Incidence of malignant lesions in patients with clinically benign thyroid nodules: observational and prospective study in a cohort of 50 patients followed during two years

INTRODUCTION: To study the frequency of malignant lesions in patients with clinically benign thyroid nodules and the value of the repetition of fine needle aspiration biopsy (FNAB). METHODS: Observational and prospective 2-year study in a cohort of 50 patients with clinically benign thyroid nodules. Patients were initially submitted to clinical examination, ultrasound (US) and FNAB1 patients, followed by a second FNAB and US. RESULTS: Palpation is not a good test for diagnosis and follow-up of thyroid nodules. On the other hand, the initial consideration that these patients should harbor benign lesions is a very useful parameter, since 47/50 patients (94%) did not present malignant lesions during the follow-up. FNAB1 and FNAB2 were concordant in 33/39 patients when FNAB1 was negative (85%); 11 patients were operated, 8 by suspicious FNAB and 3 due to nodule growth. We observed 2 patients with non-invasive papillary microcarcinoma and 1 patient with papillary carcinoma outside of the main nodules. CONCLUSION: there was concordance between initial clinical benign diagnosis, FNAB and the follow-up. In one case there was a papillary carcinoma. In addition, ultrasonography should be considered for all patients with suspected thyroid nodules. Finally, we demonstrated that a second cytology usually confirms the result of the first cytology in benign thyroid nodules.OBJETIVOS: Verificar a ocorrência de lesões malignas em pacientes com nódulos tiroidianos clinicamente benignos e o valor da repetição da citologia aspirativa da tiróide (PAAF). MÉTODOS: Estudo observacional prospectivo por 2 anos em coorte de 50 mulheres com nódulos tiroidianos clinicamente benignos, com exame clínico, ultra-sonografia (US) e PAAF inicial, seguidas por acompanhamento clínico, US e repunção dos mesmos nódulos (PAAF2). RESULTADOS: A palpação não é bom método para o seguimento dos nódulos quando comparada ao US. O quadro clínico foi parâmetro de confiança, pois 47/50 pacientes (94%) evoluíram sem malignidade durante o seguimento. PAAF1 e PAAF2 concordaram em 33/39 pacientes quando PAAF1 foi negativa (85%); 11 pacientes foram operadas, 8 por PAAF suspeita e 3 por aumento do volume nodular durante o seguimento. O anátomo-patológico (AP) foi benigno nas lesões suspeitas (8 adenomas e 3 bócios colóides). Houve 2 casos de microcarcinoma papilífero não invasivo em área distante dos nódulos e 1 caso de carcinoma papilífero não invasivo em bócio multi-nodular. CONCLUSÕES: Houve concordância entre características clínicas de benignidade com PAAF, US e acompanhamento clínico ou cirurgia; numa paciente encontramos carcinoma papilífero. O US deve ser considerado em pacientes com suspeita de nódulos de tiróide ao exame clínico; na maioria das vezes quando o resultado da PAAF1 é negativo para malignidade, o segundo exame citológico confirma o primeiro.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de MedicinaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de Otorrinolaringologia e Cirurgia de Cabeça e PescoçoUNIFESP, EPM, Depto. de MedicinaUNIFESP, EPM, Depto. de Otorrinolaringologia e Cirurgia de Cabeça e PescoçoSciEL

Evaluation of clinical, laboratorial and ultrasonographic predicting factors of malignancy in thyroid nodules

OBJECTIVE: To evaluate the risk of malignancy in thyroid nodules through clinical, laboratory, ultrasonographic and cytological aspects. PATIENTS AND METHODS: 741 nodules of 407 patients. RESULTS: The cytology was benign (60,5%), indeterminate (23,3%), malignant (8,3%) or nondiagnostic (7,6%). The prevalence of cancer in indeterminate citology was 18,5% (16% in follicular lesions, 44% in suspicious). The diagnosis of malignancy was 17,2% (n = 70). The frequency of cancer in women (15,2%) was lower than in men (27,9%). There was an inverse relation between age and cancer risk. There was no statistical significance in the prevalence of cancer according to number, size of nodules or TSH levels. Hypoechogenicity and microcalcifications on ultrasound were risk factors. CONCLUSION: The risk of malignancy was higher in men, hypoechoic nodules, with microcalcifications and was inversely related to age. The TSH level was not an independent factor predictive of malignancy.OBJETIVO: Avaliar risco de malignidade de nódulos tiroidianos por meio de aspectos clínicos, laboratoriais, ultrassonográficos e citológicos. PACIENTES E MÉTODOS: 741 nódulos de 407 pacientes. RESULTADOS: A citologia foi benigna (60,5%), indeterminada (23,3%), maligna (8,6%) ou não diagnóstica (7,6%). A prevalência de câncer nas citologias indeterminadas foi 18,5% (16% nas lesões foliculares, 44% nas suspeitas). O diagnóstico de malignidade foi 17,2% (n = 70). A frequência de câncer em mulheres (15,2%) foi menor do que em homens (27,9%). Houve uma relação inversa entre idade e risco de câncer. Não houve significância estatística na prevalência de câncer de acordo com número, tamanho dos nódulos ou níveis de TSH. Hipoecogenicidade e microcalcificações ao ultrassom foram fatores de risco. CONCLUSÃO: O risco de malignidade foi maior em homens, nódulos hipoecogênicos, com microcalcificações e inversamente relacionado à idade. O nível de TSH não foi um preditor independente de malignidade.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de MedicinaInstituto Israelita de Ensino e Pesquisa Albert Einstein Centro de Doenças TiroidianasFleury Medicina e SaúdeUNIFESP, EPM, Depto. de MedicinaSciEL

Development of a Sensitive and Specific Quantitative Reverse Transcription-Polymerase Chain Reaction Assay for Blood Thyroglobulin Messenger Ribonucleic Acid in the Follow-Up of Patients with Differentiated Thyroid Carcinoma

Context: Serum thyroglobulin is a sensitive tumor marker in the follow-up of patients with differentiated thyroid carcinoma (DTC), but the presence of endogenous anti-thyroglobulin antibodies (TgAb) can interfere on its measurement. To prevent interference by TgAb, several investigators have tried to quantify blood mRNA Tg by real-time RT-PCR, but the results have been variable, not reporting a correlation between mRNA Tg and the presence of metastases.Objective: the aim of the study was to evaluate the development of a sensitive and specific quantitative RT-PCR assay for blood mRNA Tg in the follow-up of patients with DTC.Design and Patients: An assay employing primers located in a region not affected by alternative splicing or single nucleotide polymorphisms was developed to study 104 DTC patients (13 of 104 with positive TgAb).Results: the assay is specific for thyroid tissue because we found mRNA Tg expression in normal thyroid tissue, but we did not find any mRNA Tg expression in any extrathyroidal tissues. Quantitative mRNA Tg levels were significantly different between patients free of disease (82 of 104) and those with metastases (22 of 104) (2.61 +/- 0.26 vs. 27.58 +/- 1.62 pg mRNA Tg/mu g RNA) (P < 0.0001). A cutoff point of 5.51 was able to discriminate between the two groups. in addition, the measurement of mRNA Tg was not affected by the presence of TgAb.Conclusion: This new mRNA Tg quantification is a reliable method that allowed us to differentiate patients free of disease from those with metastases, and it could represent an appropriate molecular marker for the follow-up of patients with DTC, especially those with positive TgAb. (J Clin Endocrinol Metab 95: 1726-1733, 2010)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Research-Fellowship GrantUniversidade Federal de São Paulo, Dept Med, Escola Paulista Med, Div Endocrinol,Lab Mol Endocrinol, BR-04039032 São Paulo, BrazilInst Israelita Ensino & Pesquisa Albert Einstein, Thyroid Dis Ctr, BR-05652000 São Paulo, BrazilFleury Med & Hlth, BR-01243001 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Med, Escola Paulista Med, Div Endocrinol,Lab Mol Endocrinol, BR-04039032 São Paulo, BrazilFAPESP: 04/09934-7Research-Fellowship Grant: 05/55842-0Web of Scienc