Celestino Neves

A polymorphism in the promoter region of the selenoprotein S gene (SEPS1) contributes to Hashimoto's thyroiditis susceptibility.

CONTEXT The association between selenium and inflammation and the relevance of selenoproteins in follicular thyroid cell physiology have pointed to a putative role of selenoproteins in the pathogenesis of autoimmune thyroid diseases. OBJECTIVE The aim of this study was to evaluate the role of a promoter variation in SEPS1, the selenoprotein S gene, in the risk for developing Hashimotos thyroiditis (HT). DESIGN A case-control study was performed to assess the association of genetic variation in the SEPS1 gene (SEPS1 -105G/A single-nucleotide polymorphism, rs28665122) and HT. SETTING The study was conducted in north Portugal, Porto, in the period of 2007-2013. PATIENTS OR OTHER PARTICIPANTS A total of 997 individuals comprising 481 HT patients and 516 unrelated controls were enrolled in the study. MAIN OUTCOME MEASURES Genetic variants were discriminated by real-time PCR using TaqMan single-nucleotide polymorphism genotyping assays. RESULTS There is a significant association between the SEPS1 -105 GA and AA genotypes and HT [odds ratio (OR) 2.24, confidence interval (CI) 1.67-3.02, P < 5.0 × 10(-7), and OR 2.08, CI 1.09-3.97, P = .0268, respectively]. The A allele carriers are in higher proportion in the patient group than in the control population (46.2% vs 28.1%, P < 5.0 × 10(-7)) with an OR (CI) of 2.22 (1.67-2.97). The proportion of patients carrying the A allele is significantly higher in male patients with HT, representing a 3.94 times increased risk (P = 7.9 × 10(-3)). CONCLUSION Our findings support the existence of a link between SEPS1 promoter genetic variation and HT risk.

Relations entre stabilité de l'agrégation et matière organique totale et soluble à l'eau chaude dans des sols ferrallitiques argileux (Congo, Brésil)

Organic matter (OM) generally plays an important role in soil aggregate stability. The objective of this work was to characterize the hot water-extractable OM and its role in the aggregate stability of clayey ferrallitic soils under different land use management. The macroaggregate (>200 µm) stability of these soils was determined before (AS) and after hot-water extraction (ASe). The contents in total organic carbon and in carbon present as carbohydrates, as well as the sugar composition, were determined on the bulk soils and their hot-water extracts.The carbon and macroaggregate contents decreased upon land-clearing and cultivation, but to a lesser extent when some cultural practices were used. Whatever the situation considered, the hot-water extract always presented a higher carbohydrate content than the bulk soil. The high values of ratios r = (galactose + mannose)/(arabinose + xylose) suggested that a large proportion of carbohydrates was of microbial origin. There were significant correlations betwee...

Antineutrophil cytoplasmic antibody (ANCA)-positive cutaneous leukocytoclastic vasculitis induced by propylthiouracil confirmed by positive patch test: a case report and review of the literature.

A 43-year-old female with antiphospholipid syndrome and Graves’ disease developed a cutaneous leukocytoclastic vasculitis associated with antineutrophil cytoplasmic antibody (ANCA) against myeloperoxidase (MPO-ANCA) and proteinase-3 (PR3-ANCA), whilst treated with propylthiouracil (PTU). The skin lesions were progressively resolved after withdrawal of PTU and treatment with oral steroids. Patch testing with PTU at 1%, 5%, and 10% in petrolatum was positive at 48 h. Despite positive ANCA titers after 1 year of follow-up, the patient maintains complete clinical remission. PTU is a common antithyroid drug, which has been known to induce ANCA-positive vasculitis. Although most patients with this rare side effect have a good outcome, some fatal cases have been reported. Therefore, patients treated with PTU should be carefully followed and monitored, not only for their thyroid state but also for early detection of potential serious complications of this drug. Early diagnosis and prompt cessation of PTU therapy are essential to improve the outcome. Also key aspects of PTU-induced ANCA-positive vasculitis are reviewed.

Selenium and Selenoproteins in Immune Mediated Thyroid Disorders

Selenium is an essential micronutrient that is required for the synthesis of selenocysteine-containing selenoproteins, processing a wide range of health effects. It is known that the thyroid is one of the tissues that contain more selenium. The “selenostasis” maintenance seems to contribute to the prevention of immune mediated thyroid disorders. Prospective, observational studies, randomized, controlled studies evaluating selenium supplementation, and review articles that are available in Medline and PubMed have undergone scrutiny. The differences concerning methodology and results variability have been analyzed. Several authors support the idea of a potential efficacy of selenium (mainly selenomethionine) supplementation in reducing antithyroperoxidase antibody levels and improve thyroid ultrasound features. In mild Graves’ orbitopathy, selenium supplementation has been associated with a decrease of the activity, as well as with quality of life improvement. Future research is necessary to clearly understand the selenium supplementation biologic effects while considering the basal selenium levels/biomarkers, selenoprotein gene polymorphisms that may be involved, underlying comorbidities and the major clinical outcomes.

Evaluation of interrelationships between thyroid function, autoimmunity, insulin resistance and lipid profile in Graves' disease

Introduction: Thyroid hormones modulate the lipoprotein and glucose metabolisms. In hyperthyroidism, insulin resistance is a frequent finding. The aim of our study was to assess the interrelationships between thyroid function, autoimmunity, lipid profile, glucose metabolism and other cardiovascular risk factors in patients with Graves’ disease. Material & Methods: We recorded free T3, free T4, TSH, TSH receptor antibodies, parameters of the lipid profile, glucose metabolism (including insulin resistance markers like homeostasis model assessment for insulin resistance - HOMA-IR), C reactive protein and homocysteine in 126 patients with Graves’ disease in the first cycle of treatment with methimazole (92.9% females, mean age 44.9 ± 15.2 years). Patients were divided in subgroups according to: TSH receptor antibodies [positive (n = 57) or negative (n = 69)] and thyroid function [euthyroidism (n = 74), subclinical (n = 29) or clinical hyperthyroidism (n = 22)]. Spearman correlations, t-tests and Mann-Whitney tests were performed for statistical analysis. Results: Comparing the positive and negative TSH receptor antibodies groups, significantly lower apolipoprotein B (80.3 ± 23.9 vs 89.7 ± 23.8 mg/dL; p = 0.047) and TSH [0.180 (0.002-1.080) vs 1.020 (0.235-2.055) μUI/mL; p < 0.001] were found in the positive TSH receptor antibodies group. Comparing with the normal thyroid function group, patients in the clinical hyperthyroid group presented significantly lower apolipoprotein B (70.9 ± 25.8 vs 89.8 ± 24.0 mg/dL; p = 0.007] and higher fasting glucose (96.0 ± 24.4 vs 86.4 ± 10.0 mg/dL; p = 0.019), insulin [10.4 (6.2-15.8) vs 7.5 (4.8-9.7) μUI/mL; p = 0.021], HOMA-IR [2.09 (1.29-4.53) vs 1.55 (0.96-2.13); p = 0.023] and C reactive protein [0.57 (0.20-0.93) vs 0.20 (0.07-0.38) mg/L; p = 0.005]. No significant differences were found between the subclinical hyperthyroid and the normal groups. There was a negative correlation between TSH and the TSH receptor antibodies (r = -0.386; p < 0.001). Apolipoprotein B was positively correlated with TSH (r = 0.236; p = 0.016), and negatively with the TSH receptor antibodies (r = -0.211; p = 0.030). Both free T3 and free T4 were positively correlated with fasting insulin (r = 0.268; p = 0.008 and r = 0.226; p = 0.025, respectively) and HOMA-IR (r = 0.258; p = 0.010 and r = 0.259; p = 0.010, respectively). Free T4 was also positively correlated with fasting glucose (r = 0.269; p = 0.008). Conclusion: In patients with Graves’ disease, the interrelationships between thyroid function, autoimmunity, insulin resistance and lipid profile may contribute to the increased cardiovascular risk. The lipid profile suggests a hypolipidemic effect.

Cardiovascular risk factors in patients with autoimmune thyroiditis

Introduction: Thyroid dysfunction has been related to an increased cardiovascular risk resulting from alterations in lipid profile, insulin resistance, homocysteine levels and low grade systemic inflammation. The impact of normal TSH levels and subclinical hypothyroidism and autoimmunity in the increased cardiovascular risk remains controversial. Our objective was to evaluate the interrelations between thyroid function, thyroid autoimmunity and cardiovascular risk factors, in patients with autoimmune thyroiditis. Methods: 353 subjects with autoimmune thyroiditis were evaluated. We defined three groups based on TSH levels: TSH 0.5-2.5 μUI/mL, TSH 2.5-5.0 μUI/mL and TSH 5.0-10.0 μUI/mL. We recorded thyroid function tests, thyroid autoimmunity, insulin resistance markers including HOMA-IR (Homeostasis Model Assessment for Insulin Resistance), lipid profile, homocysteine, high-sensitivity C-reactive protein (hs-CRP) and vitamin B12 levels. Statistical analysis was performed using KruskalWallis test and Spearman correlations. Results: Our sample comprised 94% females with a mean age of 47.0 ± 16.3 years. The group TSH 5.0-10.0 μUI/mL presented higher levels of HOMA-IR when compared to the other two groups [2.96 (1.76-4.59) in TSH 5.0-10.0 μUI/mL vs 1.86 (0.97-2.56) in TSH 2.5-5.0 μUI/mL and 1.58 (1.06-2.46) in TSH 0.5-2.5 μUI/mL, p = 0.002]. In the total group we observed positive correlations between free T3 and both HDL (r = 0.118, p = 0.028) and apolipoprotein A-I (Apo A-I) (r = 0.129, p = 0.024); TSH was positively correlated with HOMA-IR (r = 0.146, p = 0.018) while free T4 was negatively correlated with homocysteine (r = -0.119, p = 0.041). In the group TSH 0.5-2.5 μUI/mL, positive correlations were found between TSH and both HDL (r = 0.136, p = 0.031) and homocysteine (r = 0.147, p = 0.028), between free T4 and CRP (r = 0.136, p = 0.037) and between anti-thyroglobulin antibodies and apolipoprotein B (r = 0.165, p = 0.013); anti-thyroglobulin antibodies were negatively correlated with homocysteine (r = -0.186, p = 0.006). Negative correlations between anti-thyroglobulin antibodies, total cholesterol (r = 0.371, p = 0.004), LDL (r = -0.325, p = 0.011), apolipoprotein B (r = -0.342, p = 0.022) and lipoprotein(a) (r = -0.470, p = 0.001) were revealed in the group TSH 2.5-5.0 μUI/mL. Regarding the group TSH 5.0-10.0 μUI/mL, we found positive correlations between free T3 and HDL (r = 0.358, p = 0.030), vitamin B12 (r = 0.398, p = 0.024) and HOMA-IR (r = 0.424, p = 0.031), and between anti-thyroglobulin and homocysteine (r = 0.383, p = 0.033). Conclusion: We observed significant correlations between thyroid function, thyroid autoimmunity, insulin resistance, lipid profile and homocysteine that may contribute to an increased cardiovascular risk in patients with autoimmune thyroiditis.

Subclinical hypothyroidism, autoimmune thyroiditis, and cardiovascular risk factors

Background and objectives: There is increasing evidence that subclinical hypothyroidism is related with an increased cardiovascular risk. The objective is to evaluate the relationship between autoimmune thyroiditis, subclinical hypothyroidism and cardiovascular risk factors. Methods: We recorded thyroid function tests, anti-TPO and antithyroglobulin antibodies, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, apolipoproteinA1, apolipoproteinB, lipoprotein(a), homocysteine, high sensitivity CRP, folic acid, vitamin B12, HOMA-IR, HOMA-β, QUICKI, HISI, WBISI, IGI in 185 subjects with autoimmune thyroiditis and in euthyroid state and in 69 subjects with autoimmune thyroiditis and subclinical hypothyroidism. Statistical analysis was performed with Mann-Whitney test, logistic regression and Spearman correlations. The results were adjusted for age and body mass index. Statistical significance was considered for a bilateral value of p<0.05. Results: 94% of subjects were female. The median age was significantly higher in the euthyroid group. Patients with higher levels of total cholesterol (OR=1.008; p=0.034), CRP (OR=1.684; p=0.041) or anti-thyroglobulin antibodies (OR=1.002; p=0.021) had an increased likelihood of having subclinical hypothyroidism. In the total group of patients, we observed positive correlations between TSH, CRP and HOMA-IR, between free T3 and HDLcholesterol and between free T4 and IGI. TSH levels correlated negatively with QUICKI, HISI and WBISI. In the group with subclinical hypothyroidism, we found negative correlations between free T3 and homocysteine and between free T4 and anti-TPO antibodies.

P73. UM FEOCROMOCITOMA NA UCICARDIOLOGIA – MIOCARDIOPATIA DE TAKOTSUBO INVERTIDA

desafio no diagnostico diferencial. Sao varios os casos publicados de bacos acessorios interpretados como tumores neuroendocrinos. Caso clinico: Mulher, 64 anos, com antecedentes de litiase renal, hiperuricemia, dislipidemia, sindrome depressivo, doenca cerebrovascular e colecistectomia. Em Agosto de 2008, no contexto de um internamento por pielonefrite, e-lhe diagnosticado um hiperparatiroidismo primario. Submetida a paratiroidectomia infer ior esquerda a 29.09.2009 com normalizacao da P TH intra-operatoriamente. Diagnostico histologico (DH) de adenoma da paratiroide. Pos-operatorio com quadro de pancreatite aguda de etiologia nao esclarecida. Foi posteriormente documentada lesao solida com 13 mm na vertente posterior da cauda do pâncreas. Citologia da lesao revelando alteracoes inflamatorias e CgA normal. Em Fev2010, mantinha hiperparatiroidismo. Coloca-se a hipotese de se tratar de um caso de MEN I e da lesao pancreatica traduzir um tumor neuroendocrino. Estudo de DOTA-NOC (Jan2012) sugestivo de TNE da cauda do pâncreas. Repete CgA com 101,8 (< 100). Sugerida pancreatecomia caudal, realizada em Abril 2012. DH de baco acessorio intrapancreatico. Pâncreas sem alteracoes. Discussao: O diagnostico diferencial imagiologico entre um baco acessorio intra-pancreatico e um tumor pancreatico (nomeadamente um NE) nao e simples nem frequente. O Octreoscan e o DOTA-NOC nao permitem uma distincao entre estas 2 entidades. Na TC, a semelhanca de densidade entre a lesao pancreatica e o baco, pode fazer suspeitar da presenca de um baco acessorio. A citologia endoscopica podera ter um importante papel nesta distincao assim como a RM ou a cintigrafia com eritrocitos marcados com Tc99. Para um diagnostico atempado, e necessario um grau de suspeicao clinica na interpretacao dos resultados imagiologicos, o que podera evitar uma cirurgia desnecessaria.

CO030. RELAÇÃO ENTRE A QUALIDADE DE VIDA NA NEFROPATIA DIABÉTICA COM O SEXO, COMORBILIDADES E EXERCÍCIO FÍSICO

Introducao: A utilizacao da PTH intra-operatoria (PTHio) durante a cirurgia cervical de doentes com hiperparatiroidismo primario (HTP) tem-se generalizado nas ultimas duas decadas. Possibilita uma abordagem cervical minimamente invasiva ao permitir monitorizar o sucesso da intervencao. Objetivo: Correlacionar a descida da PTHio com o sucesso a longo prazo do tratamento cirurgico de doentes com HTP. Metodos: Durante 10 anos, 137 doentes consecutivos com diagnostico de HTP foram operados e a PTHio foi medida antes e 5, 10, 20 e 30 minutos apos excisao da glândula paratiroideia suspeita. A cirurgia foi considerada com sucesso sempre que se verificou descida da PTHio superior ou igual a 50% 10 minutos apos a excisao. Foram definidos 2 grupos – com PTHio normal (grupo I) e acima do normal (grupo II) apos 10 minutos. O material excisado foi enviado para analise anatomo-patologica. Os niveis sericos de calcio e PTH foram monitorizados aos 1.5, 3, 6 e 12 meses de follow-up. Foi efectuada analise estatistica com o programa SPSS versao 20.0 para Windows. A amostra era constituida predominantemente por mulheres (78%), com idade media 61 ± 16 anos. Cerca de 97% dos doentes cumpriam o criterio estabelecido de descida da PTHio aos 10 minutos. Destes, 67% tinham PTH com valor normal e os restantes com valor acima do normal. Resultados: O grupo II apresentava peso das gândulas excisadas, valor maximo de calcio pre-operatorio e PTHio aos 10 minutos signif icativamente mais elevados (p < 0,01). Aos 6 meses de follow-up os valores de PTH eram significativamente inferiores no grupo I e maior proporcao destes doentes apresentava calcio e PTH normais (p < 0,05). Aos 12 meses, a taxa de recorrencia era de 3,7% (doentes do grupo II). Conclusao: A normalizacao da PTH durante a cirurgia, para alem do criterio de descida de 50%, e um factor preditivo de cura no HTP.