A variety of neurologic illnesses including peripheral and cranial neuropathies, central vestibular disease, seizures and coma have been associated with hypothyroidism in dogs. Repeated studies have shown that there is loss of blood brain barrier (BBB) integrity in these animals. Current research has also shown the development cerebrospinal fluid abnormalities in neurologically normal hypothyroid dogs; a finding that is related to BBB degradation. This derangement may be secondary to atherosclerosis and vascular accidents. One possible mediator of vasospasm and ischemic brain injury is endothelin-1 (ET-1). Another group of mediators of vascular dysfunction that has been found in CSF of dogs with various other CNS diseases is matrix metalloproteinases (MMP). The purpose of this study was to assay molecular markers that may contribute to disruption in the blood brain barrier in chronically hypothyroid canines. We hypothesized that BBB disruption in hypothyroidism is mediated by ET-1 and MMPs, as evidenced by increased concentrations of these proteins in CSF compared to controls. Cerebrospinal fluid (CSF) previously collected from 9 control and 9 experimentally induced hypothyroid dogs was used. Administration of I-131 was used to create the experimental model. CSF from time points 0, 6, 12, and 18 months post-induction were evaluated using an ELISA kit for endothelin-1. CSF from each time point was also evaluated using gelatinase zymography to detect MMP-2,9, and 14. The endothelin assay was able to detect ET-1 in CSF as determined by a spike and recovery method. However, ET-1 was undetectable in CSF of control and hypothyroid dogs at all time points. Constitutively expressed MMP-2 was detectable in all dogs at all time points. No other MMPs were detectable in CSF. ET-1 and gelatinase MMP,-9, and -14 are not primary mediators of BBB damage in chronically hypothyroid dogs. They could be involved secondarily and may be better evaluated with different assays or in temporal association with the development of clinical signs of neurologic dysfunction. Additional research is needed to confirm this finding and to evaluate biomarkers of non-vascular components of the BBB. / Master of Science

Many aspects of biological function are affected by hormones, from physiology to behavior, and the synthesis and release of hormones in vertebrates are regulated by the endocrine axes of control. A growing body of research shows that the mechanisms underlying the endocrine axes of control are complex and interconnected, with many hormones having multiple effects, and with many interactions between axes. In this study, I examined the effects of decreased thyroid function on the glucocorticoid stress response in Japanese quail, a potential interaction between the hypothalamic-pituitary thyroid (HPT) and hypothalamic-pituitary adrenal (HPA) axes of control. I used the thyroid inhibitor ammonium perchlorate (AP) for 2 weeks and 5 weeks to induce two states of decreased thyroid function: a thyroid challenged state, in which birds have depleted thyroidal T4 content, but still maintain euthyroid (normal) concentrations of plasma T4, and a hypothyroid state, in which birds have depleted thyroidal T4 content and decreased concentrations of plasma T4. Thyroid function was assessed by measuring plasma T4 concentrations, thyroidal T4 content, and thyroid gland mass. I took blood samples from birds both immediately prior to and immediately following a 30 minute confinement and agitation stressor to evaluate the effects of decreases in thyroid function on basal and stress-induced plasma corticosterone and plasma T4 concentrations. I found two key results: First, although baseline levels of plasma corticosterone were unchanged, the corticosterone stress response was significantly blunted in both the thyroid challenged and hypothyroid birds as compared to controls. This finding suggests that the HPT and HPA axes are functionally connected in birds, and other evidence suggests this connection is likely at the pituitary or hypothalamic level. Second, in hypothyroid birds, plasma T4 concentrations were elevated (into the euthyroid range) in response to the experimental stressor, although no change in plasma T4 was observed in thyroid challenged or control birds. This finding suggests that plasma T4 may have a permissive role in mounting a stress response. / Master of Science in Life Sciences

Avaliamos a função cardíaca frente a Isquemia e reperfusão, em corações isolados de ratas intactas, com hipotireoidismo (Hipo), hipotireoidismo subclínico (HTS), redução dos níveis de hormônios ovarianos (OO) e a ambas condições (HTS+OO). Na estabilização, a Pressão Desenvolvida pelo Ventrículo Esquerdo (LVDP), Pressão Diastólica Final (EDP) e Pressão de Perfusão não diferiram. Porém, a Primeira Derivada Positiva das Pressões (+dP/dt), Primeira Derivada Negativa das Pressões (-dP/dt) e frequência cardíaca foram menores no grupo Hipo. Na reperfusão, os corações Hipo tiveram EDP, +dP/dt e -dP/dt semelhantes a estabilização. Assim, sugere-se que o HTS, a OO e o HTS + OO não alteraram a recuperação cardíaca após a isquemia. E que o Hipo é resistente à lesão por isquemia, apesar da função cardíaca deprimida. / We evaluate the cardiac function in relation to an ischemia and reperfusion event in hearts isolated from intact rats, With hypothyroidism (Hypo), subclinical hypothyroidism (HTS), decreased levels of ovarian hormones (OO) and both conditions (HTS + OO). At etabilization the Left Ventricle Developed Pressure (LVDP), Final Diastolic Pressure (EDP) and Perfusion Pressure did not differ. However, the First Positive Pressure Derivative (+ dP / dt), First Negative Pressure Derivative (-dP / dt) and heart rate were lower in the Hypo group. On reperfusion the hypothyroid hearts presented EDP, + dP / dt and -dP / dt Similar to stabilization. Thus, it is suggested that HTS, a OO e o HTS + OO Did not change cardiac recovery after ischemia.Is that hipo is resistant to ischemia injury, despite depressed cardiac function.

Data of histochemical studies suggest that THs exert significant influences on myelination and the process of neuron degenerations leading to deficit in brain development. Results of IHC in this study are not fully matched to gene transcription results. It indicates that gene transcriptions may not be synonymous with gene translation. The ratio of RNA transcripts to proteins may differ among genes. It suggested that the transcriptional and morphological studies are supplementary to each other. / In this study, hypothyroidism was induced by different regimens. They are 0.05% methimazole (MMI), 0.02% MMI plus 1% NaC1O4, and 0.1% propyl-thiouracil in drinking water of mother rats from day 16 of their pregnancies, postnatal day 1 or day 4 to day 24. The replacement therapy was done by giving either a single s.c. injection of 300 nM T4 18 hrs before sacrifice on postnatal day 16, or by giving s.c. daily injections of 1.5 ng T3 plus 9 ng T4 per gram body weight from postnatal day 11 to 15. Olfactory bulb (OB), hippocampus (H) and cerebellum (CM) and in some cases also cerebral cortex (CX) were studied. The axon guidance molecules and their related genes, Galpha proteins, RGSs and small GTPases mRNA levels were examined with Real-Time quantitative RT-PCR. Special staining on sagittal frozen brain sections with histochemical and immunohistochemical (IHC) techniques were also studied. / It is well established that neonatal hypothyroidism causes defective development of the brain. As signals for synaptogenesis, growth factors and their receptors regulate the gene expression of the growth cone proteins and axon guidance molecules, and control the differentiation of neurons during brain development. Galpha proteins are signal transducers and regulators of G protein signaling (RGS) proteins are recently identified family of proteins that dampen G protein-coupled receptor-mediated signaling by accelerating the intrinsic GTPase activity of Galpha proteins. They play important roles in determining the intensity and specificity of signaling pathways in brain and their adaptations to synaptic activities. / The transcript abundance of some genes, such as Galphai1, Galphai2, Galphaol, Galphas, RGS 2, - 4, -5, -7, -8, -12, -16, -17, Mfn2, TRalpha1, TRbeta 1, Rheb, Rhes, Dexras1, Plexin1, Citron-Kinase, GAP-43, CRMP1, CRMP3, CRMP4 and CRMP5 in CM; Galpha12, Galphai3, G alphaol, Galphaolf, Galphaq, RGS 5, - 7, -8, -16, cdc42, Rhes, TC10, Dexras1, Citron-Kinase, TRalpha1, CRMP2, Wnt7A, Sema3A and GAP43 in OB and Galpha12, Galphai1 , Galphai2, Galphao2, RGS 5, -8, - 16, Mfn1, Mfn2, TRalpha1, Rhes, TC10, Dexras1, Citron-Kinase, GAP-43, CRMPI1, CRMP4, CRMP5 and Gda in H; TRalpha1, CRMP1, CRMP4, CRMP5, Plexin1, Plexin2, Gda and GAP-43 in CX are significantly altered in the neonatal hypothyroid rats. Of note, the mRNA levels of several genes were normalized by TH replacement therapy. Close correlations were found among various Galpha proteins, RGS genes, small GTPases and some axon guidance molecules in a brain- region- specific manner. Our results indicate certain direct or indirect transcriptional effects of the THs on the expression of brain development-related genes and these effects are probably under both temporal and spatial regulations during brain development. / by Yan, Ran. / "January 2007." / Advisers: Michael S. C. Tam; Chun Cheung Wong. / Source: Dissertation Abstracts International, Volume: 68-09, Section: B, page: 5776. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (p. 199-238). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

Thesis (M.Sc.)--University of Alberta, 2010. / A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfillment of the requirements for the degree of Master of Science in Environmental Health Sciences, School of Public Health. Title from pdf file main screen (viewed on April 27, 2010). Includes bibliographical references.

Introduction: Thyroid hormones (TH) during gestation are critical for fetal growth and development of hearing organ. The lack of maternal TH leads an inadequate development of Organ of Corti with malformation of internal sulcus, tectorial membrane, cochlear ductus and a hair cells differentiation. It can adversely affect the auditory system, which can cause a hearing loss. Experimental studies are performed with postnatal period hypothyroidism induction, but there are no investigations that induce at gestational period. The impact of thyroid hypofunction restricted to the embryonic period remains unknown, which makes this study unpublished. Objective: To evaluate the effect of gestational hypothyroidism on auditory function of adult offspring in rats. Methods: The research was composed by Wistar rats and it was approved by the Ethics Committee on Animal Research of Federal University of Sergipe (Protocol #21/15). Pregnant Wistar rats were given the antithyroid drug methimazole (0.02% - 1-methylimidazole-2-thiol – MMI, in drinking water, ad libitum) from gestational day (GD) 9 to delivery day (GD 21-22), and comprises a offspring from gestational MMI-treated dams group (OGMTD). To lactation hypothyroidism group [offspring from perinatal MMI-treated dams group (OPMTD)] the drug was given from 9ºGD to the 15th postnatal day (PND). Part of the OGMTD and OPMTD groups received replacement of HT with levothyroxine at the concentration of 50 μg / 100 mL in drinking water. All animals were evaluated by tympanometry, distortion product otoacoustic emission (DPOAE) and auditory evoked brainstem response (ABR) at 30, 60, 90 and 120 PND. Results: Our data demonstrated no middle ear dysfunction; regardless of hypothyroidism groups, compliance was lower than the control group (p<0,005). DPOAE was lower in OGMTD from 4 up to 12 kilohertz (kHz) and absent in OPMTD (p<0,001). On the other hand, ABR revealed normal integrity of neural auditory pathways up to brainstem level in the central nervous system, with no latency modification. Additionally, hypothyroidism groups presented a higher electrophysiological threshold (i.e., hearing loss), worse repercussion in OPMTD (p<0,001). Groups treated with levothyroxine did not reveal difference on hearing behavior compared to hypothyroidism groups. Our data suggest that gestational hypothyroidism leads to a cochlear damage function in offspring, with normality of the auditory pathways to the brainsten with moderate to profound sensorineural hearing loss. / Introdução: Os hormônios tireoidianos (HT) durante a gestação são críticos para o desenvolvimento do órgão da audição. A hipofunção da tireoide neste período provoca má formação do órgão de Corti, caracterizada por alteração no sulco interno, membrana tectorial, ducto colcear, além de dificuldade na diferenciação das células ciliadas. Estas alterações repercutem negativamente no sistema auditivo, que pode culminar em perda auditiva. Estudos experimentais são realizados com a indução do hipotireoidismo até o período pós-natal, porém não há pesquisas que induzam apenas no período gestacional. O impacto da hipofunção tireoidiana restrita ao período embrionário permanece desconhecida, o que torna este estudo inédito.Objetivo: Avaliar o efeito do hipotireoidismo gestacional experimental na função auditiva da prole adulta em ratos. Material e Método: A pesquisa foi realizada com ratos Wistar e foi aprovada pelo Comite de ética em pesquisa com animais da UFS, sob o número 21/2015. Foi administrado às ratas Wistar prenhes o fármaco antitireoidiano metimazol (0,02% - 1-metilimidazol-2-tiol, em água potável, ad libitum.) do nono dia gestacional (DG) até o dia do parto (21-22DG), e formaram o grupo da prole de mães induzidas ao hipotireodismo gestacional (PMHG). No grupo até a lactação [prole de mães induzidas ao hipotireodismo perinatal (PMHPN)], o fármaco metimazol foi administrado do 9ºDG ao 15º dia pós natal (DPN). Parte dos grupos PMHG e PMHPN receberam reposição dos HT com Levotiroxina na concentração de 50 μg/100 mL na água de beber. Todos os animais foram submetidos aos seguintes procedimentos: exames de timpanometria, emissão otoacústica por produto de distorção (EOAPD) e potencial evocado auditivo de tronco encefálico (PEATE) nas idades de 30, 60, 90 e 120 DPN. Resultados: Os dados não demonstraram disfunção da orelha média; porém os grupos induzidos ao hipotireidismo apresentaram menores valores de compliância que o grupo prole de mães eutiroidianas (p<0,05). EOAPD foi menor no PMHG de 4 a 12 kilohertz (kHz), com ausência de respostas no PMHPN (p<0,001). Por outro lado, o PEATE revelou integridade das vias auditivas neurais até o nível do tronco encefálico no sistema nervoso central, sem modificação de latência. Além disso, os grupos com hipofunção tireoidiana apresentaram maiores limiares eletrofisiológicos (isto é, perda auditiva), com pior repercussão no grupo PMHPN (p<0,001). Não foi observada reversão da hipofunção tireoidiana nos grupos que receberam o reposição dos HT, uma vez que apresentaram o mesmo comportamento auditivo funcional que os grupos sem o tratamento com levotiroxina. Conclusão: O hipotireoidismo gestacional altera a função coclear da prole, com normalidade da integridade das vias auditivas até tronco encefálico e presença de perda auditiva sensório neural de grau moderado a profundo. / Aracaju, SE

Secondary hypothyroidism is caused by treatment for hyperthyroidism and is a chronic condition. After adequate treatment, people can continue to experience persistent physical and depressive symptoms. There is a lack of research into the psychological factors involved in the condition, such as how people adjust to hypothyroidism. The study used Kelly’s (1955) Personal Construct Theory to explore the way in which patients construe (appraise) themselves with hypothyroidism and how this relates to coping, depression and hypothyroid symptoms. Twenty participants were recruited from an endocrinology clinic and online, through thyroid support organisations. Participants completed a semi-structured interview called a repertory grid and self-report measures of coping (Brief COPE), depression (HADS) and hypothyroid symptoms (ThySRQ). Repertory grid measures were extracted such as distances between different views of the self. The results showed that how unfavourably the self now was viewed compared to self before a thyroid disorder was positively correlated with depression, dysfunctional coping and hypothyroid symptoms. Identification with a negative view of hypothyroidism was associated with poorer mental and physical health and with dysfunctional coping. Polarized (i.e. black-and-white) construing and tight (i.e. rigid) construing were significantly and positively related to depression scores. Tightness of construing was also related to the number of hypothyroid symptoms experienced. Dysfunctional coping was positively correlated with depression and hypothyroid symptoms. Those with a history of depression experienced significantly more hypothyroid symptoms. Exploratory multiple regression analyses uncovered that how unfavourably the person viewed themselves now compared with before any thyroid problem, hypothyroid symptom frequency and dysfunctional coping accounted for 82.9% of the variance in depression. This highlights the importance of understanding how people construe the experience of hypothyroidism and their coping strategies and therefore psychological interventions may be helpful. Limitations include a small sample size and a correlational design, whereby cause and effect conclusions cannot be drawn.

Thyroxine is the main thyroid gland's hormone. The state, when the thyroid gland does not produce enough of it into the bloodstream is called hypothyroidism. Hypothyroidism is related with several health complications; therefore it is required to take replacement therapy in adequate doses. Concerning pregnant women, it is important especially to keep the blood level of thyroxine in the normal, because increasing or decreasing of it, has an adverse effect on the health of the mother and also on the normal child development. The objective of my thesis was to describe malformations spectra of thyroxine, to find out the beginning of its embryotoxicity dose range for chick embryos, and recalculate this value for human embryos, allowing us to decide, if the level of thyroxine was increased by a replacement therapy, this could be embryotoxic for human. The experimental part of my work was to search an alternative method for testing embryotoxicity on chick embryos in ovo - CHEST, testing of embryotoxic potential of the thyroxine. Embryotoxicity is a feature of the external factors affecting the embryo, it may manifest as lethality, growth retardation, and teratogenicity; which is an ability of the external factor to induce the developmental defect. The most common manifestation of embryotoxicity in this...

O objetivo deste estudo foi investigar os efeitos do hipotiroidismo experimental sobre o leito vascular da aorta torácica. Para a análise histológica foram realizadas colorações de hematoxilina-eosina, picrosirius e Weigert. Na análise de expressão proteica, foram realizadas as quantificações para colágeno I e III, elastina, MMP-9 e MMP-2, TIMP-1 e TIMP-2. As análises histológicas demonstraram uma diminuição da AST das aortas dos animais hipo e juntamente a esta alteração, foi constatada a diminuição da expressão proteica de colágeno do tipo I. Em relação à elastina, foi possível observar aumento da expressão deste elemento nas aortas dos animais hipotiroideos. Na avaliação da expressão proteica para MMP-9, foi possível verificar uma redução desta proteína no grupo hipotiroideo, assim como um aumento da expressão de TIMP-2. Frente aos presentes resultados, é possível sugerir que o estado hipometabólico desencadeado pelo hipotiroidismo afeta as CMLVs comprometendo mecanismos de síntese/degradação, alterando o importante arranjo da MEC presente na aorta torácica. / The aim of this study was to investigate hypothyroidism effects on thoracic aorta wall. For histological analyses were performed stains like hematoxilin-eosin, picrosirius and Weigert. In the protein expression assays were performed quantification for collagen I and III, elastin, MMP-9, MMP-2, TIMP-1 and TIMP-2. The histological analyses showed a decrease in aortas CSA and also a decrease in protein expression of collagen I in the hypo group. As regards to elastin, was possible to see an increase of this protein expression in hypo animals. In the evaluation for MMP-9 expression, was found a decrease in this protein and for TIMP-2 an increase in hypothyroidism group. Facing to these results, is possible to suggest that the hypometabolic state triggered by hypothyroidism, affects the VSMCs compromising mechanisms of synthesis/degradation and changing the important constitution of thoracic aorta ECM.

Contexto: Pacientes com tireoidite autoimune crônica com anticorpos de peroxidase tireoideana (Anti-TPO) podem progredir para hipotireoidismo subclínico e clínico. Estudos anteriores mostraram uma redução no anti-TPO em pacientes com hipotireoidismo que receberam tratamento de reposição de LT4 e suplementação de selênio. Objetivos: Avaliar se a selenometionina (SeMet) reduz o anti-TPO em pacientes anti-TPO positivos eutireoideos tratados com LT4 e melhora a ecogenecidade da tireoide em comparação com grupo de pacientes tratados com placebo. Desenho: Estudo duplo-cego aleatório controlado com placebo. Pacientes e métodos: Um total de 55 pacientes consecutivos com TCA (50 mulheres, 5 homens, idade mediana de 48 anos variando de 20 a 58), 4 tabagistas, 4 anos desde o diagnóstico da doença (mediana), com TSH normal ou levemente elevado, T4L dentro dos níveis normais, anti-TPO maior que 100 U/ml foram aleatoriamente selecionados para receber uma dose diária de 200 ?g de selenometionina (grupo SeMet; n = 28) ou placebo (grupo P; n = 27) por 3 meses. Anticorpos da tireoperoxidase e tireoglobulina (TPO-Ab; TG-Ab), TSH, FT4, T3, T4, proteína C-reativa (PCR), citocinas (IL6, IL10, TNF), glicose sanguínea em jejum, calcitonina, selênio plasmático, concentração de iodo na urina, atividade da peroxidase de glutationa 1 em eritrócitos (GPx1) foram dosados no basal, após 3 e 6 meses de acompanhamento. Polimorfismo do GPx1-Pro198Leu foi avaliado no basal. Foi efetuado ultrassom de tireoide (US) em cada ponto de acompanhamento. Ecogenecidade do tecido foi caracterizada por análise histográfica computadorizada em escala de cinza e expressa como índice de ecogenecidade (EI). A relação entre concentração de Selênio e atividade GPx1 nos eritrócitos foi analisada para cada genótipo. O IE e associações de variáveis clínicas também foram avaliadas. Resultados: Não houve diferenças nas características iniciais (basais) entre o grupo SeMet e P. Selênio plasmático e atividade GPx1 aumentaram no grupo SeMet mas não variaram no grupo P durante a suplementação de SeMet. Anti-TPO, anti-TG, TSH e hormônios tireoidianos não variaram significativamente no grupo P. Anti-TPO no grupo SeMet era de 1009 (176- >3000) no basal, 958 (161- > 3000) aos 3 meses e 768 (65-2821) U/ml aos 6 meses. Neste grupo, as variações em relação ao basal foram de -5% aos 3 meses e -24% aos 6 meses, respectivamente. No grupo P, as mudanças em relação ao basal foram de 1206 (154- >3000), 1404 (231- >3000), 1430 (140- >3000 U/ml), respectivamente (valores médios e limítrofes); +16% aos 3 meses e +18% aos 6 meses, respectivamente. Níveis de TSH, no grupo SeMet, foram de 1,7 (0,8 - 2,5) no basal, 3,0 (1,1 - 6,3) aos 3 meses e 3,2 (1,1 - 6,5) ?U/mL aos 6 meses, no grupo P, os níveis de TSH foram de 1,7 (0,8 - 2,5) no basal, 2,2 (0,6 - 6,8) e 2,5 (0,9 - 5,5) ?U/mL, respectivamente (valores médios e limítrofes). Valores médios da proteína C-reativa foram inferiores a 10mg/L nos dois grupos. O percentual dos genótipos no grupo SeMet eram de 7,1%, 64,3% e 28,6% para Leu/Leu, Pro/Leu e Pro/Pro (o genótipo mais frequente), respectivamente; no grupo P, a distribuição foi 0,0%, 51,9% e 48,1% para Leu/Leu, Pro/Leu e Pro/Pro, respectivamente, comparado com controles normais (11,4%, 39,2% e 49,4% Leu/Leu, Pro/Leu e Pro/Pro respectivamente). O IE exibiu tendência a uma diferença significativa indo de 1,2 no basal para 1,0 aos 3 meses e 1,1 aos 6 meses para o grupo SeMet, respectivamente, enquanto que permaneceu constante (1,2 no basal, 1,2 aos 3 meses e 1,2 aos 6 meses) para o grupo P, respectivamente. Após o período de suplementação, o coeficiente de correlação r = 0,95 (p < 0,001) para Pro/Pro e a tendência foi a mesma que o basal para o grupo Pro/Leu. No grupo SeMet, o IE correlacionou-se positivamente com a velocidade sistólica de pico nas artérias inferiores da tireoide no basal (r = 0,5, p = 0,008) e após o período de suplementação (r = 0,46; p = 0,025). Anti-TG correlacionou-se com valores do fator de necrose tumoral médios no grupo placebo (r = 0,46; p = 0,015). Conclusão: A suplementação por 3 meses aumentou os marcadores do status de selênio. SeMet parece ser eficaz em reduzir a ecogenecidade da tireoide e em reduzir o anti-TPO (porém não o anti-TG) após 3 meses de intervenção, mas não influencia o TSH ou os hormônios tireoideanos / Context: Autoimmune chronic thyroiditis (ACT) euthyroid subjects with positive thyroid peroxidase antibodies (TPO-Ab) may progress to subclinical and overt autoimmune hypothyroidism. Previous studies have shown a decrease in TPO-Ab in hypothyroid patients receiving LT4 replacement therapy plus selenium supplementation. Objectives: To evaluate in euthyroid TPOAb-positive LT4-treated subjects whether selenometionine (SeMet) decreases TPO-Ab and improves thyroid ecogenicity in comparison with placebo. Design: Randomized, placebo-controlled, double-blind study. Patients and methods: A total of 55 consecutive patients with ACT (50 F, 5 M, age median: 48, range: 20-58 years), 4 smokers, duration of disease (median) 4 years, normal or slightly elevated TSH and FT4 within the normal range, TPO-Ab >= 100 U/mL were randomized to receive 200 ?g selenometionine daily ((group SeMet; n = 28) or placebo (group P; n = 27) for 3 months. Thyroperoxidase and thyroglobulin autoantibodies (TPO-Ab; TG-Ab), TSH, FT4, T3, T4, C-reactive protein (CRP), cytokines (IL6, IL10, TNF), fasting blood glucose, calcitonin, plasma selenium, urine iodine concentrations, activity of glutathione peroxidase 1 in erythrocytes (GPx1) were estimated at baseline, after 3 and 6 months of follow-up; GPx1-Pro198Leu polymorphism was assessed at baseline. Thyroid ultrasound (US) was performed at each follow-up point. Tissue ecogenicity was characterized by computerized grey-scale histographic analysis and expressed as ecogenicity index (EI). The relationship between Se concentration and GPx1 erytrocyte activity was analysed for each genotype group. EI and clinical variables associations were also evaluated. Results: There were no differences in baseline characteristics between the SeMet group and the P group. During SeMet supplementation, plasma Se and GPx1 activity did not change in the P group, but increased in the SeMet group. TPO-Ab, anti-TG, TSH and thyroid hormones did not change significantly in group P. TPO-Ab in the SeMet group were 1009 (176- >3000) at baseline, 958 (161- >3000) at 3 months and 768 (65-2821) U/mL at 6 months. In this group change from baseline were -5 at 3 months and -24% at 6 months, respectively. In the P group change from baseline were 1206 (154- >3000), 1404 (231- >3000) and 1430 (140- >3000) U/mL, respectively (mean values with range); from baseline were +16 at 3 months and +18% at 6 months, respectively. TSH in the SeMet group were 1.7 (0·8-2·5) at baseline, 3·0 (1·1-6·3) at 3 months and 3.2 (1,1-6,5) uU/mL at 6 months; in the P group were 1·7 (0·8-2·4), 2·2 (0·6-6·8) and 2.5 (0.9-5.5) ?U/mL, respectively (mean values with range). C-reative protein mean level was <10 mg/L in both groups. Genotype proportions in the SeMet group were 7.1, 64.3, and 28,6% for Leu/Leu, Pro/Leu and Pro/Pro (the wild-type genotype), respectively; in the P group were 0.0, 51.9 and 48.1 for Leu/Leu, Pro/Leu and Pro/Pro, respectively compared with normal controls (11.4, 39.2 and 49.4%, Leu/Leu, Pro/Leu and Pro/Pro, respectively). EI exhibited a tendency towards a significant difference from 1.2 at baseline to 1.0 at 3 months and 1.1 at 6 months for the SeMet group, respectively and remained the same (1.2 at baseline, 1.2 at 3 months and 1.2 at 6 months) for the P group, respectively. For the SeMet group there was no significant correlation for Pro/Pro and Pro/Leu genotypes at the baseline. After the supplementation period, the correlation coefficient was r = 0.95 (p < 0.001) for Pro/Pro and the trend was the same as baseline for Pro/Leu. In the Semet group EI correlated positively with systolic peak velocity in the inferior thyroid arteries at baseline (r = 0.50; p = 0.008) and after supplementation period (r = 0,46; p = 0,025). Anti-TG correlated with tumor necrosis factor mean values in the Placebo group at baseline (r = 0,46; p = 0,015). Conclusion: Three months selenometionine supplementation increased markers of selenium status. SeMet seems to be effective in reducing thyroid echogenicity and in reducing TPO-Ab (but not TG-Ab) after 3 months of intervention, but does not influence TSH or thyroid hormones