Tratamiento con TRIAC en pacientes pediátricos con deficiencia de MCT8 / Treatment with TRIAC in pediatric patients with MCT8

Los transportadores de monocarboxilatos (MCT) permiten el ingreso celular de hormonas tiroideas, especialmente en el sistema nervioso central (SNC), donde son indispensables para el neurodesarrollo. La deficiencia de MCT8 produce la combinación de hipotiroidismo en SNC e hipertiroidismo periférico, caracterizada por T3 elevada. El único tratamiento actualmente disponible es el ácido 3,3',5-triyodotiroacético (TRIAC), un análogo de hormonas tiroideas que tiene como objetivo mejorar la tirotoxicosis periférica y prevenir la progresión del deterioro neurológico. En el presente artículo, se evalúan las características clínicas, imagenológicas, bioquímicas y genéticas de 4 pacientes con deficiencia de MCT8 tratados con TRIAC hasta la fecha, las dosis utilizadas y la respuesta al tratamiento.

Monocarboxylate transporters (MCTs) allow the cellular entry of thyroid hormones, especially into the central nervous system (CNS), where they are crucial for neurodevelopment. MCT8 deficiency results in the combination of hypothyroidism in the CNS and peripheral hyperthyroidism, characterized by elevated T3 levels. The only treatment currently available is 3,3',5-triiodothyroacetic acid (TRIAC), a thyroid hormone analogue aimed at improving peripheral thyrotoxicosis and preventing the progression of neurological impairment. Here we assess the clinical, imaging, biochemical, and genetic characteristics of 4 patients with MCT8 deficiency who have received TRIAC to date, the doses used, and the response to treatment.

Genetic variants in the SLC16A11 gene are associated with increased BMI and insulin levels in nondiabetic Chilean population

ABSTRACT Objective: To study the association of SLC16A11 gene variants with obesity and metabolic markers in nondiabetic Chilean adults. Materials and methods: This cross-sectional study included 263 non-diabetic adults. The genotype of the rs75493593 polymorphism of SLC16A11 gene was performed by real-time PCR. It's association with adiposity markers (body weight, BMI, waist circumference and fat mass percentage), metabolic markers (glucose, insulin, HOMAIR, leptin, total cholesterol, LDLc, HDLc, triglycerides, ALT, GGT and hsCRP) and blood pressure was analyzed by linear regression. Results: The minor allele (T) of the SLC16A11 gene (rs75493593) has a frequency of 29.7% among Chileans. Risk genotypes (GT and TT) were associated with a significant 1.49 mU/l increase in plasmatic insulin for each copy of the minor allele (95% CI: 0.12, 2.87, p < 0.05). This association remained significant after adjusting for socio-demographic variables, physical activity and smoking (1.36 mU/l, 95% CI: 0.16, 2.58 p < 0.05), but was lost when BMI was included as a confounding factor. Higher BMI was also significantly associated with polymorphic genotypes in SLC16A11, independent of socio-demographic variables. Conclusion: The minor allele of the SLC16A11 gene (T) is highly prevalent among Chileans and is associated with increased insulin and BMI in nondiabetic individuals. These findings suggest that the genetic variant in SLC16A11 is not only associated with type 2 diabetes as previously shown in Mexicans, but is also related to early metabolic alterations in healthy subjects that may lead to type 2 diabetes.

Loss of monocarboxylate transporter 1 aggravates white matter injury after experimental subarachnoid hemorrhage in rats / 医学前沿

Monocarboxylic acid transporter 1 (MCT1) maintains axonal function by transferring lactic acid from oligodendrocytes to axons. Subarachnoid hemorrhage (SAH) induces white matter injury, but the involvement of MCT1 is unclear. In this study, the SAH model of adult male Sprague-Dawley rats was used to explore the role of MCT1 in white matter injury after SAH. At 48 h after SAH, oligodendrocyte MCT1 was significantly reduced, and the exogenous overexpression of MCT1 significantly improved white matter integrity and long-term cognitive function. Motor training after SAH significantly increased the number of ITPR2

Prevalência de depressão em bombeiros / Prevalence of depression among firefighters / Prevalencia de depresión en bomberos

A depressão apresenta alta carga de doença no mundo. Fatores socioeconômicos e exposição a situações extremas no trabalho podem estar associados à doença. O objetivo do trabalho é investigar a prevalência e fatores associados à depressão em bombeiros de Belo Horizonte, Minas Gerais, Brasil. Estudo transversal foi realizado em universo de bombeiros do sexo masculino em Belo Horizonte (n = 711). O Inventário Beck para Depressão (IBD) foi utilizado para avaliar a presença de depressão. Modelos de regressão logística (uni e multivariada) foram utilizados para estudar a associação entre características sociodemográficas, estressores ocupacionais, situação de saúde e depressão. A prevalência de depressão na amostra estudada foi 5,5%. A chance de depressão foi maior entre bombeiros que relataram sintomas de estresse pós-traumático (OR = 12,47; IC95%: 5,64-27,57) e uso abusivo de álcool (OR = 5,30; IC95%: 2,35-11,96). Os resultados são discutidos considerando as inter-relações entre transtornos mentais, o efeito do trabalhador sadio e o reconhecimento social do trabalho dos bombeiros.

Depression burder is high worldwide. Socioeconomic factors and exposure to extreme situations at work may be associated with the illness. This study focused on the prevalence of depression and associated factors among firefighters in Belo Horizonte, Minas Gerais State, Brazil. A cross-sectional study was conducted among male firefighters in Belo Horizonte (n = 711). The Beck Depression Inventory (BDI) was used to assess depression. Univariate and multivariate logistic regression models were used to study the association between socio-demographic characteristics, occupational stressors, health status, and depression. Prevalence of depression in the sample was 5.5%. The likelihood of developing depression was higher among firefighters who reported post-traumatic stress symptoms (OR = 12.47; 95%CI: 5.64-27.57) and alcohol abuse (OR = 5.30; 95%CI: 2.35-11.96). The results are discussed considering the interrelationships between mental disorders, the healthy worker effect, and social recognition of firefighters' work.

La depresión tiene una alta carga como enfermedad mundial. Factores socioeconómicos y la exposición a situaciones extremas en el trabajo pueden estar asociados con la enfermedad. El objetivo de este trabajo es investigar la prevalencia y los factores asociados con la depresión en los bomberos de Belo Horizonte, Minas Gerais, Brasil. Se trata de un estudio transversal, realizado entre los bomberos de sexo masculino de Belo Horizonte (n = 711). Se utilizó el Inventario de Depresión de Beck (IDB) para evaluar la presencia de depresión. Se utilizaron modelos de regresión logística para estudiar la asociación entre características sociodemográficas, estrés ocupacional, estado de salud y depresión. La prevalencia de depresión fue de un 5,5%. La posibilidad de depresión fue mayor entre los bomberos que informaron síntomas de estrés postraumático (OR = 12,47; IC95%: 5,64-27,57) y abuso de alcohol (OR = 5,30, IC95%: 2,35-11,96). Los resultados son discutidos considerando las interrelaciones entre los trastornos mentales, el efecto en trabajadores sanos y el reconocimiento social de la labor de bomberos.

Novel mutation in MCT8 gene in a Brazilian boy with thyroid hormone resistance and severe neurologic abnormalities / Mutação nova do gene MCT8 em menino Brasileiro com resistência ao hormônio tireioidiano e neuropatia grave

O MCT8 é um transportador celular de hormônios tireoidianos, importante para sua ação e metabolização. Relatamos o caso de um menino com a nova mutação inativadora 630insG no éxon 1 do MCT8. O paciente caracterizou-se por grave comprometimento neurológico (inicialmente com hipotonia global, evoluindo com hipertonia generalizada), crescimento normal nos dois primeiros anos de vida, reduzido ganho ponderal e ausência dos sinais e sintomas típicos de hipotireoidismo. A sua avaliação sérica revelou elevação do T3, redução do T4 total e livre e TSH levemente aumentado. O tratamento com levotiroxina melhorou o perfil hormonal tireoidiano, mas não modificou o quadro clínico do paciente. Esses dados reforçam o conceito de que o papel do MCT8 é tecido-dependente: enquanto os neurônios são altamente dependentes do MCT8, o osso, o tecido adiposo, o músculo e o fígado são menos dependentes do MCT8 e, portanto, podem sofrer as consequências da exposição a níveis séricos elevados de T3.

MCT8 is a cellular transporter of thyroid hormones important in their action and metabolization. We report a male patient with the novel inactivating mutation 630insG in the coding region in exon 1 of MCT8. He was characterized clinically by severe neurologic impairment (initially with global hypotonia, later evolving with generalized hypertonia), normal growth during infancy, reduced weight gain, and absence of typical signs and symptoms of hypothyroidism, while the laboratory evaluation disclosed elevated T3, low total and free T4, and mildly elevated TSH serum levels. Treatment with levothyroxine improved thyroid hormone profile but was not able to alter the clinical picture of the patient. These data reinforce the concept that the role of MCT8 is tissue-dependent: while neurons are highly dependent on MCT8, bone tissue, adipose tissue, muscle, and liver are less dependent on MCT8 and, therefore, may suffer the consequences of the exposition to high serum T3 levels.

Allan-Herndon-Dudley syndrome.

Allan-Herndon-Dudley Syndrome (AHDS) is a rare X-linked disorder caused by mutation in the gene encoding the monocarboxylate transporter-8. Abnormal transport function is reflected by elevated free T3 and decreased free T4 levels along with clinical features characterized by neurological abnormalities including global developmental delay, central hypotonia, rotatory nystagmus, impaired hearing, spasticity and contractures of joints. We report a child with classical clinical features along with confirmatory deranged thyroid levels in blood.