Prevalence of DICER1 variants in large multinodular goiter: thyroid function, clinical and imaging characteristics

ABSTRACT Objective: Mutations in DICER1 are found in differentiated thyroid carcinoma (DTC) and in multinodular goiter (MNG) at a younger age with other tumors, which characterizes DICER1 syndrome. DICER1 is one driver to DTC; however, it is also found in benign nodules. We speculated that patients with mutations in DICER1 may present long-lasting MNG. Our aim was to investigate the frequency of DICER1 variants in patients with MNG. Subjects and methods: Patients who submitted to total thyroidectomy due to large MNG with symptoms were evaluated. DICER1 hotspots were sequenced from thyroid nodule samples. To confirm somatic mutation, DNA from peripheral blood was also analyzed. Results: Among 715 patients, 154 were evaluated with 56.2 ± 12.3 years old (28-79) and the thyroid volume was 115.7 ± 108 mL (16.2-730). We found 11% with six DICER1 variations in a homo or heterozygous state. Only rs12018992 was a somatic DICER1 variant. All remaining variants were synonymous and likely benign, according to the ClinVar database. The rs12018992 was previously described in an adolescent with DTC, measuring 13 mm. There were no significant differences according to gender, familial history of goiter, age, thyroid volume, TSH and TI-RADS classification between DICER1 carriers. Free T4 were lower in patients with DICER1 polymorphisms (13.77 ± 1.8 vs. 15.44 ± 2.4 pmol/L, p = 0.008), regardless of TSH levels. Conclusions: We conclude that germline DICER1 variants can be found in 11% of large goiters but no second-hit somatic mutation was found. DICER1 is one driver to thyroid lesion and a second-hit event seems unnecessary in the MNG development.

Diagnostic performance of thyroid ultrasound in Hürthle cell carcinomas

ABSTRACT Objective Hürthle cell carcinomas (HCCs) of the thyroid have been recently reclassified as a separate entity due to their distinct clinical and molecular profiles. Few studies have assessed the ability of preoperative characteristics in differentiating HCCs from Hürthle cell adenomas (HCAs) due to the low prevalence of both lesions. This study aimed to compare the preoperative features of HCCs and HCAs and evaluate the diagnostic performance of ultrasound in distinguishing between both. Subjetcs and methods Retrospective study including 101 patients (52 HCCs and 49 HCAs) who underwent thyroid surgery from 2000 to 2016. Clinical, ultrasonographic, and histological data were reviewed. Diagnostic performance of suspicious sonographic features was analyzed in 51 cases (24 HCCs and 27 HCAs). Results Hürthle cell neoplasms were predominant in females. Subjects ≥ 55 years represented 58% of the cases of HCCs and 53% of those of HCAs. Carcinomas were significantly larger (p < 0.001), and a tumor size ≥ 4 cm significantly increased the risk of malignancy (odds ratio 3.67). Other clinical, cytologic, and sonographic data were similar between HCCs and HCAs. Among the HCCs, the lesions were purely solid in 54.2%, hypoechoic in 37.5%, and had coarse calcifications in 12.5%, microcalcifications in 8.3%, irregular contours in 4.2%, and a taller-than-wide shape in 16.7%. Predominantly/exclusive intranodular vascularization was observed in 52.6%. Overall, 58% of the HCCs were classified as TI-RADS 4 or 5 compared with 48% of the HCAs. TI-RADS 4 or 5 had a specificity of only 51.8% and a positive likelihood ratio of 1.21. Conclusions Apart from the lesion size, no other preoperative feature adequately distinguished HCCs from HCAs. Sonographic characteristics raising suspicion for malignancy, which are mostly present in papillary carcinomas, were infrequent in HCCs. New tools must be developed to improve preoperative diagnosis and deferral of surgery in cases of adenomas.

Thyroidectomy in children

Introduction: Surgical management of thyroid disease in children presents several peculiarities and has increasingly developed in recent years, but historically few studies conducted with this population have been published. Objective: Analysis of the surgical approach and postoperative outcomes of 59 pediatric patients submitted to thyroidectomy between 2003 and 2019. Methods: An outpatient postoperative follow-up of 59 patients aged 3-18 years submitted to thyroidectomy for different causes was performed, and immediate and late postoperative outcomes were analyzed. The operations were performed at a University Hospital as well as at Private Tertiary Hospitals. Results: The following postoperative outcomes were observed: three tracheostomies, 22 patients with transient hypoparathyroidism, eight patients with definitive hypoparathyroidism, and three patients with vocal fold paralysis. Conclusion: Thyroidectomy in children is a procedure with a higher complication rate and needs to be performed by a team of high-volume surgeons. This study focuses on the adverse events, so that those interested in the subject are aware of them.

Diagnosis and treatment of hypoparathyroidism: a position statement from the Brazilian Society of Endocrinology and Metabolism

ABSTRACT Objective To present an update on the diagnosis and treatment of hypoparathyroidism based on the most recent scientific evidence. Materials and methods The Department of Bone and Mineral Metabolism of the Sociedade Brasileira de Endocrinologia e Metabologia (SBEM; Brazilian Society of Endocrinology and Metabolism) was invited to prepare a document following the rules set by the Guidelines Program of the Associação Médica Brasileira (AMB; Brazilian Medical Association). Relevant papers were retrieved from the databases MEDLINE/PubMed, LILACS, and SciELO, and the evidence derived from each article was classified into recommendation levels according to scientific strength and study type. Conclusion An update on the recent scientific literature addressing hypoparathyroidism is presented to serve as a basis for the diagnosis and treatment of this condition in Brazil.

Categorias citopatológicas III, IV e V de bethesda: correlação entre achados histopatológicos e epidemiológicos / Bethesda cytopathological categories III, IV and, V: correlation between histopathological and epidemiologic findings

Introdução: A padronização do Sistema de Bethesda declassificação citopatológica surgiu para facilitar a análise dosnódulos tireoidianos a avaliar seu risco de malignidade. Objetivo:O objetivo do estudo é analisar 92 pacientes submetidos àressecção parcial ou total de tireoide entre outubro/2010 ejunho/2013 em projeto de tratamento de doenças da tireoideem parceria entre a UNIFESP/EPM e o Hospital Albert Einsteinque foram classificados nas categorias III (19), IV (46) e V(27)de Bethesda. Dentre eles havia 84 mulheres e 8 homens, comidade média de 47 anos (23 - 73), 41 apresentando nódulo únicoe 51, mais de um nódulo. Resultados: A análise histopatológicaevidenciou carcinoma em 44 pacientes de modo que a incidêncianas categorias Bethesda III, IV e V foi 36%; 45,6% e 74%,respectivamente. Conclusão: Conclui-se que a opção deobservar nódulos Bethesda III é válida, mas de maneira criteriosa.

Parathyroid hormone: an early predictor of symptomatic hypocalcemia after total thyroidectomy / Hormônio da paratireoide: um preditor precoce da hipocalcemia sintomática após a tireoidectomia total

OBJECTIVE: The purpose of this study was to evaluate if the measurement of peri-operative parathyroid hormone (PTH) is able to identify patients with increased risk of developing symptoms of hypocalcemia. SUBJECTS AND METHODS: Forty patients who underwent total thyroidectomy were studied prospectively. Ionized serum calcium and PTH were measured after induction of anesthesia, one hour (PTH1) and one day after surgery (PTH24). Patients were evaluated for symptoms of hypocalcemia and treated with calcium and vitamin D supplementation as necessary. RESULTS: Symptomatic hypocalcemia developed in 16 patients. Symptomatic patients had significant lower PTH1 and greater drops in PTH levels. The selection of 12.1 ng/L as PTH1 level cutoff level divided patients with and without symptoms with 93.7% sensitivity and 91.6% specificity. The selection of 73.5% as the cutoff value for PTH decrease resulted in 91.6% sensitivity and 87.5% specificity. CONCLUSION: PTH1 levels and the drop in PTH levels are reliable predictors of developing symptomatic hypocalcemia after total thyroidectomy.

OBJETIVO: O objetivo deste estudo é avaliar se a medida perioperatória do hormônio da paratireoide (PTH) pode identificar os pacientes com maior risco de desenvolver sintomas de hipocalcemia. SUJEITOS E MÉTODOS: Foram estudados quarenta pacientes submetidos à tireodiectomia total. A medida do cálcio sérico e do PTH foi feita após a indução anestésica, uma hora (PTH1) e um dia após a cirurgia. Os pacientes foram avaliados quanto à presença de sintomas de hipocalcemia e tratados com suplementação de cálcio e vitamina D quando necessário. RESULTADOS: Dezesseis pacientes apresentaram sintomas de hipocalcemia. Os pacientes sintomáticos apresentaram PTH1 significantemente menor e queda no PTH significativamente maior. Usando o valor de 12,1 ng/L como corte, conseguimos distinguir pacientes com e sem sintomas de hipocalcemia com sensibilidade de 93,7% e especificidade de 91,6%. Utilizando como corte a queda de 73,5% no valor do PTH, temos sensibilidade de 91,6% e especificidade de 87,5%. CONCLUSÃO: O PTH1 e a queda no PTH são bons preditores de hipocalcemia no pós-operatório de tireoidectomia total.

"Cruzeiro do Sul": Técnica simplificada para autotransplante de paratireoide / "Southern Cross": A simplified technique for parathyroid autotransplantation

Introdução: A paratireoidectomia total com autotransplante imediato é utilizada no tratamento do hiperparatireoidismo renal. A descrição inicial do autotransplante de paratireoide utilizou vinte lojas com um fragmento em cada loja. Objetivo: O presente estudo analisa aspectos técnicos e funcionais de um método simplificado de autotransplante. Método: Análise retrospectiva do tempo empregado para realizar o implante de paratireoide pela técnica tradicional (grupo A, 18 to 20 lojas) e pela simplificada (grupo B, 5 lojas). A função do tecido autotransplantado foi avaliada de acordo com os níveis sistêmicos do paratormônio (PTH). A função do implante foi classificada em quatro grupos, de acordo com os níveis de PTH, como a seguir: estado funcional 1 (EF1), PTH abaixo da faixa normal para o método; estado funcional 2 (EF2), PTH dentro dos limites da normalidade; estado funcional 3 (EF3), PTH elevado não mais que três vezes o limite superior da normalidade e estado funcional 4 (EF4), PTH elevado acima de três vezes o limite superior da normalidade. Resultados: No grupo A, o tempo empregado para realizar o auto-implante variou de 30 a 60 minutos (média 44,0) e no grupo B, o tempo variou de 10 a 30 minutos (média 18,6) (p< 0,0001). A mediana do nível sistêmico do PTH foi de 43,1 pg/mL no grupo A e 39pg/mL no grupo B. A distribuição dos estados funcionais no grupo A e B foram, respectivamente: EF1 17% e14,6%; EF2 50% e 58,5%; EF3 23% e 22%; EF4 10% e 4,9%. (p=0,8). Conclusões: A redução do número de lojas criadas para autotransplante de paratireoide para cinco lojas não afetou o estado funcional e reduziu o tempo empregado para o implante.

Introduction: Total parathyroidectomy with immediate autotransplantation is employed in the management of renal hyperparathyroidism. The initial description of parathyroid autotransplantation employed twenty pockets with one fragment of parathyroid in each pocket. Objective: The present study analyzes technical and functional aspects of a simplified method of autotransplantation. Methods: Retrospective analysis of time spent to perform a traditional (Group A, 18 to 20 pockets) parathyroid autotransplantation and a simplified (Group B, 5 pockets) technique. The function of the transplanted tissue was evaluated according to systemic levels of parathyroid hormone (PTH). Graft function was classified into four groups according to PTH levels, as follows: Implant Functional Status 1(FS1): PTH below the normal range; FS2: PTH within the normal range; FS3:PTH elevated to no more than three times the upper limit, and FS4: PTH levels more than three times the upper limit. Results: In Group A, the time spent to perform the autograft varied from 30 to 60 minutes (mean 44.0) and in Group B it varied from 10 to 30 min (mean 18.6) (p< 0.0001). The median level of postoperative systemic PTH was 43.1 pg/mL in group A and 39 pg/mL in group B. Functional status distribution in Group A and B were, respectively: FS1 17% and 14.6%; FS2 50% and 58.5%; FS3 23% and 22%; FS4 10% and 4.9%. (p=0.8). Conclusions: The reduction of the number of pockets created for parathyroid autotransplantation to five pockets did not affect parathyroid transplant functional status and reduced the time spent for implantation.

Tres anos de atividades da liga de prevencao e controle do cancer da cavidade oral / Three years of activities of the league for prevention and control of oral cavity cancer

A Liga de Prevencao e Controle do Cancer da Cavidade Oral foi criada em 1995 na Faculdade de Medicina da Universidade de Sao Paulo com objetivo de divulgar informacoes sobre cancer de boca, incentivar o exame da cavidade oral entre os profissionais da saude e promover o diagnostico em fases mais precoces dos tumores da regiao. E formada por academicos do terceiro ao sexto anos da FMUSP e por professores e medicos da Disciplina de Cirurgia de Cabeca e Pescoco da FMUSP. Nesses tres anos de atividade foram atendidos 160 individuos (675 consultas) portadores de cancer de boca e outras afeccoes benignas e malignas da regiao cervicofacial. As atividades de 1998 da Liga se concentraram no desenvolvimento de programas de incentivo ao diagnostico precoce dos tumores da cavidade oral

Importancia do exame da cavidade oral no diagnostico precoce dos tumores de boca / Importance of the oral cavity examination in precocious diagnosis of the mouth tumors

O cancer da cavidade oral representa serio problema de saude no Brasil, estando entre os dez canceres mais frequentes na populacao. Do ponto de vista histologico, cerca de 90 por cento dos tumores da cavidade oral sao carcinomas epidermoides. Sua genese esta associada a fatores de risco conhecidos e preveniveis, como o fumo e o alcool, que, quando associados, podem aumentar o risco de desenvolvimento tumoral em ate 141,6 vezes. Apesar da deteccao precoce dos tumores de boca ser possivel com o exame cuidadoso e rotineiro da cavidade oral, uma vez que mais de 3/4 dos canceres orais estao localizados em regioes de facil visualizacao e palpacao, aproximadamente 90 por cento das neoplasias malignas dessa regiao sao detectadas em estadios avancados...