Relación entre linfocitos T reguladores (T regs) y anticuerpos anti-receptores de TSH (TRab) y el riesgo de cáncer de tiroides en enfermedad de Graves / Relationship between T regulatory lymphocytes (Tregs) and TSH receptor antibodies (TRab) on risk of thyroid cancer in Graves disease

Durante los últimos años se ha estudiado la relación entre enfermedad de Graves (EG), TSH, TRAb y cáncer de tiroides, existiendo estudios que demuestran mayor prevalencia y agresividad del cáncer de tiroides en pacientes con EG, mientras otros refutan estos hallazgos sugiriendo que serían producto del sesgo de selección. Aquellos estudios que plantean una relación causal entre EG y el desarrollo de cáncer de tiroides, la atribuyen a la presencia de autoanticuerpos TSI, que estimularían el foco de malignidad. Se cree que las citoquinas producidas localmente en pacientes con EG trabajarían en conjunto con los TRAb para determinar la agresividad del cáncer papilar de tiroides en estos pacientes. Dentro de las células reclutadas por el tumor para evadir la respuesta inmune se encuentran los linfocitos Treg, que estarían elevados en paciente con EG, llevando a la disminución de la respuesta inmune y creando un ambiente permisivo para la proliferación celular. Por tratarse de una línea de investigación reciente, no existe consenso sobre el tema y sus implicancias en el tratamiento de los pacientes con EG. La finalidad de este artículo es realizar una revisión de la literatura que exponga y contraste la información disponible a la fecha.

In recent years the relationship between Graves’ disease (GD), TSH, TRAb and thyroid carcinoma has been studied. Research studies show a higher prevalence and aggressiveness of thyroid carcinoma in patients with GD, however other researchers refute these findings suggesting it’s due to selection bias. Increasing evidence suggests a causal relationship between GD and the development of thyroid carcinoma, mainly because of the existence of TSI autoantibodies that could stimulate the focus of malignancy. It is believed that cytokines produced locally in patients with GD work alongside with TRAb regulating the aggressiveness of papillary thyroid carcinoma in these patients. Within the cells recruited by the tumor to elude the immune system we find Treg lymphocytes, which have been found to be increased in patients with GD, leading to a diminished immune response, creating a permissive environment for cell proliferation. Since this is a relatively new line of research, there is no consensus on the subject and its relevance for the treatment of patients with GD. The aim of this article is to show recent literature available on the subject.

Factors associated with reporting of abuse against children and adolescents by nurses within Primary Health Care / Fatores associados à notificação de maus-tratos em crianças e adolescentes realizada por enfermeiros na Atenção Primária à Saúde / Factores asociados a la notificación del maltrato en niños y adolescentes realizada por enfermeros en la Atención Primaria a la Salud

OBJECTIVE: to analyze the factors associated with the underreporting on the part of nurses within Primary Health Care of abuse against children and adolescents. METHOD: cross-sectional study with 616 nurses. A questionnaire addressed socio-demographic data, profession, instrumentation and knowledge on the topic, identification and reporting of abuse cases. Bivariate and multivariate logistic regression was used. RESULTS: female nurses, aged between 21 and 32 years old, not married, with five or more years since graduation, with graduate studies, and working for five or more years in PHC predominated. The final regression model showed that factors such as working for five or more years, having a reporting form within the PHC unit, and believing that reporting within Primary Health Care is an advantage, facilitate reporting. CONCLUSION: the study's results may, in addition to sensitizing nurses, support management professionals in establishing strategies intended to produce compliance with reporting as a legal device that ensures the rights of children and adolescents. .

OBJETIVO: analisar os fatores associados à notificação de maus-tratos em crianças e adolescentes, realizada por enfermeiros que atuam na Atenção Primária à Saúde. MÉTODO: estudo transversal, realizado com 616 enfermeiros. Foi utilizado um questionário contendo dados sociodemográficos, formação profissional, instrumentação e conhecimento sobre o tema, identificação e notificação de casos de maus-tratos. Análises bivariada e multivariada por regressão logística foram realizadas. RESULTADOS: predominaram enfermeiros do sexo feminino, na faixa etária entre 21 e 32 anos, não casados, com cinco ou mais anos de formado, com pós-graduação e com cinco ou mais anos de trabalho. O modelo logístico final evidenciou que fatores como tempo de trabalho de cinco ou mais anos, a unidade de saúde possuir a ficha de notificação, saber para onde encaminhar os casos, não ter medo de envolvimento legal e achar vantajosa a notificação na atenção primária facilitam a efetivação do ato notificatório. CONCLUSÃO: os resultados desta pesquisa, além de sensibilizar os enfermeiros para o problema, poderão ser utilizados pelos profissionais da gestão na orientação de estratégias para o cumprimento da notificação como dispositivo legal de garantia dos direitos de crianças e adolescentes. .

OBJETIVO: analizar los factores asociados a la notificación de maltrato en niños y adolescentes realizado por enfermeros que actúan en la Atención Primaria a la Salud. MÉTODO: estudio transversal realizado con 616 enfermeros. Fue utilizado un cuestionario conteniendo datos sociodemográficos, formación profesional, instrumentación y conocimiento sobre el tema, identificación, y notificación de casos de maltrato. Análisis bivariado y multivariado por regresión logística. RESULTADOS: predominaron enfermeros del sexo femenino, en la franja etaria de 21 a 32 años, no casados, con cinco o más años de graduación, con postgraduación y con cinco o más años de trabajo. El modelo logístico final evidenció que factores como tiempo de trabajo de cinco o más años, la unidad de salud poseer ficha de notificación, saber para donde encaminar los casos, no tener miedo de involucramiento legal y encontrar ventaja en la notificación en la atención primaria, son aspectos que facilitan la efectividad del acto de la notificación. CONCLUSIÓN: los resultados de esta investigación, además de sensibilizar a los enfermeros para el problema, podrán ser utilizados por profesionales de la gestión en la orientación de estrategias para el cumplimiento de la notificación como dispositivo legal de garantía de los derechos de niños y adolescentes. .

Interleukin-10 but not interleukin-18 may be associated with the immune response against well-differentiated thyroid cancer

OBJECTIVES: The aim of this study was to investigate the role of the interleukin-18 +105A/C and interleukin-10 -1082A/G germline polymorphisms in the development and outcome of differentiated thyroid carcinoma associated or not with concurrent thyroiditis. METHODS: We studied 346 patients with differentiated thyroid carcinomas, comprising 292 papillary carcinomas and 54 follicular carcinomas, who were followed up for 12-298 months (mean 76.10 ± 68.23 months) according to a standard protocol. We genotyped 200 patients and 144 control individuals for the interleukin-18 +105A/C polymorphism, and we genotyped 183 patients and 137 controls for the interleukin-10 -1082A/G polymorphism. RESULTS: Interleukin-18 polymorphisms were not associated with chronic lymphocytic thyroiditis or any clinical or pathological feature of tumor aggressiveness. However, there was an association between the presence of interleukin-10 variants and chronic lymphocytic thyroiditis. Chronic lymphocytic thyroiditis was present in 21.74 percent of differentiated thyroid carcinoma patients, most frequently affecting women previously diagnosed with Hashimoto's thyroiditis who had received a lower 131I cumulative dose and did not present lymph node metastases. CONCLUSIONS: We conclude that the inheritance of a G allele at the interleukin-10 -1082A/G polymorphism may favor a concurrent thyroid autoimmunity in differentiated thyroid carcinoma patients, and this autoimmunity may favor a better prognosis for these patients.

Uso do infliximabe e aparecimento sequencial de autoanticorpos e neoplasia em paciente com espondiloartrite / Infliximab use and sequential occurrence of autoantibodies and neoplasia in a patient with spondyloarthritis

O aparecimento de anticorpos antinucleares tem sido relatado após o uso prolongado de anti-TNFs. A emergência de neoplasias linfoproliferativas também tem sido descrita e, com menor frequência, os tumores sólidos. Nós descrevemos o aparecimento simultâneo dessas duas condições clínicas em uma paciente com espondiloartrite na vigência de infliximabe. Uma revisão da literatura é apresentada e a possível correlação com o aparecimento de tumor sólido é discutida.

The development of antinuclear antibodies after long-term use of anti-TNF therapy has been reported by several authors. The occurrence of lymphoproliferative neoplasms and, less commonly, solid tumors has also been reported. We present a case ofsimultaneous development of antinuclear antibodies and solid tumor in a patient with spondyloarthritis while on infliximab therapy. The implications and possible correlations with a solid tumor occurrence are reviewed and discussed.

High prevalence of thyroid disorders in relatives of patients with familial papillary thyroid cancer / Elevada prevalencia de alteraciones tiroideas en familiares de pacientes con diagnóstico de carcinoma papilar familiar

In the familial form of papillary thyroid cancer (PTC), two or more members of the same family have to be affected with PTC. Prevalence is around 5% of all PTC. We performed a clinical analysis in 79 relatives of 16 patients of 7 unrelated kindred with the diagnosis of familial papillary thyroid carcinoma (FPTC). The results were compared with a control group. Thyroid palpation and TSH and TPO-Ab assessment was carried out in the relatives without a diagnosed PTC. Additionally, molecular analysis was performed in the sixteen affected patients. Clinical screening of the 79 family members showed the presence of goiter in 22/79 (29 %). This frequency was much higher than that observed in the control group (8.7%), p < 0.001. Hypothyroidism was found in 4 of the relatives (5%) vs. 2.5% observed in the control group, p < 0.01, and anti-thyroid antibodies (TPO-Ab) were positive in 14% of the relative's group vs. 10 % in the control group, (p = NS). In the molecular analysis, only a protooncogene TRK rearrangement was observed in family # 6. In conclusion, we found a higher incidence of goiter and hypothyroidism in the relatives of patients with FPTC. Nevertheless, TPO-Ab frequency was not different. No molecular abnormalities were indicative of a specific pattern in this subset of patients with FPTC.

En la forma familiar del carcinoma papilar de tiroides (CPT), dos o más miembros de la misma familia deben presentar CPT. Esta entidad ocurre en aproximadamente el 5% de todos los CPT. En este estudio, realizamos una evaluación de 79 familiares de 16 pacientes con diagnóstico de carcinoma papilar familiar (CPF) provenientes de 7 familias diferentes. Los resultados se compararon con los hallados en un grupo control. Se realizó palpación tiroidea y medición de TSH y anticuerpos anti-tiroperoxidasa (TPO-Ab) en todos los familiares. Además, se llevó a cabo el análisis molecular en los 16 sujetos que presentaban el diagnóstico de CPF. La evaluación de los 79 familiares de estos pacientes demostró la presencia de bocio en 22/79 (29%). Esta frecuencia fue mucho mayor que la observada en el grupo control (8.7%), p < 0.001. Se diagnosticó hipotirodismo en 4 familiares (5%) vs. 2.5%, observado en el grupo control, p < 0.01, y los TPO-Ab fueron positivos en 14% de los familiares vs. 10% del grupo control, (p = ns). En el análisis molecular, solamente se halló un rearreglo del protoncogen TRK en una de las 7 familias con CPF. En conclusión, hallamos una elevada prevalencia de bocio e hipotiroidismo en los familiares de pacientes con CPT. Sin embargo, la frecuencia de autoinmunidad no fue diferente. No se hallaron alteraciones moleculares distintivas en estos pacientes con CPF.

Non-cancerous thyroid lesions: immunologic and surgical evaluation

The present study was designed to determine T helper-l/T helper-2 [Th[1]/Th[2]] pattern in patients with Graves' disease [GD], benign multinodular goiter [MNG] and Hashimoto thyroiditis [HT] and evaluate the applicability of near-total thyroidectomy as a therapeutic strategy for surgical interference. The study included 75 patients [56 females and 19 males; with mean age of 43.8 +/- 8.2 years] with thyroid swelling and 15 healthy volunteers [control group]. Patients underwent clinical examination including direct laryngoscopy using fiberoptic endoscopy, laboratory investigations and ultrasonographic and [99m] Tc pertechnetate scintigraphy for establishment of diagnosis. Patients with HT received medical treatment and were followed-up, while patients with GD and MNG underwent near-total thyroidectomy. Preoperative blood samples were collected from patients and control subjects for ELISA estimation of serum levels of interleukin-2 [IL-2], IL-18, IL-4 and IL-5. Patients were observed for appearance of postoperative manifestations of recurrent laryngeal nerve [RLN] palsy and/or hypoparathyroidism. Mean operative time, duration of wound drainage and hospital stay were recorded. The study included 43 patients with GD [8 of them had thyroid orbitopathy], 17 patients had MNG and the remaining 15 patients had HT. All patients had smooth intraoperative course and no patient had permanent RLN palsy, but 4 [6.7%] patients had transient unilateral RLN palsies that recovered spontaneously after a mean duration of 24.5 +/- 11.6 days. Temporary hypocalcaemia occurred in 9 patients [15%] and permanent hypoparathyroidism resulted in one [1.7%]. All patients developed wound edema, 7 patients had wound seroma and 2 patients had wound infection. Mean serum levels of lL-2, IL-4 and IL-5 were significantly higher in patients compared to control levels irrespective of the type of thyroid lesion. Mean serum levels of IL-18 were significantly higher in patients with HT and MNG disease and non-significantly higher in patients with GD compared to control levels. Moreover, mean serum levels of IL-2 and IL-18 were significantly higher and mean serum levels of IL-4 and IL-5 were significantly lower in patients with HT and MNG disease compared to those with GD and in MNG patients compared to those with HT. The percentage of postoperative increase of serum IL-2 and IL-18 levels relative to the median control level were significantly higher in patients with HT than in patients with GD or MNG with a significantly higher percentage of increase in patients with MNG compared to those with GD. On the other hand, the percentages of increase of IL-4 and IL-5 were significantly higher in patients with GD compared to patients with HT or MNG with a significantly but non-significantly higher percentage of increase of IL-5 and IL-4, respectively, in patients with MNG compared to those with HT. It could be concluded that there was a disturbed pattern of Th[1]/Th[2] cytokines in patients with non-cancerous thyroid lesion in favor of humoral pattern of immune response in GD with predominance of Th[2] cytokines and a Th[1]-pattern of immune response characteristic of cellular immunity is dominant in HT. Also, near total thyroidectomy was found appropriate therapeutic modality with transient minimal complications for patients with MNG or GD

Antithyroglobulin antibodies in patients with differentiated thyroid carcinoma: methods of detection, interference with serum thyroglobulin measurement and clinical significance

Anticorpos anti-tireoglobulina (TgAb) foram medidos por um imunoensaio de quimioluminescência (ICMA) e um teste de aglutinação. Avaliamos a interferência clínica e laboratorial dos TgAb com as medidas de Tg. A evolução da concentração dos TgAb e o estado da doença foram comparados durante 3 anos após o início do tratamento. O teste de aglutinação falhou em detectar todos o títulos <10UI/mL (ICMA). Interferência dos TgAb foi comum com títulos altos, mas mesmo títulos baixos dos anticorpos (<5UI/mL) interferiram na medida de Tg. Casos com metástases à distância e Tg indetectável (por IRMA) e aqueles aparentemente livres da doença e sem remanescentes tireoidenos com Tg >2ng/ml (por RIA) foram identificados entre pacientes com TgAb. O teste de recuperação da Tg exógena foi normal (>80%) por ambos os métodos em 22% dos pacientes com TgAb, confirmando a interferência laboratorial. Ausência de redução dos níveis de TgAb foi um marcador de persistência da doença. Em conclusão, TgAb deve ser determinada por imunoensaios; interferência com as medidas de Tg ocorreram principalmente mas não somente em altas concentrações, com um teste normal de recuperação de Tg não excluindo esta interferência. O comportamento dos TgAb está relacionado à persistência ou à cura da doença.

Frequency and clinical Importance of Anti - TG auto antibodies [ATG]

To note the frequency of anti thyroglobulin autoantibodies [ATG] and its clinical importance in 25 follow-up cases of differentiated thyroid cancer [DTC]. Design: A case control study. Place and Duration of Study: The total duration of study was one year [September 2000 to August 2001]. Majority of the patients included were the routine follow-up cases at IRNUM, Peshawar. However, few of the cases were also included from NORI, Islamabad and AFIP, Rawalpindi. Subjects and All the patients who had undergone sub-total or total thyroidectomy followed by I-131 ablation therapy were selected for this study. Thyroglobulin [Tg] and ATG were measured using immunometric assay technique with reference range of non-detectable to 40 IU/L. Patients with serum Tg level ' 10 ng/mL were included in group-1 [n=15] and all the remaining [n=10] in group-2. Overall, 11 patients showed ATG titer above the pre-defined threshold level. In group -1 patients, 8 had positive anti-Tg antibodies in their sera while in group-2, it was positive in only 3 cases. Risk of relapsing metastatic/recurrent disease in association with ATG was calculated which showed that patients with positive ATG have almost seven - fold increased risk of having recurrent/metastatic disease than those who do not. Samples for s-Tg measurements must also be evaluated for ATG status because more than one-third of these patients have positive ATG titer in their sera. Although in the presence of positive ATG, the risk of concurrent metastatic/recurrent thyroid disease is increased but still more studies are required to support its significance

Mucoepidermoid carcinoma of the thyroid: report of a case with immunohistochemical studies

En el presente trabajo se describe un carcinoma mucoepidermoide de tiroides que mostró prácticamente el mismo cuadro clínico del carcinoma papilar de tiroides. La presencia de células mucinosas y de tipo epidermoide, junto con la ausencia de tiroglobulina en las células neoplásicas, fueron parámetros esenciales para el diagnóstico preciso de carcinoma mucoepidermoide. El antígeno carcinoembrionario fue detectado en las células tumorales y se discute su posible importancia como marcador histológico y clínico de esta relativamente nueva entidad patológica de tiroides

Estudios inmunohistoquímicos en lesiones foliculares tiroideas: demostración de tiroglobulina y tiroxina / Immunohistochemical studies of thy roid follicular lesions: thyroxine and thyroglobulin localization demonstration

Se ha estudiado con el método de peroxidasa-antiperoxidasa la presencia y distribución de tiroglobulina y tiroxina en una serie de 38 muestras de lesiones tiroideas y extratiroideas. Las muestras tiroideas estudiadas correspondían a glandulas normales, lesiones no tumorales, adenomas y carcinomas. Con tiroglobulina fueron positivos el 93% de las lesiones de origen tiroideo incluyendo todas las tiroides normales y lesiones no tumorales, 3 de los 4 adenomas, los 8 carcinomas foliculares y 9 de los 10 carcinomas papilares. Los 6 carcinomas papilares no tiroideos y una metástasis tiroidea de origen mamario fueron negativos. Con tiroxina la tinción fue menos constante e intensa. Sólo se tiñeron el 53% de las lesiones tiroideas incluyendo 1 de 3 tiroides normales, 3 de 4 lesiones no tomorales, 1 de 4 adenomas foliculares, los 3 carcinomas foliculares y 1 de 3 carcinomas papilares. Esta serie y otros trabajos en la literatura demuestran que la tiroglobulina es un excelente marcador de lesiones foliculares tiroideas siendo de utilidad diagnóstica en carcinomas pobremente diferenciados y lesiones metastásicas de posible origen tiroideo. La demonstración de tiroxina si bien es útil como la anterior para determinar el estado funcional de la célula tiroidea es de evidente menor valor diagnóstico