SERGIO PEREIRA DE ALMEIDA TOLEDO
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Departamento de Clínica Médica, Faculdade de Medicina - Docente
LIM/25 - Laboratório de Endocrinologia Celular e Molecular, Hospital das Clínicas, Faculdade de Medicina
LIM/25 - Laboratório de Endocrinologia Celular e Molecular, Hospital das Clínicas, Faculdade de Medicina
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- Risk Profiles and Penetrance Estimations in Multiple Endocrine Neoplasia Type 2A Caused by Germline RET Mutations Located in Exon 10(2011) FRANK-RAUE, Karin; RYBICKI, Lisa A.; ERLIC, Zoran; SCHWEIZER, Heiko; WINTER, Aurelia; MILOS, Ioana; TOLEDO, Sergio P. A.; TOLEDO, Rodrigo A.; TAVARES, Marcos R.; ALEVIZAKI, Maria; MIAN, Caterina; SIGGELKOW, Heide; HUEFNER, Michael; WOHLLK, Nelson; OPOCHER, Giuseppe; DVORAKOVA, Sarka; BENDLOVA, Bela; CZETWERTYNSKA, Malgorzata; SKASKO, Elzbieta; BARONTINI, Marta; SANSO, Gabriela; VORLAENDER, Christian; MAIA, Ana Luiza; PATOCS, Attila; LINKS, Thera P.; GROOT, Jan Willem de; KERSTENS, Michiel N.; VALK, Gerlof D.; MIEHLE, Konstanze; MUSHOLT, Thomas J.; BIARNES, Josefina; DAMJANOVIC, Svetozar; MURESAN, Mihaela; WUESTER, Christian; FASSNACHT, Martin; PECZKOWSKA, Mariola; FAUTH, Christine; GOLCHER, Henriette; WALTER, Martin A.; PICHL, Josef; RAUE, Friedhelm; ENG, Charis; NEUMANN, Hartmut P. H.Multiple endocrine neoplasia type 2 is characterized by germline mutations in RET. For exon 10, comprehensive molecular and corresponding phenotypic data are scarce. The International RET Exon 10 Consortium, comprising 27 centers from 15 countries, analyzed patients with RET exon 10 mutations for clinical-risk profiles. Presentation, age-dependent penetrance, and stage at presentation of medullary thyroid carcinoma (MTC), pheochromocytoma, and hyperparathyroidism were studied. A total of 340 subjects from 103 families, age 4-86, were registered. There were 21 distinct single nucleotide germline mutations located in codons 609 (45 subjects), 611 (50), 618 (94), and 620 (151). MTC was present in 263 registrants, pheochromocytoma in 54, and hyperparathyroidism in 8 subjects. Of the patients with MTC, 53% were detected when asymptomatic, and among those with pheochromocytoma, 54%. Penetrance for MTC was 4% by age 10, 25% by 25, and 80% by 50. Codon-associated penetrance by age 50 ranged from 60% (codon 611) to 86% (620). More advanced stage and increasing risk of metastases correlated with mutation in codon position (609-620) near the juxtamembrane domain. Our data provide rigorous bases for timing of premorbid diagnosis and personalized treatment/prophylactic procedure decisions depending on specific RET exon 10 codons affected. Hum Mutat 32:51-58, 2011. (C) 2010 Wiley-Liss, Inc.
- Lymph node distribution in the central compartment of the neck: An anatomic study(2014) TAVARES, Marcos Roberto; CRUZ, Jose Arnaldo Shiomi da; WAISBERG, Daniel Reis; TOLEDO, Sergio Pereira de Almeida; TAKEDA, Flavio Roberto; CERNEA, Claudio Roberto; CAPELOZZI, Vera Luiza; BRANDAO, Lenine GarciaBackground. Dissection of the central compartment of the neck (CCN) is performed for proven or suspected lymph node metastases of thyroid carcinoma. During this procedure, the recurrent laryngeal nerves and the parathyroid glands are at risk. The purpose of this study was to determine the anatomic distribution of the lymph nodes in the CCN. Methods. The anatomic distribution of the lymph nodes in the CCN was studied by dissection of 30 fresh cadavers. The soft tissue between the cricoid cartilage and the innominate vein, carotid arteries, and prevertebral fascia was removed and divided according to CCN sublevels. Nodules were identified by palpation in the specimen and sent for pathological examination. Results. Three to 44 (18.5 +/- 10.29) nodules were identified macroscopically. Two to 42 nodules were confirmed as lymph nodes after microscopic examination. The lymph node distribution was as follows: precricoid: 0 to 2 (0.9 +/- 0.72); pretracheal: 1 of 35 (12.4 +/- 8.19); lateral to the right recurrent laryngeal nerve (RLN): 0 to 11 (3.4 +/- 2.34); and lateral to the left: 0 to 4 (1.7 +/- 1.30). Twenty-six parathyroid glands were removed by 14 dissections. The innominate vein was found at 15 mm above the superior border of the clavicles to 35 mm below on the left side of the neck and 5 to 45 mm on the right side. Conclusion. The number of confirmed lymph nodes in the central neck varied from 2 to 42. Sixty-seven percent of the lymph nodes were in the pretracheal sublevel. There was no division between level VI and VII lymph nodes. Additionally, the innominate vein was found to be from 15 mm above the superior border of the clavicles to 35 mm below on the left side of the neck and 5 to 45 mm on the right side. Parathyroid glands were identified to be far away from the thyroid gland. (C) 2014 Wiley Periodicals, Inc.
- Surgical approach to medullary thyroid carcinoma associated with multiple endocrine neoplasia type 2(2012) TAVARES, Marcos R.; TOLEDO, Sergio P. A.; MONTENEGRO, Fabio L. M.; MOYSES, Raquel A.; TOLEDO, Rodrigo A.; SEKYIA, Tomoko; CERNEA, Claudio R.; BRANDAO, Lenine G.We briefly review the surgical approaches to medullary thyroid carcinoma associated with multiple endocrine neoplasia type 2 (medullary thyroid carcinoma/multiple endocrine neoplasia type 2). The recommended surgical approaches are usually based on the age of the affected carrier/patient, tumor staging and the specific rearranged during transfection codon mutation. We have focused mainly on young children with no apparent disease who are carrying a germline rearranged during transfection mutation. Successful management of medullary thyroid carcinoma in these cases depends on early diagnosis and treatment. Total thyroidectomy should be performed before 6 months of age in infants carrying the rearranged during transfection 918 codon mutation, by the age of 3 years in rearranged during transfection 634 mutation carriers, at 5 years of age in carriers with level 3 risk rearranged during transfection mutations, and by the age of 10 years in level 4 risk rearranged during transfection mutations. Patients with thyroid tumor >5 mm detected by ultrasound, and basal calcitonin levels >40 pg/ml, frequently have cervical and upper mediastinal lymph node metastasis. In the latter patients, total thyroidectomy should be complemented by extensive lymph node dissection. Also, we briefly review our data from a large familial medullary thyroid carcinoma genealogy harboring a germline rearranged during transfection Cys620Arg mutation. All 14 screened carriers of the rearranged during transfection Cys620Arg mutation who underwent total thyroidectomy before the age of 12 years presented persistently undetectable serum levels of calcitonin (<2 pg/ml) during the follow-up period of 2-6 years. Although it is recommended that preventive total thyroidectomy in rearranged during transfection codon 620 mutation carriers is performed before the age of 5 years, in this particular family the surgical intervention performed before the age of 12 years led to an apparent biochemical cure.
- Total parathyroidectomy in a large cohort of cases with hyperparathyroidism associated with multiple endocrine neoplasia type 1: experience from a single academic center(2012) MONTENEGRO, Fabio Luiz de Menezes; LOURENCO JUNIOR, Delmar Muniz; TAVARES, Marcos Roberto; ARAP, Sergio Samir; NASCIMENTO JUNIOR, Climerio Pereira; MASSONI NETO, Ledo Mazzei; D'ALESSANDRO, Andre; TOLEDO, Rodrigo Almeida; COUTINHO, Flavia Lima; BRANDAO, Lenine Garcia; SILVA FILHO, Gilberto de Britto e; CORDEIRO, Anoi Castro; TOLEDO, Sergio Pereira AlmeidaMost cases of sporadic primary hyperparathyroidism present disturbances in a single parathyroid gland and the surgery of choice is adenomectomy. Conversely, hyperparathyroidism associated with multiple endocrine neoplasia type 1 (hyperparathyroidism/multiple endocrine neoplasia type 1) is an asynchronic, asymmetrical multiglandular disease and it is surgically approached by either subtotal parathyroidectomy or total parathyroidectomy followed by parathyroid auto-implant to the forearm. In skilful hands, the efficacy of both approaches is similar and both should be complemented by prophylactic thymectomy. In a single academic center, 83 cases of hyperparathyroidism/multiple endocrine neoplasia type 1 were operated on from 1987 to 2010 and our first surgical choice was total parathyroidectomy followed by parathyroid auto-implant to the non-dominant forearm and, since 1997, associated transcervical thymectomy to prevent thymic carcinoid. Overall, 40% of patients were given calcium replacement (mean intake 1.6 g/day) during the first months after surgery, and this fell to 28% in patients with longer follow-up. These findings indicate that several months may be needed in order to achieve a proper secretion by the parathyroid auto-implant. Hyperparathyroidism recurrence was observed in up to 15% of cases several years after the initial surgery. Thus, long-term follow-up is recommended for such cases. We conclude that, despite a tendency to subtotal parathyroidectomy worldwide, total parathyroidectomy followed by parathyroid auto-implant is a valid surgical option to treat hyperparathyroidism/multiple endocrine neoplasia type 1. Larger comparative systematic studies are needed to define the best surgical approach to hyperparathyroidism/multiple endocrine neoplasia type 1.