Introdução: O Selênio é um mineral fundamental para o homem, participa dos mecanismos antioxidantes, influencia o sistema imune e participa ativamente da homeostase da glândula tireóide. Objetivo: Avaliar o estado nutricional relativo ao selênio de pacientes adultos portadores de hipotireoidismo e hipertireoidismo em atendimento ambulatorial no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo e no Hospital Universitário Walter Cantídio da Universidade Federal do Ceará. Metodologia: Foram avaliados quatro grupos de pacientes com doença de Graves (Graves), Bócio Multinodular Tóxico (BMNT), Hipotireoidismo pós-tireoidectomia (Hipotireoidismo) e tireoidite de Hashimoto (Hashimoto) em dois estados, São Paulo e Ceará e paralelamente dois grupos controle (São Paulo e Ceará). Foram realizadas caracterização antropométrica e clínica. O Se foi analisado no plasma e eritrócitos, foi medida a atividade da GSH-Px, iodúria, MDA plasmático e dosagens de hormônios tireoidianos e Anti-TPO. O consumo alimentar foi estimado utilizando-se a técnica de recordatório 24 horas. Resultados: Houve predomínio do sexo feminino em todos os grupos (70-90%); os pacientes e controles apresentaram sobrepeso. O TSH estava aumentado no grupoHashimoto do Ceará (116 ± 63,68 µU/mL) e o Anti-TPO no grupo Graves de São Paulo (1277,71 ± 1077,99U/mL). A maior concentração de Se no plasma foi encontrada no grupo BMNT de São Paulo (154,09µ/L) e nos eritrócitos no grupo BMNTdo Ceará (147,68µ/L). Os individuos do Ceará apresentaram maior consumo alimentar de iodo.Conclusões: Nosso estudo demonstrou que os pacientes do Ceará apresentaram melhor estado nutricional relativo ao selênio que os pacientes de São Paulo. Os grupos de São Paulo apresentaram deficiência leve em relação ao selênio. O consumo aumentado de selênio (Ceará) parece reduzir as concentrações de Anti-TPO e desta forma poderia ser um fator positivo para a redução da gravidade das doenças autoimunes da glândula tireóide. / Introduction: The Selenium is a mineral essential to human, part of antioxidant mechanisms, influences the immune system and participates actively in homeostasis of the thyroid gland. Objective: To evaluate the nutritional status of selenium on adult patients bearers of hypothyroidism and hyperthyroidism in ambulatory care at the Hospital of the Faculty of Medicine of the University of Sao Paulo and the University Hospital Walter Cantídio Federal University of Ceara. Methodology: We evaluated four groups of patients with Graves\' disease (Graves), multinodular toxic goiter (BMNT), hypothyroidism after thyroidectomy (hypothyroidism) and Hashimoto\'s thyroiditis (Hashimoto) in two states, Sao Paulo and Ceara and in two groups control (Sao Paulo and Ceara). We performed anthropometric and clinicai characterization. Selenium were analyzed in plasma and red blood cells, was measured the activity of GSH-Px, urinary iodine, MDA and plasma levels of thyroid hormones and anti-TPO. The food consumption was estimated using the technique to recall 24 hours. Results: There was a preponderance of females in all groups (70-90%); the patients and controls were overweight. The TSH was increased in the Hashimoto group of Ceará (116 ± 63.68 µU / ml) and Anti-TPO in the Graves group of Sao Paulo (1277.71 ± 1077.99 U / ml). The highest concentration of plasmatic selenium was found in BMNTgroup of Sao Paulo (154.09 &#181 / L) and the red cells in the BMNTgroup of Ceará (147.68 µ / L). The individuaLs from Ceara had higher dietary intake of iodine. Conclusions: Our study showed that patients from Ceara had better nutritional status on selenium that patients in Sao Paulo. Groups of Sao Paulo showed mild disabilities in relation to selenium. The increased consumption of selenium (Ceara) appears to reduce the concentrations of anti-TPO and thus could be a positive factor in reducing the severity of autoimmune diseases of the thyroid gland.

Le traitement initial des cancers différenciés de la thyroïde (CTD) consiste en une thyroïdectomie totale suivie, dans de nombreux cas par l’administration d’iode 131. Après thyroïdectomie totale, un traitement par iode 131 est indiqué en fonction des caractéristiques tumorales initiales. Chez les patients à risque élevé de rechute il est recommandé d’administrer une forte activité d’iode 131. Chez les patients à très faible risque il est recommandé de ne pas administrer d’iode 131. Dans le groupe intermédiaire, il a été montré par deux études prospectives multicentriques randomisées (ESTIMABL et HILO) qu’une activité de 1,1 GBq (30 mCi) administrée après TSHrh (Thyroid Stimulating Hormon recombinante humaine) était adaptée. La désescalade thérapeutique se poursuit dans le cadre d’un autre essai prospectif randomisé (ESTIMABL 2) comparant une activité de 30 mCi après injection de TSHrh à une simple surveillance. Chez les patients avec maladie résiduelle la tomographie par émission de positon couplée à un scanner (TEP/TDM) au fluorodesoxyglucose (FDG) est un examen clé avec une valeur à la fois diagnostique et thérapeutique. Les fixations de FDG permettent de localiser la maladie résiduelle, surtout lorsqu’elle ne capte pas l’iode. Chez les patients dont le site de récidive n’est pas déterminé par l’échographie cervicale, la TEP/TDM au FDG est plus sensible que la scintigraphie post-thérapeutique réalisée après administration d’une forte activité d’iode 131 (dite activité empirique) et est considéré comme l’examen de première intention. La réalisation d’une stimulation par TSHrh avant la TEP au FDG augmente le nombre de lésions détectées et donc sa sensibilité sans que les modifications thérapeutiques qui en découlent soient néanmoins significatives. Le rôle de la TEP FDG dans la sélection des patients nécessitant un traitement par inhibiteur de tyrosine kinase et dans l’évaluation antitumorale des inhibiteurs de tyrosine kinase reste à démontrer. L’utilisation d’ITK pour ré-induire les fixations d’iode 131 sont une voie majeure de développement pour les patients ayant une maladie réfractaire à l’iode 131. / Initial treatment of differentiated thyroid cancer is based on a total thyroidectomy and in many cases on the administration of radioactive iodine. Following total thyroidectomy, radioactive iodine is given, based on the primary tumor characteristics. In case of a very low risk of recurrence it is recommended not to give radioactive treatment. In case of high risk patients, a high activity of radioactive iodine is given after TSH stimulation. In case of intermediate risk patients, two randomized prospective studies (ESTIMABL and HILO) have shown that an activity of 1,1 GBq (30 mCi) given after rhTSH (recombinant human Thyroid Stimulating Hormon) was adequate. A further step is taken towards less treatment has now been undertaken with the ESTIMABL2 study, a prospective randomized study comparing a treatment with 1,1 GBq (30 mCi) of radioactive iodine treatment to follow-up without ablation. In patients with persistent disease, positron emission tomography with computed tomography (PET/CT) is a key examination used for its diagnostic and prognostic value. Foci of FDG uptake can localize residual disease, especially when it does not take up radioactive iodine. In patients in whom the site of recurrence remains unknown after a neck ultrasonography PET/CT with FDG is more sensitive than a post-therapeutic whole body scan performed after the administration of a high activity of radioactive iodine (empiric iodine) and should be considered as the first examination to perform. Injections of rhTSH before doing FDG PET/CT allow to increase the number of lesions detected, however the treatment changes linked to this preparation remains minor. The role of FDG PET/CT in the selection of patients to tyrosine kinase inhibitors (TKI) and to assess metabolic tumor response remains to be explored. The use of TKI to reinduce radioactive iodine uptake is a major research subject for patients with radioactive iodine refractory disease.

Cette thèse se divise en trois parties. La première partie concerne nos approches vers la fonctionnalisation régiosélective d’imines, générées in situ dans le milieu réactionnel. En particulier, nous avons développé une méthode de synthèse d’α-amidosulfures qui furent ensuite utilisés comme plateforme pour accéder à des α-aryles amines aliphatiques par réaction de Friedel-Crafts déclenchée par du NIS. La seconde partie de ce travail rapporte la synthèse de spirobiindane rigides optiquement actifs, que nous avons ensuite utilisés comme plateforme pour former des organocatalyseurs de type acides phosphoriques. Ces derniers furent ensuite exploités dans le développement d’une réaction de cycloaddition [3+2] -optionnellement amorcée par du PIDA- donnant accès à des 2,3-dihydrobenzofuranes optiquement actifs. Enfin, dans une dernière partie, deux séquences réactionnelles furent développées, donnant accès à des iodoarènes iodés : les BINIs et SPINIs ortho-diarylés. Ces structures furent engagées en organocatalyse, et ont permis d’apporter une approche rationnelle aux mécanismes d’induction asymétrique impliquant des espèces iodés hypervalentes. / This thesis is divided in three parts. The first part deals with our approaches toward regioselective functionalization of in situ generated imines. In particular, we had developed a synthesis of α-amidosulfides, which were used as substrates to access aliphatics α-aryles amines through a NIS-triggered Friedel-Crafts reaction. Second part of this work describe the synthesis of spirobiindane-based organocatalysts, which were used in a [3+2] cycloaddition - optionally triggered with PIDA - leading to optically actives 2,3-dihydrobenzofurans. Finally, two synthetic pathways were developed to form new class of aryliodides: diaryls BINIs & SPINIs. Those scaffolds were exploited to bring a rational explanation of chirality transfer in reactions using hypervalent iodine species.

Ces travaux concernent le développement de nouveaux iodanes chiraux et leur application à des réactions d’oxygénation asymétriques. Ces réactifs à base d’iode hypervalent constituent une alternative intéressante aux réactifs à base de métaux lourds en termes de réactivité et de toxicité. La première partie de ce travail a été consacrée à la synthèse de nouvelles structures originales C 2 -symétriques énantiopures de type S alen. Un criblage de conditions oxydantes a ensuite montré que seul le 3,3-diméthyldioxirane (DMDO) permet une oxydation propre et sélective de ces iodoarènes en iodanes-λ5 correspondants, composés isolables par simple filtration et dont la nature a pu être déterminée sans ambiguïté par analyse spectroscopique RMN 13C. Dans un second temps, ces nouveaux iodanes-λ5 chiraux ont été appliqués à des réactions d’oxygénation asymétriques, et plus particulièrement à la désaromatisation hydroxylante (réaction HPD) de 2-alkylphénols tels que le carvacrol et le thymol. Les meilleurs excès énantiomériques (ee) sont obtenus lorsque la réaction HPD est réalisée à température ambiante dans un mélange 85:15 de dichlorométhane/ trifluoroéthanol. Le carvacrol est ainsi converti en son cyclodimère [4+2] d’ortho -quinol naturel, le biscarvacrol, avec 55% de ee, et le thymol en bisthymol avec 68% de ee. / This work focuses on the development of new chiral iodanes and their application to asymmetric oxygenation reactions. These hypervalent iodine-based reagents represent an interesting alternative to heavy metal-based reagents in terms of reactivity and toxicity. The first part of this work consisted in the synthesis of new enantiopure C 2 -symmetrical Salen-type structures. A screening of oxidizing conditions then showed that only 3,3-dimethyldioxirane (DMDO) is able to mediate a clean and selective oxidation of these iodoarenes into to the corresponding λ5-iodanes, which were isolated by simple filtration and further characterized by 13C NMR spectroscopic analysis. In a second part, these new chiral λ5-iodanes were applied to asymmetric oxygenation reactions, in particular the Hydroxylative Phenol Dearomatization reaction (HPD reaction) of 2-alkylphenols such as carvacrol and thymol. Best enantiomeric excesses (ee) where obtained when the HPD reaction was performed in a 85:15 mixture of dichloromethane/ trifluoroethanol. Carvacrol was converted into its natural ortho -quinol-based [4+2] cyclodimer biscarvacrol with ee up to 55%, and thymol into bisthymol with ee up to 68%.

O desenvolvimento da Medicina Nuclear, aliado à evolução dos equipamentos de diagnóstico e terapia, necessita, cada vez mais, da disponibilidade comercial de radioisótopos. Nesse contexto, o IPEN tem buscado atender e abastecer o mercado nacional. Um dos investimentos nesta área foi a aquisição de um ciclotron de 30 MeV, modelo Cyclone-30, que permitiu a produção dos radioisótopos tais como, o 18F, 67Ga, 201Tl e o 123I, sendo este último o foco do presente trabalho. Através de dados de produções rotineiras de 123I via irradiação com prótons em alvo gasoso de Xenônio com enriquecimento superior a 99,8% em 124Xe, foi realizado um estudo para identificar os fatores relevantes que influenciam diretamente o rendimento de obtenção de 123I com altíssimo grau de pureza. Embora a metodologia seja bem conhecida, quando se trata de produção comercial há uma escassez de dados sobre os parâmetros operacionais utilizados. Os parâmetros avaliados foram: pressão do gás 124Xe, intensidade de corrente de feixe de prótons, tempo de irradiação, temperatura de operação do sistema durante a irradiação, tempo de espera para formação de 123I, tempo de aquecimento do porta-alvo para recuperação do 123I formado, temperatura de aquecimento da solução de lavagem e influência do revestimento interno da câmara de irradiação com Ni. Com os resultados obtidos, foi possível alterar as condições operacionais nas produções rotineiras, conduzindo a um aumento de eficiência do processo em torno de 30%. / The development of diagnosis equipment and therapy procedures in nuclear medicine depends on the availability of commercial radioisotopes. IPEN is the most important institution that provides radioisotopes for national market. In order to achieve this function, IPEN had invested in the acquisition of a 30 MeV Cyclone-30 cyclotron to produce mainly 18F, 67Ga, 201Tl and 123I. The 123I production is the aim of the present work. With the 123I routine production data obtained by proton irradiation of Xe targets with an enrichment greater than 99.8%, it was possible to identify the important parameters that have direct influence on the production yield of high purity degree 123I. Even though the methodology for the commercial production of 123I, there are an scarcity of operational parameters data for this task. In this work the evaluated parameters were: 124Xe pressure, proton beam quality, irradiation time, operational temperature of the irradiation system under irradiation, waiting time to obtain 123I, temperature of washing solution and the impact of the internal Ni coating in the target. With the obtained results it was possible to modify the operational conditions for routine production and increasing the efficiency in about 30%.

A Organização Mundial da Saúde (OMS) relata o câncer como uma das principais causas de morte no mundo. O câncer de próstata é o segundo tipo de câncer mais prevalente em homens. Uma modalidade de tratamento que vem sendo bastante utilizada é a braquiterapia, que consiste na introdução de sementes com material radioativo no interior do orgão. Sementes de Iodo-125 podem ser inseridas soltas ou em cordas poliméricas bioabsorvíveis. As sementes em cordas poliméricas apresentam algumas vantagens, pois reduzem a taxa de migração das sementes, evento que poderia afetar a dosimetria da região e causar danos desnecessários a tecidos ou órgãos sadios. Para as sementes de Iodo-125 em cordas poliméricas, utiliza-se a poliglactina 910, (poli(ácido lático-co-ácido glicólico)) (PLGA), com cobertura de poliglactina 370 (Vicryl®). Foi proposto neste trabalho, o estudo e desenvolvimento da metodologia de síntese do biopolímero PLGA, via polimerização por abertura de anéis, assim como sua caracterização, com o propósito de utilizar o material sintetizado para fabricar um material similar ao RAPID-Strand®. Os resultados obtidos demonstram que, através da metodologia utilizada, foi possível determinar os melhores parâmetros de reação (tempo e temperatura) para o PLGA na proporção 80/20 (lactídeo/glicolídeo). Com uma temperatura de 110ºC e tempo de reação de 24h, foi possível obter 86% de rendimento, e com o aumento o tempo de reação para 72h, o rendimento é superior a 90%. Os valores de massas moleculares obtidas entre os testes, ainda são muito baixos quando comparados com os valores obtidos por outros autores na literatura (cerca de 20%). Falhas na selagem das ampolas, deixando-os vulneráveis à umidade e oxigênio, ou a falta de uma sistema eficiente de agitação podem ser possíveis explicações para estes resultados. Um reator químico adequado poderia solucionar o problema. Em relação à caracterização, as técnicas utilizadas confirmaram a estrutura esperada do polímero, e a maior proporção das unidades provenientes do dímero lactídeo, em relação ao glicolídeo. / According to World Health Organization (WHO), cancer is a leading cause of death worldwide. Prostate cancer is the second most common cancer in men. A method of radiotherapy which has been extensively used is brachytherapy, where radioactive seeds are placed inside the area requiring treatment. Iodine-125 seeds can be placed loose or stranded in bioabsorbable polymers. Stranded seeds show some advantages, since they reduce the rate of seed migration, an event that could affect the dosimetry of the prostate and cause unnecessary damage to healthy tissues or organs. For Iodine-125 stranded seeds, polyglactin 910 (poly(lactic-co-glycolic acid)) (PLGA), with a coverage of polyglactin 370 (Vicryl ®) is used. It was purposed in this dissertation, the study and development of the synthesis methodology for PLGA via ring-opening polymerization, as well as its characterization, with the objective of using the synthesized material to manufacture a material similar to RAPID Strand®. The results obtained show that it was possible to determine the optimal reaction parameters (time and temperature) for PLGA in 80/20 (lactide/glycolide) ratio. Using a temperature of 110 ° C and reaction time of 24h, a yield of 86% was obtained, and increasing the reaction time to 72 hours, the yield was higher than 90%. The molecular mass values obtained from the samples are still very low compared to those obtained by other authors in the literature (about 20%). Failures in the sealing of vials, leaving them vulnerable to moisture and oxygen, or lack of an efficient stirring system might be possible explanations for these results. A suitable chemical reactor could solve the problem. Regarding polymer characterization, all techniques used not only confirmed the expected structure of the polymer, but also showed the highest proportion of lactide units compared to to glycolide units.

As expectativas da Organização Mundial de Saúde para o ano de 2030 são que o número de mortes por câncer seja de aproximadamente 13,2 milhões, evidenciando a elevada parcela desta doença no problema de saúde mundial. Com relação ao câncer de próstata, de acordo com o Instituto Nacional do Câncer, o número de casos diagnosticados no mundo em 2012 foi de aproximadamente 1,1 milhão, enquanto que no Brasil os dados indicam a incidência de 68 mil novos casos. O tratamento deste tipo de neoplasia pode ser realizado com cirurgia (prostatectomia) ou radioterapia. Dentre a radioterapia, podemos destacar a técnica de braquiterapia, a qual consiste na introdução (implante) de pequenas fontes radioativas (sementes) no interior da próstata, onde será entregue um valor elevado de dose no volume de tratamento e baixa dose nos tecidos ao redor. No Brasil, a classe médica estima uma demanda de aproximadamente 8000 sementes/mês, sendo o custo unitário de cada semente de pelo menos U$ 26,00. A Associação Americana de Físicos na Medicina publicou alguns documentos descrevendo quais parâmetros e análises devem ser realizadas para avaliações da distribuição de dose, como por exemplo, os parâmetros Constante de taxa de dose, Função radial e Função de anisotropia. Estes parâmetros podem ser obtidos através de medidas experimentais da distribuição de dose ou por simulações computacionais. Neste trabalho foram determinados os parâmetros dosimétricos da semente OncoSeed-6711 da empresa Oncura-GEHealthcare e da semente desenvolvida pelo Grupo de Dosimetria de Fontes de Braquiterapia do Centro de Tecnologia das Radiações (CTR IPEN-CNEN/SP) por simulação computacional da distribuição de dose utilizando o código MCNP5, baseado no Método de Monte Carlo. A semente 6711 foi modelada, assim como um sistema dosimétrico constituído por um objeto simulador cúbico de 30x30x30 cm3 preenchido com água. Os valores obtidos da semente 6711 foram comparados com alguns apresentados na literatura, onde o parâmetro Constante de taxa de dose apresentou erro relativo em relação ao valor publicado no TG- 43 de 0,1%, sendo que os outros parâmetros analisados também apresentaram boa concordância com os valores publicados na literatura. Deste modo, pode-se considerar que os parâmetros utilizados nas simulações (espectro, modelagem geométrica e avaliação de resultados) estão compatíveis com outros estudos, sendo estes parâmetros também utilizados nas simulações da semente do IPEN. Considerando as análises de incerteza estatística, os valores obtidos da semente do IPEN são semelhantes aos valores da semente 6711. / Expectations of the World Health Organization for the year 2030 are that the number of cancer deaths is approximately 13.2 million, reflecting the high proportion of this disease in global health issue. With respect to prostate cancer, according to the National Cancer Institute, the number of cases diagnosed worldwide in 2012 was approximately 1.1 million, while in Brazil the data demonstrated the incidence of 68,000 new cases. The treatment of cancer can be performed with surgery (prostatectomy) or radiation therapy. Among radiotherapy, we can highlight the brachytherapy technique, which consists in the introduction of small radioactive sources (seeds) within the prostate, which is delivered a high dose value in the treatment volume and low dose in the surrounding tissues. In Brazil, the medical profession estimates a demand of approximately 8000 seeds / month, and the unit cost of each seed at least US $ 26.00. The AAPM protocol TG-43 recommend the dose-rate constant, radial dose function and anisotropy function for dosimetric analysis LDR brachytherapy seeds. In this work, Monte Carlo simulations were performed in order to assess the dosimetric parameters of the OncoSeed-6711, manufactured by Oncura-GEHealthcare, and a seed developed by Radiation Technology Center, using the MCNP5 code. A 6711 seed, anIPEN seed and the 30x30x30cm3phantom filled with water were modeled to simulatethe dose distribution. The 6711 seed parameters were compared with literature, and the results presented relative error less than 0.1% for Λ. In comparison with the 6711 seed, the IPEN model seed dosimetric parameters were similar, account the statistical uncertainty.

O iodo em excesso promove o efeito Wolff-Chaikoff. Oligominerais já foram descritos como potenciais reguladores da expressão de proteínas. Tornou-se interessante avaliar se o iodo interferiria com a expressão do mRNA da NIS, em curtos períodos de tempo. Foram realizados, em ratos e células (de 30 min24h), estudos de expressão, comprimento de cauda poli-A e recrutamento para polissomos, do mRNA de NIS. Observou-se, in vivo e in vitro, que o excesso de iodo promoveu diminuição da expressão e do comprimento da cauda poli-A do mRNA de NIS, em todos os períodos estudados, além de promover menor recrutamento deste mRNA para os polissomos. A diminuição da cauda poli-A do mRNA de NIS pode ter aumentado sua instabilidade/degradação e também ter sido responsável por uma menor eficiência de tradução deste transcrito. Conclui-se que: (a) o iodo regula pós-transcricionalmente a expressão gênica da NIS, sendo fundamental nos processos que norteiam o efeito Wolff-Chaikoff e (b) oligoelementos têm relevância na regulação da expressão de proteínas relacionadas ao seu transporte. / Iodide in excess exerts the Wolff-Chaikoff effect. It is described that some minerals can regulate the expression of proteins. This study aimed to investigate if the iodide could modify the expression of NIS mRNA, in short periods of time. Rats and cells, divided in time-groups of 30 min up to 24h, were used in studies of expression, poly-A tale length and polysomal profile of NIS mRNA. Both in vivo and in vitro studies showed that the iodide treatment promoted a reduction in the expression and the poly-A length of NIS mRNA, in all time-groups, and decreased its recruitment to the polysomes. It is possible that the reduction of NIS mRNA poly-A tale length has increased the instability/degradation of this transcript, and impaired the translation efficiency of it. Concluding: a) the iodine exerts a post-transcriptional regulation of NIS mRNA expression, being essencial in the processes that guide the Wollf-Chaikoff effect; b) the oligoelements have an extremely important role in the expression regulation of proteins related to their transport.

<p>Studies were performed to improve iodine deficiency control programs. Goitre rates and cassava processing practices were compared in three Central African Republic (CAR) populations. Short-cuts in cassava processing were associated with elevated urinary thiocyanate and increased goitre rates, suggesting a goitrogenic effect in one population. While improved cassava processing may be beneficial, the priority is to correct the iodine deficiency. </p><p>The use of the urinary iodine/tiocyanate ratio as indicator of goitrogenic effects was explored using data from Tanzania and CAR. As the ratio can be calculated in four mathematically different ways and has physiological shortcomings, its use is discouraged.</p><p>Biannual iodised oil capsule (IOC) distribution in a Tanzanian population of 7 million during nine years was studied. Mean distribution coverage was 64%, mean delay of subsequent distribution 1.25 years, and only 43% of targeted person-time was covered. The cost of capsules constituted more than 90% of total program costs. It is cost-effective to invest more funds in communication, support of peripheral staff and supervision.</p><p>In a highland Tanzanian village, salt iodine content was highly variable compared to national standards. While school-children had adequate urinary iodine, women at delivery and newborns showed signs of in adequate iodine status. Salt iodine concentrations should be monitored during production and distribution down to household level, and iodine status assessed in all vulnerable groups before adjusting recommended salt iodization levels at production.</p><p>WHO's 1994 change in palpation goitre definition considerably lowered specificity and increased measured goitre rates by 25% in Tanzanian school-children compared to the previous system. Ultrasound estimation of thyroid volume under rugged field conditions requires considerable human and material resources yet had a precision only slightly better than palpation. In resource poor settings appropriately trained palpators using the 1960 WHO definition of goitre remain optimal for estimating thyroid size until precision and cost of ultrasound has improved.</p><p>Monitoring of process indicators needs to be an ongoing priority activity, separate from periodic evaluations of impact.</p>

Studies were performed to improve iodine deficiency control programs. Goitre rates and cassava processing practices were compared in three Central African Republic (CAR) populations. Short-cuts in cassava processing were associated with elevated urinary thiocyanate and increased goitre rates, suggesting a goitrogenic effect in one population. While improved cassava processing may be beneficial, the priority is to correct the iodine deficiency. The use of the urinary iodine/tiocyanate ratio as indicator of goitrogenic effects was explored using data from Tanzania and CAR. As the ratio can be calculated in four mathematically different ways and has physiological shortcomings, its use is discouraged. Biannual iodised oil capsule (IOC) distribution in a Tanzanian population of 7 million during nine years was studied. Mean distribution coverage was 64%, mean delay of subsequent distribution 1.25 years, and only 43% of targeted person-time was covered. The cost of capsules constituted more than 90% of total program costs. It is cost-effective to invest more funds in communication, support of peripheral staff and supervision. In a highland Tanzanian village, salt iodine content was highly variable compared to national standards. While school-children had adequate urinary iodine, women at delivery and newborns showed signs of in adequate iodine status. Salt iodine concentrations should be monitored during production and distribution down to household level, and iodine status assessed in all vulnerable groups before adjusting recommended salt iodization levels at production. WHO's 1994 change in palpation goitre definition considerably lowered specificity and increased measured goitre rates by 25% in Tanzanian school-children compared to the previous system. Ultrasound estimation of thyroid volume under rugged field conditions requires considerable human and material resources yet had a precision only slightly better than palpation. In resource poor settings appropriately trained palpators using the 1960 WHO definition of goitre remain optimal for estimating thyroid size until precision and cost of ultrasound has improved. Monitoring of process indicators needs to be an ongoing priority activity, separate from periodic evaluations of impact.