment of thyroid nodules: Role of ultrasonography and fine needle aspiration biopsy followed by cytology (2007) Clinics, 62 (4), pp. 411-418Kang, H.W., No, J.H., Chung, J.H., Min, Y.K., Lee, M.S., Lee, M.K., Prevalence, clinical and ultrasonographic characteristics of thyroid incidentalomas (2004) Thyroid, 14 (1), pp. 29-33Shimura, H., Haraguchi, K., Hiejima, Y., Fukunari, N., Fujimoto, Y., Katagiri, M., Distinct diagnostic criteria for ultrasonographic examination of papillary thyroid carcinoma: A multicenter study (2005) Thyroid, 15 (3), pp. 251-258Cappelli, C., Castellano, M., Pirola, I., Cumetti, D., Agosti, B., Gandossi, E., The predictive value of ultrasound findings in the management of thyroid nodules (2007) Qjm, 100 (1), pp. 29-35Holden, A., The role of colour and duplex Doppler ultrasound in the assessment of thyroid nodules (1995) Australas Radiol, 39 (4), pp. 343-349Papini, E., Guglielmi, R., Bianchini, A., Crescenzi, A., Taccogna, S., Nardi, F., Risk of malignancy in nonpalpable thyroid nodules: Predictive value of ultrasound and color-Doppler features (2002) J Clin Endocrinol Metab, 87 (5), pp. 1941-1946Chammas, M.C., Gerhard, R., de Oliveira, I.R., Widman, A., de Barros, N., Durazzo, M., Thyroid nodules: Evaluation with power Doppler and duplex Doppler ultrasound (2005) Otolaryngol Head Neck Surg, 132 (6), pp. 874-882Frates, M.C., Benson, C.B., Doubilet, P.M., Cibas, E.S., Marqusee, E., Can color Doppler sonography aid in the prediction of malignancy of thyroid nodules? (2003) J Ultrasound Med, 22 (2), pp. 127-131Rago, T., Vitti, P., Chiovato, L., Mazzeo, S., de Liperi, A., Miccoli, P., Role of conventional ultrasonography and color flow-doppler sonography in predicting malignancy in 'cold' thyroid nodules (1998) Eur J Endocrinol, 138 (1), pp. 41-46Lyshchik, A., Moses, R., Barnes, S.L., Higashi, T., Asato, R., Miga, M.I., Quantitative analysis of tumor vascularity in benign and malignant solid thyroid nodules (2007) J Ultrasound Med, 26 (6), pp. 837-846Tamsel, S., Demirpolat, G., Erdogan, M., Nart, D., Karadeniz, M., Uluer, H., Power Doppler US patterns of vascularity and spectral Doppler US parameters in predicting malignancy in thyroid nodules (2007) Clin Radiol, 62 (3), pp. 245-251Pacini, F., Burroni, L., Ciuoli, C., di Cairano, G., Guarino, E., Management of thyroid nodules: A clinicopathological, evidence-based approach (2004) Eur J Nucl Med Mol Imaging, 31 (10), pp. 1443-1449Kim, T.Y., Kim, W.B., Ryu, J.S., Gong, G., Hong, S.J., Shong YK. 18F-fluorodeoxyglucose uptake in thyroid from positron emission tomogram (PET) for evaluation in cancer patients: High prevalence of malignancy in thyroid PET incidentaloma (2005) Laryngoscope, 115 (6), pp. 1074-1078Danese, D., Sciacchitano, S., Farsetti, A., Andreoli, M., Pontecorvi, A., Diagnostic accuracy of conventional versus sonography-guided fine-needle aspiration biopsy of thyroid nodules (1998) Thyroid, 8 (1), pp. 15-21de la Serna Saravia, C., Cuellar, F., Accuracy of aspiration cytology in thyroid cancer: A study in 1 institution (2006) Acta Cytol, 50 (4), pp. 384-387Giorgadze, T., Rossi, E.D., Fadda, G., Gupta, P.K., Livolsi, V.A., Baloch, Z., Does the fine-needle aspiration diagnosis of "Hurthle-cell neoplasm/follicular neoplasm with oncocytic features" denote increased risk of malignancy? (2004) Diagn Cytopathol, 31 (5), pp. 307-312Niepomniszcze, H., Garcia, A., Faure, E., Castellanos, A., del Carmen Zalazar, M., Bur, G., Long-term follow-up of contralateral lobe in patients hemithyroidectomized for solitary follicular adenoma (2001) Clin Endocrinol (oxf), 55 (4), pp. 509-513Alcantara-Jones, D.M., Araujo, L.M., Almeida, A.M., Jones, D.A., Cardoso, L.J., Passos, M.C., Percutaneous ethanol injection for the treatment of thyroid nodules (2006) Arq Bras Endocrinol Metabol, 50 (1), pp. 97-104Lippi, F., Ferrari, C., Manetti, L., Rago, T., Santini, F., Monzani, F., Treatment of solitary autonomous thyroid nodules by percutaneous ethanol injection: Results of an Italian multicenter study. The Multicenter Study Group (1996) J Clin Endocrinol Metab, 81 (9), pp. 3261-3264Hegedüs, L., Hansen, B.M., Knudsen, N., Hansen, J.M., Reduction of size of thyroid with radioactive iodine in multinodular non-toxic goitre (1988) Bmj, 297 (6649), pp. 661-662Huysmans, D., Hermus, A., Edelbroek, M., Barentsz, J., Corstens, F., Kloppenborg, P., Radioiodine for nontoxic multinodular goiter (1997) Thyroid, 7 (2), pp. 235-239Nygaard, B., Hegedus, L., Ulriksen, P., Nielsen, K.G., Hansen, J.M., Radioiodine therapy for multinodular toxic goiter (1999) Arch Intern Med, 159 (12), pp. 1364-1368Huysmans, D.A., Hermus, A.R., Corstens, F.H., Barentsz, J.O., Kloppenborg, P.W., Large, compressive goiters treated with radioiodine (1994) Ann Intern Med, 121 (10), pp. 757-762Nygaard, B., Soes-Petersen, U., Hoilund-Carlsen, P.F., Veje, A., Holst, P.E., Vestergaard, A., Improvement of upper airway obstruction after 131I-treatment of multinodular nontoxic goiter evaluated by flow volume loop curves (1996) J Endocrinol Invest, 19 (2), pp. 71-75Nygaard, B., Faber, J., Hegedus, L., Acute changes in thyroid volume and function following 131I therapy of multinodular goitre (1994) Clin Endocrinol (oxf), 41 (6), pp. 715-718Huysmans, D.A., Nieuwlaat, W.A., Erdtsieck, R.J., Schellekens, A.P., Bus, J.W., Bravenboer, B., Administration of a single low dose of recombinant human thyrotropin significantly enhances thyroid radioiodide uptake in nontoxic nodular goiter (2000) J Clin Endocrinol Metab, 85 (10), pp. 3592-3596Nieuwlaat, W.A., Hermus, A.R., Sivro-Prndelj, F., Corstens, F.H., Huysmans, D.A., Pretreatment with recombinant human TSH changes the regional distribution of radioiodine on thyroid scintigrams of nodular goiters (2001) J Clin Endocrinol Metab, 86 (11), pp. 5330-5336Nieuwlaat, W.A., Huysmans, D.A., van den Bosch, H.C., Sweep, C.G., Ross, H.A., Corstens, F.H., Pretreatment with a single, low dose of recombinant human thyrotropin allows dose reduction of radioiodine therapy in patients with nodular goiter (2003) J Clin Endocrinol Metab, 88 (7), pp. 3121-3129Duick, D.S., Baskin, H.J., Utility of recombinant human thyrotropin for augmentation of radioiodine uptake and treatment of nontoxic and toxic multinodular goiters (2003) Endocr Pract, 9 (3), pp. 204-209Silva, M.N., Rubio, I.G., Romao, R., Gebrin, E.M., Buchpiguel, C., Tomimori, E., Administration of a single dose of recombinant human thyrotrophin enhances the efficacy of radioiodine treatment of large compressive multinodular goitres (2004) Clin Endocrinol (oxf), 60 (3), pp. 300-308Albino, C.C., Mesa Jr., C.O., Olandoski, M., Ueda, C.E., Woellner, L.C., Goedert, C.A., Recombinant human thyrotropin as adjuvant in the treatment of multinodular goiters with radioiodine (2005) J Clin Endocrinol Metab, 90 (5), pp. 2775-2780Friguglietti, C.U., Lin, C.S., Kulcsar, M.A., Total thyroidectomy for benign thyroid disease (2003) Laryngoscope, 113 (10), pp. 1820-1826Rezzonico, J., Rezzonico, M., Pusiol, E., Pitoia, F., Neipomniszcze, H., Introducing the thyroid gland as another victim of the insulin resistance syndrome (2008) Thyroid, 18 (4), pp. 461-464Vella, V., Sciacca, L., Pandini, G., Mineo, R., Squatrito, S., Vigneri, R., The IGF system in thyroid cancer: New concepts (2001) Mol Pathol, 54 (3), pp. 121-124Rezzonico, J., Rezzonico, M., Pusiol, E., Pitoia, F., Neipomniszcze, H., 2008 Metformin treatment of benign thyroid nodules in euthytoid patients with insulin resistance (2008) Diabetes Vasc Dis Reas, 5, p. 223Papini, E., Guglielmi, R., Bizzarri, G., Graziano, F., Bianchini, A., Brufani, C., Pacella, S., Pacella, C.M., Treatment of benign cold thyroid nodules: A randomized clinical trial of percutaneous lases ablation versus levothyroxine therapy or follow-up (2007) Thyroid, pp. 229-235Spiezia, S., Garberoglio, R., Milone, F., Ramundo, V., Caiazzo, C., Assanti, A.P., Thyroid nodules and related symptoms are stably controlled two years after radiofrequency thermal ablation (2009) Thyroid, 19 (3), pp. 219-225Alexander, E.K., Hurwitz, S., Heering, J.P., Benson, C.B., Frates, M.C., Doubilet, P.M., Natural history of benign solid and cystic thyroid nodules (2003) Ann Intern Med, 138 (4), pp. 315-318Carmeci, C., Jeffrey, R.B., McDougall, I.R., Nowels, K.W., Weigel, R.J., Ultrasound-guided fine-needle aspiration biopsy of thyroid masses (1998) Thyroid, 8 (4), pp. 283-289Ylagan, L.R., Farkas, T., Dehner, L.P., Fine needle aspiration of the thyroid: A cytohistologic correlation and study of discrepant cases (2004) Thyroid, 14 (1), pp. 35-41Hung, W., Anderson, K.D., Chandra, R.S., Kapur, S.P., Patterson, K., Randolph, J.G., Solitary thyroid nodules in 71 children and adolescents (1992) J Pediatr Surg, 27 (11), pp. 1407-1409Yip, F.W., Reeve, T.S., Poole, A.G., Delbridge, L., Thyroid nodules in childhood and adolescence (1994) Aust N Z J Surg, 64 (10), pp. 676-678Hegedus, L., Clinical practice. The thyroid nodule (2004) N Engl J Med, 351 (17), pp. 1764-1771Niedziela, M., Pathogenesis, diagnosis and management of thyroid nodules in children (2006) Endocr Relat Cancer, 13 (2), pp. 427-453Degnan, B.M., McClellan, D.R., Francis, G.L., An analysis of fine-needle aspiration biopsy of the thyroid in children and adolescents (1996) J Pediatr Surg, 31 (7), pp. 903-907Lugo-Vicente, H., Ortiz, V.N., Irizarry, H., Camps, J.I., Pagan, V., Pediatric thyroid nodules: Management in the era of fine needle aspiration (1998) J Pediatr Surg, 33 (8), pp. 1302-1305Corrias, A., Einaudi, S., Chiorboli, E., Weber, G., Crino, A., Andreo, M., Accuracy of fine needle aspiration biopsy of thyroid nodules in detecting malignancy in childhood: Comparison with conventional clinical, laboratory, and imaging approaches (2001) J Clin Endocrinol Metab, 86 (10), pp. 4644-4648Amrikachi, M., Ponder, T.B., Wheeler, T.M., Smith, D., Ramzy, I., Thyroid fine-needle aspiration biopsy in children and adolescents: Experience with 218 aspirates (2005) Diagn Cytopathol, 32 (4), pp. 189-192Gharib, H., Papini, E., Valcavi, R., Baskin, H.J., Crescenzi, A., Dottorini, M.E., Duick, D.S., Zini, M., AACE/AME Task Force on Thyroid Nodules. American Association of Clinical Endocrinologists and Associazione Medici Endocrinologi medical guidelines for clinical practice for the diagnosis and management of thyroid nodules (2006) Endocr Pract, 12 (1), pp. 63-102Wiersinga, W.M., Management of thyroid nodules in children and adolescents (2007) Hormones (athens), 6 (3), pp. 194-199Moosa, M., Mazzaferri, E.L., Outcome of differentiated thyroid cancer diagnosed in pregnant women (1997) J Clin Endocrinol Metab, 82 (9), pp. 2862-286

65 YEARS OF THE DOUBLE HELIX Genetics informs precision practice in the diagnosis and management of pheochromocytoma

Although the authors of the present review have contributed to genetic discoveries in the field of pheochromocytoma research, we can legitimately ask whether these advances have led to improvements in the diagnosis and management of patients with pheochromocytoma. The answer to this question is an emphatic Yes! In the field of molecular genetics, the well-established axiom that familial (genetic) pheochromocytoma represents 10% of all cases has been overturned, with >35% of cases now attributable to germline disease-causing mutations. Furthermore, genetic pheochromocytoma can now be grouped into five different clinical presentation types in the context of the ten known susceptibility genes for pheochromocytoma-associated syndromes. We now have the tools to diagnose patients with genetic pheochromocytoma, identify germline mutation carriers and to offer gene-informed medical management including enhanced surveillance and prevention. Clinically, we now treat an entire family of tumors of the paraganglia, with the exact phenotype varying by specific gene. In terms of detection and classification, simultaneous advances in biochemical detection and imaging localization have taken place, and the histopathology of the paraganglioma tumor family has been revised by immunohistochemical-genetic classification by gene-specific antibody immunohistochemistry. Treatment options have also been substantially enriched by the application of minimally invasive and adrenal-sparing surgery. Finally and most importantly, it is now widely recognized that patients with genetic pheochromocytoma/paraganglioma syndromes should be treated in specialized centers dedicated to the diagnosis, treatment and surveillance of this rare neoplasm.Peer reviewe

Primary hyperparathyroidism as first manifestation in multiple endocrine neoplasia type 2A: an international multicenter study.

Multiple endocrine neoplasia type 2A (MEN 2A) is a rare syndrome caused by RET germline mutations and has been associated with primary hyperparathyroidism (PHPT) in up to 30% of cases. Recommendations on RET screening in patients with apparently sporadic PHPT are unclear. We aimed to estimate the prevalence of cases presenting with PHPT as first manifestation among MEN 2A index cases and to characterize the former cases. An international retrospective multicenter study of 1085 MEN 2A index cases. Experts from MEN 2 centers all over the world were invited to participate. A total of 19 centers in 17 different countries provided registry data of index cases followed from 1974 to 2017. Ten cases presented with PHPT as their first manifestation of MEN 2A, yielding a prevalence of 0.9% (95% CI: 0.4-1.6). 9/10 cases were diagnosed with medullary thyroid carcinoma (MTC) in relation to parathyroid surgery and 1/10 was diagnosed 15 years after parathyroid surgery. 7/9 cases with full TNM data were node-positive at MTC diagnosis. Our data suggest that the prevalence of MEN 2A index cases that present with PHPT as their first manifestation is very low. The majority of index cases presenting with PHPT as first manifestation have synchronous MTC and are often node-positive. Thus, our observations suggest that not performing RET mutation analysis in patients with apparently sporadic PHPT would result in an extremely low false-negative rate, if no other MEN 2A component, specifically MTC, are found during work-up or resection of PHPT.S D received a national grant (AZV 16-32665A).S