Nível De Atividade Física De Mulheres Menopausadas Com Baixa Densidade Mineral óssea

Introduction Proper physical activity is related to the prevention and the treatment of osteoporosis. Purpose To assess the level of physical activity (PA) in post-menopausal women with low bone mineral density (BMD). Methods This cross-sectional clinicai study included 123 post-menopausal women. The inclusión criteria were: age of ≥ 45 years with last menses at least 12 months prior to the Initiation of the study, and bone density sean (BDS) valúes measured over the preceding 12 months. Women with severe Osteoarthritis were excluded. Women were allocated into three groups, according to BMD measured by BDS [osteoporosis (OP; 54 women), osteopenia (35 women), and normal bone density (NBD; 35 women)], and compared for general, clinicai, and anthropometric data, and for PA level. The latter was assessed using the International Physical Activity Questionnaire (IPAQ), in metabolic equivalent of task (MET) units. Participants were classified as sedenta ry, active or very active. Quantitative variables were compared using ANOVA followed by Tukey's test. Associations between qualitative variables were tested by chi-square (χ2) or Fisher's exact test. In order to check for differences among groups and IPAQ domains, a generalized linear model with Gamma distribution was adjusted for valúes in METs. Results The OP group differed from the NBD group regarding age (61.8 ± 10.1 and 52.9 ± 5.4 years), percentage of participants with self-declared white ethnicity (43.9 and 28.0%), body mass index (BMI - 25.7 ± 5.4 and 30.9 ± 5.1 kg/m2), and time since menopause (15.5 ± 7.5 and 5.8 ± 4.5 years). Smoking rates were higher in the OP (55.6%) and NBD groups (33.3%) than in the osteopenia group (11.1%). Within the OP group, the rate of subjects with sedentary lifestyles was higher (42.6%), and time spent sitting was greater (344.3 ± 204.8 METs) than in the groups with osteopenia (20.0% and 300.9 ± 230.6 METs) and NBD (17.7% and 303.2 ± 187.9 METs). Conclusions The rate of sedentary lifestyles was higher in post-menopausal women with OP than in those with either osteopenia or NBD. In order to change this physical inactivity profile, strategies should be created to address this group of patients. © 2016 by Thieme Publicações Ltda, Rio de Janeiro, Brazil.38522523

The Brazilian Consensus For The Clinical Approach And Treatment Of Subclinical Hypothyroidism In Adults: Recommendations Of The Thyroid Department Of The Brazilian Society Of Endocrinology And Metabolism [consenso Brasileiro Para A Abordagem Clínica E Tratamento Do Hipotireoidismo Subclínico Em Adultos: Recomendações Do Departamento De Tireoide Da Sociedade Brasileira De Endocrinologia E Metabologia]

Introduction: Subclinical hypothyroidism (SCH), defined as elevated concentrations of thyroid stimulating hormone (TSH) despite normal levels of thyroid hormones, is highly prevalent in Brazil, especially among women and the elderly. Although an increasing number of studies have related SCH to an increased risk of coronary artery disease and mortality, there have been no randomized clinical trials verifying the benefit of levothyroxine treatment in reducing these risks, and the treatment remains controversial. Objective: This consensus, sponsored by the Thyroid Department of the Brazilian Society of Endocrinology and Metabolism and developed by Brazilian experts with extensive clinical experience with thyroid diseases, presents these recommendations based on evidence for the clinical management of SCH patients in Brazil. Materials and methods: After structuring the clinical questions, the search for evidence in the literature was initially performed in the MedLine-PubMed database and later in the Embase and SciELO - Lilacs databases. The strength of evidence was evaluated according to the Oxford classification system and established based on the experimental design used, considering the best available evidence for each question and the Brazilian experience. Results: The topics covered included SCH definition and diagnosis, natural history, clinical significance, treatment and pregnancy, and the consensus issued 29 recommendations for the clinical management of adult patients with SCH. Conclusion: Treatment with levothyroxine was recommended for all patients with persistent SCH with serum TSH values ≥ 10 mU/L and for certain patient subgroups.573166183Surks, M.I., Ortiz, E., Daniels, G.H., Sawin, C.T., Col, N.F., Cobin, R.H., Subclinical thyroid disease: Scientific review and guidelines for diagnosis and management (2004) JAMA., 291, pp. 228-238Cooper, D.S., Biondi, B., Subclinical thyroid disease (2012) Lancet., 379, pp. 1142-1154Romaldini, J.H., Sgarbi, J.A., Farah, C.S., Subclinical thyroid disease: Subclinical hypothyroidism and hyperthyroidism (2004) Arq Bras Endocrinol Metab., 48, pp. 147-158Hollowell, J.G., Staehling, N.W., Flanders, W.D., Hannon, W.H., Gunter, E.W., Spencer, C.A., Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III) (2002) J Clin Endocrinol Metab., 87, pp. 489-499Canaris, G.J., Manowitz, N.R., Mayor, G., Ridgway, E.C., The Colorado Thyroid Disease Prevalence Study (2000) Arch Int Med., 160, pp. 526-534Parle, J.V., Franklyn, J.A., Cross, K.W., Jones, S.C., Sheppard, M.C.L., Prevalence and follow up of abnormal thyrotrophin (TSH) concentrations in the elderly in the United Kingdom (1991) Clin Endocrinol (Oxf)., 34, pp. 77-83Vanderpump, M.P., Tunbridge, W.M., French, J.M., Appleton, D., Bates, D., Clark, F., The incidence of thyroid disorders in the community: A twenty-year follow-up of the Whickman Survey (1995) Clin Endocrinol (Oxf)., 43, pp. 55-68Sichieri, R., Baima, J., Marante, T., de Vasconcellos, M.T., Moura, A.S., Vaisman, M., Low prevalence of hypothyroidism among black and Mulatto people in a population-based study of Brazilian women (2007) Clin Endocrinol (Oxf)., 66, pp. 803-807Camargo, R.Y., Tomimori, E.K., Neves, S.C., Rubio, I.G., Galrão, A.L., Knobel, M., Thyroid and the environment: Exposure to excessive nutritional iodine increases the prevalence of thyroid disorders in Sao Paulo, Brazil (2008) Eur J Endocrinol., 159, pp. 293-299Sgarbi, J.A., Matsumura, L.K., Kasamatsu, T.S., Ferreira, S.R., McIel, R.M., Subclinical thyroid dysfunctions are independent risk factors for mortality in a 7.5-year follow-up: The Japanese-Brazilian thyroid study (2010) Eur J Endocrinol., 162, pp. 569-577Benseñor, I.M., Goulart, A.C., Lotufo, P.A., Menezes, P.R., Scazufca, M., Prevalence of thyroid disorders among older people: Results from the São Paulo Ageing & Health Study (2011) Cad Saude Publica., 27, pp. 155-161Walsh, J.P., Bremner, A.P., Bulsara, M.K., O'Leary, P., Leedman, P.J., Feddema, P., Subclinical thyroid dysfunction as a risk factor for cardiovascular disease (2005) Arch Intern Med., 165, p. 2467Cappola, A.R., Fried, L.P., Arnold, A.M., Danese, M.D., Kuller, L.H., Burke, G.L., Thyroid status, cardiovascular risk, and mortality in older adults (2006) JAMA., 295, pp. 1033-1041Iervasi, G., Molinaro, S., Landi, P., Taddei, M.C., Galli, E., Mariani, F., Association between increased mortality and mild thyroid dysfunction in cardiac patients (2007) Arch Intern Med., 167, pp. 1526-1532Asvold, B.O., Bjoro, T., Nilsen, T.I., Gunnell, D., Vatten, L.J., Thyrotropin levels and risk of fatal coronary heart disease: The HUNT study (2008) Arch Intern Med., 168, pp. 855-860Boekholdt, S.M., Titan, S.M., Wiersinga, W.M., Chatterjee, K., Basart, D.C., Luben, R., Initial thyroid status and cardiovascular risk factors: The EPIC-Norfolk prospective population study (2010) Clin Endocrinol (Oxf)., 72, pp. 404-410McQuade, C., Skugor, M., Brennan, D.M., Hoar, B., Stevenson, C., Hoogwerf, B.J., Hypothyroidism and moderate subclinical hypothyroidism are associated with increased all-cause mortality independent of coronary heart disease risk factors: A PreCIS database study (2011) Thyroid., 21, pp. 837-843Asvold, B.O., Bjøro, T., Platou, C., Vatten, L.J., Thyroid function and the risk of coronary heart disease: 12-year follow-up of the HUNT Study in Norway (2012) Clin Endocrinol (Oxf)., 77, pp. 911-917Biondi, B., Cooper, D.S., The clinical significance of subclinical thyroid dysfunction (2008) Endocr Rev., 29, pp. 76-131Rodondi, N., Aujesky, D., Vittinghoff, E., Cornuz, J., Bauer, D.C., Subclinical hypothyroidism and the risk of coronary heart disease: A meta-analysis (2006) Am J Med., 119, pp. 541-551Volzke, H., Schwahn, C., Wallaschofski, H., Dorr, M., Review: The association of thyroid dysfunction with all-cause and circulatory mortality: Is there a causal relationship? (2007) J Clin Endocrinol Metab., 92, pp. 2421-2429Razvi, S., Weaver, J.U., Vanderpump, M.P., Pearce, S.H., The incidence of ischemic heart disease and mortality in people with subclinical hypothyroidism: Reanalysis of the Whickham Survey cohort (2010) J Clin Endocrinol Metab., 95, pp. 1734-1740Singh, S., Duggal, J., Molnar, J., Maldonado, F., Barsano, C.P., Arora, R., Impact of subclinical thyroid disorders on coronary heart disease, cardiovascular and all-cause mortality: A meta-analysis (2008) Int J Cardiol., 125, pp. 41-48Ochs, N., Auer, R., Bauer, D.C., Nanchen, D., Gussekloo, J., Cornuz, J., Meta-analysis: Subclinical thyroid dysfunction and the risk for coronary heart disease and mortality (2008) Ann Intern Med., 148, pp. 832-845Cooper, D.S., Halpern, R., Wood, L.C., Levin, A.A., Ridgway, E.C., L-thyroxine therapy in subclinical hypothyroidism. A doubleblind, placebo-controlled trial (1984) Ann Intern Med., 101, pp. 18-24Nystrom, E., Caidahl, K., Fager, G., Wikkelso, C., Lundberg, P.A., Lindstedt, G.A., Double-blind cross-over 12-month study of L-thyroxine treatment of women with 'subclinical' hypothyroidism (1988) Clin Endocrinol (Oxf)., 29, pp. 63-67Jaeschke, R., Guyatt, G., Gerstein, H., Patterson, C., Molloy, W., Cook, D., Does treatment with L-thyroxine influence health status in middle-aged and older adults with subclinical hypothyroidism? (1996) J Gen Intern Med., 11, pp. 744-749Bono, G., Fancellu, R., Blandini, F., Santoro, G., Mauri, M., Cognitive and affective status in mild hypothyroidism and interactions with L-thyroxine treatment (2004) Acta Neurol Scand., 110, pp. 59-66Volpato, S., Guralnik, J.M., Fried, L.P., Remaley, A.T., Cappola, A.R., Launer, L.J., Serum thyroxine level and cognitive decline in euthyroid older women (2002) Neurology., 58, pp. 1055-1061Kong, W.M., Sheikh, M.H., Lumb, P.J., Naoumova, R.P., Freedman, D.B., Crook, M., A 6-month randomized trial of thyroxine treatment in women with mild subclinical hypothyroidism (2002) Am J Med., 112, pp. 348-354Jorde, R., Waterloo, K., Storhaug, H., Nyrnes, A., Sundsfjord, J., Jenssen, T.G., Neuropsychological function and symptoms in subjects with subclinical hypothyroidism and the effect of thyroxine treatment (2006) J Clin Endocrinol Metab., 91, pp. 145-153Parle, J., Roberts, L., Wilson, S., Pattison, H., Roalfe, A., Haque, M.S., A randomized controlled trial of the effect of thyroxine replacement on cognitive function in community-living elderly subjects with subclinical hypothyroidism: The Birmingham Elderly Thyroid study (2010) J Clin Endocrinol Metab., 95, pp. 3623-3632Rodondi, N., den Elzen, W.P., Bauer, D.C., Cappola, A.R., Razvi, S., Walsh, J.P., Subclinical hypothyroidism and the risk of coronary heart disease and mortality. Thyroid Studies Collaboration (2010) JAMA., 304, pp. 1365-1374Meier, C., Staub, J.J., Roth, C.B., Guglielmetti, M., Kunz, M., Miserez, A.R., TSH-controlled L-thyroxine therapy reduces cholesterol levels and clinical symptoms in subclinical hypothyroidism: A double blind, placebo-controlled trial (Basel Thyroid Study) (2001) J Clin Endocrinol Metab., 86, pp. 4860-4866Caraccio, N., Ferranini, E., Monzani, F., Lipoprotein profile in subclinical hypothyroidism: Response to levothyroxine replacement, a randomized placebo-controlled study (2002) J Clin Endocrinol Metab., 87, pp. 1533-1538Monzani, F., Caraccio, N., Kozàkowà, M., Dardano, A., Vittone, F., Virdis, A., Effect of levothyroxine replacement on lipid profile and intima-media thickness in subclinical hypothyroidism: A double-blind, placebo-controlled study (2004) J Clin Endocrinol Metab., 89, pp. 2099-2106Adrees, M., Gibney, J., El-Saeity, N., Boran, G., Effects of 18 months of L-T4 replacement in women with subclinical hypothyroidism (2009) Clin Endocrinol (Oxf)., 71, pp. 298-303Teixeira, P.F., Reuters, V.S., Ferreira, M.M., Treatment of subclinical hypothyroidism reduces atherogenic lipid levels in a placebocontrolled double-blind clinical trial (2008) Horm Metab Res., 40, pp. 50-55Biondi, B., Fazio, S., Palmieri, E.A., Carella, C., Panza, N., Cittadini, A., Left ventricular diastolic dysfunction in patients with subclinical hypothyroidism (1999) J Clin Endocrinol Metab., 84, pp. 2064-2067Brenta, G., Mutti, L.A., Schnitman, M., Fretes, O., Perrone, A., Matute, M.L., Assessment of left ventricular diastolic function by radionuclide ventriculography at rest and exercise in subclinical hypothyroidism, and its response to L-thyroxine therapy (2003) Am J Cardiol., 91, pp. 1327-1330Arem, R., Rokey, R., Kiefe, C., Escalante, D.A., Rodriguez, A., Cardiac systolic and diastolic function at rest and exercise in subclinical hypothyroidism: Effect of thyroid hormone therapy (1996) Thyroid., 6, pp. 397-402Franzoni, F., Galetta, F., Fallahi, P., Tocchini, L., Merico, G., Braccini, L., Effect of L-thyroxine treatment on left ventricular function in subclinical hypothyroidism (2006) Biomed Pharmacother., 60, pp. 431-436Razvi, S., Weaver, J.U., Butler, T.J., Pearce, S.H., Levothyroxine treatment of subclinical hypothyroidism, fatal and nonfatal cardiovascular events, and mortality (2012) Arch Intern Med., 172 (10), pp. 811-817Garber, J.R., Cobin, R.H., Gharib, H., Hennessey, J.V., Klein, I., Mechanick, J.I., Clinical practice guidelines for hypothyroidism in adults: Cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association (2012) Thyroid., 22, pp. 1200-1235. , American Association of Clinical Endocrinologists and American Thyroid Association Taskforce on Hypothyroidism in AdultsSimonsick, E.M., Newman, A.B., Ferrucci, L., Satterfield, S., Harris, T.B., Rodondi, N., Subclinical hypothyroidism and functional mobility in older adults (2009) Arch Intern Med., 169, pp. 2011-2017. , for the Health ABC StudyVaisman, F., Coeli, C.M., Ward, L.S., Graf, H., Carvalho, G., Montenegro Jr., R., How good is the levothyroxine replacement in primary hypothyroidism patients in Brazil?-Data of a multicentre study (2013) J Endocrinol Invest, , Jan 14. [Epub ahead of print] PMID:23324400Collet, T.H., Gussekloo, J., Bauer, D.C., den Elzen, W.P., Cappola, A.R., Balmer, P., Thyroid Studies Collaboration. Subclinical hyperthyroidism and the risk of coronary heart disease and mortality (2012) Arch Intern Med., 172, pp. 799-809Sawin, C.T., Geller, A., Wolf, P.A., Belanger, A.J., Baker, E., Bacharach, P., Low serum thyrotropin concentrations as a risk factor for atrial fibrillation in older persons (1994) N Engl J Med., 331, pp. 1249-1252Faber, J., Galløe, A.M., Changes in bone mass during prolonged subclinical hyperthyroidism due to L-thyroxine treatment: A metaanalysis (1994) Eur J Endocrinol., 130, pp. 350-356Stagnaro-Green, A., Abalovich, M., Alexander, E., Azizi, F., Mestman, J., Negro, R., American Thyroid Association Task Force on Thyroid Disease During Pregnancy and Postpartum. Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum (2011) Thyroid., 21, pp. 1081-1125Stricker, R., Echenard, M., Eberhart, R., Chevailler, M.C., Perez, V., Quinn, F.A., Evaluation of maternal thyroid function during pregnancy: The importance of using gestational age-specific reference intervals (2007) Eur J Endocrinol., 157, pp. 509-514Lee, R.H., Spencer, C.A., Mestman, J.H., Miller, E.A., Petrovic, I., Braverman, L.E., Free T4 immunoassays are flawed during pregnancy (2009) Am J Obstet Gynecol., 200, pp. 260.e1-260.e6Vieira, J.G.H., Kanashiro, I., Tachibana, T.T., Ghiringhello, M.T., Hauache, O.M., McIel, R.M.B., Definição de valores normais de tiroxina livre durante a gravidez (2004) Arq Bras Endocrinol Metab., 48, pp. 305-309Benhadi, N., Wiersinga, W.M., Reitsma, J.B., Vrijkotte, T.G., Bonsel, G.J., Higher maternal TSH levels in pregnancy are associated with increased risk for miscarriage, fetal or neonatal death (2009) Eur J Endocrinol., 160, pp. 985-991Levels of Evidence and Grades of Recommendations-Oxford Centre for Evidence-Based Medicine, , http://www.cebm.net/index.aspx?o=1025, Disponível em URLNegro, R., Schwartz, A., Gismondi, R., Tinelli, A., Mangieri, T., Stagnaro-Green, A., Thyroid antibody positivity in the first trimester of pregnancy is associated with negative pregnancy outcomes (2011) J Clin Endocrinol Metab., 96, pp. E920-E924Allan, W.C., Haddow, J.E., Palomaki, G.E., Williams, J.R., Mitchell, M.L., Hermos, R.J., Maternal thyroid deficiency and pregnancy complications: Implications for population screening (2000) J Med Screen., 7, pp. 127-130Casey, B.M., Dashe, J.S., Wells, C.E., McIntire, D.D., Leveno, K.J., Cunningham, F.G., Subclinical hyperthyroidism and pregnancy outcomes (2006) Obstet Gynecol., 107, pp. 337-341Cleary-Goldman, J., Malone, F.D., Lambert-Messerlian, G., Sullivan, L., Canick, J., Porter, T.F., Maternal thyroid hypofunction and pregnancy outcome (2008) Obstet Gynecol., 112, pp. 85-92Lavado-Autric, R., Ausó, E., García-Velasco, J.V., Arufe Mdel, C., del Escobar Rey, F., Berbel, P., Early maternal hypothyroxinemia alters histogenesis and cerebral cortex cytoarchitecture of the progeny (2003) J Clin Invest., 111, pp. 1073-1082Pop, V.J., Kuijpens, J.L., van Baar, A.L., Verkerk, G., van Son, M.M., de Vijlder, J.J., Low maternal free thyroxine concentrations during early pregnancy are associated with impaired psychomotor development in infancy (1999) Clin Endocrinol (OxfPrograma Diretrizes, , http://www.projetodiretrizes.amb.org.br, Associação Médica Brasileira. Disponível em URLBaloch, Z., Carayon, P., Conte-Devolx, B., Demers, L.M., Feldt-Rasmussen, U., Henry, J.F., Laboratory Medicine Practice Guidelines: Laboratory Support for the Diagnosis and Monitoring of Thyroid Disease (2003) Thyroid., 13, pp. 57-67Kratzsch, J., Fiedler, G.M., Leichtle, A., Brügel, M., Buchbinder, S., Otto, L., New reference intervals for thyrotropin and thyroid hormones based on National Academy of Clinical Biochemistry criteria and regular ultrasonography of the thyroid (2005) Clin Chem., 51, pp. 1480-1486Boucai, L., Hollowell, J.G., Surks, M.I., An approach for development of age-, gender-, and ethnicity-specific thyrotropin reference limits (2011) Thyroid., 21, pp. 5-11Rosario, P.W., Xavier, A.C., Calsolari, M.R., TSH reference values for adult Brazilian population (2010) Arq Bras Endocrinol Metab., 54, pp. 603-606Razvi, S., Shakoor, A., Vanderpump, M., Weaver, J.U., Pearce, S.H., The influence of age on the relationship between subclinical hypothyroidism and ischemic heart disease: A metaanalysis (2008) J Clin Endocrinol Metab., 93, pp. 2998-3007Atzmon, G., Barzilai, N., Hollowell, J.G., Surks, M.I., Gabriely, I., Extreme longevity is associated with increased serum thyrotropin (2009) J Clin Endocrinol Metab., 94, pp. 1251-1254Verburg, F.A., Kirchgässner, C., Hebestreit, H., Steigerwald, U., Lentjes, E.G., Ergezinger, K., Reference ranges for analyses of thyroid function in children (2011) Horm Metab Res., 43, pp. 422-426Kapelari, K., Kirchlechner, C., Högler, W., Schweitzer, K., Virgolini, I., Moncayo, R., Pediatric reference intervals for thyroid hormone levels from birth to adulthood: A retrospective study (2008) BMC Endocr Disord., 27, pp. 8-15Soldin, O.P., Soldin, D., Sastoque, M., Gestation-specific thyroxine and thyroid stimulating hormone levels in the United States and worldwide (2007) Ther Drug Monit., 29, pp. 553-559Balthazar, U., Steiner, A.Z., Periconceptional changes in thyroid function: A longitudinal study (2012) Reprod Biol Endocrinol., 10, p. 20. , doi: 10.1186/1477-7827-10-20.XXHaddow, J.E., Knight, G.J., Palomaki, G.E., McClain, M.R., Pulkkinen, A.J., The reference range and within-person variability of thyroid stimulating hormone during the first and second trimesters of pregnancy (2004) J Med Screen., 11 (4), pp. 170-174Bocos-Terraz, J.P., Izquierdo-Alvarez, S., Bancalero-Flores, J.L., Alvarez-Lahuerta, R., Aznar-Sauca, A., Real-López, E., Thyroid hormones according to gestational age in pregnant Spanish women (2009) BMC Res Notes., 2, p. 237Surks, M.I., Hollowell, J.G., Age-specific distribution of serum thyrotropin and antithyroid antibodies in the US population: Implications for the prevalence of subclinical hypothyroidism (2007) J Clin Endocrinol Metab., 92, pp. 4575-4582Ladenson, P.W., Braverman, L.E., Mazzaferri, E.L., Brucker-Davis, F., Cooper, D.S., Garber, J.R., Comparison of administration of recombinant human thyrotropin with withdrawal of thyroid hormone for radioactive iodine scanning in patients with thyroid carcinoma (1997) N Engl J Med., 337, pp. 888-896Ismail, A.A., Burr, W.A., Walker, P.L., Acute changes in serum thyrotrophin in treated Addison's disease (1989) Clin Endocrinol (Oxf)., 30, pp. 225-230Ward, G., McKinnon, L., Badrick, T., Hickman, P.E., Heterophilic antibodies remain a problem for the immunoassay laboratory (1997) Am J Clin Pathol., 108, pp. 417-421Jordan, N., Williams, N., Gregory, J.W., Evans, C., Owen, M., Ludgate, M., The W546X mutation of the thyrotropin receptor gene: Potential major contributor to thyroid dysfunction in a Caucasian population (2003) J Clin Endocrinol Metab., 88, pp. 1002-1005Fatourechi, V., Aniszewski, J.P., Fatourechi, G.Z., Atkinson, E.J., Jacobsen, S.J., Clinical features and outcome of subacute thyroiditis in an incidence cohort: Olmsted County, Minnesota, study (2003) J Clin Endocrinol Metab., 88, pp. 2100-2105Peden, N.R., Hart, I.R., The early development of transient and permanent hypothyroidism following radioiodine therapy for hyperthyroid Graves' disease (1984) Can Med Assoc J., 130, pp. 1141-1144Bhakri, H.L., Fisher, R., Khadri, A., McMahon, D.G., Longitudinal study of thyroid function in acutely ill elderly patients using a sensitive TSH assay-defer testing until recovery (1990) Gerontology., 36, pp. 140-144Meyerovitch, J., Rotman-Pikielny, P., Sherf, M., Battat, E., Levy, Y., Surks, M.I., Serum thyrotropin measurements in the community: Fiveyear follow-up in a large network of primary care physicians (2007) Arch Intern Med., 167, pp. 1533-1538Díez, J.J., Iglesias, P., Burman, K.D., Spontaneous normalization of thyrotropin concentrations in patients with subclinical hypothyroidism (2005) J Clin Endocrinol Metab., 90, pp. 4124-4127Diez, J.J., Iglesias, P., Spontaneous subclinical hypothyroidism in patients older than 55 years: An analysis of natural course and risk factors for the development of overt thyroid failure (2004) J Clin Endocrinol Metab., 89, pp. 4890-4897Karmisholt, J., Andersen, S., Laurberg, P.A., Variation in thyroid function in subclinical hypothyroidism: Importance of clinical follow-up and therapy (2011) Eur J Endocrinol., 164, pp. 317-323Walsh, J.P., Bremner, A.P., Feddema, P., Leedman, P.J., Brown, S.J., O'Leary, P., Thyrotropin and thyroid antibodies as predictors of hypothyroidism: A 13-year, longitudinal study of a communitybased cohort using current immunoassay techniques (2010) J Clin Endocrinol Metab., 95, pp. 1095-1104Huber, G., Staub, J.J., Meier, C., Mitrache, C., Guglielmetti, M., Huber, P., Prospective study of the spontaneous course of subclinical hypothyroidism: Prognostic value of thyrotropin, thyroid reserve, and thyroid antibodies (2002) J Clin Endocrinol Metab., 87, pp. 3221-3226Rosario, P.W., Bessa, B., Valadao, M.M., Purisch, S., Natural history of mild subclinical hypothyroidism: Prognostic value of ultrasound (2009) Thyroid., 19, pp. 9-12Marcocci, C., Vitti, P., Cetani, F., Catalano, F., Concetti, R., Pinchera, A., Thyroid ultrasonography helps to identify patients with diffuse lymphocytic thyroiditis who are prone to develop hypothyroidism (1991) J Clin Endocrinol Metab., 72, pp. 209-213Li, Y., Teng, D., Shan, Z., Teng, X., Guan, H., Yu, X., Antithyroperoxidase and antithyroglobulin antibodies in a five-year follow-up survey of populations with different iodine intakes (2008) J Clin Endocrinol M

The Brazilian Consensus For The Diagnosis And Treatment Of Hyperthyroidism: Recommendations By The Thyroid Department Of The Brazilian Society Of Endocrinology And Metabolism [consenso Brasileiro Para O Diagnóstico E Tratamento Do Hipertireoidismo: Recomendações Do Departamento De Tireoide Da Sociedade Brasileira De Endocrinologia E Metabologia]

Introduction: Hyperthyroidism is characterized by increased synthesis and release of thyroid hormones by the thyroid gland. Thyrotoxicosis refers to the clinical syndrome resulting from excessive circulating thyroid hormones, secondary to hyperthyroidism or due to other causes. This article describes evidence-based guidelines for the clinical management of thyrotoxicosis. Objective: This consensus, developed by Brazilian experts and sponsored by the Department of Thyroid Brazilian Society of Endocrinology and Metabolism, aims to address the management, diagnosis and treatment of patients with thyrotoxicosis, according to the most recent evidence from the literature and appropriate for the clinical reality of Brazil. Materials and methods: After structuring clinical questions, search for evidence was made available in the literature, initially in the database Medline, PubMed and Embase databases and subsequently in SciELO - Lilacs. The strength of evidence was evaluated by Oxford classification system was established from the study design used, considering the best available evidence for each question. Results: We have defined 13 questions about the initial clinical approach for the diagnosis and treatment that resulted in 53 recommendations, including the etiology, treatment with antithyroid drugs, radioactive iodine and surgery. We also addressed hyperthyroidism in children, teenagers or pregnant patients, and management of hyperthyroidism in patients with Graves' ophthalmopathy and various other causes of thyrotoxicosis. Conclusions: The clinical diagnosis of hyperthyroidism usually offers no difficulty and should be made with measurements of serum TSH and thyroid hormones. The treatment can be performed with antithyroid drugs, surgery or administration of radioactive iodine according to the etiology of thyrotoxicosis, local availability of methods and preferences of the attending physician and patient.573205232Andrade, V.A., Gross, J.L., Maia, A.L., Effect of methimazole pretreatment on serum thyroid hormone levels after radioactive treatment in Graves' hyperthyroidism (1999) J Clin Endocrinol Metab., 84 (11), pp. 4012-4016Boelaert, K., Torlinska, B., Holder, R.L., Franklyn, J.A., Older subjects with hyperthyroidism present with a paucity of symptoms and signs: A large cross-sectional study (2010) J Clin Endocrinol Metab., 95 (6), pp. 2715-2726Nordyke, R.A., Gilbert Jr., F.I., Harada, A.S., Graves' disease. Influence of age on clinical findings (1988) Arch Intern Med., 148 (3), pp. 626-631Woeber, K.A., Thyrotoxicosis and the heart (1992) N Engl J Med., 327 (2), pp. 94-98de los Santos, E.T., Starich, G.H., Mazzaferri, E.L., Sensitivity, specificity, and cost-effectiveness of the sensitive thyrotropin assay in the diagnosis of thyroid disease in ambulatory patients (1989) Arch Intern Med., 149 (3), pp. 526-532Rajatanavi, R., Braverman, L.E., Euthyroid hyperthyroxinemia (1983) J Endocrinol Invest., 6 (6), pp. 493-505Rajatanavin, R., Liberman, C., Lawrence, G.D., D'Arcangues, C.M., Young, R.A., Emerson, C.H., Euthyroid hyperthyroxinemia and thyroxine-binding prealbumin excess in islet cell carcinoma (1985) J Clin Endocrinol Metab., 61 (1), pp. 17-21Mariotti, S., Martino, E., Cupini, C., Lari, R., Giani, C., Baschieri, L., Low serum thyroglobulin as a clue to the diagnosis of hyperthyroidism factitia (1982) N Engl J Med., 307 (7), pp. 410-412Luton, D., le Gac, I., Vuillard, E., Castanet, M., Guibourdenche, J., Noel, M., Management of Graves' disease during pregnancy: The key role of fetal thyroid gland monitoring (2005) J Clin Endocrinol Metab., 90 (11), pp. 6093-6098Vos, X.G., Smit, N., Endert, E., Tijssen, J.G., Wiersinga, W.M., Frequency and characteristics of TBII-seronegative patients in a population with untreated Graves' hyperthyroidism: A prospective study (2008) Clin Endocrinol (Oxf)., 69 (2), pp. 311-317Al-Shariff, A., Abujbara, A.A., Chiacchio, S., Ajlouni, K.M., Mariani, G., Contribution of radioiodine uptake measurement and thyroid scintigraphy to the differential diagnosis of thyrotoxicosis (2010) Hell J Nucl Med., 13 (2), pp. 132-137Baek, J.B., Lee, J.H., Valcavi, R., Pacella, C.M., Rhim, H., Gyu, D., Thermal ablation for benign thyroid nodules: Radiofrequency and laser (2011) Korean J Radiol., 12 (5), pp. 525-540Burch, H.B., Wartofsky, L., Life-threatening thyrotoxicosis. Thyroid storm (1993) Endocrinol Metab Clin North Am., 22 (2), pp. 263-277Akamizu, T., Satoh, T., Isozaki, O., Suzuki, A., Wakino, S., Iburi, T., Diagnostic criteria, clinical features, and incidence of thyroid storm based on nationwide surveys (2012) Thyroid., 22 (7), pp. 661-679Laurberg, P., Vestergaard, H., Nielsen, S., Christensen, S.E., Seefeldt, T., Helleberg, K., Sources of circulating 3,5,3'-triiodothyronine in hyperthyroidism estimated after blocking of type 1 and type 2 iodothyronine deiodinases (2007) J Clin Endocrino Metab., 92 (6), pp. 2149-2156Giles, H.G., Roberts, E.A., Orrego, H., Sellers, E.M., Disposition of intravenous propylthiouracil (1981) J Clin Pharmacol., 21 (11-12 PART 1), pp. 466-471Nabil, N., Miner, D.J., Amatruda, J.M., Methimazole: An alternative route of administration (1982) J Clin Endocrino Metab., 54 (1), pp. 180-181Walter Jr., R.M., Bartle, W.R., Rectal administration of propylthiouracil in the treatment of Graves' disease (1990) Am J Med., 88 (1), pp. 69-70Yeung, S.C., Go, R., Balasubramanyam, A., Rectal administration of iodide and propylthiouracil in the treatment of thyroid storm (1995) Thyroid., 5 (5), pp. 403-405Jongjaroenprasert, W., Akarawut, W., Chantasart, D., Chailurkit, L., Rajatanavin, R., Rectal administration of propylthiouracil in hyperthyroid patients: Comparison of suspension enema and suppository form (2002) Thyroid., 12 (7), pp. 627-631Hodak, S.P., Huang, C., Clarke, D., Burman, K.D., Jonklaas, J., Janicic-Kharic, N., Intravenous methimazole in the treatment of refractory hyperthyroidism (2006) Thyroid., 16 (7), pp. 691-695Bogazzi, F., Martino, E., Dell'Unto, E., Brogioni, S., Cosci, C., Aghini-Lombardi, F., Thyroid color flow Doppler sonography and radioiodine uptake in 55 consecutive patients with amiodarone-induced thyrotoxicosis (2003) J Endocrinol Investigation., 26 (7), pp. 635-640Baeza, A., Aguayo, J., Barria, M., Pineda, G., Rapid preoperative preparation in hyperthyroidism (1991) Clin Endocrinol (Oxf)., 35 (5), pp. 439-445Robuschi, G., Manfredi, A., Salvi, M., Gardini, E., Montermini, M., d'Amato, L., Effect of sodium ipodate and iodide on free T4 and free T3 concentrations in patients with Graves' disease (1986) J Endocrinol Invest., 9 (4), pp. 287-291Tsatsoulis, A., Johnson, E.O., Kalogera, C.H., Seferiadis, K., Tsolas, O., The effect of thyrotoxicosis on adrenocortical reserve (2000) Eur J Endocrinol., 142 (3), pp. 231-235Solomon, B.L., Wartofsky, L., Burman, K.D., Adjunctive cholestyramine therapy for thyrotoxicosis (1993) Clin Endocrinol (Oxf)., 38 (1), pp. 39-43Vyas, A.A., Vyas, P., Fillipon, N.L., Vijayakrishnan, R., Trivedi, N., Successful treatment of thyroid storm with plasmapheresis in a patient with methimazole-induced agranulocytosis (2010) Endocr Pract., 16 (4), pp. 673-676Glaser, N.S., Styne, D.M., Organization of Pediatric Endocrinologists of Northern California Collaborative Graves' Disease Study Group. Predicting the likelihood of remission in children with Graves' disease: A prospective, multicenter study (2008) Pediatrics., 121, pp. e481-e488Dötsch, J., Siebler, T., Hauffa, B.P., Doeker, B., Andler, W., Bettendorf, M., Diagnosis and management of juvenile hyperthyroidism in Germany: A retrospective multicenter study (2000) J Pediatr Endocrinol Metab., 13 (7), pp. 879-885Poyrazoǧlu, S., Saka, N., Bas, F., Isguven, P., Dogu, A., Turan, S., Evaluation of diagnosis and treatment results in children with Graves' disease with emphasis on the pubertal status of patients (2008) J Pediatr Endocrinol Metab., 21 (8), pp. 745-751Kaguelidou, F., Alberti, C., Castanet, M., Guitteny, M.A., Czernichow, P., Leger, J., French Childhood Graves' Disease Study Group. Predictors of autoimmune hyperthyroidism relapse in children after discontinuation of antithyroid drug treatment (2008) J Clin Endocrinol Metab., 93 (10), pp. 3817-3826Barrio, R., López-Capapé, M., Martinez-Badás, I., Carrillo, A., Moreno, J.C., Alonso, M., Graves' disease in children and adolescents: Response to long-term treatment (2005) Acta Paediatr., 94 (11), pp. 1583-1589Maia, A.L., Ward, L.S., Carvalho, G.A., Graf, H., McIel, R.M., McIel, L.M., Thyroid nodules and differentiated thyroid cancer: Brazilian consensus (2007) Arq Bras Endocrinol Metab., 51 (5), pp. 867-893Abraham, P., Avenell, A., McGeoch, S.C., Clark, L.F., Bevan, J.S., Antithyroid drug regimen for treating Graves' hyperthyroidism (2010) Cochrane Database Syst Rev., 20, pp. CD003420Léger, J., Gelwane, G., Kaguelidou, F., Benmerad, M., Alberti, C., Positive impact of long-term antithyroid drug treatment on the outcome of children with Graves' disease: National long-term cohort study (2012) J Clin Endocrinol Metab., 97 (1), pp. 110-119Perrild, H., Grüters-Kieslich, A., Feldt-Rasmussen, U., Grant, D., Martino, E., Kayser, L., Diagnosis and treatment of thyrotoxicosis in childhood. A European questionnaire study (1994) Eur J Endocrinol., 131 (5), pp. 467-473Mussa, G.C., Corrias, A., Silvestro, L., Battan, E., Mostert, M., Mussa, F., Factors at onset predictive of lasting remission in pediatric patients with Graves' disease followed for at least three years (1999) J Pediatr Endocrinol Metab., 12 (4), pp. 537-541Slyper, A.H., Wyatt, D., Boudreau, C., Effective methimazole dose for childhood Graves' disease and use of free triiodothyronine combined with concurrent thyroid-stimulating hormone level to identify mild hyperthyroidismand delayed pituitary recovery (2005) J Pediatr Endocrinol Metab., 18 (6), pp. 597-602Cassio, A., Corrias, A., Gualandi, S., Tato', L., Cesaretti, G., Volta, C., Influence of gender and pubertal stage at diagnosis on growth outcome in childhood thyrotoxicosis: Results of a collaborative study (2006) Clin Endocrinol (Oxf)., 64 (1), pp. 53-57Sato, H., Harada, S., Yokoya, S., Tanaka, T., Asayama, K., Mori, M., Treatment for childhood-onset Graves' disease in Japan: Results of a nationwide questionnaire survey of pediatric endocrinologists and thyroidologists (2007) Thyroid., 17 (1), pp. 67-72Smith, J., Brown, R.S., Persistence of thyrotropin (TSH) receptor antibodies in children and adolescents with Graves' disease treated using antithyroid medication (2007) Thyroid., 17 (11), pp. 1103-1107Rivkees, S.A., Stephenson, K., Dinauer, C., Adverse events associated with methimazole therapy of graves' disease in children (2010) Int J Pediatr Endocrinol., 2010, p. 176970Lazar, L., Kalter-Leibovici, O., Pertzelan, A., Weintrob, N., Josefsberg, Z., Phillip, M., Thyrotoxicosis in prepubertal children compared with pubertal and postpubertal patients (2000) J Clin Endocrinol Metab., 85 (10), pp. 3678-3682Ota, H., Amino, N., Morita, S., Kobayashi, K., Kubota, S., Fukata, S., Quantitative measurement of thyroid blood flow for differentiation of painless thyroiditis from Graves' disease (2007) Clin Endocrinol (Oxf)., 67 (1), pp. 41-45Rivkees, S.A., Szarfman, A., Dissimilar hepatotoxicity profiles of propylthiouracil and methimazole in children (2010) J Clin Endocrinol Metab., 95 (7), pp. 3260-3267Sato, H., Hattori, M., Fujieda, M., Sugihara, S., Inomata, H., Hoshi, M., High prevalence of antineutrophil cytoplasmic antibody positivity in childhood onset Graves' disease treated with propylthiouracil (2000) J Clin Endocrinol Metab., 85 (11), pp. 4270-4273Jafarzadeh, A., Poorgholami, M., Izadi, N., Nemati, M., Rezayati, M., Immunological and hematological changes in patients with hyperthyroidism or hypothyroidism (2010) Clin Invest Med., 33 (5), pp. 271-279Sarinnapakorn, V., Noppavetchwich, P., Sunthorntepwarakul, T., Deerochanawong, C., Ngongamrut, S., Abnormal liver function test in Graves' disease: A prospective study of comparison between the hyperthyroid state and the euthyroid state (2011) J Med Assoc Thai., 94 (SUPPL. 2), pp. S11-S16Sandrini, R., França, S.N., Lacerda, L., Graf, H., Treatment of hyperthyroidism in infancy and adolescence (2001) Arq Bras Endocrinol Metab., 45 (1), pp. 32-36Hamerschlak, N., Maluf, E., Biasi Cavalcanti, A., Avezum Júnior, A., Eluf-Neto, J., Passeto Falcão, R., Incidence and risk factors for agranulocytosis in Latin American countries--the Latin Study: A multicenter study (2008) Eur J Clin Pharmacol., 64 (9), pp. 921-929Takata, K., Kubota, S., Fukata, S., Kudo, T., Nishihara, E., Ito, M., Methimazole-induced agranulocytosis in patients with Graves' disease is more frequent with an initial dose of 30 mg daily than with 15 mg daily (2009) Thyroid., 19 (6), pp. 559-563Salpeter, S.R., Ormiston, T.M., Salpeter, E.E., Cardioselective betablockers in patients with reactive airway disease: A meta-analysis (2002) Ann Intern Med., 137 (9), pp. 715-725Sato, H., Minagawa, M., Sasaki, N., Sugihara, S., Kazukawa, I., Minamitani, K., Comparison of methimazole and propylthiouracil in the management of children and adolescents with Graves' disease: Efficacy and adverse reactions during initial treatment and long-term outcome (2011) J Pediatr Endocrinol Metab., 24 (5-6), pp. 257-263Chen, D.Y., Chen, T.H., Comparison of efficacy of 131I and antithyroid drugs in the treatment of Graves' disease in children (2005) Chin J Pediatr., 43 (7), pp. 507-509Bogazzi, F., Vitti, P., Could improved ultrasound and power Doppler replace thyroidal radioiodine uptake to assess thyroid disease? (2008) Nat Clin Pract Endocrinol Metab., 4 (2), pp. 70-71Hu, B., Wei, Y.F., Huang, C., Chen, L.X., The treatment strategy for pediatric Graves' disease and the relevant problems of radioiodine treatment (2006) J Med Forum., 27, pp. 67-68Ma, C., Kuang, A., Xie, J., Liu, G., Radioiodine treatment for pediatric Graves' disease (2008) Cochrane Database Syst Rev., 16, pp. CD006294Rivkees, S.A., Cornelius, E.A., Influence of iodine-131 dose on the outcome of hyperthyroidism in children (2003) Pediatrics., 111 (4 PART 1), pp. 745-749Zantut-Wittmann, D.E., Ramos, C.D., Santos, A.O., Lima, M.M., Panzan, A.D., Facuri, F.V., High pre-therapy [99mTc]pertechnetate thyroid uptake, thyroid size and thyrostatic drugs: Predictive factors of failure in [131I]iodide therapy in Graves' disease (2005) Nucl Med Commun., 26 (11), pp. 957-963Nebesio, T.D., Siddiqui, A.R., Pescovitz, O.H., Eugster, E.A., Time course to hypothyroidism after fixed-dose radioablation therapy of Graves' disease in children (2002) J Pediatr., 141 (1), pp. 99-103Monte, O., Calliari, L.E.P., Longui, C.A., Utilização do 131I no tratamento da doença de Basedow-Graves na infância e adolescência (2004) Arq Bras Endocrinol Metab., 48 (1), pp. 166-170Kalinyak, J.E., McDougall, I.R., How should the dose of iodine-131 be determined in the treatment of Graves' hyperthyroidism? (2003) J Clin Endocrinol Metab., 88 (3), pp. 975-977Kadmon, P.M., Noto, R.B., Boney, C.M., Goodwin, G., Gruppuso, P.A., Thyroid storm in a child following radioactive iodine (RAI) therapy: A consequence of RAI versus withdrawal of antithyroid medication (2001) J Clin Endocrinol Metab., 86 (5), pp. 1865-1867Freitas, J.E., Swanson, D.P., Gross, M.D., Sisson, J.C., Iodine-131: Optimal therapy for hyperthyroidism in children and adolescents? (1979) J Nucl Med., 20 (8), pp. 847-850Rivkees, S.A., Dinauer, C., An optimal treatment for pediatric Graves' disease is radioiodine (2007) J Clin Endocrinol Metab., 92 (3), pp. 797-800Bogazzi, F., Bartalena, L., Brogioni, S., Mazzeo, S., Vitti, P., Burelli, A., Color flow Doppler sonography rapidly differentiates type I and type II amiodarone-induced thyrotoxicosis (1997) Thyroid., 7 (4), pp. 541-545Imaizumi, M., Usa, T., Tominaga, T., Neriishi, K., Akahoshi, M., Nakashima, E., Radiation dose-response relationships for thyroid nodules and autoimmune thyroid diseases in Hiroshima and Nagasaki atomic bomb survivors 55-58 years after radiation exposure (2006) JAMA., 295 (9), pp. 1011-1022Cheetham, T.D., Hughes, I.A., Barnes, N.D., Wraight, E.P., Treatment of hyperthyroidism in young people (1998) Arch Dis Child., 78 (3), pp. 207-209Feliciano, D.V., Lyons, J.D., Thyroidectomy is optimal treatment for Graves' disease (2011) J Am Coll Surg., 212 (4), pp. 714-720Sugino, K., Ito, K., Nagahama, M., Kitagawa, W., Shibuya, H., Ito, K., Surgical management of Graves' disease-10-year prospective trial at a single institution (2008) Endocr J., 55 (1), pp. 161-167Kriplani, A., Buckshee, K., Bhargava, V.L., Takkar, D., Ammini, A.C., Maternal and perinatal outcome in thyrotoxicosis complicating pregnancy (1994) Eur J Obstet Gynecol Reprod Biol., 54 (3), pp. 159-163Davis, L.E., Lucas, M.J., Hankins, G.D., Roark, M.L., Cunningham, F.G., Thyrotoxicosis complicating pregnancy (1989) Am J Obstet Gynecol., 160 (1), pp. 63-70Millar, L.K., Wing, D.A., Leung, A.S., Koonings, P.P., Montoro, M.N., Mestman, J.H., Low birth weight and preeclampsia in pregnancies complicated by hyperthyroidism (1994) Obstet Gynecol., 84 (6), pp. 946-949Stagnaro-Green, A., Abalovich, M., Alexander, E., Azizi, F., Mestman, J., Negro, R., Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and Postpartum The American Thyroid Association Taskforce on Thyroid Disease During Pregnancy and Postpartum (2011) Thyroid., 21 (10), pp. 1081-1125Mandel, S.J., Cooper, D.S., The use of antithyroid drugs in pregnancy and lactation (2001) J Clin Endocrinol Metab., 86 (6), pp. 2354-2359Clementi, M., Di Gianantonio, E., Pelo, E., Mammi, I., Basile, R.T., Tenconi, R., Methimazole embryopathy: Delineation of tTrzepacz, P.T., Klein, I., Roberts, M., Greenhouse, J., Levey, G.S., Graves' disease: An analysis of thyroid hormone levels and hyperthyroid signs and symptoms (1989) Am J Med., 87 (5), pp. 558-561Geffner, D.L., Hershman, J.M., Beta-adrenergic blockade for the treatment of hyperthyroidism (1992) Am J Med., 93 (1), pp. 61-68McDevitt, D.G., Nelson, J.K., Comparative trial of atenolol and propranolol in hyperthyroidism (1978) Br J Clin Pharmacol., 6 (3), pp. 233-237Duggal, J., Singh, S., Kuchinic, P., Butler, P., Arora, R., Utility of esmolol in thyroid crisis (2006) Can J Clin Pharmacol., 13 (3), pp. 292-295Henderson, J.M., Portmann, L., van Melle, G., Haller, E., Ghika, J.A., Propranolol as an adjunct therapy for hyperthyroid tremor (1997) Eur Neurol., 37 (3), pp. 182-185Milner, M.R., Gelman, K.M., Phillips, R.A., Fuster, V., Davies, T.F., Goldman, M.E., Double-blind crossover trial of diltiazem versus propranolol in the management of thyrotoxic symptoms (1990) Pharmacotherapy., 10 (2), pp. 100-106Kelestimur, F., Aksu, A., The effect of diltiazem on the manifestations of hyperthyroidism and thyroid function tests (1996) Exp Clin Endocrinol Diabetes., 104 (1), pp. 38-42Cooper, D.S., Antithyroid drugs (2005) N Engl J Med., 352 (9), pp. 905-917Russo, M.W., Galanko, J.A., Shrestha, R., Fried, M.W., Watkins, P., Liver transplantation for acute liver failure from drug induced liver injury in the United States (2004) Liver Transpl., 10 (8), pp. 1018-1023Bahn, R.S., Burch, H.B., Cooper, D.S., Garber, J.R., Greenlee, M.C., Klein, I., Hyperthyroidism and other causes of thyrotoxicosis: Management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists (2011) Endocr Pract., 17 (3), pp. 456-520Shivakumar, S.K., Dwarakanath, S., Swaroop, G., Venkataramana, N.K., Aplasia cutis congenita of the scalp: Therapeutic modalities (2006) Neurol India., 54 (3), pp. 312-313Reinwein, D., Benker, G., Lazarus, J.H., Alexander, W.D., A prospective randomized trial of antithyroid drug dose in Graves' disease therapy (1993) J Clin Endocrinol Metab., 76 (6), pp. 1516-1521Pearce, S.H., Spontaneous reporting of adverse reactions to carbimazole and propylthiouracil in the UK (2004) Clin Endocrinol (Oxf)., 61 (5), pp. 589-594Williams, K.V., Nayak, S., Becker, D., Reyes, J., Burmeister, L.A., Fifty years of experience with propylthiouracil-associated hepatotoxicity: What have we learned? (1997) J Clin Endocrinol Metab., 82 (6), pp. 1727-1733Fibbe, W.E., Claas, F.H.J., van der Star-Dijkstra, W., Schaafsma, M.R., Meyboom, R.H., Falkenburg, J.H., Agranulocytosis induced by propylthiouracil: Evidence of a drug dependent antibody reacting with granulocytes, monocytes and haematopoietic progenitor cells (1986) Br J Haematol., 64 (2), pp. 363-373Cooper, D.S., The side effects of antithyroid drugs (1999) The Endocrinologist., 9, pp. 457-467Schleusener, H., Schwander, J., Fischer, C., Holle, R., Holl, G., Badenhoop, K., Prospective multicentre study on the prediction of relapse after antithyroid drug treatment in patients with Graves' disease (1989) Acta Endocrinol., 120 (6), pp. 689-701Vitti, P., Rago, T., Chiovato, L., Pallini, S., Santini, F., Fiore, E., Clinical features of patients with Graves' disease undergoing remission after antithyroid drug treatment (1997) Thyroid., 7 (3), pp. 369-375Tamai, H., Nakagawa, T., Fukino, O., Ohsako, N., Shinzato, R., Suematsu, H., Thionamida therapy in Graves' disease: Relation of relapse rate to duration of therapy (1980) Ann Intern Med., 92 (4), pp. 488-490Allannic, H., Fauchet, R., Orgiazzi, J., Madec, A.M., Genetet, B., Lorcy, Y., Antithyroid drugs and Graves' disease: A prospective randomized evaluation of the efficacy of treatment duration (1990) J Clin Endocrinol Metab., 70 (3), pp. 675-679Benker, G., Rjenwein, D., Kahaly, G., Teglu, L., Alexander, W.D., Fassbinder, J., Is there a methimazole dose effect on remission rate in Graves' disease? Results from a long-term prospective study (1998) Clin Endocrinol (Oxf)., 49 (4), pp. 451-457Wood, L.C., Ingbar, S.H., Hypothyr