A pioneering RET genetic screening study in the State of Ceará, Brazil, evaluating patients with medullary thyroid cancer and at-risk relatives: experience with 247 individuals.

OBJECTIVE: Initial diagnosis of medullary thyroid carcinoma (MTC) is frequently associated with advanced stages and a poor prognosis. Thus, the need for earlier diagnoses and detection in relatives at risk for the disease has led to increased use of RET genetic screening. SUBJECTS AND METHODS: We performed RET screening in 247 subjects who were referred to the Brazilian Research Consortium for Multiple Endocrine Neoplasia (BRASMEN) Center in the State of Ceará. Direct genetic sequencing was used to analyze exons 8, 10, 11, and 13-16 in MTC index cases and specific exons in at risk relatives. Afterward, clinical follow-up was offered to all the patients with MTC and their affected relatives. RESULTS: RET screening was performed in 60 MTC index patients and 187 at-risk family members. At the initial clinical assessment of the index patients, 54 (90%) were diagnosed with apparently sporadic disease and 6 (10%) diagnosed with hereditary disease. After RET screening, we found that 31 (52%) index patients had sporadic disease, and 29 (48%) had hereditary disease. Regarding at-risk relatives, 73/187 were mutation carriers. Mutations in RET codon 804 and the rare p.M918V mutation were the most prevalent. CONCLUSIONS: Performing RET screening in Ceará allowed us to identify a different mutation profile in this region compared with other areas. RET screening also enabled the diagnosis of a significant number of hereditary MTC patients who were initially classified as sporadic disease patients and benefited their relatives, who were unaware of the risks and the consequences of bearing a RET mutation.

A pioneering RET genetic screening study in the State of Ceará, Brazil, evaluating patients with medullary thyroid cancer and at-risk relatives: experience with 247 individuals

ABSTRACT Objective: Initial diagnosis of medullary thyroid carcinoma (MTC) is frequently associated with advanced stages and a poor prognosis. Thus, the need for earlier diagnoses and detection in relatives at risk for the disease has led to increased use of RET genetic screening. Subjects and methods: We performed RET screening in 247 subjects who were referred to the Brazilian Research Consortium for Multiple Endocrine Neoplasia (BRASMEN) Center in the State of Ceará. Direct genetic sequencing was used to analyze exons 8, 10, 11, and 13-16 in MTC index cases and specific exons in at risk relatives. Afterward, clinical follow-up was offered to all the patients with MTC and their affected relatives. Results: RET screening was performed in 60 MTC index patients and 187 at-risk family members. At the initial clinical assessment of the index patients, 54 (90%) were diagnosed with apparently sporadic disease and 6 (10%) diagnosed with hereditary disease. After RET screening, we found that 31 (52%) index patients had sporadic disease, and 29 (48%) had hereditary disease. Regarding at-risk relatives, 73/187 were mutation carriers. Mutations in RET codon 804 and the rare p.M918V mutation were the most prevalent. Conclusions: Performing RET screening in Ceará allowed us to identify a different mutation profile in this region compared with other areas. RET screening also enabled the diagnosis of a significant number of hereditary MTC patients who were initially classified as sporadic disease patients and benefited their relatives, who were unaware of the risks and the consequences of bearing a RET mutation.

Nervo laríngeo inferior não-recorrente / Non-recurrent inferior laryngeal nerve

Introdução: A lesão do nervo laríngeo inferior é uma das complicações dos procedimentos cirúrgicos da glândula tireóide. O risco torna-se maior quando o nervo, que normalmente é recorrente, apresenta variação anatômica, constituindo o nervo laríngeo inferior não-recorrente. Essa variação apresenta-se mais comumente à direita (0,2% a 4%) e, de forma mais rara, à esquerda (0,07%) e está associada a alterações anatômicas de artérias subclávias. O diagnóstico pode ser realizado no pré-operatório através de exames de imagem, o que não é rotina nos serviços de cirurgia. Pacientes e método: Relatamos a detecção intra-operatória do nervo laríngeo inferior não recorrente, todos à direita, em cinco pacientes submetidas à tireoidectomia total. O nervo foi identificado e preservado estruturalmente em todas as pacientes, apesar das dificuldades técnicas para sua localização. Resultados: Exames de videolaringoestroboscopia pós-cirúrgicos confirmaram a preservação funcional dos nervos. Conclusão: O cirurgião que realiza procedimentos de cervicotomia (tireoidectomia, em especial) deve estar alerta a respeito da existência dessa rara variação anatômica e da importância da identificação sistemática do nervo laríngeo inferior, de modo a evitar sua lesão acidental.

Introduction: The injury of the inferior laryngeal nerve is a complication of the surgical procedures on the thyroid gland. It occurs with increased frequency when this nerve has an anomalous anatomy and constitutes the non-recurrent inferior laryngeal nerve. This variation, that is associated with anatomic alterations of subclavian arteries, is more frequent at the right side (0.2% to 4%) and occurs less frequently at the left side (0.07%). The diagnosis can be performed preoperatively with image examinations. However, it is not a routine procedure in the surgery services. Patients and methods: We report the intraoperative detection of the non-recurrent inferior laryngeal nerve at the right side in five patients undergoing total thyroidectomy. In despite of the difficulties, the nerve was identified and preserved structurally in all patients. Results: The postoperative direct laringostroboscopy confirmed the functional preservation of the nerves. Conclusion: The surgeons who work with cervicotomy procedures (principally thyroidectomy) must be aware about the existence of this rare anatomic variation and the importance of the systematic identification of the inferior laryngeal nerve in order to avoid its accidental injury.