Iodo nutricional no Brasil: como estamos?

Brazilian legislation, since 1955, failed to achieve its objectives because the issue was not properly addressed: iodized salt was only available in endemic areas, at a low amount of 10 mg Iodine/kg salt. Lack of surveillance and cooperation were common errors. From 1982 to 1992, the INAN distributed potassium iodate to the industry free of charge, but it was abolished in 1991. Only four years later (1995) was a new law enacted effective in determining that all salt for human use should be iodized at levels established by the Health Authorities. During the period comprising 1998 to 2004, excessive iodination of salt (40 to 100 mg/kg) could lead to an increased prevalence of chronic autoimmune thyroiditis and iodine-induced hyperthyroidism. In 2003, the content of iodine/kg of salt was lowered to 20 to 60 mg I/kg salt. A national survey of schoolchildren is currently underway and will indicate the changes required for adequate iodine in salt for human use.A legislação para corrigir deficiência crônica de iodo no Brasil iniciou-se em 1955. O sal iodado seria distribuído somente em áreas endêmicas de bócio, com dose fixa de 10 mg Iodo/kg de sal. Na década de 1982 a 1992, o Instituto Nacional de Alimentação e Nutrição assumiu o Programa Nacional para a Deficiência Crônica de Iodo e forneceu o iodato de potássio a todos os produtores de sal. Em 1992, o INAN foi dissolvido. Nova legislação foi promulgada em 1995. A Anvisa ficou encarregada de supervisionar o teor de iodo em amostras de sal. No período de 1998 a 2004, o teor de iodo no sal foi elevado para 40 a 100 mg I/kg de sal. O excesso nutricional de iodo na população possivelmente aumentou a prevalência de tireoidite de Hashimoto e hipertireoidismo. Inquérito epidemiológico nacional (PNAISAL) em escolares, em execução, indicará as futuras determinações para a adição de iodo no sal

Avaliação preoperatória de nódulos thireóides: papel da ultrassonografia e da biópsia de aspiraçào por agulha fina, seguida de citologia

PURPOSE:To evaluate the preoperative assessment of thyroid nodules using ultrasound studies and cytology of nodular aspirates. SUBJECTS AND METHODS: 2,468 patients with thyroid nodules were examined from 1999 to 2005. All patients were clinically examined and underwent ultrasonography followed by fine-needle aspiration biopsy (FNAB) and cytology. RESULTS:Nodules larger than 10 mm were classified ultrasonographically in a 4-tier system and received a score according to the criterion of possible malignancy. Cytological examinations were conducted independently by 2 cytologists and classified as benign (score 1), indeterminate (score 2), suspicious (score 3), and malignant (score 6). Combining both scores, an index was generated that would indicate a higher probability of malignancy (benign, doubtful, suspicious, and malignant). Thyroid surgery was performed in 274 patients. Of those, 115 patients had a score of 2 to 5 and only 8 had a histological diagnosis of thyroid cancer (6.9%). For patients with a score of 5 (n = 51), 11.5% had a malignant lesion, and 51% of the 61 patients with a score of 6 had confirmed thyroid cancer. Of the 98 patients with a combined score of 7 to 10, 99% had a histological confirmation of malignancy. CONCLUSIONS: The index score had a sensitivity of 94.1% and specificity of 77.5%. The overall accuracy was 85.8%. Therefore, we concluded that this methodology may improve the preoperative diagnosis of thyroid cancer in nodules larger than 10 mm. Association with other methods such as color Doppler echography, serum TSH concentration, galectin-3 expression analysis, and FDG/PET scan would be useful in avoiding the higher costs of thyroid surgical procedures.OBJETIVO: Avaliar a possibilidade de diagnóstico pré-operativo de nódulos da tireóide (de diâmetro superior a 10mm) usando ultra-sonografia da glândula tireóide e citologia de punção aspirativa por agulha fina guiada pela ultra-sonografia. CASUÍSTICA E MÉTODOS: Nódulos tireóideos (maiores que 10mm) foram classificados ultra-sonograficamente em graus de I a IV e escores numéricos de 1 a 4, de acordo com crescente possibilidade de malignidade. O exame citológico, subseqüentemente, classificou os nódulos como benigno (escore 1) indeterminado (escore 2) suspeito (escore 3) e maligno (escore 6). Somando-se os escores obtidos nas duas metodologias obtém-se um índice considerado benigno (índice combinado 2-4), duvidoso (índice combinado 5) suspeito para malignidade (índice combinado 6) e elevada probabilidade de malignidade (índice combinado 7 a 10). Cirurgia da Tireóide foi realizada em 274 pacientes, dos quais 64 apresentavam índice de 2-4; destes, apenas 2 pacientes (3,1%) apresentaram comprovação histológica de câncer. Em pacientes com índice 5 (n= 51), 11,8% apresentaram câncer de tireóide e, em 61 pacientes com índice 6, (n= 31), 51% tiveram diagnóstico confirmado de malignidade. O índice combinado de 7-10 (n= 98) apresentou 99% de pacientes com câncer de tireóide. CONCLUSÕES: O índice combinado apresentou sensibilidade de 94,1% e especificidade de 77,5%. A precisão desta metodologia foi de 85,8%. Concluímos que o índice combinado pode ser útil no diagnóstico pré-cirúrgico do nódulo tireóideo, mormente se associado com outras metodologias como a ecografia com Doppler colorido, nível elevado de TSH sérico, análise de expressão de galectina-3 e imagens por FDG/PET

Congenital goiter with hypothyroidism caused by a 5′ splice site mutation in the thyroglobulin gene

In this work we have extended our initial molecular studies of a consanguineous family with two affected goitrous siblings (H.S.N. and Ac.S.N.) with defective thyroglobulin (Tg) synthesis and secretion because of a homozygotic deletion of a fragment of 138 nucleotides (nt) in the central region of the Tg mRNA, identified previously in H.S.N. In order to identify the intron/exon boundaries and to analyze the regions responsible for pre-mRNA processing corresponding to a 138 nt deletion, we performed a screening of a human genomic library. The intron/exon junction sequences were determined from one positive clone by sequencing both strands of the DNA template. The results showed that the deletion mapped between positions 5549 and 5686 of the Tg mRNA and corresponded to exon 30. The positions of the exon limits differed by three nucleotides from the previously reported data obtained from direct sequencing of the deleted reverse transcriptase-polymerase chain reaction fragment from H.S.N. These variations are because the intron/exon junctions in this region were not available at the time when the deletion was first described. The deletion does not affect the reading frame of the resulting mRNA and is potentially fully translatable into a Tg polypeptide chain that is shortened by 46 residues. The same 138 nt deletion was observed in reverse transcriptase-polymerase chain reaction studies performed in the thyroid tissues from Ac.S.N. Genomic DNA analysis showed that a G to T transversion was observed at position +1 in the donor site of intron 30. Both affected patients (H.S.N. and Ac.S.N.) are homozygous for the mutation whereas the normal sister (At.S.N.) had a normal allele pattern. The functional consequences of the deletion are related to structural changes in the protein molecule that either could modify the normal routing of the translation product through the membrane system of the cell or could impair the coupling reaction. Probably the mutant Tg polypeptide might be functionally active in the production of thyroid hormone, because in the presence of a normal iodine ingestion (∼150 μg/day), Ac.S.N. was able to maintain normal serum levels of total triiodothyronine (T3) associated with relatively low serum total thyroxine (T4) with normal somatic development without signs of brain damage.Fil: Targovnik, Hector Manuel. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Rivolta, Carina Marcela. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Mendive, Fernando M.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Moya, Christian M.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Vono, Jussara. Universidade de Sao Paulo; BrasilFil: Medeiros Neto, Geraldo. Universidade de Sao Paulo; Brasi

The Prevalence of Thyroid Dysfunction in Elderly Cardiology Patients with Mild Excessive Iodine Intake in the Urban Area of São Paulo

OBJECTIVES: To evaluate the prevalence of thyroid dysfunction in elderly cardiac patients in an outpatient setting. SUBJECTS AND METHODS: A total of 399 consecutive patients (268 women, age range 60-92 years) who were followed at Heart Institute were evaluated for thyroid dysfunction with serum free T4, TSH, anti-Peroxidase antibodies, urinary iodine excretion measurements and thyroid ultrasound. RESULTS: Hyperthyroidism (overt and subclinical) was present in 29 patients (6.5%), whereas hypothyroidism (overt and subclinical) was found in 32 individuals (8.1%). Cysts were detected in 11 patients (2.8%), single nodules were detected in 102 (25.6%), and multinodular goiters were detected in 34 (8.5%). Hashimoto's thyroiditis was present in 16.8% patients, most of whom were women (83.6%). The serum TSH increased with age and was significantly higher (p= <0.01) in patients, compared to the normal control group. No significant differences in serum TSH and free T4 values were observed when patients with atrial fibrillation (AF) where compared with those without arrhythmia. The median urinary iodine levels were 210 µg/L (40-856 µg/L), and iodine levels were higher in men than in women (p<0.01). Excessive iodine intake (urinary iodine >300 µg/L) was observed in one-third of patients (30.8%). CONCLUSIONS: Elderly patients have a higher prevalence of both hypo- and hyperthyroidism as well as thyroid nodules when compared with the general population. About one-third of the older patients had elevated urinary secretion of iodine and a higher prevalence of chronic Hashimoto's thyroiditis. It is recommended that ultrasonographic studies, tests for thyroid function and autoimmunity should be evaluated in elderly patients

Mutação monoalélica no gene da tireoperoxidase em paciente com hipotireoidismo congênito com defeito total de incorporação de iodeto

The aim of this study was to identify the genetic defect of a patient with dyshormonogenetic congenital hypothyroidisms (CH) with total iodide organification defect (TIOD). A male child diagnosed with CH during neonatal screening. Laboratory tests confirmed the permanent and severe CH with TIOD (99% perchlorate release). The coding sequence of TPO, DUOX2, and DUOXA2 genes and 2957 base pairs (bp) of the TPO promoter were sequenced. Molecular analysis of patient's DNA identified the heterozygous duplication GGCC (c.1186_1187insGGCC) in exon 8 of the TPO gene. No additional mutation was detected either in the TPO gene, TPO promoter, DUOX2 or DUOXA2 genes. We have described a patient with a clear TIOD causing severe goitrous CH due to a monoallelic TPO mutation. A plausible explanation for the association between an autosomal recessive disorder with a single TPO-mutated allele is the presence of monoallelic TPO expression.O objetivo deste estudo foi identificar defeitos genéticos em paciente com hipotireoidismo congênito (HC) por disormonogênese e defeito total de incorporação de iodeto (DIIT). Neonato do sexo masculino com HC diagnosticado pelo rastreamento neonatal. Exames clínicos e radiológicos confirmaram que o paciente apresentava HC severo e permanente com DIIT (teste de perclorato: 99%). A região codificadora dos genes TPO, DUOX2, DUOXA2 e 2957 pares de bases (pb) do promotor de TPO foram sequenciados. No paciente foi identificada a duplicação em heterozigose GGCC no éxon 8 do gene TPO (c.1186_1187insGGCC). Nenhuma outra mutação foi localizada nos genes TPO, incluindo o promotor, DUOX2 ou DUOXA2. Descrevemos paciente com grave defeito de organificação de iodeto, provocando HC severo com bócio, em consequência de uma única mutação monoalélica no gene TPO. A expressão monoalélica no tecido tireoideano explicaria a associação de uma doen­ça autossômica recessiva com uma única mutação monoalélica

Histopathological Characterization and Whole Exome Sequencing of Ectopic Thyroid: Fetal Architecture in a Functional Ectopic Gland from Adult Patient

Ectopic thyroid results from a migration defect of the developing gland during embryogenesis causing congenital hypothyroidism. But it has also been detected in asymptomatic individuals. This study aimed to investigate the histopathological, functional, and genetic features of human ectopic thyroids. Six samples were histologically examined, and the expression of the specific thyroid proteins was assessed by immunohistochemistry. Two samples were submitted to whole exome sequencing. An oropharynx sample showed immature fetal architecture tissue with clusters or cords of oval thyrocytes and small folliclesone sample exhibited a normal thyroid pattern while four showed colloid goiter. All ectopic thyroids expressed the specific thyroid genes and T4 at similar locations to those observed in normal thyroid. No somatic mutations associated with ectopic thyroid were found. This is the first immature thyroid fetal tissue observed in an ectopic thyroid due to the arrest of structural differentiation early in the colloid stage of development that proved able to synthesize thyroid hormone but not to respond to TSH. Despite the ability of all ectopic thyroids to synthetize specific thyroid proteins and T4, at some point in life, it may be insufficient to support body growth leading to hypothyroidism, as observed in some of the patients.FAPESP Grant [2009/53840-0]Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP), Sao Paulo, Brazil [2010/12005-9, 2014/24549-4]Instituto da TiroideUniv Sao Paulo FMUSP, Fac Med, Cellular & Mol Endocrine Lab, Thyroid Unit,LIM 25, Ave Doutor Arnaldo 455, BR-01246904 Sao Paulo, SP, BrazilSao Paulo Publ Hlth Serv, Adolfo Lutz Inst, Av Dr Arnaldo 355, BR-01246000 Sao Paulo, SP, BrazilHead & Neck Surg Santa Catarina Hosp, Av Paulista 200, BR-01310000 Sao Paulo, SP, BrazilUNESP, Botucatu Sch Med, Dept Internal Med, Av Prof Montenegro,S-N Dist Rubiao Jr, BR-18618687 Botucatu, SP, BrazilHosp Pediat Dr Juan Garrahan, Serv Endocrinol, Combate Pozos 1881,C1245AAM, Buenos Aires, DF, ArgentinaUniv Estadual Campinas, Fac Ciencias Med, Dept Cirurgia, Disciplina Cirurgia Cabeca & Pescoco, R Tessalia Vieira Camargo 126, BR-13083887 Campinas, SP, BrazilUniv Fortaleza Unifor, Med Sch, Av Washington Soares 1321, BR-60811905 Fortaleza, CE, BrazilUniv Fed Sao Paulo UNIFESP, Postgrad Program Biotechnol, Pedro Toledo 669, BR-04039903 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Postgrad Programs Biotechnol & Struct & Funct Bio, Dept Ciencias Biol, Thyroid Mol Sci Lab,UNIFESP, Pedro Toledo 669, BR-04039903 Sao Paulo, SP, BrazilHosp Sirio Libanes, Mol Oncol Ctr, Rua Prof Daher Cutait 69, BR-01308060 Sao Paulo, SP, BrazilUniv Fed Sao Paulo UNIFESP, Postgrad Program Biotechnol, Pedro Toledo 669, BR-04039903 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Postgrad Programs Biotechnol & Struct & Funct Bio, Dept Ciencias Biol, Thyroid Mol Sci Lab,UNIFESP, Pedro Toledo 669, BR-04039903 Sao Paulo, SP, BrazilFAPESP [2009/53840-0]FAPESP[2010/12005-9, 2014/24549-4]Web of Scienc

Anatomy and function of the vertebral column lymphatic network in mice

Cranial lymphatic vessels (LVs) are involved in the transport of fluids, macromolecules and central nervous system (CNS) immune responses. Little information about spinal LVs is available, because these delicate structures are embedded within vertebral tissues and difficult to visualize using traditional histology. Here we show an extended vertebral column LV network using three-dimensional imaging of decalcified iDISCO(+)-clarified spine segments. Vertebral LVs connect to peripheral sensory and sympathetic ganglia and form metameric vertebral circuits connecting to lymph nodes and the thoracic duct. They drain the epidural space and the dura mater around the spinal cord and associate with leukocytes. Vertebral LVs remodel extensively after spinal cord injury and VEGF-C-induced vertebral lymphangiogenesis exacerbates the inflammatory responses, T cell infiltration and demyelination following focal spinal cord lesion. Therefore, vertebral LVs add to skull meningeal LVs as gatekeepers of CNS immunity and may be potential targets to improve the maintenance and repair of spinal tissues.Peer reviewe