CONSTRUCTION AND VALIDATION OF A BUNDLE FOR EVALUATION OF THYROID FUNCTION IN PATIENTS WITH CIRRHOSIS.

Thyroid dysfunction has been reported in association with several chronic diseases, including advanced liver disease. •The bundle discussed here is aimed at proposing systematic assistance according to the best evidence-based practices available. •The process of constructing and validating the bundle was carried out in the following stages: a) bibliographic survey; b) bundle elaboration; and c) content validation. •The bundle was considered valid to facilitate medical decision making, aiding physicians to manage, in a practical and effective manner, the thyroid function of patients with liver cirrhosis. Background - Thyroid dysfunction has been reported in association with several chronic diseases, including advanced liver disease. This disease and its management are often neglected in clinical practice. The bundle discussed here is aimed at proposing systematic assistance according to the best evidence-based practices available. Objective - To construct and validate a bundle to evaluate thyroid function in patients with liver cirrhosis. Methods - The process of constructing and validating the bundle was carried out in the following stages: a) bibliographic survey; b) bundle elaboration; and c) content validation. The bibliographic survey was carried out in an integrative review about evidence related with the thyroid function of patients with liver cirrhosis. The findings from the integrative review were considered as supporting evidence for the elaboration of the bundle. The tool then created used accessible language and was evidence-based, ensuring that information was based on current literature. Results - The bundle was restructured to provide guidance on the management of patients with liver dysfunctions, including: cirrhosis due to general causes, cirrhosis due to hepatitis C, non-alcoholic fatty liver disease, primary biliary cholangitis, and hepatocellular carcinoma. The orientations in the bundle included: exams to be requested to screen for thyroid disorders, and guidance about the treatment of these dysfunctions and their associated complications. We analyzed specialist evaluation of the bundle using the Content Validity Index (CVI). We carried out a binomial test to evaluate consistency and specialist agreement regarding the items in the bundle, considering values >0.61 as a good level. The items in the bundle were considered to be valid (CVI >0.80). The general CVI of the instrument was 0.95 (CI95%: 0.91-0.98). Conclusion - The bundle was considered valid to facilitate medical decision making, aiding physicians to manage, in a practical and effective approach, the thyroid function of patients with liver cirrhosis. This tool should not be used as a replacement for individual, evaluation of the physician providing assistance. We recommend the structured bundle to be added to medical practice, considering its simple application, low cost, and potential to contribute for the management of these patients.

Construção e validação de um Bundle para avaliação da função tireoidiana em pacientes com cirrose hepatica / Construction and validation of a bundle for evaluation of thyroid function in patients with cirrhosis

ABSTRACT Background: Thyroid dysfunction has been reported in association with several chronic diseases, including advanced liver disease. This disease and its management are often neglected in clinical practice. The bundle discussed here is aimed at proposing systematic assistance according to the best evidence-based practices available. Objective: To construct and validate a bundle to evaluate thyroid function in patients with liver cirrhosis. Methods: The process of constructing and validating the bundle was carried out in the following stages: a) bibliographic survey; b) bundle elaboration; and c) content validation. The bibliographic survey was carried out in an integrative review about evidence related with the thyroid function of patients with liver cirrhosis. The findings from the integrative review were considered as supporting evidence for the elaboration of the bundle. The tool then created used accessible language and was evidence-based, ensuring that information was based on current literature. Results: The bundle was restructured to provide guidance on the management of patients with liver dysfunctions, including: cirrhosis due to general causes, cirrhosis due to hepatitis C, non-alcoholic fatty liver disease, primary biliary cholangitis, and hepatocellular carcinoma. The orientations in the bundle included: exams to be requested to screen for thyroid disorders, and guidance about the treatment of these dysfunctions and their associated complications. We analyzed specialist evaluation of the bundle using the Content Validity Index (CVI). We carried out a binomial test to evaluate consistency and specialist agreement regarding the items in the bundle, considering values >0.61 as a good level. The items in the bundle were considered to be valid (CVI >0.80). The general CVI of the instrument was 0.95 (CI95%: 0.91-0.98). Conclusion: The bundle was considered valid to facilitate medical decision making, aiding physicians to manage, in a practical and effective approach, the thyroid function of patients with liver cirrhosis. This tool should not be used as a replacement for individual, evaluation of the physician providing assistance. We recommend the structured bundle to be added to medical practice, considering its simple application, low cost, and potential to contribute for the management of these patients.

RESUMO Contexto: A disfunção tireoidiana tem sido relatada em associação com várias doenças crônicas, incluindo a doença hepática avançada. O seu reconhecimento e manejo são, muitas vezes, negligenciados na prática clínica. O bundle consiste em um pacote de cuidados, com a finalidade de promover a assistência de forma sistematizada, a partir da melhor prática baseada em evidências. Objetivo: Construir e validar um bundle para avaliação da função tireoidiana em pacientes com cirrose hepática. Métodos: O processo de construção e validação do bundle foi realizado a partir das seguintes etapas: a) levantamento bibliográfico; b) elaboração do bundle; e c) validação do conteúdo. O levantamento bibliográfico foi realizado a partir de revisão integrativa sobre as evidências relacionadas à função tireoidiana em pacientes com cirrose hepática. Os achados encontrados na revisão integrativa foram considerados como subsídios para construção do bundle. A ferramenta construída se baseou em evidências científicas, de forma a garantir informação pautada em literatura atual e com linguagem acessível. Resultados: O bundle foi estruturado com base nas seguintes finalidades: fornecer orientações sobre o manejo de pacientes com disfunção hepática, categorizado por: cirrose por causas gerais, cirrose por vírus da hepatite C, doença hepática gordurosa não alcoólica, colangite biliar primária e carcinoma hepatocelular. As orientações do bundle incluíram: exames a serem solicitados no rastreio dos distúrbios tireoidianos; orientações sobre indicação de tratamento destas disfunções e possíveis complicações associadas. A análise da avaliação do bundle pelos especialistas foi realizada a partir do cálculo do Índice de Validade do Conteúdo (IVC). Foi feito o cálculo do teste binomial para avaliar a concordância e consistência dos especialistas em relação aos itens do bundle, aceitando-se como bom nível o valor >0,61. Os itens do bundle foram considerados validados (IVC >0,80). O instrumento apresentou IVC geral de 0,95 (IC95%: 0,91-0,98). Conclusão: O bundle foi considerado válido para facilitar a tomada de decisão para o médico conduzir, de maneira prática e efetiva, o manejo da função tireoidiana em pacientes com cirrose hepática. Defende-se que a ferramenta não deve ser utilizada em substituição à avaliação individualizada e autonomia do médico assistente. Recomenda-se que a forma estruturada seja incorporada ao atendimento médico tendo em vista a fácil aplicabilidade, o baixo custo e o potencial para contribuir com o manejo desses pacientes.

Determination of cell proliferation using Mcm2 antigen and evaluation of apoptosis and TGF-beta1 expression in GH-secreting or clinically nonfunctioning pituitary adenomas.

Pituitary adenomas (PA) occasionally show aggressive behavior, with invasion of the surrounding tissues. The identification of markers able to recognize aggressive PA in early stages remains a challenge. We aimed to determine the expression of a new cell proliferation marker, Mcm2, and the presence of apoptosis in PA, and to evaluate the association of clinicopathological features with the apoptotic and proliferative indices. Additionally, the TGF-beta1 expression, an inducer of apoptosis, was determined. The proliferative index was determined in GH-secreting or clinically nonfunctioning PA using immunohistochemical (IH) methods for Mcm2 and Ki-67 antigens. The apoptosis was assessed by the TUNEL method and the TGF-beta1 expression by IH. A significant positive correlation was found between log Mcm2 index and log Ki-67 index (p < 0.001). Mcm2 and Ki-67 detected a similar number of proliferating cells. Mcm2 index showed a significant association with tumor extension (p = 0.02), but not with tumor invasion. Apoptosis was detected in 17% of the adenomas, with a maximum apoptotic index of 0.77%. Immunoreactivity to TGF-beta1 was observed in 77% of the adenomas, showing an association with tumor extension. We concluded that, in this sample, Mcm2 was similar to Ki-67 in the identification of the proliferating cells and that apoptosis was rare.

Possibilidade de associação de melanoma e acromegalia / Possibility of an association between melanoma and acromegaly

Neoplasias como câncer de próstata, mama e cólon estão relacionadas à acromegalia. Raras vezes foi mencionada a associação com melanoma. Descreve-se caso de paciente com acromegalia no qual foi identificada lesão melanocítica suspeita, com posterior confirmação de melanoma. A excisão cirúrgica da lesão levou à cura da neoplasia. Chama-se a atenção para a necessidade de exame cuidadoso da pele de pacientes com acromegalia.

Neoplasias such as prostate, breast, and colon cancer are commonly associated with acromegaly. However, the association of the latter with melanoma has been rarely mentioned. We describe the case of a patient with acromegaly in whom a suspicious melanocytic lesion was detected, and later confirmed to be melanoma by means of biopsy. Surgical excision of the lesion led to the cure of the neoplasia. More attention should be drawn to the need for careful skin examination of patients with acromegaly.

Two cases of Kallmann syndrome associated with empty sella.

Kallmann syndrome (KS) is a developmental disease characterized by the association of isolated hypogonadotropic hypogonadism and anosmia/hyposmia. We report an unusual presentation of two females with KS and empty sella. These females, aged at 20 and 29-year-old, presented primary amenorrhea with prepubertal estradiol and low gonadotropin levels. No other significant clinical signs were observed. Empty sella was observed on MRI in both cases. Sequencing of FGFR1 gene, recently implicated in autosomal form of KS, was performed and one splicing mutation (IVS14 + 1G > A) was identified in one patient.

Hyperprolactinemia and immunohistochemical expression of intracellular prolactin and prolactin receptor in primary central nervous system tumors and their relationship with cellular replication.

The role of prolactin (PRL) in the CNS remains uncertain. We evaluated the presence of hyperprolactinemia, intracellular prolactin (ICP), and prolactin receptor (PRL-R) in primary CNS tumors, and their relationship with cellular replication with a prospective cross-sectional study of 82 consecutive patients with primary CNS tumors admitted for neurosurgical resection between October 2003 and September 2005. Patients submitted to a questionnaire, and venous blood samples were obtained for measurement of serum PRL and TSH. Immunohistochemical analyses were performed to evaluate the presence of ICP, PRL-R, and Ki-67. Serum PRL levels ranged from 2 to 70 ng/ml, and hyperprolactinemia was detected in 25 cases (30.5%). ICP was detected in 18 patients (21.9%), in whom PRL ranged from 2 to 32 ng/ml. A positive correlation was found between PRL levels and the presence of ICP (Student's t test, P = 0.022). The PRL-R was observed immunohistochemically in 32 cases (39%). The frequencies of hyperprolactinemia, ICP, and PRL-R were similar across the several histological types of CNS tumors. Ki-67 index was similar in all groups. Hyperprolactinemia and intracellular presence of PRL and PRL-R were common findings in this population, suggesting a role for PRL in CNS tumor genesis.