Overexpression of estrogen receptor GPER1 and G1 treatment reduces SARS-CoV-2 infection in BEAS-2B bronchial cells.

Gender-bias in COVID-19 severity has been suggested by clinical data. Experimental data in cell and animal models have demonstrated the role of sex hormones, particularly estrogens, in viral infections such as in COVID-19. SARS-CoV-2 uses ACE2 as a receptor to recognize host cells, and the protease TMPRSS2 for priming the Spike protein, facilitating virus entry into cells. However, the involvement of estrogenic receptors in SARS-CoV-2 infection are still being explored. Thus, in order to investigate the role of estrogen and its receptors in COVID-19, the estrogen receptors ERα, ERß and GPER1 were overexpressed in bronchial BEAS-2B cell, and then infected with SARS-CoV-2. Interestingly, the levels of ACE2 and TMPRSS2 mRNA were higher in SARS-CoV-2-infected cells, but no difference was observed in cells with estrogen receptors overexpression. GPER1 can be involved in virus infection or replication, since its higher levels reduces SARS-CoV-2 load. On the other hand, pharmacological antagonism of GPER1 enhanced viral load. Those data suggest that GPER1 has an important role in SARS-CoV-2 infection.

The impact of the genetic background in a patient with papillary thyroid cancer and familial adenomatous polyposis

SUMMARY Thyroid cancer is the most common endocrine malignancy, and papillary thyroid carcinoma (PTC) is the main subtype. The cribriform morular variant is a histological phenotype of PTC characterized by its relationship with familial adenomatous polyposis (FAP). Description of the case: We report the genetic assessment of a 20-year-old female patient diagnosed with a cribriform-morular variant of PTC and FAP. We aimed to assess the genetic background of the reported patient, looking for variants that would help us explain the predisposition to tumorigenesis. Genomic DNA was extracted from peripheral blood lymphocytes, and whole exome sequencing was performed. We applied an overrepresentation and gene-set enrichment analysis to look for an accumulation of effects of variants in multiple genes at the genome. We found an overrepresentation of single nucleotide variants (SNVs) in extracellular matrix interactions and cell adhesion genes. Underrepresentation of SNVs in genes related to the regulation of autophagy and cell cycle control was also observed. We hypothesize that the package of alterations of our patient may help to explain why she presented colonic manifestations and thyroid cancer. Our findings suggest that multiple variants with minor impact, when considered together, may be helpful to characterize one particular clinical condition.

Comprehensive Assessment of Copy Number Alterations Uncovers Recurrent AIFM3 and DLK1 Copy Gain in Medullary Thyroid Carcinoma.

Medullary thyroid carcinoma (MTC) is a malignant tumor originating from thyroid C-cells that can occur either in sporadic (70-80%) or hereditary (20-30%) form. In this study we aimed to identify recurrent copy number alterations (CNA) that might be related to the pathogenesis or progression of MTC. We used Affymetrix SNP array 6.0 on MTC and paired-blood samples to identify CNA using PennCNV and Genotyping Console software. The algorithms identified recurrent copy number gains in chromosomes 15q, 10q, 14q and 22q in MTC, whereas 4q cumulated losses. Coding genes were identified within CNA regions. The quantitative PCR analysis performed in an independent series of MTCs (n = 51) confirmed focal recurrent copy number gains encompassing the DLK1 (14q32.2) and AIFM3 (22q11.21) genes. Immunohistochemistry confirmed AIFM3 and DLK1 expression in MTC cases, while no expression was found in normal thyroid tissues and few MTC samples were found with normal copy numbers. The functional relevance of CNA was also assessed by in silico analysis. CNA status correlated with protein expression (DLK1, p = 0.01), tumor size (DLK1, p = 0.04) and AJCC staging (AIFM3p = 0.01 and DLK1p = 0.05). These data provide a novel insight into MTC biology, and suggest a common CNA landscape, regardless of if it is sporadic or hereditary MTC.

17ß-estradiol reduces SARS-CoV-2 infection in vitro.

The COVID-19 has originated from Wuhan, China, in December 2019 and has been affecting the public health system, society, and economy in an unheard-of manner. There is no specific treatment or vaccine available for COVID-19. Previous data showed that men are more affected than women by COVID-19, then we hypothesized whether sex hormones could be protecting the female organism against the infection. VERO E6 cells have been commonly used as in vitro model for SARS-CoV-2 infection. In our experimental approach, we have treated VERO E6 cells with 17ß-estradiol to evaluate the modulation of SARS-CoV-2 infection in this cell line. Here we demonstrated that estrogen protein receptors ERα, ERß, and GPER1 are expressed by VERO E6 cells and could be used to study the effects of this steroid hormone. Previous and 24-hours post-infection, cells treated with 17ß-estradiol revealed a reduction in the viral load. Afterward, we found that SARS-CoV-2 infection per se results in ACE2 and TMPRSS2 increased gene expression in VERO E6-cell, which could be generating a cycle of virus infection in host cells. The estrogen treatment reduces the levels of the TMPRSS2, which are involved with SARS-CoV-2 infectiveness capacity, and hence, reducing the pathogenicity/genesis. These data suggest that estrogen could be a potential therapeutic target promoting cell protection against SARS-CoV-2. This opens new possibilities for further studies on 17ß-estradiol in human cell lines infected by SARS-CoV-2 and at least in part, explain why men developed a more severe COVID-19 compared to women.

Maternal glyphosate-based herbicide exposure alters antioxidant-related genes in the brain and serum metabolites of male rat offspring.

In response to the rapid development of genetically engineered glyphosate-tolerant crops, the use of glyphosate-based herbicides (GBHs), in agriculture, has increased substantially. Currently, it is estimated that 747 million kg of GBHs are applied per year. Although several epidemiological studies have demonstrated that there are health risks associated with GBH exposure, the effects these chemicals have on the oxidative and inflammatory response in the brain are still unclear. In fact, alterations in these processes could contribute to the development of neurological diseases, such as Alzheimer's disease and autism spectrum disorders. The present study exposed pregnant rats to GBH and evaluated changes in the expression of genes related to oxidnte defense and inflammation response and monitored the serum metabolome in the adult male offspring. Pregnant Wistar rats were administered distilled water or Roundup®, at either 5 and 50 mg/kg/day, (p.o.) from gestational day (GD) 18 to postnatal day (PND) 5. There was a significant increase in the gene expression levels of Neuroglobin (Ngb - oxygen storage and tissue protection) (105%, p = 0.031), Glutathione Peroxidase 1 (Gpx1 - oxidative stress) (95%, p = 0.005), Prostaglandin-Endoperoxidase Synthase 1 (Ptgs1 - inflammation) (109%, p = 0.033) and Hypoxia inducible factor 1 subunit alpha (Hif1α - oxygen sensor) (73%, p = 0.017), in the cerebellum of PND90 rats perinatally exposed to 50 mg GBH/kg/day. Moreover, both GBH-exposed groups displayed a significant decrease in the expression of Catalase (Cat - oxidative stress) (49%, p = 0.003; and 31% p = 0.050, respectively) expression, in the cortex. Serum metabolites analyses, from the same animals of each group, demonstrated that there were significant changes in the concentrations of lysophosphatidylcholine and phosphatidylcholine, which have been associated with neurodegenerative diseases. The results of the present study suggest GBH exposure during pregnancy alters the expression of genes associated with oxidant defense, inflammation and lipid metabolism. It is plausible that maternal GBH exposure could have lasting neuronal effects on the offspring later in life.

Evaluation of globins expression in brain, heart, and lung in rats exposed to side stream cigarette smoke.

The side stream cigarette smoke (SSCS) is a contributing factor in the pathogenesis of cigarette smoking-induced toxicity. Hemoglobin (Hb), myoglobin (Mb), neuroglobin (Ngb), and cytoglobin (Cygb) are globins with different distributions and functions in the tissues and have similar actions by providing O2 (oxygen) for respiratory chain, detoxification of ROS and nitric oxide (NO), and protect tissues against irreversible lesions. We aimed to investigate the effects of SSCS exposure on gene and protein expression of Ngb, Cygb, and Mb in different tissue. The Ngb and Cygb gene and protein expression in the cerebral cortex increased after 1 week of rat exposure to SSCS. In hippocampus, the Ngb gene and protein expression increased after 1 week or more of exposure and no change was observed in Cygb gene and protein expression. In myocardium, Mb and Cygb gene expression increased at 1 and 4 weeks of exposure, while protein expression of both increased at 1, 2, 3, and 4 weeks. In lung, observed an increase in Cygb gene and protein expression after 2, 3, and 4 weeks of exposure. The findings suggest that SSCS modulates Ngb, Cygb, and Mb in central and peripheral tissue © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1252-1261, 2017.

Clinical follow-up of two Brazilian subjects with glucokinase-MODY (MODY2) with description of a novel mutation / Seguimento clínico de dois pacientes brasileiros com MODY-glicoquinase (MODY2) e descrição de uma nova mutação

Mutations in the glucokinase gene (GCK) account for many cases of monogenic diabetes featuring maturity-onset diabetes of the young type 2 (MODY2). The clinical pattern of this form of hyperglycemia is rather stable, with a slight elevation in blood glucose, which is usually not progressive. Patients rarely require pharmacological interventions and microvascular complications related to diabetes are unusual. We describe the clinical follow-up of two cases of MODY2 with two different mutations in GCK gene, one in exon 7, p.Glu265Lys (c.793 G> A), which has been previously described, and a novel one, in exon 2, p.Ser69Stop (c. 206C> G). The clinical course of both cases shows similarity in metabolic control of this form of diabetes over the years. Arq Bras Endocrinol Metab. 2012;56(8):490-5.

Mutações no gene da glicoquinase (GCK) são determinantes de uma forma de diabetes monogênico denominada de MODY2 (maturity-onset diabetes of the young, tipo 2). O padrão clínico dessa forma de distúrbio glicêmico é bastante estável, com hiperglicemia leve, geralmente não progressiva. Intervenções farmacológicas raramente são necessárias e complicações crônicas secundárias ao diabetes são infrequentes. Descrevemos o acompanhamento clínico de dois casos de MODY2 com duas mutações diferentes, uma no éxon 7, p.Glu265Lys (c.793 G>A) já descrita anteriormente, e outra inédita no éxon 2 p.Ser69Stop (c. 206C>G). A evolução clínica de ambos os casos demonstra uma semelhança no padrão metabólico dessa forma de diabetes ao longo dos anos. Arq Bras Endocrinol Metab. 2012;56(8):490-5.

Lithium as an adjuvant in the postoperative ablation of remnant tissue in low-risk thyroid carcinoma.

BACKGROUND: Thyroid remnant ablation (RA) with 30 mCi of radioactive iodine (131I) in patients thyroidectomized for treatment of low-risk differentiated thyroid carcinoma (DTC) has a success rate of 64% to 84%. Lithium increases the residence time of 131I in the thyroid tissue. The aim of this study was to determine if lithium treatment added to 30 mCi 131I would enhance the success rate of this treatment compared with 30 mCi 131I alone in patients who were thyroidectomized for treatment of low-risk DTC. METHODS: This was a randomized study with endpoint at one year. Sixty one consecutive patients were enrolled and randomized into two groups: group A (n=32) treated with 30 mCi 131I; group B (n=29) treated with 30 mCi 131I plus an oral dose of lithium 900 mg/day, for 7 days. All patients were evaluated by whole body scan (WBS) with 123I and had serum TSH, thyroglobulin (Tg), and anti-Tg antibodies (TgAb) determined when they were hypothyroid on no thyroid hormone. Patients were reevaluated after one year with serum TSH, Tg, and TgAb determinations and WBS with 123I. The criteria for defining a successful outcome was a negative WBS and a serum Tg of <1. RESULTS: Group A was composed of 28 women and four men (ages 25-71 years) with 2 having follicular thyroid carcinoma (FTC), 22 having papillary thyroid carcinoma (PTC) of 1-4.5 cm, and 8 having micro PTCs (mPTC) of 0.3-0.8 cm. Group B was composed of 26 women and 3 men (ages 20-63 years) with 3 having FTC, 15 having PTC of 1.2-3.5 cm, and 11 having mPTC of 0.2-0.8 cm. All patients had a history of a WBS after their post-therapeutic 131I dose that showed uptake in the cervical region. After one year, 22 patients from group A had a negative WBS (68.75%) and in group B, 27 patients had a negative WBS (93.1%). The successful rates for the follow-up WBS were significantly different (p=0.017). There were 19 patients in group A in whom the initial Tg was positive. Of these, 14 had a negative follow-up Tg (73.7%). Group B had 9 patients with a positive initial Tg and all of them had a negative follow-up Tg (100%). CONCLUSION: The addition of lithium to treatment with 30 mCi 131I in thyroidectomized patients with low-risk DTC improved the efficacy of thyroid RA and therefore might be a better alternative than using higher doses of 131I for remnant ablation in these patients.

Humanidades médicas no Reino Unido: uma tendência mundial em educação médica hoje / Medical humanities in the UK: a world trendin medical education today

Este artigo tem por objetivo apresentar uma análise crítica do estado-da-arte da literatura sobre o movimento deintrodução das Humanidades Médicas em Educação Médica no Reino Unido, assim como as percepções e atitudes de estudantes de Medicina, acadêmicos e pesquisadores na área. Para tal foi realizada uma revisão crítica de literatura nas bases Ovid-SP e Scopus para os descritores na língua inglesa ‘medical humanities’, ‘medical education’, ‘humanities’, ‘humanisation’, ‘physicians’, ‘patients’, ‘medical students’, ‘British’, ‘England’, no período de 2000 a 2011, com publicações em língua inglesa e por referência cruzada. Tal pesquisa gerou um resultado de 34 artigos, dos quais 29 encontram-se diretamente referenciados neste texto que mostra a maneira como as Humanidades Médicaspassaram a ser uma florescente disciplina a ser introduzida em Escolas Médicas a partir da década de 1950, paralelamente entre E.U.A. e Reino Unido. Neste panorama, historicizamos as origens do processo de dissolução do ‘bom médico’ e delineamos o caminho por meio do qual o Reino Unido configurou-se como o berço da atual tendência mundial de humanização doscuidados em saúde. Desta maneira, o Reino Unido tem liderado o debate mundial com sua ampla experiência nas Humanidades em Saúde, primeiramente como instrumento de formação éticaem saúde e, mais recentemente, como linha de pesquisa para investigar os efeitos observados na integralidade da formação de médicos produzidos pelos variados modelos de sua implementaçãoem suas Escolas Médicas após a publicação dos Médicos de Amanhã pelo General Medical Council em 1995, cujo objetivo é o de resgatar o ‘good doctor’, o ‘bom médico’, para a prática clínica...

This editorial aims to present a critical analysis of the state-of-the-art literature on the initiative of introduction of the Medical Humanities into Medical Education in the United Kingdom, as well as the perceptions and attitudes of medical students,scholars and researchers in this field. For such purpose, a critical literature review was performed at the online bases Ovid-SP and Scopus for the keywords in the English language ‘medical humanities’, ‘medical education’, ‘humanities’, ‘humanisation’, ‘physicians’, ‘patients’, ‘medical students’, ‘British’, ‘England’,during the period from 2000 to 2011, also collecting publications by cross-referencing. This search produced a result of 34 papers, from which 29 were directly referenced in this work that shows the way through which the Medical Humanities became a flourishing discipline to be introduced in Medical Schools from the 1950’s on, simultaneously in the US and the UK. At this panorama, we historicised the origins of the dissolution process of the ‘good doctor’ and delineated the pathway by which the UK has becomethe focus of a worldwide trend in humanisation of the health care. As such, raising the world debate with the British both wide and effective experience of introduction of the Medical Humanities, firstly as an instrument for the ethical education in health, then, more recently, as a research strength to investigate the observed effects of the integrity in the education od doctors produced by itsseveral formats implementation across the Medical Schools in the UK, after the publication of Tomorrow’s Doctors by the General Medical Council in 1995, whose main aim was to “rescue” the‘good doctor’ back into the healthcare...

Clinical follow-up of two Brazilian subjects with glucokinase-MODY (MODY2) with description of a novel mutation.

Mutations in the glucokinase gene (GCK) account for many cases of monogenic diabetes featuring maturity-onset diabetes of the young type 2 (MODY2). The clinical pattern of this form of hyperglycemia is rather stable, with a slight elevation in blood glucose, which is usually not progressive. Patients rarely require pharmacological interventions and microvascular complications related to diabetes are unusual. We describe the clinical follow-up of two cases of MODY2 with two different mutations in GCK gene, one in exon 7, p.Glu265Lys (c.793 G> A), which has been previously described, and a novel one, in exon 2, p.Ser69Stop (c. 206C> G). The clinical course of both cases shows similarity in metabolic control of this form of diabetes over the years.

[Evaluation of clinical, laboratorial and ultrasonographic predicting factors of malignancy in thyroid nodules]. / Avaliação de fatores clínicos, laboratoriais e ultrassonográficos preditores de malignidade em nódulos tiroidianos.

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.

Avaliação de fatores clínicos, laboratoriais e ultrassonográficos preditores de malignidade em nódulos tiroidianos / Evaluation of clinical, laboratorial and ultrasonographic predicting factors of malignancy in thyroid nodules

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 por cento), indeterminada (23,3 por cento), maligna (8,6 por cento) ou não diagnóstica (7,6 por cento). A prevalência de câncer nas citologias indeterminadas foi 18,5 por cento (16 por cento nas lesões foliculares, 44 por cento nas suspeitas). O diagnóstico de malignidade foi 17,2 por cento (n = 70). A frequência de câncer em mulheres (15,2 por cento) foi menor do que em homens (27,9 por cento). 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.

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 percent), indeterminate (23,3 percent), malignant (8,3 percent) or nondiagnostic (7,6 percent). The prevalence of cancer in indeterminate citology was 18,5 percent (16 percent in follicular lesions, 44 percent in suspicious). The diagnosis of malignancy was 17,2 percent (n = 70). The frequency of cancer in women (15,2 percent) was lower than in men (27,9 percent). 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.

Ausência de mutações no proto-oncogene RET relacionadas com carcinoma medular de tireoide em pacientes com doença de Hirschsprung / Absence of RET proto-oncogene mutations related with medullary thyroid carcinoma in patients with Hirschsprung disease

Objetivo: O objetivo desse estudo é avaliar, em pacientes com Doença de Hirschsprung, a incidência e o tipo de mutações no proto-oncogene RET encontradas. Método: Foram estudados 15 pacientes com diagnóstico de Doença de Hirschsprung. As características fenotípicas foram obtidas através de entrevista com os pacientes e familiares e através de revisão de prontuário. As características genotípicas foram obtidas como se segue: dos leucócitos do sangue periférico foi extraído o DNA genômico. Amplificamos os exons 10, 13 e 16 através da Reação de Polimerase em Cadeia (PCR). O produto PCR foi purificado e submetido à sequenciamento direto, e os resultados do sequenciamento foram analisados utilizando sequências previamente depositadas no GeneBank. Resultados: Os pacientes apresentaram a distribuição por sexo de 13 do sexo masculino (86,7%) e 2 do sexo feminino (13,3%).A idade atual variou de 2 a 16 anos, com a média de 7 anos. Nenhum dos pacientes apresentou características fenotípicas de Neoplasia Endócrina Múltipla tipo 2A, 2B ou Carcinoma Medular de Tireoide Familiar, ou havia antecedente familiar positivo para essas doenças. Quanto às características genotípicas: o produto do sequenciamento genético, não apresentou alterações nos exons 10 e 16 em nenhum paciente, mas foi encontrado um polimorfismo em heterozigose no exon 13 no códon 769 em 4 pacientes. Conclusões: não foram encontradas mutações no proto-oncogene RET concomitantes à Neoplasia Endócrina Múltipla tipo 2A, 2B ou Carcinoma Medular de Tireoide Familiar, nos pacientes com Doença de Hirschsprung estudados, sendo encontrado polimorfismo no códon 769 em 4 pacientes.

Objective: To assess the frequency of mutations of the RET proto-oncogene in patients with Hirschsprung´s Disease and its association with Multiple Endocrine Neoplasia type 2. Method: 15 patients with Hirschsprung´s Disease were evaluated, regarding the phenotypic and genotypic characteristics. The phenotypic characteristics were obtained by interview and patients´ charts evaluation. Genotypic characteristics evaluation: genomic DNA was extracted from peripheral blood lymphocytes. Primers specific for exons 10, 13 e 16 of the RET gene were designed and used to generate Polimerase Chain Reaction products, which were purified and directly sequenced. The 3 exons were sequenced in both directions - sense and antisense - and the results analyzed using the sequences deposited on GeneBank. Results: Thirteen (86.7%) patients were male and 2 (13.3%) female. The age mean age was 7 years old, ranging from 2 to 16 years old. No patient presented phenotypic characteristics of Multiple Endocrine Neoplasia type 2, or familial history. Regarding the genotypic characteristics, no patient presented mutations on exons 10 or 16, but 4 patients presented a heterozigotic polymorphism on exon 13, codon 769. Conclusion: there was no concomitant mutation on the RET proto-oncogene, of Multiple Endocrine Neoplasia type 2 and Hirschsprung´s Disease in the patients studied.

Diagnóstico de metástase de carcinoma papilífero de tiróide através da pesquisa do RNA mensageiro da tiroglobulina / Diagnsotic of thyroid pappilary carcinoma metastasis by research of messenger RNA of thyroglobulin

É descrito um caso de carcinoma papilífero de tiróide pesquisado pelo RNA mensageiro da tiroglobulina (mRNA-Tg). A importância do método do mRNA-Tg no seguimento de pacientes com carcinoma diferenciado de tiróide em reposição tiroidiana é analisado.

Thyroid stimulating hormone levels in cord blood are not influenced by non-thyroidal mothers' diseases

CONTEXT: Screening programs not only offer the opportunity to trace and treat almost all cases of congenital hypothyroidism but also mean large savings to the health system. However, carefully planned strategies are necessary to extend their benefits and reduce costs. OBJECTIVE: To determine the possible influence of maternal diseases that affect maternal-fetal placenta dynamics on primary thyroid stimulating hormone (TSH) screening for congenital hypothyroidism. DESIGN: Prospective non-randomized clinical trial with at least 3 months of follow-up. SETTING: A public university referral center [CAISM/Hospital das Clínicas, Faculty of Medicine, University of Campinas, Campinas, SP]. PARTICIPANTS: 415 neonates divided into 5 groups: eighty-three infants born from cardiac mothers; 98 from mothers that had toxemia; 54 of the mothers had diabetes mellitus; 40 were HIV positive and 140 had no diseases. INTERVENTION: All newborns had cord blood samples collected on filter paper at birth. MAIN MEASUREMENTS: TSH was measured from dried blood spots using a homemade immunofluorescence assay (sensitivity in dried blood spots = 0.1 mU/L). RESULTS: There was no significant difference in the mean TSH levels among the 5 groups. Moreover, TSH levels were around 5 mU/L in 48 percent of the newborns, indicating that our region is severely deficient in iodine. CONCLUSIONS: Our results indicate that primary TSH screening programs using cord blood are not affected by maternal diseases. We suggest that, besides its technical advantages over heel punctures with T4 primary approaches, neonatal screening using primary cord blood TSH may also be used as a monitoring tool for evaluation and control of iodine deficiency disorders (IDD)

Desenvolvimento de um método imunofluorométrico para a medina de anticorpos séricos contra tiroglobulina / Development of an immunofluorometric method for measurement of serum antibodies against thyroglobulin

A pesquisa e quantificaçao de anticorpos séricos contra os antígenos tiroideanos tiroglobulina e tiroperoxidase apresenta grande interesse clínico. Neste trabalho descrevemos o desenvolvimento de um novo método para a pesquisa de anticorpos anti-tiroglobulina e a comparaçäo dos resultados obtidos com este método e os obtidos com um ensaio competitivo de referência para anticorpos anti-peroxidase tiroideana (anti-TPO). Tiroglobulina humana purificada é adsorvida em placas de microtitulaçäo e amostras ou controles säo adicionados numa diluiçäo de 1/100. Após duas horas de incubaçao a placa é lavada e acrescenta-se um monoclonal anti-IgG humana marcado com Európio. O monoclonal foi produzido em nossos laboratórios e reage com as quatro subclasses de IgG humano. A sensibilidade do método foi calculada em 40 UI/mL, e o erro interensaio é inferior a 5 por cento ao longo de toda a curva padräo. O método foi aplicado em 602 amostras de soro de rotina diagnóstica nos quais foi também realizada a pesquisa de anticorpos anti-TPO. Em 302 soros (50,2 por cento) ambos os testes foram negativos; em 178 (29,6 por cento) ambos foram positivos; em 62 (10,2 por cento) apenas o teste para anticorpos anti-tiroglobulina foi positivo e em 60 (10,0 por cento) apenas o teste para anticorpos anti-TPO foi positivo. O método nao sofre interferência de níveis elevados de tiroglobulina na amostra. Nossos achados sugerem que os resultados da pesquisa de anticorpos anti-tiroglobulina e anti-TPO com métodos sensíveis e específicos säo complementares no diagnóstico de doenças autoimunes da tiróide.

Estudo prospectivo dos efeitos da amiodarona na funçäo tiroidiana de pacientes chagásicos em área de deficiência de iodo / Prospective study of the effects of amiodarone of thiroid function in chagasic patients in an area of iodine deficiency

Com o objetivo de avaliar a funçao tiroidiana após uso crônico da amiodarona, em área de deficiência de iodo e endemia chagásica, 24 pacientes foram analisados antes e após três e nove meses de uso da droga. A avaliaçao constou de exame clínico, dosagem sérica de T4, T3, rT3, TSH, anticorpo antitiroglobulina e TSH 30 minutos após infusao venosa de uma ampola de 200 mug de TRH. A captaçao do iodo radioativo 131 e a cintilografia da tiróide foram realizadas antes e aos 9 meses após tratamento. Disfunçao tiroidiana ocorreu em 20,8 por cento dos pacientes sendo 12,5 por cento de hipertiroidismo e 8,3 por cento de hipotiroidismo, com anticorpos antitiroglobulina negativos. Captaçao do iodo radioativo 131 foi positiva em um paciente hipertiroide com bócio. O diagnóstico de hipertiroidismo foi melhor evidenciado pela resposta reduzida ou bloqueada do TSH ao TRH e nao pela concentraçao do T3 no soro e o de hipotiroidismo pela concentraçao elevada do TSH. O TSH elevado desde o início do tratamento pode predispor ao aparecimento de bócio. Concluímos que o uso da amiodarona em nossa regiao deve ser judiciosamente analisado, sendo a funçao tiroidiana cuidadosamente monitorizada antes e durante o tratamento.

Dosagem da tiroxina livre entre índios da floresta Amazônica oriental / Free thyroxine dosage of the Western Amazon

Os índios Xikrin do Cateté, Paracana do Paranati, Paracana do Marudjewara e Paracana do Bom Jardim, da floresta Amazônica Oriental, com dieta da caça, pesca, coleta e agricultura de subsistência, mostraram valores médios da tiroxina livre dentro dos valores da normalidade. Os valores médios da tiroxina livre dos Xikrin do Cateté, Paracana do Marudjewara e Paracana do Bom Jardim foram significantemente menores que o valor médio da tiroxina livre dos caucasóides urbanizados de Säo Paulo. O valor médio da tiroxina livre dos civilizados, significantemente maior que os valores médios da tiroxina livre dos Xikrin do Cateté, Paracana dos Marudjewara e Paracana do Bom Jardim, pode ser explicado pelo acesso ao sal iodetado e alimentos industrializados por parte dos que vivem em Sao Paulo. Os Paracanas do Paranati, o único dos grupos estudados com estrada, mostraram valor médio da tiroxina livre significantemente maior que o valor médio dos Paracana do Bom Jardim que é o grupo mais isolado e por último contatado.

A sindrome do T3 baixo e o crescimento da crianca com Diabetes Mellitus Insulino-Dependente / Syndrome of the T3 low and the growth of the child with Diabetes Mellitus Insulin-Dependent

Os hormonios tiroidianos sao de importancia fundamental para o crescimento somatico. Realizou-se um estudo de 35 criancas diabeticas com o objetivo de analisar se os niveis diminuidos do hormonio metabolicamente ativo, T3, pelo Diabetes Mellitus Insulino - Dependente teria uma possivel repercussao no crescimento estatural destas criancas. Os pacientes foram divididos em 2 grupos, conforme o grau de controle metabolico, medindo pelos niveis de hemoglobina glicosilada (HbAl). O grupo DI com 19 pacientes, apresentando controle metabolico bom e regular, HbAl < 12%, e o grupo DII com 16 pacientes de mau controle metabolico, HbAl < 12%. Os niveis medios de T3 dos diabeticos sem divisao em grupos (108 +- 25 ng/dl) foram significativamente menores que dos controle 132 +- 3l ng/dl,128 +- 24 ng/dl e 135 +- 34 ng/dl, respectivamente). Nao foram verificadasdiferencas nos outros parametros de funcao tiroidiana estudados (T4; T3/T4; rT3;rT3/rT3 e TSH) dos pacientes e das criancas nao diabeticas. No grupo de controlemetabolico bom e regular as concentracoes baixas de T3 relacionaram-se com os menores percentis de altura, mas nao houve correlacao entre essas variaveis no grupo do mau controle metabolico nem nos 35 pacientes sem divisao em grupos. O estudo sugeriu que o DMID alterou o metabolismo dos HT ao diminuir os niveis de T3, mas nao se pode afirmar que essas alteracoes interfiram no crescimento da crianca diabetica .