Mutação E449X no receptor β do hormônio tireoidiano associada com doença tireoidiana auto-imune e retardo neuropscicomotor grave

OBJECTIVE: To report the clinical and molecular aspects of a patient with a diagnosis of Resistance to Thyroid Hormone (RTH) harboring the E449X mutation associated with autoimmune thyroid disease and severe neuropsychomotor retardation. METHODS: We present a case report including clinical and laboratory findings, and molecular analysis of a Brazilian patient with RTH. RESULTS: A 23-year old male presented hyperactivity disorder, attention deficit, delayed neuropsychomotor development, and goiter. Since the age of 1 year and 8 months, his mother had sought medical care for her son for the investigation of delayed neuropsychomotor development associated with irritability, aggressiveness, recurrent headache, profuse sudoresis, intermittent diarrhea, polyphagia, goiter, and low weight. Laboratory tests revealed normal TSH, increased T3, T4, antithyroglobulin and antimicrosomal antibody titers. Increasing doses of levothyroxine were prescribed, reaching 200 µg/day, without significant changes in his clinical-laboratory picture. Increasing doses of tiratricol were introduced, with a clear clinical improvement of aggressiveness, hyperactivity, tremor of the extremities, and greater weight gain. Molecular study revealed a nonsense mutation in exon 10, in which a substitution of a guanine to tyrosine in nucleotide 1345 (codon 449) generates the stop codon TAA, confirming the diagnosis of RTH. CONCLUSION: This patient has severe neuropsychomotor retardation not observed in a single previous report with the same mutation. This may reflect the lack of a genotype-phenotype correlation in affected cases with this syndrome, suggesting that genetic variability of factors other than β receptor of thyroid hormone (TRβ) might modulate the phenotype of RTH.OBJETIVOS: Descrever aspectos clínicos e moleculares de um paciente com resistência ao hormônio tireoidiano (RHT) portador da mutação E449X associada a doença tireoideana auto-imune e retardo neuropscicomotor grave. MÉTODOS: Relatamos um caso incluindo achados clínicos, laboratoriais e análise molecular de um paciente brasileiro com RHT. RESULTADOS: Paciente masculino, 23 anos de idade, apresentou-se com distúrbio de hiperatividade, déficit de atenção, retardo no desenvolvimento neuropsicomotor e bócio. Desde 1 ano e 8 meses de idade, sua mãe procurou assistência médica para investigação do retardo do desenvolvimento neuropsicomotor associado com irritabilidade, agressividade, cefaléia recorrente, sudorese profusa, diarréia intermitente, polifagia, bócio e perda de peso. Avaliação laboratorial evidenciou TSH normal e aumento do T3, T4 e anticorpos antimicrossomal e antitireoglobulina. Doses crescentes de levotiroxina foram prescritas, máximo de 200 µg/dia, sem significativas alterações em seu quadro clínico-laboratorial. Doses crescentes de tiratricol foram introduzidas com melhora clínica evidente da agressividade, da hiperatividade, do tremor de extremidades e maior ganho de peso. O estudo molecular revelou uma mutação nonsense no éxon 10, no qual a substituição da guanina pela tirosina no nucleotídeo 1345 (códon 449) gerou um stop códon TAA, confirmando o diagnóstico da RHT. CONCLUSÃO: Este paciente tem um grave retardo neuropiscomotor não observado em um relato único anterior com a mesma mutação. Isto pode refletir a falta de relação genotipo-fenótipo nos casos afetados com esta síndrome sugerindo que a variabilidade genética de outros fatores, além do receptor do hormônio tireoidiano (HT), possa modular o fenótipo da RHT

Challenges associated with insulin therapy progression among patients with type 2 diabetes: Latin American MOSAIc study baseline data

Background: Poor glycemic control in patients with type 2 diabetes is commonly recorded worldwide; Latin America (LA) is not an exception. Barriers to intensifying insulin therapy and which barriers are most likely to negatively impact outcomes are not completely known. The objective was to identify barriers to insulin progression in individuals with type 2 diabetes mellitus (T2DM) in LA countries (Mexico, Brazil, and Argentina). Methods: MOSAIc is a multinational, non-interventional, prospective, observational study aiming to identify the patient-, physician-, and healthcare-based factors affecting insulin intensification. Eligible patients were ≥18 years, had T2DM, and were treated with insulin for ≥3 months with/without oral antidiabetic drugs (OADs). Demographic, clinical, and psychosocial data were collected at baseline and regular intervals during the 24-month follow-up period. This paper however, focuses on baseline data analysis. The association between glycated hemoglobin (HbA1c) and selected covariates was assessed. Results: A trend toward a higher level of HbA1c was observed in the LA versus non-LA population (8.40 ± 2.79 versus 8.18 ± 2.28; p ≤ 0.069). Significant differences were observed in clinical parameters, treatment patterns, and patient-reported outcomes in LA compared with the rest of the cohorts and between Mexico, Brazil, and Argentina. Higher number of insulin injections and lower number of OADs were used, whereas a lower level of knowledge and a higher level of diabetes-related distress were reported in LA. Covariates associated with HbA1c levels included age (-0.0129; p < 0.0001), number of OADs (0.0835; p = 0.0264), higher education level (-0.2261; p = 0.0101), healthy diet (-0.0555; p = 0.0083), self-monitoring blood glucose (-0.0512; p = 0.0033), hurried communication style in the process of care (0.1295; p = 0.0208), number of insulin injections (0.1616; p = 0.0088), adherence (-0.1939; p ≤ 0.0104), and not filling insulin prescription due to associated cost (0.2651; p = 0.0198). Conclusion: MOSAIc baseline data showed that insulin intensification in LA is not optimal and identified several conditions that significantly affect attaining appropriate HbA1c values. Tailored public health strategies, including education, should be developed to overcome such barriers.Centro de Endocrinología Experimental y Aplicad

Challenges associated with insulin therapy progression among patients with type 2 diabetes: Latin American MOSAIc study baseline data

Background: Poor glycemic control in patients with type 2 diabetes is commonly recorded worldwide; Latin America (LA) is not an exception. Barriers to intensifying insulin therapy and which barriers are most likely to negatively impact outcomes are not completely known. The objective was to identify barriers to insulin progression in individuals with type 2 diabetes mellitus (T2DM) in LA countries (Mexico, Brazil, and Argentina). Methods: MOSAIc is a multinational, non-interventional, prospective, observational study aiming to identify the patient-, physician-, and healthcare-based factors affecting insulin intensification. Eligible patients were ≥18 years, had T2DM, and were treated with insulin for ≥3 months with/without oral antidiabetic drugs (OADs). Demographic, clinical, and psychosocial data were collected at baseline and regular intervals during the 24-month follow-up period. This paper however, focuses on baseline data analysis. The association between glycated hemoglobin (HbA1c) and selected covariates was assessed. Results: A trend toward a higher level of HbA1c was observed in the LA versus non-LA population (8.40 ± 2.79 versus 8.18 ± 2.28; p ≤ 0.069). Significant differences were observed in clinical parameters, treatment patterns, and patient-reported outcomes in LA compared with the rest of the cohorts and between Mexico, Brazil, and Argentina. Higher number of insulin injections and lower number of OADs were used, whereas a lower level of knowledge and a higher level of diabetes-related distress were reported in LA. Covariates associated with HbA1c levels included age (-0.0129; p < 0.0001), number of OADs (0.0835; p = 0.0264), higher education level (-0.2261; p = 0.0101), healthy diet (-0.0555; p = 0.0083), self-monitoring blood glucose (-0.0512; p = 0.0033), hurried communication style in the process of care (0.1295; p = 0.0208), number of insulin injections (0.1616; p = 0.0088), adherence (-0.1939; p ≤ 0.0104), and not filling insulin prescription due to associated cost (0.2651; p = 0.0198). Conclusion: MOSAIc baseline data showed that insulin intensification in LA is not optimal and identified several conditions that significantly affect attaining appropriate HbA1c values. Tailored public health strategies, including education, should be developed to overcome such barriers.Centro de Endocrinología Experimental y Aplicad

Bloqueio Atrioventricular Total Associado a Hipertireoidismo por Doença de Graves

Descrevemos o caso de uma paciente jovem, portadora de hipertireoidismo por doença de Graves, que durante admissao hospitalar desenvolveu quadro grave de instabilidade hemodinâmica, evoluindo com bloqueio atrioventricular total (BAVT) e necessidade de marcapasso provisório. Após introduçao de droga antitireoidiana e uso de corticóide, houve recuperaçao do grau de bloqueio com 36 horas. Um possível mecanismo, no estado de hipertireoidismo, seria o efeito direto do hormônio tireoidiano no sistema de conduçao ou a infiltraçao linfocitária na regiao do sistema de conduçao cardíaco, considerando a natureza auto-imune da doença de base. Esses mecanismos sao discutidos por nós e por outros autores na literatura

Bloqueio Atrioventricular Total Associado a Hipertireoidismo por Doença de Graves

Descrevemos o caso de uma paciente jovem, portadora de hipertireoidismo por doença de Graves, que durante admissao hospitalar desenvolveu quadro grave de instabilidade hemodinâmica, evoluindo com bloqueio atrioventricular total (BAVT) e necessidade de marcapasso provisório. Após introduçao de droga antitireoidiana e uso de corticóide, houve recuperaçao do grau de bloqueio com 36 horas. Um possível mecanismo, no estado de hipertireoidismo, seria o efeito direto do hormônio tireoidiano no sistema de conduçao ou a infiltraçao linfocitária na regiao do sistema de conduçao cardíaco, considerando a natureza auto-imune da doença de base. Esses mecanismos sao discutidos por nós e por outros autores na literatura

Protocol for detection, diagnosis and treatment of diabetes mellitus during pregnancy

The authors present the approach to pregnant woman for screening and diagnosis of gestational diabetes mellitus (GDM) and treatment of the diabetes mellitus during pregnancy, established as routine by the Sector of High Risk Pregnancy of the Department and Gynecology and Obstetric and Division of Endocrinology and Metabolism of Medicine School of Ribeirão Preto - University of São Paulo and it was assumed as a routine pre-natal evaluation for screening and diagnosis of GDM at Ribeirão Preto Health Secretary’s Office. This protocol was based on the recommendations of the World Health Organization and the American Diabetes Organization.Os autores apresentam a abordagem da paciente gestante, para rastreamento e diagnóstico do Diabetes mellitus Gestacional (DMG) e tratamento do Diabetes mellitus durante a gravidez, estabelecida como procedimento rotineiro pelo Setor de Gestação de Alto Risco do Departamento de Ginecologia e Obstetrícia e Divisão de Endocrinologia e Metabologia do Departamento de Clínica Médica da Faculdade de Medicina de Ribeirão Preto - Universidade de São Paulo e adotado na avaliação pré-natal da Secretaria Municipal de Saúde de Ribeirão Preto para rastreamento e diagnóstico do DMG. Este protocolo foi baseado nas recomendações da Organização Mundial da Saúde e American Diabetes Association

Race/ethnicity and challenges for optimal insulin therapy

AimsWe aimed to review insulin dosing recommendations, insulin regulation and its determinants, glycaemic response to carbohydrates, and the efficacy and safety of insulin therapy in different races/ethnicities. MethodsWe searched for articles in PubMed and Google Scholar databases up to 31 March 2021, with the following keywords: “ethnicity”, “diabetes”, “insulin”, “history of insulin”, “insulin therapy”, “food/rice”, “carbohydrate intake”, “insulin resistance”, “BMI”, “insulin dosing”, “insulin sensitivity”, “insulin response”, “glycaemic index”, “glycaemic response”, “efficacy and safety”, with interposition of the Boolean operator “AND”.In addition, we reviewed the reference lists of the articles found. ResultsThe differential effect of race/ethnicity has not yet been considered in current insulin therapy guidelines. Nevertheless, body size and composition, body mass index, fat distribution, diet, storage, and energy expenditure vary significantly across populations. Further, insulin sensitivity, insulin response, and glycaemicresponse to carbohydrates differ by ethnicity. These disparities may lead to different insulin requirements, adversely impacting the efficacy and safety of insulin therapy among ethnic groups. ConclusionsRace/ethnicity affects glucose metabolism and insulin regulation.Until now, international guidelines addressing racial/ethnic-specific clinical recommendations are limited. Comprehensive updated insulin therapy guidelines by ethnicity are urgently needed

Determinants of intensive insulin therapeutic regimens in patients with type 1 diabetes: data from a nationwide multicenter survey in Brazil

Background: To evaluate the determinants of intensive insulin regimens (ITs) in patients with type 1 diabetes (T1D).Methods: This multicenter study was conducted between December 2008 and December 2010 in 28 public clinics in 20 Brazilian cities. Data were obtained from 3,591 patients (56.0% female, 57.1% Caucasian). Insulin regimens were classified as follows: group 1, conventional therapy (CT) (intermediate human insulin, one to two injections daily); group 2 (three or more insulin injections of intermediate plus regular human insulin); group 3 (three or more insulin injections of intermediate human insulin plus short-acting insulin analogues); group 4, basal-bolus (one or two insulin injections of long-acting plus short-acting insulin analogues or regular insulin); and group 5, basal-bolus with continuous subcutaneous insulin infusion (CSII). Groups 2 to 5 were considered IT groups.Results: We obtained complete data from 2,961 patients. Combined intermediate plus regular human insulin was the most used therapeutic regimen. CSII was used by 37 (1.2%) patients and IT by 2,669 (90.2%) patients. More patients on IT performed self-monitoring of blood glucose and were treated at the tertiary care level compared to CT patients (p < 0.001). the majority of patients from all groups had HbA1c levels above the target. Overweight or obesity was not associated with insulin regimen. Logistic regression analysis showed that economic status, age, ethnicity, and level of care were associated with IT (p < 0.001).Conclusions: Given the prevalence of intensive treatment for T1D in Brazil, more effective therapeutic strategies are needed for long term-health benefits.Farmanguinhos/Fundacao Oswaldo Cruz/National Health MinistryBrazilian Diabetes SocietyFundacao do Amparo a Pesquisa do Estado do Rio de JaneiroConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Univ Estado Rio de Janeiro, Unit Diabet, BR-20551030 Rio de Janeiro, BrazilBaurus Diabet Assoc, São Paulo, BrazilFed Univ São Paulo State, Diabet Unit, São Paulo, BrazilFed Univ Hosp Porto Alegre, Porto Alegre, BrazilUniv Hosp São Paulo, Diabet Unit, São Paulo, BrazilUniv Fed Rio de Janeiro, Rio de Janeiro, BrazilUniv Fed Ceara, Fortaleza, Ceara, BrazilSanta Casa Misericordia, Belo Horizonte, MG, BrazilSanta Casa Misericordia São Paulo, São Paulo, BrazilUniv Fed Amazonas, Manaus, Amazonas, BrazilHosp Geral de Bonsucesso, Rio de Janeiro, BrazilHosp Univ Clementino Fraga Filho IPPMG, Rio de Janeiro, BrazilUniv Hosp São Paulo, São Paulo, BrazilFac Ciencias Med Santa Casa São Paulo, São Paulo, BrazilUniv São Paulo, Inst Crianca, Hosp Clin, São Paulo, BrazilUniv São Paulo, Fac Med Ribeirao Preto, Hosp Clin, Ribeirao Preto, BrazilAmbulatorio Fac Estadual Med Sao Jose Rio Preto, Ribeirao Preto, BrazilEscola Paulista Med, Ctr Diabet, Ribeirao Preto, BrazilClin Endocrinol Santa Casa Belo Horizonte, Belo Horizonte, MG, BrazilUniv Estadual Londrina, Londrina, BrazilUniv Fed Parana, Hosp Clin, Porto Alegre, RS, BrazilInst Crianca Com Diabet Rio Grande Sul, Rio Grande Do Sul, RS, BrazilGrp Hosp Conceicao, Inst Crianca Com Diabet, Porto Alegre, RS, BrazilHosp Univ Santa Catarina, Florianopolis, SC, BrazilInst Diabet Endocrinol Joinville, Joinville, BrazilHosp Reg Taguatinga, Brasilia, DF, BrazilHosp Geral Goiania, Goiania, Go, BrazilCtr Diabet & Endocrinol Estado Bahia, Goiania, Go, BrazilUniv Fed Maranhao, Sao Luis, BrazilCtr Integrado Diabet & Hipertensao Ceara, Fortaleza, Ceara, BrazilUniv Fed Sergipe, Aracaju, BrazilHosp Univ Alcides Carneiro, Campina Grande, BrazilHosp Univ Joao de Barros Barreto, Belem, Para, BrazilFed Univ São Paulo State, Diabet Unit, São Paulo, BrazilUniv Hosp São Paulo, Diabet Unit, São Paulo, BrazilUniv Hosp São Paulo, São Paulo, BrazilEscola Paulista Med, Ctr Diabet, Ribeirao Preto, BrazilWeb of Scienc