Efecto combinado de la interacción genética sobre el desarrollo del bocio nodular con tiroiditis autoinmune y adenoma tiroideo en los habitantes de Bucovina del Norte / Combined effect of gene-gene interaction on the development of nodular goiter with autoimmune thyroiditis and thyroid adenoma in the inhabitants of Northern Bukovyna

ABSTRAC This article presents the results of a comprehensive analysis of the combined influence of genetic polymorphisms associated with various links of apoptosis regulation (BCL-2, CTLA-4 and APO-1/Fas) on the development of nodular goiter with autoimmune thyroiditis and thyroid adenoma in the studied population. The analysis was performed using the Multifactor Dimensionality Reduction (MDR) method by calculating the prediction potential. Graphic models of gene-gene interaction with the highest cross-validation consistency created by the MDR method showed complex "synergistic or independent" impact of polymorphic loci of the CTLA-4 (+49G/A), Fas (-1377G/A) and BCL-2 (63291411 A>G) genes on the onset of thyroid pathology in general, or its individual types (nodular goiter with autoimmune thyroiditis and thyroid adenoma) in the population of Northern Bukovyna.

RESUMEN Este artículo presenta los resultados de un análisis exhaustivo de la influencia combinada de polimorfismos genéticos asociados a diversos enlaces en la regulación de la apoptosis (BCL-2, CTLA-4 y APO-1/FAS) sobre el desarrollo de bocio nodular con tiroiditis autoinmune y adenoma tiroideo en la población estudiada. Para ello, se utilizó el método de reducción de dimensionalidad multifactorial (MDR) mediante el cálculo de los potenciales de predicción. Los modelos gráficos de interacción gen-gen con la mayor consistencia de validación cruzada creada por el método MDR mostraron un complejo impacto «sinérgico o independiente¼ de los loci polimórficos de los genes CTLA-4 (+49G/A), FAS (-1377G/A) y BCL-2 (63291411A>G) en el inicio de la patología tiroidea en general, o sus tipos individuales (bocio nodular con tiroiditis autoinmune y adenoma tiroideo) en la población de Bucovina septentrional.

Prevalência de disfunção tireoidiana e anticorpos antitireoidianos em pacientes portadores de diabetes melito tipo 1 e em seus familiares de primeiro grau / Prevalence of thyroid dysfunction and antithyroid antibodies in type 1 diabetic mellitus patients and their first degree relatives

O diabetes melito tipo 1 (DM1) freqüentemente encontra-se associado à doença auto-imune da tireóide (DAT). A prevalência de DAT varia de 3 por cento a 50 por cento entre diabéticos, e é maior também entre seus familiares, comparada à população geral. OBJETIVOS: Investigar a prevalência da DAT em pacientes com DM1, avaliar possíveis diferenças de comportamento clínico-evolutivo do DM1 entre diabéticos com e sem DAT e estudar a prevalência de DAT nos familiares dos pacientes diabéticos. MATERIAIS E MÉTODOS: Os prontuários de 124 diabéticos tipo 1 foram revisados e coletados os dados referentes à função e aos anticorpos tireoidianos; pacientes com e sem DAT foram comparados em relação à média de Hb glicosilada, complicações agudas e crônicas, idade ao diagnóstico e tempo de evolução do DM, dose de insulina e outros. Um estudo caso-controle foi realizado com 54 familiares em primeiro grau destes pacientes; foram avaliadas a função tireoidiana e a presença de anticorpos antitireoidianos em 32 familiares de diabéticos sem DAT e 22 familiares de diabéticos com DAT. RESULTADOS: As prevalências de DAT e de disfunção hormonal entre os diabéticos foram de 35,5 por cento e 19,3 por cento, respectivamente. Quanto à avaliação dos parâmetros de evolução do DM1, comportamento clínico e controle metabólico não houve diferenças significantes entre os diabéticos com e sem DAT. Houve maior prevalência de DAT nos familiares de diabéticos com DAT do que no grupo dos familiares dos diabéticos sem DAT, sem diferença significativa quanto à prevalência de disfunção hormonal. CONCLUSÕES: A prevalência de doença auto-imune de tireóide em diabéticos e em seus familiares é elevada, justificando-se, nesses casos, a investigação rotineira da função tireoidiana, particularmente dos familiares de primeiro grau de diabéticos com DAT.

Diabetes Mellius Type 1 (DM1) is frequently associated to Autoimmune Thyroid Disease (AITD). The prevalence of AITD among diabetic patients varies between 3 to 50 percent and the incidence is also big among their family members, when compared to the population in general. OBJECTIVES: To investigate the prevalence of AITD in patients with DM1; to evaluate possible differences concerning the clinical-evolutive behavior of DM1 among diabetic patients with or without AITD and to study the prevalence of AITD among the diabetes patients' relatives. MATERIALS AND METHODS: 124 prontuaries of diabetic patients (type 1) were revised and data was gathered concerning the thyroid function and the anti-thyroid antibodies. Patients with and without AITD were compared in relation to the level of glycosylated hemoglobin, the presence of acute and chronic complications, the age of the patient at the time of the diagnosis, time of evolution of the disease, daily dose of insulin and other factors. A control case study was conducted with 54 first degree relatives of the diabetic patients who took part in the study; the thyroid function as well as the presence of anti-thyroid antibodies were evaluated in 32 of those first degree relatives with AITD, and in 22 of those without AITD. RESULTS: The prevalence of AITD and of hormonal dysfunction among diabetic patients was 35.5 percent and 19.3 percent, respectively. No significant differences were found between groups in respect to clinical outcome or to diabetic chronic complications. However, prevalence of AITD and hormonal dysfunction were found to be higher among first degree relatives of diabetic patients with AITD than among relatives of diabetic patients without AITD. CONCLUSIONS: The prevalence of autoimmune thyroid disease in diabetic patients and in their first degree relatives is high. Thyroid function screening is therefore justified in these cases, especially in first degree relatives of diabetics ...

Lack of association between a polymorphism of human thyrotropin receptor gene and autoimmune thyroid disease.

A polymorphism in codon 52 of the human thyrotropin receptor results in a proline to threonine substitution in the extracellular domain of the receptor, but the association with autoimmune thyroid disease has been uncertain and there is no report the prevalence of this polymorphism in Orientals. To investigate this polymorphism and the association with autoimmune thyroid disease, we studied 113 normal unrelated individuals, 142 autoimmune thyroid disease patients including 112 Graves' disease and 30 Hashimoto's thyroiditis in the Thai population. We screened genomic DNAs of these subjects for the presence of A253 by PCR amplification using a degenerate oligonucleotide primer which produces a Tth111 I restriction site only in the presence of A253. The variant allele was present in 5.3 per cent of normal and 3.5 per cent of autoimmune thyroid disease, 2.7 per cent of Graves' disease and 6.7 per cent of Hashimoto's thyroiditis. The allele distribution in autoimmune thyroid disease patients did not differ significantly from that observed in controls. No association was found between this TSH-R polymorphism and the occurrence of autoimmune thyroid disease.

Tireoidite crônica autoimune: relato de caso com alta prevalência familiar / Chronic autoimmune thyroiditis: report of case with high familiar prevalence

A tiroidite crônica autoimune (TCA) é a causa mais comum de hipotireoidismo em adultos e pode ocorrer na forma de bócio difuso ou nodular ou na forma atrófica. Pode ser determinada por fatores genéticos (HLA-DR3, HLA-DR4, HLA-DR5, HLA-B8) ou ocorrer esporadicamente. Descrevemos uma família com 13 membros afetados, acometendo 9 irmäos e 4 sobrinhas. Em todos os irmäos o diagnóstico da doença foi feito após os 35 anos de idade (exceto uma, aos 25 anos), com predomínio acima dos 50 anos e todos possuem clínica e laboratório compatível com hipotireoidismo primário, com anticorpos anti-tireoideanos positivos e apenas três com diagnóstico recente possuem bócio. Há, portanto, forte sugestäo de herança autossômica dominante de TCA.

The tumor necrosis factor beta * 1 allele is linked significantly to HLA-DR8 in Koreans with atrophic autoimmune thyroiditis who are positive for thyrotropin receptor blocking antibody

The localization and functional characteristics of tumor necrosis factor(TNF) beta gene raise the possibility that it may be involved in the susceptibility to autoimmune thyroid diseases. To investigate whether a TNF beta gene polymorphism is associated with autoimmune thyroiditis, we analyzed the TNF beta gene polymorphism with the restriction enzyme NcoI in 48 Korean patients with atrophic autoimmune thyroiditis [23 were found to be thyrotropin binding inhibitor immunoglobulin(TBII) positive, 25 TBII negative], 52 goitrous autoimmune thyroiditis, and 129 healthy controls. Two TNF beta alleles were identified from the restriction fragment length polymorphism studies of amplified genomic DNA. In atrophic autoimmune thyroiditis patients positive for TBII, 7 of 23 patients were homozygous for the TNF beta * 1 allele, 3 were homozygous for the TNF beta * 2 allele, and 13 were TNF beta * 1/2 heterozygous compared to controls(P = 0.20). Also, there were no associations between the TNF beta gene polymorphism and either TBII-negative atrophic autoimmune thyroiditis or goitrous autoimmune thyroiditis. Of the HLA-class II antigens, the frequency of HLA-DR8 was significantly greater among the 23 Korean patients with TBII-positive atrophic autoimmune thyroiditis compared to control subjects (Pc = 0.003). When the HLA-DR8 positive patients with TBII-positive atrophic autoimmune thyroiditis and controls were analyzed separately, the DR8 positive patients with TBII-positive atrophic autoimmune thyroiditis had more homozygotes for the TNF beta * 1 allele(6/12, 50.0%) and no homozygotes for the TNF beta * 2 allele, as compared to the DR8 negative patients with TBII-positive atrophic autoimmune thyroiditis and DR8 positive controls(P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Tiroiditis de Hashimoto. Estudio de 100 casos

Presentamos 100 casos de tiroiditis de Hashimoto (TH) cuyo diagnóstico se basó en la presencia de bocio y anticuerpos antitiroideos positivos y/o informe de citología del aspirado de tiroides compatible con TH. El promedio de edad fue de 35 años con su mayor incidencia hacia la cuarta década de la vida; la razón mujer a hombre fue 24:1. A 62 pacientes se les realizó aspirado de tiroides; en 54 la citología fue informada como TH. Los anticuerpos antimicrosomales y antitiroglobulina fueron positivos en 83 por ciento y 52 por ciento de los pacientes respectivamente; ambos anticuerpos fueron negativos en 12 pacientes discriminados así: clínico en 57 y subclínico en 23. De los 20 pacientes eutiroideos, seis elevaron la TSH entre uno y medio y tres años después del diagnóstico. Los hallazgos predominantes en los estudios gamagráficos de tiroides con 99mTc fueron: bocio con distribución homogénea y normo o hipercaptación del radiotrazados. Concluimos que la TH no es tan rara en nuestro medio y que se requieren estudios de mayor envergadura para determinar su prevalencia.