Unraveling the molecular architecture of autoimmune thyroid diseases at spatial resolution.

Autoimmune thyroid diseases (AITD) such as Graves' disease (GD) or Hashimoto's thyroiditis (HT) are organ-specific diseases that involve complex interactions between distinct components of thyroid tissue. Here, we use spatial transcriptomics to explore the molecular architecture, heterogeneity and location of different cells present in the thyroid tissue, including thyroid follicular cells (TFCs), stromal cells such as fibroblasts, endothelial cells, and thyroid infiltrating lymphocytes. We identify damaged antigen-presenting TFCs with upregulated CD74 and MIF expression in thyroid samples from AITD patients. Furthermore, we discern two main fibroblast subpopulations in the connective tissue including ADIRF+ myofibroblasts, mainly enriched in GD, and inflammatory fibroblasts, enriched in HT patients. We also demonstrate an increase of fenestrated PLVAP+ vessels in AITD, especially in GD. Our data unveil stromal and thyroid epithelial cell subpopulations that could play a role in the pathogenesis of AITD.

Mapping Thyroid Changes in Size and Position During Enlargement in Adult Mice With Hyperthyroidism.

The thyroid in Graves' disease undergoes a considerable divergence in size and position from the normal anatomy. However, knowledge of the pathological anatomy related to the change, which is required before planned surgical or local intervention, or diagnosis, is neglected. To investigate Graves' disease, we established a model of mice that successfully mimicked all the signs presented in the clinic. Under a long-term immunization (35 weeks), the animals displayed large heterogeneity in thyroid size, such as the cases of natural occurrence. These thyroids in the model were sized into various phases and registered. A blend of the registered thyroids and the thyroid and tracheal cartilage landmarks led to the production of site-dependent incidence graphs of thyroid in the front view and on the section for each phase. The merger of the incidence graphs of all the phases resulted in thyroid phase-dependent topography. The depicted graphs illustrate the fine localization of the thyroid in various sizes and their dynamic changes during enlargement, which may facilitate currently used fine-needle aspiration biopsy and ultrasonography-guided biopsy techniques. Familiarity with this knowledge might avoid misclassifying an abnormality as normal, or vice versa, and be helpful for imaging diagnosis and local surgery therapy in Graves' disease.

Case report: A rare combination of aldosterone-secreting adrenocortical carcinoma and papillary thyroid carcinoma with Graves' disease.

Adrenocortical carcinoma (ACC) is a rare malignancy originating in the adrenal glands, aldosterone-producing ACC, even rarer. Papillary thyroid carcinoma (PTC), by contrast, accounts for the majority of thyroid carcinomas. We herein describe the first reported case of a female with comorbidities of aldosterone-producing ACC, PTC, and Graves' Disease(GD). The patient achieved transient clinical remission following adrenalectomy. However, three months later, aldosterone-producing ACC lung metastases emerged. Subsequently, within another three-month interval, she developed thyroid eye disease(TED). The patient died roughly one year after the adrenal operation. Exome sequencing did not reveal associations between aldosterone-producing ACC, PTC, and GD, and the underlying concurrence mechanism has yet to be elucidated. Further research of similar cases are needed to confirm potential links between the three pathologies.

An easy approach to ultrasonographic volumetry of the thyroid.

To establish an easy way to perform volumetry of the thyroid gland using ultrasonography, we evaluated the accuracy of the products of the depth and width of the right thyroid lobe as indices of thyroid volume. The depth and width of both thyroid lobes were measured using ultrasonography before surgery in 193 patients with Graves' disease. The products were compared with the weight of the thyroid obtained from operative records. We also evaluated the depth and width of the right thyroid lobe in 312 subjects who presented without any thyroid disease. The products of depth and width of the right and left lobes of patients with Graves' disease correlated similarly well with the weight of the thyroid obtained from operative records (ρ = 0.896 for right, ρ = 0.886 for left, p < 0.0001). Because the right lobes were larger than the left lobes, the products of the depth and width of the right lobe were adopted as novel parameters for an easy volumetric approach. The relationship between the weight and the measurements of the right lobe was described using the following regression equation: weight (g) = [11.8 × depth (cm) × width (cm)] - 16.0. The products of the subjects without any thyroid diseases were distributed between 0.6 cm2 and 4.4 cm2, with a median of 2.0 cm2. The upper limit of these values in these subjects was estimated to be 3.8 cm2. This easy ultrasonographic volumetric technique makes it possible to perform a semi-quantitative assessment of thyroid volume and to differentiate diffuse goiter from normal-sized thyroids.

Calcium oxalate crystals as a cause of multiple punctate echogenic foci in benign thyroid lesions.

PURPOSE: Multiple punctate echogenic foci (MPEF) on thyroid ultrasonography reflects psammoma bodies in papillary thyroid carcinomas. However, MPEF is also observed in benign thyroid lesions. The aim of this study was to determine the origin of MPEF in patients with benign thyroid lesions. METHODS: We enrolled 26 patients with Graves' disease (GD) and 24 with follicular nodular disease (FND) who exhibited MPEF and underwent surgery. As controls, we enrolled 40 patients with GD and 32 with FND, but without MPEF, who underwent surgery. RESULTS: MPEF was observed in both lobes in 80.8% of GDs with MPEF, but was limited to a single lobe in the remaining cases. MPEF was diffusely distributed in 72.3% of the cases and focally distributed in the remaining cases. On ultrasonography, most (92.3%) FNDs with MPEF were solid lesions, and seven nodules (26.9%) were interpreted as intermediate suspicion and their frequencies were higher than in those without MPEF (p < 0.01). Microscopically, calcium oxalate (CaOx) crystals were observed more frequently in GDs and FNDs with MPEF (100% and 88.5%, respectively) than in those without MPEF (p < 0.001). These differences were particularly significant for CaOx crystals > 100 µm. In GD cases, large CaOx crystals were observed more frequently in the lobes with MPEF than in those without (p < 0.05). No psammoma bodies were present in any of the cases. CONCLUSION: Appearance of MPEF in GDs and FNDs is not because of psammoma bodies; it is attributable to CaOx crystals larger than 100 µm. Therefore, MPEF is not an indicator of malignancy.

Toll-like receptor 7 and tumor necrosis factor alpha polymorphisms in Egyptian patients with autoimmune thyroid diseases.

Hashimoto's thyroiditis (HT) and Graves' disease (GD) susceptibility depends on a complex interaction between environmental and genetic factors. Genes for tumor necrosis factor alpha (TNF-α) and toll-like receptors (TLRs) have been incorporated into the pathophysiology of autoimmune disorders. Our aim is to assess the association between TLR7 (rs179009) and TNF-α (rs1800629) polymorphisms and susceptibility to autoimmune thyroid disorders. One-hundred ninety-nine individuals, divided into 68 HT patients in group I, 57 GD patients in group II, and 74 age- and gender-matched healthy subjects in group III, underwent laboratory investigations, including the detection of TLR7 and TNF-α polymorphisms using real-time PCR technique. TLR7 (rs179009) genotypes, A/G and G/G, were significantly more prevalent in HT patients (group I) compared to normal controls. Meanwhile, TNF-α (rs1800629) genotypes in GD patients (group II) showed a six fold increase in the risk of the disease in the G/A and A/A genotypes. Our findings propose the fact that the polymorphisms of TLR7 (rs179009) play a role in the susceptibility and the development of Hashimoto's thyroiditis, whereas TNF-α (rs1800629) polymorphisms play a role in the susceptibility and development of Graves' disease.

Armadilhas no diagnóstico do carcinoma papilífero associado à doença de graves: relato de caso / Pitfalls in papillary carcinoma diagnosis associated with graves' disease: case report

A Doença de Graves constitui a forma mais comum de hipertireoidismoem áreas suficientes em iodo (60-80%)10. Por sua vez,o carcinoma papilífero, é o tumor tireoidiano mais frequentee é responsável por 80% dos casos de câncer de tireoide nosEUA12. Carcinomas da tireoide incidentais em pacientes comDG não são incomuns, mas a maioria deles são microcarcinomapapilar de tireoide de baixo risco, sem metástases em linfonodosou invasão extratireoidiana4. Exames complementares quandorealizado por profissionais experientes tornam-se instrumentode grande valia ao diagnóstico. Relata-se o caso de uma pacientefeminina, 41 anos, em seguimento ambulatorial, com sintomastípicos de DG cujos exames iniciais mostravam-se normais ecom subsequente avaliação apresentava nódulo tireoidiano comcaracterísticas de malignidade. A punção aspirativa por agulhafina (PAAF) foi compatível com Carcinoma Papilífero e a terapêuticacirúrgica indicada, seguida de dose ablativa iodo radioativo(131I) e supressiva com levotiroxina (LT4).(AU)

The Graves Disease is one of the most common clinical formsof hyperthyroidism in iodine sufficient areas (60-80%). At the same time, papillary thyroid carcinoma is the most frequent andresponsible for 80% of thyroid cancer cases in US. Incidentalthyroid cancer is common among patients with Graves disease,with no linphonodal metastasis nor local extrathyroidal invasion.Complementary exams performed by experienced physiciansare a valuable diagnostic tool. Here we describe of a 41 yearoldfemale patient that was in outpatient care for classic Graveswith typical symptoms, but with primary exams all normal.In the follow-up examination a single nodule with malignantcharacteristics was visualized and for the patient was indicatedto Fine Needle Aspiration (FNA), which was positive forPapillary Carcinoma. Patient underwent surgical treatmentfollowed by radioactive iodine therapy and a suppressing doseof levothyroxine.(AU)

Pre-tibial myxedema: treatment with intralesional corticosteroid

The pretibial myxedema is a manifestation of Graves' disease characterized by accumulation of glycosaminoglycans in the reticular dermis. The dermopathy is self-limiting but in some cases may cause cosmetic and functional damage. Conventional treatment is use of topical steroids under occlusive dressing, however the intralesional application has shown good results. We present a case of pretibial myxedema treated with single injection of intralesional corticosteroid.

Thyroid nodules and thyroid cancer in Graves’ disease / Nódulos tiroidianos e câncer de tiroide na doença de Graves

Objective The frequency of thyroid nodules accompanying Graves’ disease and the risk of thyroid cancer in presence of accompanying nodules are controversial. The aim of this study was to evaluate the frequency of thyroid nodules and the risk of thyroid cancer in patients operated because of graves’ disease. Subjects and methods Five hundred and twenty-six patients in whom thyroidectomy was performed because of Graves’ disease between 2006 and 2013 were evaluated retrospectively. Patients who had received radioactive iodine treatment and external irradiation treatment in the neck region and who had had thyroid surgery previously were not included in the study. Results While accompanying thyroid nodule was present in 177 (33.6%) of 526 Graves’ patients, thyroid nodule was absent in 349 (66.4%) patients. Forty-two (8%) patients had thyroid cancer. The rate of thyroid cancer was 5.4% (n = 19) in the Graves’ patients who had no nodule, whereas it was 13% (n = 23) in the patients who had nodule. The risk of thyroid cancer increased significantly in presence of nodule (p = 0.003). Three patients had recurrence. No patient had distant metastasis. No patient died during the follow-up period. Conclusions Especially Graves’ patients who have been decided to be followed up should be evaluated carefully during the follow-up in terms of thyroid cancer which may accompany. Arq Bras Endocrinol Metab. 2014;58(9):933-8 .

Objetivo A frequência da ocorrência de nódulos tiroidianos acompanhando a doença de Graves e o risco de câncer de tiroide na presença desses nódulos é controversa. O objetivo deste estudo foi avaliar a frequência de nódulos tiroidianos e o risco de câncer de tiroide em pacientes operados por doença de Graves. Sujeitos e métodos Quinhentos e vinte e seis pacientes anteriormente submetidos à tiroidectomia por doença de Graves entre 2006 e 2013 foram avaliados retrospectivamente. Os pacientes que receberam tratamento com iodo radioativo e irradiação externa da região do pescoço e que anteriormente passaram por cirurgia de tiroide não foram incluídos no estudo. Resultados Enquanto os nódulos de tiroide se apresentaram em 177 (33,6%) dos 526 pacientes com doença de Graves, eles estiveram ausentes em 349 (66,4%) pacientes. Um total de 42 (8%) dos pacientes teve câncer de tiroide. A ocorrência de câncer de tiroide foi 5,4% (n = 19) nos pacientes com doença de Graves que não apresentaram nódulos, e 13% (n = 23) nos pacientes com nódulos. O risco de câncer de tiroide aumentou significativamente na presença de nódulos (p = 0,003). Três pacientes apresentaram recidivas. Nenhum paciente apresentou metástase distante e nenhum paciente veio a óbito durante o período de acompanhamento. Conclusões Pacientes com doença de Graves devem ser avaliados cuidadosamente no acompanhamento para a possível ocorrência de câncer de tiroide. Arq Bras Endocrinol Metab. 2014;58(9):933-8 .

Two cases of thyroid sarcoidosis presentation as painful, recurrent goiter in patients with Graves' disease / Dois casos de sarcoidose na tireoide com apresentação na forma de bócios recorrentes dolorosos em pacientes com doença de Graves

Sarcoidosis rarely involves the thyroid gland. Pain in the thyroid gland area was only sporadically reported in patients suffering from this disease. The aim of this paper is to report and discuss the cases of two female patients with Graves' disease who presented painful, rapidly growing, recurrent goiters (after strumectomy in their early adult lives). Invasive treatment was applied and sarcoidosis was revealed histologically. The first patient suffered from dysphagia and dyspnoea due to large goiter; skin lesions were present as well. Sarcoidosis was diagnosed in histological examination of the thyroid tissue specimens. Steroid treatment was ineffective; thus, the thyroid was removed. Two years later thyroid sarcoidosis recurred as a painful goiter and surgical treatment was applied once again. In the second case, thyroid ultrasound findings suggesting malignancy, and prompted the decision to perform thyroidectomy despite the fact that FNAB (fine needle aspiration biopsy) revealed cells indicative of a "granulomatous disease in the post-resection scar" and results of the thorax high-resolution computed tomography scan suggested pulmonary sarcoidosis. Pathological examination confirmed sarcoidosis. However, a papillary cancer focus was also found.

A sarcoidose raramente envolve a glândula tireoide, e apenas esporadicamente foi relatada dor na região da glândula em pacientes que sofrem dessa doença. O objetivo deste trabalho é relatar e discutir os casos de duas mulheres que apresentavam bócios dolorosos, de rápido crescimento e recorrentes (após tireoidectomia na adolescência). Foi usado um tratamento invasivo e a sarcoidose foi revelada pelos achados histológicos. A primeira paciente sofria de disfagia e dispneia em decorrência de um grande bócio; lesões cutâneas também estavam presentes. A sarcoidose foi diagnosticada em um exame histológico das amostras de tecido da tireoide. O tratamento com esteroides foi ineficaz; foi feita assim a ressecção da glândula. Dois anos depois, houve recidiva da sarcoidose da tireoide como um bócio doloroso, e o tratamento cirúrgico foi feito mais uma vez. No segundo caso, os resultados do ultrassom da tireoide sugeriam malignidade e levaram à decisão de se realizar a tireoidectomia, apesar de as células de PAAF indicarem uma doença granulomatosa na cicatriz pós-ressecção e os resultados da tomografia computadorizada de alta resolução de tórax sugerirem sarcoidose pulmonar. O exame histopatológico da glândula revelou sarcoidose. Entretanto, também foi encontrado um foco de câncer papilar.

El carcinoma diferenciado incidental de tiroides es menos prevalente en la enfermedad de Graves que en el bocio multinodular / Incidental differentiated thyroid carcinoma is less prevalent in Graves’ disease than in multinodular goiter

Objetivos Entre los factores moduladores de prevalencia de carcinoma diferenciado de tiroides (CDT) destacan la concentración plasmática de TSH, la nodularidad tiroidea y la asociación con la autoinmunidad. La TSH estimula la proliferación de células foliculares normales y neoplásicas. Los anticuerpos contra el receptor de TSH (TSI), por su acción TSH-like, deberían estimular el crecimiento del CDT. El objetivo fue comparar la prevalencia de CDT incidental en pacientes tiroidectomizados por enfermedad benigna. Pacientes y métodos Se estudió la anatomía patológica de 372 pacientes con diagnósticos prequirúrgicos de bocio multinodular normofuncionante (BMN) o hipertiroidismo. La gammagrafía, y/o presencia de TSI diferenció entre bocio multinodular hiperfuncionante (BMH) y enfermedad de Graves (EG). Se comparó la prevalencia de CDT en cada categoría (χ). Resultados Se encontraron 221 sujetos con BMN, 125 con EG y 26 con BMH. Se hallaron 58 CDT con la siguiente distribución: BMN, 49 (22,2%); EG, 8 (6,4%) y BMH, 1 (3,8%). La diferencia de prevalencia de CDT entre los grupos fue estadísticamente significativa (p<0,001). Ajustando por edad, el BMN tiene mayor prevalencia de CDT respecto a EG, con OR de 4,17 (p<0,001). El tamaño (mm) tumoral (media±DE) fue: 6,92±11,26; 1,97±1,85 y 9,0 en BMN, EG y BMH respectivamente (p=0,017). Conclusiones La prevalencia de CDT incidental es menor en EG que en BMN, siendo el resultado independiente de la edad. Este hallazgo puede indicar una predisposición hacia el desarrollo de CDT en pacientes con enfermedad nodular tiroidea y/o que la reacción autoinmunitaria puede resultar un factor protector contra el desarrollo de enfermedad neoplásica (AU)

Objective Risk factors for differentiated thyroid carcinoma (DTC) are poorly understood, but serum TSH levels, thyroid nodularity, and presence of autoimmunity are well-recognized factors that modulate DTC prevalence. TSH stimulates proliferation of both normal and neoplastic follicular cells. Consequently, thyroid-stimulating immunoglobulins (TSI), because of its TSH-like action, should induce DTC progression in patients with Graves’ disease (GD). The study objective was to compare the prevalence of incidental DTC in patients undergoing thyroidectomy for benign thyroid disease. Methods The pathology reports of 372 patients with preoperative diagnosis of euthyroid multinodular goiter (EMG) or hyperthyroidism were reviewed. Scintigraphy results and serum TSI levels were used to diagnosed either GD or hyperactive MG (HMG) to hyperthyroid subjects. Prevalence of DTC in each category was calculated using a Chi-square test. Results EMG, GD, and HMG were diagnosed in 221, 125, and 26 patients. There were 58 DTCs, distributed as follows [n (%)]: EMG, 49 (22.2%); GD, 8 (6.4%), and HMG, 1 (3.8%). Difference in prevalence of incidental DTC between the groups was statistically significant (p<0.001). After adjustment for age, patients with EMG had a greater DTC prevalence than GD patients, with an OR of 4.17 (p<0.001). Tumor size (mm, mean±SD) was 6.92±11.26, 1.97±1.85, and 9.0 for EMG, GD and HMG respectively (p=0.017). Conclusions Incidental DTC was less prevalent in GD as compared to EMG irrespective of age. This finding may suggest a predisposition to develop DTC in patients with thyroid nodular disease and/or a potential effect of autoimmunity to protect against development of neoplastic disease (AU)

Espessamento do tendão muscular na oftalmopatia de Graves / Muscle tendon enlargment in Graves´ophthalmopathy

OBJETIVO: Estudar a frequência do espessamento do tendão muscular em pacientes com oftalmopatia de Graves buscando estabelecer correlações com as diferentes formas clínicas da doença. A diversidade clínica e laboratorial na oftalmopatia de Graves pode levar à confusão quanto ao diagnóstico, conduta e prognóstico. Os achados radiológicos variam desde o aumento isolado do tecido adiposo até o espessamento da musculatura extraocular, caracteristicamente poupando os tendões. Em 2004,no entanto, Ben Simon descreveu o espessamento do tendão muscular na oftalmopatia de Graves. MÉTODOS: Foram avaliados 20 pacientes, de ambos os sexos, com idades entre 20 e 80 anos, com formas clínicas designadas como :forma benigna (retração palpebral),forma intermediária (diplopia na posição primária do olhar) e forma maligna ou infiltrativa (sinais de comprometimento do nervo óptico).Todos os pacientes foram submetidos à tomografias computadorizadas de órbita. Os pacientes estavam eutiroideanos, há pelo menos um ano. Os padrões tomográficos foram estudados e divididos em dois grupos: com e sem espessamento dos tendões da musculatura extraocular. RESULTADOS: Uma relação estatisticamente significativa entre espessamento do tendão e a forma clínica intermediária foi encontrada (p <0,012). CONCLUSÃO: O espessamento do tendão extraocular, encontrado em 30 por cento dos pacientes com oftalmopatia de Graves, relaciona-se positivamente com a forma intermediária da doença, caracterizada pela presença de diplopia e que constitui um achado de grande valor clínico.

PURPOSE: The aim is therefore to study the frequency of tendon enlargment in Graves' ophthalmopathy, seeking to estabilish its clinical correlations. Clinical and laboratory diversity in Graves' Ophthalmopathy sometimes may mislead its diagnosis. Radiological findings are more reliable for the diagnosis of Graves' Ophthalmopathy. Since then, a number of patterns have been described. Extraocular muscle involvement in this pathology is considered as always sparing the tendons. In 2004, Ben Simon described extraocular muscles tendon enlargment in some patients with diplopia in Graves' orbitopathy. METHODS: 20 patients, aged between 20 and 80 years, of both sexes, designated as benign (eyelid retraction), intermediate(diplopia in primary sight position) and malignant or infiltrative(signs of optic nerve compromise) forms were evaluated by orbital tomography. All patients had already been euthyroidean for at least one year. Tomographic patterns were studied and divided into two groups: with or without extraocular muscle tendons enlargment. RESULTS: Statistically significant relationship was found between tendon enlargment and intermediate form (p<0.012). CONCLUSION: Extraocular tendon involvement present in 30 percent of the patients with Graves' ophthalmopathy, and is positively correlated to intermediary form of the disease, characterized by diplopia, a very important clinical landmark.

Fatal outcome of a young woman with papillary thyroid carcinoma and graves' disease: possible implication of "cross-signalling" mechanism / Desfecho Fatal de uma Paciente com Carcinoma Papilífero de Tiróide e Doença de Graves: possível Implicação do Mecanismo de Sinalização Cruzada

A 29 yrs-old patient was referred to our hospital due to generalized convulsions. She had hyperthyroidism treated with methimazole. Her MRI showed 4 metastatic lesions in the brain. She had a goiter with a "cold" nodule and a palpable ipsilateral lymph node. The FNAB disclosed a papillary thyroid carcinoma. Under 5 mg of MMI treatment, she had a subclinical hyperthyroidism and TRAb were 47.8 percent (n.v. < 10 percent). The CT scan also showed lung metastasis. She underwent a total thyroidectomy with a modified neck dissection and she received an accumulated radioiodine dose of 700 mCi during the following two years. She died from the consequences of multiple metastatic lesions. Studies were performed in DNA extracted from paraffin-embedded tissue from the tumor, the metastatic lymph node and the non-tumoral thyroid. The genetic analysis of tumoral DNA revealed point mutations in two different genes: the wild type CAA at codon 61 of N-RAS mutated to CAT, replacing glycine by histidine (G61H) and the normal GCC sequence at codon 623 of the TSHR gene was replaced by TCC, changing the alanine by serine (A623S). In the non-tumoral tissue no mutations were found. In vitro studies showed a constitutive activation of the TSHR. It is very probable that this activating mutation of the TSHR is unable to reach the end point of the PKA cascade in the tumoral tissue. One possibility that could explain this is the presence of a cross-signaling mechanism generating a deviation of the TSH receptor cascade to the more proliferative one involving the MAPKinase, giving perhaps a more aggressive behavior of this papillary thyroid cancer.

Paciente de 29 anos foi encaminhada ao Hospital de Clínicas por causa de convulsões generalizadas. Apresentava hipertiroidismo tratado com metimazol (MMI). A ressonância magnética mostrava quatro lesões metastáticas cerebrais. Possuía bócio com nódulo frio e linfonodo palpável ipsilateral. Usando 5 mg de MMI, a paciente apresentava hipertiroidismo subclínico e TRAb = 47,8 por cento (normal < 10 por cento). A tomografia computadorizada também mostrava metástases pulmonares. A paciente foi submetida a tiroidectomia total com dissecção cervical modificada e recebeu dose acumulada de radioiodo de 700 mCi durante o período de dois anos. Foi analisado o DNA extraído de tecido emblocado em parafina do tumor, do linfonodo metastático e de tecido tiroidiano não-tumoral. Foram encontradas mutações pontuais em dois genes: uma substituição do genótipo selvagem CAA no códon 61 de /N-RAS/ por CAT, substituindo a glicina pela histidina (G61H) e uma substituição da seqüência normal GCC no códon 623 do gene TSHR por TCC, trocando a alanina pela serina (A623S). Não foram encontradas mutações no tecido não-tumoral. Estudos in vitro mostraram ativação constitutiva de TSHR. Já que esta mutação ativadora de TSHR foi incapaz de atingir o final da cascata PKA no tecido tumoral, sugere-se que um mecanismo de cross-signaling possa explicar o desvio da cascata do receptor de TSH para outra mais proliferativa, envolvendo MAPKinase e levando ao comportamento mais agressivo deste câncer papilífero.

Afección de los oblicuos superiores en la enfermedad de Graves / Superior oblique muscle disorder in Graves'Disease

El objetivo del trabajo es describir las características clínicas y tomográficas de pacientes con estrabismo por Enfermedad de Graves, en quienes se verificó la afección de los músculos oblicuos superiores, hallazgo poco frecuente y escasamente reportado en la bibliografía médica.

Estado de salud de un grupo de pacientes esquizofrénicas crónicas internadas / Health condition in a group of chronic boarding schizophrenic patients

Introducción: Los pacientes esquizofrénicos presentan una tasa elñevada de morbilidad de otras enfermedades médicas, particularmente: obesidad, diabetes, hipertensión, consumo de tabaco y otras sustancias, etc. Así mismo, presentan una conducta más pasiva, aislamiento social y contactos deficientes con los servicios sanitarios. Objetivos: Estudiar la comorbilidad y la conducta de salud de un grupo de pacientes esquiénicos, crónicas e institucionalizados. Material y método: - Población: 66 pacientes diagnosticadas de esquizofrenia según CIE-10. Con una edad media de 57,85 años y con un tiempo medio de internamiento de 27,3 años. Material: se recogieron datos de la historia clínica y como instrumento evaluativo de la salud física usamos el Índice Acumulativo de Enfermedad (IAE). Se utilizó también la Escala de Evaluación de la Actividad Global (EEAG) y la escala de Impresión Clínica Global (CGI). Método: estudio transversal de carácter descriptivo. Resultados: La puntuación media dela EEAG es de 34,24 y según la CGI es de 89,4% de las pacientes son severa o extremadamente enfermas. Según el IAE, el total del número de categorías incluidas arroja una media de 3,36 por paciente, con un índice de gravedad medio por paciente de 1,9. En cuanto a las enfermedades más habituales destacan las de sistemas: cardíaco, vascular y endocrinometabólico. La demanda de asistencia sanitaria está elevada. La conducta es muy deteriorada, con un número importante de pacientes que no reciben visitas, o no salen, o no participan en programas terapéuticos. Conclusiones: Nuestras pacientes presentan una elevada tasa de otras enfermedades médicas: obesidad, hipertensión, diabetes, consumo de tabaco. Así como una conducta muy pasiva y deteriorada

Introduction: The schizophrenic patients have high rates of morbility of other diseases, in particular: obesity, diabetes, hipertensión, drugs abuse, specially nicotina, etc. Likewise they present a more pasive behaviour, social isolation, and deficient contacts with the sanitary services. Objective: To study the comorbidity and the health behaviour in a group of chronic schizophrenic patients patients with long internment. Material and method: Population: 66 patients diagnosed of schizophrenia according to Cie-10. With an average age of 57.85 years, and with an average time of internment of 27.3 years. Material: data taken from medical history and we used the EEAG scale of evaluation of a global activity the IAE accumulative of disease index, and as well the Cgi scale of global clinical impression. Method: cross-sectional study of descrptive character. Results: the average the EEAG is 34.24 and according to the GGI a 89.4% of the patients are severely or extremely ill. The IAE show an average of the total the category of the 3.6 for patient, the index of severity for patients is the 1.9. The more usualy disease are of the cardiac, vascular and endocrine-metabolic systems. Teh demand of attendances is high. Teh behaviour id very damaged, there is an important number of patients that not receives visits, or not go out into the street, or not are participants into therapeutic programes. Conclusions: Our patients have a high rate of the other medical disease, obesity, hypertension, diabetes, tobacco consuncion. Anyway a very passive an damaged behaviour

Remission of Graves' hyperthyroidism treated with methimazole / Remisión del hipertiroidismo de la enfermedad de Graves tratado con metimazol Antecedentes

BACKGROUND: Long-term thionamide treatment is considered one of the main resources for Graves' hyperthyroidism. Although a 54.2 remission rate in patients so treated in Mexico was previously reported, most articles have shown a wide variation over time. In the present article we report the actual remission rate of long-term methimazole (MMZ) therapy of Graves' hyperthyroidism in Mexico. METHODS: We carried out a retrospective study of long-term MMZ treatment in 80 patients with Graves' hyperthyroidism with a postreatment follow-up of at least twelve months. Remission was considered by clinical as well as biochemical criteria. RESULTS: We studied 63 females and 17 males, mean age 37.7 +/- 10.4 years. Duration of symptoms was 13.3 +/- 20.7 months. Daily MMZ dose: 20.0 +/- 8.8 mg, treatment duration 16.7 +/- 8.9 months and follow-up was 34.8 +/- 60.3 months. Fourteen patients (17.5) are in remission and sixty six relapsed (82.5). Relapse occurred after a mean of an 11.9 +/- 11.8 month follow-up. Goiter size was the only statistically significant remission sign whereas age, disease duration, MMZ dose, exophthalmos, treatment duration or 1-thyroxine concomitant use were not useful predictive factors. CONCLUSIONS: Remission rate of long-term MMZ treatment of Graves' hyperthyroidism has substantially decreased in Mexico, since the previous report. We suggest that our results may be related to an increase of iodine intake or poor treatment, compliance. Goiter size was the only remission predictive sign. Due to our low remission rate we suggest Graves' disease patients must be selected for this kind of treatment.

Hipertiroidismos intervenidos en nuestro servicio en 5 años: resultados / Hyperthyroidisms taken part in our service in 5 years: results

El objetivo de nuestro estudio es revisar los resultados del tratamiento quirúrgico de todos los tipos de hipertiroidismo (enfermedad de Graves-Basedow, Bocio multinodular tóxico y nódulo tóxico). Para ello se diseñó un estudio retrospectivo con 60 pacientes consecutivos intervenidos en el servicio de otorrinolaringología del hospital Dr. Peset de Valencia entre 1993 y 1998. 4 pacientes se excluyeron del estudio por falta de seguimiento.Se realizó tiroidectomía subtotal a 22 pacientes con enfermedad de Graves-Basedow y 6 pacientes con bocio multinodular, tiroidectomía total a 8 pacientes con enfermedad de Graves-Basedow y 3 pacientes con bocio multinodular y hemitiroidectomía a 10 pacientes con nódulo tóxico y 6 pacientes con bocio multinodular.Los resultados fueron: Mortalidad: 0 por ciento, un paciente (1,8 por ciento) con parálisis de cuerda vocal transitoria, un paciente (1,8 por ciento) con parálisis de cuerda vocal definitiva, 3 pacientes (5,3 por ciento) con serohematoma, 2 pacientes (3,5 por ciento) con sangrado postoperatorio que necesitaron reintervención, un paciente con infección local, 10 pacientes (17,85 por ciento) con hipocalcemia transitoria, 2 pacientes (3,5 por ciento) con hipocalcemia definitiva.En cuanto a la función tiroidea el 35,7 por ciento quedaron eutiroideos, hipotiroideos el 57,1 por ciento e hipertiroideos el 7,1 por ciento.Por todo ello creemos que la cirugía es un buen procedimiento para la cura de todos los tipos de hipertiroidismo. (AU)

Orbitopatia tireóidea: análise clínica e epidemiológica / Thyroid Orbitopathy: Clinical and epidemiological analysis

Objetivo: Fazer uma análise estatística dos aspectos clínicos e epidemiológicos dos pacientes portadores de orbitopatia tireóidea. Local: Setor de Oftalmologia do Hospital Universitário Pedro Ernesto, Universidade do Estado do Rio de Janeiro. Método: Realizou-se um estudo prospectivo de 14 pacientes portadores de orbitopatia tireóidea, os quais foram submetidos a exame oftalmológico completo. Resultado: As queixas mais freqüentes foram ardência e sensaçäo de corpo estranho em 85.71 dos casos. Ao exame, foi detectado diminuiçäo do tempo de ruptura do filme lacrimal em 85.71 por cento dos casos, retraçäo palpebral em 78.57 por cento (unilateral em 28.65 por cento e bilateral em 50 por cento), proptose em 50 por cento (unilateral em 14.29 por cento e bilateral em 35.71 por cento), alteraçöes corneanas em 21.43 por cento e de motilidade extrínseca em 14.29 por cento. Em nehum caso foi diagnosticada neuropatia óptica. Conclusäo: Os pacientes com orbitopatia tireóidea, em grande parte das vezes, apresentam queixas inespecíficas que devem ser consideradas como elementos de suspeiçäo para o diagnóstico.

Cáncer tiroideo en el hipertiroidismo: una asociación no tan excepcional / Thyroid cancer in hyperthyroidism: not such an uncommon association

Objetivo. Analizar la tasa de asociación entre hipertiroi dismo y cáncer tiroideo en nuestra experiencia, así como la que existe con los distintos tipos de enfermedades tiroideas que cursan con hipertiroidismo. Pacientes y métodos. Se han estudiado, de forma retrospectiva, las piezas quirúrgicas y los historiales clínicos de aquellos pacientes intervenidos por hipertiroidismo y en los que se detectó un cáncer tiroideo en el estudio anatomopatológico. Los pacientes fueron agrupados según presentaran enfermedad de Graves-Basedow, bocio multinodular o adenoma tóxico. Resultados. En 10 casos de 265 pacientes se detectó un cáncer tiroideo asociado (3,8 por ciento). Fueron mayoría los pacientes con enfermedad de Graves (63 por ciento), aunque sólo el 3,5 por ciento de éstos presentaron asociación con cáncer, frente al 5,5 por ciento de los bocios multinodulares. No se encontró ningún caso en los pacientes con adenoma tóxico. Todos los casos de tumor correspondieron a cáncer papilar. En 3 casos se encontró multicentricidad del tumor en el mismo lóbulo. Conclusiones. Debe realizarse un estudio detallado de las piezas quirúrgicas en los pacientes intervenidos por hipertiroidismo y considerar siempre la posibilidad de esta asociación al planificar el tratamiento de estos pacientes (AU)